NO Deficiency Compromises Inter- and Intrahemispheric Blood Flow Adaptation to Unilateral Carotid Artery Occlusion.

Carotid artery stenosis (CAS) affects approximately 5-7.5% of older adults and is recognized as a significant risk factor for vascular cognitive impairment (VCI). The impact of CAS on cerebral blood flow (CBF) within the ipsilateral hemisphere relies on the adaptive capabilities of the cerebral microcirculation. In this study, we aimed to test the hypothesis that the impaired availability of nitric oxide (NO) compromises CBF homeostasis after unilateral carotid artery occlusion (CAO). To investigate this, three mouse models exhibiting compromised production of NO were tested: NOS1 knockout, NOS1/3 double knockout, and mice treated with the NO synthesis inhibitor L-NAME. Regional CBF changes following CAO were evaluated using laser-speckle contrast imaging (LSCI). Our findings demonstrated that NOS1 knockout, NOS1/3 double knockout, and L-NAME-treated mice exhibited impaired CBF adaptation to CAO. Furthermore, genetic deficiency of one or two NO synthase isoforms increased the tortuosity of pial collaterals connecting the frontoparietal and temporal regions. In conclusion, our study highlights the significant contribution of NO production to the functional adaptation of cerebrocortical microcirculation to unilateral CAO. We propose that impaired bioavailability of NO contributes to the impaired CBF homeostasis by altering inter- and intrahemispheric blood flow redistribution after unilateral disruption of carotid artery flow.

Relationship between subjectively-rated and objectively-tested physical function across six different medical diagnoses.

OBJECTIVE: To quantify and compare associations and relationships between self-rated and tested assessments of mainly mobility-related physical function in different diagnoses. DESIGN: Six longitudinal cohort studies before and after inpatient rehabilitation. PATIENTS: Patients with whiplash-associated disorder (n = 71), low back pain (n = 121), fibromyalgia (n = 84), lipoedema (n = 27), lymphoedema (n = 78), and post-acute coronary syndrome (n = 64). METHODS: Physical function was measured with the self-rated Short-Form 36 Physical functioning (SF-36 PF) and with the tested 6-Min Walk Distance (6MWD) and assessed by correlation coefficients. Across the 6 cohorts, the relationship between the 2 scores was compared using the ratio between them. RESULTS: The correlations between the 2 scores were mostly moderate to strong at baseline (up to r = 0.791), and weak to moderate for the changes to follow-up (up to r = 0.408). The ratios SF-36 PF to 6MWD were 1.143-1.590 at baseline and 0.930-3.310 for the changes, and depended on pain and mental health. CONCLUSION: Moderate to strong cross-sectional and moderate to weak longitudinal correlations were found between the 6MWD and the SF-36 PF. Pain and mental health should be considered when interpreting physical function. For a comprehensive assessment in clinical practice and research, the combination of self-rated and tested physical function measures is recommended.

Occipital transcranial direct current stimulation in episodic migraine patients: effect on cerebral perfusion.

Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic migraine patients and healthy controls and investigates the influence of anodal transcranial direct current stimulation (tDCS) over the occipital cortex. We included healthy adult controls and episodic migraineurs. After a 28-day baseline period and the baseline visit, migraine patients received daily active or sham anodal tDCS over the occipital lobe for 28 days. All participants underwent a MRI scan at baseline; migraineurs were also scanned shortly after the stimulation period and about five months later. At baseline, brain perfusion of migraine patients and controls differed in several areas; among the stimulated areas, perfusion was increased in the cuneus of healthy controls. At the first visit, the active tDCS group had an increased blood flow in regions processing visual stimuli and a decreased perfusion in other areas. Perfusion did not differ at the second follow-up visit. The lower perfusion level in migraineurs in the cuneus indicates a lower preactivation level. Anodal tDCS over the occipital cortex increases perfusion of several areas shortly after the stimulation period, but not 5 months later. An increase in the cortical preactivation level could mediate the transient reduction of the migraine frequency.Trial registration: NCT03237754 (registered at clincicaltrials.gov; full date of first trial registration: 03/08/2017).

Carrier-envelope phase on-chip scanner and control of laser beams.

The carrier-envelope phase (CEP) is an important property of few-cycle laser pulses, allowing for light field control of electronic processes during laser-matter interactions. Thus, the measurement and control of CEP is essential for applications of few-cycle lasers. Currently, there is no robust method for measuring the non-trivial spatial CEP distribution of few-cycle laser pulses. Here, we demonstrate a compact on-chip, ambient-air, CEP scanning probe with 0.1 µm3 resolution based on optical driving of CEP-sensitive ultrafast currents in a metal-dielectric heterostructure. We successfully apply the probe to obtain a 3D map of spatial changes of CEP in the vicinity of an oscillator beam focus with pulses as weak as 1 nJ. We also demonstrate CEP control in the focal volume with a spatial light modulator so that arbitrary spatial CEP sculpting could be realized.

Assessing the Risk of Developing Delirium on Admission to Inpatient Rehabilitation: A Clinical Prediction Model.

OBJECTIVES: To develop a clinical model to predict the risk of an individual patient developing delirium during inpatient rehabilitation, based on patient characteristics and clinical data available on admission. DESIGN: Retrospective observational study based on electronic health record data. SETTING AND PARTICIPANTS: We studied a previously validated data set of inpatients including incident delirium episodes during rehabilitation. These patients were admitted to ZURZACH Care, Rehaklinik Bad Zurzach, a Swiss inpatient rehabilitation clinic, between January 1, 2015, and December 31, 2018. METHODS: We performed logistic regression analysis using backward and forward selection with alpha = 0.01 to remove any noninformative potential predictor. We subsequentially used the Akaike information criterion (AIC) to select the final model among the resulting "intermediate" models. Discrimination of the final prediction model was evaluated using the C-statistic. RESULTS: Of the 20 candidate predictor variables, 6 were included in the final prediction model: a linear spline of age with 1 knot at 60 years and a linear spline of the functional independence measure (FIM), a measure of the functional degree of patients independency, with 1 knot at 64 points, diagnosis of disorders of fluid, electrolyte, and acid-base balance (E87), use of other analgesic and antipyretics (N02B), use of anti-parkinson drugs (N04B), and an anticholinergic burden score (ACB) of ≥3 points. CONCLUSIONS AND IMPLICATIONS: Our clinical prediction model could, upon validation, identify patients at risk of incident delirium at admission to inpatient rehabilitation, and thus enable targeted prevention strategies.

Guideline on multimodal rehabilitation for patients with post-intensive care syndrome.

BACKGROUND: Intensive Care Unit (ICU) survivors often experience several impairments in their physical, cognitive, and psychological health status, which are labeled as post-intensive care syndrome (PICS). The aim of this work is to develop a multidisciplinary and -professional guideline for the rehabilitative therapy of PICS. METHODS: A multidisciplinary/-professional task force of 15 healthcare professionals applied a structured, evidence-based approach to address 10 scientific questions. For each PICO-question (Population, Intervention, Comparison, and Outcome), best available evidence was identified. Recommendations were rated as "strong recommendation", "recommendation" or "therapy option", based on Grading of Recommendations, Assessment, Development and Evaluation principles. In addition, evidence gaps were identified. RESULTS: The evidence resulted in 12 recommendations, 4 therapy options, and one statement for the prevention or treatment of PICS. RECOMMENDATIONS: early mobilization, motor training, and nutrition/dysphagia management should be performed. Delirium prophylaxis focuses on behavioral interventions. ICU diaries can prevent/treat psychological health issues like anxiety and post-traumatic stress disorders. Early rehabilitation approaches as well as long-term access to specialized rehabilitation centers are recommended. Therapy options include additional physical rehabilitation interventions. Statement: A prerequisite for the treatment of PICS are the regular and repeated assessments of the physical, cognitive and psychological health in patients at risk for or having PICS. CONCLUSIONS: PICS is a variable and complex syndrome that requires an individual multidisciplinary, and multiprofessional approach. Rehabilitation of PICS should include an assessment and therapy of motor-, cognitive-, and psychological health impairments.

Effects of Inpatient Rehabilitation in Leg Lymphedema: A Naturalistic Prospective Cohort Study With Intra-individual Control of Effects.

OBJECTIVE: To quantify therapy-attributable effects of a comprehensive inpatient rehabilitation program for lower limb lymphedema (LLL) and to compare the levels of health-related quality of life (HRQL) to population-based norms. DESIGN: Naturalistic prospective cohort study with intra-individual control of effects. SETTING: Rehabilitation hospital. PARTICIPANTS: Patients with LLL (N=67; 46 women). INTERVENTIONS: Comprehensive, multidisciplinary inpatient rehabilitation with 45-60 hours of therapy. MAIN OUTCOME MEASURES: Short Form 36 (SF-36) for HRQL, lymphedema-specific Freiburg Quality of Life Assessment for lymphatic disorders, Short Version (FLQA-lk), knee-specific Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), and Symptom Checklist-90Standard (SCL-90S). Observed pre/post rehabilitation effects were individually corrected by subtracting the home waiting-time effects and expressed as standardized effect sizes (ESs) and standardized response means (SRMs). Score differences to norms were quantified by standardized mean differences (SMDs). RESULTS: Participants were on average aged 60.5 years, not yet obese, and had 3 comorbidities (n=67). The greatest improvement was in HRQL on the FLQA-lk with ES=0.767/SRM=0.718, followed by improvements in pain and function with ES/SRM=0.430-0.495 on the SF-36, FLQA-lk, and KOS-ADL (all P<.001). Vitality, mental health, emotional well-being, and interpersonal sensitivity improved most by ES/SRM=0.341-0.456 on all 4 measures (all P≤.003). Post rehabilitation scores were significantly higher than population norms on SF-36 bodily pain (SMD=1.140), vitality (SMD=0.886), mental health (SMD=0.815), and general health (SMD=0.444) (all P<.001), and comparable on the other scales. CONCLUSIONS: Those affected by LLL stages II and III benefited substantially from the intervention, attaining equal or higher levels of HRQL than expected compared with the general population norms. Multidisciplinary, inpatient rehabilitation should be recommended for LLL management.

Metabolic markers of short and long-term exogenous DL-beta-hydroxybutyrate supplementation in episodic migraine patients: an exploratory analysis of a randomized-controlled-trial.

Background: Emerging findings propose that the pathophysiology of migraine may be associated with dysfunctional metabolic mechanisms. Recent findings suggest that migraine attacks are a response to the cerebral energy deficit, and ingestion of ketone bodies stabilizes the generation of a migraine attack. Based on these findings, ketone body supplementation is postulated as a prophylactic treatment approach to restore cerebral metabolism deficiency. Metabolic markers are unexplored after exogenous ketone body supplementation in episodic migraineurs. Therefore, the present single-arm uncontrolled explorative analysis evaluated blood ketone body and glucose concentration after short and long-term 6 g exogenous DL-Mg-Ca-beta-hydroxybutyrate (DL-ßHB) supplementation. Methods: The presented data are part of the MigraKet randomized-control cross-over clinical trial of 41 episodic migraineurs (Number NCT03132233). Patients were given a single dose of 6 g DL-ßHB. Ketone body and glucose blood concentration were assessed before intake, 20, and 40 min after DL-ßHB intake. Ketone body, glucose concentration and glycated hemoglobin values were evaluated after 12 weeks of 18 g DL-ßHB ingestion (total dose), taken three times daily (6g/dose; 3x/day). Linear models explored the association between the ketone body and glucose levels. Results: Ketone body concentration increased within-group to a mean of 0.46 (0.30) mmol/L after 40 min post- DL-ßHB supplementation [estimate = 0.24 mmol/L, CI = (0.20.0.27), p < 0.01]. This within-group increase of ketone body concentration did not change after repeated daily intake of DL-ßHB supplementation over 12 weeks [estimate = 0.00 mmol/L, CI = (-0.03.0.04), p = 0.794]. DL-ßHB intake significantly reduced blood glucose concentration within-group from a mean baseline of 4.91 (0.42) mmol/L to 4.75 (0.47) mmol/L 40 min post-DL-ßHB supplementation [estimate = -0.16 mmol/L, CI = (-0.15, 0.03), p < 0.01]. Repeated DL-ßHB supplementation for 12 weeks showed no change within-group in acute ketone bodies concentration [estimate = 0.00 mmol/L, CI = (-0.03.0.04), p = 0.794] and in the HbA1c value [estimate = 0.02, CI = (-0.07.0.11), p = 0.69]. Conclusion: A single dose of 6 g DL-ßHB significantly elevated blood ketone bodies and decreased blood glucose concentration within-group in episodic migraineurs. Long-term DL-ßHB supplementation for 12 weeks showed no effect within-group on acute ketone body concentration and had not impact on HbA1c. The elevation of the ketone body concentration was moderate, indicating that nutritional ketosis was not reached. Therefore, a dose higher than 6 g of DL-ßHB is required to reach the nutritional level of ketosis. ClinicalTrials.gov Identifier: NCT03132233.

Potential Risk Factors for, and Clinical Implications of, Delirium during Inpatient Rehabilitation: A Matched Case-Control Study.

OBJECTIVES: To investigate the association between a wide set of baseline characteristics (age, sex, rehabilitation discipline), functional scores [Functional Independence Measure (FIM), cumulative Illness Rating Scale (CIRS)], diseases, and administered drugs and incident delirium in rehabilitation inpatients and, furthermore, to assess clinical implications of developing delirium during rehabilitation. DESIGN: Matched case-control study based on electronic health record data. SETTING AND PARTICIPANTS: We studied rehabilitation stays of inpatients admitted between January 1, 2015, and December 31, 2018, to ZURZACH Care, Rehaklinik Bad Zurzach, an inpatient rehabilitation clinic in Switzerland. METHODS: We conducted unconditional logistic regression analyses to estimate adjusted odds ratios (AORs) with 95% CIs of exposures that were recorded in ≥5 cases and controls. RESULTS: Among a total of 10,503 rehabilitation stays, we identified 125 validated cases. Older age, undergoing neurologic rehabilitation, a low FIM, and a high CIRS were associated with an increased risk of incident delirium. Being diagnosed with a bacterial infection (AOR 2.62, 95% CI 1.06-6.49), a disorder of fluid, electrolyte, or acid-base balance (AOR 2.76, 95% CI 1.19-6.38), Parkinson's disease (AOR 5.68, 95% CI 2.54-12.68), and administration of antipsychotic drugs (AOR 8.06, 95% CI 4.26-15.22), antiparkinson drugs (AOR 2.86, 95% CI 1.42-5.77), drugs for constipation (AOR 2.11, 95% CI 1.25-3.58), heparins (AOR 2.04, 95% CI 1.29-3.24), or antidepressant drugs (AOR 1.88, 95% CI 1.14-3.10) during rehabilitation, or an increased anticholinergic burden (ACB ≥ 3) (AOR 2.59, 95% CI 1.41-4.73) were also associated with an increased risk of incident delirium. CONCLUSIONS AND IMPLICATIONS: We identified a set of factors associated with an increased risk of incident delirium during inpatient rehabilitation. Our findings contribute to detect patients at risk of delirium during inpatient rehabilitation.

Prevalence and Burden of Migraine in Switzerland: Cross-Sectional Study in ten Specialised Headache Centres from the BECOME Study.

INTRODUCTION: There is limited real-world evidence on the burden of migraine among patients with prior preventive treatment failure (PPTF). In the BECOME Swiss subanalysis, we aimed to assess current prevalence of PPTF in patients with migraine seen at specialised headache centres in Switzerland and burden of migraine in these patients. Furthermore, we assessed this burden in subgroups stratified by monthly migraine days (MMDs) and number of PPTFs. METHODS: BECOME was a prospective, multicentre, non-interventional two-part study conducted in 17 countries across Europe and Israel. This subanalysis includes patients visiting ten headache specialist centres in Switzerland. In part 1, patients visiting the centres over 3 months were screened by physicians for frequency of PPTF, MMD and other migraine characteristics. Patients with ≥ 1 PPTF and ≥ 4 MMDs were invited to take part in part 2. The primary endpoint was the proportion of patients with ≥ 1 PPTF (part 1). Other endpoints included proportion of patients specified by number of PPTF and MMD (part 1, part 2), and impact of migraine on patient-reported outcomes (PROs; part 2). RESULTS: Patients (1677) from ten Swiss centres were included in part 1, of which 855 (51.0%) reported ≥ 1 PPTF. One hundred fifty-five patients were included in part 2: 6.5% reported ≥ 4 PPTFs and 43.2% reported ≥ 15 MMDs. Mean EuroQoL 5 and EuroQoL visual analogue scale (EQ-VAS) were 0.8 ± 0.2 and 69.6 ± 20.2, respectively, suggesting a mild level of impairment in the daily functioning and self-reported health of the patients. Mean six-item Headache Impact Test (HIT-6) and modified Migraine Disability Assessment (mMIDAS) scores were 63.3 ± 6.5 and 22.7 ± 21.8, respectively, corresponding to severe migraine burden. Patients also reported impairment in work-related productivity and general activities (48.6 ± 22.8) but no associations of anxiety (7.2 ± 4.4) or depression (6.0 ± 4.4) with migraine were noted. Burden of migraine increased with increasing frequency of PPTF and MMD. CONCLUSIONS: Migraine-related quality of life, as well as work productivity are significantly affected in Swiss patients with migraine. Increasing migraine burden is associated with increasing migraine frequency and prior treatment failures.

The longitudinal influence of tDCS on occipital GABA and glutamate/glutamine levels in episodic migraineurs.

This study investigated differences in the concentration of gamma-aminobutyric acid (GABA) and the combination of glutamine and glutamate (as GLX) in the early visual cortex of patients with episodic migraine and the influence of transcranial direct current stimulation (tDCS) on GABA and GLX. In this single-blind, sham-controlled trial, we randomly assigned patients with episodic migraine to receive daily anodal tDCS or sham stimulation. In addition, we included healthy controls. We acquired proton MR spectroscopy data of the visual cortex with 3 Tesla MRI at baseline and from migraine patients directly after the stimulation period and 4 months later. In 22 migraineurs and 25 controls, the GABA and the GLX concentrations did not differ at baseline between the groups. tDCS resulted in reduced concentrations of GABA but not GLX or the migraine frequency directly after the stimulation period, but not 4 months later. The changes in the levels of GABA in the early visual cortex of patients with episodic migraine in the interictal period suggest an effect of tDCS that allowed for subsequent changes in the migraine frequency. However, we might have missed relevant variations in the concentrations of these neurotransmitters during the follow-up period, as changes in migraine frequency appeared after the first MRI and disappeared before the second.

Comparison of Swiss versus Standard Acupuncture in Patients with Chronic Low Back Pain. A Study Protocol for a Randomized, Controlled, Single-Blind, Parallel Trial.

Introduction: Chronic low back pain (CLBP) cannot sufficiently be treated by pharmacological therapy and generates substantial health-care costs worldwide. Acupuncture, a cost-effective, safe and non-pharmacological therapy, has shown promising results in relieving acute low back pain; however, the optimal acupuncture therapy for CLBP remains controversial. This study will compare two acupuncture methods for pain relief in CLBP. Methods and Analysis: This randomized, controlled, single-blind, parallel trial will be conducted in patients with clinically diagnosed CLBP with a disease duration ≥3 months and an average pain intensity of ≥4 points on an 11-point Pain Intensity Numerical Rating Scale (pain-NRS) on the previous 7 days. Patients will be randomized to 9-week acupuncture therapy using Jiu Gong Points (termed Swiss low back acupuncture, SLBA) or standard acupuncture (SA) therapy (weeks 1-6: two sessions/week, weeks 7-9: one session/week, 15 sessions/patient in total). Measurements will be conducted before the first session (T1), at the end of the 9-week therapy (T2) and after 3- and 6-month follow-up (T3 and T4). The primary hypothesis is that 9 weeks of SLBA will be superior in reducing the pain severity assessed by the pain-NRS compared to SA therapy for CLBP. Secondary outcomes will be derived from the Short-Form 36, Oswestry Disability Index, Multidimensional Pain Inventory questionnaire, Symptom Checklist-90 - Revised questionnaire and a daily pain diary. Assuming a minimal clinically important difference in the pain-NRS of 0.39 and an effect size of ≥0.6 between SLBA and SA, 80% power, 0.05 alpha level and 20% dropouts, a total of 55 patients/arm will be required. The primary outcome will be analyzed in the intention-to-treat population using chained linear regression models. Patients, outcome assessors and data analysts will be blinded to the treatment arm. Trial Registration: Clinicaltrials.gov Identifier: NCT05232487.

Mental and psychosocial health and health related quality of life before and after cardiac rehabilitation: a prospective cohort study with comparison to specific population norms.

BACKGROUND: Data on mental health improvement after cardiac rehabilitation (CR) are contradictory. The aim was to examine the mental and psycho-social health of patients admitted to our rehabilitation center following hospital treatment for acute coronary syndrome, before and after multidisciplinary CR. METHODS: Outcome was measured at admission and discharge by the 36-Item Short Form Survey (SF-36), the Symptom Checklist-90 Revised (SCL-90R), the Coping Strategy Questionnaire (CSQ) and the 6-min-walking distance test. The patients' health status was compared with norms of sex-, age- and comorbidity-matched data from the German general population. Score differences from norms were measured by standardized mean differences (SMDs); health changes were quantified by standardized effect sizes (ESs). Their importance for comprehensive assessment was quantified by explorative factor analysis. RESULTS: Of n = 70 patients followed-up (male: 79%; mean age: 66.6 years), 79% had ≥ 3 comorbidities. At baseline, SF-36 Physical functioning (SMD = - 0.75), Role physical (- 0.90), Social functioning (SMD = - 0.44), and Role emotional (SMD = - 0.45) were significantly worse than the norm. After CR, almost all scores significantly improved by ES = 0.23 (SCL-90R Interpersonal sensitivity) to 1.04 (SF-36 Physical functioning). The strongest factor (up to 41.1% explained variance) for health state and change was the mental health domain, followed by function & pain (up to 26.3%). CONCLUSIONS: Normative deficits in physical and psycho-social health were reported at baseline. After CR, at follow-up, all scores, except phobia, showed significant improvement. The comprehensive measurement of bio-psycho-social health should not be limited to depression and anxiety but include, especially, the somatization and social participation dimensions.

Catastrophizing as a prognostic factor for pain and physical function in the multidisciplinary rehabilitation of fibromyalgia and low back pain.

BACKGROUND: Quantitative data on longitudinal associations between catastrophizing and pain or physical function are patchy. The study aimed to quantify the prognostic value of catastrophizing for pain and function in fibromyalgia and low back pain before and after rehabilitation. METHODS: The associations of state and change on the Multidimensional Pain Inventory (MPI) Pain severity scale, the Short Form 36 (SF-36) Physical functioning scale and the Six-Minute Walking Distance (6MWD) with the Coping Strategies Questionnaire (CSQ) Catastrophizing scale were quantified by multiple regression modelling to adjust for confounders. RESULTS: Sex- and age-matched cohorts (n = 71 each) were compared. Pain and catastrophizing were worse in fibromyalgia than in low back pain, whereas the function levels were comparable. Baseline catastrophizing predicted pain change by adjusted correlations of 0.552 (fibromyalgia) and 0.450 (low back pain), self-rated function by 0.403 and 0.308, and the 6MWD by 0.270 and - 0.072. The change in catastrophizing was associated to the change in pain by 0.440 (fibromyalgia) and 0.614 (low back pain), self-rated function by 0.122 and 0.465, and the 6MWD by 0186 and 0.162. CONCLUSIONS: Catastrophizing (pain-related worrying) was a potential prognostic factor, especially for pain and somewhat less for self-rated physical function but it was only weakly predictive for the walking distance in both conditions, independently of potential confounders, such as sex, age, baseline severity and others. Reduction of maladaptive coping should be integrated into the management of chronic pain. SIGNIFICANCE: Our study showed surprisingly high associations between state and change in catastrophizing to pain relief and functional improvement in chronic pain patients. This is supported by clinical experience and research data, even if the construct and measurement of catastrophizing is under debate. Our findings and those of literature point to more pessimistic self-rating of pain and catastrophizing in fibromyalgia when compared to other conditions. This might obscure positive effects on pain and function achieved by adaptive coping in fibromyalgia.

Nonadiabatic Nano-optical Tunneling of Photoelectrons in Plasmonic Near-Fields.

Nonadiabatic nano-optical electron tunneling in the transition region between multiphoton-induced emission and adiabatic tunnel emission is explored in the near-field of plasmonic nanostructures. For Keldysh γ values between ∼1.3 and ∼2.2, measured photoemission spectra show strong-field recollision driven by the nanoscale near-field. At the same time, the photoemission yield shows an intensity scaling with a constant nonlinearity, which is characteristic for multiphoton-induced emission. Our observations in this transition region were well reproduced with the numerical solution of Schrödinger's equation, mimicking the nanoscale geometry of the field. This way, we determined the boundaries and nature of nonadiabatic tunneling photoemission, building on a key advantage of a nanoplasmonic system, namely, that high-field-driven recollision events and their signature in the photoemission spectrum can be observed more efficiently due to significant nanoplasmonic field enhancement factors.

Cluster Headache and the Comprehension Paradox.

Patients with primary headache disorders such as cluster headache cycle between being entirely healthy and almost completely incapacitated. Sick leave or reduced performance due to headache attacks demands flexibility by their social counterparts. The objective of this study is to test the hypothesis that headache patients cause frustration that grows with the times colleagues have to take over their work. In this study, we analysed cluster headache patients' answers to an online questionnaire. Participants self-reported their number of sick days, the number of days on which leisure activities were missed and whether they felt understood by colleagues and family. We then investigated the correlation between the number of sick days and the proportion of patients feeling understood by colleagues and friends. We found that feeling understood by colleagues and friends decreases with a growing number of sick days. However, when sick days accrue further, this proportion increases again. The number of sick days correlates similarly with both colleagues' and friends' understanding. The number of cluster headache patients feeling understood by others decreases with an increasing number of sick days. Their social circles' frustration with the patients' failure to meet obligations and expectations are a likely reason. With a growing number of sick days, however, the portion of patients feeling understood rises again despite patients meeting others' expectations even less. This 'comprehension paradox' implies the influence of other factors. We suspect that growing numbers of sick days foster understanding as the disability of the disease becomes increasingly apparent.

Efficacy and safety of exogenous beta-hydroxybutyrate for preventive treatment in episodic migraine: A single-centred, randomised, placebo-controlled, double-blind crossover trial.

BACKGROUND: Several studies propose that brain energy deficit might be partially involved in the pathophysiology of migraine. Previously, studies demonstrated that ketogenic diet causes a substantial reduction in migraine frequency. Since the ketogenic diet is restricting and its adherence is difficult, we proposed to supplement ketone bodies exogenously to provide a prophylactic effect in migraineurs. AIM: To evaluate the prophylactic effect of exogenous DL-beta-hydroxybutyrate supplementation in episodic migraineurs. METHODS: A double-blind, placebo-controlled, randomised crossover trial was conducted, involving 41 patients with episodic migraine. Patients were randomised 1:1 into placebo or beta-hydroxybutyrate group before entering the first treatment period. Each treatment period was 12 weeks long, followed by four weeks of washout phase and four weeks of run-in phase before entering into the corresponding second treatment period. The primary endpoint was the number of migraine days in the last four weeks of treatment, adjusted for baseline. RESULTS: We observed no clinically significant amelioration of migraine frequency or intensity under DL-beta-hydroxybutyrate treatment as compared to placebo regarding number of migraine days (mean difference [95% CI]: -1.1[-5.07, 2.85]), migraine intensity (0-10 VAS: 1.5[-0.8, 3.7]). CONCLUSION: The selected dose of supplemented exogenous DL-beta-hydroxybutyrate did not demonstrate efficacy in episodic migraineurs.ClinicalTrials.gov Identifier: NCT03132233.

Clinical features of migraine with onset prior to or during start of combined hormonal contraception: a prospective cohort study.

Many studies have described the features of menstrually related migraines but there is a lack of knowledge regarding the features of migraine in combined hormonal contraceptive users (CHC). Hormone-withdrawal migraines in the pill-free period could differ from those in the natural cycle. Gynaecologic comorbidities, like dysmenorrhea and endometriosis, but also depression or a family history might modify the course of migraine. A better understanding of migraine features linked to special hormonal situations could improve treatment. For this prospective cohort study, we conducted telephone interviews with women using a CHC and reporting withdrawal migraine to collect information on migraine frequency, intensity, triggers, symptoms, pain medication, gynaecologic history and comorbidities (n = 48). A subset of women agreed to also document their migraines in prospective diaries. The mean number of migraine days per cycle was 4.2 (± 2.7). Around 50% of these migraines occurred during the hormone-free interval. Migraine frequency was significantly higher in women who suffered from migraine before CHC start (5.0 ± 3.1) (n = 22) in comparison to those with migraine onset after CHC start (3.5 ± 2.1) (n = 26). Menstrually related attacks were described as more painful (57.5%), especially in women with migraine onset before CHC use (72%) (p < 0.02). Comorbidities were rare, except dysmenorrhea. The majority of migraine attacks in CHC users occur during the hormone-free interval. Similar as in the natural cycle, hormone-withdrawal migraines in CHC users are very intense and the response to acute medication is less good, especially in those women, who developed migraine before CHC use.

Detecting Incident Delirium within Routinely Collected Inpatient Rehabilitation Data: Validation of a Chart-Based Method.

BACKGROUND: Delirium is a brain condition associated with poor outcomes in rehabilitation. It is therefore important to assess delirium incidence in rehabilitation. PURPOSE: To develop and validate a chart-based method to identify incident delirium episodes within the electronic database of a Swiss rehabilitation clinic, and to identify a study population of validated incident delirium episodes for further research purposes. DESIGN: Retrospective validation study. SETTINGS: Routinely collected inpatient clinical data from ZURZACH Care. PARTICIPANTS: All patients undergoing rehabilitation at ZURZACH Care, Rehaklinik Bad Zurzach between 2015 and 2018 were included. METHODS: Within the study population, we identified all rehabilitation stays for which ≥2 delirium-predictive key words (common terms used to describe delirious patients) were recorded in the medical charts. We excluded all prevalent delirium episodes and defined the remaining episodes to be potentially incident. At least two physicians independently confirmed or refuted each potential incident delirium episode by reviewing the patient charts. We calculated the positive predictive value (PPV) with 95% confidence interval (95% CI) for all potential incident delirium episodes and for specific subgroups. RESULTS: Within 10,515 rehabilitation stays we identified 554 potential incident delirium episodes. Overall, 125 potential incident delirium episodes were confirmed by expert review. The PPV of the chart-based method varied from 0.23 (95% CI 0.19-0.26) overall to 0.69 (95% CI 0.56-0.79) in specific subgroups. CONCLUSIONS: Our chart-based method was able to capture incident delirium episodes with low to moderate accuracy. By conducting an additional expert review of the medical charts, we identified a study population of validated incident delirium episodes. Our chart-based method contributes towards an automated detection of potential incident delirium episodes that, supplemented with expert review, efficiently yields a validated population of incident delirium episodes for research purposes.

Tracking tDCS induced grey matter changes in episodic migraine: a randomized controlled trial.

BACKGROUND: Occipital transcranial direct current stimulation (tDCS) is an effective and safe treatment for migraine attack prevention. Structural brain alterations have been found in migraineurs in regions related to pain modulation and perception, including occipital areas. However, whether these structural alterations can be dynamically modulated through tDCS treatment is understudied. OBJECTIVE: To track longitudinally grey matter volume changes in occipital areas in episodic migraineurs during and up to five months after occipital tDCS treatment in a single-blind, and sham-controlled study. METHODS: 24 episodic migraineurs were randomized to either receive verum or sham occipital tDCS treatment for 28 days. To investigate dynamic grey matter volume changes patients underwent structural MRI at baseline (prior to treatment), 1.5 months and 5.5 months (after completion of treatment). 31 healthy controls were scanned with the same MRI protocol. Morphometry measures assessed rate of changes over time and between groups by means of tensor-based morphometry. RESULTS: Before treatment, migraineurs reported 5.6 monthly migraine days on average. A cross-sectional analysis revealed grey matter volume increases in the left lingual gyrus in migraineurs compared to controls. Four weeks of tDCS application led to a reduction of 1.9 migraine days/month and was paralleled by grey matter volume decreases in the left lingual gyrus in the treatment group; its extent overlapping with that seen at baseline. CONCLUSION: This study shows that migraineurs have increased grey matter volume in the lingual gyrus, which can be modified by tDCS. Tracking structural plasticity in migraineurs provides a potential neuroimaging biomarker for treatment monitoring. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03237754 . Registered 03 August 2017 - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03237754 .