Patient Clinical Measures Research Articles

Reliability of tele-assessment of five repetition sit to stand and timed up and go tests in patients with non-specific chronic low back pain

BackgroundTelerehabilitation has become a frequently preferred option in the follow-up and treatment processes of non-specific low back pain (NSLBP) in recent years. One of the most important components in the rehabilitation of patients with NSLBP is a comprehensive assessment. Physical performance assessments such as the Five Repetition Sit to Stand Test (5xSTS) and Timed Up and Go (TUG) stand out as tests often used in clinical measurements in patients with NSLBP.AimsThis study aimed to assess reliability of tele-assessment of 5xSTS and TUG tests in patients with NSLBP.MethodsPatients with NSLBP with low back pain for at least 3 months were included in the study. All tests were performed face-to-face and remotely. Intra-rater and inter-rater reliability were used to determine the intraclass correlation coefficients (ICCs).ResultsInter-rater reliability results between face-to-face and tele-assessment were excellent for both 5xSTS (ICC = 0.966) and TUG (ICC = 0.900). In addition, the intra-rater reliability results obtained between face-to-face and tele-assessment showed excellent for both 5xSTS (ICC = 0.979) and TUG (ICC = 0.958).ConclusionsThis study suggests that these tests can be used reliably at home or remotely in different settings as well as in the clinic.

The Effect of Telehealth-Based Rehabilitation on Patient Reported Outcomes and Objective Clinical Measurements in Patients With Degenerative Meniscal Tear

Aim: The study aimed to compare the effectiveness of telehealth-based home exercises and conventionally prescribed home exercises in patients with degenerative meniscal tears. Material and Method: A two-armed, randomized controlled study was conducted with 49 participants with degenerative meniscal disease. Patients were randomized into Telerehabilitation (TR=25) and Conventional Home Exercise Rehabilitation (CR=24) groups. The TR group provided video exercises and self-management education via an online platform. The same protocol was given to the CR group in the clinical setting. Pain with Visual Analog Scale, muscle strength with Hand-Held Dynamometer, proprioception with Baseline bubble inclinometer, functional status with Western Ontario and McMaster Universities Osteoarthritis Index, exercise adherence with Exercise Adherence Rating Scale, quality of life with Short Form-12 were evaluated at baseline and after eight weeks of intervention. In addition, satisfaction and usability were assessed with the Telemedicine Satisfaction and Usefulness Questionnaire at week 8. Results: The TR group improved activity pain, proprioception, some parameters of the muscle strength outcomes, and exercise adherence scores (p0.05). In addition, 52 percent of the TR group reported high levels of satisfaction and usability. Conclusion: Despite increased participation and satisfaction, the telerehabilitation group noticed improvements in clinician-based measures (proprioception, strength) but not in rest pain, function, and quality of life. As a result, telerehabilitation-based home exercises prescribed to these patient groups are more effective.

An Intervention Program Using the Health Belief Model to Modify Lifestyle in Coronary Heart Disease: Randomized Controlled Trial.

Most effective interventions to control coronary heart disease (CHD) and prevent negative outcomes involve behavioral modification. This study examined how such modification based on the Health Belief Model (HBM) might improve lifestyle and clinical outcomes. A total of 120 people with CHD seeking help at a general hospital in Iran were randomly assigned to either the intervention or control group. Information was collected using an HBM-specific questionnaire and the Health Promoting Lifestyle II (HPLP-II) scale. Clinical outcomes (blood pressure, body mass index, and fasting blood sugar) were also measured. The intervention group received a tailored education based on HBM principles plus routine care, while those in the control group received only routine care. Three months after the intervention, both groups were reassessed using Student's t test and analysis of covariance. All HBM subscale scores indicated significant improvements in the intervention group, in contrast to the control group, where scores worsened or stayed the same. Perceived severity and susceptibility were the dimensions that changed most. Total score on the HPLP-II improved significantly in the intervention group (p < 0.001, F = 747.5); however, subscale scores on spiritual growth and interpersonal relationships did not demonstrate significant between-group differences at follow-up. After adjustment for baseline scores, significant improvements in lifestyle subscales were also accompanied by significant improvements in clinical measures. This HBM-based behavior modification program improved both lifestyle and clinical measures in patients with CHD. Utilizing this program in patients with other cardiovascular diseases may in the future demonstrate similar results.

Cortico-basal ganglia networks dysfunction associated with disease severity in patients with idiopathic blepharospasm.

Structural changes occur in brain regions involved in cortico-basal ganglia networks in idiopathic blepharospasm (iBSP); whether these changes influence the function connectivity patterns of cortico-basal ganglia networks remains largely unknown. Therefore, we aimed to investigate the global integrative state and organization of functional connections of cortico-basal ganglia networks in patients with iBSP. Resting-state functional magnetic resonance imaging data and clinical measurements were acquired from 62 patients with iBSP, 62 patients with hemifacial spasm (HFS), and 62 healthy controls (HCs). Topological parameters and functional connections of cortico-basal ganglia networks were evaluated and compared among the three groups. Correlation analyses were performed to explore the relationship between topological parameters and clinical measurements in patients with iBSP. We found significantly increased global efficiency and decreased shortest path length and clustering coefficient of cortico-basal ganglia networks in patients with iBSP compared with HCs, however, such differences were not observed between patients with HFS and HCs. Further correlation analyses revealed that these parameters were significantly correlated with the severity of iBSP. At the regional level, the functional connectivity between the left orbitofrontal area and left primary somatosensory cortex and between the right anterior part of pallidum and right anterior part of dorsal anterior cingulate cortex was significantly decreased in patients with iBSP and HFS compared with HCs. Dysfunction of the cortico-basal ganglia networks occurs in patients with iBSP. The altered network metrics of cortico-basal ganglia networks might be served as quantitative markers for evaluation of the severity of iBSP.

Design and Development of Halyos: A Patient-Facing Visual EHR Interface for Longitudinal Risk Awareness

Abstract Objectives We have developed Halyos, a visual electronic health record (EHR) web application that complements existing patient portals. Halyos is designed to integrate with existing EHR systems to help patients interpret their health data. Methods The Halyos application utilizes the Substitutable Medical Applications and Reusable Technologies on Fast Healthcare Interoperability Resources (SMART on FHIR) platform to create an interoperable interface that provides interactive visualizations of clinically validated risk scores and longitudinal data derived from a patient's clinical measurements. Results These visualizations allow patients to investigate the relationships between clinical measurements and risk over time. Discussion By enabling patients to set hypothetical future values for these clinical measurements, patients can see how changes in their health will impact their risks. Conclusion Using Halyos, patients are provided with the opportunity to actively improve their health based on increased understanding of longitudinal information available in EHRs and to begin a dialogue with their providers.

0795 Association of Nasal and Sleep Apnea Clinical Measures

Abstract Introduction The association between nasal measures and polygsomnography measures is modest. However, nasal treatment can improve sleep quality in people without sleep apnea. The association of nasal and sleep apnea clinical measures in patients with sleep apnea is unknown. Our primary hypothesis is that the subjective nasal obstruction is associated with reduced sleep apnea-specific quality of life at baseline and with sleep apnea treatment after 6 months. Methods This prospective cohort study included patients with newly diagnosed sleep apnea who were prescribed CPAP. Data were collected before CPAP and 6 months later, including the validated Nasal Obstruction Symptom Evaluation (NOSE, range 0-100, higher worse) scale and validated Symptoms of Nocturnal Obstruction &amp; Related Events (SNORE-25, range 0-5, higher worse) quality of life instrument. Additional nasal measures, sleep apnea clinical measures, and covariates were collected. We tested the association between nasal and sleep apnea clinical measures with multivariate linear regression, adjusting for important confounding variables. Results The cohort (N=242) was middle-aged (47+/-12 years), included both sexes (65% men), and had severe sleep apnea (apnea-hypopnea index 33+/-24 events/hour). The baseline NOSE was strongly associated with SNORE-25, independent of demographics, comorbidity, and sleep apnea severity: beta 18, 95% CI 15-22, p&amp;lt;0.001, meaning for every unit of SNORE-25 increase there was an adjusted increase in NOSE score of 18. The 6-month changes in NOSE and SNORE-25 were strongly associated, independent of demographics, comorbidity, sleep apnea severity, and CPAP use: beta 17, 95%CI 13-22, p&amp;lt;0.001. Secondary nasal and sleep apnea clinical measures were associated, but nasal and polysomnography measures were not associated. Conclusion Nasal clinical measures are associated with sleep apnea clinical measures at baseline and with sleep apnea treatment, while the nasal measures are not associated with polysomnography measure. These data support the importance of the nasal airway on sleep apnea clinical outcomes. Support (If Any) R01 HL084139 (Weaver), T32 DC000018 (Stone), Seattle Veterans Affairs Medical Center

Item-Level Analysis of Clinical Measures in Patients With Early Symptomatic Alzheimer’s Disease Following Treatment With High-Dose Aducanumab in the Phase 3 EMERGE Study (P1-1.Virtual)

Item-Level Analysis of Clinical Measures in Patients With Early Symptomatic Alzheimer’s Disease Following Treatment With High-Dose Aducanumab in the Phase 3 EMERGE Study (P1-1.Virtual)

BOND study: a randomised double-blind, placebo-controlled trial over 12 months to assess the effects of benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes with symptomatic polyneuropathy

IntroductionDiabetic sensorimotor polyneuropathy (DSPN) affects approximately 30% of people with diabetes, while around half of cases are symptomatic. Currently, there are only few pathogenetically oriented pharmacotherapies for DSPN, one of...

Biomarkers associated with rhythm status after cardioversion in patients with atrial fibrillation

Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF). In this study we sought to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up. Significant between-group changes were observed for bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were − 10.4%, − 62.0% and − 25.6% in patients with sinus rhythm, and 3.1%, 1.1% and − 9.4% in patients with recurrent AF, for a between-group difference of − 13.5% (95% confidence interval [CI] − 19.3% to − 7.6%; P < 0.001), − 63.1% (95% CI − 76.6% to − 49.6%; P < 0.001) and − 16.3% (95% CI − 27.9% to − 4.7%; P = 0.007). In multivariable models, the reductions of BMP10 and NT-proBNP were significantly associated with follow-up rhythm status (β coefficient per 1 − SD decrease, − 3.85; 95% CI − 6.34 to − 1.35; P = 0.003 for BMP10 and − 5.84; 95% CI − 10.22 to − 1.47; P = 0.009 for NT-proBNP. In conclusion, changes in BMP10 und NT-proBNP levels were independently associated with rhythm status after cardioversion, suggesting that these markers may be dependent on the actual heart rhythm.

Item‐level analysis of clinical measures in patients with early symptomatic Alzheimer’s disease following treatment with high‐dose aducanumab in the phase 3 study EMERGE

AbstractBackgroundEMERGE (NCT02484547), 1 of 2 Phase 3 trials evaluating aducanumab in patients with early Alzheimer’s disease (AD), demonstrated a statistically significant drug‐placebo difference in the prespecified primary and secondary clinical endpoints. We examined in EMERGE participants the change from baseline item‐level scores in primary, secondary, and tertiary clinical endpoints that, in combination, comprised a set of cognitive, functional, and neuropsychiatric instruments that provide a comprehensive assessment of AD.MethodEMERGE (N=1643) included participants aged 50‐85 years who met clinical criteria for MCI due to AD or mild AD dementia, with confirmed amyloid pathology. Participants were randomized to receive high‐dose aducanumab, low‐dose aducanumab, or placebo. The primary endpoint was change from baseline in CDR‐SB score at Week 78. Secondary outcome measures included MMSE, ADAS‐Cog13, and ADCS‐ADL‐MCI scores. NPI‐10 score was a tertiary outcome. Item‐level analyses using mixed model for repeated measures (MMRM) were conducted on these clinical efficacy endpoints using the ITT population. This analysis is considered descriptive due to its deviation from the normality assumption and thus no multiplicity adjustment was considered.ResultThe aducanumab high‐dose group demonstrated a consistent drug‐placebo difference across 5 clinical efficacy endpoints, slowing clinical decline over 78 weeks. Treatment effects were observed across all 6 domains of the CDR. An aducanumab treatment effect was evident by slowing of decline on the ADAS‐Cog13 items sensitive to change in early symptomatic AD (e.g., orientation, word recall [immediate and delayed], word recognition, and number cancellation). Additionally, clinical benefit of aducanumab with respect to preserving daily function was observed across a broad range of items on the ADCS‐ADL‐MCI. Finally, aducanumab treatment was associated with an attenuation of behavioral and psychiatric symptoms associated with AD, as measured by NPI‐10, and an accompanying decrease in caregiver distress.ConclusionAducanumab treatment effects, observed across a broad array of outcome measures, are clinically relevant. Item‐level analyses demonstrated consistency across cognitive, function, and behavioral domains sensitive to impairments that are detectable even in the early stages of AD. Holistically, these measures reflect the perspectives of patients, caregivers, and clinicians, thereby supporting the importance and meaningfulness of an aducanumab treatment effect in early AD.

Abstract 9085: Phenome-Wide Association Study (phewas) Identifies Clinical Factors Associated With Plasma Ketones from Four Large Studies

Background: Ketosis is an adaptive mechanism to the stress imposed by cardiovascular disease, including heart failure (HF), with ketones constituting a more efficient myocardial fuel. Contributing factors to the development of ketosis and its association with adverse events have not been well studied. Methods: We performed a phenome-wide association study (PHeWAS) for serum ketone (beta-hydroxybutyrate [BHB]) levels in four cohorts with a total of 6,508 participants across a broad array of cardiovascular health, including CATHGEN (N=4,374), RELAX (N=161), TECOS (N=995), and EXSCEL(N=978). On cross-sectional analysis, we performed a random effects meta-analysis relating clinical and echocardiographic predictor variables to log transformed BHB using linear regression (with false discovery rate adjusted p-values). The relationship between BHB and HF metrics (HF history, ejection fraction, right ventricular systolic pressure [RSVP]) with markers of insulin resistance was assessed in each cohort. The association between BHB and death or HF hospitalization was assessed using Cox regression. Results: The mean age was 62 years, 36% female, and 75% white. Log BHB was associated with higher heart rate (beta-coefficient 0.009, p=0.001), HF (0.188, p=0.02), ejection fraction &lt; 55% (-0.138, p=0.008), RVSP (0.010, p=0.02), ischemic heart disease (-0.094, p=0.002), and statin use (-0.13, p=0.002). The association between HF phenotypes and BHB was not explained by markers of insulin resistance. Higher BHB levels were associated with increased risk for death and HF hospitalization ( Figure ), driven primarily by death. Conclusions: We identified several novel non-diabetic associations between ketosis and clinical measures in patients with cardiovascular disease. The link between ketosis and HF was independent of insulin resistance. BHB is a powerful predictor of outcomes, particularly death, across a spectrum of cardiovascular disease, including HF.

Ferric carboxymaltose in patients with pulmonary arterial hypertension and iron deficiency: a long‐term study

BackgroundPulmonary arterial hypertension (PAH) is a progressive disease with limited survival. Iron deficiency (ID) correlates with disease severity and mortality. While oral iron supplementation was shown to be insufficient in such patients, the potential impact of parenteral iron on clinical measures warrants further investigation.MethodsWe retrospectively analysed the long‐term effects of intravenous ferric carboxymaltose (FCM) on iron status and clinical measures in patients with PAH and ID [ferritin < 100 μg/L or ferritin 100–300 μg/L and transferrin saturation (TSAT) < 20%] who were on stable targeted PAH therapy, compared with matched controls without ID. Patients with ID received a single infusion of FCM (500 to 1000 mg). Clinical measures monitored included exercise capacity, World Health Organization (WHO) functional class, ESC/ERS risk status, and hospitalizations. The observation period was up to 18 months.ResultsOne hundred and seventeen patients (mean age 60.9 ± 16.1 years; 64.1% females) with confirmed PAH and on stable targeted therapy for ≥3 months were included (58 with and 59 patients without ID who did not receive FCM). In patients with ID, iron supplementation with FCM resulted in an immediate and sustained improvement of iron status for up to 18 months (serum iron, ferritin, TSAT, all P < 0.01). Fourteen patients in the FCM group received a second FCM infusion after 9.6 ± 4.8 months due to recurrent ID. At 6 and 18 months after FCM infusion, 6 min walk distance improved from 377.5 ± 15.9 at baseline to 412.5 ± 15.1 and 400.8 ± 14.5 m, respectively (both P < 0.05). WHO functional class (P < 0.05) and ESC/ERS risk status also improved, and there was a reduction of hospitalizations for worsening PAH in the 12 months post vs. prior to iron repletion (P = 0.029). No significant changes were observed in the control group. FCM was well tolerated in all patients, with no severe adverse events.ConclusionsIn addition to targeted therapy, correction of ID by parenteral iron supplementation with FCM appears feasible and safe, has sustained effects on iron status, and may improve the clinical status and hospitalization rates in patients with PAH. Larger controlled studies are required to confirm this finding.

ARTIFICIAL INTELLIGENCE MACHINE LEARNING MODELING TO PREDICT SINGLE EUPLOID BLASTOCYST TRANSFER OUTCOMES

An evidence-based algorithm for the probability of predicting successful live birth has significant clinical utility in counseling infertility patients regarding embryo transfer outcomes. Towards this objective, we examined an artificial intelligence (AI), machine learning classification model using patient clinical measurements and IVF cycle characteristics to assess the prognostic value in estimating treatment outcomes including live birth.

Effectiveness of delayed-release dimethyl fumarate on patient-reported outcomes and clinical measures in patients with relapsing-remitting multiple sclerosis in a real-world clinical setting: PROTEC.

BackgroundPatient-reported outcomes (PRO) and clinical outcomes give a broad assessment of relapsing–remitting multiple sclerosis (RRMS) disease.ObjectiveThe aim is to evaluate the effectiveness of delayed-release dimethyl fumarate (DMF) on disease activity and PROs in patients with RRMS in the clinic.MethodsPROTEC, a phase 4, open-label, 12-month observational study, assessed annualized relapse rate (ARR), proportion of patients relapsed, and changes in PROs. Newly diagnosed and early MS (≤3.5 EDSS and ≤1 relapse in the prior year) patient subgroups were evaluated.ResultsUnadjusted ARR at 12 months post-DMF versus 12 months before DMF initiation was 75% lower (0.161 vs. 0.643, p < 0.0001) overall (n = 1105) and 84%, 77%, and 71% lower in newly diagnosed, ≤3.5 EDSS, and ≤1 relapse subgroups, respectively. Overall, 88% of patients were relapse-free 12 months after DMF initiation (84%, newly diagnosed; 88%, ≤3.5 EDSS; 88%, ≤1 relapse). PRO measures for fatigue, treatment satisfaction, daily living, and work improved significantly over 12 months of DMF versus baseline.ConclusionAt 12 months after versus 12 months before DMF initiation, ARR was significantly lower, the majority of patients were relapse-free, and multiple PRO measures showed improvement (overall and for subgroups), suggesting that DMF is effective based on clinical outcomes and from a patient perspective.Clinical trial: A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes (PROTEC), NCT01930708, https://clinicaltrials.gov/ct2/show/NCT01930708.

Quantifying changes on susceptibility weighted images in amyotrophic lateral sclerosis using MRI texture analysis

Objective: Susceptibility-weighted imaging (SWI) has been used to identify neurodegeneration in amyotrophic lateral sclerosis (ALS) through qualitative gross visual comparison of signal intensity. The aim of this study was to quantitatively identify cerebral degeneration in ALS on SWI using texture analysis. Methods: SW images were acquired from 17 ALS patients (58.4 ± 10.3 years, 13M/4F, ALSFRS-R 41.2 ± 4.1) and 18 healthy controls (56.3 ± 17.6 years, 9M/9F) at 4.7 tesla. Textures were computed within the precentral gyrus and basal ganglia and compared between patients and controls using ANCOVA with age and gender as covariates. Texture features were correlated with clinical measures in patients. Texture features found to be significantly different between patients and controls in the precentral gyrus were then used in a whole-brain 3D texture analysis. Results: The texture feature autocorrelation was significantly higher in ALS patients compared to healthy controls in the precentral gyrus and basal ganglia (p < 0.05). Autocorrelation correlated significantly with clinical measures such as disease progression rate and finger tapping speed (p < 0.05). Whole brain 3D texture analysis using autocorrelation revealed differences between ALS patients and controls within the precentral gyrus on SWI images (p < 0.001). Conclusion: Texture analysis on SWI can quantitatively identify cerebral differences between ALS patients and controls.

A preliminary investigation of impulsivity, aggression and white matter in patients with bipolar disorder and a suicide attempt history

BackgroundImpulsivity and aggression may be associated with suicide attempts in bipolar disorder (BD), but findings have been inconsistent. Abnormalities in anterior white matter tracts that project to the frontal lobes mediate top-down regulation of emotion and may contribute to this clinical phenomenology. MethodsWe assessed white matter (i.e., fractional anisotropy) in anterior and posterior brain regions using diffusion tensor imaging in 18 patients with BD and no prior suicide attempt (BD-S), 12 patients with BD and a prior suicide attempt (BD+S), and 12 healthy volunteers. Patients completed the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency (UPPS-P) Impulsive Behavior Scale and Impulsive Premeditated Aggression Scale (IPAS). All individuals completed the Barratt Impulsiveness Scale (BIS-11). ResultsPatients with BD+S had higher overall impulsivity (assessed using both the UPPS-P Impulsive Behavior Scale and BIS-11) and premeditated aggression compared to patients with BD-S. There were no significant group differences on measures of fractional anisotropy (FA). In patients with BD+S, however, higher FA in the anterior (but not the posterior) brain regions correlated with greater overall impulsivity on the UPPS-P Impulsive Behavior Scale. There were no significant correlations between either anterior or posterior brain regions with clinical measures in patients with BD-S. LimitationsCross-sectional study, sample size and possible contribution of psychotropic medications. ConclusionImpulsivity and aggression may be risk factors for a suicide attempt in BD. White matter in the anterior limb of the internal capsule and anterior corona radiata may play a role in this phenomenology.

Short- to Mid-Term Outcomes Following the Use of an Arthroereisis Implant as an Adjunct for Correction of Flexible, Acquired Flatfoot Deformity in Adults.

The use of an arthroereisis implant for the treatment of adolescent flatfoot deformity has been described. However, data that address the outcomes of patients treated with an arthroereisis implant in adults are limited. The purpose of this study was to investigate the radiographic and clinical outcomes and complications following the use of a subtalar arthroereisis implant as an adjunct for correction acquired flatfoot deformity secondary to posterior tibial tendon dysfunction. A retrospective case-control study was performed querying all patients undergoing surgical flatfoot correction between January 1, 2010 and January 1, 2015. The experimental group included patients undergoing arthroereisis augmentation at the time of flatfoot correction. Patients undergoing the same flatfoot correction without the use of an arthroereisis implant were used as controls. Radiographic measurements were evaluated preoperatively and at final radiographic follow-up and included talonavicular (TN) coverage angle, and lateral talar-first metatarsal angle (T1MA). Patient-reported outcomes were assessed using preoperative visual analog scale (VAS) pain scores and postoperative Short Form-36, VAS, and satisfaction at final orthopedic follow-up. A total of 15 patients underwent flatfoot correction and were augmented with an arthroereisis implant and were matched with 30 controls. Postoperative, mid-term T1MA and regional analysis was found to be improved in the experimental group versus control. Patients undergoing adjunct subtalar arthroereisis demonstrated an increased likelihood of achieving radiographically normal talonavicular coverage <7° compared with our control group at follow-up. The adjunct use of an arthroereisis implant resulted in improved and maintained radiographic and clinical measurements in patients undergoing stage II flatfoot. These results suggest utility of a subtalar arthroereisis implant as an adjunct to flatfoot correction with little additional risk of harm to the patient. Level III: Case-control study.

Levels of Anti-Retinal Antibodies in Retinal Detachment and Proliferative Vitreoretinopathy

ABSTRACTPurpose: The purpose of the study is to investigate the correlation between intraocular anti-retinal antibodies and clinical measurements in patients with rhegmatogenous retinal detachment (RRD) and proliferative vitreoretinopathy (PVR).Material and methods: Aqueous humor and vitreous samples were collected from patients with RRD, PVR, and from control subjects with macular hole. The levels of total protein (TP), IgG, and anti-retinal antibodies were determined with a bicinchoninic acid assay, enzyme-linked immunosorbent assay, and dot blot, respectively. Correlations between these measurements were assessed using Pearson’s correlation test. Analysis of variance followed by a post-hoc test or the Student t-test was used to compare differences between groups.Results: The levels of anti-retinal antibodies and IgG were correlated with each other (P < 0.010). The IgG concentration was higher in patients with PVR than in controls in both the aqueous humor (P < 0.001) and the vitreous (P < 0.001), but not in patients with RRD. Conversely, TP levels and anti-retinal antibodies in both ocular fluids from RRD and PVR patients did not significantly differ from the controls. In a subgroup analysis, vitreal anti-retinal antibody levels were correlated with average macular thickness in the re-attached macula following surgery for macula-off RRD/PVR (P = 0.012). Furthermore, patients with post-operative cystoid macular edema had a higher level of vitreal anti-retinal antibodies than those without (P = 0.009).Conclusions: Intravitreal anti-retinal antibodies were increased in the eyes with maculopathy after surgical intervention for RRD/PVR.

EEG Reflection of Clinical Effects Dynamics during Botulinum Toxin Therapy of Movement Disorders under Long-Term Consciousness Disorders

When studying the dynamics of brain electric activity (BEA) in the course of botulinum toxin (Incobotulinumtoxin A) injections into all hypertonic muscles of 16 patients suffering from post-coma longterm consciousness disorders, BEA changes were observed to start within the first minutes after the first intramuscular injection of botulinum toxin, while not being associated with any pain stimulus response. Despite the diversity of brain lesions in these patients, the dynamics of BEA reorganisation during botulinum toxin therapy showed the presence of pathological sensorimotor integration involving the whole brain in case of long-term consciousness disorders. In our opinion, it is expressed in a pathological state developing in the brain, which affects the polyfunctional capabilities of neurons. This state is unbalanced due to destabilizing effect at the beginning of the reduction by pathological hyperafferentation from muscles and, in principle, can be disrupted at a complete reduction. It is, however, maintained by memory matrix, which manifests itself in the shape of oscillation process during its disruption when the newly build-up BEA is occasionally displaced by the previous one. During the reduction of sensory hyperafferentation, BEA reorganisation initially involved the motor cortex (in 15 out of 16 patients) and then spread to other brain areas, including those responsible for the higher mental functions, vision, and hearing. The first transiently decreased muscle tone (in all patients) and improvement of neurological signs of awareness (in some patients) were observed immediately after injecting all hypertonic muscles with widespread BEA changes. The appearance of high-frequency EEG activity in the frontal areas was considered as a universal marker of an improved functional state of the brain during the disruption of pathological sensorimotor integration even before clinical signs, suggesting neuronal readiness to maintain various activities. In view of data obtained, the first-stage clinical measures in patients with disorders of consciousness should focus on disrupting pathological sensorimotor integration, opening a way for restoring neuronal functional activity, provided that all “pathological afferents” are reduced.

Multiscale network representation of physiological time series for early prediction of sepsis

Objective and Approach: Sepsis, a dysregulated immune-mediated host response to infection, is the leading cause of morbidity and mortality in critically ill patients. Indices of heart rate variability and complexity (such as entropy) have been proposed as surrogate markers of neuro-immune system dysregulation with diseases such as sepsis. However, these indices only provide an average, one dimensional description of complex neuro-physiological interactions. We propose a novel multiscale network construction and analysis method for multivariate physiological time series, and demonstrate its utility for early prediction of sepsis. Main results: We show that features derived from a multiscale heart rate and blood pressure time series network provide approximately 20% improvement in the area under the receiver operating characteristic (AUROC) for four-hour advance prediction of sepsis over traditional indices of heart rate entropy ( versus ). Our results indicate that this improvement is attributable to both the improved network construction method proposed here, as well as the information embedded in the higher order interaction of heart rate and blood pressure time series dynamics. Our final model, which included the most commonly available clinical measurements in patients’ electronic medical records and multiscale entropy features, as well as the proposed network-based features, achieved an AUROC of . Significance: Prediction of the onset of sepsis prior to clinical recognition will allow for meaningful earlier interventions (e.g. antibiotic and fluid administration), which have the potential to decrease sepsis-related morbidity, mortality and healthcare costs.