Fluctuations In Severity Research Articles

Predicting land use dynamics, surface temperature and urban thermal field variance index in mild cold climate urban area of Pakistan

Rapid urbanization attributed to population growth is affecting the built environment's thermal and landscape dynamics. Using Landsat satellite datasets, this study investigated the complex interplay between urban Land Cover (LC) modification, fluctuation in Land Surface Temperature (LST) and severity of Urban Heat Island (UHI) from 1990 to 2020 in Peshawar City, Pakistan. Thermal bands were used to calculate LST and severity of UHI using the Urban Thermal Field Variance Index (UTFVI). Furthermore, through Cellular Automata (CA), Logistic Regression (LR), and Artificial Neural Network (ANN), future predictions on thermal characteristics associated with land use changes were made. The results showed that the urban areas expanded by ∼25 % from 1990 to 2020, while a ∼10 % decrease occurred in urban vegetation. The city is projected to expand by ∼45 % and ∼56 % in 2035 and 2050, respectively. Notably, the results also demonstrated that urban hotspots were found the warmest with the strongest UHI severity (∼34 °C), followed by the barren land (∼32 °C), and vegetation. The results further predicted an increase of LST (∼55 % and ∼82 %) and UTFVI (∼62 % and ∼83 %) in 2035 and 2050, respectively. These findings provide useful insights for policymakers and city planners to mitigate heat stress and create a sustainable urban environment through the development of effective urban land use policies and urban greening.

Intracranial Directed Connectivity Links Subregions of the Prefrontal Cortex to Major Depression.

Understanding the neural basis of major depressive disorder (MDD) is vital to guiding neuromodulatory treatments. The available evidence supports the hypothesis that MDD is fundamentally a disease of cortical disinhibition, where breakdowns of inhibitory neural systems lead to diminished emotion regulation and intrusive ruminations. Recent research also points towards network changes in the brain, especially within the prefrontal cortex (PFC), as primary sources of MDD etiology. However, due to limitations in spatiotemporal resolution and clinical opportunities for intracranial recordings, this hypothesis has not been directly tested. We recorded intracranial EEG from the dorsolateral (dlPFC), orbitofrontal (OFC), and anterior cingulate cortices (ACC) in neurosurgical patients with MDD. We measured daily fluctuations in self-reported depression severity alongside directed connectivity between these PFC subregions. We focused primarily on delta oscillations (1-3 Hz), which have been linked to GABAergic inhibitory control and intracortical communication. Depression symptoms worsened when connectivity within the left vs. right PFC became imbalanced. In the left hemisphere, all directed connectivity towards the ACC, from the dlPFC and OFC, was positively correlated with depression severity. In the right hemisphere, directed connectivity between the OFC and dlPFC increased with depression severity as well. This is the first evidence that delta oscillations flowing between prefrontal subregions transiently increase intensity when people are experiencing more negative mood. These findings support the overarching hypothesis that MDD worsens with prefrontal disinhibition.

Diurnal and Daily Symptom Variation in Patients with End Stage Kidney Disease: An Ecological Momentary Assessment Study.

Patients with end-stage kidney disease (ESKD) on hemodialysis (HD) experience a high symptom burden which is compounded by unpredictable fluctuations in symptom severity. Few studies have used ecological momentary assessment (EMA) to determine how symptoms vary over time. This study aimed to characterize the diurnal and day-to-day variability in symptoms among HD patients. Patients enrolled in the Technology Assisted Collaborative Care (TĀCcare) trial rated the intensity of physical, cognitive, and mood symptoms using an automated telephone-administered version of the Daytime Insomnia Symptom Scale (DISS) at four time-points (morning, early afternoon, late afternoon, evening) for seven consecutive days at baseline. Confirmatory factor analysis (CFA) was used to verify the original four-factor solution for the DISS: sleepiness/fatigue (SF), alert cognition (AC), positive mood (PM), and negative mood (NM). Symptom domain scores were calculated for each time point and mixed modeling with random patient effects was used to examine differences in daily symptoms daily time points between HD and non-HD days after controlling for age, gender, race, and comorbidity burden. One hundred and sixty patients were enrolled (mean±SD age 58±14 years, 45% women, 52% White). Diurnal symptom variation existed; trends were non-linear and differed by HD vs. non-HD days. Day-to-day symptom variation also existed; patients endorsed better physical, cognitive, and mood states (i.e., higher AC and PM) as well as lower symptom burden (i.e., lower SF and NM) on non-HD days compared to HD days at all time-points. The greatest day-to-day mean differences (MDs) were observed in the early afternoon for all symptom domains: AC (MD=0.17 p<0.001), PM (MD=0.28, p<0.001), SF (MD=-0.66, p<0.001), and NM (MD=-0.26, p<0.001). Patients with ESKD demonstrate diurnal variation in symptoms and greater symptom burden on HD days compared to non-HD days, with the most extreme differences in symptom severity occurring in the early afternoon.

Linguistic style as a digital marker for depression severity: An ambulatory assessment pilot study in patients with depressive disorder undergoing sleep deprivation therapy.

Digital phenotyping and monitoring tools are the most promising approaches to automatically detect upcoming depressive episodes. Especially, linguistic style has been seen as a potential behavioral marker of depression, as cross-sectional studies showed, for example, less frequent use of positive emotion words, intensified use of negative emotion words, and more self-references in patients with depression compared to healthy controls. However, longitudinal studies are sparse and therefore it remains unclear whether within-person fluctuations in depression severity are associated with individuals' linguistic style. To capture affective states and concomitant speech samples longitudinally, we used an ambulatory assessment approach sampling multiple times a day via smartphones in patients diagnosed with depressive disorder undergoing sleep deprivation therapy. This intervention promises a rapid change of affective symptoms within a short period of time, assuring sufficient variability in depressive symptoms. We extracted word categories from the transcribed speech samples using the Linguistic Inquiry and Word Count. Our analyses revealed that more pleasant affective momentary states (lower reported depression severity, lower negative affective state, higher positive affective state, (positive) valence, energetic arousal and calmness) are mirrored in the use of less negative emotion words and more positive emotion words. We conclude that a patient's linguistic style, especially the use of positive and negative emotion words, is associated with self-reported affective states and thus is a promising feature for speech-based automated monitoring and prediction of upcoming episodes, ultimately leading to better patient care.

Gut microbiota-based discovery of Houttuyniae Herba as a novel prebiotic of Bacteroides thetaiotaomicron with anti-colitis activity

Ulcerative colitis (UC) represents an inflammatory disease characterized by fluctuations in severity, posing substantial challenges in treatment. The gut microbiota plays a pivotal role in the pathogenesis of UC. This study sought to identify drugs specifically targeting the gut microbiota to mitigate UC. We initiated a meta-analysis on gut microbiota in UC patients to identify UC-associated bacterial strains. Subsequently, we screened 164 dietary herbal medicines in vitro to identify potential prebiotics for the UC-associated bacterium, Bacteroides thetaiotaomicron. The DSS-induced colitis mouse model was utilized to evaluate the anti-colitis efficacy of the identified dietary herbal medicine. Full-length 16 S rRNA amplicon sequencing was employed to observe changes in gut microbiota following dietary herbal medicine intervention. The relative abundance of Bacteroides was notably diminished in UC patients compared to their healthy counterparts. B. thetaiotaomicron exhibited an inverse relationship with UC symptoms, indicating its potential as an anti-colitis agent. In vitro assessments revealed that H. Herba significantly bolstered the proliferation of B. thetaiotaomicron. Further experiments showed that treating DSS-induced mice with an aqueous extract of H. Herba considerably alleviated colitis indicators such as weight loss, colon shortening, disease activity score (DAI), and systemic inflammation. Microbial analysis revealed B. thetaiotaomicron as the sole bacterium substantially augmented by H. Herba in vivo. Overall H. Herba emerges as a promising prebiotic for B. thetaiotaomicron, offering significant anti-colitis benefits. Employing a gut microbiota-centric approach proves valuable in the quest for drug discovery.This study provides a new paradigm for drug discovery that targets the gut microbiota to treat UC.

Intrainstitutional Changes of the Treatment of Supracondylar Humerus Fracture in Children over a Period of 9 Years.

To assess changes in treatment modalities for supracondylar humerus fractures (SCHFs) at a large pediatric university hospital, we analyzed patient data from 2014 to 2022. A total of 233 SCHFs treated surgically at our hospital were included. To evaluate postoperative outcome and quality of life, DASH and EuroQol-5D-Y questionnaires were sent to patients. In addition to a significant fluctuation in fracture severity, we found an increase in training interventions (more surgeries were performed by trainees) and a significant decrease in surgery times after 2016. From 2020, there was a significant shift in the type of surgical method away from closed reduction with elastic stable intramedullary nailing (ESIN) and towards closed reduction and crossed K-wire osteosynthesis (CRK). Surgeries performed in the morning and evening hours increased, while those performed in the afternoon and after midnight decreased. After a mean follow-up of 4 years, there was no difference in elbow function between ESIN and open reduction and K-wires (ORK). Treatment with ESIN was equivalent to ORK in terms of function, at least in the medium-term follow-up. In summary, the combination of shifting treatment from SCHF to daytime hours, increasing trainee participation and using cross K-wire fixation instead of ESIN had no negative impact on surgery times. In our setting, these measures have reduced resource utilization and increased efficiency without compromising patient care.

Use of the experience sampling method in adolescents with Duchenne muscular dystrophy: a feasibility study

Experience sampling methods (ESM) using mobile health (mHealth) technology with a smartphone application are increasingly used in clinical practice and research. Still, recommendations are limited in young people, and adaptations may be necessary. Patients with Duchenne muscular dystrophy (DMD) are chronically treated with steroids from a young age. However, the impact of intermittent treatment schedules on fluctuations in somatic, cognitive and behavioural symptoms is poorly investigated. Existing studies are often cross-sectional and occur in controlled clinical settings, which do not provide sufficiently detailed insights into possible correlations. ESM might alleviate these problems. ESM innovates data collection with a smartphone application, which repeatedly assesses specific symptoms and contextual factors at random moments in daily life. We aimed to evaluate its feasibility in adolescents with DMD. In three (without/with/without steroids) 4-day periods of ESM, that were nested in 10/10 or 11/9 day on/off-medication periods, we evaluated its user-friendliness and compliance, and explored its ability to objectify fluctuations in somatic, cognitive and behavioural symptom severity and their relationship with contextual factors in seven DMD patients (age range 12–18 years) using intermittent corticosteroid treatment (dosage range 0.3–0.6 mg/kg/day). Patients reported that ESM was convenient and user-friendly. We were able to capture extensive intra-individual symptom fluctuations during intermittent corticosteroid treatment that were not revealed by routine clinical assessment. Implementing ESM to evaluate symptom fluctuation patterns in relation to treatment effects shows promise in adolescents with DMD. Optimization in further research is needed.

What do people living with chronic pain want from a pain forecast? A research prioritization study.

Because people with chronic pain feel uncertain about their future pain, a pain-forecasting model could support individuals to manage their daily pain and improve their quality of life. We conducted two patient and public involvement activities to design the content of a pain-forecasting model by learning participants' priorities in the features provided by a pain forecast and understanding the perceived benefits that such forecasts would provide. The first was a focus group of 12 people living with chronic pain to inform the second activity, a survey of 148 people living with chronic pain. Respondents prioritized forecasting of pain flares (100, or 68%) and fluctuations in pain severity (94, or 64%), particularly the timing of the onset and the severity. Of those surveyed, 75% (or 111) would use a future pain forecast and 80% (or 118) perceived making plans (e.g., shopping, social) as a benefit. For people with chronic pain, the timing of the onset of pain flares, the severity of pain flares and fluctuations in pain severity were prioritized as being key features of a pain forecast, and making plans was prioritized as being a key benefit.

Adaptation to changes in COVID-19 pandemic severity: Across older adulthood and time scales.

The COVID-19 pandemic has been observed to negatively affect older adults' psychological health compared with prepandemic levels. However, older adults' coping efficacy may differ depending on their age, and little is known about effects of fluctuations in pandemic severity. Two longitudinal studies tested the hypothesis that pandemic severity would affect psychological health and be moderated by age. In Study 1 (N = 111), older adults (aged 62-96) were assessed semiannually before and after the first United States COVID-19 case over up to 10 years. Depressive symptoms and stress, but not cognitive difficulties, were higher during COVID-19; pandemic severity had little effect. Estimated increases were smaller for a 65-year-old than for an 85-year-old. In Study 2 (N = 221), older adults (aged 51-95) were assessed weekly over up to 8 weeks during the COVID-19 pandemic. Higher national pandemic severity was associated with more cognitive difficulties, more depressive symptoms, and more stress. In an opposite pattern from Study 1, estimated increases were larger for a 65-year-old than for an 85-year-old. Old-old adults might be most susceptible to long-term psychological effects of the pandemic era, as in Study 1, but more resilient to short-term effects, as in Study 2. Coping strategies associated with increasing age may be less efficacious for more chronic and severe problems. Conversely, the same coping strategies may be more efficacious for shorter, less severe problems. Differentiating between reactivity to longer term and shorter term pandemic stressors can identify the most resilient or vulnerable ages within older adulthood. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Circadian Regulation of Macrophages and Osteoclasts in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) represents one of the best examples of circadian fluctuations in disease severity. Patients with RA experience stiffness, pain, and swelling in afflicted joints in the early morning, which tends to become milder toward the afternoon. This has been primarily explained by the higher blood levels of pro-inflammatory hormones and cytokines, such as melatonin, TNFα, IL-1, and IL-6, in the early morning than in the afternoon as well as insufficient levels of anti-inflammatory cortisol, which rises later in the morning. Clinical importance of the circadian regulation of RA symptoms has been demonstrated by the effectiveness of time-of-day-dependent delivery of therapeutic agents in chronotherapy. The primary inflammatory site in RA is the synovium, where increased macrophages, T cells, and synovial fibroblasts play central roles by secreting pro-inflammatory cytokines, chemokines, and enzymes to stimulate each other, additional immune cells, and osteoclasts, ultimately leading to cartilage and bone erosion. Among these central players, macrophages have been one of the prime targets for the study of the link between circadian rhythms and inflammatory activities. Gene knockout experiments of various core circadian regulators have established that disruption of any core circadian regulators results in hyper- or hypoactivation of inflammatory responses by macrophages when challenged by lipopolysaccharide and bacteria. Although these stimulations are not directly linked to RA etiology, these findings serve as a foundation for further study by providing proof of principle. On the other hand, circadian regulation of osteoclasts, downstream effectors of macrophages, remain under-explored. Nonetheless, circadian expression of the inducers of osteoclastogenesis, such as TNFα, IL-1, and IL-6, as well as the knockout phenotypes of circadian regulators in osteoclasts suggest the significance of the circadian control of osteoclast activity in the pathogenesis of RA. More detailed mechanistic understanding of the circadian regulation of macrophages and osteoclasts in the afflicted joints could add novel local therapeutic options for RA.

The State Fear of Missing Out Inventory: Development and validation

Across the multitude of Fear of Missing Out (FoMO) research, the common notion is that FoMO is a dispositional trait which is generally stable over time. However, provided FoMO is conceptualized as a form of an anxiety regarding the concern one is absent from a rewarding experience, and how anxiety is quantified as both a state and trait, FoMO could also be studied as a behavioral state. Moreover, research has proposed situational factors, such as the level of entertainment one is currently experiencing, could influence the extent someone experiences FoMO at that moment. This in turn, suggests temporary fluctuations in FoMO severity occur and viewing FoMO merely as a trait is not adequate. To measure state FoMO, the State Fear of Missing Out Inventory (SFoMOI) was developed. Exploratory and confirmatory factor analyses were conducted and derived a one-factor unidimensional scale of 8 items. Support for convergent, discriminate, and criterion validity was found, and the SFoMOI was sensitive to detect differences in participants primed for the experience of FoMO and those who were not. Lastly, the measure had excellent internal reliability. Suggestions for future use and limitations of the SFoMOI are outlined.

Associations and Prognostic Significance of Fluctuations in Diabetic Retinopathy Severity in Eyes Treated for Diabetic Macular Edema

Introduction: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR). Methods: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses. Results: We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (β = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (β = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st–3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR. Conclusion: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early.

Conceptualising the episodic nature of disability among adults living with Long COVID: a qualitative study

IntroductionOur aim was to describe episodic nature of disability among adults living with Long COVID.MethodsWe conducted a community-engaged qualitative descriptive study involving online semistructured interviews and participant visual illustrations. We...

A library of quantitative markers of seizure severity.

Understanding fluctuations in seizure severity within individuals is important for determining treatment outcomes and responses to therapy, as well as assessing novel treatments for epilepsy. Current methods for grading seizure severity rely on qualitative interpretations from patients and clinicians. Quantitative measures of seizure severity would complement existing approaches to electroencephalographic (EEG) monitoring, outcome monitoring, and seizure prediction. Therefore, we developed a library of quantitative EEG markers that assess the spread and intensity of abnormal electrical activity during and after seizures. We analyzed intracranial EEG (iEEG) recordings of 1009 seizures from 63 patients. For each seizure, we computed 16 markers of seizure severity that capture the signal magnitude, spread, duration, and postictal suppression of seizures. Quantitative EEG markers of seizure severity distinguished focal versus subclinical seizures across patients. In individual patients, 53% had a moderate to large difference (rank sum , ) between focal and subclinical seizures in three or more markers. Circadian and longer term changes in severity were found for the majority of patients. We demonstrate the feasibility of using quantitative iEEG markers to measure seizure severity. Our quantitative markers distinguish between seizure types and are therefore sensitive to established qualitative differences in seizure severity. Our results also suggest that seizure severity is modulated over different timescales. We envisage that our proposed seizure severity library will be expanded and updated in collaboration with the epilepsy research community to include more measures and modalities.

Predictors of suicidal ideation severity among treatment-seeking young people with major depressive disorder: The role of state and trait anxiety.

Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy. Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants (N = 283) were 15-25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use. Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use. Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression.

Relationship between daily rated depression symptom severity and the retrospective self-report on PHQ-9: A prospective ecological momentary assessment study on 80 psychiatric outpatients

BackgroundDepression-related negative bias in emotional processing and memory may bias accuracy of recall of temporally distal symptoms. We tested the hypothesis that when responding to the Patient Health Questionnaire (PHQ-9) the responses reflect more accurately temporally proximal than distal mood states. MethodsCurrently, depressed psychiatric outpatients (N = 80) with depression confirmed in semi-structured interviews had the Aware application installed on their smartphones for ecological momentary assessment (EMA). The severity of “low mood”, “hopelessness”, “low energy”, “anhedonia”, and “wish to die” was assessed on a Likert scale five times daily during a 12-day period, and thereafter, the PHQ-9 questionnaire was completed. We used auto- and cross-correlation analyses and linear mixed-effects multilevel models (LMM) to investigate the effect of time lag on the association between EMA of depression symptoms and the PHQ-9. ResultsAutocorrelations of the EMA of depressive symptom severity at two subsequent days were strong (r varying from 0.7 to 0.9; p < 0.001). “Low mood” was the least and “wish to die” the most temporally stable symptom. The correlations between EMA of depressive symptoms and total scores of the PHQ-9 were temporally stable (r from 0.3 to 0.6; p < 0.001). No effect of assessment time on the association between EMA data and the PHQ-9 emerged in the LMM. LimitationsAltogether 11.5 % of observations were missing. ConclusionsDespite fluctuations in severity of some of the depressive symptoms, patients with depression accurately recollect their most dominant symptoms, without a significant recall bias favouring the most recent days, when responding to the PHQ-9.

Dual-site transcranial direct current stimulation to treat tinnitus: a randomized controlled trial.

Transcranial direct current stimulation (tDCS) has been proposed as a potential intervention for subjective tinnitus, but supporting evidence remains limited. We aimed to investigate the effect of anodal high-definition tDCS of the left temporal area and right dorsolateral prefrontal cortex on tinnitus severity. This double-blind randomized controlled trial included 77 patients (age range 18-79, 43 male) with chronic subjective tinnitus as their primary complaint. Thirty-eight subjects received six consecutive sessions of dual-site sequential high-definition-tDCS with electrodes positioned over the left temporal area and right dorsolateral prefrontal cortex. Both areas were stimulated for 15 min per session, with total stimulation time amounting to 30 min. Thirty-nine subjects received sham stimulation. The primary outcome measure was the change in tinnitus severity, as evaluated by the Tinnitus Functional Index, from baseline to a follow-up visit at 8 ± 2 weeks after treatment completion. Secondary outcomes included changes in perceived tinnitus loudness, as measured with a visual analogue scale and a tinnitus matching procedure, as well as scores on the Hospital Anxiety and Depression Scale, and the Hyperacusis Questionnaire. No differences in Tinnitus Functional Index change scores were identified between the active treatment and sham control groups (linear regression: P = 0.86). The Tinnitus Functional Index scores decreased significantly over time in both groups (P = 0.0012), indicating the presence of a considerable placebo effect. These change scores were significantly influenced by sex (linear regression: P = 0.037) and baseline symptoms of anxiety (linear regression: P = 0.049) in both groups. In general, Tinnitus Functional Index scores decreased more profoundly in males and in subjects with a higher degree of anxiety at baseline. None of the included secondary measures differed significantly between experimental arms. Our results suggest that dual-site sequential high-definition-tDCS of the left temporal area and right dorsolateral prefrontal cortex does not alleviate tinnitus severity. Interestingly, in our study population, fluctuations in tinnitus severity were influenced by gender and concurrent mental condition. It is therefore important to take these factors into account when conducting or planning randomized controlled trials in tinnitus populations.

Understanding the Symptom Burden and Impact of Myasthenia Gravis from the Patient's Perspective: A Qualitative Study.

Patients with generalized myasthenia gravis (gMG) experience functional impairment due to MG symptoms. This study aimed to assess, from the patient perspective, the symptoms, impacts, and treatment goals of individuals diagnosed with gMG. Semi-structured, in-depth concept-elicitation interviews were conducted with 28 individuals diagnosed with gMG in the United States. Participants reported gMG symptoms that affected many body regions and functions, with an average of 16 symptoms per participant. The most frequently reported symptoms were eyelid drooping (93%), physical fatigue (89%), symptoms affecting the legs (82%), difficulty breathing (82%), and difficulty holding head up (82%). Nearly all participants (96%) reported fluctuations in symptoms and severity. Participants' most bothersome symptoms were blurry/double vision (43%), breathing difficulties (36%), all-over fatigue (36%), and swallowing problems (29%). Impacts on physical functioning included an inability to participate in hobbies/sports, need for increased planning, and difficulties performing activities of daily living. All participants reported emotional impacts and impacts on their work and finances. Their treatment goals included reduced fatigue and weakness, improved symptom stability, and minimization of the impact of symptoms, in particular the emotional impact. The fluctuating and unpredictable nature of gMG symptoms was found to have a substantial impact on patients' emotional, social, and economic well-being. Participants' goals for symptom management suggest that greater focus is needed to help them quickly resume a normal lifestyle by achieving symptom stability. Impacts of fluctuating and unpredictable symptoms are difficult to measure, but it is important to consider symptom fluctuation as well as ongoing symptomatology when making treatment decisions, and to recognize the impact of uncontrolled symptoms on patients, their partners/caregivers, and family/friends. These factors are often not reflected in burden/cost-of-illness studies.

A systematic review of local field potential physiomarkers in Parkinson’s disease: from clinical correlations to adaptive deep brain stimulation algorithms

Deep brain stimulation (DBS) treatment has proven effective in suppressing symptoms of rigidity, bradykinesia, and tremor in Parkinson’s disease. Still, patients may suffer from disabling fluctuations in motor and non-motor symptom severity during the day. Conventional DBS treatment consists of continuous stimulation but can potentially be further optimised by adapting stimulation settings to the presence or absence of symptoms through closed-loop control. This critically relies on the use of ‘physiomarkers’ extracted from (neuro)physiological signals. Ideal physiomarkers for adaptive DBS (aDBS) are indicative of symptom severity, detectable in every patient, and technically suitable for implementation. In the last decades, much effort has been put into the detection of local field potential (LFP) physiomarkers and in their use in clinical practice. We conducted a research synthesis of the correlations that have been reported between LFP signal features and one or more specific PD motor symptoms. Features based on the spectral beta band (~ 13 to 30 Hz) explained ~ 17% of individual variability in bradykinesia and rigidity symptom severity. Limitations of beta band oscillations as physiomarker are discussed, and strategies for further improvement of aDBS are explored.

Optimizing Obsessive-Compulsive Symptom Measurement With the Yale-Brown Obsessive-Compulsive Scales-Second Edition.

The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a widely used measure for assessing the presence and severity of obsessive-compulsive disorder symptoms. The Yale-Brown Obsessive-Compulsive Scale-Second Edition (Y-BOCS-II) was developed, in part, to more comprehensively evaluate symptom severity, especially in extremely ill patients, and improve consistency in detecting and incorporating avoidance behaviors. We present 3 case studies that demonstrate the enhanced ability of the Y-BOCS-II to: (1) detect fluctuations in symptom severity among extremely ill patients, (2) systematically incorporate avoidance variables for more accurate ratings, and (3) maintain strong convergence with the Y-BOCS in assessing patients presenting with mild to moderate symptoms. In addition, we outline how to obtain both Y-BOCS and Y-BOCS-II scores within 1 administration by adding Y-BOCS item 4 to the Y-BOCS-II assessment, then "back-coding" the Y-BOCS-II ratings to Y-BOCS ratings and using Y-BOCS item 4 in place of Y-BOCS-II item 2. The use of this method allows for more robust data collection while providing comparability across the literature.