Diagnosis of Sports-Related Concussion Using Symptom Report or Standardized Assessment of Concussion.

Importance: The Sports Concussion Assessment Tool-5 (SCAT5) has been recommended for concussion evaluation and utilizes both a subjective reported symptom grading scale and objective measures of concussion including a cognitive evaluation: the Standardized Assessment of Concussion (SAC). The SAC includes testing for orientation, immediate memory, concentration, and delayed recall; a 10-word list is used to assess immediate memory and delayed recall. Objective: To determine the diagnostic accuracy of components of the SCAT5 and to provide a framework for clinical interpretation. Design, Setting, and Participants: This prospective case-control study of National Collegiate Athletic Association Division I athletes from any sport was conducted from July 2020 to December 2022 at 4 universities. Athletes completed baseline SCAT5 testing using the 10-word list. When an athlete presented acutely with suspected concussion (sideline or within 2 days), the tests were repeated. If a concussion was diagnosed, a control athlete underwent the same tests. Controls were identified and matched on comorbid conditions, sex and gender, sport, season, and baseline scores. Data analysis was conducted from August to October 2023. Main Outcomes and Measures: The primary outcomes were area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive and negative predictive value, and test-retest reliability of the symptom score; symptom severity score; the total SAC score; and the orientation, immediate memory, concentration, and delayed memory subcomponent scores on the SCAT5 compared with clinical diagnosis of concussion. Results: Baseline and postinjury data were collected on 92 athletes with concussion and 92 matched control athletes (96 men [52%] and 88 women [48%]; 110 who played a sport other than football [59%]). Diagnostic utility was considered excellent for symptom score (AUC, 0.93; 95% CI, 0.89-0.96) and symptom severity score (AUC, 0.94; 95% CI, 0.90-0.97). An increase of 2 points on the symptom score was associated with a sensitivity of 86% (95% CI, 78%-92%), specificity of 80% (95% CI, 70%-87I%), and positive predictive value of 81% (95% CI, 72%-88%). The total SAC score had poor to fair diagnostic utility (AUC, 0.70; 95% CI, 0.63-0.77); however, 41 athletes with concussion (45%) had a total SAC score at or above their baseline score (ie, within normal limits). The diagnostic utility was poor to fair for immediate memory (AUC, 0.68, 95%CI, 0.61-0.75) and delayed recall (AUC, 0.69; 95% CI, 0.62-0.77) and not useful for orientation (AUC, 0.49; 95% CI, 0.43-0.56) and concentration (AUC, 0.52 95% CI, 0.44-0.61). Test-retest reliability was fair for total SAC and poor for immediate memory and delayed recall, orientation, and concentration. Conclusions and Relevance: In this case-control study of the diagnostic accuracy of reported symptoms and the SAC, reported symptoms were the most accurate indicator of concussion while the 10-word SAC had limited sensitivity. These findings suggest that understanding the properties of the SAC is important when making the diagnosis of concussion.

Investigating the Impact of Polypharmacy and Anticholinergic Medication Burden on Objective Cognitive Performance in Adults With Multiple Sclerosis.

BACKGROUND: Polypharmacy, or the use of 5 or more daily medications, is common in adults with multiple sclerosis (MS), and is often due to various physical, cognitive, and emotional symptoms. However, research regarding the association between polypharmacy and cognitive outcomes in MS is sparse. Furthermore, individuals with MS often use medications with anticholinergic properties, which are commonly associated with cognitive impairment and other central nervous system adverse effects. Currently, the utility of scales measuring anticholinergic burden in MS is unknown. This study aims to investigate the relationship between polypharmacy, anticholinergic burden, and objective cognitive performance in MS. METHODS: We recruited 90 individuals with MS during routine visits at an MS specialty clinic in Kansas City. Participants completed a brief, virtual cognitive assessment and answered questions about their health. Participants provided their medication lists from which we determined polypharmacy and scores on several anticholinergic burden scales. Statistical analyses included Spearman correlations and linear regression models. RESULTS: Approximately 44% of the individuals surveyed met the criteria for polypharmacy. The number of daily medications was negatively correlated with cognitive performance (rs = -0.45, P < .001). Further, the Drug Burden Index accounted for additional variance in cognitive performance beyond that explained by age, education, MS disease duration, and comorbidities [ΔR2 = .12, F(5, 84) = 7.84, P < .001.]. CONCLUSIONS: Clinicians should consider the possible negative consequences of polypharmacy when addressing cognitive concerns in MS. Anticholinergic burden scales may be valuable in this regard. Future investigations could explore behavioral and pharmacological interventions aimed at reducing polypharmacy in MS.

The Influence of Mesoscopic Surface Structure on the Electrocatalytic Selectivity of CO2 Reduction with UHV-Prepared Cu(111) Single Crystals.

The key role of morphological defects (e.g., irregular steps and dislocations) on the selectivity of model Cu catalysts for the electrocatalytic reduction of CO2 (CO2RR) is illustrated here. Cu(111) single-crystal surfaces prepared under ultrahigh vacuum (UHV) conditions and presenting similar chemical and local microscopic surface features were found to display different product selectivity during the CO2RR. In particular, changes in selectivity from hydrogen-dominant to hydrocarbon-dominant product distributions were observed based on the number of CO2RR electrolysis pretreatment cycles performed prior to a subsequent UHV surface regeneration treatment, which lead to surfaces with seemingly identical chemical composition and local crystallographic structure. However, significant mesostructural changes were observed through a micron-scale microscopic analysis, including a higher density of irregular steps on the samples producing hydrocarbons. Thus, our findings highlight that step edges are key for C-C coupling in the CO2RR and that not only atomistic but also mesoscale characterization of electrocatalytic materials is needed in order to comprehend complex selectivity trends.

Association between frailty and sleep quality in people living with multiple sclerosis and obesity: An observational cross-sectional study.

BACKGROUND: A majority of the people with multiple sclerosis (pwMS) experience sleep disturbances. Frailty is also common in pwMS. The geriatric literature strongly suggests that frailty is associated with worse sleep outcomes in community-dwelling older adults, but this association has yet to be explored among pwMS. This study focused on examining the association between frailty and sleep quality in pwMS. METHODS: Seventy-six people with both MS and obesity (mean age: 47.6 ± 10.9 years, 81.6 % female, mean body mass index (BMI): 37.10 ± 5.5 kg/m2, mean Patient Determined Disease Steps (PDDS): 0.82 ± 1.20) were included in this cross-sectional secondary analysis. A comprehensive frailty index (FI) based on 41 health deficits from various health domains was calculated based on standardized procedures. Sleep quality was determined by the Pittsburgh Sleep Quality Index questionnaire (PSQI). RESULTS: Overall, 67.1 % of the participants were identified as non-frail (FI ≤ 0.25), and 32.9 % were identified as frail (FI > 0.25). A significant correlation was observed between FI scores and global PSQI scores (ρ = 0.43, p < 0.05). Cross-tabulation analyses revealed that frail participants had worse subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and higher use of sleep medications compared to non-frail participants (p < 0.05). CONCLUSIONS: The current study identified a significant association between frailty and sleep quality in people with both MS and obesity with minimal disability. These findings underscore the importance of untangling the relationship between frailty and sleep quality in pwMS. These results could lead to a more targeted approach for rehabilitation interventions aiming to improve frailty in MS.

Concussion Characteristics in the National Hockey League Before and After the Introduction of Rule 48.

Importance: A rule prohibiting a direct hit to the lateral side of the head (ie, Rule 48-Illegal Check to the Head) was introduced in the National Hockey League (NHL) in the 2010-2011 season and refined in the 2011-2012 season to widen the application to include direct contact to all areas of the head. Objective: To compare the incidence and proportion of concussions that occurred following hits to the head before and after the implementation of Rule 48. Design, Setting, and Participants: This retrospective cohort study used a before and after design to evaluate concussions among NHL players in regular season games. Data from the 4 seasons preceding the implementation of Rule 48 (2006-2007 to 2009-2010) were compared with data from 5 seasons following its implementation (2014-2015 to 2018-2019). Data were analyzed from October 31, 2021, to November 30, 2022. Main Outcomes and Measures: The incidence and relative proportion of concussion characteristics and mechanisms before and after the introduction of Rule 48. Results: In the analysis of 688 concussions for NHL seasons spanning 2006 to 2010 (n = 231) and 2014 to 2019 (n = 457), there was an overall increase in the incidence of concussion between the 2 time frames, although the incidence of concussions due to hits to the lateral aspect of the head decreased from 1.6/100 games to 1.0/100 games (estimated difference, 0.6/100 games [90% credible interval (CrI), 0.30/100 games to 0.90/100 games). There was also a reduction of 18.8 (90% CrI, 13.0-23.7) percentage points in the proportion of concussions due to hits to the lateral aspect of the head from 80 of 231 concussions (34.6%) to 61 of 457 concussions (13.3%). The incidence of concussions following hits to the head from body checks using the shoulder, arm, and glove was similar before and following the implementation of Rule 48. However, the proportion was reduced 14.7 percentage points from 113 of 231 concussions (48.9%) before to 149 of 457 concussions (32.6%) after implementation of Rule 48 (90% CrI of the difference, 8.9-20.7 percentage points). Conclusions and Relevance: The findings of this cohort study of NHL players suggest that after the introduction of Rule 48, the incidence rate and proportion of concussions from contact to the lateral aspect of the head decreased, as did the proportion of concussions following direct hits to the head.

Modifying diet and exercise in multiple sclerosis (MoDEMS): A randomized controlled trial for behavioral weight loss in adults with multiple sclerosis and obesity.

BACKGROUND: Obesity is a risk factor for developing multiple sclerosis (MS) and MS-related disability. The efficacy of behavioral weight loss interventions among people with MS (pwMS) remains largely unknown. OBJECTIVE: Examine whether a group-based telehealth weight loss intervention produces clinically significant weight loss in pwMS and obesity. METHODS: Seventy-one pwMS were randomized to the weight loss intervention or treatment-as-usual (TAU). The 6-month program promoted established guidelines for calorie reduction and increased physical activity. Anthropometric measurements, mobility tasks, self-report questionnaires, and accelerometry were used to assess changes at follow-up. RESULTS: Mean percent weight loss in the treatment group was 8.6% compared to 0.7% in the TAU group (p < .001). Sixty-five percent of participants in the intervention achieved clinically meaningful weight loss (⩾ 5%). Participants in the treatment group engaged in 46.2 minutes/week more moderate-to-vigorous physical activity than TAU participants (p = .017) and showed improvements in quality of life (p = .012). Weight loss was associated with improved mobility (p = .003) and reduced fatiguability (p = .008). CONCLUSION: Findings demonstrate the efficacy of a behavioral intervention for pwMS and obesity, with clinically significant weight loss for two-thirds of participants in the treatment condition. Weight loss may also lead to improved mobility and quality of life.

A pilot study evaluating the prefeasibility of a behavioral weight loss program in people with multiple sclerosis.

Weight loss interventions seldom include individuals with neurologic disease. The aims of the present study were to: 1) develop and assess the prefeasibility of a 6-month telehealth behavioral weight loss program for people with multiple sclerosis (MS) and obesity and 2) examine changes in weight loss (primary outcome), physical activity, and fruit/vegetable consumption at follow-up. Participants with obesity and MS engaged in a 24-week weight loss program. Participants followed established diet, exercise, and self-monitoring guidelines and attended weekly online group meetings. Median percentage weight loss was 10.54 % (SD = 7.19). Participants who adhered more closely to the self-monitoring guidelines (r = 0.81, p =.02), and who averaged higher weekly active minutes (r = 0.91, p =.002) achieved greater percentage weight loss. Six of the eight pilot participants achieved clinically meaningful weight loss (>5%) after 6-months.

Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and mortality. Despite its clinical relevance, there are few treatment options for depression associated with multiple sclerosis and confirmatory trials are scarce. We aimed to evaluate the safety and efficacy of a multiple sclerosis-specific, internet-based cognitive behavioural therapy (iCBT) programme for the treatment of depressive symptoms associated with the disease. METHODS: This parallel-group, randomised, controlled, phase 3 trial of an iCBT programme to reduce depressive symptoms in patients with multiple sclerosis was carried out at five academic centres with large outpatient care units in Germany and the USA. Patients with a neurologist-confirmed diagnosis of multiple sclerosis and depressive symptoms were randomly assigned (1:1:1; automated assignment, concealed allocation, no stratification, no blocking) to receive treatment as usual plus one of two versions of the iCBT programme Amiria (stand-alone or therapist-guided) or to a control condition, in which participants received treatment as usual and were offered access to the iCBT programme after 6 months. Masking of participants to group assignment between active treatment and control was not possible, although raters were masked to group assignment. The predefined primary endpoint, which was analysed in the intention-to-treat population, was severity of depressive symptoms as measured by the Beck Depression Inventory-II (BDI-II) at week 12 after randomisation. This trial is registered at ClinicalTrials.gov, NCT02740361, and is complete. FINDINGS: Between May 3, 2017, and Nov 4, 2020, we screened 485 patients for eligibility. 279 participants were enrolled, of whom 101 were allocated to receive stand-alone iCBT, 85 to receive guided iCBT, and 93 to the control condition. The dropout rate at week 12 was 18% (50 participants). Both versions of the iCBT programme significantly reduced depressive symptoms compared with the control group (BDI-II between-group mean differences: control vs stand-alone iCBT 6·32 points [95% CI 3·37-9·27], p<0·0001, effect size d=0·97 [95% CI 0·64-1·30]; control vs guided iCBT 5·80 points [2·71-8·88], p<0·0001, effect size d=0·96 [0·62-1·30]). Clinically relevant worsening of depressive symptoms was observed in three participants in the control group, one in the stand-alone iCBT group, and none in the guided iCBT group. No occurrences of suicidality were observed during the trial and there were no deaths. INTERPRETATION: This trial provides evidence for the safety and efficacy of a multiple sclerosis-specific iCBT tool to reduce depressive symptoms in patients with the disease. This remote-access, scalable intervention increases the therapeutic options in this patient group and could help to overcome treatment barriers. FUNDING: National Multiple Sclerosis Society (USA).

Dysfunction of basal ganglia functional connectivity associated with subjective and cognitive fatigue in multiple sclerosis.

Objectives: Central fatigue is one of the most common symptoms in multiple sclerosis (MS). It has a profound impact on quality of life and a negative effect on cognition. Despite its widespread impact, fatigue is poorly understood and very difficult to measure. Whilst the basal ganglia has been implicated in fatigue the nature of its role and involvement with fatigue is still unclear. The aim of the present study was to establish the role of the basal ganglia in MS fatigue using functional connectivity measures. Methods: The present study examined the functional connectivity (FC) of the basal ganglia in a functional MRI study with 40 female participants with MS (mean age = 49.98 (SD = 9.65) years) and 40 female age-matched (mean age = 49.95 (SD = 9.59) years) healthy controls (HC). To measure fatigue the study employed the subjective self-report Fatigue Severity Scale and a performance measure of cognitive fatigue using an alertness-motor paradigm. To distinguish physical and central fatigue force measurements were also recorded. Results: The results suggest that decreased local FC within the basal ganglia plays a key role in cognitive fatigue in MS. Increased global FC between the basal ganglia and the cortex may sub serve a compensatory mechanism to reduce the impact of fatigue in MS. Conclusion: The current study is the first to show that basal ganglia functional connectivity is associated with both subjective and objective fatigue in MS. In addition, the local FC of the basal ganglia during fatigue inducing tasks could provide a neurophysiological biomarker of fatigue.

Acute evaluation of sport-related concussion and implications for the Sport Concussion Assessment Tool (SCAT6) for adults, adolescents and children: a systematic review.

OBJECTIVES: To systematically review the scientific literature regarding the acute assessment of sport-related concussion (SRC) and provide recommendations for improving the Sport Concussion Assessment Tool (SCAT6). DATA SOURCES: Systematic searches of seven databases from 2001 to 2022 using key words and controlled vocabulary relevant to concussion, sports, SCAT, and acute evaluation. ELIGIBILITY CRITERIA: (1) Original research articles, cohort studies, case-control studies, and case series with a sample of >10; (2) ≥80% SRC; and (3) studies using a screening tool/technology to assess SRC acutely (<7 days), and/or studies containing psychometric/normative data for common tools used to assess SRC. DATA EXTRACTION: Separate reviews were conducted involving six subdomains: Cognition, Balance/Postural Stability, Oculomotor/Cervical/Vestibular, Emerging Technologies, and Neurological Examination/Autonomic Dysfunction. Paediatric/Child studies were included in each subdomain. Risk of Bias and study quality were rated by coauthors using a modified SIGN (Scottish Intercollegiate Guidelines Network) tool. RESULTS: Out of 12 192 articles screened, 612 were included (189 normative data and 423 SRC assessment studies). Of these, 183 focused on cognition, 126 balance/postural stability, 76 oculomotor/cervical/vestibular, 142 emerging technologies, 13 neurological examination/autonomic dysfunction, and 23 paediatric/child SCAT. The SCAT discriminates between concussed and non-concussed athletes within 72 hours of injury with diminishing utility up to 7 days post injury. Ceiling effects were apparent on the 5-word list learning and concentration subtests. More challenging tests, including the 10-word list, were recommended. Test-retest data revealed limitations in temporal stability. Studies primarily originated in North America with scant data on children. CONCLUSION: Support exists for using the SCAT within the acute phase of injury. Maximal utility occurs within the first 72 hours and then diminishes up to 7 days after injury. The SCAT has limited utility as a return to play tool beyond 7 days. Empirical data are limited in pre-adolescents, women, sport type, geographical and culturally diverse populations and para athletes. PROSPERO REGISTRATION NUMBER: CRD42020154787.

Reinforcer pathology, probabilistic choice, and medication adherence in patients with multiple sclerosis.

The reinforcer pathology model posits that core behavioral economic mechanisms, including delay discounting and behavioral economic demand, underlie adverse health decisions and related clinical disorders. Extensions beyond substance use disorder and obesity, however, are limited. Using a reinforcer pathology framework, this study evaluates medical adherence decisions in patients with multiple sclerosis. Participants completed behavioral economic measures, including delay discounting, probability discounting, and a medication purchase task. A medical decision-making task was also used to evaluate how sensitivity to mild side effect risk and efficacy contributed to the likelihood of taking a hypothetical disease-modifying therapy. Less steep delay discounting and more intense (greater) medication demand were independently associated with greater adherence to the medication decision-making procedure. More generally, the pattern of interrelations between the medication-specific and general behavioral economic metrics was consistent with and contributes to the reinforcer pathology model. Additional research is warranted to expand these models to different populations and health behaviors, including those of a positive health orientation (i.e., medication adherence).

Characterizing Symptoms Before and Following Concussion in Professional Hockey.

OBJECTIVE: Examine SCAT5 baseline and acute symptom subscales in professional hockey players. DESIGN: Longitudinal case-control. SETTING: Preseason medical evaluations and suspected concussion evaluations. PARTICIPANTS: NHL/AHL players were given the NHL-modified SCAT5 before the 2018-2019 season (n = 1924). During the season, English-speaking players evaluated within 1 day of injury and diagnosed with concussion (n = 140) were compared with players evaluated for possible concussion, but not given a concussion diagnosis (n = 174). INDEPENDENT VARIABLES: Concussion diagnosis and demographic characteristics. MAIN OUTCOME MEASURES: Postconcussion Symptoms Scale (PCSS) items were subdivided into affective/emotional, cognitive, somatic/physical, sleep, and headache subscales. RESULTS: Cognitive (13%), somatic/physical (10%), sleep (26%), affective (18%), and headache (6%) symptoms were reported by players at baseline. Concussed players reported more acute symptoms than active controls on each of the subscales (all P's < 0.001). Players who underwent a suspected concussion evaluation were more likely to be diagnosed with concussion if they reported affective/emotional symptoms at baseline (P < 0.001). Postinjury cognitive (P < 0.001), somatic/physical (P < 0.001), and headache (P < 0.001) symptoms best differentiated concussed players and active controls. CONCLUSIONS: Player reports of increased cognitive difficulties, somatic/physical difficulties, and headache were most associated with concussion diagnosis at the acute evaluation. An abbreviated "acute" PCSS that includes only headache, cognitive, and/or physical symptoms may be useful for diagnostic purposes when evaluation time is limited. Approximately 2% of players reported significantly elevated affective/emotional symptoms at baseline and report of affective/emotional symptoms at baseline was associated with an increased likelihood of concussion diagnosis among players referred for a suspected concussion evaluation.

Abuse of tropicamide eye drops: review of clinical data

Over the past 15 years, the increasing nonmedical use of tropicamide ophthalmic drops has been reported in Europe, coinciding with an increase in opioid addiction and drug-related mortality. Although tropicamide is generally known as a cheap alternative to heroin in Eastern Europe, it still appears to be a relatively new phenomenon that has arisen over the last decade. A narrative review was conducted of all the relevant sources published in more than five countries between January 1, 1975 and January 10, 2021. For bibliographic accuracy, the materials published in Russian and Italian were professionally translated to English. During the preparation of this report, we were able to interview five Russian-speaking patients who injected tropicamide in the past and we discuss another case of intravenous tropicamide use. This review was acknowledged by the institutional review board of the University of Missouri-Kansas City. All patients interviewed at the Unica Medical Center consented for their clinical information to be reported in a medical publication. We analyzed data from 50+ various sources and covered a variety of drug-related issues, including information on the extent, patterns, and trends in tropicamide use, its health consequences, and other clinical findings. The information provided in this article may help providers better detect tropicamide abuse and incorporate new rehabilitation strategies into the management of these patients.

Covalent Adsorption of N-Heterocyclic Carbenes on a Copper Oxide Surface.

Tuning the properties of oxide surfaces through the adsorption of designed ligands is highly desirable for several applications, such as catalysis. N-Heterocyclic carbenes (NHCs) have been successfully employed as ligands for the modification of metallic surfaces. On the other hand, their potential as modifiers of ubiquitous oxide surfaces still needs to be developed. Here we show that a model NHC binds covalently to a copper oxide surface under UHV conditions. In particular, we report the first example of a covalent bond between NHCs and oxygen atoms from the oxide layer. This study demonstrates that NHC can also act as a strong anchor on oxide surfaces.