Odour discrimination and identification as a biomarker of long-term disability worsening in multiple sclerosis.

BACKGROUND: Odour discrimination and identification (DI) are markers associated with disability worsening and neuroaxonal damage in multiple sclerosis (MS). OBJECTIVE: The main objective of this research is to investigate whether longitudinal change of DI predicts long-term MS disease course. METHODS: This is a 6-year prospective longitudinal study on MS patients at the MS Clinic Innsbruck. Clinical, bi-annual visits assessed patients' history and Expanded Disability Status Scale (EDSS) score. DI and cognitive function were assessed at baseline (BL), Year 1 (Y1), Year 2 (Y2) and Year 6 (Y6) by the 'Sniffin' Sticks'/Symbol Digit Modalities Test. RESULTS: Around 92 of 139 patients were available for Y6 follow-up. Mean DI scores significantly decreased over time (BL = 27.8, Y1 = 27.5, Y2 = 26.3 and Y6 = 26.3; p < 0.001) and negatively correlated with patients' age (rs = -0.120, p = 0.032) and disease duration (rs = -0.103, p = 0.041). Multivariable regression analyses revealed that lower absolute DI scores and larger DI score loss over time were associated with higher probability of EDSS worsening (per -1 point: hazard ratio (HR) = 1.40 (1.16-1.68) and 2.34 (1.27-4.21)), progression independent of relapse activity (PIRA) (HR = 1.49 (1.20-1.85) and 2.22 (1.33-3.31)) and cognitive deterioration (HR = 1.75 (1.35-2.27) and 4.29 (1.26-2.84)) at Y6, but not with time to first relapse. CONCLUSION: Odour DI is an irreversible marker of neuroaxonal damage, associated with PIRA, cognitive deterioration and EDSS worsening.

Retinal layer thinning for monitoring disease-modifying treatment in relapsing multiple sclerosis-Evidence for applying a rebaselining concept.

BACKGROUND: Employing a rebaselining concept may reduce noise in retinal layer thinning measured by optical coherence tomography (OCT). METHODS: From an ongoing prospective observational study, we included patients with relapsing multiple sclerosis (RMS), who had OCT scans at disease-modifying treatment (DMT) start (baseline), 6-12 months after baseline (rebaseline), and ⩾12 months after rebaseline. Mean annualized percent loss (aL) rates (%/year) were calculated both from baseline and rebaseline for peripapillary-retinal-nerve-fiber-layer (aLpRNFLbaseline/aLpRNFLrebaseline) and macular-ganglion-cell-plus-inner-plexiform-layer (aLGCIPLbaseline/aLGCIPLrebaseline) by mixed-effects linear regression models. RESULTS: We included 173 RMS patients (mean age 31.7 years (SD 8.8), 72.8% female, median disease duration 15 months (12-94) median baseline-to-last-follow-up-interval 37 months (18-71); 56.6% moderately effective DMT (M-DMT), 43.4% highly effective DMT (HE-DMT)). Both mean aLpRNFLbaseline and aLGCIPLbaseline significantly increased in association with relapse (0.51% and 0.26% per relapse, p < 0.001, respectively) and disability worsening (1.10% and 0.48%, p < 0.001, respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFLrebaseline nor aLGCIPLrebaseline was dependent on relapse or disability worsening before baseline, while HE-DMT significantly lowered aLpRNFLrebaseline (by 0.31%, p < 0.001) and aLGCIPLrebaseline (0.25%, p < 0.001) compared with M-DMT. CONCLUSIONS: Applying a rebaselining concept significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity.

Nudging Online Gamblers to Withdraw Money: The Impact of Personalized Messages on Money Withdrawal Among a Sample of Real-World Online Casino Players.

A number of scholars have argued that online gambling can be more problematic than land-based gambling. Motivating gamblers to withdraw money from their online gambling account could lower losses because there would be less money available to lose. Therefore, the present study investigated whether personalized messages are an effective way of 'nudging' gamblers to withdraw money from their online gambling account. The authors were given access to a secondary dataset by Nederlandse Loterij (the national Dutch Lottery operator) comprising 4049 online gamblers. Two types of messages were used to 'nudge' gamblers to withdraw money from their gambling account (i.e., a 'winning streak' message and a 'withdrawal' message). The findings indicated that (i) 38% of gamblers reading the 'winning streak' messages withdrew money from their gambling account on the same day, and (ii) 18% of gamblers reading the 'withdrawal' messages withdrew money from their gambling account on the same day. Gamblers who read personalized messages also withdrew larger amounts of money from their gambling accounts compared to gamblers who did not read personalized messages. The findings suggest that the personalized messages can have an impact on both the likelihood to withdraw money as well as the amount of money which was withdrawn and could help reduce gambling-related harm.

Immunization status in patients with multiple sclerosis: A cross-sectional, monocenter study in Austria.

BACKGROUND AND PURPOSE: Patients with multiple sclerosis (MS) under certain disease-modifying therapies (DMT) show a higher risk of infection and a lower immune response to vaccination. Hence, assessing immunization status prior to DMT start and, where necessary, performing vaccinations is  recommended. We aimed to determine the immunization status in MS patients and to identify factors associated with low vaccination rates. METHODS: Patients with MS who were seen at the MS clinic of the Medical University of Innsbruck throughout a period of 14 months in 2020 and 2021 were eligible for inclusion into this prospective, single-center study. Immunization status against 17 different pathogens was obtained from vaccination certificate and by patient questionnaire. Antibody detection against seven antigens was performed in peripheral blood. RESULTS: Of 424 patients with MS at a mean age of 43 ± 12 years, the vast majority had vaccinations against tetanus (94%), diphtheria (92%), and poliomyelitis (90%), whereas a lower proportion had vaccinations against tick-borne encephalitis (70%), pertussis (69%), hepatitis B (65%), rubella (55%), hepatitis A (50%), measles (49%), mumps (47%), and only a minority against influenza (10%), pneumococcal (6%) and meningococcal disease (4%), human papillomavirus (4%), yellow fever (2%), and varicella zoster virus (1%). A total of 87% received vaccination against SARS-CoV-2. Overall, higher vaccination rates were associated with younger age, relapsing disease course, and education level. Misinformation on infectious diseases and vaccines was associated with lower vaccination rates. CONCLUSIONS: The majority of MS patients did not fulfil vaccination recommendations. Efforts to increase vaccination rates, preferentially before DMT start, should be promoted.

Sexual dysfunction in female and male people with multiple sclerosis: disability, depression and hormonal status matter.

BACKGROUND AND PURPOSE: Sexual dysfunction (SD) in people with multiple sclerosis (pwMS) is common and an often underestimated issue in the care of pwMS. The objective of the study was to evaluate risk factors for SD in pwMS, correlate its prevalence with patient-reported measures (quality of life and physical activity) and analyse its association with hormonal status. METHODS: Sexual dysfunction was determined in 152 pwMS using the Multiple Sclerosis Intimacy and Sexuality Questionnaire 19. A logistical regression model was used to identify independent risk factors for SD. RESULTS: The prevalence of SD in pwMS was 47%. Independent risk factors for the development of SD were ever-smoking (odds ratio [OR] 3.4, p = 0.023), disability as measured by the Expanded Disability Status Scale (OR 2.0, p < 0.001), depression (OR 4.3, p = 0.047) and bladder and bowel dysfunction (OR 8.8, p < 0.001); the use of disease-modifying treatment was associated with a lower risk for SD (OR 0.32, p = 0.043). SD was associated with worse quality of life (Multiple Sclerosis Impact Scale 29: physical score 6.3 vs. 40.0; psychological score 8.3 vs. 33.3; both p < 0.001) and lower physical activity (Baecke questionnaire, p < 0.001). Laboratory analysis revealed significantly higher luteinizing hormone and follicle-stimulating hormone levels and lower 17-beta oestradiol, androstenedione, dehydroepiandrosterone sulfate, oestrone and anti-Mullerian hormone levels in female pwMS with SD. In male pwMS and SD, there was a significant decrease in inhibin B levels. CONCLUSIONS: Our findings highlight the requirement of a holistic approach to SD in MS including physical, neurourological and psychosocial factors. Active screening for SD, especially in patients with disability, depression or bladder and bowel dysfunction, is recommended.

Retinal layer thickness predicts disability accumulation in early relapsing multiple sclerosis.

BACKGROUND AND PURPOSE: This study was undertaken to investigate baseline peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness for prediction of disability accumulation in early relapsing multiple sclerosis (RMS). METHODS: From a prospective observational study, we included patients with newly diagnosed RMS and obtained spectral-domain optical coherence tomography scan within 90 days after RMS diagnosis. Impact of pRNFL and GCIPL thickness for prediction of disability accumulation (confirmed Expanded Disability Status Scale [EDSS] score ≥ 3.0) was tested by multivariate (adjusted hazard ratio [HR] with 95% confidence interval [CI]) Cox regression models. RESULTS: We analyzed 231 MS patients (mean age = 30.3 years, SD = 8.1, 74% female) during a median observation period of 61 months (range = 12-93). Mean pRNFL thickness was 92.6 µm (SD = 12.1), and mean GCIPL thickness was 81.4 µm (SD = 11.8). EDSS ≥ 3 was reached by 28 patients (12.1%) after a median 49 months (range = 9-92). EDSS ≥ 3 was predicted with GCIPL < 77 µm (HR = 2.7, 95% CI = 1.6-4.2, p < 0.001) and pRNFL thickness ≤ 88 µm (HR = 2.0, 95% CI = 1.4-3.3, p < 0.001). Higher age (HR = 1.4 per 10 years, p < 0.001), incomplete remission of first clinical attack (HR = 2.2, p < 0.001), ≥10 magnetic resonance imaging (MRI) lesions (HR = 2.0, p < 0.001), and infratentorial MRI lesions (HR = 1.9, p < 0.001) were associated with increased risk of disability accumulation, whereas highly effective disease-modifying treatment was protective (HR = 0.6, p < 0.001). Type of first clinical attack and presence of oligoclonal bands were not significantly associated. CONCLUSIONS: Retinal layer thickness (GCIPL more than pRNFL) is a useful predictor of future disability accumulation in RMS, independently adding to established markers.

Using artificial intelligence algorithms to predict self-reported problem gambling with account-based player data in an online casino setting.

In recent years researchers have emphasized the importance of artificial intelligence (AI) algorithms as a tool to detect problem gambling online. AI algorithms require a training dataset to learn the patterns of a prespecified group. Problem gambling screens are one method for the collection of the necessary input data to train AI algorithms. The present study's main aim was to identify the most significant behavioral patterns which predict self-reported problem gambling. In order to fulfil the aim, the study analyzed data from a sample of real-world online casino players and matched their self-report (subjective) responses concerning problem gambling with the participants' actual (objective) gambling behavior. More specifically, the authors were given access to the raw data of 1,287 players from a European online gambling casino who answered questions on the Problem Gambling Severity Index (PGSI) between September 2021 and February 2022. Random forest and gradient boost machine algorithms were trained to predict self-reported problem gambling based on the independent variables (e.g., wagering, depositing, gambling frequency). The random forest model predicted self-reported problem gambling better than gradient boost. Moreover, problem gamblers showed a distinct pattern with respect to their gambling based on the player tracking data. More specifically, problem gamblers lost more money per gambling day, lost more money per gambling session, and deposited money more frequently per gambling session. Problem gamblers also tended to deplete their gambling accounts more frequently compared to non-problem gamblers. A subgroup of problem gamblers identified as being at greater harm (based on their response to PGSI items) showed even higher values with respect to the aforementioned gambling behaviors. The study showed that self-reported problem gambling can be predicted by AI algorithms with high accuracy based on player tracking data.

An Empirical Attempt to Operationalize Chasing Losses in Gambling Utilizing Account-Based Player Tracking Data.

In recent years, account-based player tracking data have been utilized as a potential tool to identify problem gambling online and associated markers of harm. One established marker of harm among problem gamblers is chasing losses, and chasing losses is a key criterion for gambling disorder in the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders. Given the paucity of research with respect to chasing losses among online casino players using account-based data, the present study developed five metrics that may be indicative of chasing behavior: These were (i) within-session chasing, (ii) across-session chasing, (iii) across-days chasing, (iv) regular gambling account depletion, and (v) frequent session depositing. The authors were given access by a European online casino to raw data of all players who had placed at least one bet or wagered at least once during December 2021 (N = 16,771 players from the UK, Spain, and Sweden). Results indicated that frequent session depositing reflected chasing losses better than any of the other four metric operationalizations used. While frequent session depositing appears to be more indicative of chasing losses than the other four metrics, all the metrics provide useful information which can be used to help identify problematic gambling behavior online.

The Impact of Personalized Feedback Interventions by a Gambling Operator on Subsequent Gambling Expenditure in a Sample of Dutch Online Gamblers.

Player protection has become an important area for the gambling industry over the past decade. A number of gambling regulators now require gambling operators to interact with customers if they suspect they are gambling in a problematic way. The present study provided insight on the impact of personalized feedback interventions (PFIs) on subsequent gambling behavior among a Dutch sample of real-world gamblers. Nederlandse Loterij (the national Dutch Lottery operator) provided access to a secondary dataset comprising tracking data from online casino and sports betting gamblers (N = 2,576) who were contacted either by e-mail or telephone between November 2021 and March 2022 if they showed signs of problematic gambling as identified using behavioral tracking software. Compared to matched controls (n = 369,961 gamblers), Dutch gamblers who received a PFI (via e-mail [n = 1876] or a telephone call [n = 700]) from the gambling operator had a significant reduction in amount of money deposited, amount of money wagered, number of monetary deposits, and time spent gambling in the 30 days after being contacted. Gambling frequency as measured by the number of gambling days did not change significantly after a PFI. Telephone calls did not lead to a significant larger reduction with respect to the aforementioned behavioral metrics. High-intensity players reduced their gambling behavior as frequently as low-intensity players, which means that the intervention's success was independent of gambling intensity. The impact on subsequent gambling was the same across age groups and gender. The results of the present study are of use to many different stakeholder groups including researchers in the gambling studies field and the gambling industry as well as regulators and policymakers who can recommend or enforce that gambling operators utilize responsible gambling tools such as using PFIs to those who may be displaying problematic gambling behaviors as a way of minimizing harm and protecting gamblers.

The Effect of a Mandatory Play Break on Subsequent Gambling Behavior among British Online Casino Players: A Large-Scale Real-World Study.

In recent years, various novel responsible gambling (RG) tools have been implemented to aid harm-minimization. One such RG tool has been the implementation of enforced mandatory play breaks. Despite many responsible gambling operators using mandatory play breaks, only three previous studies have examined their efficacy and the findings were mixed. Therefore, the present investigation was a large-scale real-world study which was designed to see whether a 60-minute mandatory play break influenced subsequent depositing and wagering. The authors were given access to 27 days of player data prior to the introduction of a mandatory play break and 27 days of player data after the mandatory play break was introduced. The study comprised British online gamblers from Skillonnet (a European online gambling operator). Between July 23 and September 15 (2021), 2,021 players deposited at least ten times or more on a calendar day, at least once. The 2,201 players generated 2,994 corresponding events (i.e., the depositing of money at least 10 times in one day). The percentage of players who stopped depositing money as a consequence of the mandatory play break rose from 27% to 68% on the day of a play break. Moreover, the percentage of players who stopped wagering as a consequence of the mandatory play break rose from 0.1% to 45% on the day of a play break. The findings of the present study demonstrated that a 60-minute mandatory play break impacts players' depositing and wagering immediately after the play break. This means that a mandatory hour-long play break in an online casino setting appears to prevent overspending during a short period of time. The effects of a 60-minute mandatory break on the next day's behavior were inconclusive.

The relationship between structural characteristics and gambling behaviour: An online gambling player tracking study.

Structural characteristics of games have been regarded as important aspects in the possible development of problematic gambling. The most important factors along with individual susceptibility and risk factors of the individual gambler are the structural characteristics such as the speed and frequency of the game (and more specifically event frequency, bet frequency, event duration, and payout interval). To date, the association between structural characteristics and behavior has not been studied in an online gambling environment. The present study investigated the association between structural characteristics and online gambling behavior in an ecologically valid setting using data from actual gamblers. The authors were given access to data from a large European online gambling operator with players from Germany, Austria, UK, Poland, and Slovenia. The sample comprised 763,490 sessions between November 27, 2020 and April 15, 2021 utilizing data from 43,731 players. A machine learning tree-based algorithm with structural characteristics and session metrics explained 26% of the variance of the number of games played in a session. The results also showed that only 7.7% of the variance in the number of bets placed in a session was explained by the game's structural characteristics alone. The most important structural characteristic with respect to the number of games played in a session was the event frequency of the game followed by the maximum amount won on a single bet in a session.

Attitude Towards Deposit Limits and Relationship with Their Account-Based Data Among a Sample of German Online Slots Players.

Social responsibility and duty of care have become major cornerstones for gambling operators. This has led to the introduction of many different responsible gambling tools such as limit-setting, mandatory play breaks, and personalized messaging. In the present study, the authors were given access to two secondary datasets provided by a German online slots game operator. The first dataset was from an online survey carried out by the gambling operator among 1000 of its players concerning their attitude towards deposit limits as well as self-reported problem gambling. In addition to the survey responses, the authors were given access to a second dataset of account-based data concerning each customer's wagers, wins, monetary deposits, and monetary withdrawals. These datasets were then combined. The majority of players had a positive attitude towards the maximum deposit monthly deposit limit which was introduced by the German State Treaty on Gambling in 2021. Players who disagreed with the maximum monthly deposit limit, deposited significantly more money in the 30 days prior to answering the survey questions compared to players who agreed with the monthly deposit limit. The tracking data found only 7.6% of players had deposited the maximum amount of money allowed in one month. However, 60.5% of players in the survey data said that they did so. Players who said that they continued to gamble after reaching the deposit limit wagered and deposited significantly more money in the 30 days prior to the survey compared to players who said they stopped gambling after reaching the deposit limit. Two-fifths of players said they continued to gamble after reaching the monthly deposit limit (42%). The majority of the players said they chose a personal deposit limit because it helped them to better control their gambling expenditure. A quarter of the players reported gambling problems using the Brief Biosocial Gambling Screen (27%). Self-reported problem gambling was not correlated with depositing, wagering or any other player tracking metric.

Self-reported Deposits Versus Actual Deposits in Online Gambling: An Empirical Study.

In recent years a number of studies have used objective gambling data from online gambling operators to study gambling behavior. A few of these studies have compared gamblers' actual gambling behavior (using account-based tracking data) with their subjective gambling behavior (using responses from survey data). The present study extended previous studies by comparing self-reported money deposited with the actual amount of money deposited. The authors were given access to an anonymized secondary dataset of 1,516 online gamblers from a European online gambling operator. After removing those who had not deposited any money in the previous 30 days, the final sample size for analysis was 639 online gamblers. The results indicated that gamblers were able to estimate fairly accurately how much money they had deposited in the past 30 days. However, the higher the amount of money deposited, the more likely gamblers underestimated the actual amount of money deposited. With respect to age and gender, there were no significant differences between male and female gamblers in their estimation biases. However, a significant age difference was found between those who overestimated and underestimated their deposits, with younger gamblers tending to overestimate their deposits. Providing feedback as to whether the gamblers overestimated or underestimated their deposits did not lead to any additional significant changes in the amount of money deposited when considering the overall reduction in deposits after self-assessment. The implications of the findings are discussed.

Predicting self-exclusion among online gamblers: An empirical real-world study.

Protecting gamblers from problematic gambling behavior is a major concern for clinicians, researchers, and gambling regulators. Most gambling operators offer a range of so-called responsible gambling tools to help players better understand and control their gambling behavior. One such tool is voluntary self-exclusion, which allows players to block themselves from gambling for a self-selected period. Using player tracking data from three online gambling platforms operating across six countries, this study empirically investigated the factors that led players to self-exclude. Specifically, the study tested (i) which behavioral features led to future self-exclusion, and (ii) whether monetary gambling intensity features (i.e., amount of stakes, losses, and deposits) additionally improved the prediction. A total of 25,720 online gamblers (13% female; mean age = 39.9 years) were analyzed, of whom 414 (1.61%) had a future self-exclusion. Results showed that higher odds of future self-exclusion across countries was associated with a (i) higher number of previous voluntary limit changes and self-exclusions, (ii) higher number of different payment methods for deposits, (iii) higher average number of deposits per session, and (iv) higher number of different types of games played. In five out of six countries, none of the monetary gambling intensity features appeared to affect the odds of future self-exclusion given the inclusion of the aforementioned behavioral variables. Finally, the study examined whether the identified behavioral variables could be used by machine learning algorithms to predict future self-exclusions and generalize to gambling populations of other countries and operators. Overall, machine learning algorithms were able to generalize to other countries in predicting future self-exclusions.

The Efficacy of Voluntary Self-Exclusions in Reducing Gambling Among a Real-World Sample of British Online Casino Players.

Online gambling is a socially acceptable means of entertainment, but it can also have a negative impact on many areas of life and lead to problem gambling for a minority of individuals. In recent years, gambling operators have increasingly implemented responsible gambling tools to help at-risk gamblers control and limit their gambling. One such tool is voluntary self-exclusion (VSE), where gamblers can exclude themselves from the gambling platform for a self-selected period of time. Despite the widespread use of VSE, there are few published studies on the efficacy of VSE among online gamblers and none on whether (and what type of) gamblers return to gambling after self-exclusion and how VSE affects their wagering if they return. Using a secondary dataset, the present study empirically analyzed a real-world sample of 3,203 British online casino players who opted for a VSE between January 2021 and August 2022. Analysis showed that most players who took a short-term VSE (up to 38 days) started gambling again on the platform after their self-exclusion ended, while players who opted for long-term self-exclusion (more than 90 days) did not start gambling again on the platform. A return to the gambling platform after VSE was positively associated with (i) a shorter duration of the self-exclusion, (ii) being female, (iii) gambling on more days, (iv) placing more bets, (v) playing fewer type of games, and (vi) having a lower average number of deposits per day. Players who returned from VSE did not change their wagering compared to a matched control group. These results suggest that short-term VSE may not be as effective as long-term VSE in reducing gambling. Overall, the present findings suggest that gamblers returning from VSE should be closely monitored, especially if the reason for self-exclusion is related to problem gambling.

Retinal layer thinning as a biomarker of long-term disability progression in multiple sclerosis.

BACKGROUND: Peripapillary retinal nerve fibre layer and macular ganglion cell plus inner plexiform layer thinning are markers of neuroaxonal degeneration in multiple sclerosis. OBJECTIVE: We aimed to investigate the value of peripapillary retinal nerve fibre layer and ganglion cell plus inner plexiform layer thinning for prediction of long-term disability. METHODS: This is a 6-year prospective longitudinal study on 93 multiple sclerosis patients. Optical coherence tomography scans were performed at baseline, after 1, 2 and 6 years. Primary endpoint was disability progression after 6 years, defined as expanded disability status scale worsening and/or cognitive deterioration. Univariate and multivariate analysis was used to investigate the value of peripapillary retinal nerve fibre layer and ganglion cell plus inner plexiform layer to predict the primary endpoint. RESULTS: A total of 57 (61.3%) patients had disability worsening, 40 (43.0%) expanded disability status scale worsening and 34 (36.6%) cognitive deterioration. Mean peripapillary retinal nerve fibre layer and ganglion cell plus inner plexiform layer baseline thickness were 93.0 and 75.2 µm, and mean annualised peripapillary retinal nerve fibre layer and ganglion cell plus inner plexiform layer thinning rates over 6 years were 1.3 and 1.6 µm, respectively. Univariate and multivariate analysis revealed lower peripapillary retinal nerve fibre layer and ganglion cell plus inner plexiform layer baseline thickness and higher annualised thinning rates in patients with disability progression after 6 years. Effects were more pronounced for ganglion cell plus inner plexiform layer and expanded disability status scale worsening than for peripapillary retinal nerve fibre layer models and cognitive deterioration. CONCLUSION: Ganglion cell plus inner plexiform layer and peripapillary retinal nerve fibre layer measurements depict neurodegeneration and predict disability progression in multiple sclerosis.

Olfactory threshold predicts treatment response in relapsing multiple sclerosis.

BACKGROUND: Olfactory threshold (OT) is associated with short-term inflammatory activity in relapsing multiple sclerosis (RMS). OBJECTIVE: We aimed to investigate OT for prediction of treatment response in RMS. METHODS: In this 5-year prospective study on 123 RMS patients, OT was measured at disease-modifying treatment (DMT) initiation (M0), after 3 months (M3), and 12 months (M12) by Sniffin' Sticks test. Primary endpoint was defined as an absence of relapse during the observation period, with Expanded Disability Status Scale (EDSS) progression and magnetic resonance imaging (MRI) activity being the secondary endpoints. Optimal cutoff values were determined by receiver operating characteristic analyses and their predictive value assessed by multivariable Cox regression models. RESULTS: Higher OT scores at M0, M3, and M12 were independently associated with decreased relapse probability with the strongest risk reduction at M3 (hazard ratio (HR) = 0.44, p < 0.001). Improvement of OT scores from M0 to M3 (ΔOTM3) was also associated with reduced relapse risk (HR = 0.12, p < 0.001). OT score > 6.5 at M3 was the strongest predictor of relapse freedom (HR = 0.10, p < 0.001) with high diagnostic accuracy (positive predictive value (PPV) = 87%), closely followed by ΔOTM3 ⩾ 0.5 (HR = 0.12, p < 0.001, PPV = 86%). CONCLUSIONS: OT is an independent predictor of freedom of disease activity upon DMT initiation within 5 years and may be a useful biomarker of treatment response.

Sudomotor dysfunction in people with neuromyelitis optica spectrum disorders.

BACKGROUND AND PURPOSE: The aim was to determine the extent of sudomotor dysfunction in people with neuromyelitis optica spectrum disorder (pwNMOSD) and to compare findings with a historical cohort of people with relapsing-remitting multiple sclerosis (pwRRMS). METHODS: Forty-eight pwNMOSD were enrolled from four clinical centers. All participants completed the Composite Autonomic Symptom Score 31 to screen for symptoms of sudomotor dysfunction. Sudomotor function was assessed using the quantitative sudomotor axon reflex test. The results were compared with a historical cohort of 35 pwRRMS matched for age, sex and disease duration. RESULTS: Symptoms of sudomotor dysfunction, defined by a score in the Composite Autonomic Symptom Score 31 secretomotor domain >0, were present in 26 (54%) of pwNMOSD. The quantitative sudomotor axon reflex test confirmed a sudomotor dysfunction in 25 (52.1%) of pwNMOSD; in 14 of them (29.2%) sudomotor dysfunction was moderate or severe. No difference was observed between pwNMOSD and pwRRMS in any of the studied parameters. However, symptomatic sudomotor dysfunction was more frequent in pwNMOSD (n = 8, 22.9%) compared to pwRRMS (n = 1, 3%; p = 0.028). In a multivariable logistic regression analysis, statistically significant predictors for symptomatic sudomotor failure were age and diagnosis of neuromyelitis optica spectrum disorder. CONCLUSIONS: Sudomotor dysfunction is common in pwNMOSD and more often symptomatic compared to pwRRMS.

The Effect of Mandatory Play Breaks on Subsequent Gambling Behavior Among Norwegian Online Sports Betting, Slots and Bingo Players: A Large-scale Real World Study.

In order to protect gamblers, gambling operators have introduced a wide range of responsible gambling (RG) tools. Mandatory play breaks (i.e., forced termination of a gambling session) and personalized feedback about the gambling expenditure are two RG tools that are frequently used. While the motivation behind mandatory play breaks is simple (i.e., gambling operators expect gamblers to reduce their gambling significantly as a result of an enforced break in play), empirical evidence supporting the efficacy of the mandatory breaks is still limited. The present study comprised a real-world experiment with the clientele of Norwegian gambling operator Norsk Tipping. On the Norsk Tipping gambling website, which offers slots, bingo and sports-betting, forced termination occurs if gamblers have played continuously for a one-hour period. The study tested the effect of different lengths of mandatory play breaks (90 s, 5 min, 15 min) on subsequent gambling behavior, as well as the effect of combined personalized feedback concerning money wagered, won, and net win/loss. In total 21,129 online players (61% male; mean age = 47.4 years) experienced at least one play break between April 17 and May 21 (2020) with 156,989 mandatory play breaks in total. Results indicated that a 15-min mandatory play break led to a disproportionately longer voluntary play pause compared to 5-min and 90-s mandatory play breaks. Personalized feedback appeared to have no additional effect on subsequent gambling and none of the mandatory play breaks appeared to affect the increase or decrease in money wagered once players started to gamble again.

Natalizumab treatment during pregnancy in multiple sclerosis-clinical and bioethical aspects of an ongoing debate.

BACKGROUND: Natalizumab is an approved treatment for relapsing remitting multiple sclerosis; however, its safety during pregnancy is not formally proven. CASE PRESENTATION: We report a woman with multiple sclerosis being treated with natalizumab before pregnancy. After withdrawal of natalizumab, she suffered a severe, disabling rebound. In agreement with the patient, natalizumab was restarted during pregnancy. Our patient improved substantially and gave birth to a healthy boy. CONCLUSION: Use of natalizumab during pregnancy may be an option in highly active multiple sclerosis.