Olfactory threshold as a biomarker of long-term relapse activity in multiple sclerosis.

BACKGROUND: Olfactory threshold (OT) is a marker of short-term inflammatory activity in multiple sclerosis (MS). OBJECTIVE: To investigate whether OT predicts long-term MS clinical disease course. METHODS: This was a 6-year prospective longitudinal study on MS patients at the MS clinic Innsbruck. Clinical visits assessing the occurrence of relapses, Expanded Disability Status Scale (EDSS) scores, and disease-modifying treatment (DMT), were conducted biannually. OT testing was performed at baseline (BL), year 1 (Y1), year 2 (Y2) and year 6 (Y6), using the threshold subscore of the "Sniffin' Sticks" test. Cognitive function was assessed by the Symbol Digit Modalities Test. RESULTS: Of 139 MS patients, 92 were eligible for Y6 follow-up. 68% experienced relapses, 53% EDSS worsening, 29% progression independent of relapse activity (PIRA) and 41% cognitive deterioration. OT scores were lower at BL, Y1 and Y2 in patients requiring DMT escalation. In multivariable analysis, higher OT scores at BL, Y1, Y2 and Y6 were associated with lower risk of relapse (hazard ratio, HR: 0.65-0.92) and EDSS worsening (HR: 0.86-0.89), while no associations were found for PIRA and cognitive deterioration. CONCLUSIONS: OT is a potential surrogate marker for long-term inflammatory disease activity and DMT failure in MS.

Multiple sclerosis in the elderly: a retrospective cohort study.

BACKGROUND: There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients. OBJECTIVE: To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients. METHODS: This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria. Data were collected from 15 MS centers including demographics, first symptom at onset, number of relapses, evolvement of disability, medication, and comorbidities. RESULTS: Median observation time was 17.1 years with 957 (80%) relapsing and 243 (20%) progressive onsets. Average age at diagnosis was 45 years with a female predominance of 71%. Three-hundred and twenty-six (27%) patients were never treated with a DMT, while most treated patients received interferons (496; 41%) at some point. At last follow-up, 420 (35%) patients were still treated with a DMT. No difference was found between treated and never-treated patients in terms of clinical outcome; however, patients with worse disability progression had significantly more DMT switches. Pyramidal onset, number of comorbidities, dementia, epilepsy, and psychiatric conditions as well as a higher number of relapses were associated with worse outcome. The risk of reaching EDSS 6 rose with every additional comorbidity by 22%. In late and very-late-onset MS (LOMS, VLOMS) time to diagnosis took nearly twice the time compared to adult and early onset (AEOMS). The overall annualized relapse rate (ARR) decreased over time and patients with AEOMS had significantly higher ARR compared to LOMS and VLOMS. Four percent of MS patients had five medications or more fulfilling criteria of polypharmacy and 20% of psychiatric drugs were administered without a matching diagnosis. CONCLUSIONS: In this study, we identified number of comorbidities, pyramidal and cerebellar signs, and a higher number of relapses as unfavorable prognostic factors in elderly MS patients filling gaps of knowledge in patients usually underrepresented in clinical trials and may guide future therapeutic studies.

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.

Development of the Online Problem Gaming Behavior Index: A New Scale Based on Actual Problem Gambling Behavior Rather Than the Consequences of it.

Many items in current problem gambling screens focus on negative consequences of gambling and gambling-related harms. However, few problem gambling screens comprise items that are totally based on actual gambling behavior such as gambling duration, gambling frequency, or gambling late at night. The aim of the present study was to develop and validate the 12-item Online Problem Gambling Behavior Index (OPGBI). A total of 10,000 online Croatian gamblers were administered the OPGBI alongside the nine-item Problem Gambling Severity Index (PGSI), as well as questions regarding types of gambling engaged in and socio-demographic factors. The 12 OPGBI items mainly concern actual gambling behavior. The correlation between OPGBI and PGSI was highly significant (r = 0.68). Three latent factors in the OPGBI were identified (gambling behavior, limit setting, communication with operator). The three factors all significantly correlated with the PGSI score (R2- = 51.8%). The fact that pure gambling behavior related items explained over 50% of the PGSI score strengthens the idea that player tracking could be an important approach in identifying problem gambling.

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.

Diagnostic Performance of Adding the Optic Nerve Region Assessed by Optical Coherence Tomography to the Diagnostic Criteria for Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The optic nerve has been recommended as an additional region for demonstrating dissemination in space (DIS) in diagnostic criteria for multiple sclerosis (MS). The aim of this study was to investigate whether adding the optic nerve region as determined by optical coherence tomography (OCT) as part of the DIS criteria improves the 2017 diagnostic criteria. METHODS: From a prospective observational study, we included patients with a first demyelinating event who had complete information to assess DIS and a spectral domain OCT scan obtained within 180 days. Modified DIS criteria (DIS + OCT) were constructed by adding the optic nerve to the current DIS regions based on validated thresholds for OCT intereye differences. Time to second clinical attack was the primary endpoint. RESULTS: We analyzed 267 patients with MS (mean age 31.3 years [SD 8.1], 69% female) during a median observation period of 59 months (range: 13-98). Adding the optic nerve as a fifth region improved the diagnostic performance by increasing accuracy (DIS + OCT 81.2% vs DIS 65.6%) and sensitivity (DIS + OCT 84.2% vs DIS 77.9%) without lowering specificity (DIS + OCT 52.2% vs DIS 52.2%). Fulfilling DIS + OCT criteria (≥2 of 5 DIS + OCT regions involved) indicated a similar risk of a second clinical attack (hazard ratio [HR] 3.6, CI 1.4-14.5) compared with a 2.5-fold increased risk when fulfilling DIS criteria (HR 2.5, CI 1.2-11.8). When the analysis was conducted according to topography of the first demyelinating event, DIS + OCT criteria performed similarly in both optic neuritis and nonoptic neuritis. DISCUSSION: Addition of the optic nerve, assessed by OCT, as a fifth region in the current DIS criteria improves diagnostic performance by increasing sensitivity without lowering specificity. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that adding the optic nerve as determined by OCT as a fifth DIS criterion to the 2017 McDonald criteria improves diagnostic accuracy.

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.

Immune profiling in multiple sclerosis: a single-center study of 65 cytokines, chemokines, and related molecules in cerebrospinal fluid and serum.

Introduction: The understanding of the pathophysiology of multiple sclerosis (MS) has evolved alongside the characterization of cytokines and chemokines in cerebrospinal fluid (CSF) and serum. However, the complex interplay of pro- and anti-inflammatory cytokines and chemokines in different body fluids in people with MS (pwMS) and their association with disease progression is still not well understood and needs further investigation. Therefore, the aim of this study was to profile a total of 65 cytokines, chemokines, and related molecules in paired serum and CSF samples of pwMS at disease onset. Methods: Multiplex bead-based assays were performed and baseline routine laboratory diagnostics, magnetic resonance imaging (MRI), and clinical characteristics were assessed. Of 44 participants included, 40 had a relapsing-remitting disease course and four a primary progressive MS. Results: There were 29 cytokines and chemokines that were significantly higher in CSF and 15 in serum. Statistically significant associations with moderate effect sizes were found for 34 of 65 analytes with sex, age, CSF, and MRI parameters and disease progression. Discussion: In conclusion, this study provides data on the distribution of 65 different cytokines, chemokines, and related molecules in CSF and serum in newly diagnosed pwMS.

Screening for osteoporosis in people with MS: A new risk score.

BACKGROUND: Due to the demographic development and improved treatment options, the role of comorbidities is of increasing importance in the medical care of people with MS (pwMS). A higher risk of osteoporosis is well known in chronic autoimmune diseases, and is also described in MS. While there are several screening guidelines in the elderly or in patients with rheumatoid arthritis, there are no generally accepted recommendations when to perform bone mineral testing in pwMS under the age of 65 years. We aimed to determine risk factors of osteoporosis in pwMS and to develop a risk score which can be applied in daily clinical routine. METHODS: Densitometry (hip and lumbar spine) was performed in 159 pwMS aged ≤65 years and in 81 age- and sex-matched healthy controls (HC). Osteoporosis was defined according to WHO criteria as a bone density 2.5 standard deviation or more below the mean of young adults. Risk factors were identified by logistic regression analysis. RESULTS: Osteoporosis occurred more frequently in postmenopausal pwMS and male pwMS as compared to HC. Besides age, sex, menopausal status in females, body-mass-index and smoking, a higher degree of disability - as assessed by the Expanded Disability Status Scale - was identified as MS specific risk factor for osteoporosis, whereas the cumulative glucocorticoid dose was not associated with osteoporosis risk. Based on these risk factors, we developed an MS-specific risk score which allows to estimate the individual probability of osteoporosis. CONCLUSION: This risk score enables individual screening recommendation for pwMS and, subsequently, early prevention of osteoporosis which probably should result in reduction of fractures and morbidity.

Kappa free light chain and neurofilament light independently predict early multiple sclerosis disease activity-a cohort study.

BACKGROUND: Inter-individual courses of multiple sclerosis (MS) are extremely variable. The objective of this study was to investigate whether κ-free light chain (κ-FLC) index and serum neurofilament light (sNfL) have an additive predictive value for MS disease activity. METHODS: Patients with early MS who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for four years. At baseline, age, sex, disease duration, number of T2-hyperintense (T2L), and contrast-enhancing T1 lesions (CEL) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying treatment (DMT) were registered. κ-FLC was measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. sNfL was determined by single-molecule array, and age- and body-mass-index adjusted Z scores were calculated. FINDINGS: A total of 86 patients at a mean age of 33 ± 10 years and with a female predominance of 67% were included; 36 (42%) patients experienced a second clinical attack during follow-up. Cox regression analysis adjusted for age, sex, T2L, CEL, disease and follow-up duration, and DMT use during follow-up revealed that both κ-FLC index as well as sNfL Z score independently predict time to second clinical attack. The chance for freedom of relapse within 12 months was 2% in patients with high levels of κ-FLC index (>100) and high sNfL Z score (>3), 30% in patients with high κ-FLC index (>100) and lower sNfL Z score (≤3), 70% in patients with lower κ-FLC index (≤100) but high sNfL Z score (>3), and 90% in patients with lower levels of κ-FLC index (≤100) and sNfL Z score (≤3). INTERPRETATION: κ-FLC index and sNfL Z score have an additive predictive value for early MS disease activity that is independent of known predictors. FUNDING: This study was funded by a grant of the charitable foundation of the Austrian Multiple Sclerosis Society.

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.

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.

Cooling Off and the Effects of Mandatory Breaks in Online Gambling: A Large-Scale Real-World Study.

The prevention of problematic online gambling behavior is a topic of major interest for regulators, the gambling industry, and researchers. Many gambling operators approach this issue by using responsible gambling tools. Among such tools, mandatory play breaks are used to interrupt long online gambling sessions, providing "cooling off" periods for players to take a reflective "time out". The present study investigated the effects of mandatory play breaks in a large-scale experiment with 23,234 online gamblers engaging in more than 870,000,000 gambling transactions on Norsk Tipping's gambling platform over a 1-month period. The gamblers were randomly assigned to several intervention groups with varying duration of mandatory play breaks and one control group with Norsk Tipping's standard play break duration. More specifically, the study analyzed the relationship between the mandatory break received and the gambler's acceptance of this tool, the interaction patterns with the tool, and how quickly they started to gamble again, as well as post-intervention effects on gambling behavior. Results showed that gamblers who were treated with longer mandatory breaks (i) tended to take longer voluntary breaks, and (ii) interacted more frequently with the tool (for instance, by clicking the "logout" button). Furthermore, gamblers appeared to accept longer mandatory play breaks. However, only a fraction of post-intervention effects remained, and mainly only for gamblers who received a substantial number of long mandatory play breaks. Overall, the present study provides actionable insights for both researchers and the gambling industry to improve the effectiveness of mandatory play breaks as a responsible gambling tool.

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.

Chasing shadows: Cytologically detected shadow cells in the cerebrospinal fluid of patients with multiple sclerosis.

BACKGROUND: Pathophysiology of multiple sclerosis (MS) is dominated by both inflammation and neurodegeneration. A correlation between inflammation and regulated cell death has been suggested previously. Shadow cells in the cerebrospinal fluid (CSF) are considered apoptotic cells. OBJECTIVE: To assess the occurrence of shadow cells in MS patients in comparison to other neurological diseases (OND). METHODS: We conducted cytological examination of CSF in 114 MS patients and 125 patients with OND, who had diagnostic lumbar puncture at the Department of Neurology, Medical University of Innsbruck, with time to laboratory processing ≤0.5 h, showed a CSF white blood cell (WBC) count ≤50/µl and a red blood cell (RBC) count ≤500/µl. Shadow cells were counted by two blinded, independent, experienced investigators, using a standardized approach on microscopic slides. RESULTS: The number of shadow cells did not statistically significantly differ between patients with MS (median: 12, IQR: 0-85) and OND (median 6, IQR: 0-94; p = 0.106). Multivariable regression analysis including age, sex, time to laboratory processing, CSF WBC and RBC count, CSF/serum glucose ratio, CSF/serum albumin quotient and disease group as independent variables, identified WBC count as significant predictor of shadow cells (ß [ln WBC count]=0.73, p<10-9), whereas the disease group had no impact (p = 0.466). CONCLUSIONS: Occurrence of shadow cells in the CSF seems to depend on the extent of inflammatory cells rather than MS disease-specific mechanisms.

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.

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.

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.