Sex Differences in Amyotrophic Lateral Sclerosis Survival and Progression: A Multidimensional Analysis.

OBJECTIVE: To investigate sex-related differences in amyotrophic lateral sclerosis (ALS) prognosis and their contributing factors. METHODS: Our primary cohort was the Piemonte and Aosta Register for ALS (PARALS); the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) and the Answer ALS databases were used for validation. Survival analyses were conducted accounting for age and onset site. The roles of forced vital capacity and weight decline were explored through a causal mediation analysis. Survival and disease progression rates were also evaluated after propensity score matching. RESULTS: The PARALS cohort included 1,890 individuals (44.8% women). Men showed shorter survival when stratified by onset site (spinal onset HR 1.20, 95% CI 1.00-1.44, p = 0.0439; bulbar onset HR 1.36, 95% CI 1.09-1.70, p = 0.006917), although women had a steeper functional decline (+0.10 ALSFRS-R points/month, 95% CI 0.07-0.15, p < 0.00001) regardless of onset site. Instead, men showed worse respiratory decline (-4.2 forced vital capacity%/month, 95% CI -6.3 to -2.2, p < 0.0001) and faster weight loss (-0.15 kg/month, 95% CI -0.25 to -0.05, p = 0.0030). Causal mediation analysis showed that respiratory function and weight loss were pivotal in sex-related survival differences. Analysis of patients from PRO-ACT (n = 1,394, 40.9% women) and Answer ALS (n = 849, 37.2% women) confirmed these trends. INTERPRETATION: The shorter survival in men is linked to worse respiratory function and weight loss rather than a faster disease progression. These findings emphasize the importance of considering sex-specific factors in understanding ALS pathophysiology and designing tailored therapeutic strategies. ANN NEUROL 2024.

Can we predict adolescent cannabis use? A Bayesian semi-parametric approach to project future trends.

Despite its decrease in many Western countries, cannabis remains the most used illicit substance among adolescents. This study aims to summarize cannabis consumption during the last two decades and project trends among 15-year-olds in the 2021-22 HBSC survey. A Bayesian semi-parametric hierarchical model was adopted to estimate the trend of cannabis consumption using data of about 287,000 adolescents from the 2001/2002 to the 2017/2018 HBSC wave and the 38 countries that met the inclusion criteria. Data show an overall decline in most countries for both boys and girls. However, in 22 countries of 38 cannabis use is expected to increase again in our projection. The discussion of these findings should take into account cultural, policy, social factors and unpredictable events such as the Covid-19 pandemic, that can significantly impact future trends leading to discrepancies between the projected and observed values. However, these discrepancies can provide insight into understanding the potential impact of preventive strategies and the underlying processes responsible for changes in cannabis use over time.

Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy.

Introduction: There are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type. Research question: This study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures. Materials and methods: In this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted. Results: The study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors. Discussion and conclusions: In patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.

Giving Breath to Motor Neurons: Noninvasive Mechanical Ventilation Slows Disease Progression in Amyotrophic Lateral Sclerosis.

OBJECTIVE: Noninvasive mechanical ventilation (NIMV) improves amyotrophic lateral sclerosis (ALS) quality of life and survival. However, data about its effect on disease progression are still lacking. Here, we test whether NIMV use changed the rate of functional decline among ALS patients. METHODS: In this retrospective observational study, we included 448 ALS patients followed up at the ALS Center in Turin, Italy, who underwent NIMV during the disease course. The primary outcome was the change in functional decline after NIMV initiation adjusting for covariates. Functional decline was based on the nonrespiratory items of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). RESULTS: NIMV initiation resulted in a slower functional decline (mean improvement = 0.16 points per month, 95% confidence interval = 0.12-0.19, p < 0.001), with consistent effects observed across various demographic factors, including sex, age at diagnosis, and disease duration before NIMV initiation. This finding was replicated using the PRO-ACT (Pooled Resource Open-Access ALS Clinical Trials) dataset. The favorable impact of NIMV on ALSFRS-R progression was evident independently of disease stages. Notably, NIMV benefits were not dose-dependent but were particularly prominent for nighttime respiratory support. INTERPRETATION: NIMV significantly influences the rate of motor progression in ALS, and this effect is not determined by the nonlinearity of ALSFRS-R trajectory. The functional decline slowed following NIMV initiation, independently of the site of disease onset or disease severity at the time of NIMV initiation. Our findings underscore the importance of timely NIMV initiation for all ALS patients and highlight the need to consider NIMV-induced slowing of disease progression when evaluating clinical trial outcomes. ANN NEUROL 2024;95:817-822.

Risk Behaviors among Migrant Adolescents in Italy.

Adolescence is a critical period for engaging in health risk behaviors. Migrant adolescents may face unique challenges due to acculturation stress. This study aims to monitor substance use and problem gambling among migrant adolescents living in Italy. Data from the 2017/18 Health Behavior in School-Aged Children survey in Italy were analyzed. The 18,794 participants included 15-year-olds, categorized as native or migrants, with ethnic backgrounds from Western, Eastern European, or non-Western/non-European countries. Girls had higher smoking rates, while boys exhibited higher prevalence of alcohol-related risk behaviors, cannabis use, and gambling. Boys from Eastern European countries displayed a greater risk of drunkenness (OR: 1.58, 95% CI: 1.06-2.37), particularly in the first generation, while those from Western countries showed a higher risk of multiple substance use (OR: 1.44, 95% CI: 1.05-1.96). Girls from Eastern European and non-Western/non-European countries had a lower risk of alcohol consumption (OR: 0.50, 95% CI: 0.29-0.85; OR: 0.55, 95% CI: 0.33-0.91, respectively). Finally, boys, especially those from Eastern European and non-Western/non-European countries, had a significantly higher risk of problem gambling (OR: 1.83, 95% CI: 1.04-3.22; OR: 2.10, 95% CI: 1.29-3.42, respectively). This disparity was more pronounced in the first generation, possibly due to acculturation challenges and socio-economic factors. Risk behaviors in adolescents are influenced by complex interplays of gender, cultural factors, and migration generation. Preventive strategies should consider these factors to effectively address substance use and gambling in this heterogeneous population.

Who Stays, Who Moves on and the Host Population: A Picture of Adolescents' Perceived Well-Being and Risk Behaviours.

The study aims to evaluate the health profile of first- and second-generation Romanian immigrants living in Italy compared to their adolescent peers in the country of origin (Romania) and the host population (Italian-borns). Analyses were performed on the 2013/2014 Health Behaviour in School-aged Children (HBSC) survey data. Romanian natives showed lower levels of health complaints and higher life satisfaction than Romanian migrants, who were similar to the host population, especially the second-generation ones. A comparable prevalence of being bullied was registered among Romanians, both native and immigrant, with significantly lower levels among Italian natives. Bullying others showed the second-generation migrants share a similar prevalence with the host population. The prevalence of liking school a lot was three times higher among the Romanian natives than among their peers living in Italy. Thanks to the HBSC data, this study is the first to examine the health of adolescent migrants from both the perspective of the host country and the population of origin. The results highlight the need for a more nuanced approach to studying immigrant populations, taking into account both the host country's perspective and the health patterns of the population of origin.

Suicide spectrum among young people during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: There are concerns that suicidal behaviors are arising among adolescents. The COVID-19 pandemic could have worsened the picture, however, studies on this topic reported contrasting results. This work aimed to summarise findings from the worldwide emerging literature on the rates of suicidality among young people during the COVID-19 pandemic. Methods: A systematic review and meta-analysis were performed, searching five electronic databases for studies published from January 1, 2020 until July 27, 2022. Studies reporting rates for each of the three considered outcomes (suicide, suicidal behaviors, and suicidal ideation) among young people under 19 years old during the COVID-19 pandemic were included. Random-effects meta-analyses were conducted, and the intra-study risk of bias was assessed. When pre-COVID-19 data were available, incidence rate ratio (IRR) and prevalence ratio (PR) estimates were calculated between the two periods. All the analyses were performed according to the setting explored: general population, emergency department (ED), and psychiatric services. The review protocol was registered on PROSPERO (CRD42022308014). Findings: Forty-seven observational studies were selected for more than 65 million subjects. The results of the meta-analysis showed a pooled annual incidence rate of suicides of 4.9 cases/100,000 during 2020, accounting for a non-statistically significant increase of 10% compared to 2019 (IRR 1.10, 95% CI: 0.94-1.29). The suicidal behaviors pooled prevalence during the COVID-19 pandemic was higher in the psychiatric setting (25%; 95% CI: 17-36%) than in the general population (3%; 1-13%) and ED (1%; 0-9%). The pooled rate of suicidal ideation was 17% in the general population (11-25%), 36% in psychiatric setting (20-56%) and 2% in ED (0-12%). The heterogeneity level was over 97% for both outcomes in all settings considered. The comparison between before and during COVID-19 periods highlighted a non-statistically significant upward trend in suicidal behaviors among the general population and in ED setting. The only significant increase was found for suicidal ideation in psychiatric setting among studies conducted in 2021 (PR 1.15; 95% CI: 1.04-1.27), not observed exploring 2020 alone. Interpretation: During the pandemic, suicide spectrum issues seemed to follow the known pattern described in previous studies, with higher rates of suicidal ideation than of suicidal behaviors and suicide events. Governments and other stakeholders should be mindful that youth may have unique risks at the outset of large disasters like the COVID-19 pandemic and proactive steps are necessary to address the needs of youth to mitigate those risks. Funding: The present study was funded by the University of Torino (CHAL_RILO_21_01).

The Association between Greenness and Urbanization Level with Weight Status among Adolescents: New Evidence from the HBSC 2018 Italian Survey.

Recent studies have examined how the environment can influence obesity in young people. The research findings are conflicting: in some studies, green spaces have shown a protective association with obesity and urbanization has turned out to worsen this condition, while other studies contradicted these results. The aim of the study was to examine the relationships between greenness, urbanization, and weight status among Italian adolescents. Student data (11-13 years old) on weight and height, physical activity (PA), and demographic characteristics were extracted from the 2018 Health Behaviour in School-aged Children (HBSC) survey in Piedmont, Northwest of Italy. Data on Normalized Difference Vegetation Index (NDVI) and urbanization were obtained from satellite images and the National Institute of Statistics (ISTAT). A multilevel regression model was used to assess the association between NDVI, urbanization, and obesity, controlling for PA. Students living in greener areas reported a lower likelihood of being obese [OR = 0.11, 95% CI 0.02-0.56, p = 0.007], while students living in areas with a higher level of urbanization showed a significantly increased risk of obesity [OR = 2.3, 95% CI:1.14-4.6, p = 0.02]. Living surrounded by higher amounts of greenness and lower levels of urbanization may positively influence health status through lower risk of obesity among youth.