The economic impact of comorbidity in multiple sclerosis.

BACKGROUND: Comorbid conditions are common in people with multiple sclerosis (pwMS). They can delay diagnosis and negatively impact the disease course, progression of disability, therapeutic management, and adherence to treatment. OBJECTIVE: To quantify the economic impact of comorbidity in multiple sclerosis (MS), based on cost-of-illness estimates made using a bottom-up approach. METHODS: A retrospective study was carried out in two northern Italian areas. The socio-demographic and clinical information, including comorbidities data, were collected through ad hoc anonymous self-assessment questionnaire while disease costs (direct and indirect costs of disease and loss of productivity) were estimated using a bottom-up approach. Costs were compared between pwMS with and without comorbidity. Adjusted incremental costs associated with comorbidity were reported using generalized linear models with log-link and gamma distributions or two-part models. RESULTS: 51.0% of pwMS had at least one comorbid condition. Hypertension (21.0%), depression (15.7%), and anxiety (11.7%) were the most prevalent. PwMS with comorbidity were more likely to use healthcare resources, such as hospitalizations (OR = 1.21, p < 0.001), tests (OR = 1.59, p < 0.001), and symptomatic drugs and supplements (OR = 1.89, p = 0.012), and to incur non-healthcare costs related to investment (OR = 1.32, p < 0.001), transportation (OR = 1.33, p < 0.001), services (OR = 1.33, p < 0.001), and informal care (OR = 1.43, p = 0.16). Finally, they experienced greater productivity losses (OR = 1.34, p < 0.001) than pwMS without comorbidity. The adjusted incremental annual cost per patient due to comorbidity was €3,106.9 (13% of the overall costs) with MS disability found to exponentially affect annual costs. CONCLUSION: Comorbidity has health, social, and economic consequences for pwMS.

ALLiance for sEcondary PREvention after an acute coronary syndrome. The ALLEPRE trial: A multicenter fully nurse-coordinated intensive intervention program.

The main objective of cardiovascular disease prevention is to reduce morbidity and mortality by promoting a healthy lifestyle, reducing risk factors, and improving adherence to medications. Secondary prevention after an acute coronary syndrome has proved to be effective in reducing new cardiovascular events, but its limited use in everyday clinical practice suggests that there is considerable room for improvement. The short-term results of evidence-based studies of nurse-coordinated secondary prevention programs have been positive, but there is a lack of long-term outcome data. The Alliance for the Secondary Prevention of Cardiovascular Disease in the Emilia-Romagna region (ALLEPRE) is a multicenter, randomized, controlled trial designed to compare the effects of a structured nurse-coordinated intensive intervention on long-term outcomes and risk profiles after an acute coronary syndrome with those of the standard of care. All of the patients randomized to the intervention group take part in 9 one-to-one sessions with an experienced nurse from the participating centers with the aim at promoting healthy lifestyles, reducing risk factors, and increasing adherence to medication over a mean period of 5 years. The primary clinical end point is the reduction in the risk of the 5-year occurrence of major adverse events (a composite of cardiovascular mortality, nonfatal reinfarction, and nonfatal stroke). The primary surrogate end point is the achievement of prespecified targets relating to classical risk factors, lifestyle modifications, and adherence to pharmacological therapy after 2 years of follow-up. Coronary heart disease is a chronic degenerative disease, and patients who recover from an acute coronary syndrome (ACS) are at high risk of developing recurrent events.1 Although secondary prevention measures have proved to be effective and are strongly recommended by all of the international guidelines,2., 3. the 4 EUROASPIRE surveys4., 5., 6., 7., 8. showed that there was still a high prevalence of conventional risk factors, that secondary prevention measures were inadequately implemented, and that their main goals were often not reached. In addition, there were considerable discrepancy in secondary prevention practices between centers and countries, and a widespread underuse of cardiac prevention and rehabilitation programs despite their demonstrated effectiveness in reducing cardiovascular risk over time.9., 10. Over the last 10 years, nurses have been increasingly involved in successful cardiovascular risk management,11., 12., 13. but although this has improved levels of cardiovascular risk, no clear reduction in hard end points such as major cardiovascular adverse events and mortality has been demonstrated.10 The aim of the ALLEPRE trial is to evaluate the benefit of a homogeneous, structured, secondary prevention intervention program, fully coordinated by nurses from in- and outpatient clinics, in terms of cardiovascular risk profiles and major clinical events in ACS patients living in the large Emilia-Romagna region of Italy.

Cognitive function in DMD carriers: personal case series and literature review.

Improvement in clinical conditions allowed physicians to pay more attention to the cognitive function in DMD patients, leading to description of a cognitive impairment not only in affected males, but in female carriers as well. This study aimed to investigate the cognitive involvement in a cohort of DMD carriers and to summarize the current knowledge about the intellectual involvement and neuropsychological profile in DMD/BMD carriers. Our case series consisted of 22 carrier patients from two different centers (IRCCS Mondino, Pavia and Policlinico Gemelli, Rome), for whom we retrospectively collected cognitive, clinical and genetic data. For literature review, we selected 9 studies published in English language from 2011 to 2023 and cited in PubMed. We found that the average IQ of DMD carriers was lower (74; very low) than the average score on normal curve (100 as average standard score). Furthermore, about 50% of them fell in the "extremely low IQ" range, compared with 2-3% of general population. A higher incidence of intellectual disability was confirmed in symptomatic DMD carriers (mean IQ 66; extremely low) from IRCCS Mondino, but not in the asymptomatic ones (mean IQ 99; average), when compared to the general population. Current literature, albeit limited, seems to confirm the presence of a cognitive impairment in carriers, although milder than in affected males but with a similar neuropsychological profile. However, further studies are necessary to delve deeper into this issue and provide adequate educational support.

Evidence for novel cell defense mechanisms sustained by dimethyl fumarate in multiple sclerosis patients: the HuR/SOD2 cascade.

BACKGROUND: Dimethyl fumarate (DMF) is an effective treatment for relapsing remitting Multiple Sclerosis (MS) and its mechanisms of action encompass immunomodulatory and cytoprotective effects. Despite DMF is known to activate the Nrf2 pathway, Nrf2-independent mechanisms have been also reported and new insights on the underlying molecular mechanisms are still emerging including transcriptional and post-transcriptional events. At this regard, we focused on a small family of RNA-binding proteins, the ELAV-like proteins, that play a pivotal role in post-transcriptional mechanisms and are involved in the pathogenesis of several psychiatric and neurologic disorders. HuR, the ubiquitously expressed member of the family, is implicated in many cellular functions, including survival, inflammation and proper functioning of the immune system. We previously documented the potential entanglement of HuR in MS pathogenesis. In the present work, we explored HuR protein levels in peripheral blood mononuclear cells (PBMCs) from MS patients before and after DMF treatment compared to healthy controls (HC). Considering that HuR may act on various targets, playing a protective role against oxidative stress, our main goals were to evaluate whether manganese-dependent superoxide dismutase transcript (SOD2) could represent a new molecular target of HuR and to study the potential influence of DMF treatment on this interaction. METHODS: PBMCs from 20 patients with MS and 20 frequency-matched HC by sex and age were used to evaluate HuR, MnSOD (the protein coded by SOD2) and Nrf2 protein content by Western blot, before and after 12 months of DMF treatment. Immunoprecipitation experiments coupled with RNA extraction in PBMCs were performed to explore whether SOD2 mRNA could be physically bound by HuR and whether the expression of MnSOD protein could be affected by 12 months of DMF treatment. RESULTS: In PBMCs, HuR protein binds SOD2 transcript in HC and in MS patients naïve to disease modifying treatment. The expression of MnSOD protein is positively affected by 12 months of DMF treatment. PBMCs from MS patients have a lower HuR and MnSOD protein content compared to matched HC (HuR: p<0.01, MnSOD: p<0.01). Of interest, 12 months of DMF treatment in MS patients restores the amount of both HuR protein and MnSOD enzyme to the levels observed in HC. We also confirmed that Nrf2 is an HuR target, and we report that its levels are significantly increased in MS patients naïve to disease modifying treatment and remain elevated following DMF administration. CONCLUSION: SOD2 transcript is a new target of HuR protein. DMF induces an increased expression of HuR protein, which ultimately interacts more strongly with SOD2 transcript promoting the expression of this antioxidant protein. The activation of this molecular cascade can constitute an additional tool that the cells can exploit to counteract the oxidative stress associated with MS development, and can account for the multifaceted molecular mechanisms underlying DMF efficacy in MS.