Literacy in the time of Coronavirus: an Italian perspective: Value of literacy in the context of a pandemic.

Background: COVID-19 pandemic, with its dramatic impact on society, poses a challenge to Health Pro-motion and to its principles of empowerment, social cohesion and citizens' democratic participation in health policies. In this pressing emergency, public health strategies aimed at preventing the spread of the pandemic have been primarily oriented towards restrictive measures (travel restrictions, use of PPE) in absence of an adequate educational communication, aimed at increasing citizens' knowledge and skills in regard to the emergency context. Aim: To offer a perspective on the Italian situation, in terms of health literacy and life skills in the context of COVID-19 pandemic, aimed not only at identifying deficits, but particularly at determining opportuni-ties and resources (assets) - offered by the peculiar context of crisis - useful to provide citizens with the necessary tools to comprehend the criticalities linked with the emergency and to shape their behaviour to new requirements, in absence of external obligations, as well as to promote future participation of the population - both effective and informed - in a social and political context. Methods: A non-systematic review of literature on the subject of health literacy and social cohesion in emergency contexts has been supported by a qualitative assessment, based on the model of assets and on the Italian condition in the last trimester of 2020. Results: The scarce ability of the population to independently adequate habits and behaviour to new criti-calities required by the risk of infection - as well as the necessity to suspend their empowerment and capa-bility from government authorities to protect public health - has been firstly traced back to a widespread lack of literacy and life skills at a general population level. The current situation of crisis offers a peculiar opportunity of tools, circumstances and receptiveness to highlight such deficits, as well as an intervention on multiple fronts, in order to increase literacy and capability, both on an individual and on a community level, through inclusive and sustainable initiatives. Conclusion: A prevention strategy based on the critical understanding of risk and risk-related criticalities is the only one which can aspire to last over time, while offering an effective tool for the safeguarding of public health, along with an opportunity of being prepared to contrast future emergencies more effectively. The development of such strategies represents one of the most significant contributions Health Promotion can offer in the time of Coronavirus.

Order out of chaos: Sense of coherence and the mediating role of coping resources in explaining mental health during COVID-19 in 7 countries.

In the midst of the COVID-19 pandemic and the universal chaos created by it, this study explores the role of sense of coherence (Soc, Antonovsky, 1979) and how it enables coping with a stressful situation and staying well. SOC is a generalized orientation which allows one to perceive the world as comprehensible, manageable, and meaningful. In an attempt to understand 'how does the SOC work' we employed the salutogenic assumption that a strong SOC allows one to reach out in any given situation and find those resources appropriate to the specific stressor. Thus, we hypothesized that the positive impact of SOC on mental health outcomes would be mediated through coping resources that are particularly salient in times of crisis. One resource is related to the micro level (perceived family support) and the other concerns the macro level (trust in leaders and social-political institutions). Data collection was conducted in different countries during May-June 2020 via online platforms. The data included 7 samples of adult participants (age 18-90) from Israel (n â€‹= â€‹669), Italy (n â€‹= â€‹899), Spain (n â€‹= â€‹476), Germany (n â€‹= â€‹708), Austria (n â€‹= â€‹1026), Switzerland (n â€‹= â€‹147), and the U.S. (n â€‹= â€‹506). The questionnaires included standard tools (MHC-SF, SOC-13) as well as questionnaires of perceived family support and trust that were adapted to the pandemic context. As expected, SOC was associated with mental health in all the samples. Perceived family support and trust in leaders and social-political institutions mediated the relationships between SOC and mental health, controlling for age, gender, and level of financial risk. It appears that SOC has a universal meaning, not limited by cultural and situational characteristics. The discussion focuses on the theoretical, social, and political applications of the salutogenic model - and its core concept of SOC - in the context of coping with a global pandemic across different cultural contexts and countries.

Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients.

Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.

Relationship between albuminuric CKD and diabetic retinopathy in a real-world setting of type 2 diabetes: Findings from No blind study.

BACKGROUND AND AIMS: Recently, the albuminocentric view of diabetic kidney disease (DKD) in type 2 diabetes (T2DM) has been changing. Therefore, the relationship between diabetic retinopathy (DR) and chronic kidney disease (CKD) has to be addressed according to this new clinical presentation of DKD. The aim of this study was to evaluate, in a real-world setting, the correlation DR-DKD in T2DM. METHODS AND RESULTS: A total of 2068 type 2 diabetic patients enrolled in a multicenter cross-sectional study were investigated. Albuminuric subjects were largely prevalent among subjects with DR (p = 0.019). In the whole study population, no difference in albumin excretion rate (AER) was observed between presence/absence of DR; instead, AER was significantly higher among patients with glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (CKD) (p = 0.009), above all in those with CKD and AER ≥0.03 g/24 h (p = 0.005). Multivariate analysis confirmed that eGFR (O.R. 0.976; 95% C.I.: 0.960-1.028; p < 0.001) and AER (O.R. 1.249; 95% C.I. 1.001-1.619; p = 0.004) were independently associated with DR and HDL-cholesterol (O.R.: 1.042; 95% C.I.: 1.011-1.120; p = 0.014). Additionally, among patients with eGFR <60 mL/min/1.73 m2 and albuminuria, both eGFR and AER significantly varied between those with/without DR (p = 0.012 and p = 0.005, respectively), and this finding was observed among only albuminuric patients. Analogous results were obtained considering DR classification. AER was significantly higher among subjects with either proliferative DR (PDR) or severe nonproliferative DR (NPDR), with regard to mild NPDR (0.498 and 0.938 g/die vs. 0.101 g/die; p < 0.001, respectively). Similar results were obtained in the specular subgroups. CONCLUSION: In T2DM with DKD, the AER seems to be related to the presence of DR. This association is confirmed above all in those with more severe DR.

Knowledge about cancer screening programmes in Sardinia.

BACKGROUND: High level of attendance by population is considered a proof of the efficacy in the screening programmes. Public health aims to increase people's attendance to cancer screening. The study aimed at assessing the level of knowledge and awareness about screening of citizens in Cagliari, from June to July 2016. METHODS: Recruitment took place near the atrium of the two main shopping centres of the city. The sample included 270 adults (138 men), 18-75 years old (mean age 46 years old). The information gathered from interviews were categorized by dichotomizing answers according to the knowledge and understanding of the discussed topics. Descriptive analysis was performed. The Chi-square test was used to assess gender and educational differences. RESULTS: Results show that population's knowledge of screening is limited. Although the word "screening" is known, only half of the people who declared to have heard of this word know about the aim of screening. Colorectal cancer screening is the least known. Men and people with lower education are less informed than women and those with high education level. CONCLUSION: In order to raise knowledge and awareness about cancer screening, special attention should be paid to communication and to the use of plain language. Future action should highlight the benefit of the screening procedure and thus contributing to spread the cancer prevention culture. Gender and socioeconomic inequalities must be taken into account when planning screening communication campaigns. General practitioner are highly trusted by people. They could play a decisive role to promote screening attendance.

Pregnancy planning and outcomes in patients with multiple sclerosis after mitoxantrone therapy: a monocentre assessment.

BACKGROUND AND PURPOSE: Patients with multiple sclerosis (MS) have many pregnancy-related doubts and fears. Careful counselling is thus important. Mitoxantrone (MITO) is used in patients with aggressive MS and may affect reproductive capacity. The aim of this study was to investigate pregnancy planning and outcomes in patients with MS treated with MITO, both before and after the treatment. METHODS: Patients with MS previously treated with MITO were recruited. Clinical, demographic and treatment data were recorded. A questionnaire regarding the planning and outcomes of all pregnancies was administered. Parametric and non-parametric tests were performed using SPSS 22 software. RESULTS: A total of 238 patients (female/male, 158/80) were included; 106 subjects planned a pregnancy before MITO and 40 after MITO. Of these, respectively, 102 (97%) and 35 (85%) resulted in conception, 19 (19%) and 7 (18%) in miscarriage, 6 (6%) and 1 (3%) in abortion and 98 (96%) and 32 (91%) were full-term pregnancies. A total of 96 patients (40%) planned a pregnancy only before MITO (and not after), whereas 30 (13%) planned a pregnancy only after MITO (and not before) (P < 0.01). A total of 103 patients did not plan a pregnancy before MITO and 198 did not plan a pregnancy after MITO. The reasons included lack of interest or a partner, fear of MS and infertility. All of the babies born were healthy until the end of follow-up. CONCLUSIONS: Mitoxantrone does not affect the ability to conceive or pregnancy outcomes. We found no differences in pregnancies, abortions or miscarriages before and after MITO. The tendency to plan pregnancies decreased significantly after MITO. Our findings may be useful for improving the quality of life of patients and the approach taken by neurologists.

Combining HLA-DRB1-DQB1 and Mycobacterium Avium Subspecies Paratubercolosis (MAP) antibodies in Sardinian multiple sclerosis patients: associated or independent risk factors?

BACKGROUND: Amongst Sardinians the human leukocyte antigen (HLA) DRB1-DQB1 haplotypes *15:02-*06:01, *16:01-*05:02, *14:01-4-*05:03 are protective for multiple sclerosis (MS), while *13:03-*03:01, *04:05-*03:01, *03:01-*02:01, *15:01-*06:02 and Mycobacterium avium subspecies paratubercolosis (MAP) are predisposing factors. We studied the correlation between MAP and HLA. METHODS: Five hundred thirty-one patients were searched for anti-MAP2694 antibodies, DRB1-DQB1 genotyping was performed. The haplotypes were classified as predisposing, neutral or protective. RESULTS: Anti-MAP2694 were found in 23 % of subjects carrying one protective HLA versus 32 % without (p = 0.04). CONCLUSIONS: We showed a lower frequency of Abs in patients with protective HLA. These haplotypes could have a protective role for both MS and MAP.

Telemonitoring in heart failure patients treated by cardiac resynchronisation therapy with defibrillator (CRT-D): the TELECART Study.

AIM: Telemonitoring (TM) is a safe and efficient monitoring system for internal cardioverter defibrillator device (ICD) recipients. TM has been used to track info on the clinical status of heart failure patients treated by ICD and/or cardiac resynchronisation therapy defibrillator (CRT-D). The aim of this study was to investigate the impact of TM on clinical outcomes in a population of CRT-D patients with heart failure. METHODS: In a multicentre, randomised study, patients with chronic heart failure, New York Heart Association (NYHA) functional class II or III, left bundle branch block, severe left ventricle ejection fraction reduction (LVEF < 35%) have been identified and screened. RESULTS: One hundred and ninety-one patients have been randomised to receive either a CRT-D with TM or a CRT-D with traditional ambulatory monitoring (control group) and completed the 12-month study follow-up. Primary endpoints were all cause death, cardiac death and hospital admission for heart failure. Secondary endpoints were atrial fibrillation, sustained episodes, non-sustained and self terminated ventricular tachyarrhythmia, sustained ventricular tachycardia, and ventricular fibrillation, ICD shocks and percentage of CRT-D responder patients. Univariate analysis identified the following factors predicting hospitalisation: TM, age, chronic kidney disease, hypercholesterolaemia, LVEF and NYHA class. At multivariate analysis, TM was the only factor predicting heart failure hospitalisation (hazard ratio 0.6, 0.42-0.79, 95% CI, p = 0.002), without affecting overall mortality and cardiac deaths events. CONCLUSIONS: Taken together, our data indicate the importance of TM in predicting heart failure hospitalisation in patients treated with CRT-D.

Community of practice in healthcare: an investigation on nursing students' perceived respect.

In the healthcare setting, Community of Practice (CoP) can be defined as the learning environment where nursing students develop their attitudes toward the nursing profession. Although being part of a CoP is important for nursing students, it can sometimes result in a negative experience where students often perceive a lack of respect. The aim of this study was to expand the knowledge of the CoP in the healthcare setting by analyzing students' perception of respect during clinical placements. Important aspects, such as a professional role concept (role ambiguity and role conflict), tutor support, feedback and relationship with tutors and staff were investigated as predictors of student's perceived respect. A total of 188 Nursing Science Degree undergraduate students were recruited during 2012. Data were analyzed by using regression analysis. The findings supported the importance of role stress, feedback from CoP members, tutor support, and relationship with CoP members on nursing students' perceived respect. The results suggest that when studying nursing students in a CoP, the social context can contribute to affect students' perceived respect.

Mycobacterium avium subsp. paratuberculosis and multiple sclerosis in Sardinian patients: epidemiology and clinical features.

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is an infectious factor recently found in association with multiple sclerosis (MS) in Sardinia. OBJECTIVES: The objectives of this study were to confirm this association and evaluate its role in clinical features. METHODS: A total of 436 patients and 264 healthy controls (HCs) were included. We examined the blood of each individual for MAPDNA and MAP2694 antibodies using IS900-specific PCR and ELISA, respectively. Differences in MAP presence between the MS group and HCs were evaluated. In MS patients, we considered: gender, age, age at onset, duration of disease, course, EDSS, therapy, relapse/steroids at study time, and oligoclonal bands (OBs). RESULTS: MAPDNA and MAP2694 antibodies were detected in 68 MS and six HCs (p = 1.14 × 10(-11)), and 123 MS and 10 HCs (p = 2.59 × 10(-23)), respectively. OBs were found with reduced frequency in MAP-positive patients (OR = 0.52; p = 0.02). MAP2694 antibodies were detected more in patients receiving MS treatments (OR = 2.26; p = 0.01), and MAPDNA in subjects on steroids (OR = 2.65; p = 0.02). CONCLUSION: Our study confirmed the association of MAP and MS in Sardinia. The low OB frequency in MAP patients suggests a peripheral role as a trigger in autoimmunity. MAP positivity might be influenced by steroids and MS therapy. Studies in other populations are needed to confirm the role of MAP in MS.

Multiple sclerosis risk: interaction between human leukocyte antigen and the environment in Sardinian population.

BACKGROUND: The island of Sardinia features a high incidence of multiple sclerosis (MS) characterized by early age at onset and a progressively increasing trend. The current study was aimed at examining variations in human leukocyte antigen-risk genotypes occurring over time in a cohort of patients. METHODS: Susceptible and neutral DRB1-DQB1 genotypes were identified in 1660 patients. Age at onset was established in 1436 patients divided into two cohorts, an older cohort (subjects born before 1949, N = 233) and a younger one (subjects born from 1960 to 1989, N = 850). Patients from the older cohort were randomly assigned to patients of the same sex from the younger cohort, matched for age at onset. The final sample included 170 pairs. Logistic conditional analysis was performed to determine the probability of a neutral genotype in both cohorts. Kaplan-Meier analysis was applied to ascertain the influence of predisposing and neutral genotypes in age at onset for both cohorts. FINDINGS: The probability of carrying a neutral genotype was 1.76-fold higher in the younger than in the older cohort (P = 0.02) and 3.67-fold higher in men (P = 0.005). Kaplan-Meier analysis revealed an earlier age at onset in patients of the young cohort carrying the predisposing genotype (P = 0.004). INTERPRETATION: In the Sardinian population, an environment more prone and propitious to autoimmunity may contribute toward the rising incidence of MS or anticipate overt manifestation of the disease in genetically predisposed subjects.

The Italian national trends in smoking initiation and cessation according to gender and education.

UNLABELLED: OBJECTIVES. This study aims to assess the trend in initiation and cessation of smoking across successive birth cohorts, according to gender and education, in order to provide useful suggestion for tobacco control policy. STUDY DESIGN. The study is based on data from the "Health conditions and resort to sanitary services" survey carried out in Italy from October 2004 to September 2005 by the National Institute of Statistics. Through a multisampling procedure a sample representative of the entire national territory was selected. METHODS: In order to calculate trends in smoking initiation and cessation, data were stratified for birth cohorts, gender and education level, and analyzed through the life table method. RESULTS: The cumulative probability of smoking initiation, across subsequent generations, shows a downward trend followed by a plateau. This result highlights that there is not a shred of evidence to support the hypothesis of an anticipation in smoking initiation. The cumulative probability of quitting, across subsequent generations, follows an upward trend, highlighting the growing tendency of smokers to become an "early quitter", who give up within 30 years of age. CONCLUSION: Results suggest that the Italian antismoking approach, for the most part targeted at preventing the initiation of smoking emphasising the negative consequences, has an effect on the early smoking cessation. Health policies should reinforce the existing trend of "early quitting" through specific actions. In addition our results show that men with low education exhibit the higher probability of smoking initiation and the lower probability of early quitting, and therefore should be targeted with special attention.

Frequency and risk factors of mitoxantrone-induced amenorrhea in multiple sclerosis: the FEMIMS study.

BACKGROUND: Improved prognosis in women with multiple sclerosis (MS) undergoing immunosuppressive treatment with mitoxantrone (MITO) has led to an increased interest in the effect of such treatments on fertility. FErtility and Mitoxantrone In MS (FEMIMS) is a collaborative retrospective study aimed at evaluating the impact of MITO treatment on fertility in women with MS. METHODS: Occurrence of chemotherapy-induced amenorrhea (CIA) was evaluated in 189 women with MS treated with MITO before the age of 45. An "ad hoc" questionnaire, paying particular attention to onset of CIA either during or post-MITO treatment, was administered to each patient. The probability of CIA was calculated using a multivariate logistic regression analysis taking into account age at exposure, cumulative dose, and use of estroprogestinic (EP) drugs during treatment. RESULTS: Forty-eight (26%) patients presented CIA following MITO. The probability of CIA was increased by 2%/mg/m(2) of cumulative dose and by 18% for each year of age, whereas it was reduced by administration of EP during treatment. CONCLUSIONS: MITO treatment may affect reproductive capacity in women with MS. Patients of childbearing age should be properly counseled before MITO treatment and EP therapy should be administered to reduce the risk of CIA.

Mitoxantrone treatment in patients with early relapsing-remitting multiple sclerosis.

We investigated the clinical and MRI effects of mitoxantrone (MITOX) administered to 45 patients during the first five years of highly active relapsing-remitting multiple sclerosis. Differences occurring between the end of treatment and follow-up (clinical mean: 3.6 years; brain MR: 1.8 years) with respect to baseline variables (EDSS, annualized relapse rate, active T2 lesions, new T1 lesions and number of Gd-enhancing lesions) were analysed using parametric and non-parametric tests. One patient developed leukemia four months after the end of the treatment; no other serious adverse events occurred during treatment and the follow-up period. A clinically relevant reduction in the annualized relapse rate ( P < 0.0001 at end of treatment and P < 0.0001 at follow-up) and improvement in the EDSS (P < 0.0001 at end of treatment and P = 0.0005 at follow-up) was found. At the end of treatment, 53% of patients experienced no increase in active T2 lesions, while 73% showed no increase in the number of new T1 lesions. At follow-up, 41 out of 45 (91%) patients showed a stable MRI pattern and were active-scan free. Despite potential serious adverse events, MITOX may be considered an option in selected patients with very active early MS.

Participative risk communication in an industrial village in Sardinia.

OBJECTIVE: In Italy the law on industrial risk has emphasised the necessity of building a local information process to answer people's questions on safety and provide greater community participation in risk management. The aim of this research is to analyse the local population's ideas and expectations of a participatory approach in risk management in order to design a risk communication programme based on health promotion principles. DESIGN, SETTING AND PARTICIPANTS: The study was carry out in Portoscuso (Italy), an industrial district. A questionnaire was administrated through home interviews to 147 citizens. MAIN RESULTS: Six risk management styles were identified on the basis of citizens' trust in the different stakeholders. Additional parameters (importance of information, organisations they would trust to get information on industrial risks, preferred risk communication methodologies) were analysed according to the management styles. CONCLUSIONS: On the basis of these elements, a multi-approach strategy could be proposed. Each management style can have different roles. A programme of public forums could involve citizens with an interactive approach, interactive courses could involve citizens with a semi-participative approach, and leaflets and booklets could inform citizens oriented towards unidirectional communication. The participative process should always be open to new contributions from citizens who are not directly involved, and should allow for flexibility in the form and nature of partnership, as well as the details of implementation.

Smoking trends in Italy from 1950 to 2000.

STUDY OBJECTIVE: To assess how the prevalence of smokers in Italy from 1950 to 2000 has changed, in parallel with law development and the growing attention towards smoking prevention. DESIGN, SETTING, AND PARTICIPANTS: Historical data on smoking trends have been obtained using data collected in 2000 by the National Institute of Statistics. A correction coefficient is proposed to overcome the bias of differential mortality reported in other papers. The sample is made up of 102 261 people aged 15-69 years. MAIN RESULTS: A general downward trend is seen; there is a more pronounced decrease starting from 1975 to 1980. In both sexes the peak prevalence tends to decrease according to the birth cohort because of the earlier age in which they gave up. A partial exception to the decline of tobacco use in recent years may be made for the 15-19 year-old age group, which has remained stable since 1990. CONCLUSIONS: Although a comprehensive community programme against tobacco was not developed, the different prevention actions implemented in Italy have contributed to a change in attitude and behaviour. The effect of tobacco control strategies implemented in Italy until now is more evident in relation to the breaking of the smoking habit, which happens at an increasingly younger age, although it is not clear how much it is able to prevent people from starting smoking.

Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with Type 2 diabetes mellitus.

BACKGROUND: Oxidative stress and increased inflammation have been reported to be increased in subjects with diabetes and to be involved in the pathogenesis of cardiovascular complications after myocardial infarction (MI). It is well recognized that red wine has antioxidant and anti-inflammatory activities. We examined the effects of moderate red wine intake on echocardiographic parameters of functional cardiac outcome in addition to inflammatory cytokines and nitrotyrosine (oxidative stress marker), in subjects with diabetes after a first uncomplicated MI. METHODS: One hundred and fifteen subjects with diabetes who had sustained a first non-fatal MI were randomized to receive a moderate daily amount of red wine (intervention group) or not (control group). Echocardiographic parameters of ventricular dys-synchrony, circulating levels of nitrotyrosine, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP) were investigated at baseline and 12 months after randomization. RESULTS: After 1 year of diet intervention, concentrations of nitrotyrosine (P < 0.01), CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01) and IL-18 (P < 0.01) were increased in the control group compared with the intervention group. In addition, myocardial performance index (P < 0.02) was higher, and transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02) and ejection fraction (P < 0.05) were lower in the control group, indicating ventricular dys-synchrony. The concentrations of nitrotyrosine, CRP, TNF-alpha and IL-6 were related to echocardiographic parameters of ventricular dys-synchrony. CONCLUSIONS: In subjects with diabetes, red wine consumption, taken with meals, significantly reduces oxidative stress and pro-inflammatory cytokines as well as improving cardiac function after MI. Moderate red wine intake with meals may have a beneficial effect in the prevention of cardiovascular complications after MI in subjects with diabetes.

Interaction of loci within the HLA region influences multiple sclerosis course in the Sardinian population.

We examined the influence of alleles at the HLA loci, previously found to be associated with multiple sclerosis (MS) in Sardinia, on the clinical course of the disease in 835 relapsing (R) and 100 primary progressive (PP) patients. Multivariate analysis was carried out on predisposing 0301 or non-associated DPB1 alleles, susceptible or non-associated DRB1-DQB1 haplotypes, both predisposing and non-predisposing, and negatively and non-negatively associated D6S1683 alleles, taking interaction between them into account. Intra-patient analysis showed that the presence of the susceptible or protective D6S1683 allele interacting with predisposing DP 0301 modulated risk of PP disease. These findings suggest that a locus telomeric to HLA class I exerts an effect on alleles at the DPB1 locus in modulating disease course.