Incidence and Prevalence of Dementia: A 2015-2020 Population-Based Study in the Campania Region of Italy.

OBJECTIVE: The aims of this study were to provide population-based estimates of prevalence and incidence of any dementia and Alzheimer's dementia (AD) in the Campania region (South Italy) and to validate towards a clinical registry. METHODS: This was a population-based study, using routinely collected healthcare data of individuals living in the Campania region (South Italy) from 2015 to 2020. We included individuals aged ≥65 years alive at the prevalence day (January 1, 2021) who had at least one administrative record for dementia and/or AD from 2015 to 2020. Age-and sex-standardised prevalence rates were calculated using direct standardisation method (European population in 2020 as the reference population). To estimate the incidence, we tested three possible algorithms, which differed for the duration of the time interval between study baseline (January 1, 2015) and index date (first record for dementia and/or AD in administrative databases). We employed a clinical database for the validation of our algorithms towards neuropsychological test results. RESULTS: Among individuals aged over 65 years, 80,392 had dementia, of which 35,748 had AD. The age- and sex-standardised prevalence rates per 1,000 individuals for any dementia and AD were 77.64 (95% confidence interval [CI] = 77.57; 77.68) and 34.05 (95% CI = 34.01; 34.09), respectively. There were 82.10 incident cases of any dementia per 100,000 per year (0.79 sensitivity and 0.62 specificity) and 59.89 incident cases of AD per 100,000 per year (0.80 sensitivity and 0.59 specificity). The capture-recapture method showed a very low number of undetected cases (1.7% for any dementia and 3.0% for AD). Our algorithms showed acceptable performance with the area under the curve ranging from 0.59 to 0.72 and a double likelihood ratio of correctly identifying individuals above and below mini-mental status examination (MMSE) standard cut-offs (24 and 26). CONCLUSIONS: Prevalence and incidence of any dementia and AD in the Campania region (South Italy) from 2015 to 2020 are in line with previous estimates from other countries. Our algorithm, integrating administrative and clinical data, holds potential for assessing dementia's epidemiological burden, identifying risk factors, planning healthcare access, and developing prevention strategies.

Fertility, pregnancy and childbirth in women with multiple sclerosis: a population-based study from 2018 to 2020.

BACKGROUND: We aim to evaluate whether fertility, pregnancy, delivery and breastfeeding have been actually improving in women with multiple sclerosis (MS), compared with general population, and in relation to treatment features. METHODS: We included 2018-2020 population-level healthcare data on women with MS living in the Campania region (Italy). Fertility, pregnancy and delivery outcomes were obtained from Certificate of Delivery Assistance; breastfeeding was collected up to 6 months after delivery by trained personnel. RESULTS: Out of 2748 women with MS in childbearing age, 151 women delivered 156 babies. Fertility rate was 0.58 live births per woman with MS, compared with 1.29 in Campania region and 1.25 in Italy. Disease-modifying treatment (DMT) continuation during pregnancy was associated with lower birth weight (coeff -107.09; 95% CI -207.91 to -6.26; p=0.03). Exposure to DMTs with unknown/negative effects on pregnancy was associated with birth defects (OR 8.88; 95% CI 1.35 to 58.41; p=0.02). Birth defects occurred in pregnancies exposed to dimethyl fumarate (2/21 exposed pregnancies), fingolimod (1/11 exposed pregnancies) and natalizumab (2/30 exposed pregnancies). After delivery, 18.8% of women with MS were escalated of DMT efficacy, while 50.7% started on same/similar-efficacy DMTs, and 30.5% did not receive DMT. The probability of breastfeeding was higher in women who were treated with breastfeeding-safe DMTs (OR 5.57; 95% CI 1.09 to 28.55; p=0.03). CONCLUSIONS: Fertility rate in women with MS remains below the general population. Family planning and subsequent DMT decisions should aim to achieve successful pregnancy, delivery and breastfeeding outcomes, while controlling disease activity.

Management of vascular risk in people with multiple sclerosis at the time of diagnosis in England: A population-based study.

BACKGROUND: Vascular management in People with Multiple Sclerosis (PwMS) is important given the higher vascular burden than the general population, associated with increased disability and mortality. OBJECTIVES: We assessed differences in the prevalence of type 2 diabetes and hypertension; and the use of antidiabetic, antihypertensive and lipid-lowering medications at the time of the MS diagnosis. METHODS: This is a population-based study including PwMS and matched controls between 1987 and 2018 in England. RESULTS: We identified 12,251 PwMS and 72,572 matched controls. PwMS had a 30% increased prevalence of type 2 diabetes (95% confidence interval (CI) = 1.19, 1.42). Among those with type 2 diabetes, PwMS had a 56% lower prevalence of antidiabetic usage (95% CI = 0.33, 0.58). Prevalence of hypertension was 6% greater in PwMS (95% CI = 1.05, 1.06), but in those with hypertension, usage of antihypertensive was 66% lower in PwMS (95% CI = 0.28, 0.42) than controls. Treatment with lipid-lowering medications was 63% lower in PwMS (95% CI = 0.54, 0.74). PwMS had a 0.4-mm Hg lower systolic blood pressure (95% CI = -0.60, -0.13). 3.8% of PwMS were frail. CONCLUSION: At the time of diagnosis, PwMS have an increased prevalence of vascular risk factors, including hypertension and diabetes though paradoxically, there is poorer treatment. Clinical guidelines supporting appropriate vascular assessment and management in PwMS should be developed.

Impact of COVID-19 and system recovery in delivering healthcare to people with multiple sclerosis: a population-based Study.

BACKGROUND: COVID-19 pandemic has affected the management of multiple sclerosis (MS). OBJECTIVE: To explore the impact of COVID-19 on healthcare delivery to people with MS and the subsequent recovery of the system. METHODS: In this population-based study in the Campania Region (Italy), we included people with MS across pre-COVID-19, lockdown, pre-vaccination, and vaccination periods. Differences in continuous outcomes between periods were explored using linear mixed models (annualized hospitalization rate (AHR) and adherence measured as medication possession ratio (MPR)). Differences in disease-modifying treatment (DMT) prescription rates (first DMT prescription, any DMT switch, switch from platform to highly effective DMT, and combination of first DMT prescription and any DMT switch) were assessed using an interrupted time series design. RESULTS: Compared with pre-COVID-19, AHR decreased during the lockdown (Coeff = 0.64;95%CI = -0.69, -0.59; p < 0.01), and remained lower during pre-vaccination and vaccination periods. Adherence decreased during pre-vaccination (Coeff = -0.04;95%CI = -0.05, -0.03; p < 0.01) and vaccination periods (Coeff = -0.07;95%CI = -0.08, -0.07; p < 0.01). After the lockdown, there was an increase in any DMT switch (IRR 2.05 95%CI 1.38,3.05; p < 0.01), in switch from platform to highly effective DMTs (IRR 4.45;95%CI 2.48,8.26; p < 0.01) and in first DMT prescriptions (IRR 2.48;95%CI 1.64,3.74; p < 0.01). CONCLUSIONS: DMT prescriptions quickly returned to pre-pandemic levels, reflecting good health system recovery. However, adherence has remained lower than the past, as from suboptimal care. Assessing long-term COVID-19 impact on MS healthcare is warranted.

Clinically relevant profiles of myelin content changes in patients with multiple sclerosis: A multimodal and multicompartment imaging study.

OBJECTIVE: To investigate the clinical relevance of individual profiles of cortical and white matter lesion myelin content changes combining magnetisation transfer imaging (MTI) and 11C-PiB-positron emission tomography (PET) in patients with multiple sclerosis (MS). METHODS: MTI and [11C]PiB-PET acquired in 19 patients with MS followed up over 2-4 months and in seven healthy controls (HCs), were employed to generate individual maps of cortical and white matter (WM) lesion myelin content changes, respectively. These maps were used to calculate individual indices of demyelination and remyelination, and to investigate their association with clinical scores. RESULTS: Cortical remyelination ranged between 1% and 5% of the total cortical volume (17%-45% of the cortical volume demyelinated at baseline). WM lesion remyelination ranged between 8% and 22% of the lesional volume. An extensive cortical remyelination was associated with a shorter disease duration (rho = -0.63, p = 0.01) and, in combination with WM lesion remyelination, explained 68%-70% of the variance of clinical scores (p < 0.01). CONCLUSION: Our multimodal and multicompartment approach allows us to explore single-patient cortical and WM lesion demyelination and remyelination, and to generate clinically relevant indices of myelin repair. These indices may be used as outcome measures in clinical trials, thus increasing the chance to identify successful promyelinating treatments in patients with MS.

Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy).

BACKGROUND: Emergency hospital admissions are common in multiple sclerosis (MS), and can highlight unmet medical needs. OBJECTIVES: To evaluate burden, predictors and outcomes of MS emergency admissions. METHODS: This is a population-based study, conducted in the Campania Region (South Italy) from 2015 to 2019, using hospital discharge records, drug prescriptions and outpatients. The risk of emergency hospital admissions and the likelihood of worse outcomes were evaluated using the Cox regression and multinomial logistic regression models, respectively, in relation to age, sex, disease-modifying treatments (DMTs), comorbidities and adherence. RESULTS: We recorded 1225 emergency admissions for 1001 patients (out of 5765 prevalent MS patients), overall costing 4,143,764.67 EUR. The risk of emergency admissions increased with age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) = 1.01, 1.03; p < 0.01) and comorbidities (HR = 1.62; p < 0.01), and decreased in patients using DMTs (interferon beta/peg-interferon beta/glatiramer acetate HR = 0.19; p < 0.01; teriflunomide/dimethyl-fumarate/fingolimod HR = 0.18; p < 0.01, and alemtuzumab/cladribine/natalizumab/ocrelizumab HR = 0.21; p < 0.01), and with higher adherence (HR = 0.18; 95% CI = 0.13, 0.26; p < 0.01). Following emergency admission, older age was associated with probability of death (n = 63) (odds ratio (OR) = 1.06; p < 0.01) and discharge to long-term facility (n = 65) (OR = 1.03; p = 0.01). CONCLUSION: With 17% people with MS requiring emergency medical care over 5 years, improved management of DMTs and comorbidities could potentially reduce their medical, social and financial burden.

Multiple sclerosis and genetic polymorphisms in fibrinogen-mediated hemostatic pathways: a case-control study.

INTRODUCTION: Blood coagulation constituents might exert immunomodulatory functions in the CNS and may trigger neuroinflammation and demyelination. We evaluated whether particular single-nucleotide polymorphisms (SNPs), thought to be involved in fibrinogen-mediated hemostatic pathways, are overrepresented in patients with MS compared with controls. METHODS: The case-control study consisted of 119 MS patients recruited consecutively at our clinic, and 68 healthy controls. Afterwards, we created a cumulative genetic risk score (CGRS) which included the 5 selected hemostatic risk alleles (Beta-Fibrinogen 455G/A, Glycoprotein IIIa P1A2, Factor V Leiden, Factor V H2R, and Prothrombin 20210G/A). Multivariate ordinal logistic regression and multivariate multinomial logistic regression were applied to evaluate the effect of CGRS on MS susceptibility. RESULTS: The FGB 455 G/A and Factor V H1299R variants might be associated with MS status, in the recessive and dominant model, respectively. A cumulative association of the five SNPs investigated with the disease was observed. DISCUSSION: We found that MS patients carried more pro-hemostatic variants than healthy controls. An increasing number of unfavorable alleles might increase the likelihood of being in the MS group, in the cumulative analysis. Our findings encourage to evaluating these variants in a larger population-based cohort.

Disability assessment using Google Maps.

OBJECTIVES: To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). MATERIALS AND METHODS: This is a cross-sectional multicenter study. AS and EDSS were calculated using GM® and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. RESULTS: Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM® and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1-7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01-1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04-1.17, p = 0.002) were associated with discrepancies between GM® and routine clinical scoring. CONCLUSION: GM® could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM® should be considered for validation in further clinical studies.

Relationship of the Intake of Water and Other Beverages With Renal Endpoints: Cross-Sectional and Longitudinal Data-Observational, Population-Based Study.

OBJECTIVES: The relationship of water intake with kidney function in the population is uncertain. This study investigated cross-sectionally and longitudinally the relationship of the intake of water and other beverages with kidney function within an adult Italian population sample. METHODS: In 4,554 Gubbio Study examinees (54.4% women, age 18-95 years), data collection at baseline included demographics, anthropometry, questionnaires on habitual intakes of water and other beverages (non-water fluids), a timed overnight urine collection, estimated glomerular filtration rate (eGFR), decreased eGFR (<60 mL/minute/1.73 m2), and other variables including urinary markers of diet. At 15-year follow-up, the incidence of renal/kidney replacement therapy, the eGFR change from baseline, and the incidence of decreased eGFR were used as indices of kidney function change over time. RESULTS: In multivariable analyses, higher water intake is independently related to higher urine flow (beta = 0.163, P < .001), lower urine osmolality (beta = 0.184, P < .001), lower eGFR (beta = 0.030, P = .002), and higher prevalence of decreased eGFR (logistic coefficient ± standard error = 1.13 ± 0.32, P < .001). Water intake did not relate to kidney function change over time. Intake of non-water fluids did not independently relate to urinary indices nor to kidney function. CONCLUSIONS: In the general population, water intake relates cross-sectionally to urine flow, urine concentration, and kidney function but it does not relate to kidney function change over time. The intake of other beverages does not relate to urinary indices or kidney function. Results do not support a role of water intake in kidney function decline over time in the population.

Thalamic energy dysfunction is associated with thalamo-cortical tract damage in multiple sclerosis: A diffusion spectroscopy study.

BACKGROUND: Diffusion-weighted 1H magnetic resonance spectroscopy (DW-MRS) allows to quantify creatine-phosphocreatine brain diffusivity (ADC(tCr)), whose reduction in multiple sclerosis (MS) has been proposed as a proxy of energy dysfunction. OBJECTIVE: To investigate whether thalamic ADC(tCr) changes are associated with thalamo-cortical tract damage in MS. METHODS: Twenty patients with MS and 13 healthy controls (HC) were enrolled in a DW-MRS and DW imaging (DWI) study. From DW-MRS, ADC(tCr) and total N-acetyl-aspartate diffusivity (ADC(tNAA)) were extracted in the thalami. Three thalamo-cortical tracts and one non-thalamic control tract were reconstructed from DWI. Fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD), reflecting microstructural integrity, were extracted for each tract. Associations between thalamic ADC(tCr) and tract metrics were assessed using linear regression models adjusting for age, sex, thalamic volume, thalamic ADC(tNAA), and tract-specific lesion load. RESULTS: Lower thalamic ADC(tCr) was associated with higher MD and RD of thalamo-cortical projections in MS (MD: p = 0.029; RD: p = 0.017), but not in HC (MD: p = 0.625, interaction term between thalamic ADC(tCr) and group = 0.019; RD: p = 0.320, interaction term = 0.05). Thalamic ADC(tCr) was not associated with microstructural changes of the control tract. CONCLUSION: Reduced thalamic ADC(tCr) correlates with thalamo-cortical tract damage in MS, showing that pathologic changes in thalamic energy metabolism are associated with structural degeneration of connected fibers.

The Framingham cardiovascular risk score and 5-year progression of multiple sclerosis.

BACKGROUND AND PURPOSE: Cardiovascular risk factors and comorbidities can affect the prognosis of multiple sclerosis (MS). The Framingham risk score is an algorithm that can estimate the 10-year risk of developing macrovascular disease. Our objectives were to evaluate the possible association between the Framingham risk score at baseline and MS relapses, disability, and disease-modifying therapy (DMT) choices over a 5-year follow-up. METHODS: This is a retrospective cohort study including 251 MS subjects. At baseline, we calculated the Framingham risk score considering the following variables: age, sex, diabetes, smoking, systolic blood pressure, and body mass index. MS outcomes including relapses, disability, and treatments were collected over 5 years. Cox proportional regression models were employed to estimate hazard ratios (HRs). RESULTS: A one-point increase in the Framingham risk score was associated with 31% higher risk of relapse (HR = 1.31; 95% confidence interval [CI] = 1.03, 1.68), 19% higher risk of reaching of EDSS 6.0 (HR = 1.19; 95% CI = 1.05, 3.01), and 62% higher risk of DMT escalation (HR = 1.62; 95% CI = 1.22, 3.01). CONCLUSIONS: Higher cardiovascular risk was associated with higher risk of relapses, disability, and DMT escalation in MS. Early identification, correction, and treatment of cardiovascular comorbidities should be carefully considered within MS management.

Persistence, adherence, healthcare resource utilisation and costs for interferon Beta in multiple sclerosis: a population-based study in the Campania region (southern Italy).

BACKGROUND: To differentiate five formulations of Interferon Beta for the treatment of multiple sclerosis (MS) in clinical practice, by analysing persistence, adherence, healthcare resource utilisation and costs at population level. METHODS: In this population-based study, we included individuals with MS living in the Campania Region of Italy from 2015 to 2017, on treatment with intramuscular Interferon Beta-1a (Avonex® = 618), subcutaneous pegylated Interferon Beta-1a (Plegridy® = 259), subcutaneous Interferon Beta-1a (Rebif® = 1220), and subcutaneous Interferon Beta-1b (Betaferon® = 348; and Extavia® = 69). We recorded healthcare resource utilisation from administrative databases (hospital discharges, drug prescriptions, MS-related outpatients), and derived costs from the Regional formulary. We classified hospital admissions into MS-related and non-MS-related. Persistence (time to switch to other disease modifying treatments (DMTs)), and adherence (medication possession ratio (MPR) = medication supply obtained/medication supply expected during follow-up period) were calculated. RESULTS: Patients treated with Rebif® were younger, when compared with other Interferon Beta formulations (p < 0.01). The probability of switching to other DMTs was 60% higher for Betaferon®, 90% higher for Extavia®, and 110% higher for Plegridy®, when compared with Rebif® (p < 0.01). Plegridy® presented with 7% higher adherence (p < 0.01), and Betaferon® with 3% lower adherence (p = 0.03), when compared with Rebif®. The probability of MS-related hospital admissions was 40% higher in Avonex® (p = 0.03), 400% higher in Betaferon® (p < 0.01), and 60% higher in Plegridy® (p = 0.04), resulting into higher non-DMT-related costs, when compared with Rebif®. DISCUSSION: Interferon Beta formulations presented with different prescription patterns, persistence, adherence, healthcare resource utilisation and costs, with Rebif® being used in younger patients and with less MS-related hospital admissions.

[Impact assessment of the implementation of an integrated care model for thyroid disease at the University Hospital "Federico II" of Naples (Campania Region, Southern Italy): an interrupted time series analysis]. / Valutazione dell'impatto dell'implementazione di un percorso multidisciplinare di presa in carico della patologia nodulare tiroidea presso l'Azienda ospedaliera universitaria "Federico II" di Napoli: studio quasi sperimentale a serie temporale interrotta semplice.

OBJECTIVES: to evaluate the implementation of an integrated care model for thyroid disease on thyroid surgery at the University Hospital "Federico II" of Naples (Campania Region, Southern Italy). DESIGN: quasi-experimental design employing an interrupted time series analysis. SETTING AND PARTICIPANTS: all subjects who were admitted to the University Hospital "Federico II" for thyroid surgery between January 2008 and December 2018. The integrated care model for thyroid disease was implemented starting from January 2016. MAIN OUTCOME MEASURES: rate of partial thyroidectomies over all thyroidectomies; rate of diagnosed thyroid cancers over all diagnosed thyroid tumours; length of stay (LOS). Differences pre- and post-interventions were assessed employing Poisson (for count outcomes) and linear (for continuous outcomes) regression models. Models were adjusted for age, gender, tumour diagnosis (none, benign, malignant), Charlson index, and discharge month. RESULTS: data on 4,233 thyroidectomies were included. There was no difference between pre- and post-intervention trends for the rate of partial thyroidectomies over all thyroidectomies (pre-intervention: IRR 1.00; 95%CI 0.99;1.00 - post-intervention: IRR 1.00; 95%CI 0.98;1.02) and for the rate of diagnosed thyroid cancers over all thyroid tumours (pre-intervention IRR 0.99; 95%CI 0.99;1.00 - post-intervention IRR 1.00; 95%CI 0.99;1.01). On the contrary, the LOS reduced from 4.5 (±4.3) days in 2008 to 3.2 (±3.2) days in 2018. The multivariate analysis confirmed this reduction, estimated to be 1.1 days on average in the pre-intervention eight-year period (pre-intervention coefficient -0.01; 95%CI -0.02;-0.01), followed by an even greater reduction in the post-intervention three-year period which was estimated to be 1.1 day (post-intervention: coefficient -0.03; 95%CI -0.05;-0.01). CONCLUSIONS: the implementation of an integrated care model for thyroid disease contributed to reduce the LOS for thyroidectomies, improving the efficiency in the management of thyroid disease. However, this intervention had no impact in reducing the rate of total thyroidectomies.

Ubiquitin protease Ubp8 is necessary for S. cerevisiae respiration.

Healthy mitochondria are required in cell metabolism and deregulation of underlying mechanisms is often involved in human diseases and neurological disorders. Post-translational modifications of mitochondrial proteins regulate their function and activity, accordingly, impairment of ubiquitin proteasome system affects mitochondria homeostasis and organelle dynamics. In the present study we have investigated the role of the ubiquitin protease Ubp8 in S. cerevisiae respiration. We show that Ubp8 is necessary for respiration and its expression is upregulated in glycerol respiratory medium. In addition, we show that the respiratory defects in absence of Ubp8 are efficiently rescued by disruption of the E3 Ub-ligase Psh1, suggesting their epistatic link. Interestingly, we found also that Ubp8 is localized into mitochondria as single protein independently of SAGA complex assembly, thus suggesting an independent function from the nuclear one. We also show evidences on the importance of HAT Gcn5 in sustaining Ubp8 expression and affecting the amount of protein in mitochondria. Collectively, our results have investigated the role of Ubp8 in respiratory metabolism and highlight the role of ubiquitin related pathways in the mitochondrial functions of S. cerevisiae.

Cardiovascular profile improvement during Natalizumab treatment.

Cardiovascular comorbidities are associated with the risk of MS progression. Thus, we aim to measure variations of cardiovascular risk factors during Natalizumab treatment and their possible clinical associations. Seventy-one relapsing-remitting MS patients treated with Natalizumab were followed-up during a 12.9 ± 6.2 months. Cardiovascular risk factors were recorded on first and last study visits: systolic blood pressure, uric acid, total cholesterol, LDL, HDL, and triglycerides. EDSS progression and relapse occurrence were recorded. At multilevel mixed-effects linear regression models, the population presented with a significant reduction of total cholesterol (Coeff = -7.340; 95%CI = -13.152--1.527; p = 0.013), and of HDL cholesterol (Coeff = -3.473; 95%CI = -6.333--0.613; p = 0.017), and a non-significant reduction of LDL cholesterol (Coeff = -1.872; 95%CI = -8.481-0.736; p = 0.053), and of triglycerides (Coeff = -8.815; 95%CI = -34.011-5.380; p = 0.094). Uric acid levels increased during the study period (Coeff = 0.159; 95%CI = 0.212-0.340; p = 0.038). No significant associations were found with clinical outcomes. Serum lipids decreased and anti-oxidant uric acid increased during Natalizumab treatment. These biomarkers need to be further explored in relation to clinical outcomes on larger cohorts with longer follow-ups.

Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression.

BACKGROUND: Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing-remitting (RR). OBJECTIVE: To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. METHODS: The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. RESULTS: 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0±1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater (p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects (p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test-Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period (p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). CONCLUSION: Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS.

Associations between multimorbidity, healthcare utilisation and health status: evidence from 16 European countries.

BACKGROUND: with ageing populations and increasing exposure to risk factors for chronic diseases, the prevalence of chronic disease multimorbidity is rising globally. There is little evidence on the determinants of multimorbidity and its impact on healthcare utilisation and health status in Europe. METHODS: we used cross-sectional data from the Survey of Health, Ageing and Retirement in Europe (SHARE) in 2011-12, which included nationally representative samples of persons aged 50 and older from 16 European nations. Negative binomial and logistic regression models were used to assess the association between number of chronic diseases and healthcare utilisation, self-perceived health, depression and reduction of functional capacity. RESULTS: overall, 37.3% of participants reported multimorbidity; the lowest prevalence was in Switzerland (24.7%), the highest in Hungary (51.0%). The likelihood of having multimorbidity increased substantially with age. Number of chronic conditions was associated with greater healthcare utilisation in both primary (regression coefficient for medical doctor visits = 0.29, 95% CI = 0.27-0.30) and secondary setting (adjusted odds ratio (AOR) for having any hospitalisation in the last year = 1.49, 95% CI = 1.42-1.55) in all countries analysed. Number of chronic diseases was associated with fair/poor health status (AOR 2.13, 95% CI = 2.03-2.24), being depressed (AOR 1.48, 95% CI = 1.42-1.54) and reduced functional capacity (AOR 2.12, 95% CI = 2.02-2.22). CONCLUSION: multimorbidity is associated with greater healthcare utilisation, worse self-reported health status, depression and reduced functional capacity in European countries. European health systems should prioritise improving the management of patients with multimorbidity to improve their health status and increase healthcare efficiency.

Association of searching for health-related information online with self-rated health in the European Union.

BACKGROUND: The Internet is widely accessed for health information, but poor quality information may lead to health-worsening behaviours (e.g. non-compliance). Little is known about the health of individuals who use the Internet for health information. METHODS: Using the Flash Eurobarometer survey 404, European Union (EU) citizens aged ≥15 (n = 26 566) were asked about Internet utilisation for health information ('general' or 'disease-specific'), the sources used, self-rated health, and socioeconomic variables. Multivariable logistic regression was employed to assess the likelihood of bad self-rated health and accessing different health information sources (social networks, official website, online newspaper, dedicated websites, search engines). RESULTS: Those searching for general information were less likely to report bad health [odds ratios (OR) = 0.80; 95% confidence intervals (CI): 0.70-0.92], whilst those searching for disease-specific information were more likely (OR = 1.22; 95% CI: 1.07-1.38). Higher education and frequent doctor visits were associated with use of official websites and dedicated apps for health. Variation between EU member states in the proportion of people who had searched for general or disease-specific information online was high. CONCLUSIONS: Searching for general health information may be more conducive to better health, as it is easier to understand, and those accessing it may already be or looking to lead healthier lives. Disease-specific information may be harder to understand and assimilate into appropriate care worsening self-rated health. It may also be accessed if health services fail to meet individuals' needs, and health status is currently poor. Ensuring individuals' access to quality health services and health information will be key to addressing inequalities in health.