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.

An ecological analysis of socio-economic determinants associated with paediatric vaccination coverage in the Campania Region: A population-based study, years 2003-2017.

Introduction: Vaccines are the most cost-effective and straightforward intervention against severe infectious diseases. However, in Europe and in Italy, paediatric vaccination coverage for certain vaccines remains suboptimal, with considerable regional differences in Italy. Vaccine coverage varies significantly due to socio-economic and organisational factors. Aim of this study was to assess the influence of the Deprivation Index, the density of General Practitioners and General Paediatricians per inhabitants on the coverage of both mandatory and non-mandatory paediatric vaccinations across local health authorities and health districts in the Campania Region for birth cohorts from 2001 to 2015. Materials and methods: Population-based, ecological time series analysis focusing on the Campania Region, most populous region in the south of Italy. Vaccination coverage data were extracted from the regional immunization database, whilst information on the Deprivation Index and number of primary care doctors and primary care paediatricians per local health district were extracted from public health records. Univariate descriptive statistics were employed to describe study characteristics, as appropriate, whilst and mixed-effect linear regression models were employed to assess the associations between variables of interest and vaccination coverage. Results: Overall vaccination coverage has generally increased, except for the MMR vaccine, which showed coverage fluctuations. An increase in the Deprivation Index, indicative of less favourable socio-economic conditions, was associated with decreased vaccination coverage in the 24-month age group for some mandatory vaccines (DTaP: Coef -0.97, 95% CI -1.77 | -0.17; Poliomyelitis: Coef -0.98, 95% CI -1.78 | -0.17; Hepatitis B: Coef -0.90, 95% CI -1.71 | -0.10). Moreover, areas with a greater density of General Paediatricians per inhabitants saw increased coverage for Haemophilus influenzae type b in the 6-year age group (Coef 9.78, 95% CI 1.00 | 18.56). Conclusions: It is necessary to target public health policies to address vaccination inequalities. These efforts should include expanding vaccination campaigns, enhancing catch-up programs, and increase resource allocation in primary care settings to facilitate the role of General Practitioners and Paediatricians in fostering awareness and adherence.

Utilization of Ocrelizumab within Different Treatment Strategies for Multiple Sclerosis: A 5-Year Population-Based Study.

BACKGROUND: We aim to provide up-to-date real-world evidence on the persistence, adherence, healthcare resource utilization, and costs of multiple sclerosis (MS) by comparing ocrelizumab to other disease-modifying treatments (DMTs) and within different DMT sequences. METHODS: We included 3371 people with MS who first received or switched DMT prescriptions from January 2018 to December 2022; they were identified through hospital discharge records, drug prescriptions, and exemption codes from the Campania Region (South Italy). We calculated persistence (time from the first prescription to discontinuation or switching to another DMT), adherence (proportion of days covered (PDC)), DMT costs, and MS hospital admissions and related costs. RESULTS: The most frequently prescribed DMT was dimethyl fumarate (n = 815; age 38.90 ± 11.91 years; 69.5% females), followed by ocrelizumab (n = 682; age 46.46 ± 11.29 years; 56.3%); 28.8% of the patients treated with ocrelizumab were naïve to DMTs. Using ocrelizumab as a statistical reference, the risk of discontinuation was higher for other highly active (HR = 6.32; 95%CI = 3.16, 12.63; p < 0.01) and low-/medium-efficacy DMTs (HR = 10.10; 95%CI = 5.10, 19.77; p < 0.01); adherence was lower for other highly active DMTs (Coeff = -0.07; 95%CI = -0.10, -0.04; p < 0.01) and low-/medium-efficacy DMTs (Coeff = -0.16; 95%CI = -0.19, -0.14; p < 0.01). monthly DMT costs were higher for other highly active DMTs (Coeff = 77.45; 95%CI = 29.36, 125.53; p < 0.01) but lower for low-/medium-efficacy DMTs (Coeff = -772.31; 95%CI = -816.95, -727.66; p < 0.01). The hospital admissions and related costs of MS were similar between ocrelizumab, other highly active DMTs, and other low-/medium-efficacy DMTs, and with ocrelizumab as the first-line DMT after other highly active DMTs and after low-/medium-efficacy DMTs, which was possibly due to the low number of observations. CONCLUSIONS: From 2018 to 2022, ocrelizumab was among the most frequently prescribed DMTs, with 28.8% prescriptions to incident MS patients, confirming its relevance in clinical practice. Ocrelizumab was associated with the highest persistence and adherence, pointing towards its favorable benefit-risk profile. The costs of ocrelizumab were lower than those of other highly active DMTs.

ChatGPT vs. neurologists: a cross-sectional study investigating preference, satisfaction ratings and perceived empathy in responses among people living with multiple sclerosis.

BACKGROUND: ChatGPT is an open-source natural language processing software that replies to users' queries. We conducted a cross-sectional study to assess people living with Multiple Sclerosis' (PwMS) preferences, satisfaction, and empathy toward two alternate responses to four frequently-asked questions, one authored by a group of neurologists, the other by ChatGPT. METHODS: An online form was sent through digital communication platforms. PwMS were blind to the author of each response and were asked to express their preference for each alternate response to the four questions. The overall satisfaction was assessed using a Likert scale (1-5); the Consultation and Relational Empathy scale was employed to assess perceived empathy. RESULTS: We included 1133 PwMS (age, 45.26 ± 11.50 years; females, 68.49%). ChatGPT's responses showed significantly higher empathy scores (Coeff = 1.38; 95% CI = 0.65, 2.11; p > z < 0.01), when compared with neurologists' responses. No association was found between ChatGPT' responses and mean satisfaction (Coeff = 0.03; 95% CI = - 0.01, 0.07; p = 0.157). College graduate, when compared with high school education responder, had significantly lower likelihood to prefer ChatGPT response (IRR = 0.87; 95% CI = 0.79, 0.95; p < 0.01). CONCLUSIONS: ChatGPT-authored responses provided higher empathy than neurologists. Although AI holds potential, physicians should prepare to interact with increasingly digitized patients and guide them on responsible AI use. Future development should consider tailoring AIs' responses to individual characteristics. Within the progressive digitalization of the population, ChatGPT could emerge as a helpful support in healthcare management rather than an alternative.

Health-related quality of life in patients with aortic dissection: An unmet need.

Knowledge about the Health-related Quality of Life (HR-QoL) after Type A (TA-AAD) and Type B acute aortic dissection (TB-AAD) is still insufficient. Through this systematic review, including 22 studies (16 for TA-AAD and 6 TB-AAD -1998-2023), the entire literature on HR-QoL after surgical and/or endovascular and/or medical interventions has been investigated. In TA-AAD patients, despite overall SF-36 score was similar to the standard population, with > 80 years patients displaying a better emotional domain, the SF-12 was significant lower to controls in physical and mental well-being domains. Exercise-based cardiac rehabilitation improved HR-QoL. In TB-AAD, vitality and mental health SF-36 scores improved after thoracic endovascular aortic repair (TEVAR); long-term QoL was similar in the open surgery group compared to TEVAR. Overall, HR-QoL after AAD seems adequate irrespective of age or sex, except for some specific domains. Physical exercise and cardiac rehabilitation may improve HR-QoL in these patients. PROSPERO registry ID: CRD42023421130.

Cardiac rehabilitation and acute aortic dissection: understanding and addressing the evidence GAP a systematic review.

Despite guideline recommendations, strategies for implementing cardiac rehabilitation (CR) in patients with acute aortic dissection (AAD) are not well established with little evidence to risk stratify prudent and effective guidelines for the many required variables. We conducted a systematic review of studies (2004-2023) reporting CR following type A (TA) and type B (TB) AAD. Our review is limited to open surgical repair for TA and medical treatment for TB. A total of 5 studies were included (4 TA-AAD and 1 TB-AAD) in the qualitative analysis. In general, observational data included 311 patients who had an overall favorable effect of CR in AAD consisting of a modestly improved exercise capacity and work load during cycle cardiopulmonary exercise test (TB-AAD), and improved quality of life (QoL). No adverse events were reported during symptom limited pre-CR treadmill or cycle exercise VO2 max or CR. Given the overall potential in this high risk population without adequate evidence for important variables such as safe time from post-op to CR, intensity of training, duration and frequency of sessions and followup it is time for a moderate sized well designed safe trial for patients' post-op surgery for TA-AAD and medically treated TB-AAD who are treated with standardized evidence based medical therapy and physical therapy from discharge randomized to CR versus usual care. PROSPERO registry ID: CRD42023392896.

Co-administration with Men-B vaccine increases Rotavirus vaccination coverage: A 5-year regionwide retrospective cohort study (STORM study).

INTRODUCTION: In Italy Rotavirus vaccination (RVV) is provided free of charge from 2018, however, the coverage is scattered and suboptimal. The narrow time frame to complete the schedule is a barrier to uptake, and co-administration with other vaccines may potentially increase the coverage. Although the co-administration of RV vaccine and Meningococcal Group B vaccine (MenB) is not included in the product labels, we aimed at studying its impact on RVV coverage. METHODS: This Surveillance study on Timing and cOverage of Rotavirus and MenB vaccine co-administration (STORM study) used the Regional Vaccination Registry to collect data about children born in Campania Region between January 2016 and December 2020, and receiving vaccines scheduled in the first year of life. RESULTS: Among the 224,110 children enrolled, 60,614 (27.0%) completed the RVV schedule, with a vaccination rate that increased over time from 1.15% in 2016 to 56.92% in 2020. The first and last dose of RVV schedule were administered beyond the recommended time in 6% of the study population, respectively. Co-administration of RV vaccine with MenB vaccine increased from 0.7 % in 2016 to 46.85 % in 2020. Children receiving RV/MenB vaccines concomitantly had a significantly higher chance of completing the RV schedule compared to those receiving RVV alone during a specific appointment (94.78 % vs 72.26 %, Prevalence Ratio -PR- 1.275, 95 %CI 1.245-1.295p < 0.00001). The positive driving effect of RV/MenB co-administration was more evident for children receiving pentavalent (PR 1.288) than monovalent RVV (PR 1.115) which was confirmed when adjusted for confounding variables (i.e., year of vaccination, local district, gender). CONCLUSIONS: Although still far from the target, RVV coverage has increased in recent years in Campania Region. Co-administration with MenB vaccine may aid in increasing RVV coverage, especially for pentavalent RVV. Further safety data are needed to support co-administration as a key tool to increase coverage.

Identification of organizational barriers to HPV vaccination uptake in medical students in southern Italy: a cross-sectional study.

Introduction: Despite proven efficacy, HPV vaccination coverage is still suboptimal. Factors influencing vaccination uptake are education attainment, socio-economic position, and knowledge about HPV. This study aimed to assess HPV vaccination uptake and its correlates among medical students and identify logistic-organizational barriers, knowledge, and attitudes with regard towards HPV vaccination to improve current public health vaccination strategies. Medical students, with their acquired biological knowledge, were selected as a low-risk groups for HPV vaccination uptake. This cross-sectional study was conducted using a validated questionnaire. Methods: Students in their the first 3 years of study students were preferentially invited. Eventually, the invitation was extended to every medical student. Logistic multivariable regression was used to assess determinants of HPV vaccination uptake. Additional analysis explored determinants of knowledge of and attitude toward HPV vaccination. Finally, a sensitive analysis was conducted to further assess the effect of knowledge and attitude on the HPV vaccination rate. Results: A total of 882 medical students participated, with 74.5% enrolled in the first 3 years of their training. HPV vaccination uptake was 55.5%, ranging from 78.5% for females to 16.5% for males. Male sex and increasing age were consistently associated with a lower vaccination uptake (males sex: OR 0.03, CI 0.02-0.05; age: OR 0.77, CI 0.68-0.88), whereasilst progress in their academic career was associated with a to higher likelihood of being vaccinated (6th year: OR 3.45, CI 1.24-9.57). These associations were confirmed when considering the knowledge of and attitude towards HPV. Additionally also, an active outreach from healthcare institutions was associated with a higher likelihood of receiving HPV vaccination (OR 1.70, CI 1.09-2.65. Conclusion: HPV vaccination in medical students was higher than in the general population; however, it was still suboptimal. An active and up-to-date call strategy and extending the free-of-charge offer are essential measures for to improvinge vaccination uptake. The findings support the need to improve public health strategies and increase awareness and knowledge ofregarding HPV vaccination.

Deciphering a Prodrome: Looking for a Disease in a Haystack

In many chronic diseases, the underlying biological processes begin long before the condition is clinically recognized and diagnosed. After biologic onset of the disease an early, often nonspecific, set of symptoms, or prodrome, may develop before more characteristic symptoms of the disease present. For instance, in Parkinson disease (PD), some of the earliest manifestations, such as smell or taste dysfunction, may occur 2 decades before typical symptoms, such as tremor, appear.1 Generally, the combination of long prodromal phases and nonspecific symptoms hampers early recognition of disease. Recognizing the prodromal phase of a disease in an individual has 2 potential benefits. First, accurate identification of etiologic factors for disease depends on ensuring that the putative exposure preceded biologic onset of the disease and that the identified symptoms are not related to a delay in diagnosis. Therefore, recognition of a prodromal phase may enhance the ability to identify etiologic factors. Second, accurate prediction that an individual is in the prodromal phase of the disease offers the tantalizing possibility that intervention in this phase could prevent or delay evolution of more typical clinical manifestations.2.

Impact of SARS-CoV-2 Positivity on Delivery Outcomes for Pregnant Women between 2020 and 2021: A Single-Center Population-Based Analysis.

Despite the existing body of evidence, there is still limited knowledge about the impact of SARS-CoV-2 positivity on delivery outcomes. We aimed to assess the impact of SARS-CoV-2 infection in women who gave birth at the University Hospital "Federico II" of Naples, Italy, between 2020 and 2021. We conducted a retrospective single-center population-based observational study to assess the differences in the caesarean section and preterm labor rates and the length of stay between women who tested positive for SARS-CoV-2 and those who tested negative at the time of labor. We further stratified the analyses considering the time period, dividing them into three-month intervals, and changes in SARS-CoV-2 as the most prevalent variant. The study included 5236 women with 353 positive cases. After vaccination availability, only 4% had undergone a complete vaccination cycle. The Obstetric Comorbidity Index was higher than 0 in 41% of the sample. When compared with negative women, positive ones had 80% increased odds of caesarean section, and it was confirmed by adjusting for the SARS-CoV-2 variant. No significant differences were found in preterm birth risks. The length of stay was 11% higher in positive cases but was not significant after adjusting for the SARS-CoV-2 variant. When considering only positive women in the seventh study period (July-September 2021), they had a 61% decrease in the odds of receiving a caesarean section compared to the fourth (October-December 2020). Guidelines should be implemented to improve the safety and efficiency of the delivery process, considering the transition of SARS-CoV-2 from pandemic to endemic. Furthermore, these guidelines should aim to improve the management of airborne infections in pregnant women.

Effect of implementing a heart failure admission care bundle on hospital readmission and mortality rates: interrupted time series study.

This study aimed to evaluate the impact of developing and implementing a care bundle intervention to improve care for patients with acute heart failure admitted to a large London hospital. The intervention comprised three elements, targeted within 24 hours of admission: N-terminal pro-B-type natriuretic peptide (NT-proBNP) test, transthoracic Doppler two-dimensional echocardiography and specialist review by cardiology team. The SHIFT-Evidence approach to quality improvement was used. During implementation, July 2015-July 2017, 1169 patients received the intervention. An interrupted time series design was used to evaluate impact on patient outcomes, including 15 618 admissions for 8951 patients. Mixed-effects multiple Poisson and log-linear regression models were fitted for count and continuous outcomes, respectively. Effect sizes are slope change ratios pre-intervention and post-intervention. The intervention was associated with reductions in emergency readmissions between 7 and 90 days (0.98, 95% CI 0.97 to 1.00), although not readmissions between 0 and 7 days post-discharge. Improvements were seen in in-hospital mortality (0.96, 95% CI 0.95 to 0.98), and there was no change in trend for hospital length of stay. Care process changes were also evaluated. Compliance with NT-proBNP testing was already high in 2014/2015 (162 of 163, 99.4%) and decreased slightly, with increased numbers audited, to 2016/2017 (1082 of 1101, 98.2%). Over this period, rates of echocardiography (84.7-98.9%) and specialist input (51.6-90.4%) improved. Care quality and outcomes can be improved for patients with acute heart failure using a care bundle approach. A systematic approach to quality improvement, and robust evaluation design, can be beneficial in supporting successful improvement and learning.

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.

Evaluating local thyroid cytopathology practices by molecular quality metrics: A multi-institutional study on 4651 FNAs with a focus on the role of the interventional cytopathologist.

BACKGROUND: The diagnostic accuracy of thyroid fine-needle aspiration (FNA) can be highly influenced by the technical skills of the operator performing the procedure and by interobserver variability in microscopic interpretation. This is particularly true for the indeterminate categories. Recently, molecular testing has been proposed as an ancillary tool for monitoring the performance of different thyroid cytopathology practices. The objective of this multicenter study was to evaluate the quality of different local cytopathology practices by assessing the impact of interventional cytopathologists on FNA adequacy for molecular testing and the variations in mutation rates across different health care centers operating in the Campania region. METHODS: The study included 4651 thyroid FNA samples diagnosed in different Southern Italian clinical laboratories belonging to the TIRNET (the Tiroide Network). FNA samples were collected by different proceduralists and were classified by local cytopathologists according to The Bethesda System for Reporting Thyroid Cytopathology. FNAs classified as atypia of undetermined significance, follicular neoplasm, suspicious for malignancy, and malignant were centralized for a real-time polymerase chain reaction-based, seven-gene test at the authors' institution. RESULTS: Centers that employed interventional cytopathologists obtained fewer unsatisfactory FNA samples for molecular testing (11.3%) than centers that employed noncytopathologists (16.7%; p < .05). Furthermore, a significant variation in the mutation rate was observed in FNAs diagnosed by different local cytopathologists; indeterminate categories had the highest percentage of mutation rate variability among centers. CONCLUSIONS: Interventional cytopathologists obtained higher yields of diagnostic material for molecular testing. Finally, the current results suggest that the variability in mutation rates among different centers may highlight the low reproducibility of microscopic criteria among cytopathologists, particularly for indeterminate cases.

Knowledge and attitude factors associated with the prevalence of Tdap (tetanus, diphtheria, and acellular pertussis) booster vaccination in healthcare workers in a large academic hospital in Southern Italy in 2022: a cross-sectional study.

Introduction: In Europe, there is still suboptimal tetanus, diphtheria, and acellular pertussis (Tdap) booster coverage. This study aimed to assess coverage status, knowledge, and attitude on Tdap vaccination in healthcare workers (HcWs) of the University Hospital "Federico II" in Naples, Southern Italy, in 2022, to improve current vaccination strategies. Methods: A cross-sectional study was conducted using a validated anonymous questionnaire. Knowledge and attitude were measured as scores. Multivariable logistic and linear regression models were employed to identify correlates of Tdap booster and knowledge and attitude toward the vaccination, as appropriate. Models were controlled for age, sex, profession, department, and job seniority. Results: A total of 206 questionnaires were administered among HcWs, and 143 (69.4%) were medical doctors. In total, 71 (34.47%) HcWs received the Tdap booster. Those who have worked 5-9 years at the hospital had a 78% lower likelihood of being vaccinated with the Tdap booster (5-9 years-OR: 0.22, CI: 0.06 | 0.85) as compared with newly hired HcWs. No differences in the average knowledge score were found. Other healthcare workers had a lower attitude as compared to medical doctors (Other-Coef. -2.15; CI: -4.14 | -0.15) and, as compared with those who worked in a clinical department, those who worked in a diagnostic-therapeutic department or medical management had 3.1 and 2.0 lower attitude scores, on average, respectively (diagnostic-therapeutic-Coef. -3.12, CI: -5.13 | -1.12; public health-Coef. -1.98, CI: -3.41 | -0.56). Discussion: The study findings support the necessity to implement public health strategies and improve knowledge and attitude toward vaccinations and specifically highlight the importance of Tdap booster every 10 years as a prevention tool to protect high-risk populations.

Functional limitation as a mediator of the relationship between multimorbidity on health-related quality of life in Australia: evidence from a national panel mediation analysis.

Objective: The inverse relationships between chronic disease multimorbidity and health-related quality of life (HRQoL) have been well-documented in the literature. However, the mechanism underlying this relationship remains largely unknown. This is the first study to look into the potential role of functional limitation as a mediator in the relationship between multimorbidity and HRQoL. Methods: This study utilized three recent waves of nationally representative longitudinal Household, Income, and Labor Dynamics in Australia (HILDA) surveys from 2009 to 2017 (n = 6,814). A panel mediation analysis was performed to assess the role of functional limitation as a mediator in the relationship between multimorbidity and HRQoL. The natural direct effect (NDE), indirect effect (NIE), marginal total effect (MTE), and percentage mediated were used to calculate the levels of the mediation effect. Results: This study found that functional limitation is a significant mediator in the relationship between multimorbidity and HRQoL. In the logistic regression analysis, the negative impact of multimorbidity on HRQoL was reduced after functional limitation was included in the regression model. In the panel mediation analysis, our results suggested that functional limitation mediated ~27.2% (p < 0.05) of the link between multimorbidity and the composite SF-36 score for HRQoL. Functional limitation also mediated the relationship between the number of chronic conditions and HRQoL for each of the eight SF-36 dimensions, with a proportion mediated ranging from 18.4 to 28.8% (p < 0.05). Conclusion: Functional status has a significant impact on HRQoL in multimorbid patients. Treatment should concentrate on interventions that improve patients' functioning and mitigate the negative effects of multimorbidity.

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.

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.

Epidemiology of multiple sclerosis in the Campania Region (Italy): Derivation and validation of an algorithm to calculate the 2015-2020 incidence.

OBJECTIVE: We aim to validate an algorithm based on routinely-collected healthcare data to detect incidence of multiple sclerosis (MS) in the Campania Region (South Italy) and to explore its spatial and temporal variations. METHODS: We included individuals resident in the Campania Region who had at least one MS record in administrative datasets (drug prescriptions, hospital discharge, outpatients), from 2015 to 2020. We merged administrative to the clinical datasets to ascertain the actual date of diagnosis, and validated the minimum interval from our study baseline (Jan 1, 2015) to first MS records in administrative datasets to detect incident cases. We used Bayesian approach to explore geographical distribution, also including deprivation index as a covariate in the estimation model. We used the capture-recapture method to estimate the proportion of undetected cases. RESULTS: The best performance was achieved by the 12-month interval algorithm, detecting 2,150 incident MS cases, with 74.4% sensitivity (95%CI = 64.1%, 85.9%) and 95.3% specificity (95%CI = 90.7%, 99.8%). The cumulative incidence was 36.68 (95%CI = 35.15, 38.26) per 100,000 from 2016 to 2020. The mean annual incidence was 7.34 (95%CI = 7.03, 7.65) per 100,000 people-year. The geographical distribution of MS relative risk shows a decreasing east-west incidence gradient. The number of expected MS cases was 11% higher than the detected cases. CONCLUSIONS: We validated a case-finding algorithm based on administrative data to estimate MS incidence, and its spatial/temporal variations. This algorithm provides up-to-date estimates of MS incidence, and will be used in future studies to evaluate changes in MS incidence in relation to different risk factors.