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.
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.
Background We aim to overcome limitations of previous clinical and population-based studies by merging a clinical registry to routinely-collected healthcare data, and to specifically describe ...differences in clinical outcomes, healthcare resource utilization and costs between interferon beta formulations for multiple sclerosis (MS). Methods We included 850 patients with MS treated with interferon beta formulations, from 2015 to 2019, seen at the MS Clinical Care and Research Centre (Federico II University of Naples, Italy) and with linkage to routinely-collected healthcare data (prescription data, hospital admissions, outpatient services). We extracted and computed clinical outcomes (relapses, 6-month EDSS progression using a roving EDSS as reference), persistence (time spent on a specific interferon beta formulation), adherence (medication possession ratio (MPR)), healthcare resource utilization and costs (annualized hospitalization rate (AHR), costs for hospital admissions and DMTs). To evaluate differences between interferon beta formulations, we used linear regression (adherence), Poisson regression (AHR), mixed-effect regression (costs), and Cox-regression models (time varying variables); covariates were age, sex, treatment duration, baseline EDSS and adherence. Results Looking at clinical outcomes, rates of relapses and EDSS progression were lower than studies run on previous cohorts; there was no differences in relapse risk between interferon beta formulations. Risk of discontinuation was higher for Betaferon®/Extavia® (HR = 3.28; 95%CI = 2.11, 5.12; p<0.01). Adherence was lower for Betaferon®/Extavia® (Coeff = -0.05; 95%CI = -0.10, -0.01; p = 0.02), and Avonex® (Coeff = -0.06; 95%CI = -0.11, -0.02; p<0.01), when compared with Rebif® and Plegridy® (Coeff = 0.08; 95%CI = 0.01, 0.16; p = 0.02). AHR and costs for MS hospital admissions were higher for Betaferon®/Extavia® (IRR = 2.38; 95%CI = 1.01, 5.55; p = 0.04; Coeff = 14.95; 95%CI = 1.39, 28.51; p = 0.03). Conclusions We have showed the feasibility of merging routinely-collected healthcare data to a clinical registry for future MS research, and have confirmed interferon beta formulations play an important role in the management of MS, with positive clinical outcomes. Differences between interferon beta formulations are mostly driven by adherence and healthcare resource utilization.
Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to ...evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data.
One hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability.
RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88).
RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.
BACKGROUND: There is little published data on the potential health benefits of active travel in low and middle-income countries. This is despite increasing levels of adiposity being linked to ...increases in physical inactivity and non-communicable diseases. This study will examine: (1) socio-demographic correlates of using active travel (walking or cycling for transport) among older adults in six populous middle-income countries (2) whether use of active travel is associated with adiposity, systolic blood pressure and self-reported diabetes in these countries. METHODS: Data are from the WHO Study on Global Ageing and Adult Health (SAGE) of China, India, Mexico, Ghana, Russia and South Africa with a total sample size of 40,477. Correlates of active travel (≥150 min/week) were examined using logistic regression. Logistic and linear regression analyses were used to examine health related outcomes according to three groups of active travel use per week. RESULTS: 46.4 % of the sample undertook ≥150 min of active travel per week (range South Africa: 21.9 % Ghana: 57.8 %). In pooled analyses those in wealthier households were less likely to meet this level of active travel (Adjusted Risk Ratio (ARR) 0.77, 95 % Confidence Intervals 0.67; 0.88 wealthiest fifth vs. poorest). Older people and women were also less likely to use active travel for ≥150 min per week (ARR 0.71, 0.62; 0.80 those aged 70+ years vs. 18–29 years old, ARR 0.82, 0.74; 0.91 women vs. men). In pooled fully adjusted analyses, high use of active travel was associated with lower risk of overweight (ARR 0.71, 0.59; 0.86), high waist-to-hip ratio (ARR 0.71, 0.61; 0.84) and lower BMI (−0.54 kg/m², −0.98;− 0.11). Moderate (31–209 min/week) and high use (≥210 min/week) of active travel was associated with lower waist circumference (−1.52 cm (−2.40; −0.65) and −2.16 cm (3.07; −1.26)), and lower systolic blood pressure (−1.63 mm/Hg (−3.19; −0.06) and −2.33 mm/Hg (−3.98; −0.69)). CONCLUSIONS: In middle-income countries use of active travel for ≥150 min per week is more common in lower socio-economic groups and appears to confer similar health benefits to those identified in high-income settings. Efforts to increase active travel levels should be integral to strategies to maintain healthy weight and reduce disease burden in these settings.
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.
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•Ubiquitin protease Ubp8 is required for respiration in budding yeast.•Ubp8 expression is regulated by respiration and Gcn5 dependent acetylation.•Ubp8 is localized into mitochondria independently of SAGA complex.•Absence of E3 Ub-ligase Psh1 rescues respiration in ubp8Δ strain.
Cognition and gait appear to be closely related. The chronological interplay between cognitive decline and gait dysfunction is not fully understood. The aim of the present prospective study is ...investigating whether the dysfunction of specific gait parameters, during specific task and medication conditions, may predict subsequent cognitive impairment in Parkinson’s disease (PD). We evaluated cognition and gait in 39 Parkinsonian patients at an initial assessment and after 3 years. Cognitive performance was evaluated with a neuropsychological battery designed to assess memory, executive/attention, and visuospatial domains. Gait was investigated using a gait analysis system during both the off and on states in the following conditions: (1) normal gait; (2) motor dual task; and (3) cognitive dual task. We used regression models to determine whether gait predicts subsequent cognitive dysfunction. Overall, the cognitive test scores were stable over time with the exception of the executive/attention scores, whereas all gait parameters declined. The step length during the cognitive dual task during the on state at the initial evaluation was the only significant predictor of executive/attention domain dysfunction at follow up. The results were confirmed when executive/attention dysfunction at the initial assessment evaluation was included in the regression model as a covariate. Our longitudinal study offers additional insight into the progression of gait dysfunction, and its chronological relationship with cognitive dysfunction in PD patients. In particular, the present study indicates that step length during a cognitive task when on medication is an independent predictor of future executive/attention decline.
Purpose
Nowadays, the clinical management of thyroid nodules needs to be multi-disciplinary. In particular, the crosstalk between endocrinologists and cytopathologists is key. When FNAs are properly ...requested by endocrinologists for nodules characterised by relevant clinical and ultrasound features, cytopathologists play a pivotal role in the diagnostic work-up. Conversely, improper FNA requests can lead to questionable diagnostic efficiency. Recently, recommendations to delay all non-urgent diagnostic procedures, such as thyroid FNAs, to contain the spread of COVID-19 infection, have made the interplay between endocrinologists and cytopathologists even more essential. The objective of this study was to assess the impact of COVID-19 pandemic on our practice by evaluating the total number of FNAs performed and the distribution of the Bethesda Categories before, during, and after the lockdown.
Methods
We analysed the FNA trends before (1st January 2019 to March 13th 2020), during (March 14th to May 15th), and after (May 16th to July 7th) the lockdown.
Results
Although the total number of weekly FNAs dropped from 62.1 to 23.1, our referring endocrinologists managed to prioritise patients with high-risk nodules. In fact, in the post-lockdown, the weekly proportion of benign diagnoses dropped on average by 12% and that of high-risk diagnoses increased by 6%.
Conclusions
The lesson we have learned so far from this pandemic is that by applying safety protocols to avoid contagion and by increasing the threshold for FNA requests for thyroid nodules, we can continue to guarantee our services to high-risk patients even in times of a health crisis.
Type 2 Diabetes (T2D) is increasing but the effectiveness of large-scale diabetes screening programmes is debated. We assessed associations between coverage of a national cardiovascular and diabetes ...risk assessment programme in England (NHS Health Check) and detection and management of incident cases of non-diabetic hyperglycaemia (NDH) and T2D. Retrospective analysis employing propensity score covariate adjustment method of prospectively collected data of 348,987 individuals aged 40-74 years and registered with 455 general practices in England (January 2009-May 2016). We examined differences in diagnosis of NDH and T2D, and changes in blood glucose levels and cardiovascular risk score between individuals registered with general practices with different levels (tertiles) of programme coverage. Over the study period 7,126 cases of NDH and 12,171 cases of T2D were detected. Compared with low coverage practices, incidence rate of detection in medium and high coverage practices were 15% and 19% higher for NDH and 10% and 9% higher for T2D, respectively. Individuals with NDH in high coverage practices had 0.2 mmol/L lower mean fasting plasma glucose and 0.9% lower cardiovascular risk score at follow-up. General practices actively participating in the programme had higher detection of NDH and T2D and improved management of blood glucose and cardiovascular risk factors.
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.
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.
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®.
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.
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