Healthcare costs for treating relapsing multiple sclerosis and the risk of progression: a retrospective Italian cohort study from 2001 to 2015

Background Disease modifying treatments (DMTs) are the main responsible for direct medical costs in multiple sclerosis (MS). The current investigation aims at evaluating possible associations between healthcare costs for treating relapsing remitting MS (RRMS) and disease evolution. Methods The present cohort study retrospectively included 544 newly diagnosed RRMS patients, prospectively followed up for 10.1±3.3 years. Costs for DMT administration and management were calculated for each year of observation. Following clinical endpoints were recorded: time to first relapse, 1-point EDSS progression, reaching of EDSS 4.0, reaching of EDSS 6.0, and conversion to secondary progressive MS (SP). Covariates for statistical analyses were age, gender, disease duration and EDSS at diagnosis. Results At time varying Cox regression models, 10% increase in annual healthcare costs was associated with 1.1% reduction in 1-point EDSS progression (HR = 0.897; p = 0.018), with 0.7% reduction in reaching EDSS 6.0 (HR = 0.925; p = 0.030), and with 1.0% reduction in SP conversion (HR = 0.902; p = 0.006). Conclusion Higher healthcare costs for treating MS have been associated with a milder disease evolution after 10 years, with possible reduction of long-term non-medical direct and indirect costs

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

Hyperemesis gravidarum and subsequent breast cancer risk

Both parity and a young age at first pregnancy are associated with a reduction in breast cancer risk. The hormones involved in this process are not fully investigated. Human chorionic gonadotropin is a placental hormone, which in rats and in human breast cells in vitro has been shown to prevent against breast cancer. Hyperemesis, a severe nausea combined with vomiting during pregnancy, is associated with increased levels of human chorionic gonadotropin. We investigated the possible relationship between hyperemesis and subsequent breast cancer risk in a case–control study based on registry data. Among 13 079 breast cancer cases and 34 348 individually matched controls we found 148 cases and 405 controls who had been hospitalised for hyperemesis. Hyperemesis was not associated with breast cancer risk (adjusted odds ratio 1.05, 95% confidence interval 0.86–1.27), and similar risks were observed regardless of age at diagnosis, number of hospitalisations for hyperemesis or time of follow-up. Our results do not support the hypothesis that human chorionic gonadotropin is responsible for the protective effect of pregnancies upon breast cancer risk

Corpus callosum involvement: a useful clue for differentiating Fabry Disease from Multiple Sclerosis.

PURPOSE: Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. METHODS: In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. RESULTS: WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. CONCLUSION: FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options

Developing and implementing an integrated delirium prevention system of care:a theory driven, participatory research study

Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly

D-brane Charges in Gravitational Duals of 2+1 Dimensional Gauge Theories and Duality Cascades

We perform a systematic analysis of the D-brane charges associated with string theory realizations of d=3 gauge theories, focusing on the examples of the N=4 supersymmetric U(N)xU(N+M) Yang-Mills theory and the N=3 supersymmetric U(N)xU(N+M) Yang-Mills-Chern-Simons theory. We use both the brane construction of these theories and their dual string theory backgrounds in the supergravity approximation. In the N=4 case we generalize the previously known gravitational duals to arbitrary values of the gauge couplings, and present a precise mapping between the gravity and field theory parameters. In the N=3 case, which (for some values of N and M) flows to an N=6 supersymmetric Chern-Simons-matter theory in the IR, we argue that the careful analysis of the charges leads to a shift in the value of the B-field in the IR solution by 1/2, in units where its periodicity is one, compared to previous claims. We also suggest that the N=3 theories may exhibit, for some values of N and M, duality cascades similar to those of the Klebanov-Strassler theory.Comment: 47 pages, 9 figures; minor changes, references adde