Pattern of treatment of behavioural and psychological symptoms of dementia and pain: evidence on pharmacoutilization from a large real-world sample and from a centre for cognitive disturbances and dementia.

PURPOSE: Data concerning the number of diagnoses and of the drugs prescribed to patients affected by dementia are still scarce. Here we test whether or not (1) prescription of symptomatic drugs against Alzheimer's disease (AD) may approximate the number of patients affected by dementia in Italy and (2) adherence to this treatment affects the pattern of prescription of drugs (i.e. antipsychotics and antidepressants) for behavioural and psychological symptoms of dementia (BPSD) and the previously reported limited prescription of analgesics. METHODS: This retrospective observational study concerns 84,235 subjects older than 60 years and registered in the provincial prescription database of the health district of Cosenza accounting for a population of 298,000 inhabitants. The prescribing pattern of antipsychotics, antidepressants, and analgesics has been investigated in patients receiving concurrent prescriptions of acetylcholinesterase inhibitors (AChEI) and/or memantine. Data from a single centre for cognitive disturbances and dementia (CDCD) in the same health district were used to explore at which stage dementia was diagnosed. The study was approved by Calabria Region Ethical Committee no. 31/2017 and registered on October 31, 2017. RESULTS: The data show that 859 patients are treated with AChEI and/or memantine; 420 patients (48.89%) receive at least 80% of the recommended medications. CDCD data indicate a delay in dementia diagnosis, which often was made when the patients were moderately to severely demented (Mini Mental State Examination, MMSE ≤ 20). Adherence did not influence prescription of most of the drugs explored, but use of non-steroidal anti-inflammatory drugs was higher in non-adherent patients. Antipsychotics and antidepressants are frequently used (20.61-20.71% and 42.37-51.43%, respectively), and this, at least in part, might stem from the observed under-treatment of chronic pain (opioids are prescribed in the 4.76% and 12.46% of adherent and non-adherent patients and gabapentin and pregabalin are used in the 4.29% and 4.07% of adherent and non-adherent patients respectively), resulting in more frequent BPSD. 16.43% of patients receive antipsychotics for longer than 6-12 weeks. CONCLUSION: This 2-year period study, including a wide cohort of community demented patients, shows that dementia is diagnosed late and that prevalence of BPSD prescriptions is high and not impacted by adherence to anti-dementia drugs. The rate of prescription of potentially harmful antipsychotics and antidepressants appears to be high though whether the concomitantly observed limited prescription of analgesics might be a contributing factor needs to be further investigated. Our data support the development of strategies to improve the management of BPSD.

Administration of subcutaneous interferon beta 1a in the evening: data from RELIEF study.

BACKGROUND: Subcutaneous recombinant interferon-beta 1a (IFN-ß1a SC) is indicated for treatment of relapsing multiple sclerosis (RMS); however, it is associated with development of flu-like syndrome (FLS) in 75% of patients. No recommendations are available on whether evening or morning administration could induce better or worse FLS. OBJECTIVE: Primary objective was to investigate whether morning administration of IFN-ß1a 44 µg (Rebif) would affect the severity of FLS versus evening administration, in patients with RMS. Secondary objectives were to investigate whether timing of administration could lead to a better quality of life. METHODS: Multicenter, open-label, 12-week, randomized, controlled, parallel-group, phase 4 study. RESULTS: Of 217 patients screened at 29 Italian sites, 200 were included in the study. Among these, 104 patients were randomized to IFN-ß1a SC administration in the morning and 96 in the evening. Morning administration resulted in higher FLS scores, as measured by the Multiple Sclerosis Treatment Concern Questionnaire, at week 4 (p = 0.0083) and week 8 (p = 0.0079); however, the difference was no longer significant at the end of 12 weeks. CONCLUSION: IFN-ß1a evening injections in the first 8 weeks of treatment led to an improvement in FLS; when continuing therapy, time of administration could be decided according to patient's lifestyle and preference.

Methodologies of speech analysis for neurodegenerative diseases evaluation.

BACKGROUND AND OBJECTIVE: Neurodegenerative diseases are disorders that affect neurons in the brain resulting in a debilitating condition and progressive degeneration of nerve cells. These diseases involve different aspects among which speech impairment. Vocal signal analysis is used to evaluate this impairment and to discriminate normal from pathological voices. MATERIALS AND METHODS: In this paper, two methods of vocal signal analysis have been proposed to evaluate an anomalous condition in human speech, known as dysarthria, useful to compare pathological and healthy voices. Parkinson and Multiple Sclerosis disease have been considered and patients affected by both pathologies have been enrolled. The methods have been tested on 153 voice signals belonging to: 39 healthy subjects (HS), 60 patients with Parkinson's Disease (PD) and 54 patients with Multiple Sclerosis (MS). Acoustic (F0, jitter, shimmer, NHR) and vowel metric (tVSA, qVSA, FCR) features have been extracted. RESULTS: The results report significant differences in almost all of these features in pathological and healthy voices by performing statistical tests. F0, jitter, shimmer, NHR, tVSA and FCR are statistically significant features thus they can be used as indicators in the diagnosis of dysarthria-related diseases such as in PD and MS. The results suggest that the applied methodologies are efficient and useful in characterizing the different behavior of vocal signal in healthy and pathological subjects. Consequently, they could be a valid support for physicians in disease evaluation and progression monitoring. CONCLUSIONS: The contribution aims to evaluate, support and diagnose the comorbidity in pathological patients verifying the co-occurrence of speech and neurological disorders in the same individual. The proposed solution is studied and implemented to be efficient and low cost following the model of precision medicine to customize clinical practice in disease diagnosis and treatment.

Comparable efficacy and safety of dimethyl fumarate and teriflunomide treatment in Relapsing-Remitting Multiple Sclerosis: an Italian real-word multicenter experience.

BACKGROUND: The aim of the study was to evaluate the achievement of 'no evidence of disease activity' (NEDA) over a 12-month period in a large multicenter population with relapsing remitting multiple sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) and teriflunomide (TRF) using a propensity-score adjustment. METHODS: A time-to-event method was used to determine the percentages of patients with RRMS (pwRRMS) in both groups achieving NEDA 3 (no relapses, no 12-week confirmed disability progression, and no new T2/gadolinium-enhancing brain lesions). We described the safety profile of the investigated drugs. RESULTS: Of the 587 pwRRMS treated with DMF and the 316 pwRRMS treated with TRF, 468 pwRRMS were successfully paired by propensity score: 234 on DMF and 234 on TRF. The percentages of pwRRMS who achieved NEDA 3 were 80.3% in the DMF group and 77.2% in the TRF group. Serious adverse events occurred in four (1.9%) pwRRMS on DMF and in three (1.3%) pwRRMS on TRF. CONCLUSIONS: DMF and TRF significantly impacted RRMS disease activity in our study. Serious safety concerns were recorded in less than 2% of the studied population.

Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a large population of Italian patients (SA.FE. study).

BACKGROUND: The approval of Sativex for the management of multiple sclerosis (MS) spasticity opened a new opportunity to many patients. In Italy, the healthcare payer can be fully reimbursed by the involved pharma company with the cost of treatment for patients not responding after a 4 week (28 days) trial period (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days) treatment for other patients discontinuing (Cost Sharing, CS). The aim of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients. METHODS: We collected data of patients from 30 MS centres across the country starting Sativex between January 2014 and February 2015. Data were collected from the mandatory Italian Medicines Agency (AIFA) web-registry. Predictors of treatment discontinuation were assessed using a multivariate Cox proportional regression analysis. RESULTS: During the observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07-2.41, p<0.001) and a lower baseline NRS score (adjHR 0.51 95% CI 0.46-0.56, p<0.001) were predictive of treatment discontinuation. CONCLUSION: These data show that the first 6 weeks are useful in identifying those patients in which Sativex could be effective, thus avoiding the cost of longer term evaluation.