Evidence for widespread changes in the structure, composition, and fire regimes of western North American forests.

Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.

The patients' perspective on the perceived difficulties of dual-tasking: development and validation of the Dual-task Impact on Daily-living Activities Questionnaire (DIDA-Q).

BACKGROUND: Everyday-life activities often require performing dual tasks (DT), with consequent possible occurrence of motor-cognitive or motor-motor interference. This could reduce quality of life, in particular in people with neurological diseases. However, there is lack of validated tools to assess the patients' perspective on DT difficulties in this population. Therefore, we developed the Dual-task Impact on Daily-living Activities-Questionnaire (DIDA-Q) and tested its psychometric properties in people with multiple sclerosis (PwMS). METHODS: Items were generated based on existing scales, DT paradigms used in previous studies and the opinion of a multi-stakeholder group, including both experts and PwMS. Twenty DT constituted the preliminary version of the DIDA-Q which was administered to 230 PwMS. The psychometric properties of the scale were evaluated including internal consistency, validity and reliability. RESULTS: Nineteen items survived after exploratory factor analysis, showing a three-factor solution which identifies the components mostly contributing to DT perceived difficulty (i.e., balance and mobility, cognition and upper-limb ability). The DIDA-Q appropriately fits the graded response model, with first evaluations supporting internal consistency (Cronbach's alpha=0.95), validity (70% of the hypotheses for convergent and discriminant constructs confirmed) and reliability (intraclass correlation coefficients=0.95) of this tool. CONCLUSION: The DIDA-Q could be used in research and clinical settings to discriminate individuals with low vs. high cognitive-motor or motor-motor interference, and to develop and evaluate the efficacy of personalized DT rehabilitative treatments in PwMS.

EAN guideline on palliative care of people with severe, progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. METHODS: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score > 6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. RESULTS: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. CONCLUSIONS: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs.

Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis.

BACKGROUND AND PURPOSE: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. METHODS: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. RESULTS: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre-specified topics (from 89% for 'advance care planning' to 98% for 'multidisciplinary rehabilitation'), and <5% replied 'I prefer not to answer' to any topic. There were 569 free comments: 182 (32%) on the pre-specified topics, 227 (40%) on additional topics (16 guideline-pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient-important outcomes and of taxing issues. CONCLUSIONS: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient-important outcomes.

Multiple sclerosis incidence in Tuscany from administrative data.

BACKGROUND: Italy is a high-risk area for multiple sclerosis with 110,000 prevalent cases estimated at January 2016 and 3400 annual incident cases. To study multiple sclerosis epidemiology, it is preferable to use population-based studies, e.g., with a registry. A valid alternative to obtain data on entire population is from administrative sources. OBJECTIVE: To estimate the incidence of multiple sclerosis in Tuscany using a case-finding algorithm based on administrative data. METHODS: In a previous study, we calculated the prevalence in Tuscany using a validated case-finding algorithm based on administrative data. Incident cases were identified as a subset of prevalent cases among those patients not traced in the years before the analysis period, and the date of the first multiple sclerosis-related claim was considered the incidence date of multiple sclerosis diagnosis. We examined the period 2011-2015. RESULTS: We identified 1147 incident cases with annual rates ranged from 5.60 per 100,000 in 2011 to 6.58 in 2015. CONCLUSIONS: We found a high incidence rate, similarly to other Italian areas, especially in women, that may explain the increasing prevalence in Tuscany. To confirm this data and to calculate the possible bias caused by our inclusion method, we will validate our algorithm for incident cases.

The changing face of multiple sclerosis: Prevalence and incidence in an aging population.

OBJECTIVE: To assess multiple sclerosis (MS) incidence from 1998 to 2007, and MS prevalence on 31 December 2007, in the province of Genoa, Italy. METHODS: We identified MS cases diagnosed before 31 December 2007 by analyzing archives of hospitals with neurological or rehabilitation wards, the local Italian MS society, family doctor records and requests for oligoclonal band analysis on cerebrospinal fluid (CSF). RESULTS: A total of 1312 MS patients were residing in the province of Genoa on the prevalence day; 431 (32.85%) were men and 881 (67.15%) were women; mean age was 50.6 (± 13.9). The overall crude MS prevalence rate was 148.5/100,000; 103.1/100,000 in men and 189.1/100,000 in women. The crude mean annual MS incidence rate was 6.6 cases/100,000 (4.4/100,000 men; 8.6/100,000 women). Mean age at diagnosis was 39.5 ± 12.3 (men: 39.9 ± 13.0; women: 39.3 ± 11.9). A mean annual incidence of 4 MS patients ≥ 60 was observed. CONCLUSIONS: We observed an increased MS prevalence in the province of Genoa, compared to 1997. The mean age at diagnosis was relatively high (39 years old), 18% of our MS patients were over 65, and a notable incidence increase was seen in patients over 60. This has important implications, in terms of the need to organize the health system to better serve elderly MS patients, especially considering comorbidities and different medical needs of elderly MS patients; and to increase awareness within the medical community about the increasing risk of newly-presenting MS in the older population.

Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: results from the CoSMo study.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a possible cause of multiple sclerosis (MS). OBJECTIVES: The CoSMo study evaluated the association between CCSVI and MS. METHODS: The primary end-point of this multicentric, case-control study was to compare the prevalence of CCSVI between patients with MS, patients with other neurodegenerative diseases (ONDs) and healthy controls (HCs). Color-coded duplex sonography was performed by a sonologist and the images were sent to one of three central sonologists for a second reading. Agreement between local and central sonologists or, in case of disagreement, the predominant judgment among the three central readers, was required for a diagnosis of CCSVI. All readings, data collection and analysis were blinded. RESULTS: The study involved 35 MS centers across Italy and included 1874 subjects aged 18-55. 1767 (94%) were evaluable: 1165 MS patients, 226 patients with ONDs and 376 HCs. CCSVI prevalence was 3.26%, 3.10% and 2.13% for the MS, OND and HC groups, respectively. No significant difference in CCSVI prevalence was found amongst the three cohorts (MS versus HC, OR = 1.55, 95%CI = 0.72-3.36, p = 0.30; OND versus HC, OR = 1.47, 95%CI = 0.53-4.11, p = 0.46; MS versus OND, OR = 1.05, 95%CI = 0.47-2.39, p = 0.99). High negative and low positive agreement was found between the local and centralized readers. CONCLUSIONS: CCSVI is not associated with MS.

Psychological profile in children and adolescents with severe course Juvenile Idiopathic Arthritis.

OBJECTIVE: Juvenile Idiopathic Arthritis (JIA) is the most common chronic pediatric rheumatic disease. It is recognized that only reliance on clinical signs of disease outcome is inadequate for understanding the impact of illness and its treatment on child's life and functioning. There is a need for a multidisciplinary and holistic approach to children with arthritis which considers both physical and emotional functioning. This study investigated the psychosocial functioning of children and adolescent with JIA and the disease-related changes in their family. METHODS: The sample consisted of 33 hospitalized patients, aged 6-16 years. Both parents and the children were given a number of questionnaire to fill out. Clinical information was extracted from the interviews. RESULTS: Self-reported psychological functioning (depression, anxiety, and behavior) was not different from the normal population; however significant psychological suffering was detected by the clinical interview. CONCLUSIONS: Children and adolescents with JIA do not show overt psychopathology by structured assessment; nevertheless a more clinically oriented holistic approach confirms JIA as a disrupting event causing relevant changes in the quality of life of the affected families.

Multiple sclerosis in Italy: cost-of-illness study.

This study estimates the direct costs of multiple sclerosis (MS) in Italy from the perspective of the National Health System. Patients diagnosed with MS for ≥1 year prior to study entry were included in the analysis; neurological disability was assessed using the Expanded Disability Status Scale (EDSS). Cost variables were analyzed according to: MS phenotype, disease course over the previous year and EDSS rating. A total of 510 patients were included in the analysis. Overall costs were significantly higher for relapsing-remitting MS and secondary progressive MS than for primary progressive MS (P < 0.05). Costs were higher for EDSS scores 0.0-3.5 and 4.0-6.0 than for scores > 6.0 (P < 0.05). The extrapolated data gave an estimated annual direct cost of MS per patient of 18,030. In conclusion, relapsing-remitting MS or secondary progressive MS phenotypes and lower estimated EDSS scores appear to be associated with higher costs.

Pharmacokinetic∕pharmacodynamic modelling of intracellular gemcitabine triphosphate accumulation: translating in vitro to in vivo.

A detailed intracellular (IC) model describing the pharmacokinetics (PK) of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) was developed and linked to a systemic plasma dFdC PK model. Based on in vivo PK, pharmacodynamic (PD) effect predictions were made using a simplified cell-cycle model (CCM). A reduced-order compartmental model describing the IC metabolism of dFdC was fit to in vitro data taken from the literature to estimate the kinetic parameters of gemcitabine triphosphate (dFdCTP) generation and elimination in leukaemia cells. For comparison with in vivo patient data, the proposed detailed IC model, coupled with the systemic PK model and the CCM PD model, was simulated; Monte Carlo randomisation of the parameter vector was used to simulate interpatient variability. This comparison of model-generated IC dFdCTP concentrations with literature values in peripheral blood mononuclear cells (PBMCs) revealed qualitative and quantitative agreement. A tumour interstitial compartment connecting the plasma and IC models allowed prediction of solid tumour dFdCTP concentration.

Factors that influence the employment status of people with multiple sclerosis: a multi-national study.

Paid employment is valuable for society and for the individual. A diagnosis of a chronic illness such as multiple sclerosis (MS) can influence a person's employment status. Previous studies have reported that demographic and disease-related aspects can predict whether a person with MS will leave their job. The aim of the study was to assess the factors that people with MS believe to contribute to their employment status and to determine whether any of these differentiate people with MS who are employed from those who are not employed. A multinational questionnaire assessed aspects related to employment that facilitate or hinder job maintenance. Data was collected in 18 European countries. A total of 1,141 questionnaires were completed. Of those responding, 694 (61%) subjects were employed and 477 (39%) were unemployed. The items that significantly differentiated the groups were related to MS symptoms, workplace environment and financial considerations. While MS influences employment status for many people who face difficult symptoms, aspects like a flexible work schedule and financial security are important and perhaps key to promoting job maintenance among people with MS.

Caregiver quality of life in multiple sclerosis: a multicentre Italian study.

The purpose of this study was to evaluate the quality of life (QoL) of multiple sclerosis (MS) caregivers, and to determine relationships that may exist between caregiver and patient QoL. Patients with definite MS (n=445) and their caregivers (n=445) were required to complete the generic, 36-item short-form (SF-36) Health Survey. Median SF-36 dimension scores ranged from 55 to 100 for caregivers and from 46 to 78 for patients. Although the QoL of MS carers was not as severely affected as that of patients, caregiving was associated with lower mental health, vitality and general health scores, compared to healthy subjects. Multivariate analyses revealed significant differences between the predictors of patient QoL and caregiver QoL. The main predictors of patient QoL were Expanded Disability Status Scale (EDSS) score, MS course, fatigue and depression. Female gender and advanced age were the main predictors of lower QoL in caregivers. In addition, patient BDI score was found to be a significant predictor of almost all caregiver SF-36 dimension scores, while EDSS score, disease duration and course, and patient therapeutic characteristics were found to be predictors of some caregiver SF-36 dimension scores. Therefore, caregiver QoL was significantly influenced by patient characteristics, and supportive strategies for MS caregivers are warranted.

Prevalence of oedema of the lower limbs in multiple sclerosis patients: a vascular and lymphoscintigraphic study.

The aim of the study was to evaluate the frequency of oedema of the lower limbs in multiple sclerosis (MS) patients utilizing a multidisciplinary approach. A total of 205 patients with definite MS were included in the study. Seventy-five were male and 130 female, with a mean age of 50.53, mean Expanded Disability Status Scale (EDSS) score of 5.27 and mean disease duration of 16.6 years. Seventy-one patients had a relapsing-remitting (RR) disease course, 85 were secondary progressive (SP) and 49 were primary progressive (PP). Ninety-three patients (45%) showed oedema at the examination. EDSS, disease duration and disease course, but not gender, were statistically different between oedema and non-oedema patients. Out of 93 patients with oedema, 69 agreed to undergo a vascular examination. Of 69 patients, 45 (65.2%) had a CEAP score (specific rating scale for oedema) of 3 (presence of oedema) and 24 (34.8%) had a score of 4 (presence of a trophic disorder). Out of 69 subjects, 33 agreed to undergo a lymphoscintigraphy, which was normal in only 29 extremities out of 66. Lower limb oedema is common in MS patients, especially in those with reduced mobility. Early screening is advised in patients with an elevated EDSS.

An interdisciplinary approach to evaluating the need for assistive technology reduces equipment abandonment.

Assistive technology makes up a substantial portion of the direct cost of multiple sclerosis (MS). Equipment abandonment results in the needs of the disabled individual being unmet and places stress on the resources available for the funding of such equipment. The aim of the study was to demonstrate whether an interdisciplinary approach to evaluating and prescribing assistive technology reduces equipment abandonment in persons with MS. Data concerning assistive devices acquired by patients being followed at a rehabilitation centre in northern Italy from January 1997 to December 2002, were included in the study. Through December 1999, a physician in physical medicine and rehabilitation prescribed equipment based on a recommendation from the physical therapist. From 2000 to 2002, patients were evaluated following a standardized protocol implemented by an interdisciplinary team comprised of a physical therapist, occupational therapist, physician in physical medicine and rehabilitation and psychologist. Assistive technology obtained during the study period was divided into two datasets based on the year that the aid was obtained: pre-intervention (January 1997 to December 1999) and intervention (January 2000 to December 2002). The analysis included a comparison of the two datasets on number and types of equipment abandoned, timing of abandonment and reasons why devices were abandoned. Fifty-four subjects obtained 151 assistive devices during the study period, 67 devices during pre-intervention and 84 with the intervention. The majority of devices were abandoned immediately or within the first year following obtainment in both groups. A comparison of the number of devices obtained during pre-intervention with those obtained during the intervention showed that the rate of equipment abandonment decreased significantly from 37.3 to 9.5%. An interdisciplinary approach to evaluating assistive technology needs does decrease the risk of equipment abandonment, although it does not completely solve the problem.

Prevention and cure of rhinogenous deafness at the Thermal Baths "Bagni delle Galleraie".

INTRODUCTION: Hearing is foundamental for human social life. Secretory Otitis Media (SOM) is the most important cause of trasmissive hypoacusis in early childhood. METHODS: The Department of Physiopathology, Experimental Medicine and Public Health of Siena University in collaboration with the Thermal Baths "Bagni delle Galleraie" proposed a prevention and cure campaign of rhinogenous deafness in June 2002 in some primary schools in the Colle val D'Elsa district. A sample of 87 children was involved in the study (average age of 5,64 +/- 1,41 years). On entering the thermal baths a questionnaire was administered to the parents, to point out possible risk factors. RESULTS: Among the 87 children, 28 cases of SOM and 21 cases of severe tubal disorder were found. Only 19 cases out of 49 were already known to the parents and only 28 joined the study and were examined for three years consecutively. DISCUSSION: Out of the 35 children examined in 2002, 28 returned to "The Galleraie" for the two following years. They repeated the thermal cure for two years as a preventive measure. At present they are not affected by SOM and during the winters suffered a lower number of infections in the primary airways and took less antibiotics. CONCLUSIONS: Our study focuses on infant school children because of their critical age for linguistic and social development. Early diagnosis and therapy prevent any negative social development.

Antiepileptic medications in multiple sclerosis: adverse effects in a three-year follow-up study.

Neuropathic pain and paroxysmal symptoms are common in multiple sclerosis (MS) patients, although no double-blind clinical trial has been conducted to support antiepileptic medications (AED) use in MS. The aim of the study was to evaluate the frequency of AED utilisation and reported adverse events, in a cohort of MS patients. For a period of 3 years the rationale for prescribing AED, adverse effects, treatment duration and reasons for discontinuation were recorded in a database. Carbamazepine (CBZ) was prescribed in 36 patients, with adverse effects reported in 20 cases, of which 12 mimicked a relapse. Gabapentin (GBP) was prescribed in 94 patients, with adverse effects reported in 16 cases and in one case mimicked a relapse. Lamotrigine (LMT) was prescribed in 22 patients, with adverse effects reported in 4 cases, none mimicking a relapse. The present study found a significantly higher incidence of adverse effects in patients treated with CBZ, with a high rate of discontinuation at low dosages and episodes of evident worsening of neurological functioning compared to GBP or LMT.

The prevalence of multiple sclerosis in the north-west Italian province of Genoa.

UNLABELLED: The objective of this study was to assess the prevalence of multiple sclerosis (MS), calculated as point prevalence on 31 December 1997, in the province of Genoa, North-western Italy. METHODS: The province of Genoa is located in North-western Italy, an area of 1,835 km(2). On the point prevalence day the population consisted of 913,218 inhabitants. MS cases were identified by analysing archives of the hospitals with neurological or rehabilitation wards, neurologists serving the community, files of local chapters of the Italian MS society, all requests for oligoclonal bands analysis on CSF in the studied area. Patients included in the study were MS cases diagnosed before 31 December 1997 according to the Poser criteria resident in the province under study. RESULTS: A total of 857 subjects were alive and residing in the province of Genoa on the prevalence day. The overall crude prevalence rate was 94 per 100,000 (95% CI 88-100); 291 were males (34%) with a crude prevalence of 67 per 100,000 (95 % CI 60-76) and 566 were females (66%) with a prevalence of 118 per 100,000 (95% CI 108-128). The female/male ratio was 1.9. When age and sex were adjusted to the Italian standard population of 1991 prevalence was 85 per 100,000. Five hundred and thirty two out of the 857 patients agreed to be interviewed. The interviewed sample was representative of the prevalence sample: sex and gender distributions were identical in the two samples. The overall mean age was 48 (+/-13) years (48 +/-12 years in males; 48+/-14 years in females). Mean disease duration was 15 (+/-10) years for males and 16 (+/-11) years for females. Two hundred and ninety one (55 %) subjects had a relapsing remitting (RR) clinical course, 150 (28%) were secondary progressive (SP) and 91 (17%) were primary progressive (PP). Mean EDSS score was 5 (+/- 2; median 5). The mean age at time of onset was 33 (+/-10) years for males and 32 (+/- 11) years for females. The disease onset was monosymptomatic in 76% (n=407) patients and polysymptomatic in 24% (n=125). The mean length of time between clinical onset and diagnosis was 5 (+/- 6) years. CONCLUSION: We confirmed that the province of Genoa is a very high risk area for MS. We found a high rate of patients with a PP course; also the proportion of patients with high disability scores is greater compared to previous studies.