Uplifts and hassles are related to worsening in chronic fatigue syndrome: a prospective study.

BACKGROUND: Limited published data suggests that absence of uplifts (minor pleasant events) is associated with clinical worsening in patients with chronic fatigue syndrome (CFS). The current study aimed to assess the relation of illness worsening to the trajectories of social and non-social uplifts and hassles in a six-month prospective study in CFS. METHODS: Participants were primarily in their 40s, female, white, and ill for over a decade. All participants (N = 128) met criteria for CFS. The interview-based global impression of change rating was used to classify individual outcomes as improved, unchanged, or worsened at six- month follow-up. Uplifts and hassles, both social and non-social, were assessed with the Combined Hassles and Uplifts Scale (CHUS). The CHUS was administered weekly in online diaries over six months. Linear mixed effect models were utilized to examine linear trends for hassles and uplifts. RESULTS: No significant differences were found between the three global outcome groups for age, sex, or illness duration; however, work status was significantly lower for the non-improved groups (p < 0.001). Non-social hassles intensity showed an increasing slope for the worsened group (p = 0.03) and a decreasing slope (p = 0.05) for the improved group. For the worsened group, a downward trend was found for frequency of non-social (p = 0.01) uplifts. CONCLUSION: Individuals with worsening as compared to improving illness in CFS show significantly different six-month trajectories for weekly hassles and a deficit in uplifts. This may have clinical implications for behavioral intervention. Trial registration ClinicalTrials.gov ID: NCT02948556.

Nonimprovement in Chronic Fatigue Syndrome: Relation to Activity Patterns, Uplifts and Hassles, and Autonomic Dysfunction.

OBJECTIVE: To test a model of nonimprovement in chronic fatigue syndrome (CFS) using self-report activity patterns (e.g., "push-crash"), uplifts and hassles, and a biological measure of cardiac autonomic function. Activity pattern impacts on symptoms and objective measures of autonomic and physical activity were also examined. METHODS: This prospective study in CFS collected all data remotely, including 6 months of weekly web diaries that recorded symptom ratings, activity patterns, and hassles and uplifts. In addition, 6 months of weekly heart monitoring and 3 months of daily waking actigraphy data were collected. Improvement or nonimprovement status was assessed using semistructured interviews at the 6-month follow-up. RESULTS: A total of 148 individuals (87.2% female) were enrolled, and 12.2% were lost to follow-up. Participants reporting nonimprovement ( n = 92), as compared with improvement ( n = 38), showed greater autonomic dysfunction (lower heart rate variability, group difference = 5.93 [SE = 2.73] milliseconds; p = .032) and lower mean intensity of behavioral uplifts (group difference = 0.14 [SE = 0.16]; p = .043), but no significant differences in any activity pattern, including push-crash, limiting activity, and healthy pacing. CONCLUSIONS: This study provided evidence for linking patient-reported nonimprovement to a biological variable indexing autonomic dysfunction and a behavioral measure indicating a deficit in psychological uplifts. These findings suggest a possible marker of illness trajectory that could potentially advance the biomedical underpinnings of CFS.Trial Registration:ClinicalTrials.gov ID: NCT02948556.

The impact of the COVID-19 pandemic on the safety management in Italian Seveso industries.

The paper discusses the impact of the COVID-19 pandemic on the Italian chemical and process industries, where Directive 2012/18/EU Seveso III, for the control of Major Accident Hazard (MAH), is enforced. The Safety Management System (SMS) for the control of MAH, which has been mandatory for 20 years in Italian Seveso Establishments, has been highly stressed by the external pressure, related in some way to the COVID-19 pandemic. Fairly, most companies, in particular in oil and gas sectors, have demonstrated an adequate capability to reconcile operation continuity and health requirements. This experience is providing the establishment operators and the regulators with valuable suggestions for the improvements of the SMS-MAH. Within this framework, an innovative organisational resilience model is proposed, aiming at the development of a higher capability to face future new crisis. The current SMS-MAH already includes some basic pillars to enhance resilience, which were valuable during the pandemic crisis, but a full and rationale development is still needed. Starting from the first pandemic phase experience, this paper presents a novel tool to assess the degree of "resilience" of a SMS-MAH. It is based on a questionnaire, featuring 25 questions grouped into eight items, according to the typical SMS-MAH structure. A two level AHP model has been developed in order to define the weights to be assigned to each point. The AHP panel included industrial practitioners, regulators, authorities and researchers. The results are based on the COVID-19 experience and consequently the developed model is tailored to face health emergencies, but the approach may be easily transferred to other external crises.

Hg and Se exposure in brain tissues of striped dolphin (Stenella coeruleoalba) and bottlenose dolphin (Tursiops truncatus) from the Tyrrhenian and Adriatic Seas.

In this study we analyzed Hg and Se concentrations in dolphin brain tissues of fifteen specimens of striped dolphin (Stenella coeruleoalba) and eight specimens of bottlenose dolphin (Tursiops truncatus) stranded in the Tyrrhenian and Adriatic Seas, in order to assess the toxicological risks associated with Hg exposure. High Hg concentrations were found in brain tissues of both analyzed specie (1.86-243 mg/kg dw for striped dolphin and 2.1-98.7 mg/kg dw for bottlenose dolphin), exceeding levels associated with marine mammals neurotoxicity. Althougth the results clearly suggest that the protective effects of Se against Hg toxicity occur in cetaceans' brain tissues, a molar excess of mercury with respect to selenium was found, particularly in adult specimens of Stenella coeruleoalba. On contrary, negligible neurotoxicological risks were found for Tursiops truncatus specimens, due to detoxification processes. Data obtained allowed to prove a more marked neurotoxicological risk for adult specimens of Stenella coeruleoalba in both Tyrrhenian and Adriatic Seas.

Emissions of volatile organic compounds during the ship-loading of petroleum products: Dispersion modelling and environmental concerns.

Emissions due to ship-loading of hydrocarbons are currently not addressed neither by the Directive on the integrated pollution prevention or by other environmental regulations. The scope of this study is to point towards the environmental and safety concerns associated with such emissions, even if proper attention has not been given to this issue until now. In order to achieve this goal, the modelling of the emission volatile organic compounds (VOC), due to ship-load operations at refineries has been made by means of the definition of a simulation procedure which includes a proper treatment of the hours of calm. Afterwards, a quantitative analysis of VOC dispersion for an Italian case-study is presented with the primary aims: (i) to develop and verify the validity of the approach for the modelling of the emission sources and of the diffusion of these contaminants into the atmosphere by a proper treatment of the hours of calm and (ii) to identify their contribution to the total VOC emitted in a typical refinery. The calculated iso-concentration contours have also been drawn on a map and allowed the identification of critical areas for people protecting by the adoption of abatement solutions.

Changes in gross grasp strength and fine motor skills in adolescents with pediatric multiple sclerosis.

This study examined the gross grasp strength and fine motor dexterity of adolescents, who are diagnosed with multiple sclerosis (MS). A total sample size of 72 participants between the ages of 13 to 17 was studied. Thirty six with a diagnosis of pediatric relapse remitting MS and 36 matched control participants were selected from various local youth groups. Data on hand strength and dexterity was collected using a dynamometer, nine hole peg board and Purdue pegboard on both groups. Utilizing ANCOVA to describe the differences across the two groups by diagnosis, controlling for age and gender, it was found that the MS group demonstrated significantly decreased dexterity when compared to age and gender matched controls. There was no significant difference in gross grasp strength by diagnostic group. This preliminary study showed that children with a diagnosis of pediatric MS may have differences in fine motor dexterity, but not gross grasp strength from their peers who do not have the diagnosis. Further study is indicated to examine this phenomenon.

Psychiatric diagnoses and cognitive impairment in pediatric multiple sclerosis.

BACKGROUND: Pediatric multiple sclerosis (MS) represents approximately 5% of the MS population; information regarding clinical features is slowly accumulating. Cognitive and psychiatric impairments frequently occur, but remain poorly understood. OBJECTIVES: To describe psychiatric diagnoses among children with MS referred for psychiatric assessment and their relation to cognitive impairment. METHODS: Forty-five pediatric MS patients (aged 8 to 17 years) were referred for outpatient psychiatric evaluation including a psychiatric interview (K-SADS), a clinician-based global assessment of functioning (Children's Global Assessment Scale, CGAS), a neurologic examination including the Expanded Disability Status Scale (EDSS), and a neuropsychological test battery. RESULTS: The most common categories of psychiatric diagnoses were anxiety disorders (n=15), attention deficit hyperactivity disorder (ADHD, n=12), and mood disorders (n=11). Cognitive impairment was classified in 20/25 (80%) of patients meeting criteria for a psychiatric disorder versus 11/20 (55%) of those without psychiatric disorder (p=0.08). Those diagnosed with anxiety or mood disorder had the highest frequency of cognitive impairment, with a significantly higher rate when compared with those with psychiatric diagnoses in other categories (p=0.05). CONCLUSIONS: A variety of psychiatric diagnoses can occur in children with pediatric MS. Many of these children also had cognitive impairment, particularly those in the mood and anxiety groups.

Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis.

BACKGROUND: As remote infections with common herpes viruses are associated with modulation of the risk of multiple sclerosis (MS), we hypothesized that antibody concentrations against these viruses may further modify risk. As many common viruses are first encountered during childhood, pediatric MS offer a unique opportunity to investigate more closely their influence on susceptibility. Our aim was to determine if MS patients who were positive for these viruses had higher levels of antibodies to these viruses. We also assessed whether human leukocyte antigen (HLA)-DRB1*1501 genotype influenced viral antibody levels. METHODS: Antibody response levels toward Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1, and HLA-DRB1*1501 status were determined in pediatric MS patients (n=189) and controls (n=38). Multivariate analyses were used, adjusted for age, gender, race, ethnicity and use of disease-modifying therapies. RESULTS: The antibody concentrations against EBV (Epstein-Barr nuclear antigen 1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA)), CMV and HSV-1 were similar between pediatric MS patients and controls positive for seroconversion against the virus of interest. EBNA-1 humoral responses were higher in HLA-DRB1 positive individuals (p=0.005) whereas other viral humoral responses were similar in HLA-DRB1 positive and negative individuals. CONCLUSION: Among those positive for EBNA-1, MS patients did not have higher levels of antibody response to EBNA-1: however, titers for EBNA-1 were higher in those who were HLA-DRB1 positive. This suggests that genotype might influence the humoral response to EBV. Whether other genotypes influence antibody response to other viruses remains to be determined.

Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome.

To assess biobehavioral sex differences in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) utilizing a low burden exercise protocol, 22 females and 15 males with ME/CFS and 14 healthy controls underwent two six-min walk tests. Fifteen daily assessments were scheduled for fatigue and function ratings and heart monitoring. Six-min walk tests were conducted on days 8 and 9. The ME/CFS group showed high self-report fatigue and impaired physical function, whereas healthy controls did not show fatigue or function abnormalities. In patients, no significant post-exercise changes were found for heart rate variability (HRV); however, heart rate decreased in ME/CFS males from Day 14 to Day 15 (p = 0.046). Female patients showed increased fatigue (p = 0.006) after the initial walk test, but a downward slope (p = 0.008) in fatigue following the second walk test. Male patients showed a decrease in self-report work limitation in the days after exercise (p = 0.046). The healthy control group evidenced a decrease in HRV after the walk tests from Day 9-14 (p = 0.038). This pilot study did not confirm hypotheses that females as compared to males would show slower exercise recovery on autonomic or self-report (e.g. fatigue) measures. A more exertion-sensitive test may be required to document prolonged post-exertional abnormalities in ME/CFS.Trial registration: NCT NCT03331419.

Uplifts and hassles are related to worsening in chronic fatigue syndrome A prospective study.

Background: Limited published data suggests that absence of uplifts (minor pleasant events) is associated with clinical worsening in patients with chronic fatigue syndrome (CFS). The current study aimed to assess the relation of illness worsening to the trajectories of social and non-social uplifts and hassles in a six-month prospective study in CFS. Methods: Participants were primarily in their 40s, female, white, and ill for over a decade. All participants (N=128) met criteria for CFS. The interview-based global impression of change rating was used to classify individual outcomes as improved, unchanged, or worsened at six- month follow-up. Uplifts and hassles, both social and non-social, were assessed with the Combined Hassles and Uplifts Scale (CHUS). The CHUS was administered weekly in online diaries over six months. Linear mixed effect models were utilized to examine linear trends for hassles and uplifts. Results: No significant differences were found between the three global outcome groups for age, sex, or illness duration; however, work status was significantly lower for the non-improved groups ( p <.001). Non-social hassles intensity showed an increasing slope for the worsened group ( p =.03) and a decreasing slope ( p =0.05) for the improved group. For the worsened group, a downward trend was found for frequency of non-social ( p =0.01) uplifts. Conclusion: Individuals with worsening as compared to improving illness in CFS show significantly different six-month trajectories for weekly hassles and a deficit in uplifts. This may have clinical implications for behavioral intervention. Trial Registration: ClinicalTrials.gov ID: NCT02948556.

Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis.

OBJECTIVE: We sought to determine if vitamin D status, a risk factor for multiple sclerosis, is associated with the rate of subsequent clinical relapses in pediatric-onset multiple sclerosis. METHODS: This is a retrospective study of patients with pediatric-onset multiple sclerosis or clinically isolated syndrome who were consecutively recruited into a prospective cohort at their clinical visit at the pediatric multiple sclerosis center of University of California, San Francisco or State University of New York at Stony Brook. Of 171 eligible patients, 134 (78%) with multiple sclerosis/clinically isolated syndrome were included in the cohort; a further 24 were excluded from this analysis due to lack of available serum (n = 7) or lack of follow-up (n = 17). Serum 25-hydroxyvitamin D(3) levels were measured and were adjusted to reflect a deseasonalized value. The adjusted serum 25-hydroxyvitamin D(3) level was the primary predictor in a multivariate negative binomial regression model in which the main outcome measure was the number of subsequent relapses. RESULTS: Among the 110 subjects, the mean unadjusted 25-hydroxyvitamin D(3) level was 22 +/- 9 ng/ml. After adjustment for age, gender, race, ethnicity, disease duration, disease-modifying therapy, and length of follow-up, every 10 ng/ml increase in the adjusted 25-hydroxyvitamin D(3) level was associated with a 34% decrease in the rate of subsequent relapses (incidence rate ratio, 0.66; 95% confidence interval, 0.46-0.95; p = 0.024). INTERPRETATION: Lower serum 25-hydroxyvitamin D(3) levels are associated with a substantially increased subsequent relapse rate in pediatric-onset multiple sclerosis or clinically isolated syndrome, providing rationale for a randomized controlled trial of vitamin D supplementation.

Fatigue and quality of life in pediatric multiple sclerosis.

Fatigue and quality of life are significant concerns in adult multiple sclerosis (MS) but little is known about these factors in pediatric MS. The present investigation evaluates fatigue and quality of life in 51 pediatric MS patients to determine the rate of fatigue and reduced quality of life and assesses the relations between these variables and clinical factors. Fatigue and quality of life were assessed by self- and parent-report via the PedsQL Multidimensional Fatigue Scale and the PedsQL Quality of Life Scale. One-sample t-tests determined if scores were below published data for healthy individuals. Moreover, scores falling one standard deviation from norms were considered mildly affected, with severe difficulties being defined as scores falling two or more standard deviations from norms. Associations between self- and parent-reported difficulties and clinical factors were examined via Pearson correlation analyses. In comparison with healthy samples, pediatric MS patients reported greater difficulties with respect to fatigue, sleep, cognition, physical limitations, and academics. In addition to significant difficulties on these factors, parents reported problems with respect to emotional functioning, and tended to report greater fatigue, sleep, and cognitive difficulties than were self-reported. Expanded Disability Status Scale score was the only neurologic variable significantly related to fatigue or quality of life scores. Fatigue was significantly correlated with reports of sleep difficulties, cognitive problems, and quality of life variables. These findings suggest that fatigue and poorer quality of life is a clear concern in pediatric MS, and is related to overall physical disability.

Longitudinal neuropsychological assessment in pediatric multiple sclerosis.

Although Multiple Sclerosis (MS) occurring in childhood and adolescence has received increasing attention in recent years, the impact of the disease on cognitive function in this subgroup remains poorly understood. It has been posited that children and adolescents with MS may be particularly susceptible to cognitive dysfunction because the pathological processes, including inflammation, blood brain barrier breakdown, and demyelination, occur concurrently with ongoing myelination. Early work has documented that a number of these children present with cognitive deficits. However, there is no available information on the progression of these deficits, or on what clinical factors may predict further decline. The current article reviews what is currently known about pediatric MS and follows a cohort of pediatric MS patients and assesses cognitive function longitudinally. Participants were evaluated with a brief neuropsychological test battery on two separate occasions and correlational analyses assessed the relations between changes in cognition and several clinical variables including level of neurologic impairment, number of relapses prior to baseline assessment, number of interim relapses, age of disease onset, and disease length. The results indicate that a number of these patients experience further cognitive decline over time, or decline from previously normal functioning. Baseline level of neurologic disability was significantly correlated with changes in cognition. The number of interim relapses (i.e., relapses occurring between baseline assessment and re-evaluation) showed a modest relationship to changes in cognitive function, but this did not reach statistical significance.

[Effects of the thymectomy in a rehabilitation program and in quality of life in patients with myasthenia gravis]. / Valutazione degli aspetti riabilitativi e della Qualità di Vita nei pazienti affetti da miastenia gravis sottoposti a timectomia.

OBJECTIVE: The purpose of this study is to estimate the effects of a rehabilitation program on patients with myasthenia gravis (MG) subordinates to thymectomy. MATERIALS AND METHODS: Patients were evaluated at baseline (T1) and at the end of the pulmonary rehabilitation. (T2), by undergoing spirometric measurements, 6-Minutes Walking Test (6MWT), Berg Balance Scales (BBS), Rivermead Mobility Index (RMI) and Short 36 Form Health Survey version 2 (SF-36v2). The rehabilitation program included exercise to improve the respiratory functionality, the cardiovascular fitness and the global posture. OUTCOME: A single patient obtained improvement pulmonary function, unmodified in the others two patients. Mobility and balance, estimated by the RMI and BBS, effort tolerance, estimated by the 6-MWT QOL, estimated by means of SF36v2 improved, and dyspnoea (Borg scale) reduction was obtained in all of the patients. DISCUSSION: A specific rehabilitative protocol does not exist for the patients with MG subordinates to thymectomy. The AA. conclude that the training relieves dyspnoea, increases the capacity to walk, and improves health-related quality of life. CONCLUSION: Future studies will define the role of the rehabilitation for, these patients and will optimize the protocol.

[Evaluation of the rehabilitation program in a patient submitted to pleuropneumonectomy for malignant pleural mesothelioma]. / Valutazione degli aspetti riabilitativi in un paziente sottoposto ad intervento di pleuropneumonectomia per mesotelioma.

OBJECTIVE: The purpose of this study is to test a rehabilitation program for the patients with malignant pleural mesothelioma (MPM) subordinates to pleuropneumonectomy. MATERIALS AND METHODS: A single patient was evaluated at baseline (TI) and at the end of the pulmonary rehabilitation (T2), by undergoing spirometric measurements, emogasanalisys and 6-Minute Walking Test (6-MWT). Outcome evaluation were administered with Visual Analogic Scales (VAS), Hospital Anxiety and Depression Scales (HADS) and Short 36 Form Health Survey version 2 (SF-36). The rehabilitative program included exercise to improve the respiratory functionality, the cardiovascular fitness and the global posture. OUTCOME: Pulmonary function, effort tolerance, estimated by the 6-Minute Walking Test, quality of life, estimated by means of SF-36 v2 improved, and pain, estimated by Visual Analogic Scales, anxiety and depression estimated by Hospital Anxiety and Depression Scales reduction was obtained. DISCUSSION: Actually does not exist a specific rehabilitation protocol for MPM patients. We report that our protocol relieved dyspnoea, increased the capacity to walk, and improved health-related quality of life. CONCLUSIONS: Future studies will define the role of the rehabilitation for MPM patients and will optimize the protocol.

Clinical and imaging study of human immunodeficiency virus-1-infected youth receiving highly active antiretroviral therapy: pilot study using magnetic resonance spectroscopy.

In the initial assessment of children with new-onset seizures, the suggestion that electroencephalography (EEG) should be standard and that magnetic resonance imaging (MRI) should be optional has been questioned. The purposes of this children (four boys) with vertically transmitted stable HIV infection had a neurologic examination, neuropsychologic testing, and a neuroimaging study. The structural magnetic resonance imaging (MRI) and metabolic changes (magnetic resonance spectroscopy) were compared with the cognitive, clinical, and laboratory results. Our results for the eight children who completed the magnetic resonance spectroscopic study showed that a high N-acetylaspartate (NAA) to choline ratio correlated significantly with IQ subtests of arithmetic (r = .74; P < .034) and comprehension (r = .77; P = .025). Our results suggest that lower NAA and higher choline values represent neuronal dysfunction and inflammation that can be recognized before anatomic changes appear on MRI. In addition, a low NAA to Cho ratio correlated with poor performance. These data suggest that magnetic resonance spectroscopy can be used as a follow-up tool in addition to the structural MRI. Moreover, a change in a child's performance with a concomitant change in NAA and choline, as measured with magnetic resonance spectroscopy, could indicate the need for more aggressive intervention.

Rehabilitation and quality of life in patients undergoing surgery for esophageal cancer.

The impact of esophageal cancer surgery, postoperatively as well as on quality of life (QoL) is still largely unknown. Clinical experience and the scarce existing literature concur that these patients show difficulty in returning to their original lifestyles and previous social activities, not just due to the difficulties common to all tumor pathologies but also for the specific dietary and digestive disturbances which characterize esophageal cancer therapy. As specific rehabilitation protocols are nonexistent in the literature, in this study a rehabilitation planning program, is proposed based on evaluation of postoperative and long-term problems which can be tackled with rehabilitation.

Pediatric multiple sclerosis: Perspectives from adolescents and their families.

Supporting young people with pediatric multiple sclerosis can be challenging for families and health care providers. Adolescents may be more resilient than adults in reaction to the diagnosis but can have more difficulty planning for their futures. Appropriate, sensitive, and focused health provision should include consideration of the perspective of both the patient and parents. Multidisciplinary management strategies are often effective, as are referrals to programs that enhance individual and family coping and strengthen a sense of community.

Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica.