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Theoretical models suggest that anxiety, pain intensity, and pain catastrophizing are implicated in a cycle that leads to heightened fear of cancer recurrence (FCR). However, these relationships have not been empirically examined. The objective of this study was to examine the relationships between anxiety symptoms, pain intensity, pain catastrophizing, and FCR in childhood cancer survivors and their parents and to examine whether pain catastrophizing predicts increased FCR beyond anxiety symptoms and pain intensity.The participants were 54 survivors of various childhood cancers (Mage=13.1 y, range=8.4 to 17.9 y, 50% female) and their parents (94% mothers). Children reported on their pain intensity in the past 7 days. Children and parents separately completed measures of anxiety symptoms, pain catastrophizing, and FCR.Higher anxiety symptoms were associated with increased pain intensity, pain catastrophizing, and FCR in childhood cancer survivors. Higher anxiety symptoms and pain catastrophizing, but not child pain intensity, were associated with FCR in parents. Hierarchical linear regression models revealed that pain catastrophizing explained unique variance in both parent (ΔR2=0.11, P0.01) and child (ΔR2=0.07, P0.05) FCR over and above the effects of their own anxiety symptoms and child pain.The results of this study provides novel data on the association between pain and FCR and suggests that a catastrophic style of thinking about pain is more closely related to heightened FCR than one's anxiety symptoms or the sensory pain experience in both childhood cancer survivors and their parents. Pain catastrophizing may be a novel intervention target for survivors and parents struggling with fears of recurrence.

ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, and ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes and MeasuresThe main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.ResultsAmong 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.Conclusions and RelevanceAmong critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

The aim of this study was to examine the impact of end-of-life (EoL) circumstances on grief and internalizing symptoms among bereaved siblings. Bereaved families (N = 88) were recruited from three sites 3-12 months (M = 11.57, SD = 3.48) after their child's death from cancer. One sibling per family aged 8-17 years (M = 12.41, SD = 2.64) was randomly selected to participate. Families completed measures of siblings' grief and internalizing symptoms, as well as a structured interview about circumstances surrounding the death. Mother and sibling reports of EoL circumstances were generally concordant, except there was a discrepancy between mothers and children about whether or not children expected their sibling's death (t(75) = 1.52, p = .018). Mother reports of sibling internalizing symptoms were above the normative mean (t(83) = 4.44, p ≤ .001 (M = 56.01 ± 12.48), with 39% (n = 33) in the borderline/clinical range. Sibling opportunity to say goodbye was associated with greater grief-related growth (t(79) = - 1.95, p = .05). Presence at the death and wishing they had done something differently were both associated with greater grief (t(80) = - 2.08, p = .04 and t(80) = - 2.24, p = .028, respectively) and grief-related growth (t(80) = - 2.01, p = .048 and t(80) = - 2.31, p = .024, respectively). However, findings were primarily unique to sibling report, with few mother-reported effects. The adjustment of bereaved siblings may be affected by certain modifiable circumstances surrounding the death of their brother or sister. A proportion of bereaved siblings had elevated internalizing symptoms irrespective of circumstances at EoL. Further work is needed to understand predictors of adjustment among bereaved siblings to provide better support and optimize their outcomes.

Context Caring for a child who will die from a life-limiting illness is one of the most difficult experiences a parent may face. Pediatric palliative care (PPC) has grown as a specialty service to address the unique needs of children and families with serious illness. However, gaps remain between the needs of families in PPC and the support received. Objectives The objective of this study was to explore the concerns of parents who have a child in home-based PPC. Methods Semistructured interviews were conducted with 25 mothers and 10 fathers from 25 families shortly after their child's referral to home-based PPC. Children (57% male, Mage = 10.5 years, SD = 3.95, range = 4–18 years) had a range of diagnoses. Data were analyzed using inductive content analysis. Results Parents' concerns clustered into four main themes: 1) ensuring that their child's remaining days were spent living well physically, emotionally, and socially; 2) uncertainty regarding their child's diagnosis, prognosis, and treatments; 3) their child's death (e.g., the process of dying and when it will occur); and 4) the family, including the impact of the child's illness and death on siblings and wanting to cherish as much time together with family as possible. Conclusion Parents of children receiving home-based PPC expressed concerns across a range of domains, both about their seriously ill child and the broader family. These results highlight salient worries among parents of children in PPC and point to critical areas for intervention for seriously ill children and the broader family.

Survivors of childhood cancer may be at risk of experiencing pain, and a systematic review would advance our understanding of pain in this population. The objective of this study was to describe: 1) the prevalence of pain in survivors of childhood cancer, 2) methods of pain measurement, 3) associations between pain and biopsychosocial factors, and 4) recommendations for future research. Data sources for the study were articles published from January 1990 to August 2019 identified in the PubMed, PsycINFO, EMBASE, and Web of Science data bases. Eligible studies included: 1) original research, 2) quantitative assessments of pain, 3) articles published in English, 4) cancers diagnosed between birth and age 21 years, 5) survivors at 5 years from diagnosis and/or at 2 years after therapy completion, and 6) a sample size >20. Seventy-three articles were included in the final review. Risk of bias was considered using the Cochrane risk of bias tool. The quality of evidence was evaluated according to Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria. Common measures of pain were items created by the authors for the purpose of the study (45.2%) or health-related quality-of-life/health status questionnaires (42.5%). Pain was present in from 4.3% to 75% of survivors across studies. Three studies investigated chronic pain according the definition in the International Classification of Diseases. The findings indicated that survivors of childhood cancer are at higher risk of experiencing pain compared with controls. Fatigue was consistently associated with pain, females reported more pain than males, and other factors related to pain will require stronger evidence. Theoretically grounded, multidimensional measurements of pain are absent from the literature.

Aims Fear of cancer recurrence (FCR) is among the most prevalent and distressing concerns reported by cancer survivors. While younger age is the most consistent predictor of elevated FCR, research to date has focused almost exclusively on adult cancer survivors. This is despite the fact that children with cancer are more likely to survive compared to adults, and will become regular, lifelong users of the medical system to mitigate the effects of toxic treatment. The early experience of cancer yields unique challenges and circumstances that may impact children's capacity for and experience of FCR across the developmental trajectory. The aim of this paper is to present a developmental perspective of FCR from infancy to young adulthood. Methods Drawing on the developmental science literature and recent theoretical advancements in FCR, we outline cognitive and social factors that may influence children's capacity for and experience of FCR across the developmental trajectory. Results First, distinct developmental groups that fall under the classification of "childhood cancer survivor," and that all require attention, are summarized. Using the structure of these groupings, we centrally provide a developmental perspective of FCR that offers a useful starting point for research in pediatric populations. Key research gaps, including the need for validated assessment tools to measure FCR in child and adolescent survivors, are highlighted. Conclusions Consideration of the unique context of childhood is needed to guide the identification of childhood cancer survivors at risk for FCR as well as the development of effective FCR interventions for this population.

Fear of cancer recurrence (FCR) is a common and distressing psychosocial concern for adult cancer survivors. Data on this construct in child survivors is limited and there are no validated measures for this population. This study aimed to adapt the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) for survivors of childhood cancer aged 8-18 years (Fear of Cancer Recurrence Inventory-Child version [FCRI-C]) and their parents (Fear of Cancer Recurrence Inventory-Parent version [FCRI-P]) to self-report on their own FCR and to examine the initial psychometric properties.The FCRI-SF was adapted through expert panel input and cognitive interviews with child survivors18 years. The factor structure, internal consistency and construct and criterion validity of the FCRI-C and FCRI-P were examined in 124 survivors of childhood cancer (43% female; MAll FCRI-SF items were retained for the FCRI-C with simplified language. The internal consistencies of the FCRI-C (α = 0.88) and FCRI-P (α = 0.83) were good. Exploratory factor analyses yielded one-factor structures for both measures. Higher scores on the FCRI-C and FCRI-P were associated with greater intolerance of uncertainty and pain catastrophizing. Higher child FCR was also related to more hypervigilance to bodily symptoms. Parents with higher FCR reported contacting their child's doctors and nurses and scheduling medical appointments for their child more frequently. Children reported significantly lower FCR compared to parents.The FCRI-C and FCRI-P demonstrated strong reliability and preliminary validity. This study offers preliminary data to support the use of the FCRI-C and FCRI-P to measure FCR in survivors of childhood cancer aged 8-18 years and their parents.

Objective Today, more than 80% of children diagnosed with cancer are expected to survive. Despite the high prevalence of pain associated with the diagnosis and treatment of childhood cancer, there is a limited understanding of how having cancer shapes children's experience and meaning of pain after treatment has ended. This study addresses this gap by exploring childhood cancer survivors' (CCS') experiences of pain from their perspective and the perspective of their parents. Methods Twenty semi-structured interviews were completed with CCS (50% female; mean age = 13.20 y, range = 8-17 y) and their parents (90% mothers). Data were analyzed using interpretive phenomenological analysis. Results Analyses revealed three superordinate themes present in the data: (a) pain is a changed experience after childhood cancer; (b) new or ambiguous pains may be interpreted by CCS and parents as a threat of disease recurrence, late effects, or a secondary cancer; and (c) pain interpretation occurs within the broader context of how CCS and parents appraise their cancer experience. Parents generally appraised their child's cancer and pain as more threatening and were influential in guiding their child's interpretations. Conclusions The cancer experience played an important role in shaping CCS' and their parents' experience and interpretation of pain in survivorship. This study provides novel data to inform the development and refinement of new and existing conceptual models of pain and symptom perception after cancer. The results also point to key areas for future investigation and clinical intervention to address the issue of pain in cancer survivorship.

Cancer and its treatment can have lasting consequences on somatosensation, including pain, which is often underrecognized and undertreated. Research characterizing the impact of cancer on pain and sensory processing in survivors of childhood cancer is scarce. This study aimed to quantify generalized differences in pain and sensory processing in survivors of childhood cancer compared with reference data using a standardized thermal and mechanical quantitative sensory testing (QST) protocol. The association between demographic, clinical (eg, leukemia vs other cancers and treatment exposures), and psychosocial (eg, anxiety and pain catastrophizing) variables and sensitivity to pain and sensory stimuli were also evaluated. Participants were 56 survivors of various types of childhood cancer (52% male, Mage = 13.5 years, SD = 3.2, range = 8-17 years). On average, children were 7 years (SD = 4.1, range = 1.2-16.5) post treatment. Almost all participants (86%) had at least 1 abnormal QST parameter compared with age- and sex-matched reference data; however, few participants self-reported the presence of sensory abnormalities. Generally, participants exhibited reduced sensitivity across the QST parameters examined (Ps < 0.05, ds = 0.40-3.45). A significant minority (45%) also exhibited pain sensitization (P

Objective Children with juvenile idiopathic arthritis (JIA) are faced with a complex medical journey requiring consistent adherence to treatments to achieve disease management. Parents are intimately involved in JIA treatments; however, little is known about their experiences in this role. This is relevant as many treatments necessitate procedural pain (e.g., self-injections) or side effects (e.g., nausea), which may impact a parents' ability to follow treatment plans. The objective of this study was to explore the lived experiences of parents who identified challenges with their child's JIA treatments. Methods Parents of children with JIA who identified challenges with their child's treatments were invited to take part in semi-structured interviews. Data were analyzed using interpretative phenomenological analysis. Results Ten mothers of children with JIA (60% female, Mage =11.83 years, range=4-16 years) participated. Four superordinate themes were present in mothers' experiences: (1) treatments altered mothers' roles within the family, increasing their caregiver burden and advocacy; (2) treatments positively and negatively impacted their relationships (e.g., increased support from others, decreased time with others); (3) treatments elicited various emotional responses (e.g., frustration, grief) which affected their well-being; and (4) treatments were at times a source of internal conflict, affecting mothers' actions and adherence. Conclusion Mothers' experiences with their child's JIA treatments affects them in various ways that can subsequently impact treatment adherence. Results highlight the value of supporting parents through these complex treatment regimens and incorporating their experiences in treatment decisions to help promote optimal outcomes for children with JIA and their families.

On March 12, 2020, the World Health Organization (WHO) declared the outbreak of a new Coronavirus disease (COVID-19), to be a pandemic. From the beginning, Italy (in particular the Northern regions) was the first large European country to be hit and one of the most affected countries worldwide. This had a significant impact on the workload and psychological health of health workers. The aim of this web-based cross-sectional study is to assess the consequences of the COVID-19 pandemic on Italian doctors' well-being and psychological distress, in respect of demographic and occupational characteristics, lifestyle and habits during the lockdown period.We conducted a web-based cross-sectional survey based on Google® Forms to collect data. The participation was available during the lockdown period that started in Italy on March 9, 2020 and it was voluntary and anonymous. The questionnaire explored demographic and occupational variables, lifestyle and habits during the lockdown, perceived well-being and psychological distress. Multivariate logistic regression models were fitted.Our study reported the very alarming psychological conditions of Italian doctors, especially among those who worked in the most affected regions, where a level of psychological distress of 93.8% and poor well-being of 58.9% were registered. These percentages were even higher in the case of female hospital workers with low job seniority, and those caring for COVID-19 patients.Our findings reported a significant psychosocial impact of the COVID-19 outbreak on Italian doctors, particularly among those working in the most affected regions of the country. Further studies are necessary to better understand the effects of the COVID-19 pandemic on doctors' well-being and mental health over time, in order to implement effective prevention measures.

Pain is a common and distressing symptom of pediatric cancer, as reported by both children and their parents. Increasingly, children with cancer are cared for as outpatients, yet little is known about how parents manage their cancer-related pain. The aim of the current study was to examine pain prevalence and characteristics, and the pharmacological, physical, and psychological pain management strategies used by parents to manage their child's cancer pain.In total, 230 parents and caregivers (89% mothers) of children (mean age=8.93 y, SD=4.50) with cancer currently in treatment or who are survivors completed an online survey about their child's pain in the preceding month.Results indicated that children with cancer who were on active treatment and who were posttreatment experienced clinically significant levels of pain. Parents reported using more physical and psychological strategies than pharmacological strategies to manage their child's pain. The most frequently used physical/psychological strategy was distraction and acetaminophen was the most frequently administered pain medication. Parents' confidence in managing their child's pain was inversely associated with both how much pain they perceived their child had, and also whether they had given any pain medication.The results of this study suggest that despite parents' use of pain management strategies, management of cancer-related pain continues to be a problem for children during treatment and into survivorship.

Purpose: Adolescents and young adults (AYAs) with terminal cancer are a marginalized population with unique medical and psychosocial needs. AYAs commonly report challenges with their health care experiences, however, little is known about the experiences of the health care providers (HCPs) who deliver this specialized care. The purpose of the current study was to understand HCPs' experiences caring for AYAs with terminal cancer. Methods: Nine HCPs (four nurses and five physicians) took part in in-depth semistructured interviews. Participants were eligible if they were a nurse or physician in Atlantic Canada; cared for at least one AYA patient with terminal cancer in the past 3 years; and were able to speak and understand English. Data were analyzed using interpretive phenomenological analysis. Results: Analyses revealed four superordinate themes present in the data: (1) many unknowns and uncertainties associated with providing care for AYAs compounded by minimal or no training specifically concerning this population; (2) an intense emotional experience compared with caring for patients with terminal cancer of other ages; (3) personal identification with patients and their families; and (4) attempts to make sense of the circumstance thwarted by feelings of injustice and unfairness. Conclusions: HCPs experienced unique emotional and logistical challenges when caring for AYAs with terminal cancer, which can influence the care they provide. HCPs' experiences highlight the need for training to support clinicians in caring for AYAs with terminal cancer to optimize their own well-being and delivery of health care services to this population.

Different aspects of episodic long-term, short-term and implicit long-term memory were investigated in subjects who strictly fulfilled the criteria for the amnestic form of Mild Cognitive Impairment (a-MCI). Results showed normal short-term memory abilities in these subjects, while each of the episodic long-term memory indices explored showed poorer results in a-MCI subjects with respect to normal controls. Although some episodic memory functions were relatively well preserved, others appeared to have deteriorated to a level comparable to that of mild AD patients. The finding of an extensive impairment of all memory functions depending on hippocampal structures in a population with a high risk of developing dementia is strongly supportive of the hypothesis that a pure amnesic syndrome characterizes the preclinical phase of AD. Copyright © Taylor & Francis Ltd.

BACKGROUND/OBJECTIVES: Subjects affected by mild cognitive impairment (MCI) may improve during the observation period. This is the first study investigating qualitative features of memory deficits in subjects affected by reversible MCI [reversible cognitive impairment (RCI)]. METHODS: Baseline cognitive and memory performances of 18 subjects affected by amnestic MCI who had normalized cognitive performances at follow-ups were compared with those of 76 amnestic MCI subjects who still showed impaired cognitive performances at the 24-month follow-up (MCI) and with those of a group of 87 matched control subjects (normal controls). RESULTS: Compared with normal controls the memory deficit in the MCI group affected all aspects of explicit long-term memory functioning; in the RCI group, instead, the memory deficit only affected the free recall of verbal material, particularly when the encoding could be improved by the use of semantic strategies. CONCLUSIONS: These results are consistent with the view that the memory deficit in the MCI group is due to a very early degenerative pathology; in the RCI group, instead, a transitory reduction of processing resources, resulting a poor encoding of incoming material, is likely at the origin of the reversible memory disorder.

The early differentiation of Alzheimer’s disease (AD) from frontotemporal dementia (FTD) may be difficult. The Tower of London (ToL), thought to assess executive functions such as planning and visuo-spatial working memory, could help in this purpose. Twentytwo Dementia Centers consecutively recruited patients with early FTD or AD. ToL performances of these groups were analyzed using both the conventional statistical approaches and the Artificial Neural Networks (ANNs) modelling. Ninety-four non aphasic FTD and 160 AD patients were recruited. ToL Accuracy Score (AS) significantly (p < 0.05) The use of hidden information contained in the different items of ToL and the non linear processing of the data through ANNs allows a high discrimination between FTD and AD in individual patients. However, the discriminant validity of AS checked by ROC curve analysis, yielded no significant results in terms of sensitivity and specificity (AUC 0.63). The performances of the 12 Success Subscores (SS) together with age, gender and schooling years were entered into advanced ANNs developed by Semeion Institute. The best ANNs were selected and submitted to ROC curves. The nonlinear model was able to discriminate FTD from AD with an average AUC for 7 independent trials of 0.82. The use of hidden information contained in the different items of ToL and the non linear processing of the data through ANNs allows a high discrimination between FTD and AD in individual patients.

Objective The aim of this paper was to assess the efficacy of process-based cognitive training (pb-CT) combined with reminiscence therapy (RT) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and in healthy elderly (HE) subjects. Methods This multicenter, randomized, controlled trial involved 348 participants with mAD, MCI, and HE from four European countries. Participants were randomly assigned to two arms of a crossover design: those in arm A underwent 3 months of computerized pb-CT for memory and executive functions combined with RT and 3 months of rest; those in arm B underwent the reverse. The primary outcome was the effect of the training on memory and executive functions performance. The secondary outcome was the effect of the training on functional abilities in mAD assessed with the instrumental activities of daily living. Results We found a significant effect of the training for memory in all three groups on delayed recall of the Rey Auditory Verbal Learning Test and for executive functions in HE on the phonological fluency test. MCI and HE participants maintained these effects at follow-up. MCI and mAD participants also showed a significant effect of the training on the Mini-mental state examination scale. Participants with mAD showed more stable instrumental activities of daily living during the training versus the rest period. Conclusions Our results corroborate the positive effect of pb-CT and its maintenance primarily on memory in HE and MCI participants that did not seem to be potentiated by RT. Moreover, our results are very promising for the mAD participants. Copyright © 2015 John Wiley & Sons, Ltd.

Background: Different rates and cognitive predictors of conversion to dementia have been reported in subjects with different kinds of mild cognitive impairment (MCI). Methods: A prospective, 24-month follow-up study, involving 269 subjects who strictly fulfilled criteria for the amnestic MCI. Results: Conversion rate to dementia was 21.4% per year. Seventy-nine out of the 83 individuals who developed dementia were affected by probable Alzheimer’s disease (AD). Among others, at the 24-month follow-up 24.1% were still affected by amnestic MCI, 13.3% had changed their neuropsychological profile of impairment and 17.2% were cognitively normalised. Compared to subjects who did not convert to AD, those who did convert showed poorer immediate and delayed recall and recognition of verbal and visual material at baseline as well as reduced executive abilities. A combination of age, Clinical Dementia Rating boxes and scores on delayed recall and recognition of verbal and visual material accurately identified 86% of the subjects who developed AD. Conclusions: Elderly subjects affected by an isolated memory disorder have a high probability of developing AD. The ability of verbal and visual measures to predict incipient dementia of memory impairment may be increased by the simultaneous assessment of individual features, such as age or rate of functional impairment.

The significance of paroxysmal nocturnal haemoglobinuria (PNH(pos) ) cells and leucocyte subset telomere lengths in paediatric aplastic anaemia (AA) is unknown. Among 22 children receiving immunosuppressive therapy (IST) for AA, 73% (16/22) were PNH(pos) , of whom 94% achieved at least a partial response (PR) to IST; 11/16 (69%) achieved complete response (CR). Only 2/6 (33%) PNH(neg) patients achieved PR. PNH(pos) patients were less likely to fail IST compared to PNH(neg) patients (odds ratio 0·033; 95% confidence interval 0·002-0·468; P = 0·012). Children with AA had short granulocyte (P = 7·8 × 10(-9) ), natural killer cell (P = 6·0 × 10(-4) ), naive T lymphocyte (P = 0·002) and B lymphocyte (P = 0·005) telomeres compared to age-matched normative data.

A door-to-door prevalence survey of epilepsy was conducted in 3 Sicilian municipalities, as of November 1, 1987. In phase 1, the screening by questionnaire of 24,496 eligible subjects (participation = 92%) identified 544 suspected to have epilepsy. In phase 2, neurological evaluation of the 544 subjects yielded 111 with epilepsy. Of the 111 subjects, 103 (93%) had been previously diagnosed, 68 (61%) were taking antiepileptic medication, and 81 (73%) had active epilepsy. Referring to the 81 subjects with active epilepsy, the seizure type was generalized in 60 (74%), partial in 19 (23%) and undetermined in 2 (3%). The prevalence of active epilepsy (per 1,000 population) was 3.3 overall, 3.5 for men and 3.2 for women. The age-specific patterns for active epilepsy differed by sex, with higher figures for men at younger ages (5-19 years) and older ages (50-99 years). The age-specific prevalence figures for active epilepsy were lower than those from previous Italian surveys. Copyright © 2001 S. Karger AG, Basel.

Aim: To determine the applicability and psychometric properties of the Italian version of the Disability Assessment of Dementia scale (DAD-I) in a community-residing population with early-stage Alzheimer’s disease (AD). Methods: The DAD-I was administered to the primary caregivers of 159 patients (mean age ± SD 77.1 ± 5.2) with mild AD (mean Mini Mental State Examination, MMSE, ± SD 23.1 ± 2.2). Results: The DAD-I showed excellent internal consistency reliability (Cronbach’s α = 0.92) and good construct validity. The DAD-I score was not significantly associated with gender, education and presumed duration of the illness, and had a low negative correlation with age. The DAD-I score correlated moderately with the traditional Instrumental Activities of Daily Living and Activities of Daily Living scales, respectively, with r = 0.53 and r = 0.54 (p < 0.0001). Relatively low, but statistically significant correlations (r ranging between 0.21 and 0.31) with the MMSE were also found. Conclusion: The DAD-I was found to be a reliable and valid instrument to assess functional disability in community-dwelling Italian subjects with early-stage AD.

Background: Executive dysfunction in Alzheimer’s disease (AD) has been recently recognized as an early and prominent clinical sign. The Tower of London (ToL), a task specifically devised to test executive functions of visuospatial planning and problem solving, has frequently been used in neuropsychological experiments, but rarely in the clinical ground. Methods: One hundred and sixty-one AD patients and 212 nondemented healthy controls were administered a simplified ToL version. Results: AD patients were significantly impaired (p < 0.0001) in all ToL scores and in the total execution time. The ‘accuracy’ score of ToL at a cut off of ≤29/36 yielded a sensitivity of 71.2% and a specificity of 76.4% (AUC 0.79) for the diagnosis of AD versus controls. Conclusions: Visuospatial planning and problem solving are significantly impaired in early dementia of the Alzheimer’s type. A successful sensitivity/specificity ratio, the independence of education and the simplicity of this version of ToL make it a useful executive functioning screening test for early AD.

Previous research on patients with left tactile extinction has shown that crossing of hands, so that each hand is on the opposite side of the body midline relative to the other, improves detection of stimuli given to the left hand.To study the influence of the spatial position of limbs on left tactile extinction, and its relations with left visual neglect.Normal participants and patients with right cerebral hemisphere damage and left tactile extinction were asked to detect single or double light touch stimuli applied to their cheeks, hands, or knees with their arm and legs either in anatomical or in crossed position, increasing the attentional load of the task.In patients with left extinction, limb crossing caused a deterioration in performance for stimuli applied to right body parts, with only a tendency to an improvement in detection for left body parts (only two of 24 patients showed substantial (20%) improvement in left extinction after limb crossing). After crossing, left limb detections of double stimuli decreased with increasing degrees of visual neglect.In conditions of high attentional load, limb crossing may impair tactile detection in most patients with left extinction, and particularly in those showing signs of left visual neglect. These results underline the importance of general attentional capacity in determining tactile extinction. Attentional and somatotopic mechanisms of extinction may assume different weights in different patients.

We assessed the validity of an Italian language version of the Epworth sleepiness scale (ESS). The translated ESS was compared to the multiple sleep latency test (MSLT), considered the gold standard for the diagnosis of excessive daytime sleepiness (EDS). Within the context of a multicentric national study on narcolepsy (Gruppo Italiano Narcolessia Studio Epidemiologico Nazionale, GINSEN) involving 17 Italian sleep centres, we compared the two diagnostic tests on 91 prospectively recruited subjects with suspected EDS (34 with narcolepsy, 16 with obstructive sleep apnea syndrome, 19 with idiopathic hypersomnia, and 22 with other sleep, neurologic or psychiatric disorders). ESS scores were inversely correlated with mean sleep latency values, as measured with MSLT (rho = −0.31, p

Fourteen diabetic patients (13 males, 1 female, 7 IDDM and 7 NIDDM) were tested during wakefulness with a battery of tests examining parasympathetic and sympathetic control of the cardiovascular system. Subsequently sleep recordings including EEG, EOG, submental, left and right anterior tibialis EMGs, ECG, nasal airflow, thoracic and abdominal respirograms, nocturnal penile tumescence, were performed in each subject. The assessment of cardiovascular functions during sleep was based on the following parameters: Rbm, R-wake, apnea index, adequate penile tumescence during phase REM. Parasympathetic and sympathetic control of cardiovascular system were both impaired during wakefulness in only one patient, who also showed a low Rbm index indicative of ascertained autonomic neuropathy. Indices Rbm sufficiently low to be considered an evidence of probable autonomic neuropathy were found in 5 patients (3 IDDM and 2 NIDDM); all but one with normal cardiovascular tests during wakefulness. Five patients showed gross deficiency upon nocturnal penile tumescence monitoring. In comparison with a control group the patients showed a significantly lower overall Rbm index (p less than 0.001). IDDM patients showed an increased plasma GH response to insulin-induced hypoglycemia compared to NIDDM and normal subjects. Increased GH secretion was furthermore confirmed by GH values obtained in blood samples drawn during the first REM stage of the night in IDDM patients. The evaluation of the variables taken into consideration during sleep appears to be crucial for the assessment and prevention of autonomic neuropathies and neuroendocrine dysregulation in diabetic patients.

Chronic exposure to work-related stress (WRS) stimulates the hypothalamic-pituitary-adrenal (HPA) axis to increase glucocorticoid secretion, including cortisol, and these hormones can be measured both in serum and urine. The Health Safety Executive Toolkit (HSE) questionnaire is used to assess WRS risk objectively. The scope of our study is to investigate whether serum or urinary cortisol levels could be used as alternative objective indicators of WRS, specifically in those subjects who are chronically exposed to it.130 patients (75 males and 55 females, mean age 47.7 ± 11.3 years) were evaluated at a specialized Centre for Secondary Hypertension, where both their serum (8 AM) and 24-hours urinary cortisol were measured and they were asked to complete two questionnaires: one questionnaire to collect data about their socio-demographic and job characteristics, and the HSE questionnaire to evaluate WRS.Multiple linear regression analysis showed an association of urinary cortisol with several variables: tobacco smoke (β = 69.6; p = 0.003); female gender (β = -37.3; p = 0.041); exposure to physical risks (β = 51.8; p = 0.032); control score (β = -22.7; p = 0.039); role score (β= 39.3; p = 0.020). Age was the only variable associated with serum cortisol levels (β = -3.6; p = 0.042).Urinary cortisol levels, but not serum levels, are associated with variables linked to WRS (score control and role) and to socio-demographic variables, namely gender and tobacco smoke. Thus, urinary cortisol can be considered a useful and non-invasive biological indicator to quantify WRS.

As part of a door-to-door survey of neurologic diseases, we investigated the prevalence of lumbosacral radiculopathy (LR) in two Sicilian municipalities (N = 14,540, as of November 1, 1987).During phase 1, we administered a brief screening instrument to subjects in the study population. In phase 2, study neurologists using specified diagnostic criteria investigated those subjects who screened positive. Our case finding was restricted to subjects who manifested symptoms of LR in the six months preceding the prevalence day.We found 143 subjects affected by LR (112 definite, 31 possible) yielding a crude prevalence of 9.8 cases per 1,000 population. Age-specific prevalence was generally higher in men; it increased to a peak at age 50-59 years and decreased steadily thereafter. At the peak, prevalence was higher in factory workers, housewives, and clerks compared to workers in other occupations.LR is a common neurologic disease in the general population.

Background: Motor and inhibitory control rely on frontal cortex activity, which is known to reach full maturation only in late adolescence. The development of inhibitory control has been studied using event-related potentials (ERP), focusing on reactive processing (i.e. the N2 and the P3 components). Scarce information exists concerning pre-stimulus activity as that represented by the Bereinshafstpotential (BP) and by the prefrontal negativity (pN). Further, no literature exists concerning the post-stimulus components originating within the anterior insula (pN1, pP1, pP2). This study aims at associating children performance with these motor-cognitive processing in frontal brain areas. Methods: High-resolution EEG recordings were employed to measure ERPs from 18 children (12 years old) and 18 adults (28 years old) during a visuo-motor discriminative response task. Response time (RT), commission (CE) and omission errors, and RT variability were compared between groups. At brain level, two pre-stimulus (BP and pN) and seven post-stimulus (P1; pN1; N1; pP1; N2; pP2; P3) ERP components were compared between groups. Results: Children showed slower and more variable RTs and poorer inhibition (higher CEs) than adults. At electrophysiological level, children presented smaller BP and pN. After stimulus onset, children showed lower amplitude of N1, pP1, P3, and pP2 components. The P1, pP1, N2 and P3 were delayed compared to adults. Conclusions: Our results demonstrate that children are characterized by less intense task-related proactive activities in frontal cortex, which may account for subsequent poor and delayed reactive processing and, thus, for inaccurate and slow performance.

We carried out an fMRI study with a twofold purpose: to investigate the relationship between networks dedicated to semantic and visual processing and to address the issue of whether semantic memory is subserved by a unique network or by different subsystems, according to semantic category or feature type. To achieve our goals, we administered a word–picture matching task, with within-category foils, to 15 healthy subjects during scanning. Semantic distance between the target and the foil and semantic domain of the target–foil pairs were varied orthogonally. Our results suggest that an amodal, undifferentiated network for the semantic processing of living things and artifacts is located in the anterolateral aspects of the temporal lobes; in fact, activity in this substrate was driven by semantic distance, not by semantic category. By contrast, activity in ventral occipito-temporal cortex was driven by category, not by semantic distance. We interpret the latter finding as the effect exerted by systematic differences between living things and artifacts at the level of their structural representations and possibly of their lower-level visual features. Finally, we attempt to reconcile contrasting data in the neuropsychological and functional imaging literature on semantic substrate and category specificity.

Frontotemporal dementia (FTD) has a strong genetic basis, with familial forms occurring in 30-50% of cases. Causative genes have been identified, with an autosomal dominant pattern of inheritance. Notwithstanding, in a number of cases with positive family history no pathogenetic mutation has been reported, and the role of genetics in sporadic cases is still unclear. The aim of the present study was to estimate the genetic contribution to FTD using concordance among parent-offspring pairs. Heritability of early-onset (EO

Alzheimer's disease (AD) is characterized by altered functional cortico-cortical connectivity likely due to loss of afferent and efferent connections between different cortical areas. Here we explored parieto-frontal functional connectivity in 15 AD patients and 12 healthy control subjects by means of bifocal transcranial magnetic stimulation (TMS). Conditioning stimuli were applied over the right posterior parietal cortex (PPC) at different intensities (90% and 110% of resting motor threshold, RMT). Motor evoked potentials (MEPs) were then recorded from the ipsilateral primary motor cortex at different interstimulus intervals (ISIs) ranging between 2 and 15 ms. Results showed that in healthy subjects, a conditioning TMS pulse applied over the ipsilateral PPC at 90%, but not at 110%, of RMT intensity was able to increase the excitability of the right M1. This functional interaction peaked at ISI = 6 ms. Conversely, in AD patients the facilitatory pattern of parieto-motor connections was evident only when TMS was delivered at an intensity of 110% of RMT with a peak at ISI = 8 ms. Moreover in AD patients, treatment with cholinesterase inhibitors did not induce any significant modification in the strength of the connection. In subsequent analyses, we found that, in AD patients, the effects induced by PPC conditioning at 110% RMT correlated with neuropsychological measures of episodic memory and executive functions, implying that patients with better cognitive performance had less impaired connectivity. Our findings reveal that parieto-frontal cortico-cortical functional connectivity is altered in AD patients, providing further evidence for a disconnection-based interpretation of AD symptoms. © 2013 - IOS Press and the authors. All rights reserved

Background/Aims: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. Methods: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer’s disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson’s disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. Results: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer’s disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson’s disease dementia. Conclusion: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.

Amnestic mild cognitive impairment (a-MCI) is associated with the highest annual incidence of conversion to Alzheimer's disease (AD) (10-15%). a-MCI patients may have only a memory deficit (single domain: sd-a-MCI) or additional dysfunctions affecting other cognitive domains (multiple domain: md-a-MCI). Using functional magnetic resonance imaging (fMRI), we investigated brain activation in 16 sd-a-MCI patients and 14 controls during four different tasks assessing language, memory, attention and empathy functions. We found greater activation in sd-a-MCI compared with controls in the left inferior temporal gyrus (language), the right superior temporal gyrus (memory) and the right dorsal precentral gyrus (attention). Moreover, patients' activation correlated significantly with neuropsychological scores obtained at tests exploring the corresponding function. These findings indicate that fMRI is sensitive to detect early changes occurring in AD pathology and that individuals with sd-a-MCI show increased activation in multiple task-related brain regions. We suggest that these functional changes relate to the development of early compensatory mechanisms that reduce cognitive deficits associated with the progressive accumulation of brain damage.

The case is described of a patient who, following cerebral hypoxia, developed severe difficulty in orienting himself in new environments in the context of a mild global amnesic syndrome. Some episodes he related suggested that his main difficulty was remembering the spatial/directional value of landmarks he recognised. A neuroradiological examination documented severe bilateral atrophy of the hippocampi associated with atrophic changes in the cerebral hemispheres, most marked in the dorsal regions. Neuropsychological and experimental evaluation showed a severe deficit of spatial learning with substantially preserved ability to learn verbal and visual-object information. He was also virtually unable to learn a route in a maze task based exclusively on spatial data, but the availability of visual cues substantially improved his learning. Finally, he performed within normal limits on various tests investigating knowledge acquired premorbidly regarding famous buildings, routes in the town he had been living in since childhood, and geography. Topographical disorientation may be subtended by a specific difficulty in storing the spatial/directional value of visual landmarks in novel environments. The hippocampus appears to be involved in the acquisition of new topographical spatial knowledge.

Objective: To assess cognitive levels in an elderly Sicilian population and to evaluate the role of education and other sociodemographic characteristics in cognitive performance. Background: The pattern of cognitive performance in the elderly has not been investigated extensively in well-defined Italian populations. This study was conducted as part of a door-to-door survey of common neurologic disorders (the Sicilian Neuro-Epidemiologic Study project). Methods: Thirteen physicians administered an Italian version of the Short Portable Mental Status Questionnaire (SPMSQ) to all subjects aged 50 years or older who, on November 1, 1987, resided in either of two Sicilian municipalities (Terrasini, Palermo province, and Riposto, Catania province; n = 3,999). Performance was scored as the number of errors on the SMPSQ. To define cognitive impairment we corrected the score for education as suggested by Pfeiffer [J Am Geriatr Soc 1975;23:433–441]. Results: The median SPMSQ score was equal to 2, and cognitive impairment was present in 4.6% of the subjects. In a bivariate analysis, age, sex, education, employment status at interview and principal lifetime occupation were all significantly associated with cognitive impairment. In a multivariate analysis, the same pattern was seen, except that principal lifetime occupation lost its significance. Conclusion: Our findings suggest that age, sex, education and employment status are the sociodemographic characteristics associated with cognitive impairment in the elderly as measured by the SPMSQ.

We report the neuropsychological and MRI investigation of a patient (MV) who developed a selective impairment of visual-spatial working memory (WM) with preservation not only of verbal, but also of visual shape WM, following an ischemic lesion in the cerebral territory supplied by one of the terminal branches of the right anterior cerebral artery. MV was defective in visual-spatial WM whether the experimental procedure involved arm movement for target pointing or not. Also, in agreement with the role generally assigned to visual-spatial WM in visual imagery. MV was extremely slow in the mental rotation of visually and verbally presented objects. In striking contrast with the WM deficit, MV's visual-spatial long-term memory was intact. The behavioral and neuroanatomical investigation of MV provides support for the hypothesis that the superior frontal gyrus (BA 6) and the dorsomedial cortex of the parietal lobe (BA 7) are part of the neural circuitry underlying visual-spatial WM in humans. © 2001 Elsevier Masson Srl.

Objective To evaluate whether the survival of patients with Parkinson disease (PD) is shorter than that of the general population. Design Survival was investigated in a cohort of patients with PD previously identified during a population-based prevalence study (prevalence day, November 1, 1987; reference follow-up date, October 31, 1995). The survival of patients with PD was compared with that of a control sample randomly selected from the same population (2 controls for each case, matched for age, sex, and study municipality). The causes of death in the 2 groups were also compared. Both univariate and multivariate survival analyses were performed to investigate the association with disease-related variables. Setting A door-to-door 2-phase prevalence survey performed in 3 Sicilian municipalities. Patients Fifty-nine patients with PD and 118 controls. Results Patients with PD showed a high risk of death (relative risk, 2.3; 95% confidence interval, 1.60-3.39). Greater age at November 1, 1987, high Hoehn-Yahr score, and lack of levodopa therapy were associated with a lower survival on univariate analysis. Multivariate analysis confirmed the association between shorter survival among patients with PD and greater age on November 1, 1987. One-way analysis of variance indicated a different effect of levodopa therapy according to age. Multivariate analysis did not confirm this finding. Pneumonia was the cause of death most frequently associated with PD. Conclusion This study indicates that patients with PD have a shorter survival time than the general population.

Introduction - Because of the limited information on cervical spondylotic radiculopathy, we conducted a door-to-door two-phase survey in a Sicilian municipality. Material and methods - We first screened for cervical spondylotic radiculopathy among the inhabitants of the municipality : (N= 7653, as of the prevalence day, November 1, 1987). Study neurologists then investigated those subjects suspected to have had a cervical spondylotic radiculopathy. Diagnoses were based on specified criteria. Results - We found 27 subjects affected by CSR (17 definite, 10 possible). Prevalence (cases per 1000 population) was 3.5 in the total population ; it increased to a peak at age 50-59 years and decreased thereafter. The age-specific prevalence was consistently higher in women. Conclusions - Comparison with other prevalence studies shows similar age-specific patterns, but different magnitudes, which may partly reflect methodologic differences across studies.