Search

BackgroundDepression is associated with lower educational attainment, but there has been little investigation of long-term educational trajectories in large cohorts with diagnosed depression.AimsTo describe the educational attainment trajectories of children with a depression diagnosis in secondary care, and to investigate whether these trajectories vary by sociodemographic characteristics.MethodWe identified new referrals to South London and Maudsley's NHS Foundation Trust between 2007 and 2013 who received a depression diagnosis at under 18 years old. Linking their health records to the National Pupil Database, we standardised their performance on three assessments (typically undertaken at ages 6–7 years (school Year 2), 10–11 (Year 6) and 15–16 (Year 11)) relative to the local reference population in each academic year. We used mixed models for repeated measures to estimate attainment trajectories.ResultsIn our sample of 1492 children, the median age at depression diagnosis was 15 years (interquartile range = 14–16). Their attainment showed a decline between school Years 6 and 11. Attainment was consistently lower among males and those eligible for free school meals. Black ethnic groups also showed lower attainment than White ethnic groups between Years 2 and 6, but showed a less pronounced drop in attainment at Year 11.ConclusionsThose who receive a depression diagnosis during their school career show a drop in attainment in Year 11. Although this pattern was seen among multiple sociodemographic groups, gender, ethnicity and socioeconomic status predict more vulnerable subgroups within this clinical population who might benefit from additional educational support or more intensive treatment.

Objective: This study examined the course and predictors of supportive care needs among Mexican breast cancer patients for different cancer treatment trajectories.Methods: Data from 172 (66.4% response rate) patients were considered in this observational longitudinal study. Participants were measured after diagnosis, neoadjuvant treatment, surgery, adjuvant treatment, and the first post-treatment follow-up visit. Psychological, Health System and Information, Physical and Daily Living, Patient Care and Support, Sexual, and Additional care needs were measured with the Supportive Care Needs Survey (SCNS-SF34). Linear mixed models with maximum-likelihood estimation were computed.Results: The course of supportive care needs was similar across the different cancer treatment trajectories. Supportive care needs declined significantly from diagnosis to the first post-treatment follow-up visit. Health System and Information care needs were the highest needs over time. Depressive symptoms and time since diagnosis were the most consistent predictors of changes in course of supportive care needs of these patients.Conclusions: Health system and information care needs of Mexican breast cancer patients need to be addressed with priority because these needs are the least met. Furthermore, patients with high depressive symptoms at the start of the disease trajectory have greater needs for supportive care throughout the disease trajectory.

Objectives Occupational exposure to soft paper dust is associated with impaired lung function. Whether there is an increased risk for asthma or chronic obstructive pulmonary disease (COPD) is unclear. Methods We studied 7870 workers from three Swedish soft paper mills, and defined high-exposed workers, as having been exposed to soft paper dust exceeding 5 mg/m3 for at least 5 years. The remaining workers were classified as ‘low exposed’. Person-years at risk were calculated and stratified according to gender, age and calendar-year. The follow-up time was from 1960 to 2013. The expected numbers of deaths were calculated using the Swedish population as reference and standardised mortality ratios (SMRs) with 95% CIs were assessed. Results There was an increased mortality due to obstructive lung disease (asthma and COPD), among high-exposed workers, SMR 1.89, 95% CI 1.20 to 2.83, based on 23 observed cases. High-exposed workers had an increased mortality from asthma, SMR 4.13, 95% CI 1.78 to 8.14, based on eight observed cases. The increased asthma mortality was also observed among high-exposed men, SMR 4.38, 95% CI 1.42 to 10.2, based on five observed cases. The asthma mortality among low-exposed workers, both men and women, was not increased. The COPD mortality was not clearly increased among high-exposed workers (SMR 1.52, 95% CI 0.85 to 2.50). Conclusion High occupational exposure to soft paper dust increases the mortality due to asthma, and the results suggest that soft paper dust levels in workplaces should be below 5 mg/m3.

Background: There is increasing use of online surveys to improve data quality and timeliness and reduce costs. While there have been numerous cross-sectional studies comparing responses to online or paper surveys, there is little research from a longitudinal perspective. Objective: In the context of the well-established Australian Longitudinal Study on Women’s Health, we examined the patterns of responses to online or paper surveys across the first two waves of the study in which both modes were offered. We compared the following: differences between women born between 1946 and 1951 and between 1973 and 1978; types of device used for online completion; sociodemographic, behavioral, and health characteristics of women who responded online or using mailed paper surveys; and associations between mode of completion in the first survey and participation and mode of completion in the second survey. Methods: Participants in this study, who had responded to regular mailed surveys since 1996, were offered a choice of completing surveys using paper questionnaires or Web-based electronic questionnaires starting in 2012. Two groups of women were involved: an older cohort born between 1946 and 1951 aged in their 60s and a younger cohort born between 1973 and 1978 aged in their 30s when the online surveys were first introduced. We compared women who responded online on both occasions, women who responded online at the first survey and used the paper version of the second survey, women who changed from paper to online, and those who used paper for both surveys. Results: Of the 9663 women in their 60s who responded to one or both surveys, more than 50% preferred paper surveys (5290/9663, 54.74%, on the first survey and 5373/8621, 62.32%, on the second survey). If they chose the online version, most used computers. In contrast, of the 8628 women in their 30s, 56.04% (4835/8628) chose the online version at the first survey. While most favored computers to phones or tablets, many did try these alternatives on the subsequent survey. Many women who completed the survey online the first time preferred the paper version on the subsequent survey. In fact, for women in their 60s, the number who went from online to paper (1151/3851, 29.89%) exceeded the number who went from paper to online (734/5290, 13.88%). The online option was more likely to be chosen by better educated and healthier women. In both cohorts, women who completed paper surveys were more likely than online completers to become nonrespondents on the next survey. Due to the large sample size, almost all differences were statistically significant, with P

This paper revisits and reiterates the needs, purposes and requirements of biodosimetric assays for long-term dose and health risk assessments. While the most crucial need for biodosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure assessment. Hence, the needs for retrospective dose estimation are likely to be greater in the future. The value of biodosimetry can be considerably enhanced with the development of new or improved methods, particularly with suitability for application at long periods of time after exposure.

Background The responsiveness and the intertester reliability of the Finnish Canine Stifle Index (FCSI) were tested, and a cut-off between compromised and severely compromised performance level was set. Methods Three groups of dogs were used, 29 with any stifle dysfunction (STIF), 17 with other musculoskeletal disease except stifle (OTHER) and 11 controls (CTRL). All dogs were tested with the FCSI by the same physiotherapist at three occasions, at baseline, at six weeks and 10 weeks, and once also by another physiotherapist. Results Dogs in the STIF group demonstrated significantly higher (P

Speech perception deficits are commonly reported in dyslexia but longitudinal evidence that poor speech perception compromises learning to read is scant. We assessed the hypothesis that phonological skills, specifically phoneme awareness and RAN, mediate the relationship between speech perception and reading. We assessed longitudinal predictive relationships between categorical speech perception, phoneme awareness, RAN, language, attention and reading at ages 5½ and 6½ years in 237 children many of whom were at high risk of reading difficulties. Speech perception at 5½ years correlated with language, attention, phoneme awareness and RAN concurrently and was a predictor of reading at 6½ years. There was no significant indirect effect of speech perception on reading via phoneme awareness, suggesting that its effects are separable from those of phoneme awareness. Children classified with dyslexia at 8 years had poorer speech perception than age‐controls at 5½ years and children with language disorders (with or without dyslexia) had more severe difficulties with both speech perception and attention control. Categorical speech perception tasks tap factors extraneous to perception, including decision‐making skills. Further longitudinal studies are needed to unravel the complex relationships between categorical speech perception tasks and measures of reading and language and attention. Funding Information: Wellcome Trust. Grant Number: WT082032MA

Objective: The objective of the study is to investigate the relation between pretreatment depressive symptoms (DS) and the course of DS during the first year after cancer diagnosis, and overall survival among people with head and neck cancer (HNC). Methods: Data from the Head and Neck 5000 prospective clinical cohort study were used. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) pretreatment, at 4 and 12-month follow-up. Also, socio-demographic, clinical, lifestyle, and mortality data were collected. The association between before start of treatment DS (HADS-depression > 7) and course (never DS, recovered from DS, or persistent/recurrent/late DS at 12-month follow-up) and survival was investigated using Cox regression. Unadjusted and adjusted analyses were performed. Results: In total, 384 of the 2144 persons (18%) reported pretreatment DS. Regarding DS course, 63% never had DS, 16% recovered, and 20% had persistent/recurrent/late DS. People with pretreatment DS had a higher risk of earlier death than people without DS (hazard ratio (HR) = 1.65; 95% confidence interval (CI) 1.33-2.05), but this decreased after correcting for socio-demographic, clinical, and lifestyle-related factors (HR = 1.21; 95% CI 0.97-1.52). Regarding the course of DS, people with persistent/recurrent/late DS had a higher risk of earlier death (HR = 2.04; 95% CI 1.36-3.05), while people who recovered had a comparable risk (HR = 1.12; 95% CI 0.66-1.90) as the reference group who never experienced DS. After correcting for socio-demographic and clinical factors, people with persistent/recurrent/late DS still had a higher risk of earlier death (HR = 1.66; 95% CI 1.09-2.53). Conclusions: Pretreatment DS and persistent/recurrent/late DS were associated with worse survival among people with HNC.

Power-frequency magnetic field exposure science as it relates to men and couples have not been explored despite the advantage of this information in the design and interpretation of reproductive health epidemiology studies. This analysis examined the distribution and temporal variability of exposures in men, and the correlation of exposures within couples using data from a longitudinal study of 25 men and their female partners recruited from an infertility clinic. The average and 90th percentile demonstrated fair to good reproducibility, whereas the maximum showed poor reproducibility over repeated sampling days, each separated by a median of 4.6 weeks. Average magnetic field exposures were also strongly correlated within couples, suggesting that one partner's data could be used as a surrogate in the absence of data from the other for this metric. Environment was also an important effect modifier in these explored matters. These issues should be considered in future relevant epidemiology studies.

Objective To measure the long‐term impact of surgical treatment for vulval cancer upon health‐related quality of life and pelvic floor outcomes during the first year of therapy. Methods Prospective, longitudinal, mixed‐methods study. Twenty‐three women aged >18 years with a new diagnosis of vulval cancer were recruited. The EORTC QLQ C30, SF‐36 and an electronic pelvic floor assessment questionnaire (ePAQ‐PF) were administered at baseline (pre‐treatment) and 3, 6, 9 and 12 months post‐treatment. Mixed effects repeated measures models (all adjusted for age and BMI) were used to investigate changes over time and differences between cancer stage. Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach. Results Mean age was 59.9 years (SD = 15.3; range = 23.8–86.6 yrs). Mean BMI was 30.0 (SD = 4.5; range = 24.4–38.2). Sixteen women had early (Stage 1 to 2B), and seven women had advanced stage disease (Stage 3 to 4B). Questionnaire scores revealed that physical and social functioning, fatigue, pain and general sex life were significantly worse at 12 months than pre‐treatment (p = < 0.05). Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring. Women with advanced vulval cancer had significantly worse SF‐36 mental health scores at 12 months compared to women with early stage disease (p = 0.037). Conclusions Surgery for vulval cancer has long‐term implications which can be persistent 12 months post‐treatment. High rates of morbidity relating to lymphoedema and sexual function re‐enforce the need for specialist clinics to support women who suffer these complications. © 2015 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd.

Sleep spindles are related to sleep-dependent memory consolidation and general cognitive abilities. However, they undergo drastic maturational changes during adolescence. Here we used a longitudinal approach (across 7 years) to explore whether developmental changes in sleep spindle density can explain individual differences in sleep-dependent memory consolidation and general cognitive abilities. Ambulatory polysomnography was recorded during four nights in 34 healthy subjects (24 female) with two nights (baseline and experimental) at initial recording (age range 8-11 years) and two nights at follow-up recording (age range 14-18 years). For declarative learning, participants encoded word pairs with a subsequent recall before and after sleep. General cognitive abilities were measured by the Wechsler Intelligence Scale. Higher slow (11-13 Hz) than fast (13-15 Hz) spindle density at frontal, central, and parietal sites during initial recordings, followed by a shift to higher fast than slow spindle density at central and parietal sites during follow-up recordings, suggest that mature spindle topography develops throughout adolescence. Fast spindle density increases from baseline to experimental night were positively related to sleep-dependent memory consolidation. In addition, we found that the development of fast spindles predicted the improvement in memory consolidation across the two longitudinal measurements, a finding that underlines a crucial role for mature fast spindles for sleep-dependent memory consolidation. Furthermore, slow spindle changes across adolescence were related to general cognitive abilities, a relationship that could indicate the maturation of frontal networks relevant for efficient cognitive processing., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Cognitive impairment plays a role in Parkinson’s disease (PD) and has important consequences for patient management. However, many aspects of cognitive impairment in PD remain unclear because of the use of different and often invalid measurement instruments. In this study, a reliable and valid instrument, the SCales for Outcomes in PArkinson’s disease-COGnition (SCOPA-COG), was used. Aim: To evaluate cognitive functioning in a large cohort of patients with Parkinson’s disease and to assess the relations with demographic, disease related and clinical variables. Methods: A cohort of 400 patients with PD was evaluated for cognition, motor and non-motor domains, as well as for demographic and disease related characteristics. Results were compared with 150 controls matched for overall age, sex and education distribution. Results: Patients with PD scored significantly lower on all cognitive subdomains compared with controls, with the largest differences for executive functioning and memory. After correction for age and years of education, 22% of patients had impaired cognition, as measured by the total SCOPA-COG score, compared with controls. Across all patients, more severe cognitive impairment was associated with significantly more impairment in motor, autonomic, depressive and psychotic domains. Patients with the postural instability gait difficulty (PIGD) dominant phenotype showed more cognitive impairment compared with patients with the tremor dominant phenotype. Contrary to tremor scores, PIGD scores significantly worsened with increasing disease severity. Conclusions: Cognition is an important domain of the clinical spectrum of PD and poorer cognitive performance is associated with greater impairment in motor and non-motor domains in PD. The difference in cognitive scores between PIGD dominant patients and tremor dominant patients likely reflects more advanced disease.

Background: Patients with Alzheimer’s disease and dementia commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in Alzheimer’s disease has been demonstrated. Several studies have investigated whether the exon 4 e2/e3/e4 haplotype of the apolipoprotein E ( APOE ) gene is associated with BPSD, with variable results. Objective: We investigated the exon 4 polymorphisms and extended this study to include promoter polymorphisms and the resultant haplotypes across the gene. Methods: Our large independent cohort of 388 patients with longitudinal measures of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether any of these variants were associated with the presence of BPSD. Results: We revealed several significant relationships before correction for multiple testing. The exon 4 haplotype was associated with hallucinations and anxiety, A-491T with irritability, T-427C with agitation/aggression and appetite disturbances, and T-219C with depression. Haplotype analyses of all variants did not reveal any statistically significant findings. Conclusions: Our data and a review of previous studies showed a diversity of relationships, suggesting that these findings might be due to chance and so collectively do not support a role for the APOE gene in BPSD.

Objective To compare psychosocial outcomes (follow‐up related worries and satisfaction with follow‐up related information and support) over 30 months of two alternative management policies for women with low‐grade abnormal cervical cytology. Methods Women aged 20–59 years with low‐grade cytological abnormalities detected in the National Health Service Cervical Screening Programme were randomised to cytological surveillance or initial colposcopy. A total of 3399 women who completed psychosocial questionnaires at recruitment were invited to complete questionnaires at 12, 18, 24 and 30 months. Linear mixed models were used to investigate differences between arms in the two psychosocial outcomes. Each outcome had a maximum score of 100, and higher scores represented higher psychosocial morbidity. Results On average, over 30 months, women randomised to colposcopy scored 2.5 points (95%CI −3.6 to −1.3) lower for follow‐up related worries than women randomised to cytological surveillance. Women in the colposcopy arm also scored significantly lower for follow‐up related satisfaction with information and support (−2.4; −3.3 to −1.4) over 30 months. For both outcomes, the average difference between arms was greatest at 12th‐ and 18th‐month time points. These differences remained when the analysis was stratified by post‐school education. Conclusions Women with low‐grade cytology, irrespective of their management, have substantial initial psychosocial morbidity that reduces over time. Implementation of newer screening strategies, which include surveillance, such as primary HPV screening, need to consider the information and support provided to women. © 2016 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd.

Theoretical models of child development typically consider the home environment as a product of bidirectional effects, with parent‐ and child‐driven processes operating interdependently. However, the developmental structure of these processes during the transition from childhood to adolescence has not been well studied. In this study we used longitudinal genetic analyses of data from 6646 UK‐representative twin pairs (aged 9–16 years) to investigate stability and change in parenting and household chaos in the context of parent–child bidirectional effects. Stability in the home environment was modest, arising mainly from parent‐driven processes and family‐wide influences. In contrast, change over time was more influenced by child‐driven processes, indicated by significant age‐specific genetic influences. Interpretations of these results and their implications for researchers are discussed.

The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown.To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up.A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details.198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started.This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Objectives: To examine the development of nocturnal sleeping problems in patients with Parkinson’s disease (PD) over an 8-year period and to study the clinical and demographic correlates of insomnia. Methods: 231 patients were included in a population-based prevalence study in 1993, and re-examined in 1997 and 2001. At all study visits, we applied semi-structured interviews to obtain information on clinical and demographic data, as well as on nocturnal sleeping problems. Standardised rating scales of parkinsonism, depression and cognitive impairment were used. The relationship between insomnia and demographic and clinical variables was analysed using population-averaged logistic regression models for correlated data. 231 patients were included at baseline, 142 were available for re-evaluation in 1997 and 89 patients in 2001. Results: Most nocturnal sleeping problems varied little in prevalence over time, whereas problems related to turning in bed and vivid dreaming or nightmares increased. Insomnia was present in 54–60% of the patients at each of the three study visits and varied considerably in individual patients over time. The presence of insomnia was closely related to disease duration, higher Montgomery–Asberg Depression Rating Scale scores and female sex. Conclusion: Insomnia is a highly frequent complaint in patients with PD. It fluctuates over time in individual patients, and its origin seems to be multifactorial. Physicians should be aware of the high prevalence of insomnia in patients with PD and should examine their patients for a possible coexisting depression.

On the basis of preliminary evidence from patients with subarachnoid haemorrhage (SAH), axonal degeneration is thought to be an underestimated pathological feature.A longitudinal study in 17 patients with aneurysmal SAH. Ventricular CSF was collected daily for up to 14 days. The neurofilament heavy chain(SMI35) (NfH(SMI35), a biomarker for axonal damage) was quantified using a standard ELISA (upper limit of normal 0.73 ng/ml). The primary outcome measure was the Glasgow Outcome Score (GOS) at 3 months.Of 148 samples from patients with SAH, pathologically high NfH levels in the CSF were found in 78 (52.7%) samples, compared with 20 (5%) of 416 samples from the reference population (p0.0001). A pathological increase in NfH was observed in all patients with a bad outcome (GOS 1-3) compared with 8% of those with a good outcome (GOS 4-5, p0.0001). This increase typically became significant 7 days after the haemorrhage (p0.01). The result was confirmed by analysing the individual mean NfH concentrations in the CSF (3.45 v 0.37 ng/ml, p0.01), and was reinforced by the inverse correlation of NfH in the CSF with the GOS (r = -0.65, p0.01). Severity of injury was found to be correlated to NfH(SMI35) levels in the CSF (World Federation of Neurological Surgeons, r = 0.63, p0.01 and Glasgow Coma Score, r = -0.61, p0.01).Patients with SAH thus have secondary axonal degeneration, which may adversely affect their outcome.

Objectives: The evolutionary pattern of spontaneous recovery from acute neglect was studied by assessing cognitive deficits and motor impairments. Detailed lesion reconstruction was also performed to correlate the presence of and recovery from neglect to neural substrates. Methods: A consecutive series of right brain-damaged (RBD) patients with and without neglect underwent weekly tests in the acute phase of the illness. The battery assessed neglect deficits, neglect-related deficits, and motor impairment. Age-matched normal subjects were also investigated to ascertain the presence of non lateralised attentional deficits. Some neglect patients were also available for later investigation during the chronic phase of their illness. Results: Partial recovery of neglect deficits was observed at the end of the acute period and during the chronic phase. Spatial attention was impaired in acute neglect patients, while non spatial attentional deficits were present in RBD patients with and without acute neglect. A strong association was found between acute neglect and fronto-parietal lesions. Similar lesions were associated with neglect persistence. In the chronic stage, neglect recovery was paralleled by improved motor control of the contralesional upper limb, thus emphasising that neglect is a negative prognostic factor in motor functional recovery. Conclusions: These findings show that spatial attention deficits partially improve during the acute phase of the disease in less than half the patients investigated. There was an improvement in left visuospatial neglect at a later, chronic stage of the disease, but this recovery was not complete.

Objective Little is known about the trajectory of health and well‐being from before to after a cancer diagnosis. This study aimed to examine changes in health and well‐being across three time points (0–2 years before a cancer diagnosis, 0–2 years post‐diagnosis and 2–4 years post‐diagnosis) in individuals receiving a new cancer diagnosis, and at matched time points in a cancer‐free comparison group. Methods Data were from waves 1–6 of the English Longitudinal Study of Ageing. Repeated‐measures ANOVAs were used to examine differences in self‐rated health, mobility impairments, activities of daily living impairments, quality of life, depressive symptoms and life satisfaction by group and time, and group‐by‐time interactions. Results Of the 4565 participants with data from three time points, 444 (9.7%) reported a new cancer diagnosis. Those in the cancer group reported poorer self‐rated health (p

Background A lack of longitudinal studies has hampered the understanding of the development of posttraumatic stress symptoms (PTSS) in parents of children diagnosed with cancer. This study examines level of PTSS and prevalence of posttraumatic stress disorder (PTSD) from shortly after diagnosis up to 5 years after end of treatment or child's death, in mothers and fathers. Methods A design with seven assessments (T1–T7) was used. T1–T3 were administered during treatment and T4–T7 after end of treatment or child's death. Parents (N = 259 at T1; n = 169 at T7) completed the PTSD Checklist Civilian Version. Latent growth curve modeling was used to analyze the development of PTSS. Results A consistent decline in PTSS occurred during the first months after diagnosis; thereafter the decline abated, and from 3 months after end of treatment only minimal decline occurred. Five years after end of treatment, 19% of mothers and 8% of fathers of survivors reported partial PTSD. Among bereaved parents, corresponding figures were 20% for mothers and 35% for fathers, 5 years after the child's death. Conclusions From 3 months after end of treatment the level of PTSS is stable. Mothers and bereaved parents are at particular risk for PTSD. The results are the first to describe the development of PTSS in parents of children diagnosed with cancer, illustrate that end of treatment is a period of vulnerability, and that a subgroup reports PTSD 5 years after end of treatment or child's death. © 2015 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd.

Over 30 years ago, it was suggested that difficulties in the ‘auditory organization’ of word forms in the mental lexicon might cause reading difficulties. It was proposed that children used parameters such as rhyme and alliteration to organize word forms in the mental lexicon by acoustic similarity, and that such organization was impaired in developmental dyslexia. This literature was based on an ‘oddity’ measure of children's sensitivity to rhyme (e.g. wood, book, good) and alliteration (e.g. sun, sock, rag). The ‘oddity’ task revealed that children with dyslexia were significantly poorer at identifying the ‘odd word out’ than younger children without reading difficulties. Here we apply a novel modelling approach drawn from auditory neuroscience to study the possible sensory basis of the auditory organization of rhyming and non‐rhyming words by children. We utilize a novel Spectral‐Amplitude Modulation Phase Hierarchy (S‐AMPH) approach to analysing the spectro‐temporal structure of rhyming and non‐rhyming words, aiming to illuminate the potential acoustic cues used by children as a basis for phonological organization. The S‐AMPH model assumes that speech encoding depends on neuronal oscillatory entrainment to the amplitude modulation (AM) hierarchy in speech. Our results suggest that phonological similarity between rhyming words in the oddity task depends crucially on slow (delta band) modulations in the speech envelope. Contrary to linguistic assumptions, therefore, auditory organization by children may not depend on phonemic information for this task. Linguistically, it is assumed that ‘book’ does not rhyme with ‘wood’ and ‘good’ because the final phoneme differs. However, our auditory analysis suggests that the acoustic cues to this phonological dissimilarity depend primarily on the slower amplitude modulations in the speech envelope, thought to carry prosodic information. Therefore, the oddity task may help in detecting reading difficulties because phonological similarity judgements about rhyme reflect sensitivity to slow amplitude modulation patterns. Slower amplitude modulations are known to be detected less efficiently by children with dyslexia.

Caged common lake mussels (Anodonta piscinalis) have been used in the monitoring of organochlorine compounds in pulp and paper mill recipient watercourses of Finland annually from 1984 to 1998. Statistically significant decreasing trends of chlorophenols and chloroguaiacols originating from chlorobleaching were observed in all recipients in parallel with the decreasing discharges from the mills. Metabolites of chlorophenols, chloroanisoles and chloroveratroles had no or slightly increasing trends. Elevated PCB concentrations were measured in four watercourses. In two areas, PCBs were found to be significantly increasing, in two other cases they showed no trend. A mill producing recycled paper was apparently responsible for an increase of PCBs and DDE in recipient watercourses. Overall decreases were observed for other chlorohydrocarbons except for DDT. Material flows of chlorohydrocarbons were positively correlated with waterflows (Q) in some cases.

A cancer diagnosis poses many challenges for adolescents, and the psychological stress associated with some of these challenges may have detrimental effects. Stressors that have been identified by children and adolescents with cancer include painful procedures (Hedstrom, Ljungman, & von Essen, 2005; McCaffery, 2006; Woodgate, Degner, & Yanofsky, 2003), frequent and extended hospital stays (McCaffery, 2006), alopecia, difficult symptoms (Hedstrom et al., 2005; McCaffery, 2006; Woodgate, 2005), and uncertainty (Stewart, Lynn, & Mishel, 2010; Woodgate et al., 2003). The few studies on psychological stress in children and adolescents with cancer have noted both short- and long-term effects. In the short-term, psychological stress has been linked to greater symptom severity (Docherty, Sandelowski, & Preisser, 2006; McCaffery, 2006) and higher levels of anxiety (Hedstrom et al., 2005; Hockenberry-Eaton, Dilorio, & Kemp, 1995). In the long-term, psychological stress in survivors of cancer in childhood and adolescence has been associated with post-traumatic stress disorder (PTSD) (Rourke, Hobbie, Schwartz, & Kazak, 2007; Schrag, McKeown, Jackson, Cuffe, & Neuberg, 2008). Psychological stress in adolescents with cancer may be a targeted area for oncology nurse intervention, but the prevalence and degree have not been studied extensively. A biobehavioral approach to investigating psychosocial functioning, including psychological stress, is highly recommended for adolescents with cancer (Moore, 2004). However, validated biologic measures of pyschological stress are limited. The purpose of this study was to examine the validity of a method for collecting one biologic marker of psychological stress: salivary alpha amylase (sAA). Efficient, easy-to-obtain biologic markers of stress may enhance development of clinical research and lead to future use in clinical settings by oncology nurses.

Background: Diagnostic criteria of Alzheimer’s disease (AD) emphasize the integration of clinical data and biomarkers. In practice, collection and analysis of patient data vary greatly across different countries and clinics. Objective: The goal was to develop a versatile and objective clinical decision support system that could reduce diagnostic errors and highlight early predictors of AD. Methods: Novel data analysis methods were developed to derive composite disease indicators from heterogeneous patient data. Visualizations that communicate these findings were designed to help the interpretation. The methods were implemented with a software tool that is aimed for daily clinical practice. Results: With the tool, clinicians can analyze available patients as a whole, study them statistically against previously diagnosed cases, and characterize the patients with respect to having AD. The tool is able to work with virtually any patient measurement data, as long as they are stored in electronic format or manually entered into the system. For a subset of patients from the test cohort, the tool was able to predict conversion to AD at an accuracy of 93.6%. Conclusion: The software tool developed in this study provides objective information for early detection and prediction of AD based on interpretable visualizations of patient data.

A previous investigation of white male workers from a pulp and paper company in Berlin, New Hampshire identified decrements in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) associated with work in the pulping operations. A subset of those data were reanalyzed to consider another type of occupational exposure: gassing incidents in which workers were accidentally exposed to high levels of irritant gases, such as chlorine (Cl2) or sulfur dioxide (SO2). A total of 230 current and former workers (all white male) were included in the analysis. Gassing events were more common among pulp mill workers (34%) than workers from other parts of the company (9%). Average changes of -291.9 ml in FEV1 (p0.05) and -5.00% in FEV1/FVC (p0.05) were associated with gassing. Also, in each of the regression models for the three measures of pulmonary function (FEV1, FVC, and FEV1/FVC), there was a three-way interaction of cumulative smoking, cumulative pulp mill exposure, and gassing. The greatest decreases in FEV1 and FEV1/FVC associated with gassing were evident in the dual smoking/pulp mill exposure categories of none/high and high/none. The changes in pulmonary function appeared to be chronic effects that persisted beyond cessation of the exposure. Only limited information about the gassing episodes was requested from the subjects, and future research is discussed that will address some of the limitations.

Retrospective assessment of adverse childhood experiences is widely used in research, although there are concerns about its validity. In particular, recall bias is assumed to produce significant artifacts. Data from a longitudinal cohort (the British National Child Development Study; N = 7,710) and the retrospective Mainz Adverse Childhood Experiences Study ( N = 1,062, Germany) were compared on 10 adverse childhood experiences and psychological adjustment at age 42 yr. Between the two methods, no significant differences in risk effects were detected. Results held for bivariate analyses on all 10 childhood adversities and a multivariate model; the later comprises the childhood adversities which show significant long-term sequelae (not always with natural parent, chronically ill parent, financial hardship, and being firstborn) and three covariates. In conclusion, the present data did not show any bias in the retrospective assessment.

Background: Low levels of cerebrospinal fluid (CSF) β-amyloid 1–42 (Aβ42) and high total tau (T-tau) are diagnostic for manifest Alzheimer’s disease. It is not known, however, whether these biomarkers may be risk indicators for cognitive decline in otherwise healthy older people. Methods: The longitudinal relationship between CSF markers, Aβ42 and T-tau, measured in 1992, and change in Mini-Mental State Examination (ΔMMSE) score between 1992 and 2002 were investigated in 55 women (aged 70–84 years, mean (SD) MMSE score = 28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden. These women did not have dementia when they experienced lumbar puncture in 1992–3. Results: Over the 8-year follow-up period, ΔMMSE (range = +3 to −21 points) was correlated with Aβ42 (Spearman’s r = 0.40, p = 0.002), such that lower levels of Aβ42 were related to greater decline. This was also observed after excluding 4 women who developed dementia between 1992 and 2002 (Spearman’s r = 0.34, p = 0.019). A multivariate logistic regression model predicting a decline of ⩾5 points on the MMSE (observed in six women), or a risk of developing dementia over the 8-year follow-up period (observed in four women), including age, education, Aβ42 and T-tau as covariates, showed that Aβ42 was the sole predictor of significant cognitive decline or dementia (OR per 100 pg/ml Aβ42 = 2.24, 95% CI 1.19 to 4.22, p = 0.013). Conclusions: Low levels of CSF Aβ42 may predict cognitive decline among older women without dementia.

Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. Objective: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). Methods: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. Results: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. Conclusions: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

Background: Adhesion molecules and matrix metalloproteinases (MMPs) are known to be relevant to the ongoing development and disappearance of areas of demyelination in the white matter of the CNS of multiple sclerosis (MS) patients. This study examined whether serum matrix metalloproteinase-3 (MMP-3) levels correlate with disease activity in MS. Methods: Serum MMP-3 levels in 47 consecutive patients with relapsing-remitting MS were measured by immunoassay every 4 weeks over a 15 month period. Results: During the study period, 48 clinical relapses occurred. Serum MMP-3 levels within 1 month of relapse were significantly higher than during the remission phase. Sequential analysis showed that serum MMP-3 levels had increased transiently at the time of clinical relapse but returned to the normal range within a month. Conclusions: Circulatory MMP-3 levels are correlated with disease activity in relapsing-remitting MS. This may contribute to the breakdown of the blood-brain barrier at the time of relapse.

Evoked potentials are used in the functional assessment of sensory and motor pathways. Their usefulness in monitoring the evolution of multiple sclerosis has not been fully clarified.The aim of this longitudinal study was to examine the usefulness of multimodal evoked potential in predicting paraclinical outcomes of disease severity and as a prognostic marker in multiple sclerosis.Eighty four patients with clinically definite multiple sclerosis underwent Expanded Disability Status Scale (EDSS) and functional system scoring at study entry and after a mean (standard deviation) follow-up of 30.5 (11.7) months. Sensory and motor evoked potentials were obtained in all patients at study entry and at follow-up in 64 of them, and quantified according to a conventional score.Cross-sectionally, the severity of each evoked potential score significantly correlated with the corresponding functional system (0.32R0.60, p0.01, for all but follow-up visual evoked potential) and with EDSS (0.34R0.61; p0.001 for all but brain stem evoked potential). EDSS significantly correlated with global evoked potential score severity (baseline R = 0.60, follow-up R = 0.46, p0.001). Using longitudinal analysis, only changes in somatosensory evoked potential scores were significantly correlated with changes of sensory functional system (R = 0.34, p = 0.006). However, patients with multiple sclerosis with disability progression at follow-up had more severe baseline evoked potential scores than patients who remained stable. Patients with severe baseline global evoked potential score (higher than the median value) had a risk of 72.5% to progress on disability at follow-up, whereas patients with multiple sclerosis with lower scores had a risk of only 36.3%.These results suggest that evoked potential is a good marker of the severity of nervous damage in multiple sclerosis and may have a predictive value regarding the evolution of disability.

Background: Magnetic resonance imaging (MRI) studies in primary progressive multiple sclerosis (PPMS) have shown a reduced frequency of enhancement with the contrast agent gadolinium-DTPA (Gd-DTPA), in comparison with relapsing-remitting multiple sclerosis (RRMS), and it has been suggested that there may be a less important role for inflammation in its pathogenesis. However, the earliest clinical stages of PPMS have not been studied and thus it has not been possible to exclude the existence of an early inflammatory phase. Objective: To study the presence, characteristics, and implications of inflammation in early PPMS. Methods: 45 patients with a mean disease duration of 3.3 years had triple dose Gd enhanced MRI, expanded disability status scale (EDSS), and multiple sclerosis functional composite (MSFC) assessments at baseline. Repeat MRI was done at 1 and 2 months in 24 patients, and at 6 months in 38. Results: Enhancing brain lesions were present in 42% of patients at baseline but enhancing cord lesions were uncommon (7%); 85% of enhancing lesions enhanced for one month or less. Patients with enhancing lesions had greater disability (EDSS, p = 0.027; MSFC, p = 0.026) and more MRI abnormalities (greater T2 load, p = 0.008; greater T1 hypointensity load, p = 0.001; and reduced partial brain volume, p = 0.012) than those without enhancement. Enhancement at 6 months was seen in 32% of patients and was restricted to a subset of patients who enhanced at baseline. Conclusions: Enhancement is present in some cases of early PPMS and is associated with greater disease impact in terms of both clinical and MRI measures.

To determine risk factors for sudden cardiac death and the role of diabetic autonomic neuropathy (DAN) in the Rochester diabetic neuropathy study (RDNS).Associations between diabetic and cardiovascular complications, including DAN, and the risk of sudden cardiac death were studied among 462 diabetic patients (151 type 1) enrolled in the RDNS. Medical records, death certificates, and necropsy reports were assessed for causes of sudden cardiac death.21 cases of sudden cardiac death were identified over 15 years of follow up. In bivariate analysis of risk covariates, the following were significant: ECG 1 (evolving and previous myocardial infarctions): hazard ratio (HR) = 4.4 (95% confidence interval (CI), 1.6 to 12.1), p = 0.004; ECG 2 (bundle branch block or pacing): HR = 8.6 (2.9 to 25.4), p0.001; ECG 1 or ECG 2: HR = 4.2 (1.3 to 13.4), p = 0.014; and nephropathy stage: HR = 2.1 (1.3 to 3.4), p = 0.002. Adjusting for ECG 1 or ECG 2, autonomic scores, QTc interval, high density lipoprotein (HDL) cholesterol, 24 hour microalbuminuria, and 24 hour total proteinuria were significant. However, adjusting for nephropathy, none of the autonomic indices, QTc interval, HDL cholesterol, microalbuminuria, or total proteinuria was significant. At necropsy, all patients with sudden cardiac death had coronary artery or myocardial disease.Sudden cardiac death was correlated with atherosclerotic heart disease and nephropathy, and to a lesser degree with DAN and HDL cholesterol. Although DAN is associated with sudden cardiac death, it is unlikely to be its primary cause.

Background Longitudinal assessments of quality of life are needed to measure changes over the course of a disease and treatment. Computer versions of quality of life instruments have increased the feasibility of obtaining longitudinal measurements. However, there remain occasions when patients are not able to complete these questionnaires. This study examined whether changes measured using a computer version of the Functional Assessment of Cancer Therapy – General (FACT-G) on two occasions would be obtained if patients completed a paper version on one of the two occasions. Methods Gynecologic oncology patients completed a computer version of the FACT-G pre-operatively and at six months. Patients were given the option of using the paper version instead of the computer at either time point. Repeated measures analysis of variance was used. Results One hundred nineteen patients completed the FACT-G at both time points. Seventy-one (60%) patients used the computer at both visits, 26 (21.8%) used the computer followed by the paper version, 17 (14.3%) used the paper version followed by the computer version, and five patients (4.2%) used the paper version at both visits. Significant effects over time were obtained in the physical, functional, and emotional well-being domains, and in total scores, but there were no effects of method of administration of the questionnaires and no interaction between method of administration and changes over time. Conclusions These data indicate that women are responding to the content of the questionnaire and not method of data collection. Although using the same method of administration of instruments over time is desirable, using alternate methods is preferable to forgoing data collection entirely. Large scale studies should be conducted to determine if the multiple methods of data collection that are becoming increasingly available are producing interchangeable information.

Background: Anosognosia is a common manifestation of Alzheimer's disease. There is an association between impaired awareness and frontal-executive cognitive deficits. Anosognosia is also correlated with decreased metabolism in the right hemisphere, particularly in frontal lobe regions. Objective: To investigate pathological correlates of anosognosia in Alzheimer's disease. Design: 41 subjects followed longitudinally in the University of Pittsburgh memory disorders clinic and with necropsy verified Alzheimer's disease were divided into two groups, based on previous clinical assessment: +Aware (n = 23) and –Aware (n = 18). A subset analysis matching subjects for dementia severity using mini-mental state examination scores was also carried out (13 +Aware; 13 –Aware). Histopathological data from necropsy brain tissue consisted of senile plaque (SP) and neurofibrillary tangle (NFT) counts (regional density) from four different brain regions in the right and left hemispheres: superior and middle frontal gyri (SMF), superior temporal isocortex (ST), the prosubiculum of the hippocampus (PRO), and the entorhinal cortex (EC). Results: SP density was greater in the right PRO region of –Aware subjects (F = 6.54, p = 0.015) than +Aware subjects. Significant differences between SP or NFT density were not observed in any other regions. In the subset analysis matching for dementia severity, SP density was again greater in the right PRO region of –Aware subjects than in the other regions (F = 12.72, p = 0.002). Conclusions: Increased SP density in the right PRO region suggests that selective pathological involvement of this area contributes to awareness deficits in Alzheimer's disease. The putative role of the PRO in self appraisal may reflect its interconnections with other medial temporal and prefrontal regions.

Background:Studies have suggested that T2 lesion activity is prominent in early relapsing-remitting multiple sclerosis, whereas brain atrophy, while seen early, appears more evident in later progressive disease. The temporal relation between these processes remains unclear. Objective:To explore the association between changing brain lesion loads and subsequent tissue atrophy in multiple sclerosis. Methods:28 subjects with clinically probable or definite multiple sclerosis (mean age 46.0 years; 17 female and 11 male) were followed for 14 years after first onset of symptoms. T2 lesion loads were estimated soon after symptom onset and at around five, 10, and 14 years later. Disease related atrophy was estimated at the 14 year follow up by comparing brain tissue volumes (proportional to total intracranial volumes) determined in the multiple sclerosis group with data from 29 normal control subjects (mean age 36.7 years; 16 female, 13 male) using multiple linear regression analyses to allow for differences in age and sex distributions. Results:Change in lesion load in the first five years was more closely correlated to disease related brain atrophy at 14 years than later changes in lesion load, although the correlation was only moderate (Spearman correlation = -0.528, p = 0.004). Conclusions:From this, it appears that early rather than later focal lesion accumulation relates to subsequent brain atrophy, but factors unconnected directly with lesion formation probably also play a significant role in determining such atrophy.

Objective: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. Methods: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. Results: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. Conclusions: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.

The most common neurological outcome measure for multiple sclerosis (MS) patients is the Expanded Disability Status Scale (EDSS). Originally, Kurtzke developed this disability status scale,1 later revised to a more refined classification system, known as the EDSS.2 The EDSS is based on a neurological examination of eight functional systems usually performed by a medical doctor. While problems of standardisation, resulting in suboptimal interrater reliability, marginal sensitivity to change and bias to locomotor function have been described3–6 the EDSS remains a useful tool for classifying disability in MS patients. In a longstanding invalidating neurological disease like MS where cure is not yet possible, disability as perceived by the patient is an important measure and for this purpose the Guy’s Neurological Disability Scale (GNDS)7 was recently developed. The GNDS measures disability based on patient self report, embraces the whole range of disabilities that can be encountered in the course of MS, is patient orientated, user friendly, and not biased to any particular disability.7,8 The GNDS is a questionnaire, divided in 12 subcategories, directed to assess a patient’s disability in the previous month by patient interview and can be applied by any healthcare worker. It is therefore extremely practical and capable of incorporating patients’ views of their disability in a structured manner.8,9 In a previous study we showed good cross sectional correlations between EDSS and GNDS: these correlations were mainly attributable to the importance of spinal cord related neurological functions for both scales.9 That study also confirmed that the GNDS measures other dimensions of disability than the EDSS and incorporates patients’ perspectives, both of which can cause marked discrepancies between scores on the two scales. Such discrepancies between objective measurements and subjective complaints have been demonstrated in many studies. To give just one …

Objective: To determine the agreement between lay interviewers and experts in the diagnosis of migraine by questionnaire. Subjects: A population based sample of 1188 individuals aged 64 to 73 years. Methods: Participants who declared that they had recurrent headaches (n = 238) answered a structured questionnaire by lay interviewers with special training in migraine. A migraine expert subsequently interviewed all the headache sufferers using the same questionnaire. Migraine was defined according to the International Headache Society criteria. Results: In comparison with the expert, the diagnosis derived by the lay interviewers had high values for specificity (97%) and positive predictive value (86%), and a low sensitivity (50%) and negative predictive value (57%). Agreement between the expert and the lay interviewers was low, with a κ value of 0.36 (95% confidence interval 0.26 to 0.47). The most serious discrepancies concerned the duration of attacks, the worsening of headaches by physical activity, the presence of nausea or vomiting, and the unilaterality of headaches. As a result, the lifetime prevalence of migraine headaches was greatly underestimated by lay interviewers (6.5%) in comparison with the expert (11.1%). Conclusions: A low level of agreement between lay interviewers and a headache expert in the diagnosis of migraine headaches by structured questionnaire may result in a substantial underestimation of migraine prevalence.

Background: β 2 Adrenoreceptor expression on peripheral blood mononuclear cells is increased in progressive multiple sclerosis. This increase has been correlated with disease activity in relapsing-remitting multiple sclerosis. Objective: To determine the β 2 adrenoreceptor expression in primary and secondary progressive multiple sclerosis in relation to findings on magnetic resonance imaging (MRI) and clinical disease activity. Methods: 10 patients with multiple sclerosis were studied (five with primary progressive and five with secondary progressive forms of the disease) over a period of six months. Monthly clinical and MRI assessments of the brain and spinal cord were carried out. β 2 Adrenoreceptor expression was assessed monthly using a ligand binding assay with [ 125 I]iodocyanopindolol. Expression of β 2 adrenoceptors on peripheral blood mononuclear cells was also assessed in five normal controls over a similar period. Results: The mean (SEM) value of β 2 adrenoreceptor density for the five normal controls was 1346 (183) sites/cell, with affinity Kd of 120 (40) pM. MRI disease activity in primary progressive multiple sclerosis was reported on two occasions and on those occasions the expression of β 2 adrenoreceptors was increased in excess of 1900 sites/cell; in the remaining 28 observations β 2 adrenoreceptor expression was within the normal range (800 to 1900 sites/cell). In patients with secondary progressive disease, MRI disease activity was observed on 16 occasions. In these patients expression of β 2 adrenoreceptors was increased in excess of 2000 sites/cell in all measurements except in one subject who did not show MRI activity throughout the six months period of study. The affinity of the receptors was within the normal range in all cases. Conclusions: Increased expression of β 2 adrenoreceptors was correlated with MRI disease activity in two patients with primary progressive multiple sclerosis. In secondary progressive multiple sclerosis, increased expression of β 2 adrenoreceptors tended not to correlate with MRI disease activity. This may reflect a persistent Th1 immune reaction in the secondary progressive form of the disease.

Objectives: Research concerning the natural history after mild traumatic brain injury (TBI) faces a number of methodological challenges, including those related to subject recruitment. The aim of this study was to determine whether subjects who agree to participate in longitudinal research differ from those who do not. The presence of identifiable, selective factors operating during recruitment may be an important source of systematic bias. In Canada, given the presence of universal healthcare coverage, this issue can be examined using population based, administrative databases to obtain information about a cohort that was approached for study enrolment, regardless of whether they ultimately agreed to participate. Methods: A sample of 626 consecutive patients with mild TBI was invited to enrol in TBI outcome research. Those who agreed to participate (n=272) were compared with those who refused (n=354) on demographic, past health, and injury related variables. Thereafter, using encrypted health card data, the two groups were contrasted with respect to pre-injury and post-injury healthcare utilisation. Results: No premorbid differences between the groups emerged. However, all early indices of TBI severity were significantly worse for the participants group (p

To investigate the relations between premorbid and current mental ability, mood, and white matter signal abnormalities detected by T2 weighted brain magnetic resonance imaging (MRI) and impairment of balance and mobility in older adults.97 subjects from the Aberdeen 1921 birth cohort underwent brain MRI, evaluation of balance, and measurement of gait speed. White matter hyperintensities detected on T2 weighted MRI scans were rated by three independent raters on three variables: white matter lesions; periventricular lesions; and brain stem lesions.Decreased gait speed was correlated with impaired visual acuity (p = 0.020), shorter stature (p = 0.008), a lower childhood IQ (p = 0.030), a lower current Raven's progressive matrices score (Raven score) (p0.001), a higher hospital anxiety and depression scale (HADS) score (p = 0.004), and an increased grade of brain stem lesions on MRI. Inability to balance was correlated with Raven score (p = 0.042), brain stem lesions (p = 0.003), white matter lesions (p = 0.003), and periventricular lesions (p = 0.038). Binary logistic regression identified brain stem lesions (odds ratio (OR) 0.22; 95% confidence interval 0.09 to 0.54) and HADS depression score (OR 0.75; 0.58 to 0.97) as the only significant associations with balance. Structural equation modelling detected an association between two latent traits representing white matter disease and an integrating function, respectively.In this cohort, white matter lesions, periventricular lesions, and brain stem lesions were associated with impaired balance. Current mental ability was strongly related to gait speed. There appears to be a concordance between motor skills and intellect in old age, which is degraded by white matter disease.

Objectives: To determine if physical and/or psychological risk factors could differentiate between subtypes of primary headache (migraine, tension-type headache (TTH), and coexisting migraine and TTH (combined)) among members of a longitudinal birth cohort study. Methods: At age 26, the headache status of members of the Dunedin Multidisciplinary Health and Development Study (DMHDS) was determined using International Headache Society criteria. Headache history and potential physical and psychological correlates of headache were assessed. These factors included perinatal problems and injuries sustained to age 26; and behavioural, personality, and psychiatric disorders assessed between ages 5 to 21. Results: The 1 year prevalences for migraine, TTH, and combined headache at the age of 26 were 7.2%, 11.1%, and 4.3%, respectively. Migraine was related to maternal headache, anxiety symptoms in childhood, anxiety disorders during adolescence and young adulthood, and the stress reactivity personality trait at the age of 18. TTH was significantly associated with neck or back injury in childhood (before the age of 13). Combined headache was related to maternal headache and anxiety disorder at 18 and 21 only among women with a childhood history of headache. Headache status at the age of 26 was unrelated to a history of perinatal complication, neurological disorder, or mild traumatic head injury. Conclusions: Migraine and TTH seem to be distinct disorders with different developmental characteristics. Combined headache may also have a distinct aetiology.

To assess possible health risks associated with the manufacture of paper, we carried out a retrospective analysis of mortality among 4,242 men and women employed at a Scottish paper mill between 1955 and 1992. During follow-up to 1994, 959 subjects had died giving an SMR of 0.85 (95% CI 0.80-0.90) in comparison with the national population. Mortality from all cancer (SMR 0.77, 95% CI 0.68-0.88) and particularly from lung cancer (SMR 0.64, 95% CI 0.50-0.81) was lower than expected. An excess of lymphatic and hematopoietic cancer (11 deaths, SMR 2.17) was observed in the making department. These findings do not support an occupational hazard of lung cancer as suggested by several earlier studies. The excess of lymphatic and hematopoietic cancer in the making department was unexpected, and may be a chance occurrence.

BackgroundThe COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences.AimsTo quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic.MethodData were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale.ResultsDepression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23–26%) compared with a pre-pandemic level of 13% (95% CI 12–14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression.ConclusionsThese results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic.

Nitrocellulose-protein blotting of serum electrophoresed in agarose gels has been adapted for the study of hepatitis B surface antigen (HBsAg). 125I-labeled anti-HBs was used as the antigen probe, and the electrophoretic migration was monitored by autoradiography. The method required 3 microliter or less of serum and could detect as little as 1 pg of purified HBsAg. Typically, we observed two bands of HbsAg; a moving band which migrated about one-third the distance moved by human serum albumin and a non-migratory band which remained at the loading site. Some examples of the use of the method include: (1) empirical methods for correlating HBsAg concentration in serum to film darkness; (2) observations of mobility changes in serial sera from dialysis patients with chronic HBsAg antigenemia; and (3) detection of related antigens such as antigen from the PLC/PRF/5 hepatoma tissue culture line and the cross-reacting woodchuck patients hepatitis virus surface antigen (WHsAg).

Antibodies to Pseudomonas aeruginosa from 10 cystic fibrosis patients with chronic P. aeruginosa lung infections were quantitatively and qualitatively analyzed. The development of specific antibodies in patient serum was evaluated in a longitudinal study (1972 to 1987). The concentrations and specificities of immunoglobulin G (IgG) and IgM antibodies to purified lipopolysaccharides (LPS) from clinical isolates of P. aeruginosa and to a variety of other gram-negative bacteria were studied by immunoblotting and enzyme-linked immunosorbent assay techniques. Results were compared with the number of immunoprecipitates to P. aeruginosa whole-cell extracts detected by crossed immunoelectrophoresis. IgG, but not IgM, anti-Pseudomonas LPS concentrations increased significantly at the onset of chronic infection and continued to increase during the course of the infection. There was a good positive correlation between the concentration of IgG anti-Pseudomonas LPS antibodies and the number of crossed-immunoelectrophoresis precipitins. The increases in IgG anti-LPS antibody concentrations were much higher to Pseudomonas LPS than to other LPSs. Binding studies demonstrated an increase in binding of IgG anti-Pseudomonas LPS during infection, whereas the binding of other anti-LPS antibodies decreased. Immunoblotting studies confirmed that antibodies reacted strongly with Pseudomonas LPS and weakly with Escherichia coli core-lipid A. The specificity of the reaction with Pseudomonas LPS increased with the duration of infection. It is concluded that anti-LPS response in cystic fibrosis patients during chronic P. aeruginosa infection demonstrates a marked increase in IgG anti-Pseudomonas LPS antibody concentration, specificity, and affinity. The anti-LPS enzyme-linked immunosorbent assay is proposed as a routine test to diagnose and to follow the course of chronic P. aeruginosa lung infection in patients with cystic fibrosis.