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1.
J Intellect Disabil Res ; 65(11): 1010-1019, 2021 11.
Article in English | MEDLINE | ID: mdl-34570405

ABSTRACT

BACKGROUND: People with intellectual disability (ID) are more likely to experience chronic depression compared with the general population, which may be compounded by loneliness and lower levels of social support. Befriending aims to provide social support and promote engagement in community activities. No randomised controlled trials have examined whether befriending improves symptoms of depression and social outcomes in people with ID. The aim of this pilot trial was to assess the feasibility and acceptability of a future larger trial of one-to-one befriending by volunteers in people with ID and depressive symptoms. METHODS: Participants were adults with mild or moderate ID with a score of 5 or more on the Glasgow Depression Scale for People with Learning Disabilities (GDS-LD). They were randomised to the intervention arm (matched to a volunteer befriender for 6 months) or the control arm (usual care). Volunteers received training and supervision provided by two community befriending schemes. The main outcomes were feasibility of recruitment (minimum target n = 35), retention rate of participants, adherence (minimum 10 meetings), acceptability of the intervention, changes in depressive symptoms (assessed at baseline and 6 months) and feasibility of collecting data for a health economic analysis. RESULTS: Recruitment was challenging, and only 16 participants with ID and 10 volunteers were recruited. Six participants were matched with a volunteer and no participants dropped out (except for two volunteers). Four participants completed 10 meetings (mean 11.8). Befriending was thought to be acceptable, but modifications were suggested. An exploratory analysis suggested that GDS-LD score was lower in the intervention group compared with the control group after adjusting for baseline scores, but not significant (adjusted mean difference: -4.0; 95% confidence interval: -11.2 to 3.2). CONCLUSIONS: A large trial would not be feasible based on the recruitment strategies employed in this study. A further feasibility study addressing these challenges or the use of other study designs should be considered.


Subject(s)
Depression , Intellectual Disability , Adult , Depression/therapy , Feasibility Studies , Humans , Loneliness , Pilot Projects , Quality of Life , Volunteers
2.
Front Genet ; 11: 483, 2020.
Article in English | MEDLINE | ID: mdl-32499817

ABSTRACT

Coccidioides immitis and C. posadasii are soil dwelling dimorphic fungi found in North and South America. Inhalation of aerosolized asexual conidia can result in asymptomatic, acute, or chronic respiratory infection. In the United States there are approximately 350,000 new infections per year. The Coccidioides genus is the only known fungal pathogen to make specialized parasitic spherules, which contain endospores that are released into the host upon spherule rupture. The molecular determinants involved in this key step of infection remain largely elusive as 49% of genes are hypothetical with unknown function. An attenuated mutant strain C. posadasii Δcts2/Δard1/Δcts3 in which chitinase genes 2 and 3 were deleted was previously created for vaccine development. This strain does not complete endospore development, which prevents completion of the parasitic lifecycle. We sought to identify pathways active in the wild-type strain during spherule remodeling and endospore formation that have been affected by gene deletion in the mutant. We compared the transcriptome and volatile metabolome of the mutant Δcts2/Δard1/Δcts3 to the wild-type C735. First, the global transcriptome was compared for both isolates using RNA sequencing. The raw reads were aligned to the reference genome using TOPHAT2 and analyzed using the Cufflinks package. Genes of interest were screened in an in vivo model using NanoString technology. Using solid phase microextraction (SPME) and comprehensive two-dimensional gas chromatography - time-of-flight mass spectrometry (GC × GC-TOFMS) volatile organic compounds (VOCs) were collected and analyzed. Our RNA-Seq analyses reveal approximately 280 significantly differentially regulated transcripts that are either absent or show opposite expression patterns in the mutant compared to the parent strain. This suggests that these genes are tied to networks impacted by deletion and may be critical for endospore development and/or spherule rupture in the wild-type strain. Of these genes, 14 were specific to the Coccidioides genus. We also found that the wild-type and mutant strains differed significantly in their production versus consumption of metabolites, with the mutant displaying increased nutrient scavenging. Overall, our results provide the first targeted list of key genes that are active during endospore formation and demonstrate that this approach can define targets for functional assays in future studies.

3.
BJOG ; 126(12): 1456-1465, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31449731

ABSTRACT

OBJECTIVE: To quantify geographic variation in the use of lymphadenectomy and/or external-beam radiotherapy (EBRT) for endometrial cancer in England. DESIGN: Cross-sectional analysis of population-based data. SETTING: English cancer registry data, linked to chemotherapy, radiotherapy and hospital episodes statistics data. POPULATION: Twenty-two thousand four hundred and eighty-three women with endometrial cancer presenting without clinical or radiological evidence of distant metastatic spread, diagnosed in England from 2013 to 2016. METHODS: Proportions of patients receiving lymphadenectomy and/or EBRT were compared across 19 Cancer Alliances, to identify variations in clinical practice. Two separate logistic regression models assessed the impact on variation of adjustment for tumour and patient characteristics. MAIN OUTCOME MEASURES: Receipt of lymphadenectomy, receipt of EBRT. RESULTS: There was substantial variation by Cancer Alliance in the adjusted proportion of women with endometrial cancer receiving lymphadenectomy (range 5% [95% CI 4-6%] to 48% [95% CI 45-52%]) and EBRT (range 10% [95% CI 7-12%] to 31% [95% CI 28-33%]), after adjusting for variation in pathological grade, age, comorbidities, deprivation, ethnic group and (EBRT only) FIGO stage. Different approaches to clinical practice were identified; (i) one Cancer Alliance had significantly higher than average lymphadenectomy and significantly lower than average EBRT use, (ii) three had high use of both lymphadenectomy and EBRT, (iii) one had low lymphadenectomy use and high EBRT use, and (iv) three had low use of both lymphadenectomy and EBRT. CONCLUSIONS: Lymphadenectomy is probably used to triage for EBRT when lymphadenectomy use is high and EBRT use is low. This is probably a result of variation in local endometrial cancer management guidelines, suggesting that UK recommendations should be clarified. TWEETABLE ABSTRACT: There is geographic variation in England in the use of lymphadenectomy and radiotherapy to treat endometrial cancer.


Subject(s)
Adenocarcinoma/therapy , Endometrial Neoplasms/therapy , Adenocarcinoma/secondary , Adult , Cross-Sectional Studies , Endometrial Neoplasms/pathology , England , Female , Geography , Humans , Logistic Models , Lymph Node Excision/statistics & numerical data , Neoplasm Metastasis , Population Surveillance , Radiotherapy, Adjuvant/statistics & numerical data , Registries , State Medicine , Women's Health Services
4.
J Appl Meas ; 17(2): 227-238, 2016.
Article in English | MEDLINE | ID: mdl-28009586

ABSTRACT

The main aim of this study was to evaluate the measurement properties of the Nordic Questionnaire for Psychological and Social Factors at Work (QPS Nordic) and the domains of demand, control and support. The Rasch analysis (RUMM 2030) was based on responses from 226 subjects with back pain who completed the QPS Nordic dimensions of demand, control, and social support (30 items) at one year follow up. The Rasch analysis revealed disordered thresholds in a total of 25 of the 30 items. The domains of demand, control and support fit the Rasch model when analyzed separately. The demand domain was well targeted, whereas patients with current neck and back pain had lower control and higher support than reflected by the questions. Two items revealed DIF by gender, otherwise invariance to age, gender, occupation and sick-leave was documented. The demand, control support domains of QPS Nordic comprised unidimensional constructs with adequate measurement properties.


Subject(s)
Back Pain/epidemiology , Data Interpretation, Statistical , Neck Pain/epidemiology , Occupational Diseases/epidemiology , Psychometrics/methods , Surveys and Questionnaires , Adult , Back Pain/diagnosis , Comorbidity , Computer Simulation , Female , Humans , Incidence , Male , Models, Statistical , Neck Pain/diagnosis , Norway/epidemiology , Pain Measurement/methods , Pain Measurement/statistics & numerical data , Psychology , Reproducibility of Results , Risk Assessment/methods , Sensitivity and Specificity
5.
J Appl Meas ; 16(2): 218-27, 2015.
Article in English | MEDLINE | ID: mdl-26075669

ABSTRACT

The main aim of this study was to evaluate whether the construct validity of the Tampa Scale for Kinesiophobia (TSK) is consistent with respect to its scaling properties, unidimensionality and targeting among workers with different levels of pain. The 311 participating Danish workers reported kinesiophobia by TSK (13 statement version) and number of days with pain during the past year (less than 8 days, less than 90 days and greater than 90 days). A Rasch analysis was used to evaluate the measurement properties of the TSK in the workers across pain levels, ages, genders and ethnicities. The TSK did not fit the Rasch model, but removing one item solved the poorness of fit. Invariance was found across the pain levels, ages and genders. Thus, with a few modifications, the TSK was shown to capture a unidimensional construct of fear of movement in workers with different pain levels, ages, and genders.


Subject(s)
Culture , Employment , Models, Theoretical , Movement/physiology , Pain/psychology , Phobic Disorders/diagnosis , Self Report , Adult , Denmark , Fear , Female , Humans , Male , Middle Aged , Pain/etiology , Psychometrics
6.
Am J Transplant ; 14(11): 2633-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25250717

ABSTRACT

We describe two cases of donor-derived methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that developed after transplantation of organs from a common donor who died from acute MRSA endocarditis. Both recipients developed recurrent MRSA infection despite appropriate antibiotic therapy, and required prolonged hospitalization and hospital readmission. Comparison of S. aureus whole genome sequence of DNA extracted from fixed donor tissue and recipients' isolates confirmed donor-derived transmission. Current guidelines emphasize the risk posed by donors with bacteremia from multidrug-resistant organisms. This investigation suggests that, particularly in the setting of donor endocarditis, even a standard course of prophylactic antibiotics may not be sufficient to prevent donor-derived infection.


Subject(s)
Genome, Bacterial , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Organ Transplantation/adverse effects , Sequence Analysis, DNA , Staphylococcal Infections/transmission , Tissue Donors , DNA, Bacterial/genetics , Humans , Male , Methicillin-Resistant Staphylococcus aureus/genetics , Polymorphism, Single Nucleotide , Staphylococcal Infections/microbiology
7.
Brain Inj ; 28(12): 1542-50, 2014.
Article in English | MEDLINE | ID: mdl-25029224

ABSTRACT

PRIMARY OBJECTIVE: To evaluate longitudinal trajectories of emotional distress symptoms after traumatic brain injury (TBI). RESEARCH DESIGN: Longitudinal study. METHODS AND PROCEDURES: Patients with mild-to-severe TBI, 118 patients participated at 3 months, 109 attended at 1-year and 89 attended the 5-year follow-up. Emotional distress was measured with the Impact of Event Scale-Revised. Patients were also assessed for coping style, anxiety, depression, substance abuse and trauma severity. MAIN OUTCOMES AND RESULTS: Based on growth mixture modelling, four trajectories of emotional distress symptoms were identified: 73.5% of patients were characterized by a pattern of resilience, 6.8% by a pattern of delayed distress, 14.6% by recovery and 5.1% by chronic distress. Relative to the resilience trajectory, avoidant-coping style and psychiatric problems were related to recovery and chronic trajectories. The delayed trajectory was similar to the resilience trajectory, except for elevated depressive and anxiety symptoms at 1- and 5-years. Demographics and injury-related variables were not significantly associated with emotional distress trajectories. CONCLUSIONS: Resilience was the most common trajectory following TBI. Patients characterized by recovery and chronic trajectories required attention and long-term clinical monitoring of their symptoms. Future research would benefit from longitudinal studies to analyse emotional distress symptoms and the strength of resilience over time.


Subject(s)
Anxiety/diagnosis , Brain Injuries/psychology , Depression/diagnosis , Resilience, Psychological , Stress Disorders, Post-Traumatic/diagnosis , Substance-Related Disorders/diagnosis , Adaptation, Psychological , Adolescent , Adult , Anxiety/etiology , Anxiety/psychology , Brain Injuries/complications , Brain Injuries/physiopathology , Depression/etiology , Depression/psychology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Norway/epidemiology , Stress Disorders, Post-Traumatic/etiology , Stress Disorders, Post-Traumatic/psychology , Substance-Related Disorders/etiology , Substance-Related Disorders/psychology , Time Factors
8.
Eur J Phys Rehabil Med ; 50(6): 649-56, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24755775

ABSTRACT

BACKGROUND: Literature has suggested that patients' pretreatment expectations may influence both prognosis and outcome. Investigation of these possible benefits requires knowledge about what is actually expected among these patients. AIM: To investigate neck/back patients' expectations for treatment outcomes (pain and functional improvement) prior to their first meetings with specialists in physical medicine and rehabilitation (PMR). DESIGN: Cross-sectional pilot study. SETTING: PMR Neck/Back Outpatient Clinic, Oslo University Hospital. POPULATION: Patients with neck/back pain and/or functional problems referred for the first time to a neck/back PMR outpatient clinic. METHODS: Questionnaires were completed prior to an appointment with a PMR specialist. The forms consisted of one earlier designed instrument (PSOE) and one self-constructed part with six 11-point numeric rating scales (11-NRS). Eligible patients were randomly selected between January and June 2012. RESULTS: Approximately 42 % expected their status to remain un-changed. A total of 17 % expected exacerbation of their status. No differences were found between expectations regarding pain and function. Full recovery was not expected. Highly educated patients, and those reporting high usage of analgesics, had higher expectations for improvement. CONCLUSION: Few of the selected patients seemed to expect improvement. These expectations are quite pessimistic, in our opinion. More elaborate studies are needed to confirm these results.


Subject(s)
Attitude to Health , Back Pain/psychology , Back Pain/rehabilitation , Neck Pain/psychology , Neck Pain/rehabilitation , Treatment Outcome , Adolescent , Adult , Aged , Aged, 80 and over , Analgesics/therapeutic use , Back Pain/drug therapy , Cross-Sectional Studies , Educational Status , Female , Humans , Male , Middle Aged , Neck Pain/drug therapy , Norway , Pilot Projects , Sick Leave/statistics & numerical data , Surveys and Questionnaires , Young Adult
9.
Eur J Pain ; 18(10): 1394-401, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24692238

ABSTRACT

BACKGROUND: In the present study, the influence of cytokines on 1-year recovery in lumbar radicular pain was examined. METHODS: In total, 110 patients with symptomatic lumbar disc herniation were followed for 1 year. Uni- and multivariate linear regression was used to assess the influence of interleukin (IL)-6, IL-8, disc degeneration and endplate changes (Modic changes) on the changes in the Oswestry Disability Index (ODI change; primary outcome) and visual analogue scale (VAS) for low back pain (LBP) and leg pain (secondary outcomes). RESULTS: Less favourable ODI outcome correlated with higher serum IL-6 levels (B = -3.41, 95% CI -5.52 to -1.30, p = 0.002), non-surgical treatment (B = -7.03, 95% CI 1.21 to 12.84, p = 0.018), higher baseline back pain intensity (B = -2.28, 95% CI -3.21 to -1.35, p < 0.001) and low educational level (B = -5.57, 95% CI 0.66 to 10.47, p = 0.027). High VAS for LBP and leg pain at 1 year was associated with high levels of serum IL-6, higher back pain intensity and longer duration of lumbar radicular pain at baseline. CONCLUSIONS: High serum IL-6 levels, but not disc degeneration or Modic changes, were associated with less favourable recovery in patients with lumbar radicular pain. Intense initial back pain, non-surgical treatment, lower educational level and longer duration of radicular pain before treatment also correlated with a slower recovery the first year after disc herniation.


Subject(s)
Interleukin-6/immunology , Interleukin-8/immunology , Intervertebral Disc Displacement/therapy , Low Back Pain/therapy , Orthopedic Procedures , Physical Therapy Modalities , Radiculopathy/therapy , Adult , Cohort Studies , Educational Status , Female , Humans , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Displacement/immunology , Intervertebral Disc Displacement/pathology , Linear Models , Low Back Pain/immunology , Low Back Pain/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Prognosis , Prospective Studies , Radiculopathy/immunology , Radiculopathy/pathology , Time-to-Treatment , Treatment Outcome
10.
Acta Neurol Scand ; 128(4): 220-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23621298

ABSTRACT

AIMS: To describe health-related quality of life (HRQL) 2 years after moderate-to-severe traumatic brain injury (TBI) and to assess predictors of HRQL. MATERIALS AND METHODS: A prospective cohort study of 91 patients, aged 16-55 years, admitted with moderate-to-severe TBI to a trauma referral centre between 2005 and 2007, with follow-up at 1 and 2 years. Mean age was 31.1 (SD = 11.3) years, and 77% were men. Injury severity was evaluated by the Glasgow Coma Scale (GCS), head CT scan (using a modified Marshall Classification), Injury Severity Score (ISS) and post-traumatic amnesia (PTA). The Functional Independence Measure (FIM), Community Integration Questionnaire (CIQ), Beck Depression Inventory (BDI) and Medical Outcomes 36-item Short Form Health Survey (SF-36) were administered at follow-up visits. The main outcome measures were the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-36. RESULTS: HRQL appears to be relatively stable between 1 and 2 years after injury. In the multivariate linear regression, younger age (ß = -0.20, P = 0.032), more severe TBI (ß = 0.28, P = 0.016), more severe overall trauma (ß = 0.22, P = 0.026), higher levels of community integration (ß = 0.36, P = 0.019) and higher positive change in PCS scores from 1 to 2 years (ß = 0.41, P < 0.001) predicted better self-reported physical health 2 years post-TBI. Lower scores for depression (ß = -0.70, P < 0.001) and a higher positive change in MCS scores (ß = 0.62, P < 0.001) predicted better self-reported mental health. CONCLUSIONS: Future interventions should focus on aspects related to HRQL that are more easily modified, such as physical functioning, home and social integration, productivity, and mental and emotional status.


Subject(s)
Brain Injuries/physiopathology , Brain Injuries/psychology , Quality of Life/psychology , Adolescent , Adult , Age Factors , Cohort Studies , Female , Glasgow Coma Scale , Humans , Linear Models , Male , Middle Aged , Outcome Assessment, Health Care , Predictive Value of Tests , Psychiatric Status Rating Scales , Retrospective Studies , Surveys and Questionnaires , Time Factors , Young Adult
11.
Neuroepidemiology ; 38(4): 259-67, 2012.
Article in English | MEDLINE | ID: mdl-22678449

ABSTRACT

AIMS: The aims of this study were to assess the incidence of hospital-admitted severe traumatic brain injury (TBI) in the adult population in Norway, and to determine whether there were differences in the epidemiological characteristics of severe TBI between rural and urban regions. METHODS: A prospective population-based study on adults with severe TBI admitted to the Norwegian Trauma Referral Centres during the 2-year period (2009-2010). The electronic patient register was searched weekly for ICD-10 diagnoses of intracranial injuries (S06.0-S06.9) to identify patients. Severe TBI was defined as lowest unsedated Glasgow Coma Scale Score ≤8 during the first 24 h after injury. RESULTS: The annual age-adjusted incidence was estimated at 5.2/100,000 in 2009 and 4.1/100,000 in 2010. The highest frequency of hospitalized patients was found among the youngest and the oldest age groups. The most common causes of injury were falls and transport accidents. The highest in-hospital case-fatality rate was found among the oldest patients. There were consistent epidemiological characteristics of severe TBI from both rural and urban regions. CONCLUSIONS: The incidence of hospital-admitted patients with severe TBI in this national study supports the declining incidence of TBI reported internationally. No major differences were found in epidemiological characteristics between the urban and rural parts of Norway.


Subject(s)
Accidental Falls , Accidents, Traffic , Brain Injuries/epidemiology , Hospital Mortality , Adolescent , Adult , Age Factors , Aged , Brain Injuries/etiology , Cohort Studies , Female , Glasgow Coma Scale , Humans , Incidence , Male , Middle Aged , Norway/epidemiology , Rural Population/statistics & numerical data , Severity of Illness Index , Sex Factors , Urban Population/statistics & numerical data
12.
Eur J Pain ; 16(7): 1064-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22337560

ABSTRACT

BACKGROUND: The COMT enzyme metabolizes catecholamines and thus modulates adrenergic, noradrenergic and dopaminergic signaling. A functional polymorphism in the gene encoding this enzyme, i.e. the COMT Val158Met SNP that reduces enzyme activity, has previously been linked to pain sensitivity. METHODS: We examined if the COMT Val158Met SNP could contribute to discogenic subacute low back pain and sciatica by comparing the frequency of the Val158Met genotypes of degenerative disc disease patients with healthy controls. Moreover, we examined if this SNP could predict the clinical outcome, i.e. the progression of pain and disability. RESULTS: The present data demonstrated that there were no differences in COMT genotype frequencies between the newly diagnosed patients and controls. Analysis of pain and disability in the patients over time revealed, however, a significant or border-line significant increase in McGill sensory score and Oswestry Disability Index (ODI) score for individuals with COMT Met/Met genotype. Furthermore, significant associations between the COMT Met-allele and VAS activity score, McGill sensory score and ODI score were observed in the patients 6 months after inclusion. DISCUSSION: Although the Val158Met SNP was not a risk factor for disc herniation, patients with Met/Met had more pain and slower recovery than those with Val/Met, which in turn also had more pain and slower recovery than those with Val/Val suggesting the SNP contributes to the progression of the symptoms of disc herniation. CONCLUSION: We conclude that the functional COMT Val158Met SNP contributes to long lasting low back pain, sciatica and disability after lumbar disc herniation.


Subject(s)
Catechol O-Methyltransferase/genetics , Intervertebral Disc Displacement/genetics , Low Back Pain/genetics , Polymorphism, Single Nucleotide , Sciatica/genetics , Adolescent , Adult , Alleles , Disability Evaluation , Diskectomy , Female , Gene Frequency , Genotype , Humans , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/surgery , Low Back Pain/etiology , Low Back Pain/surgery , Lumbar Vertebrae/surgery , Male , Middle Aged , Pain Measurement , Sciatica/etiology , Sciatica/surgery , Treatment Outcome
13.
Neurology ; 76(6): 501-10, 2011 Feb 08.
Article in English | MEDLINE | ID: mdl-21228296

ABSTRACT

OBJECTIVE: To investigate factors, including cognitive and brain reserve, which may independently predict prevalent and incident dementia of the Alzheimer type (DAT) and to determine whether inclusion of identified factors increases the predictive accuracy of the CSF biomarkers Aß(42), tau, ptau(181), tau/Aß(42), and ptau(181)/Aß(42). METHODS: Logistic regression identified variables that predicted prevalent DAT when considered together with each CSF biomarker in a cross-sectional sample of 201 participants with normal cognition and 46 with DAT. The area under the receiver operating characteristic curve (AUC) from the resulting model was compared with the AUC generated using the biomarker alone. In a second sample with normal cognition at baseline and longitudinal data available (n = 213), Cox proportional hazards models identified variables that predicted incident DAT together with each biomarker, and the models' concordance probability estimate (CPE), which was compared to the CPE generated using the biomarker alone. RESULTS: APOE genotype including an ε4 allele, male gender, and smaller normalized whole brain volumes (nWBV) were cross-sectionally associated with DAT when considered together with every biomarker. In the longitudinal sample (mean follow-up = 3.2 years), 14 participants (6.6%) developed DAT. Older age predicted a faster time to DAT in every model, and greater education predicted a slower time in 4 of 5 models. Inclusion of ancillary variables resulted in better cross-sectional prediction of DAT for all biomarkers (p < 0.0021), and better longitudinal prediction for 4 of 5 biomarkers (p < 0.0022). CONCLUSIONS: The predictive accuracy of CSF biomarkers is improved by including age, education, and nWBV in analyses.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/epidemiology , Age Factors , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Apolipoprotein E4/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Prevalence , Prospective Studies , tau Proteins/cerebrospinal fluid
14.
Neurology ; 75(1): 42-8, 2010 Jul 06.
Article in English | MEDLINE | ID: mdl-20603484

ABSTRACT

OBJECTIVE: Several factors may influence the relationship between Alzheimer disease (AD) lesions and the expression of dementia, including those related to brain and cognitive reserve. Other factors may confound the association between AD pathology and dementia. We tested whether factors thought to influence the association of AD pathology and dementia help to accurately identify dementia of the Alzheimer type (DAT) when considered together with amyloid imaging. METHODS: Participants with normal cognition (n = 180) and with DAT (n = 25), aged 50 years or older, took part in clinical, neurologic, and psychometric assessments. PET with the Pittsburgh compound B (PiB) tracer was used to measure brain amyloid, yielding a mean cortical binding potential (MCBP) reflecting PiB uptake. Logistic regression was used to generate receiver operating characteristic curves, and the areas under those curves (AUC), to compare the predictive accuracy of using MCBP alone vs MCBP together with other variables selected using a stepwise selection procedure to identify participants with DAT vs normal cognition. RESULTS: The AUC resulting from MCBP alone was 0.84 (95% confidence interval [CI] = 0.73-0.94; cross-validated AUC = 0.80, 95% CI = 0.68-0.92). The AUC for the predictive equation generated by a stepwise model including education, normalized whole brain volume, physical health rating, gender, and use of medications that may interfere with cognition was 0.94 (95% CI = 0.90-0.98; cross-validated AUC = 0.91, 95% CI = 0.85-0.96), an improvement (p = 0.025) over that yielded using MCBP alone. CONCLUSION: Results suggest that factors reported to influence associations between AD pathology and dementia can improve the predictive accuracy of amyloid imaging for the identification of symptomatic AD.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Amyloid , Positron-Emission Tomography/methods , Aged , Alzheimer Disease/metabolism , Amyloid/metabolism , Female , Humans , Male , Middle Aged , Retrospective Studies
15.
Neurology ; 74(2): 106-12, 2010 Jan 12.
Article in English | MEDLINE | ID: mdl-20032288

ABSTRACT

OBJECTIVE: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). METHODS: Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study-Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer. RESULTS: The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20-0.84) and pure AD (HR = 0.31, 95% CI = 0.12-0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52-0.997) and pure AD (HR = 0.57; 95% CI = 0.36-0.90) among white subjects after adjustment for demographics, number of APOE epsilon4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD. CONCLUSIONS: In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration.


Subject(s)
Alzheimer Disease/epidemiology , Dementia, Vascular/epidemiology , Neoplasms/epidemiology , Aged , Aged, 80 and over , Alzheimer Disease/genetics , Cohort Studies , Dementia, Vascular/genetics , Female , Genetic Predisposition to Disease/genetics , Hospitalization/statistics & numerical data , Hospitalization/trends , Humans , Male , Neoplasms/genetics , Nerve Degeneration/epidemiology , Nerve Degeneration/genetics , Parkinson Disease/epidemiology , Parkinson Disease/genetics , Prevalence , Proportional Hazards Models , Prospective Studies , Risk Assessment/methods , Risk Factors , White People
16.
Curr Alzheimer Res ; 6(3): 196-204, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19519301

ABSTRACT

Cancer and Alzheimer's disease (AD) are two common disorders for which the final pathophysiological mechanism is not yet clearly defined. In a prospective longitudinal study we have previously shown an inverse association between AD and cancer, such that the rate of developing cancer in general with time was significantly slower in participants with AD, while participants with a history of cancer had a slower rate of developing AD. In cancer, cell regulation mechanisms are disrupted with augmentation of cell survival and/or proliferation, whereas conversely, AD is associated with increased neuronal death, either caused by, or concomitant with, beta amyloid (Abeta) and tau deposition. The possibility that perturbations of mechanisms involved in cell survival/death regulation could be involved in both disorders is discussed. Genetic polymorphisms, DNA methylation or other mechanisms that induce changes in activity of molecules with key roles in determining the decision to "repair and live"- or "die" could be involved in the pathogenesis of the two disorders. As examples, the role of p53, Pin1 and the Wnt signaling pathway are discussed as potential candidates that, speculatively, may explain inverse associations between AD and cancer.


Subject(s)
Alzheimer Disease , Neoplasms , Signal Transduction/physiology , Aging/physiology , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Animals , Cell Cycle/physiology , Humans , Models, Biological , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/physiopathology , Signal Transduction/genetics , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Wnt Proteins/genetics , Wnt Proteins/metabolism
17.
Eur J Phys Rehabil Med ; 45(3): 403-14, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19396057

ABSTRACT

AIM: The aim of this study was to identify candidate categories from the International Classification of Functioning, Disability and Health (ICF) to be included in the Brief ICF Core Set for low back pain (LBP) by examining their relation to general health and functionality. METHODS: This was part of an international multicentre study with 118 participating Norwegian patients with LBP. The Comprehensive ICF Core Set for LBP was filled in by health professionals. The patients reported their health-related quality of life in the Medical Outcome Study Short Form 36 (SF-36) and function in the Oswestry Disability Index. Two questions regarding the patient's general health and functioning were completed by the health professionals and the patients themselves. Regression models were developed in order to identify ICF categories explaining most of the variance of the criterion measures. RESULTS: Twelve ICF categories remained as significant explanatory factors according to the eight regression models, four of which were not included in a previously proposed Brief ICF Core Set for LBP. CONCLUSIONS: The present study complements the development of the Brief ICF Core Set for LBP, and indicates a minimum number of categories needed to explain LBP patients' functioning and health. Further elaboration of the Brief ICF Core Set for LBP with multinational data is needed.


Subject(s)
Health Status Indicators , Low Back Pain/classification , Cross-Sectional Studies , Disability Evaluation , Female , Humans , International Classification of Diseases , Linear Models , Low Back Pain/physiopathology , Low Back Pain/psychology , Male , Middle Aged , Norway , Quality of Life , Reproducibility of Results , Surveys and Questionnaires
18.
Acta Neurol Scand ; 120(1): 16-23, 2009 Jul.
Article in English | MEDLINE | ID: mdl-18976326

ABSTRACT

OBJECTIVES: To describe the functional outcome and health-related quality of life (HRQL) 10 years after moderate-to-severe traumatic brain injury (TBI). MATERIAL AND METHODS: A retrospective, population-based study of 62 survivors of working-age with moderate-to-severe TBI injured in 1995/1996, and hospitalized at the Trauma Referral Center in Eastern Norway. Functional status was measured by the Glasgow Outcome Scale-Extended (GOS-E). HRQL was assessed by the SF-36 questionnaire. RESULTS: The mean current-age was 40.8 years. The frequency of epilepsy was 19% and the depression rate 31%. A majority had good recovery (48%) or moderate disability (44%). Employment rate was 58%. Functional and employment status were associated with initial injury severity in contrast to HRQL. Study patients had significantly lower scores in all SF-36 dimensions when compared with the general Norwegian population. CONCLUSION: At 10-years follow-up, our study population is still in their most productive years and affected domains should be considered in long-term follow-up and intervention programs.


Subject(s)
Brain Injuries/complications , Quality of Life , Adolescent , Adult , Brain Injuries/epidemiology , Brain Injuries/rehabilitation , Depression/epidemiology , Depression/etiology , Employment , Epilepsy, Post-Traumatic/epidemiology , Epilepsy, Post-Traumatic/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Norway/epidemiology
19.
Eur J Phys Rehabil Med ; 44(4): 387-97, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19002088

ABSTRACT

AIM: The aim of this work was to evaluate the Norwegian form of the International Classification of Functioning, Disability and Health (ICF) Core Set for low back pain patients and investigate the feasibility of the Core Set in clinical practice. METHODS: This was part of an international multicenter study with 118 participating Norwegian patients referred to Departments of Physical Medicine and rehabilitation with low back pain (LBP). The ICF Core Set for LBP was filled in by the health professionals. The patients reported their problems using the Medical Outcome Study Short Form 36 (SF-36) and the Oswestry Low Back Pain Disability Questionnaire (ODI). RESULTS: The ICF Core Set categories capture the problems of the LBP patients, and few categories were reported to be missing. Many problems were reported within body function, and problems within work and employment were captured by the activity and participation component. The environmental factors in ICF were most frequently scored as facilitators, but the same factor could also represent a barrier in other individuals. Health professionals, family and friends were important factors within this domain. Few problems were scored as severe or complete indicating the need of collapsing the qualifier levels. Scoring of the ICF Core Set was feasibly, but rather time-consuming. CONCLUSION: The ICF Core Set for LBP captures the problems of LBP, and adds important aspects to clinical practice in the field of LBP. However, the ICF Core Set for LBP needs further elaboration in order to improve the clinical feasibility.


Subject(s)
Disability Evaluation , Health Status Indicators , Low Back Pain/rehabilitation , Adult , Aged , Aged, 80 and over , Comorbidity , Cross-Sectional Studies , Female , Humans , Low Back Pain/epidemiology , Male , Middle Aged , Norway
20.
Neurology ; 71(4): 260-4, 2008 Jul 22.
Article in English | MEDLINE | ID: mdl-18645163

ABSTRACT

BACKGROUND: Carnitine palmitoyltransferase II (CPT II) deficiency is an important cause of recurrent rhabdomyolysis in children and adults. Current treatment includes dietary fat restriction, with increased carbohydrate intake and exercise restriction to avoid muscle pain and rhabdomyolysis. METHODS: CPT II enzyme assay, DNA mutation analysis, quantitative analysis of acylcarnitines in blood and cultured fibroblasts, urinary organic acids, the standardized 36-item Short-Form Health Status survey (SF-36) version 2, and bioelectric impedance for body fat composition. Diet treatment with triheptanoin at 30% to 35% of total daily caloric intake was used for all patients. RESULTS: Seven patients with CPT II deficiency were studied from 7 to 61 months on the triheptanoin (anaplerotic) diet. Five had previous episodes of rhabdomyolysis requiring hospitalizations and muscle pain on exertion prior to the diet (two younger patients had not had rhabdomyolysis). While on the diet, only two patients experienced mild muscle pain with exercise. During short periods of noncompliance, two patients experienced rhabdomyolysis with exercise. None experienced rhabdomyolysis or hospitalizations while on the diet. All patients returned to normal physical activities including strenuous sports. Exercise restriction was eliminated. Previously abnormal SF-36 physical composite scores returned to normal levels that persisted for the duration of the therapy in all five symptomatic patients. CONCLUSIONS: The triheptanoin diet seems to be an effective therapy for adult-onset carnitine palmitoyltransferase II deficiency.


Subject(s)
Carnitine O-Palmitoyltransferase/deficiency , Carnitine O-Palmitoyltransferase/genetics , Diet Therapy/methods , Genetic Predisposition to Disease/genetics , Rhabdomyolysis/diet therapy , Rhabdomyolysis/genetics , Triglycerides/administration & dosage , Adolescent , Adult , Child , DNA Mutational Analysis , Dietary Carbohydrates/therapeutic use , Dietary Fats/adverse effects , Exercise , Female , Food, Formulated , Genetic Testing , Genotype , Humans , Male , Middle Aged , Mutation/genetics , Physical Fitness , Rest , Rhabdomyolysis/enzymology , Treatment Outcome
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