Higher Vitamin D Levels Are Associated with Better Attentional Functions: Data from the NorCog Register.

OBJECTIVES: The aim of this cross-sectional study was to evaluate which cognitive domains are mostly affected in persons with vitamin D insufficiency or deficiency, defined as 25(OH)D < 50 nmol/l and < 25 nmol/l, respectively. METHODS: Data were collected from the Norwegian register for persons assessed for cognitive symptoms (NorCog). 580 persons aged ≥ 65 years were included. The following cognitive and neuropsychiatric tests were used: Mini Mental State Examination, Norwegian Revised Version (MMSE-NR), the Clock Drawing test, the Trail Making Test A and B, the 10-word memory test and the figure copying test from CERAD - immediate and delayed recall, The Controlled Oral Word Association Test -FAS and Boston Naming test. Neuropsychiatric symptoms were assessed by Neuropsychiatric Inventory-Questionnaire and Cornell Scale for Depression in Dementia. RESULTS: Vitamin D-insufficiency was found in approx. 30 % of the study cohort. After adjustment for relevant covariates, higher serum 25(OH)D levels were associated with higher score on MMSE-NR (p=0.032) and 10-word Memory Test, immediate recall (p=0.038), as well as faster execution of Trail Making Test A and B (p=0.038 and p=0.021, respectively). Other tests were not significantly associated with 25(OH)D levels. CONCLUSION: Higher vitamin D levels appear to be associated with better cognition, especially in areas of executive function and mental flexibility.

Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer's disease.

BACKGROUND: Neuropsychiatric symptoms (NPS), such as depression, apathy, agitation, and psychotic symptoms are common in mild cognitive impairment (MCI) and dementia in Alzheimer's disease (AD). Subgroups of NPS have been reported. Yet the relationship of NPS and their subgroups to different stages of cognitive impairment is unclear. Most previous studies are based on small sample sizes and show conflicting results. We sought to examine the frequency of NPS and their subgroups in MCI and different stages of dementia in AD. METHODS: This was a cross-sectional study using data from a Norwegian national registry of memory clinics. From a total sample of 4,571 patients, we included those with MCI or AD (MCI 817, mild AD 883, moderate-severe AD 441). To compare variables across groups ANOVA or χ 2-test was applied. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI-Q) items to identify subgroups of NPS. RESULTS: The frequency of any NPS was 87.2% (AD 91.2%, MCI 79.5%; p < 0.001) and increased with increasing severity of cognitive decline. The most frequent NPS in MCI was depression. Apathy was the most frequent NPS in AD across different stages of severity. The factor analysis identified three subgroups in MCI and mild AD, and a fourth one in moderate-severe AD. We labelled the subgroups "depression," "agitation," "psychosis," and "elation." CONCLUSIONS: The frequency of NPS is high in MCI and AD and increases with the severity of cognitive decline. The subgroups of NPS were relatively consistent from MCI to moderate-severe AD. The subgroup elation appeared only in moderate-severe AD.

Change in psychotropic drug use in Norwegian nursing homes between 2004 and 2011.

ABSTRACTBackground:We aimed to assess whether there were any changes in the use of psychotropic drugs in Norwegian nursing homes between 2004 and 2011. Also, we investigated whether the predictors of use of specific psychotropic drug groups have changed. METHODS: We conducted a secondary analysis of two cohort studies of two Norwegian nursing home samples (2004/05 and 2010/11). Multivariate models were applied. RESULTS: We found a significant decrease in the prescription of antipsychotic drugs between 2004 and 2011 (0.63 OR, 95%CI = 0.49-0.82, p < 0.001) even after adjusting for relevant demographic and clinical variables. There are only minor changes for the other psychotropic drugs. We found that (1) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with more affective symptoms and (2) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with lower scores on the Physical Self-Maintenance scale. CONCLUSION: This is the first study to show a robust decrease in antipsychotic drug use in nursing home patients with dementia unrelated to possible changes in case mix. The change might be explained by treatment recommendations against its use except in the most severe conditions of aggression or psychosis. Our findings indicate that it takes several years to implement scientific knowledge in clinical practice in nursing homes.

Intake of a Protein-Enriched Milk and Effects on Muscle Mass and Strength. A 12-Week Randomized Placebo Controlled Trial among Community-Dwelling Older Adults.

OBJECTIVES: To investigate the effect of 20 g protein with breakfast and evening meal on muscle mass, muscle strength and functional performance in older adults. DESIGN: A double-blinded randomized controlled study. SETTING: Oslo and Akershus University College of Applied Sciences, Norway. PARTICIPANTS: Healthy community-dwelling men and women (≥ 70 years) with reduced physical strength and/or performance. INTERVENTION: Subjects were randomly assigned to receive either protein-enriched milk (2 x 0.4 L/d; protein group) or an isocaloric carbohydrate drink (2 x 0.4 L/d; control group) with breakfast and evening meal for 12 weeks. MEASUREMENTS: The primary endpoints were muscle mass measured by dual X-ray absorptiometry, and tests of muscle strength (one repetition maximum test of chest press and leg press) and functional performance (handgrip strength, stair calimb and repeated chair rise). RESULTS: In total, 438 subjects were screened, 50 subjects were randomized and 36 completed the study. Chest press improved significantly in the protein (1.3 kg (0.1-2.5), p=0.03) and the control group (1.5 kg (0.0-3.0), p=0.048), but with no difference between the groups (p=0.85). No significant change in leg press (p=0.93) or muscle mass (p=0.54) were observed between the protein and the control group. Nor did we observe any significant differences in the functional performance tests (p>0.05 for all tests) between the groups. CONCLUSION: Increased protein intake (2 x 20 g/d) did not significantly improve muscle mass, muscle strength or functional performance in healthy older weight stable adults. Whether intake of > 20 g protein to each meal is necessary for preservation of muscle mass and strength in older adults should be further investigated in a larger study. This underscores the need for well-designed studies that can differentiate between the effect of protein intake and increased energy. This trial was registered at Clinicaltrials.gov (ID no. NCT02218333).

Randomized clinical trial comparing collagen plug and advancement flap for trans-sphincteric anal fistula.

BACKGROUND: The role of a collagen plug for treating anal fistula is not well established. A randomized prospective multicentre non-inferiority study of surgical treatment of trans-sphincteric cryptogenic fistulas was undertaken, comparing the anal fistula plug with the mucosal advancement flap with regard to fistula recurrence rate and functional outcome. METHODS: Patients with an anal fistula were evaluated for eligibility in three centres, and randomized to either mucosal advancement flap surgery or collagen plug, with clinical follow-up at 3 and 12 months. The primary outcome was the fistula recurrence rate. Anal pain (visual analogue scale), anal incontinence (St Mark's score) and quality of life (Short Form 36 questionnaire) were also reported. RESULTS: Ninety-four patients were included; 48 were allocated to the plug procedure and 46 to advancement flap surgery. The median follow-up was 12 (range 9-24) months. The recurrence rate at 12 months was 66 per cent (27 of 41 patients) in the plug group and 38 per cent (15 of 40) in the flap group (P = 0·006). Anal pain was reduced after operation in both groups. Anal incontinence did not change in the follow-up period. Patients reported an increased quality of life after 3 months. There were no differences between the groups with regard to pain, incontinence or quality of life. CONCLUSION: There was a considerably higher recurrence rate after the anal fistula plug procedure than following advancement flap repair. Registration number: NCT01021774 (http://www.clinicaltrials.gov).

Change in pelvic organ support during pregnancy and the first year postpartum: a longitudinal study.

OBJECTIVE: To describe changes in pelvic organ support from mid pregnancy until 1 year postpartum among nulliparous pregnant women, and to examine whether delivery route affects changes in pelvic organ support. DESIGN: Prospective cohort study. SETTING: Akershus University Hospital in Norway. POPULATION: A cohort of 300 nulliparous pregnant women included at mid-pregnancy. METHODS: Pelvic organ support assessed at 21 and 37 weeks of gestation, and again at 6 weeks, 6 months, and 12 months postpartum, by the use of the Pelvic Organ Prolapse Quantification (POP-Q) system. Linear mixed model was used to assess longitudinal change in pelvic organ support. MAIN OUTCOME MEASURES: Prevalence of anatomic POP. Change in POP-Q variables over time and between delivery groups. RESULTS: The prevalence of anatomic POP ranged from 0 to 10%. Vaginal POP-Q points made a cranial shift from mid to late pregnancy, a caudal shift following delivery, and again a cranial shift after 6 weeks postpartum. Postpartum change was present following both vaginal and caesarean deliveries, but was more pronounced following vaginal delivery. The perineal body and genital hiatus became longer from mid to late pregnancy, and shortened after 6 weeks postpartum. At 12 months postpartum all POP-Q points, except cervix, had recovered to baseline in the vaginal delivery group. CONCLUSIONS: The prevalence of anatomic POP was low in this cohort. There was change in pelvic organ support both during pregnancy and following vaginal as well as caesarean delivery. The short-term ability to recover was good after the first pregnancy and delivery. TWEETABLE ABSTRACT: Pelvic organ support changes during pregnancy. A contribution to the risk of POP?

WT1 and interferon-ß-vitamin D association in MS: a longitudinal study.

BACKGROUND: It has been suggested that polymorphisms in the WT1 gene modulate the effect of IFN-ß treatment in multiple sclerosis (MS) through regulation of the relationship between IFN-ß and vitamin D. OBJECTIVE: To examine whether WT1 modulates the relationship between IFN-ß and vitamin D in a longitudinal study with repeated assessment of vitamin D before and after initiation of IFN-ß. METHODS: In a prospective study of 85 patients with relapsing remitting MS, 25-hydroxyvitamin D was measured at month 0, 1, 3, 6, 7, 9, 12, 18 and 24. None of the patients used any immunomodulatory treatment at inclusion, and all started IFN-ß treatment at month 6. RESULTS: The mean concentrations of seasonally adjusted 25-hydroxyvitamin increased slightly (3.1 ± 1.2 nmol/l, P = 0.008) after initiation of IFN-ß. The association between IFN-ß treatment and 25-hydroxyvitamin D was similar in patients carrying any of the two alleles in the WT1 SNPs (rs10767935 and rs5030244) recently reported to modulate this relationship. CONCLUSIONS: In this prospective study with repeated measurements of 25-hydroxyvitamin D before and during treatment with IFN-ß, we did not find that genetic variation in WT1 plays any role in regulating the relationship between IFN-ß and serum 25-hydroxyvitamin D.

Neurobiological correlates of depressive symptoms in people with subjective and mild cognitive impairment.

OBJECTIVE: To test the hypothesis that depressive symptoms correlate with Alzheimer's disease (AD) type changes in CSF and structural and functional imaging including hippocampus volume, cortical thickness, white matter lesions, Diffusion tensor imaging (DTI), and fluoro-deoxy-glucose positron emission tomography (FDG-PET) in patient with subjective (SCI) and mild (MCI) cognitive impairment. METHOD: In 60 patients, depressive symptoms were assessed using the Geriatric Depression Scale. The subjects underwent MRI, 18F-FDG PET imaging, and lumbar CSF extraction. RESULTS: Subjects with depressive symptoms (n=24) did not have more pathological AD biomarkers than non-depressed. Uncorrected there were trends towards larger hippocampal volumes (P=0.06), less orbital WM damage measured by DTI (P=0.10), and higher orbital glucose metabolism (P=0.02) in the depressed group. The findings were similar when SCI and MCI were analyzed separately. Similarly, in patients with pathological CSF biomarkers (i.e., predementia AD, n=24), we found that correlations between scores on GDS and CSF Aß42 and P-tau indicated less severe AD-specific CSF changes with increasing depression. CONCLUSION: Depressive symptoms are common in SCI/MCI, but are not associated with pathological imaging or CSF biomarkers of AD. Depression can explain cognitive impairment in SCI/MCI or add to cognitive impairment leading to an earlier clinical investigation in predementia AD.

Decreasing time trend in SSI incidence for orthopaedic procedures: surveillance matters!

BACKGROUND: Infection is the most common reason for early revision after hip and knee arthroplasty, and the revision rate is increasing. Surgical site infection (SSI) surveillance data are important to assess the true infection rate. There is little information regarding the potential time trend in SSI incidence following orthopaedic surgery. AIM: To evaluate whether a time trend exists in SSI incidence due to surveillance following orthopaedic surgery. METHODS: The SSI rates after hip and knee replacements and osteosynthesis of trochanteric femoral fractures and ankle fractures were recorded prospectively from May 1998 to October 2008 according to the criteria of the US Centers for Disease Control and Prevention. In total, 4177 procedures were analysed, 65.8% of which were performed on female patients. Linear regression was used to analyse trends in SSI rates. FINDINGS: SSI incidence decreased significantly from 7% in the first year to 3% in the last year; a 57% relative reduction. The duration of surgery was the only significant predictor for infection (P < 0.001) in a logistic regression model that also included age, American Society of Anesthesiologists' score and level of emergency. CONCLUSION: Surveillance following orthopaedic procedures showed a significant decrease in SSI incidence over the 11-year surveillance period. The causality between surveillance and SSI incidence is difficult to prove, but surveillance with feedback probably influences several procedures that affect the quality of health care, even if duration of surgery is the only significant predictor of this effect.

Modelling and prediction of 25-hydroxyvitamin D levels in Norwegian relapsing-remitting multiple sclerosis patients.

BACKGROUND/AIM: 25-Hydroxyvitamin D (25(OH)D) levels are suggested to influence the susceptibility and risk of disease progression in multiple sclerosis (MS). Seasonal fluctuation of 25(OH)D levels may differ in magnitude between individuals. The purpose of this paper was to model the seasonal fluctuation of vitamin D in Norwegian MS patients and to examine to which extent one single 25(OH)D measurement predicts the level at other time points throughout the year. METHODS: During December 2004 and July 2008, 762 serum samples were collected from 92 Norwegian relapsing-remitting MS patients. Time series analysis and multivariate modelling techniques were used to model seasonal fluctuations and intra- and inter-individual variations in 25(OH)D values. RESULTS: Most patients reached their lowest 25(OH)D level in March/April and the highest in July/August. There were substantial intra-individual variations in the extent of seasonal fluctuation, with 36.6% of explainable variation in seasonally adjusted 25(OH)D levels (on a logarithmic scale) attributable to the patient level. The remaining 63.4% could be accounted for by sources of inter-individual variation. Both the total and inter-individual variabilities were lowest in February, and the prediction interval in this month was up to 26% narrower compared to other months. The prediction intervals would be at least 21% wider with only one observation available per patient. CONCLUSIONS: The seasonal fluctuations of 25(OH)D levels in Norwegian relapsing-remitting MS patients are subject to pronounced intra- and inter-individual variation. The most representative measurements of 25(OH)D levels are taken in February.

Exotoxin-encoding gene content in community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus.

Reports of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) causing hospital infections are increasing, and it is questionable whether the existing molecular definition of CA-MRSA is suitable for the characterization of all strains involved. The 821 methicillin-resistant S. aureus (MRSA) isolates recovered from patients in Health Region East, Norway during the period 1991-2006 were characterized by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) gene typing, and their content of exotoxin-encoding genes. Cluster analysis based on exotoxin-encoding gene content was performed to separate the MRSA isolates into valid clusters with respect to microbiological characteristics. The analysis gave a four-cluster structure, and the four toxin clusters differed in the genetic lineages they included and in the diversity of the genetic lineages. A few genetic lineages were present in several toxin clusters. These results support the theory that mobile genetic elements encoding virulence genes do not move randomly among genetic lineages, but are restricted by the clonal lineages' genetic background. Using the molecular criteria, MLST type, SCCmec type and the presence of the lucS/F-Panton-Valentine leukocidin (PVL) gene to define a CA-MRSA isolate, it was found that the CA-MRSA isolates mainly grouped together in two toxin clusters with a low prevalence of exotoxin-encoding genes. Statistical analyses supported the conclusion that toxin clusters with CA-MRSA genetic lineages were characterized by a low prevalence of exotoxin-encoding genes, whereas toxin clusters with hospital-acquired MRSA genetic lineages were characterized by a higher prevalence of exotoxin-encoding genes.

Interobserver repeatability of three- and four-dimensional transperineal ultrasound assessment of pelvic floor muscle anatomy and function.

OBJECTIVE: To evaluate the interobserver repeatability of measurement of the pubovisceral muscle and levator hiatus, and the position of related organs, during rest, muscle contraction and Valsalva maneuver using three- and four-dimensional (3D and 4D) transperineal ultrasound. METHODS: Seventeen women were included in the study. The position and dimensions of the pubovisceral muscle and levator hiatus in patients at rest and during contraction and Valsalva were determined from stored 3D and 4D ultrasound volumes. Analyses were conducted offline by two observers blinded to the clinical data and to each others' measurements. RESULTS: Measurements of levator hiatal dimensions at rest demonstrated intraclass correlation coefficient (ICC) values of 0.92 to 0.96. The ICC values for pubovisceral muscle thickness at rest varied between good and very good (ICC, 0.61-0.93), regardless of plane. During contraction, the ICC values for all measured parameters were very good, varying between 0.61 and 0.92. Measurement of the transverse diameter of the levator hiatus during the Valsalva maneuver showed good reliability (ICC, 0.86), but assessment of the anterior and posterior borders of the levator hiatus was only possible in 29% of cases. CONCLUSIONS: 3D and 4D transperineal ultrasound measurement of the pubovisceral muscle and levator hiatus is reliable in women with no or minor symptoms of prolapse at rest and during contraction. The technique for recording during the Valsalva maneuver requires improvement if it is to be useful in the diagnosis of pelvic organ prolapse.

The Severity of Dependence Scale detects people with medication overuse: the Akershus study of chronic headache.

OBJECTIVE: To evaluate the Severity of Dependence Scale (SDS) in people with primary chronic headache and analyse the pattern of medication overuse. DESIGN: Cross sectional epidemiological survey. A posted questionnaire screened for chronic headache. Neurological residents interviewed those with self-reported chronic headache. The International Classification of Headache Disorders was used. Split file methodology was employed for data analysis. SETTING: Akershus University Hospital, Oslo, Norway. PARTICIPANTS: A random sample of 30,000 people, aged 30-44 years, from the general population of Akershus County, Norway. 405 people had primary chronic headache. MAIN OUTCOME MEASURE: SDS score in those with and without medication overuse. RESULTS: The screening questionnaire response rate was 71% and the participation rate of the interview 74%. Among 405 people with primary chronic headache, 95% had chronic tension-type headache, 4% had chronic migraine and <1% had other primary chronic headaches. Of 386 persons with chronic tension-type headache, 44% had medication overuse and 47% had co-occurrence of migraine. Simple analgesics, combination analgesics, triptans, ergotamine, opioids and a combination of acute medications were overused by 65%, 27%, 4%, <1%, 1% and 2% of people, respectively. The mean SDS score was significantly higher in those with than in those without medication overuse (5.6 vs 2.7; p<0.001). CONCLUSION: The SDS questionnaire detects medication overuse and dependency-like behaviour in persons with primary chronic headache.

Quantitative and qualitative assessment of exposure among employees in Norwegian smelters.

OBJECTIVES: To generate a job exposure matrix (JEM) for dust exposure in Norwegian smelters to be used in an epidemiologic study of respiratory diseases and to identify determinants of exposure. METHODS: The arithmetic mean and geometric mean (GM) of 2619 personal dust exposure measurements were applied in constructing the JEM, which was assigned to 2620 employees participating in a respiratory survey including yearly spirometry and a respiratory questionnaire. A qualitative exposure classification was constructed: (i) line operators were those employed full time in the production line, (ii) non-exposed employees were those who did not work in production and (iii) the remainder were classified as non-line operators. RESULTS: In the ferrosilicon alloy and silicon metal production group (FeSi/Si-metal), the median GM of dust exposure was 2.3 mg m(-3) (0.04-5.6) (10-90% percentiles) compared with 1.6 mg m(-3) (0.02-2.3) in the silicomanganese, ferromanganese and ferrochromium production group (SiMn/FeMn/FeCr). Multivariate analyses showed that dust exposure concentration levels decreased significantly with increasing age (FeSi/Si-metal), was significantly lower in females than in males and was significantly higher in current smokers than in never-smokers. Dust exposure concentration levels were also higher in employees reporting previous exposure to dust, fumes and gases than in employees without such previous exposure, though, significant only in the FeSi/Si-metal production group. CONCLUSION: The dust exposure levels of the employees were higher in the FeSi/Si-metal production group than in the SiMn/FeMn/FeCr production group. Age, gender, smoking status and previous exposure were significant determinants of dust exposure and should be evaluated in future analyses of the relationship between health outcomes and dust exposure in this industry.

Modelling and prediction of weekly incidence of influenza A specimens in England and Wales.

We propose a rather simple model, which fits well the weekly human influenza incidence data from England and Wales. A standard way to analyse seasonally varying time-series is to decompose them into different components. The residuals obtained after eliminating these components often do not reveal time dependency and are normally distributed. We suggest that conclusions should not be drawn only on the basis of residuals and that one should consider the analysis of squared residuals. We show that squared residuals can reveal the presence of the remaining seasonal variation, which is not exhibited by the analysis of residuals, and that the modelling of such seasonal variations undoubtedly improves model fit.