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Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer's disease
Get PDFPsychosis (delusions or hallucinations) in Alzheimer’s disease (AD + P) occurs in up to 50% of individuals and is associated with significantly worse clinical outcomes. Atypical antipsychotics, first developed for schizophrenia, are commonly used in AD + P, suggesting shared mechanisms. Despite this implication, little empirical research has been conducted to examine whether there are mechanistic similarities between AD + P and schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with AD + P. Schizophrenia PRS was calculated using Psychiatric Genomics Consortium data at ten GWAS p value thresholds (PT) in 3111 AD cases from 11 cohort studies characterized for psychosis using validated, standardized tools. Association between PRS and AD + P status was tested by logistic regression in each cohort individually and the results meta-analyzed. The schizophrenia PRS was associated with AD + P at an optimum PT of 0.01. The strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.18-fold increased risk (95% CI: 1.06–1.3; p = 0.001). These new findings point towards psychosis in AD—and particularly delusions—sharing some genetic liability with schizophrenia and support a transdiagnostic view of psychotic symptoms across the lifespan.publishedVersio
Gender differences in association between uric acid and all-cause mortality in patients with chronic heart failure
Get PDFBACKGROUND:
Elevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease. The purpose of the study was to investigate if SUA was an independent predictor of 5-year all-cause mortality in a propensity score matched cohort of chronic heart failure (HF) outpatients. Furthermore, to assess whether gender or renal function modified the effect of SUA.
METHODS:
Patients (n = 4684) from the Norwegian Heart Failure Registry with baseline SUA were included in the study. Individuals in the highest gender-specific SUA quartile were propensity score matched 1:1 with patients in the lowest three SUA quartiles. The propensity score matching procedure created 928 pairs of patients (73.4% males, mean age 71.4 ± 11.5 years) with comparable baseline characteristics. Kaplan Meier and Cox regression analyses were used to investigate the independent effect of SUA on all-cause mortality.
RESULTS:
SUA in the highest quartile was an independent predictor of all-cause mortality in HF outpatients (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.03-1.37, p-value 0.021). Gender was found to interact the relationship between SUA and all-cause mortality (p-value for interaction 0.007). High SUA was an independent predictor of all-cause mortality in women (HR 1.65, 95% CI 1.24-2.20, p-value 0.001), but not in men (HR 1.06, 95% CI 0.89-1.25, p-value 0.527). Renal function did not influence the relationship between SUA and all-cause mortality (p-value for interaction 0.539).
CONCLUSIONS:
High SUA was independently associated with inferior 5-year survival in Norwegian HF outpatients. The finding was modified by gender and high SUA was only an independent predictor of 5-year all-cause mortality in women, not in men.The first author is a research fellow funded by the South-Eastern Norway Regional Health Authority.publishedVersio
Exploring the trajectories of quality of life and its covariates in nursing home residents: A longitudinal study
Get PDFBackground: There is no cure for dementia and appropriate care should be offered to improve or maintain quality of life for those living with dementia. Objectives: To identify groups of residents following similar trajectories of quality of life after nursing home admission, to examine which resident, staff, and organizational characteristics at baseline differ between the identified groups, and to assess the associations between the trend in quality of life and the same characteristics measured at baseline and over the study period. Design: A prospective, observational, longitudinal cohort design over 30 months. Setting: Nursing homes in Norway. Participants: Residents admitted to nursing homes. Measurements: Resident data on quality of life, dementia, pain, activities of daily living, physical health, neuropsychiatric symptoms, medication, and demographic characteristics were obtained by interviews. Unit characteristics and the staff data on person-centered care, psychosocial factors, and job satisfaction were obtained by questionnaires and interviews. The physical environment of the unit was assessed by structured observation. Results: 694 residents admitted to a nursing home and 1161 staff from 175 nursing home units participated. Three resident groups following similar trajectories in quality of life were identified by growth mixture model; good quality of life (53.6%), moderate quality of life (32.9%), and poor quality of life (13.4%). All groups’ quality of life decreased over time. More pain, more severe dementia, and more affective symptoms at baseline were associated with belonging to the poor quality of life group. Overall decline in quality of life was associated with more severe dementia, more pain, poorer function in activities of daily living, more severe neuropsychiatric symptoms among residents, and poorer job satisfaction among staff. Conclusion: Reducing pain, reducing NPS, improving activities of daily living for the residents, and improving the staff’s job satisfaction may be factors of importance to improve the residents’ quality of life.The REDIC-NH study was administrated by the Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, and was initiated by the Norwegian Health Directorate, which also provided funding for the data collection. The first author’s Ph. D. study was funded by the Research Council of Norway.publishedVersio
Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK
Get PDFBackground:
Inflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation.
Methods:
Osteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42 months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200 μg/day) and coenzyme Q10 (200 mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates.
Results:
Significantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences.
Conclusion:
In this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group .
Trial registration:
The intervention study was registered at Clinicaltrials.gov, and has the identifier NCT01443780 and registered on 09/30/2011.Part of the analysis costs was supported by grants from Pharma Nord Aps, Denmark, the County Council of Östergötland, Linköping University. The funding organizations had no role in the design, management, analysis, or interpretation of the data, nor in the preparation, review or approval of the manuscript. No economic compensation was distributed.publishedVersio
A longitudinal study of cannabis use increasing the use of asthma medication in young Norwegian adults
Get PDFBACKGROUND:
A small number of studies have shown that the use of cannabis increases the risk of bronchial asthma. There is, however, a paucity of longitudinal studies which are able to control for known risk factors of bronchial asthma.
METHODS:
Survey data from a population-based longitudinal study encompassing 2602 young adults followed for 13 years were coupled with individual prescription data on asthma medication (β2-adrenergic receptor agonists and glucocorticoids for inhalation) from the Norwegian national prescription database, which covers the entire Norwegian population. Current cannabis use, gender, age, years of education, body mass index (BMI; kg/m2) and current smoking were measured.
RESULTS:
Prescription of asthma medication was associated with female gender, self-reported earlier asthma and allergies, daily tobacco smoking and current cannabis use. In a model adjusting for gender, age, years of education, BMI, earlier self-reported asthma and allergies and current tobacco smoking the odds ratio for a current cannabis user to fill prescriptions for asthma medication was 1.71 (95% CI: 1.06-2.77; p = 0.028).
CONCLUSIONS:
This suggests that cannabis is a risk factor for bronchial asthma or use of asthma medication even when known risk factors are taken into consideration. Intake of cannabis through smoking should be avoided in persons at risk.The data collection was funded by several grants from the Research Council of Norway. The funders had no role in the design of the study and collection, analysis, interpretation of the data, or decision to submit results.publishedVersio
A community-based intervention to increase participation in cervical cancer screening among immigrants in Norway
Get PDFBACKGROUND:
The attendance to cervical cancer screening is low among immigrants in many high-income countries. Although several interventions have been experimentally tested,implementation remains a challenge. Several factors are an impediment, including the lack of methodological descriptions of the development and implementation of such interventions. In this paper,we present in detail the development, methodological challenges and practical implementation of a community based intervention aimed to increase the participation of immigrant women in cervical cancer screening in Norway.
METHODS:
This study was initially designed as a cluster randomized trial to be carried out in four geographical areas near Oslo between Feb-October 2017. Participants were immigrant women aged 25-69 years from Pakistan and Somalia. This paper describes the theoretical background for the development of the intervention,followed by challenges,the changes in the original design and solutions adopted related to the study design,recruitment and implementation of the intervention. The intervention was developed based on two theoretical frameworks, the Ecological and the Heron's six categories intervention framework. An oral 20-25 min presentation in the language of participants encompassing topics of cervical cancer and screening was given according to the needs detected in focus groups conducted at the beginning of the study,followed by an opportunity to raise questions and answering a short questionnaire.
RESULTS:
Contrary to the initial study design, this had to be converted into a non-randomised trial due to the difficulties associated with randomization of immigrant families who are finely scattered in heavily populated towns and a high risk of contamination. We therefore adopted a pragmatic approach and recruited women in the intervention areas through a variety of channels and institutions. Neighboring areas were considered to be non-randomised controls. Female researchers with Pakistani and Somali background invited as many women as possible in the intervention areas. Among the women who were invited to participate,42% of the Pakistani and 78% of Somali attended the meetings.
CONCLUSION:
Despite the careful development of a culturally adapted health intervention in collaboration with the community; randomization and recruitment of immigrants for community trials remains challenging. Nevertheless, sharing strategies to overcome specific challenges related to promoting health interventions for immigrants, can be of potential help to scale-up interventions and for building new research projects.publishedVersio
Sexual function in people with epilepsy: Similarities and differences with the general population
Get PDFOBJECTIVE:
The potential impact of epilepsy on sexual function is important for patient welfare, but often neglected. This study explored the occurrences of different sexual problems in patients with both well-controlled and mostly refractory epilepsy, and compared these with equivalent information from the general population.
METHODS:
Between 2015 and 2017, a total of 221 adult inpatients and outpatients, mostly with intractable epilepsy, at the National Centre for Epilepsy in Norway, and 78 outpatients with well-controlled epilepsy at Lillehammer hospital participated in a questionnaire survey on sexual function. Information on the individual patient's epilepsy was collected. The results were compared with equivalent data on sexual function from 1671 adult Norwegians in the general population.
RESULTS:
Patients with epilepsy reported a significantly higher frequency of problems with orgasm, dyspareunia, erectile dysfunction, and feelings of sexual deviance. However, reduced sexual desire, premature ejaculation/climax, and vaginal dryness occurred at similar frequencies in the general population. After controlling for gender, we found no significant association between sexual problems and seizure control or use of enzyme-inducing antiepileptic drugs. In both genders, feelings of sexual deviance were associated with lower quality of life. Fewer patients with epilepsy were satisfied with their sex lives. The perception of sex as an important part of daily life was similar among women with epilepsy and women from the general population, whereas significantly fewer men with epilepsy than men in the general population reported that sex was an important part of their daily lives. Women with mostly refractory epilepsy reported asking for help with their sexual problems significantly more often than women in the other groups.
SIGNIFICANCE:
Some sexual problems occur significantly more often in patients with epilepsy than in the general population and feelings of sexual deviancy occur more frequently. No epilepsy-related factors could be identified as specific predictors.publishedVersio
Assessment of dietary intake of fluoride and maximum limits of fluoride in food supplements
Get PDFAbstract
The Norwegian Scientific Committee for Food and Environment (Vitenskapskomiteen for mat og miljø, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet, NFSA), evaluated the intake of fluoride in the diet, together with intake of fluoride from dental hygiene and caries prevention products. VKM has also evaluated suggested maximum limits for fluoride in food supplements at 0.5, 1, 5 and 7 mg/day in relation to established tolerable upper intake levels (ULs). The former maximum limit for fluoride of 0.5 mg/day in food supplements was repealed 30 May 2017. Fluorine is a gaseous halogen which occurs naturally only in anionic form as fluoride (F- ). Fluorides are ubiquitous in air, water and the lithosphere. Fluoride is found naturally in all water sources. The highest levels are found in groundwater. Surface water usually has lower concentrations of fluoride than groundwater, most often under 0.5 mg/L. Major dietary fluoride sources are water and tea. An important non-dietary source is dental hygiene products such as toothpaste and tablets for caries prevention. There is no fluoridation of drinking water or salt in Norway. Fluoride is not an essential nutrient. Caries is not a fluoride deficiency disease. However, because of the beneficial effects for caries prevention, an adequate intake (AI) of 0.05 mg per kg body weight per day has been set for fluoride by the European Food Safety Authority (EFSA). Readily soluble fluorides (sodium- and potassium fluoride) are rapidly and almost completely absorbed by passive diffusion in the stomach and the small intestine. Absorption is influenced by acidity and concomitant food intake. Absorbed fluoride is rapidly distributed in blood plasma, but is retained only in calcified tissues, that are bones and teeth. Consequently, 99% of the total fluoride content of the body is found in bone and teeth. Absorbed fluoride which is not deposited in calcified tissues is excreted almost exclusively via the kidneys. Whereas skeletal bone and dentine accumulate fluoride throughout life, enamel of teeth incorporate fluoride only at the time of tooth formation. Fluoride substitutes for hydroxyl groups in the apatite, increasing the resistance to caries. In permanent teeth enamel maturation is completed at the age of seven to eight years, except in the third molars. Posteruptive fluoride uptake by enamel occurs only in the outer layer and depends on local oral fluoride levels. A linear relationship between fluoride exposure and caries resistance has been demonstrated. Over the years, the view has shifted from systemic fluoride being most effective for caries prevention to local oral exposure being most important. Acute toxic effects may be provoked by fluoride, and deaths have been reported after intake of very large doses from fluoride tablets. The main adverse outcomes from intake of excess doses of fluoride over time, are enamel fluorosis in children up to eight years of age, and bone fluorosis in older children and adults. Dental fluorosis causing mottled teeth is largely a cosmetic effect, whereas bone fluorosis causes stiff joints and a greater tendency to fractures. Tolerable upper intake levels (UL) for fluoride have been set by the American Institute of Medicine (IOM) and by the European Food Safety Authority (EFSA). In this report, we relate estimated fluoride intakes to the upper level set by EFSA. Intakes of the main dietary fluoride sources, water and tea, in different age groups were obtained from Norwegian dietary surveys. High fluoride intakes were estimated by applying the 95 percentile of fluoride concentrations in water obtained from 2001 fluoride analyses from Norwegian waterworks in the period between 2010 and 2018 and in tea obtained from a Polish study to the daily volume consumed. Fluoride intakes from recommended use of dental hygiene and caries prevention products were then added, plus a small fixed value for undescribed sources. The estimated 95 percentile fluoride exposure calculated this way was compared to the upper level, and scenarios with additional fluoride supplementation of 0.5, 1, 5 or 7 mg/day were developed. The estimated 95-percentile of fluoride exposure from water, tea and dental hygiene products alone (before fluoride from the suggested food supplement doses at 0.5, 1, and 7 mg/day were added) was found to exceed the upper level for 2-year old children and for adults. VKM concludes that all the suggested food supplement doses considered will cause the tolerable upper intake level to be exceeded in all age groups, except for the supplement doses of 0.5 in 9- and 13-year olds and 1 mg/day in 9 year olds. VKM emphasises that the current assessment of maximum limits for fluoride in food supplements is merely based on published reports concerning upper levels from the IOM (USA, 2001), Scientific Committee on Food (EU, 2003), Expert Group on Vitamins and Minerals (UK, 2003) and Nordic Nutrition Recommendations (Nordic Countries, 2012). VKM has not conducted any review of the literature for the current opinion, as this was outside the scope of the terms of reference from the NFSA.publishedVersio
Cost analysis of day care centres in Norway
Get PDFBackground: Day care services aim to offer meaningful activities and a safe environment for the attendees and a respite for family caregivers while being cost effective. This study compares the use of formal and informal care in users and non-users of day care centres designed for persons with dementia. Method: Users of day care designed for dementia (DC group) and non-users (NDC group) were followed over a period of 24 months or until nursing home admission (NHA) respectively death. Demographic and clinical characteristics were collected at baseline and after 12 and 24 months. The use of care was recorded by Resource Utilization in Dementia (RUD). Results: A total of 257 persons with dementia participated in the study, 181 in the DC group and 76 in the NDC group. Users of day care centres cause higher costs due to the expenses for day care, while neither the use of home nursing, secondary care, informal care nor the time until NHA did show any differences between users and non-users. The overall costs were higher in the DC group at baseline and after 12 months, but this difference was no longer present at the end of the two-year study period. Conclusion: Our results indicate no potential cost-saving effect of day care designed for people with dementia, as the use of day care did neither result in a reduced use of care nor in a delay of NHA. Future research should balance the non-monetary benefits of day care against its costs for a full cost-effectiveness analysis, most favourable in a RCT-design.publishedVersio
Relationship quality and sense of coherence in dementia: Results of a European cohort study
Get PDFObjective
Quality of life of people with dementia and their family carers is strongly influenced by interpersonal issues and personal resources. In this context, relationship quality (RQ) and sense of coherence (SOC) potentially protect and promote health. We aimed to identify what influences RQ in dyads of people with dementia and their carers and to examine differences in their perspectives.
Methods
Cross‐sectional data were used from the Actifcare cohort study of 451 community‐dwelling people with dementia and their primary carers in eight European countries. Comprehensive assessments included the Positive Affect Index (RQ) and the Orientation to Life Questionnaire (SOC).
Results
Regression analyses revealed that RQ as perceived by people with dementia was associated with carer education, stress, and spouse caregiving. RQ as perceived by carers was associated with carer stress, depression, being a spouse, social support, reported neuropsychiatric symptoms of dementia, and carer SOC. Neuropsychiatric symptoms and carer stress contributed to discrepancies in RQ ratings within the dyad. The only factor associated with both individual RQ ratings and discrepancies was carer stress (negative feelings subscore). No significant differences in the overall perception of RQ were evident between spouses and adult children carers, but RQ determinants differed between the two.
Conclusions
In this European sample, carer SOC was associated with carer‐reported RQ. RQ determinants differed according to the perspective considered (person with dementia or carer) and carer subgroup. A deeper understanding of RQ and its determinants will help to tailor interventions that address these distinct perspectives and potentially improve dementia outcomes.acceptedVersio