Forskningsartikler

Abstract

Purpose: Zuclopenthixol is an antipsychotic available as oral and long-acting injectable (LAI) formulations. The aim of this study was to investigate the effect of age on zuclopenthixol exposure during oral and LAI administrations without and with adjustment for CYP2D6 genotype.

Methods: Data on serum concentrations of zuclopenthixol and CYP2D6 genotype (available for 28.2% of the population) from patients using oral or LAI zuclopenthixol were included retrospectively from a therapeutic drug monitoring service during the period 2005-2019. As a measure of exposure, dose-adjusted serum concentration (C/D ratio) was used. Based on age, patients were grouped to older (≥ 65 years) or younger (18-64 years). Linear mixed model analyses without and with adjustment for CYP2D6 genotype were used.

Results: Serum concentrations of zuclopenthixol from 1145 (14.1% older) and 899 patients (24.6% older) in the LAI and oral groups were included, respectively. Compared with younger patients, older patients had a higher C/D ratio of zuclopenthixol for LAI (+ 25-33%, p < 0.001) and oral formulation (+ 25-29%, p ≤ 0.003) without and with adjustment for CYP2D6 genotype. The doses were lower in older versus younger patients (oral: – 30%; LAI: – 20%; p < 0.001). Compared with the younger LAI users without reduced CYP2D6 function, a higher C/D ratio was observed in the older LAI users with reduced CYP2D6 function (+ 104%, p < 0.001).

Conclusion: The present study showed that zuclopenthixol exposure increases in older patients and that the older LAI users with reduced CYP2D6 function are exposed to high serum concentrations. Also, the present study showed that similar dose reductions are required for oral and LAI users.

Marit Tveito, Robert Løvsletten Smith, Espen Molden, Gudrun Høiseth

Purpose: Paliperidone palmitate is an antipsychotic medication available as long-acting injectable (LAI) formulations. The aim of this study was to investigate the effect of age and gender on paliperidone exposure after administration of LAI formulations.

Methods: Data on serum concentrations of paliperidone from patients using LAI during were included retrospectively from a therapeutic drug monitoring (TDM) service. Information about dose was obtained from the requisition forms. As a measure of exposure, daily dose-adjusted serum concentration (C/D ratio) was used. Based on initial analysis of C/D ratios versus age, a breaking point close to 50 years was observed, thus deciding the grouping of patients as older (≥50 years) or younger (15-49 years). Linear mixed model analyses, allowing multiple measurements per patients, were used.

Results: In total, 1223 patients were included, whereof 1158 patients used paliperidone LAI in once-monthly intervals. In these patients (27.9% older), older patients had significantly higher paliperidone C/D ratio than younger patients (+20%, p<0.001). Compared to males, females had higher C/D ratio (+14%; p<0.001). Subsequently, older female users of once-monthly LAI intervals had 41% higher paliperidone C/D ratios compared to younger males (15.0 vs. 21.2 nM/mg; p<0.001). Compared to females aged 21-30 years, females with high age (≥70 years) had at least 105% higher paliperidone C/D ratio (p<0.001).

Conclusion: The present study shows that older age and female gender are associated with higher paliperidone exposure than younger age and males, respectively. Particularly, older female patients (>50 years) are likely exposed to high concentration and cautious dosing in this subgroup is required.

Marit Tveito, Gudrun Høiseth, Tore Haslemo, Espen Molden, Robert Løvsletten Smith

Background: Engaging aged residential care (ARC) residents with physical activity (PA) may be a useful strategy to decelerate dependence and disability. It is unclear what volume, intensity and patterns of PA ARC residents participate in. This review aims to synthesize the literature to quantify the volume, intensity and pattern of PA that ARC residents participate in across differing care levels (e.g. low, intermediate, high, mixed), and make recommendations for future research.

Methods: 30 studies of 48,760 yielded were reviewed using systematic review strategies.

Results: Questionnaires and technological tools were used to assess PA, with accelerometers employed in 70% of studies. Overall, studies reported low volumes and intensities of PA across all care levels, and suggested limited variation in patterns of PA (e.g. little day-to-day variation in total PA). There was limited inclusion of people with cognitive impairment, potentially causing representativeness bias. Findings were limited by lack of consistency in methodological approaches and PA outcomes.

Discussion: Based on findings and limitations of current research, we recommend that total volume or low-light intensity PA are more useful interventional outcomes than higher-intensity PA. Researchers also need to consider which methodology and PA outcomes are most useful to quantify PA in ARC residents.

Ríona Mc Ardle, Karen Sverdrup, Silvia Del Din, Sue Lord, Ngaire Kerse, Lynn Rochester, Lynne Taylor

Background: Spatial navigation is a prodromal dementia marker. Exercise used alongside virtual reality improves many cognitive functions, but effects on spatial navigation are still unclear.
Objective: To investigate the effect of virtual reality-based physical exercise with 2D exergames on spatial navigation in institutionalized non-robust older persons.
Method: A total of 14 older persons (aged ≧ 60) were randomly allocated to the exergame (EG) and active control (ACG) groups. EG performed exercises with 2D exergames, while the ACG used the same movements as the EG, but without the use of virtual reality. Spatial navigation was assessed through the Floor Maze Test, where the immediate maze time (IMT) and delayed maze time (DMT) were recorded.
Results: Spatial navigation was enhanced in EG participants compared to ACG individuals. A significant (p = 0.01) IMT reduction between groups was observed, while DMT time without prior planning was significantly different at the significance threshold (p = 0.07).
Conclusions: Virtual reality-based exercise improves the spatial navigation of institutionalized non-robust older persons. This study should be replicated to confirm the findings reported herein.

Luciana Mendes Oliveira, Eric Hudson Evangelista e Souza, Mariana Rocha Alves, Lara S. F. Carneiro, Daniel Ferreira Fagundes, Alfredo Maurício Batista de Paula, Knut Engedal, Osvaldo J. M. Nascimento and Renato Sobral Monteiro-Junior

Comment.
The Lancet. Public Health Volume 6, Issue 2, February 2021, Pages e85-e86

Geir Selbæk

Age-related muscle wasting can compromise functional abilities of the elderly. Protein intake stimulates muscle protein synthesis; however, ageing muscle is more resistant to stimuli. This double-blinded, randomized, controlled trial is one of the first registered studies to evaluate the effects of a supplement of marine protein hydrolysate (MPH) on measures of physical function and strength. Eighty-six older adults received nutritional supplements containing 3 g of MPH or a placebo for up to 12 months. Short Physical Performance Battery (SPPB), grip strength and gait speed were measured, and dietary intake was registered at baseline, 6 months, and 12 months. No difference was found between the intervention and control groups in mean change in SPPB (independent sample t-test, p = 0.41) or regarding time trend in SPPB, grip strength, or gait speed (linear mixed model). The participants in our study were well functioning, causing a ceiling effect in SPPB. Further, they had sufficient protein intake and were physically active. Differences in physical function between those completing the intervention and the dropouts might also have created bias in the results. We recommend that future studies of MPH be carried out on a more frail or malnourished population.

Linda Kornstad Nygård, Ingunn Mundal , Lisbeth Dahl, Jūratė Šaltytė Benth, Anne Marie Mork Rokstad

Background: Spouses of people with young-onset frontotemporal dementia (YO-FTD) (age 65 years or younger) encounter special challenges. The diagnosis is scarcely known; the early onset is unexpected; and the disease is characterized by symptoms varying from those of other types of dementia. Caring implies increasing hardships, which can be difficult to communicate to others when applying for support. Metaphors create and communicate meaning and are increasingly used in health care and health interventions as ways to better understand the situation.
Aim: To examine the experiences of spouses of people with YO-FTD and their needs for care and support as expressed through metaphors in narratives of their experiences during the development of the dementia.
Methods: Qualitative interviews with 16 informants (ten women, six men) were conducted in 2014/2015. They were recruited from seven memory clinics, one municipality dementia team, and a nursing home. Steger’s three-step method for analyzing metaphors was applied.
Findings: The core metaphors cover experiences of the dementia and the transformation of the spouse, changed roles and relationships between spouses, the transformation of the self, a radical turn of existential life, and relationships with others. Metaphors are words and phrases used to talk about complicated, contradictory, shameful, and/or normatively difficult feelings and reactions as caring spouses. The open themes and, at the same time, provide verbal shields and defences. Metaphors are especially effective for expressing the strength of the reactions in caring as emotional work and are tools for mastering emotions and challenges in life.
Conclusion: Metaphors give insights into the significant experiences of spouses of partners with YO-FTD and offer personnel in health services a better understanding of their needs for tailored support and help.

Kirsten Thorsen og Aud Johannessen

Background:  Having accurate, up-to-date information on the epidemiology of mild cognitive impairment (MCI) and dementia is imperative.
Objective:  To determine the prevalence of MCI and dementia in Norway using data from a large population-based study.
Methods:  All people 70 + years of age, n = 19,403, in the fourth wave of the Trøndelag Health Study (HUNT4) were invited to participate in the study HUNT4 70 + . Trained health personnel assessed participants using cognitive tests at a field station, at homes, or at their nursing home. Interviewers also completed a structured carer questionnaire in regard to participants suspected of having dementia. Clinical experts made diagnoses according to DSM-5 criteria. We calculated prevalence weighing the data to ensure population representativeness.
Results:  A total of 9,930 (51.1%) of the possible 19,403 people participated, and 9,663 of these had sufficient information for analysis. Standardized prevalence of dementia and MCI was 14.6% (95% confidence interval (CI) 13.9-15.4) and 35.3% (95% CI 34.3-36.4), respectively. Dementia was more prevalent in women and MCI more prevalent in men. The most prevalent dementia subtype was Alzheimer’s disease (57%). By adding data collected from a study of persons ≤70 years in the same region, we estimate that there are 101,118 persons with dementia in Norway in 2020, and this is projected to increase to 236,789 and 380,134 in 2050 and 2100, respectively.
Conclusion:  We found a higher prevalence of dementia and MCI than most previous studies. The present prevalence and future projections are vital for preparing for future challenges to the healthcare system and the entire society.

Linda Gjøra, Bjørn Heine Strand, Sverre Bergh, Tom Borza, Anne Brækhus, Knut Engedal, Aud Johannessen, Marte Kvello-Alme, Steinar Krokstad, Gill Livingston, Fiona E Matthews, Christian Myrstad, Håvard Skjellegrind, Pernille Thingstad, Eivind Aakhus, Stina Aam, Geir Selbæk.

Biblioteket skaffer artikkelen.

Objectives: To explore factors from the acute phase, and after three and 12 months, associated with level of self-reported physical activity 12 months after a minor ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤ 3 in persons 70 years or younger.
Materials and method: In this longitudinal cohort study patients were recruited consecutively from two stroke units. Activity level were measured with three sets of questions addressing the average number of frequency (times exercising each week), the average intensity, and duration (the average time), and a sum score was constructed. The association between physical activity 12 months after stroke and sociodemographic factors, NIHSS, body mass index, balance, and neuropsychiatric symptoms were explored using multiple linear regression.
Results: This study included 101 patients, with mean age (SD) 55.5 (11.4) years, NIHSS median (Q1, Q3) 0.0 (0.0, 1.0), and 20 % were female. Multiple linear regression analyses showed sick leave status at stroke onset, balance at three and 12 months, and anxiety, depression, apathy, and fatigue at 12 months to be factors associated with physical activity at 12 months after stroke.
Conclusion: We found that pre-stroke sick leave, post-stroke balance, and neuropsychiatric symptoms were associated with the level of physical activity one year after minor stroke. This might be of importance when giving information about physical activity and deciding about post-stroke follow-up.

Charlotta Hamre, Brynjar Fure, Jorunn Lægdheim Helbostad, Torgeir Bruun Wyller, Hege Ihle-Hansen, Georgios Vlachos, Marie Helene Ursin, Gro Gujord Tangen.