Managing Pain and Psychosis Symptoms in Nursing Home Patients: Results from a Cluster-Randomized Controlled Trial (COSMOS)

Objectives In nursing homes (NHs), 30% to 60% of patients experience daily pain and >80% have dementia. This can lead to neuropsychiatric symptoms, including psychosis symptoms such as delusion. We investigated if there was a relationship between pain and psychosis symptoms over time. We also aimed to investigate the effect of a multicomponent intervention (COSMOS) on pain, psychosis symptoms, and analgesic prescription. Design COSMOS is a cluster-randomized, single blinded, controlled trial. Each NH unit was defined as a cluster and randomized to either the COSMOS intervention or care as usual. The COSMOS intervention is a multicomponent intervention, consisting of staff training in communication, pain treatment, medication review, organization of activities, and safety. The intervention lasted for 4 months with a follow-up at month 9. Setting and Participants Sixty-seven units from 33 Norwegian NHs in 8 municipalities. The study included 723 patients aged ≥65 years, residing at the NH ≥2 weeks before inclusion. Patients with a life expectancy <6 months were excluded. Measures Pain was measured using the Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale. Psychosis symptoms were measured using the Neuropsychiatric Inventory–NH version. Measurements were performed at baseline, and months 4 and 9. Results Multilevel Mixed-Effect statistical analysis found that psychosis symptoms as a group (odds ratio [OR] 2.03, P = .009), and delusion (OR 2.12, P = .007) were associated with pain over time. No significant intervention effect on psychosis symptoms was observed. Compared with the control group, people with dementia in the intervention group experienced less musculoskeletal pain (β: −0.47, P = .047). Analgesic prescription was not affected by the intervention. Conclusion and Implications Pain is associated with psychosis symptoms, and pain assessment should be done when making treatment decisions on psychosis symptoms in NH patients. The COSMOS intervention improved musculoskeletal pain in people with dementia, but not psychosis symptoms, and there is need for further studies on treatment of psychosis symptoms in NH patients.publishedVersio

Less is more: The impact of deprescribing psychotropic drugs on behavioral and psychological symptoms and daily functioning in nursing home patients. Results from the Cluster-Randomized Controlled COSMOS Trial

Objective: To investigate the impact of medication reviews using collegial mentoring and systematic clinical evaluation on psychotropic prescriptions, behavioral and psychological symptoms of dementia (BPSD), and activities of daily living (ADL). Design: Four-month multicenter, multicomponent, cluster-randomized, single-blinded controlled trial. Setting: Thirty-three Norwegian nursing homes including 67 nursing home wards (clusters). Participants: A total of 723 enrolled patients, of which 428 participated in the study; 217 were randomized to the intervention and 211 to care as usual (control). Intervention: The COSMOS intervention consisted of Communication, Systematic pain management, Medication reviews, Organization of activities, and Safety. During medication review, the nursing home physician evaluated treatment with colleagues systematically using the results from validated clinical assessments. Measurements: Mean changes from baseline to month 4 in the number of prescribed psychotropic drugs (antipsychotics, anxiolytics, hypnotics or sedatives, antidepressants, and antidementia drugs); Neuropsychiatric Inventory Nursing Home Version (NPI-NH) and Cornell Scale of Depression in Dementia (CSDD); Lawton and Brody's Physical Self Maintenance Scale (PSMS). Results: Compared to control, the mean change in prescribed psychotropic drugs was reduced both in total and regular number, while mean changes in NPI-NH and CSDD scores did not differ between the groups. Mean change in PSMS showed improvement in the intervention group, and deterioration in the control group. Conclusion: Medication reviews using collegial mentoring and systematic clinical evaluation led to safe deprescribing, as the reductions in psychotropic drug use did not negatively affect BPSD, while ADL improved.publishedVersio

Factors associated with formal and informal resource utilization in nursing home patients with and without dementia: cross-sectional analyses from the COSMOS trial

Objectives: To investigate the association between clinical, demographic, and organizational factors and formal (health professionals) and informal (relatives) resource utilization in nursing home patients with and without dementia. Methods: Baseline data from the multicomponent cluster randomized control COSMOS trial including 33 Norwegian nursing homes and 723 residents with and without dementia. Nursing home staff (n = 117) participated as proxy raters to approximate formal and informal resource use in daily care. Measurements: The primary outcome was the Resource Utilization in Dementia - Formal Care scale to assess formal and informal care time in hours/month regarding basic activities of daily living (ADL), instrumental ADL, and supervision. Secondary outcomes were hours/week spent on formal and informal leisure activities. Behavioral and psychological symptoms in dementia (BPSD) were assessed by the Neuropsychiatric Inventory-Nursing Home version, physical function by the Physical Self-Maintenance Scale, and psychotropic drug use by the Anatomical Therapeutic Chemical classification system. Organizational factors were ward size and staff ratio. Results: Generalized linear mixed-effect models and two-part modelling revealed an association between increased formal care time and poorer physical function, higher agitation and psychotropic drug use and lower cognitive function (all p < .05). Enhanced formal leisure time was related to better ADL function (p < .05) and smaller wards (p < .05). The family related leisure time was associated with agitation, decline in ADL function, smaller wards, and better staffing ratio (all p < .05). Married patients received more informal direct care (p < .05) and leisure time (p < .05) compared to unmarried/widowed. Conclusion: For nursing home staff, higher agitation and psychotropic drug use, and lower cognitive function, is associated with more direct care time, whereas leisure time activities are less prioritized in people with lower physical function. Informal caregivers’ engagement is encouraged by smaller nursing homes and better staff ratio. Therefore, we recommend stakeholders and healthcare professionals to consider these clinical and organizational factors to optimize treatment and leisure time activities in nursing home patients with various needs.publishedVersio

Impact of COVID-19 restrictions on behavioural and psychological symptoms in home-dwelling people with dementia: A prospective cohort study (PAN.DEM)

Objectives To investigate the impact of the COVID-19 restrictions on behavioural and psychological symptoms of dementia (BPSD). Design Prospective cohort study (PAN.DEM) nested within the halted parent trial ([email protected]). Setting Households in Norway immediate before and 6–9 weeks into the COVID-19 restrictions. Participants 104 dyads (persons with mild to moderate dementia aged ≥65 and their informal carers) completed both prepandemic and pandemic assessments, among 237 in the parent trial. Mini-Mental Status Examination score 15–26 or Functional Assessment Staging score 3–7 covered dementia severity. Main outcome measures Neuropsychiatric Inventory (NPI-12) total (range 0–144), psychosis (range 0–24), hyperactive behaviour (range 0–60) and mood subsyndrome (range 0–48) scores; Cornell Scale for Depression in Dementia (CSDD) total score (range 0–38). Results We found an overall increase in BPSD by NPI-12 total score comparing prepandemic to pandemic levels (median 16 IQR (4.5–29) to 20 (7–32.5), p=0.03) over a mean of 86 days (SD 19). NPI-12 total score worsened in 57 (55%) of people with dementia and was associated with postponed or averted contacts with healthcare professionals (logistic regression, OR 3.96, 95% CI 1.05 to 14.95). Psychosis subsyndrome levels increased (0 (0–3) to 0.5 (0–6), p=0.01) in 37 (36%) persons; this worsening was associated with partial insight (9.57, 1.14 to 80.71) and reduced informal carer contact (4.45, 1.01 to 19.71). Moreover, depressive symptoms increased as assessed by CSDD total score (5 (3–9) to 7 (4–12), p=0.01) and worsened for 56 (54%), which was inversely associated with psychotropic drugs on-demand (0.16, 0.03 to 0.75). Conclusions BPSD worsened during the first months of the COVID-19 restrictions, most pronounced for psychosis and depression. These BPSD exacerbations have implications for pandemic policies, emphasising that restrictions must balance COVID-19 morbidity and mortality against dementia deterioration.publishedVersio

Long-term cardiovascular mortality in women with twin pregnancies by lifetime reproductive history

Background: Women with one lifetime singleton pregnancy have increased risk of cardiovascular disease (CVD) mortality compared with women who continue reproduction particularly if the pregnancy had complications. Women with twins have higher risk of pregnancy complications, but CVD mortality risk in women with twin pregnancies has not been fully described. Objectives: We estimated risk of long-term CVD mortality in women with naturally conceived twins compared to women with singleton pregnancies, accounting for lifetime number of pregnancies and pregnancy complications. Methods: Using linked data from the Medical Birth Registry of Norway and the Norwegian Cause of Death Registry, we identified 974,892 women with first pregnancy registered between 1967 and 2013, followed to 2020. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for maternal CVD mortality were estimated by Cox regression for various reproductive history (exposure categories): (1) Only one twin pregnancy, (2) Only one singleton pregnancy, (3) Only two singleton pregnancies, (4) A first twin pregnancy and continued reproduction, (5) A first singleton pregnancy and twins in later reproduction and (6) Three singleton pregnancies (the referent group). Exposure categories were also stratified by pregnancy complications (pre-eclampsia, preterm delivery or perinatal loss). Results: Women with one lifetime pregnancy, twin or singleton, had increased risk of CVD mortality (adjusted hazard [HR] 1.72, 95% confidence interval [CI] 1.21, 2.43 and aHR 1.92, 95% CI 1.78, 2.07, respectively), compared with the referent of three singleton pregnancies. The hazard ratios for CVD mortality among women with one lifetime pregnancy with any complication were 2.36 (95% CI 1.49, 3.71) and 3.56 (95% CI 3.12, 4.06) for twins and singletons, respectively. Conclusions: Women with only one pregnancy, twin or singleton, had increased long-term CVD mortality, however highest in women with singletons. In addition, twin mothers who continued reproduction had similar CVD mortality compared to women with three singleton pregnancies.publishedVersio

Bayesian and frequentist computation with application to data from the Medical Birth Registry of Norway

In chapter 1, the field of statistics is discussed in general terms. Then, Bayes&rsquo; theorem is presented together with the posterior distribution. Finally, we consider maximum likelihood estimation and its relation to a two-step inference procedure. The thesis proceeds to introducing several numerical methods in chapter 2. One of the main methods is Hamiltonian Monte Carlo (HMC). In order to understand HMC, which is a type of Markov chain Monte Carlo (MCMC) algorithm, we first study some theory of Markov chains. Furthermore, MCMC and some examples of its well-known algorithms are encountered. As HMC is based on Hamiltonian dynamics (that originate from the field of physics), a short illustration of the dynamics is given. Furthermore, the system of differential equations used in HMC is discussed, as are several different numerical integration schemes and methods for developing them. A numerical integration scheme is a necessary part of the HMC algorithm. Paper 1 covers HMC and finding more efficient numerical integration schemes to be used in the algorithm. It is clear that there are situations where the MCMC algorithms perform poorly, especially with regards to time consumption. For certain latent variable models we should consider alternative numerical methods to MCMC. For these models, one could use integrated nested Laplace approximation (INLA). Although INLA has not been used in the model specification here, we are interested in some of the theory it applies. INLA is an efficient alternative for latent Gaussian models and uses some important properties of Gaussian fields (GFs) and Gaussian Markov random fields (GMRFs). From INLA, we here more specifically consider the relation between the computationally demanding covariance matrix and the sparse precision matrix. These two matrices are directly connected to GFs and GMRFs respectively, and we examine some the computational advantages that come with GMRFs compared to GFs. We use the template model builder (TMB) that uses automatic differentiation and Laplace approximation in the process of finding the maximum likelihood estimation of the parameters of the marginal likelihood. The combination in TMB gives the ability to handle complex latent variable models, and this is the methodology that is used for the spatial models in paper 2 and paper 3. In chapter 3 we look at the field of spatial statistics. This includes its uses and the different types of spatial data that we have. Spatial data are separated by what kind of location information that is available and what type of problem we want to model. Moreover, we discuss the stochastic partial differential equations (SPDE) approach. This is an approach that is able to link GFs and GMRFs using a triangulated grid. This grid, a weak solution to the SPDE and its use with spatial models are examined. To understand the SPDE approach we also consider the Mat&eacute;rn covariance function, which is the covariance function for certain GFs. The SPDE approach is essential for the results of paper 2 and paper 3. The spatial and spatio-temporal models are also explained and some additional results to paper 3 are presented. Finally, we look at health registry data, which is the type of data used in paper 2 and paper 3

Variation in use of Caesarean section in Norway: An application of spatio-temporal Gaussian random fields

Aims: Caesarean section (CS) is a medical intervention performed in Norway when a surgical delivery is considered more beneficial than a vaginal. Because deliveries with higher risk are centralized to larger hospitals, use of CS varies considerably between hospitals. We describe how the use of CS varies geographically by municipality. Since indications for CS should have little variation across the relatively homogenous population of Norway, we expect fair use of CS to be evenly distributed across the municipalities. Methods: Data from the Medical Birth Registry of Norway were used in our analyses (810,914 total deliveries, 133,746 CSs, 440 municipalities). We propose a spatial correlation model that takes the location into account to describe the variation in use of CS across the municipalities. The R packages R-INLA and TMB are used to estimate the yearly municipal CS rate and the spatial correlation between the municipalities. We also apply stratified models for different categories of delivering women (Robson groups). Estimated rates are displayed in maps and model parameters are shown in tables. Results: The CS rate varies substantially between the different municipalities. As expected, there was strong correlation between neighbouring municipalities. Similar results were found for different Robson groups. Conclusions: The substantial difference in CS use across municipalities in Norway is not likely to be due to specific medical reasons, but rather to hospitals’ different policies towards the use of CS. The policy to be either more or less restrictive to CS was not specific to any category of deliveries

Managing Pain and Psychosis Symptoms in Nursing Home Patients: Results from a Cluster-Randomized Controlled Trial (COSMOS)

Objectives In nursing homes (NHs), 30% to 60% of patients experience daily pain and >80% have dementia. This can lead to neuropsychiatric symptoms, including psychosis symptoms such as delusion. We investigated if there was a relationship between pain and psychosis symptoms over time. We also aimed to investigate the effect of a multicomponent intervention (COSMOS) on pain, psychosis symptoms, and analgesic prescription. Design COSMOS is a cluster-randomized, single blinded, controlled trial. Each NH unit was defined as a cluster and randomized to either the COSMOS intervention or care as usual. The COSMOS intervention is a multicomponent intervention, consisting of staff training in communication, pain treatment, medication review, organization of activities, and safety. The intervention lasted for 4 months with a follow-up at month 9. Setting and Participants Sixty-seven units from 33 Norwegian NHs in 8 municipalities. The study included 723 patients aged ≥65 years, residing at the NH ≥2 weeks before inclusion. Patients with a life expectancy <6 months were excluded. Measures Pain was measured using the Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale. Psychosis symptoms were measured using the Neuropsychiatric Inventory–NH version. Measurements were performed at baseline, and months 4 and 9. Results Multilevel Mixed-Effect statistical analysis found that psychosis symptoms as a group (odds ratio [OR] 2.03, P = .009), and delusion (OR 2.12, P = .007) were associated with pain over time. No significant intervention effect on psychosis symptoms was observed. Compared with the control group, people with dementia in the intervention group experienced less musculoskeletal pain (β: −0.47, P = .047). Analgesic prescription was not affected by the intervention. Conclusion and Implications Pain is associated with psychosis symptoms, and pain assessment should be done when making treatment decisions on psychosis symptoms in NH patients. The COSMOS intervention improved musculoskeletal pain in people with dementia, but not psychosis symptoms, and there is need for further studies on treatment of psychosis symptoms in NH patients

The impact of medication reviews by general practitioners on psychotropic drug use and behavioral and psychological symptoms in home-dwelling people with dementia: results from the multicomponent cluster randomized controlled [email protected] trial

Background There is limited knowledge regarding the process of deprescribing psychotropic drugs to people with dementia (PwD) conducted by general practitioners (GP). We investigated the impact of a multicomponent intervention, emphasizing medication reviews, on psychotropic drugs and behavioral and psychological symptoms (BPSD) in home-dwelling PwD and quantified change in patient-GP communication evaluated by their informal caregivers. Methods [email protected] is a stepped-wedge closed-cohort cluster randomized controlled trial for people with mild to moderate dementia aged ≥65 and their informal caregivers (dyads) in Norway. Complementary to health care as usual (control condition), municipal coordinators implemented the multicomponent LIVE intervention: Learning, Innovation, Volunteer support, and Empowerment (including medication review by the PwD’s regular GPs). Block-randomization was used to allocate dyads in three groups receiving the intervention sequentially in periods of 6 months duration. Prepandemic data from the first period is reported, resulting in a 1:2 intervention-to-control ratio. Primary outcome was change in psychotropic drug use. Secondary outcomes were changes in BPSD by Neuropsychiatric Inventory and Cornell Scale of Depression in Dementia and patient-GP communication by an adaption of the Clinical Global Impression of Change. Results Four hundred thirty-eight dyads were screened, 280 included, and 237 participated at 6 months (intervention group n=67; control condition n=170). At baseline, 63% used psychotropic medication regularly: antidementia drugs (47%), antidepressants (13%), hypnotics/sedatives (13%), antipsychotics (5%), and anxiolytics (2%). At 6 months, medication reviews were more frequently conducted in the intervention group compared to control (66% vs 42%, P=0.001). We found no differences regarding a change in drug use and BPSD. Patient-GP communication enhanced in the intervention group (mean score 0.95 [standard deviation 1.68] vs 0.41 [1.34], P=0.022). In the intervention group, control group, and overall sample, the informal caregivers of those who had their medications reviewed reported improved patient-GP communication compared to those who did not. Conclusions Change in psychotropic drug use and BPSD did not differ, even though patient-GP communication improved with medication reviews. Restricted psychotropic drug use among PwD likely reflects more judicious prescribing practices in recent years. Nevertheless, medication reviews could be cultivated to optimize pharmacologic treatment for this complex population. Trial registration ClinicalTrials.gov: NCT04043364; registered 15/03/2019

Factors associated with access to assistive technology and telecare in home-dwelling people with dementia: baseline data from the [email protected] trial

Background: There is a knowledge gap regarding factors that may influence the access to different devices for home-dwelling people with dementia (PwD). The aim of this study was to identify different assistive technology and telecare (ATT) devices installed in the home and key factors associated with access to such technology. Methods: The baseline data came from the [email protected] trial, a 24-month multi-component intervention including PwDs and their informal caregivers (dyads) and were collected through semi-quantitative questionnaires in three Norwegian municipalities between May and November of 2019. Regression models were applied to detect demographic and clinical factors associated with access to ATT. Results: Of 438 screened dyads, 276 were included at baseline. The mean ages of the PwDs and caregivers were 82 ± 7.0 and 66 ± 12 years, respectively, and 62.8% of the PwD were female and 73.5% had access to any type of ATT. The majority had traditional equipment such as stove guards (43.3%) and social alarms (39.5%) or everyday technology, e.g. calendar support and door locks (45.3%). Multivariate regression analyses revealed that access to a social alarm was more often available for females than males, at increased age, and when the PwD lived alone, while tracking devices (14.9%) were more often accessible at lower age. Everyday technology was more often available for females, at increased age of the PwD and the caregiver, higher comorbidity, and poor IADL (instrumental activities of daily living) function. For PwDs with severe dementia, access to ATT was significantly associated with poor IADL function, having their children as the main caregiver (61.3%), and having caregivers who contributed 81–100% to their care (49.5%). Conclusions: Home-dwelling PwDs mainly had access to traditional and obligated devices, followed by everyday technology. There is unmet potential for communication, tracking, and sensing technology, especially for devices not offered by the municipalities. Gender, ages of the PwD and caregiver, cohabitation status, and physical function were the main associated factors for access to ATT