Impact of Pain and Neuropsychiatric Symptoms on Activities in Nursing Home Residents (COSMOS Trial).

OBJECTIVE: This study aims to identify whether pain and dementia-related behavior are associated with different types of activities in nursing home residents, controlled for dementia severity. DESIGN: Cross-sectional baseline data from the multicomponent cluster randomized controlled COSMOS trial (acronym for Communication, Systematic pain treatment, Medication review, Organization of activities, and Safety). SETTING AND PARTICIPANTS: A total of 723 patients from 33 Norwegian nursing homes with 67 units (clusters). Participants aged ≥65 years, with a life expectancy of >6 months, and with valid data on activity were eligible for inclusion. METHODS: Activity was operationalized in time (hours per week) and type (cognitive, social, physical, and no activity). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), pain with the Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale (MOBID-2), and behavior with the Neuropsychiatric Inventory Nursing Home version (NPI-NH). Analyses were performed using linear and logistic regression. Sensitivity analyses for dementia severity were performed to account for effect modification. RESULTS: A total of 289 participants were included (mean age 86.2 [SD 7.6]; 74% female). A higher pain score was associated with less time spent on activity in participants with severe dementia (estimate 0.897, P = .043). A higher score for the NPI-NH mood cluster (depression and anxiety) was associated with a higher likelihood of participation in cognitive activities (odds ratio [OR], 1.073; P = .039). Apathy (OR, 0.884; P = .041) and lack of inhibition (OR, 0.904; P = .042) were associated with a lower likelihood of participation in social activities as well as no engagement in activities (apathy OR, 0.880; P = .042; lack of inhibition OR, 0.894; P = .034). CONCLUSION AND IMPLICATIONS: Pain and dementia-related behavior may influence the participation in activities in the nursing home. There is an urgent need to investigate what type of activity stimulates people in different stages of dementia.

Digital phenotyping by wearable-driven artificial intelligence in older adults and people with Parkinson's disease: Protocol of the mixed method, cyclic ActiveAgeing study.

BACKGROUND: Active ageing is described as the process of optimizing health, empowerment, and security to enhance the quality of life in the rapidly growing population of older adults. Meanwhile, multimorbidity and neurological disorders, such as Parkinson's disease (PD), lead to global public health and resource limitations. We introduce a novel user-centered paradigm of ageing based on wearable-driven artificial intelligence (AI) that may harness the autonomy and independence that accompany functional limitation or disability, and possibly elevate life expectancy in older adults and people with PD. METHODS: ActiveAgeing is a 4-year, multicentre, mixed method, cyclic study that combines digital phenotyping via commercial devices (Empatica E4, Fitbit Sense, and Oura Ring) with traditional evaluation (clinical assessment scales, in-depth interviews, and clinical consultations) and includes four types of participants: (1) people with PD and (2) their informal caregiver; (3) healthy older adults from the Helgetun living environment in Norway, and (4) people on the Helgetun waiting list. For the first study, each group will be represented by N = 15 participants to test the data acquisition and to determine the sample size for the second study. To suggest lifestyle changes, modules for human expert-based advice, machine-generated advice, and self-generated advice from accessible data visualization will be designed. Quantitative analysis of physiological data will rely on digital signal processing (DSP) and AI techniques. The clinical assessment scales are the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Geriatric Anxiety Inventory (GAI), Apathy Evaluation Scale (AES), and the REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ). A qualitative inquiry will be carried out with individual and focus group interviews and analysed using a hermeneutic approach including narrative and thematic analysis techniques. DISCUSSION: We hypothesise that digital phenotyping is feasible to explore the ageing process from clinical and lifestyle perspectives including older adults and people with PD. Data is used for clinical decision-making by symptom tracking, predicting symptom evolution, and discovering new outcome measures for clinical trials.

Age and Emotional Distress during COVID-19: Findings from Two Waves of the Norwegian Citizen Panel.

Older adults face the highest risk of COVID-19 morbidity and mortality. We investigated a one-year change in emotions and factors associated with emotional distress immediately after the onset of the pandemic, with emphasis on older age. METHODS: The online Norwegian Citizen Panel includes participants drawn randomly from the Norwegian Population Registry. Emotional distress was defined as the sum score of negative (anxious, worried, sad or low, irritated, and lonely) minus positive emotions (engaged, calm and relaxed, happy). RESULTS: Respondents to both surveys (n = 967) reported a one-year increase in emotional distress, mainly driven by elevated anxiety and worrying, but we found no difference in change by age. Multilevel mixed-effects linear regression comparing older age, economy-, and health-related factors showed that persons in their 60s (ß -1.87 (95%CI: -3.71, -0.04)) and 70s/80s (ß: -2.58 (-5.00, -0-17)) had decreased risk of emotional distress relative to persons under 60 years. Female gender (2.81 (1.34, 4.28)), expecting much lower income (5.09 (2.00, 8.17)), uncertainty whether infected with SARS-Cov2 (2.92 (1.21, 4.63)), and high self-rated risk of infection (1.77 (1.01, 2.53)) were associated with high levels of emotional distress. CONCLUSIONS: Knowledge of national determinants of distress is crucial to tailor accurate public health interventions in future outbreaks.

Sleep and its Association With Pain and Depression in Nursing Home Patients With Advanced Dementia - a Cross-Sectional Study.

Objective: Previous research suggests a positive association between pain, depression and sleep. In this study, we investigate how sleep correlates with varying levels of pain and depression in nursing home (NH) patients with dementia. Materials and methods: Cross-sectional study (n = 141) with sleep-related data, derived from two multicenter studies conducted in Norway. We included NH patients with dementia according to the Mini-Mental State Examination (MMSE ≤ 20) from the COSMOS trial (n = 46) and the DEP.PAIN.DEM trial (n = 95) whose sleep was objectively measured with actigraphy. In the COSMOS trial, NH patients were included if they were ≥65 years of age and with life expectancy >6 months. In the DEP.PAIN.DEM trial, patients were included if they were ≥60 years and if they had depression according to the Cornell Scale for Depression in Dementia (CSDD ≥ 8). In both studies, pain was assessed with the Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale (MOBID-2), and depression with CSDD. Sleep parameters were total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), wake after sleep onset (WASO), early morning awakening (EMA), daytime total sleep time (DTS) and time in bed (TiB). We registered use of sedatives, analgesics, opioids and antidepressants from patient health records and adjusted for these medications in the analyses. Results: Mean age was 86.2 years and 76.3% were female. Hierarchical regressions showed that pain was associated with higher TST and SE (p < 0.05), less WASO (p < 0.01) and more DTS (p < 0.01). More severe dementia was associated with more WASO (p < 0.05) and TiB (p < 0.01). More severe depression was associated with less TST (p < 0.05), less DTS (p < 0.01) and less TiB (p < 0.01). Use of sedative medications was associated with less TiB (p < 0.05). Conclusion: When sleep was measured with actigraphy, NH patients with dementia and pain slept more than patients without pain, in terms of higher total sleep time. Furthermore, their sleep efficiency was higher, indicating that the patients had more sleep within the time they spent in bed. Patients with more severe dementia spent more time awake during the time spent in bed. Furthermore, people with more severe depression slept less at daytime and had less total sleep time Controlling for concomitant medication use did not affect the obtained results.

Are Chronic Pain Patients with Dementia Being Undermedicated?

In dementia, neuropathological changes alter the perception and expression of pain. For clinicians and family members, this knowledge gap leads to difficulties in recognizing and assessing chronic pain, which may consequently result in persons with dementia receiving lower levels of pain medication compared to those without cognitive impairment. Although this situation seems to have improved in recent years, considerable geographical variation persists. Over the last decade, opioid use has received global attention as a result of overuse and the risk of addiction, while the literature on older persons with dementia actually suggests undertreatment. This review stresses the importance of reliable assessment and the regular evaluation and monitoring of symptoms in persons with dementia. Based on current evidence, we concluded that chronic pain is still undertreated in dementia.

Access to and interest in assistive technology for home-dwelling people with dementia during the COVID-19 pandemic (PAN.DEM).

The COVID-19 restrictions affect daily living in Norway, including home-dwelling people with dementia, and researchers conducting clinical trials in dementia care. In this paper, we 1) describe the development of a pandemic cohort (PAN.DEM) incorporated in the LIVE@Home.Path, an ongoing clinical intervention trial on resource utilisation including home-dwelling people with dementia and their caregivers (N = 438 dyads), 2) describe pre-pandemic use of assistive technology and 3) explore the extent to which COVID-19 restrictions increase caregivers interest in innovation in the PAN.DEM cohort (N = 126). Our main finding is that assistive technology is available to 71% pre-pandemic; the vast majority utilise traditional stove guards and safety alarms, only a few operate sensor technology, including GPS, fall detectors or communication aids. In response to COVID-19, 17% show increased interest in technology; being less familiar with operating a telephone and having higher cognitive functioning are both associated with increased interest. We conclude that wearable and sensor technology has not yet been fully implemented among people with dementia in Norway, and few caregivers show increased interest under the restrictions. Clinicaltrials.gov (NCT0404336).

Pain in dementia.

The ageing revolution is changing the composition of our society with more people becoming very old with higher risks for developing both pain and dementia. Pain is normally signaled by verbal communication, which becomes more and more deteriorated in people with dementia. Thus, these individuals unnecessarily suffer from manageable but unrecognized pain. Pain assessment in patients with dementia is a challenging endeavor, with scientific advancements quickly developing. Pain assessment tools and protocols (mainly observational scales) have been incorporated into national and international guidelines of pain assessment in aged individuals. To effectively assess pain, interdisciplinary collaboration (nurses, physicians, psychologists, computer scientists, and engineers) is essential. Pain management in this vulnerable population is also preferably done in an interdisciplinary setting. Nonpharmacological management programs have been predominantly tested in younger populations without dementia. However, many of them are relatively safe, have proven their efficacy, and therefore deserve a first place in pain management programs. Paracetamol is a relatively safe and effective first-choice analgesic. There are many safety issues regarding nonsteroidal anti-inflammatory drugs, opioids, and adjuvant analgesics in dementia patients. It is therefore recommended to monitor both pain and potential side effects regularly. More research is necessary to provide better guidance for pain management in dementia.

Analgesic treatments in people with dementia - how safe are they? A systematic review.

INTRODUCTION: People with dementia may be unable to verbally express pain and suffer from untreated pain. Use of analgesics in people with dementia has increased during the last decade, in particular opioid analgesics with high potential for adverse effects. AREAS COVERED: This article presents a systematic review of the current evidence for safety and tolerability of analgesic drugs from randomized controlled trials in people with dementia. Relevant trials were identified by a literature search in the EMBASE, MEDLINE, and Cochrane databases from inception to November 2018. The search included the main terms 'dementia' and 'analgesic' or their subterms, and was filtered to limit results to clinical trials. EXPERT OPINION: Although pain treatment is increasingly recognized as an important clinical issue in people with advanced dementia, there is currently a lack of evidence to support safety evaluations of commonly used analgesics in this group. To inform treatment decisions and enable care providers to appropriately monitor patients at risk of adverse effects, it is necessary to conduct well-designed clinical trials to investigate the relative efficacy and safety of analgesics in people with dementia, with particular emphasis on harmful effects of long-term opioid use as well as short-term use of nonsteroidal anti-inflammatory drugs.

Tolerability of buprenorphine transdermal system in nursing home patients with advanced dementia: a randomized, placebo-controlled trial (DEP.PAIN.DEM).

PURPOSE: Buprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population. PATIENTS AND METHODS: One hundred sixty-two people with advanced dementia and significant depression from 47 nursing homes were included and randomized to active analgesic treatment (acetaminophen/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome. RESULTS: Of the 44 patients who received active buprenorphine 5 µg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group (p<0.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (HR 23.2, 95% CI: 2.95-182, p=0.003). Adjusted for age, sex, cognitive function, pain and depression at baseline, active buprenorphine was associated with 24.0 times increased risk of discontinuation (Cox model, 95% CI: 2.45-235, p=0.006). Daytime activity dropped significantly during the second day of active treatment (-21.4%, p=0.005) and decreased by 12.9% during the first week (p=0.053). CONCLUSION: Active buprenorphine had significantly higher risk of discontinuation compared with placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine.

Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM).

BACKGROUND: Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. OBJECTIVE: The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms. METHODS: We conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events. RESULTS: The mean depression change was - 0.66 (95% confidence interval - 2.27 to 0.94) in the active group (n = 80) and - 3.30 (- 4.68 to -1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55-4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by - 1.11 (- 2.16 to - 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (- 0.11 to 6.19), p = 0.059] or pain [0.47 (- 0.77 to 1.71), p = 0.456] from 0 to 13 weeks. Thirty-five patients were withdrawn from the study because of adverse reactions, deterioration or death: 25 (31.3%) during active treatment [23 (52.3%) who received buprenorphine], and ten (12.2%) in the placebo group. The most frequently occurring adverse events were psychiatric (17 adverse reactions) and neurological (14 adverse reactions). CONCLUSION: Analgesic treatment did not reduce depression while placebo appeared to improve depressive symptoms significantly by comparison, possibly owing to the adverse effects of active buprenorphine. The risk of adverse events warrants caution when prescribing buprenorphine for people with advanced dementia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02267057 (registered 7 July, 2014) and Norwegian Medicines Agency EudraCT 2013-002226-23.

Associations between pain and depression in nursing home patients at different stages of dementia.

BACKGROUND: Pain is associated with depression in nursing home patients with dementia. It is, however, unclear whether pain increases depression. Therefore we evaluated the prospective associations between pain and depressive symptoms in nursing home patients at different stages of cognitive impairment. METHODS: Two longitudinal studies were combined, including 931 patients (≥65 years) from 65 nursing homes. One study assessed patients at admission, with 6-month follow-up (2012-2014). The other study assessed residents with varying lengths of stay, with 4-month follow-up (2014-2015). Patients were assessed with the Mini-Mental State Examination, the Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale, and the Cornell Scale for Depression in Dementia. RESULTS: At baseline, 343 patients (40% of 858 assessed) had moderate to severe pain, and 347 (38% of 924) had depression. Pain increased the risk of depression (OR 2.35, 95% CI 1.76-3.12). Using mixed model analyses, we found that a 1-point increase in pain was associated with a .48 increase in depression (p<.001). This association persisted in mild, moderate, and severe cognitive impairment. In those recently admitted, depressive symptoms decreased over time, and having less pain at follow-up was associated with a decrease in depressive symptoms (within-subject effect; p=.042). LIMITATIONS: The two cohorts had different inclusion criteria, which may reduce generalisability. The study design does not allow conclusions on causality. CONCLUSIONS: Pain and depressive symptoms are associated in patients with dementia. Because reduced pain is associated with less depressive symptoms, these patients should be assessed regularly for untreated pain. The benefit of analgesic treatment should be weighed carefully against the potential for adverse effects.

The importance of pain management in older people with dementia.

INTRODUCTION: Pain is common in people with dementia, representing a critical aspect of treatment and care. However, there remain considerable gaps in evidence to support pain assessment and treatment. SOURCES OF DATA: An updated literature search focussing on systematic reviews and randomized controlled trials. AREAS OF AGREEMENT: There are key areas of consistency around the prevalence, causes and current treatment trends for pain in dementia, the impact of untreated pain and the need for an accurate, fully validated assessment tool. AREAS OF CONTROVERSY: Accurate assessment due to inherent issues in dementia is a critical challenge. There is also a lack of evidence around alternative treatment options. GROWING POINTS: New pain predictors are being identified, including physical function, depression and specific pain types, which should inform assessment methodology. AREAS TIMELY FOR DEVELOPING RESEARCH: Future research should focus on developing integrated pain management approaches with optimized assessment and evidence-based treatment guidance.

Toxicological assessment of the anti-salmon lice drug diflubenzuron on Atlantic cod Gadus morhua.

Increasing use of the chitin synthesis inhibitor diflubenzuron against the ectoparasitic salmon louse Lepeophtheirus salmonis in marine aquaculture has raised concerns over its environmental impacts. This study evaluated how diflubenzuron affects Atlantic cod Gadus morhua, a fish species often found near Atlantic salmon Salmo salar farms, focusing on uptake kinetics and hepatic transcriptional responses. Two experiments were conducted, one time-series trial in which the fish were given a daily dose (3 mg kg-1 fish) of diflubenzuron for 14 d followed by a 3 wk depuration period, and one dose-response trial with increasing concentrations (3, 10 and 50 mg kg-1 fish). The highest diflubenzuron concentrations were found in the liver at Day 15. No detectable levels of diflubenzuron were found in liver or muscle 3 wk after the end of the treatment. At the molecular level, small effects of diflubenzuron treatment on gene transcription were observed. In the time-series experiment, the strongest effects were seen at Day 8, with 2 transcripts being upregulated (bclx2 and cpt1a) and 8 transcripts being downregulated (gstp1, gstm1, gstt1, ugt1a, nat2, cat, p53 and slc16a9a). Five transcripts (cyp3a, cpt1a, ptgs2, elovl5 and mapk1) responded significantly to diflubenzuron exposure in the dose-response experiment. This study shows that diflubenzuron can be taken up by Atlantic cod, that it is rapidly cleared from the body and that when present this pharmaceutical causes only small effects on the expression of genes involved in detoxification pathways. Taken together, our data suggest that accumulated diflubenzuron at the levels studied would have a relatively small effect on wild Atlantic cod.