The patterns and burden of multimorbidity in geriatric patients with prolonged use of addictive medications.

BACKGROUND: Multimorbidity and prolonged use of addictive medications are prevalent among older patients, and known to increase the risk of adverse drug events. Yet, the relationship between these two entities has remained understudied. AIMS: This study explored the association between multimorbidity burden and prolonged use of addictive medications in geriatric patients, adjusted for clinically important covariates. Furthermore, we identified comorbidity patterns in prolonged users. METHODS: We conducted a cross-sectional study on a consecutive sample of 246 patients, aged 65-90 years, admitted to a large public university hospital in Norway. We defined prolonged use of addictive medications as using benzodiazepines, opioids and/or z-hypnotics beyond the duration recommended by clinical guidelines (≥ 4 weeks). Multimorbidity was assessed with the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), based on diagnoses made by independent physicians. RESULTS: Compared to non-prolonged use, prolonged use was significantly more common among patients who had psychiatric (19/27, 70%), liver (19/22, 86%), upper gastrointestinal tract (21/32, 66%), musculoskeletal (52/96, 54%), or nervous system disorders (46/92, 50%). Patients with prolonged use had a higher multimorbidity burden than those without such use (CIRS-G score, mean = 7.7, SD = 2.7 versus mean = 4.6, SD = 2.2, p < 0.001). Multivariable logistic regression indicated a significant association between multimorbidity burden and prolonged addictive medication use (OR = 1.72, 95% CI 1.42-2.08). Predictive margins postestimation showed a systematic increase in the predicted CIRS-G scores when the number of addictive drug used increases. CONCLUSIONS: Multimorbidity is strongly associated with prolonged use of addictive medications. Multiple substance use may aggravate disease burden of older patients.

Magnetic Resonance Imaging in Stable Mild Cognitive Impairment, Prodromal Alzheimer's Disease, and Prodromal Dementia with Lewy Bodies.

INTRODUCTION: Fifteen percent of people with mild cognitive impairment (MCI) will progress to dementia within 2 years. There is increasing focus on the evaluation of biomarkers which point towards the underlying pathology. This enables better prediction of clinical outcomes. Early diagnosis of the dementia subtype is crucial for appropriate management and accurate prognosis. The aim of this study was to compare MRI measures in stable mild cognitive impairment patients (stable-MCI), prodromal Alzheimer's disease (pro-AD), and prodromal dementia with Lewy bodies (pro-DLB). METHODS: Out of 1,814 patients assessed in Essex memory clinic between 2002 and 2017, 424 had MCI at baseline with follow-up data. All patients underwent comprehensive clinical and cognitive assessment at each assessment. MRI scans were acquired at patients' baseline assessment, corresponding to the time of initial MCI clinical diagnosis. Patients were grouped according to their diagnosis at the end of follow-up. All baseline scans were visually rated according to established rating scales for medial temporal atrophy (MTA), global cortical atrophy (GCA), and white matter lesions (WMLs). RESULTS: MRI scans were available for 28 pro-DLB patients and were matched against 27 pro-AD and 28 stable-MCI patients for age, sex, and education. The mean follow-up duration was 34 months for the pro-AD group, 27 months for the pro-DLB group, and 21 months for the stable-MCI group. MTA scores were significantly greater in pro-AD patients compared to pro-DLB (p = 0.047) and stable-MCI patients (p = 0.012). There was no difference on GCA or WMLs between pro-AD, pro-DLB, and stable-MCI. CONCLUSIONS: This study indicates that a simple visual rating of MTA at the stage of MCI already differs at a group level between patients that progress to AD, DLB, or continue to be stable-MCI. This could aid clinicians to differentiate between MCI patients who are likely to develop AD, versus those who might progress to DLB or remain stable.

Health-related quality of life in hospitalized older patients with versus without prolonged use of opioid analgesics, benzodiazepines, and z-hypnotics: a cross-sectional study.

BACKGROUND: Central nervous system depressant medications (CNSDs) such as opioid analgesics and sedative-hypnotics are commonly prescribed to older patients for the treatment of chronic pain, anxiety and insomnia. Yet, while many studies reported potential harms, it remains unknown whether persistent use of these medications is beneficial for older patients' self-reported health-related quality of life (HRQoL). The present study clarified this knowledge gap through comparing HRQoL of hospitalized older patients with versus without using CNSD drugs for ≥4 weeks. Moreover, we explored the relationship between such use and HRQoL, adjusting for the effects of polypharmacy, comorbidity burden and other clinically relevant covariates. METHODS: The study was cross-sectional and included 246 older patients recruited consecutively from somatic departments of a large regional university hospital in Norway. We defined prolonged CNSD use as using opioids, benzodiazepines and/or z-hypnotics for ≥4 weeks. Patients' self-reported HRQoL were measured with scales of the EuroQol EQ-5D-3L instrument. Data analyses were mainly descriptive statistics and regression models. RESULTS: Patients with prolonged use of CNSDs reported lower scores on both EQ-5D index and EQ VAS compared with those without such use (p < 0.001). They had higher odds of having more problems performing usual activities (OR = 3.37, 95% CI: 1.40 to 8.13), pain/discomfort (OR = 2.06, 95% CI: 1.05 to 4.04), and anxiety/depression (OR = 3.77, 95% CI: 1.82 to 7.82). In multivariable regression models, there was no significant association between prolonged CNSD use and HRQoL when including pain as a predictor variable. In models not including pain, CNSD use was strongly associated with HRQoL (adjusted for sociodemographic background, polypharmacy, comorbidity, anxiety and depressive symptoms, regression coefficient - 0.19 (95% CI, - 0.31 to - 0.06). CONCLUSIONS: Older patients with prolonged CNSD use reported poorer HRQoL. They also had more pain and higher depression scores. Prolonged use of CNSDs was not independently associated with higher HRQoL.

"What should I do when I get home?" treatment plan discussion at discharge between specialist physicians and older in-patients: mixed method study.

BACKGROUND: During discharge from hospital, older patients and physicians discuss the plan for managing patients' health at home. If not followed at home, it can result in poor medication management, readmissions, or other adverse events. Comorbidities, polypharmacy and cognitive impairment may create challenges for older patients. We assessed discharge conversations between older in-patients and physicians for treatment plan activities and medication information, with emphasis on the role of cognitive function in the ongoing conversation. METHODS: We collected 11 videos of discharge consultations, medication lists, and self-reported demographic information from hospitalised patients ≥65 years at the Geriatric department in a general hospital. Mini Mental State Examination score < 25 was classified as low cognitive function. We used microanalysis of face-to-face dialogue to identify and characterise sequences of interaction focused on and distinguishing the treatment plan activities discussed. In addition to descriptive statistics, we used a paired-sample t-test and Mann-Whitney U test for non-parametric data. RESULTS: Patients' median age was 85 (range: 71-90);7 were females and 4 males. Median of 17 (range: 7 to 23) treatment plan activities were discussed. The proportions of the activities, grouped from a patient perspective, were: 0.40 my medications, 0.21 something the hospital will do for me, 0.18 someone I visit away from home, 0.12 daily routine and 0.09 someone coming to my home. Patients spoke less (mean 190.9 words, SD 133.9) during treatment plan activities compared to other topics (mean 759 words, SD 480.4), (p = .001). Patients used on average 9.2 (SD 3.1) medications; during the conversations, an average of 4.5 (SD 3.3) were discussed, and side effects discussed on average 1.2 (SD 2.1) times. During treatment plan discussions, patients with lower cognitive function were less responsive and spoke less (mean 116.5 words, SD 40.9), compared to patients with normal cognition (mean 233.4 words, SD 152.4), (p = .089). CONCLUSION: Physicians and geriatric patients discuss many activities during discharge conversations, mostly focusing on medication use without stating side effects. Cognitive function might play a role in how older patients respond. These results may be useful for an intervention to improve communication between physicians and older hospitalised patients.

The Severity of Dependence Scale detects medication misuse and dependence among hospitalized older patients.

BACKGROUND: In older patients, timely recognition and treatment of medication misuse and dependence are crucial to secure medication safety and to avoid increasing health expenditure. Nonetheless, the detection of this condition remains challenging due to the paucity of screening instruments validated for older people. This study assesses diagnostic accuracy, reliability, validity and the factor structure of the Severity of Dependence Scale (SDS) in detecting medication misuse and dependence among hospitalized older patients, focusing on prescribed central nervous system depressants (CNSDs): opioid analgesics, benzodiazepines and z-hypnotics. METHODS: 246 adults aged 65-90 were recruited consecutively from somatic departments of the Akershus University Hospital, Norway. Among these, 100 patients were identified as prolonged users of CNSDs. Diagnostic accuracy and validity of the SDS were assessed using DSM-IV criteria for substance abuse and dependence as the reference standard. We also performed an exploratory factor analysis and assessment of internal consistency using Cronbach's alpha. RESULTS: The area under the ROC curve was 0.86 (95%CI = 0.79-0.93; p < 0.001). A score of 5.5 was determined as the optimal cutoff for detecting CNSD misuse and dependence among older patients. Cronbach's alpha obtained was satisfactory (α = 0.73). There was a significant positive correlation between the SDS score and DSM-IV criteria for substance abuse and dependence (Pearson's correlation coefficient = 0.61, p < 0.001). The uni-dimensionality of the SDS was documented. CONCLUSIONS: The SDS is reliable, valid and capable of detecting medication misuse and dependence among hospitalized older patients, with good diagnostic performance. The scale thus holds promise for use in both clinical and research contexts. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03162081 . Registered 3 May 2017.

Measuring pain intensity in older adults. Can the visual analogue scale and the numeric rating scale be used interchangeably?

OBJECTIVES: Visual analogue scale (VAS) and numeric rating scale (NRS) are two commonly used instruments for measuring pain intensity. Both instruments are validated for use in both clinical and research settings, and share a range of similar aspects. Some studies have shown that the two instruments may be used interchangeably, but the results are conflicting. In this study we assessed whether the VAS and the NRS instruments may be used interchangeably when measuring pain intensity in older adults. METHODS: Data were collected in a cross-sectional study, as part of the follow-up in a larger longitudinal study conducted at the Akershus University Hospital, Norway 2021 to 2022 and included 39 older adults aged ≥65. Participants were regarded as a normal older adult population as they were not recruited on basis of a specific condition or reports of pain. The participants were asked to rate their pain intensity on an average day using VAS and NRS. Bland-Altman analysis was performed to assess agreement between the two instruments. RESULTS: Thirty-seven participants with mean (SD) age of 77 (5.9) were included in the analysis. Mean (SD) pain assessed by VAS and NRS was 2.8 (1.8) and NRS 4.7 (2.2), respectively. A mean difference (SD) of 2.0 (1.9) between the scores of the two instruments was statistically significantly different from zero (p < 0.001) confirming bias. The 95% limits of agreement were estimated to be -1.7 to 5.7. A post-hoc analysis, removing an outlier, resulted in similar conclusions. CONCLUSION: There was poor agreement between the VAS and NRS scale for measuring pain intensity in older adults. This suggests that the two instruments should not be used interchangeably when assessing pain intensity in this population. ETHICAL APPROVAL: Regional Committees for Medical and Health Research Ethics [2016/2289]. TRIAL REGISTRATION: NCT03162081, 22 May 2017.

Brief Intervention as a Method to Reduce Z-Hypnotic Use by Older Adults: Feasibility Case Series.

BACKGROUND: Z-hypnotics or z-drugs are commonly prescribed for insomnia and sleep difficulties in older adults. These drugs are associated with adverse events and dependence and are not recommended for long-term use. Despite evidence of older adults being more sensitive to a wide array of adverse events and clinical guidelines advocating limiting use, inappropriate use in this population is still prevalent. Previous intervention studies have focused mainly on prescriber information. Simple, individually focused intervention designs are less studied. Brief intervention (BI) is a simple, easily transferable method mainly used to treat patients at risk of alcohol overuse. OBJECTIVE: Our objective was to design and test the feasibility and acceptability of a BI intervention adapted to address individual, inappropriate use of z-hypnotics among older adults. This preparatory study aimed to optimize the intervention in advance of a quantitative randomized controlled trial investigating the treatment effect in a larger population. METHODS: This feasibility case series was conducted at Akershus University Hospital, Norway, in autumn 2021. We included 5 adults aged ≥65 years with long-term (≥4 weeks) use of z-hypnotics and 2 intervening physicians. Additionally, 2 study investigators contributed with process evaluation notes. The BI consists of information on the risk of inappropriate use and individualized advice on how to reduce use. The focus of the intervention is behavioral and aims, in cooperation with the patient and based on shared decision-making, to change patient behavior regarding sleep medication rather than physician-based detoxification and termination of z-hypnotic prescriptions. Qualitative and descriptive quantitative data were collected from intervening physicians, study investigators, and participants at baseline, immediately after the intervention, and at the 6-week follow-up. RESULTS: Data were obtained from 2 physicians, 2 study investigators, and 5 participants (4 women) with a median age of 84 years. The average time spent on the BI consultation was 15 minutes. All 5 participants completed the intervention without problems. The participants and 2 intervening physicians reported the intervention as acceptable and were satisfied with the delivery of the intervention. After the intervention, 2 participants stopped their use of z-hypnotics completely and participated in the follow-up interview. Study investigators identified logistical challenges regarding location and time requirements. Identified aspects that may improve the intervention and reduce dropouts included revising the intervention content, focusing on rebound insomnia, adding an information leaflet, and supporting the patient in the period between the intervention and follow-up. The notion that the intervention should best be located and conducted by the patient's own general practitioner was supported by the participants. CONCLUSIONS: We identified important aspects to improve the designed intervention and found that the BI is feasible and acceptable for incorporation into a larger randomized trial investigating the treatment effect of BI for reducing z-hypnotic use by older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT03162081; http://tinyurl.com/rmzx6brn.

Mortality and health-related quality of life in older adults with long-term use of opioids, z-hypnotics or benzodiazepines: a prospective observational study at 5 years follow-up.

OBJECTIVES: Disease and medication use in older age is a consequence of age-related declining health. Multimorbidity followed by polypharmacy is common. Central nervous system depressing (CNSD) drugs such as opioids, benzodiazepines and z-hypnotics are not recommended for long-term use in older adults but are in use by many. We aimed to assess mortality and change in health-related quality of life (HRQoL) in older adults with long-term use of CNSDs. METHOD: A prospective observational study was conducted at Akershus University Hospital, Norway, 2017-2019, with follow-up in 2021-2022, including 246 participants aged 65-90. At 5-year follow-up, 78 (32%) participants had passed away. Mortality data were collected from patient electronic health records. Of the surviving 168 (68%), we collected further follow-up data from 38 (16%) participants. Follow-up included demographic and clinical data. The EuroQuol Group EQ-5D-5L questionnaire was used to measure HRQoL. Analysis include Cox regression model for survival data and linear mixed model for change in HRQoL over time. RESULTS: At follow-up, 78 (31.7%) were deceased. Mean survival time was 3.3 years. Total time for survival data was 4.7 years. Mortality was higher among participants with long-term use of CNSD (HR 1.9 95% CI (1.2 to 3.2), p=0.01). The multivariable analysis found being older (HR 1.1 95% CI (1.0 to 1.1), p=0.020) and male sex (HR 2.1 95% CI (1.2 to 3.5), p=0.008) to be associated with increased risk of mortality. According to the linear mixed model (n=38), there was no significant difference between surviving users and non-users in change in HRQoL EQ-5D-5L index from baseline to follow-up. CONCLUSION: Mortality was higher for long-term users of CNSDs at 5-year follow-up. Being older and male sex were associated with mortality. Among survivors, there was no significant difference between the groups in change of HRQoL over time. TRIAL REGISTRATION NUMBER: NCT03162081; 22 May 2017.

The effect of cognitive function and central nervous system depressant use on mortality-A prospective observational study of previously hospitalised older patients.

BACKGROUND: Older patients are often users of prolonged Central Nervous System Depressants (CNSD) (Z-hypnotics, benzodiazepines and opioids), which may be associated with reduced cognition. The long-term effects of CNSD use and reduced cognitive function in older patients are unclear. The aim of this study was to examine whether cognitive function and CNSD use at baseline hospitalisation were associated with all-cause mortality two years after discharge. METHODS: We conducted a prospective observational study, including baseline data (2017-2018) from previously hospitalised older patients (65-90 years), assessing all-cause mortality two years after discharge. We used logistic regression to assess the primary outcome, all-cause mortality two years after baseline hospitalisation. The primary predictors were cognitive function measured by The Mini Mental State Examination (MMSE) and prolonged CNSD use (continuous use ≥ 4 weeks). Adjustment variables: age, gender, education, the Hospital Anxiety and Depression Scale (HADS) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), using receiver operating characteristics (ROC) to compare the predictive power of the models. In a sub-analysis we used, the Neurobehavioural Cognitive State Examination (Cognistat) and the Clock Drawing Test. RESULTS: Two years after discharge, out of 246 baseline patients, 43 were deceased at follow-up, among these 27 (63%) were CNSD users, and 16 (36%) were non-users at baseline, (p = 0.002). In the multivariable models cognitive function (MMSE score) was a predictor of mortality (OR 0.81 (95% CI 0.69; 0.96), p = 0.014). CNSD use was associated with mortality (OR 2.71 (95% CI 1.06; 6.95), p = 0.038), with ROC AUC: 0.74-0.77 for these models. Results using Cognistat supported the findings. The Clock Drawing Test was not significant predictor of mortality. CONCLUSION: Two years after discharge from the hospital, older patients with reduced cognitive function and CNSD use during hospital stay had higher mortality. This underlines that inappropriate (prolonged and concurrent) use of CNSDs should be avoided by older patients, particularly in patients with reduced cognitive function. TRIAL REGISTRATION: NCT03162081, 22 May 2017.

The association between pain and central nervous system depressing medication among hospitalised Norwegian older adults.

OBJECTIVES: Central nervous system depressant medications (CNSD) including benzodiazepines, z-hypnotics and opioids are regularly prescribed for the older patient. These medications are linked to dependence and associated with severe side effects in some older patients. Consensus recommendations for this group suggest limiting their use. We have recently described a high proportion of long-term CNSD use and dependence among older in-hospital patients. In this study, we aim to investigate factors associated with pain intensity and presentation of pain among older adults with long-term use of CNSDs compared to non-users. METHODS: Two hundred and forty six elderly hospitalised patients were recruited consecutively in a cross-sectional study. Data was collected from patients and electronic health records (EHR). Independent variables were sex, age, education, emotional symptoms (hospital anxiety and depression scale [HADS]), cognitive function (Mini-mental State Examination test [MMSE]), comorbidity (cumulative illness rating score - geriatrics [CIRS-G]), loneliness (the six-item De Jong Gierveld Loneliness Scale) and prolonged (≥4 weeks) use of any CNSDs or prolonged use of opioids (≥4 weeks). All variables, including pain intensity, were collected at one time point consistent with the cross-sectional study design. Statistical analyses included descriptive statistics and linear regression models using the above mentioned variables and pain intensity (visual analogue scale for pain intensity [VAS] pain 0-100) as outcome. Additional information regarding pain presentation was extracted from the patients' EHR. RESULTS: Mean pain intensity VAS (SD) was 35.2 (30.4) and 18.1 (24.2) respectively, for patients with vs. without prolonged use of CNSDs. In the multivariable linear regression analysis, prolonged use of CNSDs and opioids were positively associated with pain intensity (VAS) (regression coefficient (95% CI) 20.7 (11.0; 30.3), p<0.001, and 19.8 (5.7; 33.8), p=0.006, respectively), while sex, age, education, MMSE, HADS, CIRS-G and loneliness scores were not. Pain related to back (23.2%) and lower extremities (23.2%) were most common pain sites, and those with one or more pain sites reported overall higher pain intensity compared to those with no reported pain sites (p<0.006). CONCLUSIONS: Prolonged use of CNSD medications as well as prolonged use of opioids are both positively associated with pain intensity. The results may have implications for treatment and long-term pain management for older patients.

Association between prescribed central nervous system depressant drugs, comorbidity and cognition among hospitalised older patients: a cross-sectional study.

OBJECTIVES: Central nervous system depressants (CNSDs) such as opioids, benzodiazepine and Z-hypnotics are commonly used. However, CNSDs may influence cognitive function, especially in older hospitalised patients with comorbidities. The aim was to examine the association between CNSD use and cognitive function in older patients. We assessed global and domain specific cognitive function, among hospitalised older patients, including covariates for comorbidity, anxiety and depression. DESIGN: Cross-sectional hospital-based study. SETTINGS: Data was collected consecutively from inpatients at somatic wards of a general university hospital. PARTICIPANTS: Older patients between 65 and 90 years with/without CNSD use for ≥4 weeks. OUTCOME MEASURES: The main outcome was cognitive function assessed by Cognistat. Secondary outcomes were routine clinical tests in the wards (mini-mental state examination (MMSE), trail making test (TMT) A and B, and clock drawing tests). Analyses were bivariate and multiple linear regression, adjusted for age, gender, and education. Covariates were comorbidity, depression and anxiety scores. RESULTS: The main result indicated that CNSD users (n=100) had (ß=-3.4, 95% CI 6.27 to -0.58, p=0.017) lower Cognistat score than non-users (n=146), adjusted for age, gender, education, anxiety and depression, but not significant when including covariate for comorbidity (ß= -2.50 - 5.45; -0.46, p=0.097). Comorbidity was associated with cognitive function (ß=-0.77, 95% CI -1.22 to -0.14, p=0.014). Cognistat subdimensions associated with CNSD use were language (p=0.017) and calculation (p=0.003). In clock drawing test, users had lower scores than non-users (ß=-0.80, 95% CI 1.24 to -0.36, p=0.004), but no significant difference was found with MMSE and TMT A or B. Z-hypnotics were associated with reduced cognitive function. CONCLUSION: Among older hospitalised patients, global cognition and specific cognitive functions were associated with long-term use of CNSD medication as well as with somatic comorbidity. TRIAL REGISTRATION NUMBER: NCT03162081, 22 May 2017.

Sociodemographic, clinical and pharmacological profiles of medication misuse and dependence in hospitalised older patients in Norway: a prospective cross-sectional study.

OBJECTIVES: Timely recognition of medication misuse and dependence is crucial to avoid both adverse drug events and increasing health expenditure. Yet the detection of these disorders in older people remains challenging due to the paucity of evidence on characteristics of patients at risk. This study investigates sociodemographic, pharmacological and clinical characteristics and factors associated with prolonged medication use, misuse and dependence in hospitalised older patients, focusing on three commonly prescribed central nervous system depressants (CNSDs): opioid analgesics, benzodiazepines and z-hypnotics. DESIGN: A prospective, cross-sectional study complying with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. SETTING: Somatic departments of the Akershus University Hospital, Norway. PARTICIPANTS: 246 patients aged 65-90 were included. OUTCOME MEASURES: Prolonged use was defined as using CNSDs for ≥4 weeks. Misuse and dependence were assessed with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for substance abuse and dependence. We used descriptive statistics to report patients' characteristics and logistic regression to demonstrate factors associated with prolonged use, and misuse or dependence. RESULTS: Forty per cent of participants reported using CNSDs for ≥4 weeks. The odds of prolonged use were higher for patients aged 75-84 (OR=2.32, 95% CI 1.16 to 4.65) and ≥85 (OR=3.33, 95% CI 1.25 to 8.87) vs <75 years, for pain intensity (OR=1.02, 95% CI 1.01 to 1.04), and polypharmacy versus no polypharmacy (OR=5.16, 95% CI 2.13 to 12.55). The odds were lower for patients who completed secondary education (OR=0.33, 95% CI 0.13 to 0.83) compared with those with only basic education. Factors associated with misuse or dependence were pain intensity (OR=1.02, 95% CI 1.01 to 1.04) and concurrent use of ≥2 CNSDs (OR=3.99, 95% CI 1.34 to 11.88). CONCLUSION: CNSD overuse is prevalent among hospitalised older patients, despite clear guidelines and recommendations. Our findings underline a need for stronger focus on responsible prescribing, timely detection and prevention of this issue, with special attention towards older patients, those with enhanced pain, polypharmacy and/or concurrent use of several CNSDs. TRIAL REGISTRATION NUMBER: NCT03162081.