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.

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.

Outcome prediction in comatose cardiac arrest patients with initial shockable and non-shockable rhythms.

BACKGROUND: Prognosis after out-of-hospital cardiac arrest (OHCA) is presumed poorer in patients with non-shockable than shockable rhythms, frequently leading to treatment withdrawal. Multimodal outcome prediction is recommended 72 h post-arrest in still comatose patients, not considering initial rhythms. We investigated accuracy of outcome predictors in all comatose OHCA survivors, with a particular focus on shockable vs. non-shockable rhythms. METHODS: In this observational NORCAST sub-study, patients still comatose 72 h post-arrest were stratified by shockable vs. non-shockable rhythms for outcome prediction analyzes. Good outcome was defined as cerebral performance category 1-2 within 6 months. False positive rate (FPR) was used for poor and sensitivity for good outcome prediction accuracy. RESULTS: Overall, 72/128 (56%) patients with shockable and 12/50 (24%) with non-shockable rhythms had good outcome (p < .001). For poor outcome prediction, absent pupillary light reflexes (PLR) and corneal reflexes (clinical predictors) 72 h after sedation withdrawal, PLR 96 h post-arrest, and somatosensory evoked potentials (SSEP), all had FPR <0.1% in both groups. Unreactive EEG and neuron-specific enolase (NSE) >60 µg/L 24-72 h post-arrest had better precision in shockable patients. For good outcome, the clinical predictors, SSEP and CT, had 86%-100% sensitivity in both groups. For NSE, sensitivity varied from 22% to 69% 24-72 h post-arrest. The outcome predictors indicated severe brain injury proportionally more often in patients with non-shockable than with shockable rhythms. For all patients, clinical predictors, CT, and SSEP, predicted poor and good outcome with high accuracy. CONCLUSION: Outcome prediction accuracy was comparable for shockable and non-shockable rhythms. PLR and corneal reflexes had best precision 72 h after sedation withdrawal and 96 h post-arrest.

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.

Case Report: Limbic encephalitis following treatment with durvalumab for small-cell lung cancer.

Background: Durvalumab is an immune checkpoint Inhibitor (ICIs) that is used in the treatment of malignant tumors, such as lung cancer and melanoma. ICIs are associated with immune-related adverse events including autoimmune encephalitis, although both paraneoplastic phenomena and ICI treatment may lead to autoimmunity. Case presentation: We describe a 72-year old male patient with small-cell lung cancer, who during adjuvant treatment with Durvalumab developed GABABR1 and GAD65 antibodies and both diabetes and autoimmune limbic encephalitis. Because he was followed prospectively as part of a treatment study, we had access to repeated serum samples and cognitive assessments over time prior to developing encephalitis and diabetes, in addition to later assessments. A high titer of GABABR1 antibodies appeared early, while GAD65 antibodies appeared later with a lower titer in parallel with the development of diabetes. As he subsequently developed clinical signs of encephalitis, verified by EEG and brain MRI, he also had CSF GABABR1 antibodies. Durvalumab was discontinued and steroid treatment with subsequent plasmapheresis were started, resulting in reduction of both CSF and serum antibody levels. Clinical signs of encephalitis gradually improved. Conclusion: This case illustrates the importance of being aware of possible serious autoimmune adverse reactions, including neurological syndromes such as encephalitis, when treating patients with high risk of para-neoplasia with ICIs. In addition, the case shows the development of autoantibodies over time.

Transcranial Doppler during the first week after cardiac arrest and association with 6-month outcomes.

Background: Early prediction of outcomes in comatose patients after out-of-hospital cardiac arrest is challenging. Prognostication tools include clinical examination, biomarkers, and neuroradiological and neurophysiological tests. We studied the association between transcranial Doppler (TCD) and the outcome. Methods: This was a pre-defined sub-study of the prospective observational Norwegian Cardiorespiratory Arrest Study. Patients underwent standardized post-resuscitation care, including target temperature management (TTM) to 33°C for 24 h. TCD was performed at days 1, 3, and 5-7. The primary endpoint was cerebral performance category (CPC) at 6 months, dichotomized into good (CPC 1-2) and poor (CPC 3-5) outcomes. We used linear mixed modeling time-series analysis. Results: Of 139 TCD-examined patients, 81 (58%) had good outcomes. Peak systolic velocity in the middle cerebral artery (PSV) was low during TTM (Day 1) and elevated after rewarming (Day 3). Thereafter, it continued to rise in patients with poor, but normalized in patients with good, outcomes. At days 5-7, PSV was 1.0 m/s (95% CI 0.9; 1.0) in patients with good outcomes and 1.3 m/s (95% CI 1.1; 1.4) in patients with poor outcomes (p < 0.001). Conclusion: Elevated PSV at days 5-7 indicated poor outcomes. Our findings suggest that serial TCD examinations during the first week after cardiorespiratory arrest may improve our understanding of serious brain injury.

Adding eptinezumab to brief patient education to treat chronic migraine and medication-overuse headache: Protocol for RESOLUTION-A phase 4, multinational, randomized, double-blind, placebo-controlled study.

Introduction: Migraine is a highly prevalent and disabling neurological disease. Excessive use of acute medications can lead to medication-overuse headache (MOH), occurring when a patient experiences an increasing number of headache and migraine days, despite taking greater amounts of acute medication. To treat MOH, a preventive migraine treatment and/or withdrawal of the overused medication(s) are advised. Brief Educational Intervention (BEI) has been shown to be an effective tool with promising results for MOH. Here, we report the design of a clinical trial that aims to evaluate the efficacy of eptinezumab, an anti-calcitonin gene-related peptide preventive migraine treatment, as an add-on to BEI for treatment of MOH in those with chronic migraine. Methods and analysis: RESOLUTION will be a phase 4, multi-national, randomized, double-blind, placebo-controlled study. This study will enroll approximately 570 participants with dual diagnoses of chronic migraine and MOH. Eligible patients will be randomly allocated to one of two treatment groups, BEI and eptinezumab (100 mg; n = 285) or BEI and placebo (n = 285), in a 1:1 ratio. The primary endpoint is the change from baseline in monthly migraine days over weeks 1-4. Secondary and exploratory endpoints will assess monthly migraine days over weeks 1-12, MOH remission, transition from chronic to episodic migraine, health-related quality of life, work productivity, and the safety and tolerability of eptinezumab in this patient population. Ethics and dissemination: This study will be conducted in accordance with good clinical practice. All patients will be fully informed about the study, including the risks and benefits of participation, and all participants will provide informed consent for participation in the trial and dissemination of results.

Changes in health status and health related quality of life from six months to five years in out-of-hospital cardiac arrest survivors - A NORCAST sub study.

BACKGROUND: Brain injury in out-of-hospital cardiac arrest (OHCA) survivors affects health status and health-related quality of life (HRQoL). It is unknown how HRQoL evolves over time, and assessments at different time points may lead to different results. METHODS: In a NORCAST sub study, OHCA survivors eligible for health status (EQ-5D-3L) and HRQoL (SF-36) assessments were examinated six months and five years after OHCA. At five-year follow-up, survivors also retrospectively assessed their health status for each consecutive year following OHCA. The next of kin independently assessed health status and HRQoL of their respective OHCA survivors. RESULTS: Among 138 survivors alive after six months and 117 after five years, 80 (88% male) completed both follow-ups. Health status and HRQoL remained stable over time, except for increasing SF-36 mental summary score and decreasing physical functioning and physical component score. Anxiety and depression levels were generally low, although younger survivors stated more anxiety than older survivors. Retrospective assessment showed reduced health status for the first two years, which increased only from the third year. Explorative analyses revealed that younger age, longer time to return of spontaneous circulation (tROSC) and late awakening affected health status, particularly in the first two years post-arrest. CONCLUSIONS: OHCA survivors showed stable health status and HRQoL with only minor differences between six months and five years. Younger survivors with long tROSC, late awakening, and more anxiety and depression symptoms at six months, had reduced health status the first two years with significant improvements towards the fourth year.

Cognitive function in non-hospitalized patients 8-13 months after acute COVID-19 infection: A cohort study in Norway.

Studies have reported reduced cognitive function following COVID-19 illness, mostly from hospital settings with short follow-up times. This study recruited non-hospitalized COVID-19 patients from a general population to study prevalence of late cognitive impairment and associations with initial symptoms. We invited patients with PCR-confirmed COVID-19. A postal questionnaire addressed basic demographics, initial COVID-19 symptoms and co-morbidity about 4 months after diagnosis. About 7 months later, we conducted cognitive tests using the Cambridge Neuropsychological Test Automated Battery, comprising four tests for short-term memory, attention and executive function. We present descriptive statistics using z-scores relative to UK population norms and defined impairment as z-score <-1.5. We used multivariable logistic regression with impairment as outcome. Continuous domain scores were analysed by multiple linear regression. Of the initial 458 participants; 305 were invited, and 234 (77%) completed cognitive testing. At median 11 (range 8-13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001). In each domain, 4-14% were cognitively impaired; 68/232 (29%) were impaired in ≥ 1 of 4 tests. There was no association between initial symptom severity and impairment. Multivariable linear regression showed association between spatial working memory and initial symptom load (6-9 symptoms vs. 0-5, coef. 4.26, 95% CI: 0.65; 7.86). No other dimension scores were associated with symptom load. At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome.

Cognitive Impairment 13 Months After Hospitalization for COVID-19.

This study assessed cognitive function 13 months after hospital discharge for coronavirus disease 2019 (COVID-19), using computer-based cognitive tests. Compared to population norms, 14%-25% of patients were impaired in each dimension, and 53% had cognitive impairment in 1 or more of 4 tests. There was some association with acute COVID-19 disease severity.

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.

Complement ratios C3bc/C3 and sC5b-9/C5 do not increase the sensitivity of detecting acute complement activation systemically.

BACKGROUND: Complement activation plays an important pathogenic role in numerous diseases. The ratio between an activation product and its parent protein is suggested to be more sensitive to detect complement activation than the activation product itself. In the present study we explored whether the ratio between the activation product and the parent protein for C3 (C3bc/C3) and for C5 (sC5b-9/C5) increased the sensitivity to detect complement activation in acute clinical settings compared to the activation product alone. MATERIALS AND METHODS: Samples from patients with acute heart failure following ST-elevated myocardial infarction (STEMI) and from patients with out-of-hospital cardiac arrest (OHCA) were used. C3, C3bc and C5, sC5b-9 were analysed in 629 and 672 patient samples, respectively. Healthy controls (n = 20) served to determine reference cut-off values for activation products and ratios, defined as two SD above the mean. RESULTS: Increased C3bc/C3- and sC5b-9/C5 ratios were vastly dependent on C3bc and sC5b-9. Thus, 99.5 % and 98.1 % of the increased C3bc/C3- and sC5b-9/C5 ratios were solely dependent on increased C3bc and sC5b-9, respectively. Significantly decreased C3 and C5 caused increased ratios in only 3/600 (0.5 %) and 4/319 (1.3 %) samples, respectively. Strong correlations between C3bc and C3bc/C3-ratio and between sC5b-9 and sC5b-9/C5-ratio were found in the STEMI- (r = 0.926 and r = 0.786, respectively) and the OHCA-population (r = 0.908 and r = 0.843, respectively; p < 0.0001 for all). Importantly, sC5b-9 identified worse outcome groups better than sC5b-9/C5-ratio. CONCLUSION: C3bc and sC5b-9 were sensitive markers of complement activation. The ratios of C3bc/C3 and sC5b-9/C5 did not improve detection of complement activation systemically.

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.

The management and clinical knowledge of headache disorders among general practitioners in Norway: a questionnaire survey.

BACKGROUND: General practitioners (GPs) diagnose and manage a majority of headache patients seeking health care. With the aim to understand the potential for clinical improvement and educational needs, we performed a study to investigate Norwegian GPs knowledge about headache and its clinical management. METHODS: We invited GPs from a random sample of 130 Norwegian continuous medical education (CME) groups to respond to an anonymous questionnaire survey. RESULTS: 367 GPs responded to the survey (73% of invited CME groups, 7.6% of all GPs in Norway). Mean age was 46 (SD 11) years, with an average of 18 (SD 10) years of clinical experience. In general the national treatment recommendations were followed, while the International Classification of Headache Disorders and other international guidelines were rarely used. Overall, 80% (n = 292) of the GPs suggested adequate prophylactic medication for frequent episodic migraine, while 28% (n = 101) suggested adequate prophylactic medication for chronic tension-type headache (CTTH). Half (52%, n = 191)) of the respondents were aware that different types of acute headache medication can lead to medication-overuse headache (MOH), and 59% (n = 217) knew that prophylactic headache medication does not lead to MOH. GPs often used MRI in the diagnostic work-up. GPs reported that lack of good treatment options was a main barrier to more optimized treatment of headache patients. CONCLUSION: The knowledge of management of CTTH and MOH was moderate compared to migraine among Norwegian GPs.

Complement activation is associated with poor outcome after out-of-hospital cardiac arrest.

BACKGROUND: Cardiopulmonary resuscitation after cardiac arrest initiates a whole-body ischemia-reperfusion injury, which may activate the innate immune system, including the complement system. We hypothesized that complement activation and subsequent release of soluble endothelial activation markers were associated with cerebral outcome including death. METHODS: Outcome was assessed at six months and defined by cerebral performance category scale (1-2; good outcome, 3-5; poor outcome including death) in 232 resuscitated out-of-hospital cardiac arrest patients. Plasma samples obtained at admission and day three were analysed for complement activation products C3bc, the soluble terminal complement complex (sC5b-9), and soluble CD14. Endothelial cell activation was measured by soluble markers syndecan-1, sE-selectin, thrombomodulin, and vascular cell adhesion molecule. RESULTS: Forty-nine percent of the patients had good outcome. C3bc and sC5b-9 were significantly higher at admission compared to day three (p < 0.001 for both) and in patients with poor compared to good outcome (p = 0.03 and p < 0.001, respectively). Unadjusted, higher sC5b-9 at admission was associated with poor outcome (odds ratio 1.08 (95% CI 1.01-1.14), p = 0.024). Adjusted, sC5b-9 was still associated with outcome, but the association became non-significant when time to return-of-spontaneous-circulation above 25 min was included as a covariate. Endothelial cell activation markers increased from admission to day three, but only sE-selectin and thrombomodulin were significantly higher in patients with poor versus good outcome (p = 0.004 and p = 0.03, respectively) and correlated to sCD14 and sC5b-9/C3bc, respectively. CONCLUSION: Complement system activation, reflected by sC5b-9 at admission, leading to subsequent endothelial cell activation, was associated with poor outcome in out-of-hospital cardiac arrest patients.

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.

Health-related quality of life after out-of-hospital cardiac arrest - a five-year follow-up studyJurate Saltyte Benth.

BACKGROUND: Health-related quality of life (HRQoL) is affected after out-of-hospital cardiac arrest (OHCA), but data several years after the arrest are lacking. We assessed long-term HRQoL in OHCA survivors and how known outcome predictors impact HRQoL. METHODS: In adult OHCA survivors, HRQoL was assessed five years post arrest using Short-form 36 (SF-36), EQ-5D-3 L (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) among others. Results were compared to the next of kins' estimates and to a Norwegian reference population. RESULTS: Altogether 96 survivors were included mean 5.3 (range 3.6-7.2) years after OHCA. HRQoL compared well to the reference population, except for lower score for general health with 67.2 (95%CI (62.1; 72.3) vs. 72.9 (71.9; 74.0)), p = 0.03. Younger (≤58 years) vs. older survivors scored lower for general health with mean (SD) of 62.1 (27.5) vs. 73.0 (19.5), p = 0.03, vitality (55.2 (20.5) vs. 64.6 (17.3), p = 0.02, social functioning (75.3 (28.7) vs. 94.1 (13.5), p < 0.001 and mental component summary (49.0 (9.9) vs. 55.8 (6.7), p < 0.001. They scored higher for HADS-anxiety (4.8 (3.6 vs. 2.7 (2.5), p = 0.001, and had lower EQ-5D index (0.72 (0.34) vs. 0.84 (0.19), p = 0.04. Early vs. late awakeners had higher EQ-5D index (0.82 (0.23) vs. 0.71 (0.35), p = 0.04 and lower HADS-depression scores (2.5 (2.9) vs. 3.8 (2.3), p = 0.04. Next of kin estimated HRQoL similar to the survivors' own estimates. CONCLUSIONS: HRQoL five years after OHCA was good and mainly comparable to a matched reference population. Stratified analyses revealed impaired HRQoL among younger survivors and those awakening late, mainly for mental domains.

"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.

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.