Cognitive dysfunction is a common non-motor symptom of Parkinson’s disease (PD). Cognitive decline in PD is likely associated with dysfunction in the cholinergic system, which is affected by synuclein pathology early in the disease course. Recent studies have shown an association between reduced integrity of the basal forebrain (BF), which provides cholinergic innervation to most of cortex, and diminished cognitive functioning in PD. Specifically, those with PD and reduced cholinergic innervation also have higher rates of cognitive impairment. However, no study has directly investigated the relationship between basal forebrain integrity and cortical cholinergic levels. In the present study, we examined this relationship through measures of basal forebrain microstructural integrity and cholinergic nerve terminal density in cortical and subcortical gray matter.

Participants included 92 non-demented individuals with idiopathic PD (M:F=64:28; Age=67.0±7.1 yrs) who underwent structural MRI, diffusion MRI, and [18F] fluoroethoxybenzovesamicol (FEOBV) cholinergic PET imaging. We used a basal forebrain and region of interest defined by AssemblyNet, which uses ensembles of pretrained convolutional neural networks to create a full brain segmentation. Bilateral putamen from this atlas was also included as a control region. We measured microstructural integrity using free water fraction (FWF), a diffusion MRI-derived metric of extracellular water that associates with cellular density and neuroinflammation. For PET data, we computed the distribution volume ratio (DVR) by regions as defined by FreeSurfer. A factor analysis of DVR in all 88 FreeSurfer ROIs resulted in seven clusters of ROIs covering 1) widespread bilateral cortical regions (PC1); 2) subcortical and limbic regions (PC2); 3) bilateral cingulate regions (PC3); 4) left frontal regions (PC4); 5) right frontal and temporal regions (PC5); 6) cerebellum (PC6); and 7) bilateral entorhinal cortex and left temporal cortex (PC7). We performed seven separate regression analyses per ROI (controlling for age and disease duration) to evaluate the association between BF FWF and cholinergic levels in these regions. To determine if these ROIs showed unique associations with BF FWF, we then entered ROIs with a significant association with BF FWF as independent variables in a stepwise regression with forward selection with BF FWF as the dependent variable.

BF FWF was significantly and negatively associated with cholinergic levels in PC1 (AR2=.042, ß=-0.208, p=.04), PC3 (AR2=.044, ß=-0.206, p=.03), PC4 (AR2=.056, ß=-0.239, p=.02), and PC7 (ß=-0.215, p=.04). BF FWF trended towards a negative association with cholinergic levels in PC5 (AR2=.045, ß=-0.168, p=.09) and PC6 (ß=-0.188, p=.09). Putamen FWF did not significantly associate with any of the ROIs. In the follow-up stepwise regression, only PC4 contributed significantly to the overall model (AR2=.061, ß=-0.261, p=.02).

Basal forebrain FWF was inversely related to cholinergic levels in regions that are directly innervated by the basal forebrain (e.g., cingulate cortex, left frontal cortex, and bilateral entorhinal cortex). Future research should directly investigate the relationship between basal forebrain integrity, cortical cholinergic levels, and cognition. Separating the basal forebrain into specific nuclei would also be beneficial, as different nuclei may have differing associations with specific hemispheric cholinergic pathways and cognition.

The prevalence and effects of delirium in very old individuals aged ≥80 years have not yet been systematically evaluated. Therefore, this large single-center study of the one-year prevalence of delirium in 3,076 patients in 27 medical departments of the University Hospital of Zurich was conducted.

Patient scores on the Delirium Observation Screening scale, Intensive Care Delirium Screening Checklist, Diagnostic and Statistical Manual, 5th edition, and electronic Patient Assessment–Acute Care (nursing tool) resulted in the inclusion of 3,076 individuals in 27 departments. The prevalence rates were determined by simple logistic regressions, odds ratios (ORs), and confidence intervals.

Of the 3,076 patients, 1,285 (41.8%) developed delirium. The prevalence rates in the 27 departments ranged from 15% in rheumatology (OR = 0.30) to 73% in intensive care (OR = 5.25). Delirious patients were more likely to have been admitted from long-term care facilities (OR = 2.26) or because of emergencies (OR = 2.24). The length of their hospital stay was twice as long as that for other patients. Some died before discharge (OR = 24.88), and others were discharged to nursing homes (OR = 2.96) or assisted living facilities (OR = 2.2).

This is the largest study to date regarding the prevalence of delirium in patients aged ≥80 years and the medical characteristics of these patients. Almost two out of five patients developed delirium, with a high risk of loss of independence and mortality.

Caring for a relative with dementia is associated with adverse consequences for cardiovascular health. Cognitive and behavioral factors, such as high perceived activity restriction and low frequency of pleasant events have been found to be associated with higher levels of blood pressure, but the role these variables play in the stress and coping process remains understudied. The objective of this study is to analyze the associations between behavioral and psychological symptoms of dementia, activity restriction, frequency of pleasant events, and mean arterial pressure.

Face-to-face interviews and cross-sectional analyses.

Social services, healthcare centers, and adult day services of Comunidad de Madrid, Spain.

One hundred and two family caregivers of a spouse or parent with dementia.

Apart from various sociodemographic and health-related variables, behavioral and psychological symptoms of dementia, activity restriction, and frequency of leisure activities were assessed. In addition, measurement of blood pressure levels was conducted through an electronic sphygmomanometer.

The obtained model suggests that there is a significant indirect association between behavioral and psychological symptoms of dementia and mean arterial pressure through activity restriction and frequency of pleasant events.

The findings of this study provide preliminary support for a potential indirect effect between behavioral and psychological symptoms of dementia and blood pressure, through the effects of behavioral and psychological symptoms of dementia on the caregivers’ levels of activity restriction and frequency of pleasant activities. Our manuscript provides additional support for the pleasant events and activity restriction model (Mausbach et al., 2011; Chattillion et al., 2013), by highlighting the importance of considering caregiving stressors as a source of caregivers’ activity restriction in the theoretical framework of the model.

Delirium is a frequent complication in advanced cancer patients, among whom it is frequently underdiagnosed and inadequately treated. To date, evidence on risk factors and the prognostic impact of delirium on outcomes remains sparse in this patient population.

In this prospective observational cohort study at a single tertiary-care center, 1,350 cancer patients were enrolled. Simple and multiple logistic regression models were utilized to identify associations between predisposing and precipitating factors and delirium. Cox proportional-hazards models were used to estimate the effect of delirium on death rate.

In our patient cohort, the prevalence of delirium was 34.3%. Delirium was associated inter alia with prolonged hospitalization, a doubling of care requirements, increased healthcare costs, increased need for institutionalization (OR 3.22), and increased mortality (OR 8.78). Predisposing factors for delirium were impaired activity (OR 10.82), frailty (OR 4.75); hearing (OR 2.23) and visual impairment (OR 1.89), chronic pneumonitis (OR 2.62), hypertension (OR 1.46), and renal insufficiency (OR 1.82). Precipitating factors were acute renal failure (OR 7.50), pressure sores (OR 3.78), pain (OR 2.86), and cystitis (OR 1.32). On multivariate Cox regression, delirium increased the mortality risk sixfold (HR 5.66). Age ≥ 65 years and comorbidities further doubled the mortality risk of delirious patients (HR 1.77; HR 2.05).

Delirium is common in cancer patients and associated with increased morbidity and mortality. Systematically categorizing predisposing and precipitating factors might yield new strategies for preventing and managing delirium in cancer patients.

Although age and pre-existent dementia are robust risk factors for developing delirium, evidence for patients older than 90 years is lacking. Therefore, this study assesses the delirium prevalence rates and sequelae in this age group.

Based on a Diagnostic and Statistical Manual (DSM)-5, Delirium Observation screening scale (DOS), and Intensive Care Delirium Screening Checklist (ICDSC) construct, in this prospective cohort study, the prevalence rates and sequelae of delirium were determined in 428 patients older than 90 years by simple logistic regressions and corresponding odds ratios (ORs).

The overall prevalence delirium rate was 45.2%, with a wide range depending upon specialty: intermediate and intensive care services (83.1%), plastic surgery and palliative care (75%), neurology (72%), internal medicine (69%) vs. dermatology (26.5%), and angiology (14.5%). Delirium occurred irrespective of age and gender; however, pre-existent dementia was the strongest delirium predictor (OR 36.05). Delirious patients were less commonly admitted from home (OR 0.47) than from assisted living (OR 2.24), indicating functional impairment. These patients were more severely ill, as indicated by emergency (OR 3.25) vs. elective admission (OR 0.3), requirement for intensive care management (OR 2.12) and ventilation (OR 5.56–8.33). At discharge, one-third did not return home (OR 0.22) and almost half were transferred to assisted living (OR 2.63), or deceased (OR 47.76).

At age older than 90 years, the prevalence and sequelae of delirium are substantial. In particular, functional impairment and pre-existent dementia predicted delirium and subsequently, the loss of independence and death were imminent.

Patients with terminal illness are at high risk of developing delirium, in particular, those with multiple predisposing and precipitating risk factors. Delirium in palliative care is largely under-researched, and few studies have systematically assessed key aspects of delirium in elderly, palliative-care patients.

In this prospective, observational cohort study at a tertiary care center, 229 delirious palliative-care patients stratified by age: <65 (N = 105) and ≥65 years (N = 124), were analyzed with logistic regression models to identify associations with respect to predisposing and precipitating factors.

In 88% of the patients, the underlying diagnosis was cancer. Mortality rate and median time to death did not differ significantly between the two age groups. No inter-group differences were detected with respect to gender, care requirements, length of hospital stay, or medical costs. In patients ≥65 years, exclusively predisposing factors were relevant for delirium, including hearing impairment [odds ratio (OR) 3.64; confidence interval (CI) 1.90–6.99; P < 0.001], hypertension (OR 3.57; CI 1.84–6.92; P < 0.001), and chronic kidney disease (OR 4.84; CI 1.19–19.72; P = 0.028). In contrast, in patients <65 years, only precipitating factors were relevant for delirium, including cerebral edema (OR 0.02; CI 0.01–0.43; P = 0.012).

The results of this study demonstrate that death in delirious palliative-care patients occurs irrespective of age. The multifactorial nature and adverse outcomes of delirium across all age in these patients require clinical recognition. Potentially reversible factors should be detected early to prevent or mitigate delirium and its poor survival outcomes.

The general in-hospital mortality and interrelationship with delirium are vastly understudied. Therefore, this study aimed to assess the rates of in-hospital mortality and terminal delirium.

In this prospective cohort study of 28,860 patients from 37 services including 718 in-hospital deaths, mortality rates and prevalence of terminal delirium were determined with simple logistic regressions and their respective odds ratios (ORs).

Although overall in-hospital mortality was low (2.5%), substantial variance between services became apparent: Across intensive care services the rate was 10.8% with a 5.8-fold increased risk, across medical services rates were 4.4% and 2.4-fold, whereas at the opposite end, across surgical services rates were 0.7% and 87% reduction, respectively. The highest in-hospital mortality rate occurred on the palliative care services (27.3%, OR 19.45). The general prevalence of terminal delirium was 90.7% and ranged from 83.2% to 100%. Only across intensive care services (98.1%, OR 7.48), specifically medical intensive care (98.1%, OR 7.48) and regular medical services (95.8%, OR 4.12) rates of terminal delirium were increased. In contrast, across medical services (86.4%, OR 0.32) and in particular oncology (73.9%, OR 0.25), pulmonology (72%, OR 0.31) and cardiology (63.2%, OR 0.4) rates were decreased. For the remaining services, rates of terminal delirium were the same.

Although in-hospital mortality was low, the interrelationship with delirium was vast: most patients were delirious at the end of life. The implications of terminal delirium merit further studies.

Virus outbreaks such as the current SARS-CoV-2 pandemic are challenging for health care workers (HCWs), affecting their workload and their mental health. Since both, workload and HCW's well-being are related to the quality of care, continuous monitoring of working hours and indicators of mental health in HCWs is of relevance during the current pandemic. The existing investigations, however, have been limited to a single study period. We examined changes in working hours and mental health in Swiss HCWs at the height of the pandemic (T1) and again after its flattening (T2).

We conducted two cross-sectional online studies among Swiss HCWs assessing working hours, depression, anxiety, and burnout. From each study, 812 demographics-matched participants were included into the analysis. Working hours and mental health were compared between the two samples.

Compared to prior to the pandemic, the share of participants working less hours was the same in both samples, whereas the share of those working more hours was lower in the T2 sample. The level of depression did not differ between the samples. In the T2 sample, participants reported more anxiety, however, this difference was below the minimal clinically important difference. Levels of burnout were slightly higher in the T2 sample.

Two weeks after the health care system started to transition back to normal operations, HCWs' working hours still differed from their regular hours in non-pandemic times. Overall anxiety and depression among HCWs did not change substantially over the course of the current SARS-CoV-2 pandemic.

The prevalence rates and adversities of delirium have not yet been systematically evaluated and are based on selected populations, limited sample sizes, and pooled studies. Therefore, this study assesses the prevalence rates and outcome of and odds ratios for managing services for delirium.

In this prospective cohort study, based on the Diagnostic and Statistical Manual (DSM) 5, the Delirium Observation Screening (DOS) scale, and the Intensive Care Delirium Screening Checklist (ICDSC) construct, 28,118 patients from 35 managing services were included, and the prevalence rates and adverse outcomes were determined by simple logistic regressions and their corresponding odds ratios (ORs).

Delirious patients were older, admitted from institutions (OR 3.44–5.2), admitted as emergencies (OR 1.87), hospitalized twice longer, and discharged, transferred to institutions (OR 5.47–6.6) rather than home (OR 0.1), or deceased (OR 43.88). The rate of undiagnosed delirium was 84.2%. The highest prevalence rates were recorded in the intensive care units (47.1–84.2%, pooled 67.9%); in the majority of medical services, rates ranged from 20% to 40% (pooled 26.2%), except, at both ends, palliative care (55.9%), endocrinology (8%), and rheumatology (4.4%). Conversely, in surgery and its related services, prevalence rates were lower (pooled 13.1%), except for cardio- and neurosurgical services (53.3% and 46.4%); the lowest prevalence rate was recorded in obstetrics (2%).

Delirium remains underdiagnosed, and novel screening approaches are required. Furthermore, this study identified the impact of delirium on patients, determined the prevalence rates for 32 services, and elucidated the association between individual services and delirium.

Nursing instruments have the potential for daily screening of delirium; however, they have not yet been evaluated. Therefore, after assessing the functional domains of the electronic Patient Assessment — Acute Care (ePA-AC), this study evaluates the cognitive and associated domains.

In this prospective cohort study in the intensive care unit, 277 patients were assessed and 118 patients were delirious. The impacts of delirium on the cognitive domains, consciousness and cognition, communication and interaction, in addition to respiration, pain, and wounds were determined with simple logistic regressions and their respective odds ratios (ORs).

Delirium was associated with substantial impairment throughout the evaluated domains. Delirious patients were somnolent (OR 6), their orientation (OR 8.2–10.6) and ability to acquire knowledge (OR 5.5–11.6) were substantially impaired, they lost the competence to manage daily routines (OR 8.2–22.4), and their attention was compromised (OR 12.8). In addition, these patients received psychotropics (OR 3.8), were visually impaired (OR 1.8), unable to communicate their needs (OR 5.6–7.6), displayed reduced self-initiated activities (OR 6.5–6.9) and challenging behaviors (OR 6.2), as well as sleep–wake disturbances (OR 2.2–5), Furthermore, delirium was associated with mechanical ventilation, abdominal/thoracic injuries or operations (OR 4.2–4.4), and sensory perception impairment (OR 3.9–5.8).

Delirium caused substantial impairment in cognitive and associated domains. In addition to the previously described functional impairments, these findings will aid the implementation of nursing instruments in delirium screening.

Excessive pain perception may lead to unnecessary diagnostic testing or invasive procedures to result in iatrogenic complications and prolonged disability. Naturalistic studies on depressed patients with chronic pain investigating the impact of medical speciality on treatment outcome in a primary care setting are lacking.

In this observational study, we examined whether the magnitude of pain reduction in 444 depressed patients under venlafaxine would differently relate to the medical speciality of the 122 treating physicians, namely psychiatrists (n=110 patients), general practitioners (n=236 patients), and internists (n=98 patients).

Independent of demographic factors, comorbidity, severity of pain and illness at study entry, and the duration of pain and depression, patients seemed to profit significantly less in terms of pain reduction (p< .001) and of reduction in severity of their illness by psychiatrists as compared to general practitioners (p< .019) and internists (p< .002).

Worldwide data are extensively lacking in regard to patients with depressive symptoms under therapy with antidepressants in the primary care setting. We hypothesized that the magnitude of pain reduction under treatment with venlafaxine differently relates to regional origin of patients.

We conducted a prospective naturalistic observational trial on 420 pain sufferers with depressive symptoms from all over Switzerland who were treated with venlafaxine by 122 physicians in primary care. Previous and additional antidepressant medication was not taken into account. Physicians rated illness severity using the Clinical Global Impression severity scale and pain intensity by means of visual analogue scales.

Compared with Middle European patients (ME), those from Eastern Europe (EE), and Southern Europe (SE) were younger and presented more intense overall pain mainly affecting the head, extremities and back. In addition, SE patients suffered more intense thoracic pain than ME patients, and EE patients suffered less frequently from abdominal pain compared to their ME and SE counterparts. Furthermore, 3 months after study entry, ME patients were found to profit more from treatment with venlafaxine in terms of overall illness severity and pain intensity than patients from EE and SE.

Excessive pain perception may lead to unnecessary diagnostic testing or invasive procedures resulting in iatrogenic complications and prolonged disability. Naturalistic studies on patients with chronic pain and depressive symptoms investigating the impact of medical speciality on treatment outcome in a primary care setting are lacking.

In this observational study, we examined whether the magnitude of pain reduction in 444 patients with depressive symptomatology under venlafaxine would relate differently to the medical speciality of the 122 treating physicians, namely psychiatrists (n = 110 patients), general practitioners (n = 236 patients), and internists (n = 98 patients).

Independent of age, gender, patient's region of origin, comorbidity, severity and duration of pain, and depressive symptoms at study entry, patients seemed to benefit significantly less in terms of pain reduction (p < 0.001) and of reduction in severity of depressive symptomatology by psychiatrists as compared to general practitioners (p < 0.019) and internists (p < 0.002).

The findings suggest that patients referred to psychiatrists are more difficult to treat than those referred to general practitioners and internists, and might not have been adequately prepared for psychiatric interventions. A supporting cooperation and networking between psychiatrists and primary care physicians may contribute to an integrated treatment concept and therefore, may lead to a better outcome in this challenging patient group.

Nursing assessments have been recommended for the daily screening for delirium; however, the utility of individual items have not yet been tested. In a first step in establishing the potential of the electronic Patient Assessment-Acute Care (ePA-AC) as such, the impact of delirium on the functional domains was assessed.

In this prospective observational cohort study, 277 patients were assessed and 118 patients were delirious. The impact of delirium on functional domains of the ePA-AC related to self-initiated activity, nutrition, and elimination was determined with simple logistic regressions.

Patients with delirium were older, sicker, were more commonly sedated during the assessment, stayed longer in the intensive care unit (ICU) and floors, and less commonly discharged home. A general pattern was the loss of abilities and full functioning equivalent to global impairment. For self-initiated mobility, in and out of the bed sizable limitations were noted and substantial inability to transfer caused friction and shearing. Similarly, any exhaustion and fatigue were associated with delirium. For self-initiated grooming and dressing, the impairment was greater in the upper body. Within the nutritional domain, delirium affected self-initiated eating and drinking, the amount of food and fluids, energy and nutrient, as well as parenteral nutrition requirement. In delirious patients, the fluid demand was rather increased than decreased, tube feeding more often required and dysphagia occurred. For the elimination domain, urination was not affected — of note, most patients were catheterized, whereas abilities to initiate or control defecation were affected.

Delirium was associated with sizable impairment in the level of functioning. These impairments could guide supportive interventions for delirious patients and perspectively implement nursing instruments for delirium screening.

Delirium is a common complication in palliative care patients, especially in the terminal phase of the illness. To date, evidence regarding risk factors and prognostic outcomes of delirium in this vulnerable population remains sparse.

In this prospective observational cohort study at a tertiary care center, 410 palliative care patients were included. Simple and multiple logistic regression models were used to identify associations between predisposing and precipitating factors and delirium in palliative care patients.

The prevalence of delirium in this palliative care cohort was 55.9% and reached 93% in the terminally ill. Delirium was associated with prolonged hospitalization (p < 0.001), increased care requirements (p < 0.001) and health care costs (p < 0.001), requirement for institutionalization (OR 0.11; CI 0.069–0.171; p < 0.001), and increased mortality (OR 18.29; CI 8.918–37.530; p < 0.001). Predisposing factors for delirium were male gender (OR 2.19; CI 1.251–3.841; p < 0.01), frailty (OR 15.28; CI 5.885–39.665; p < 0.001), hearing (OR 3.52; CI 1.721–7.210; p < 0.001), visual impairment (OR 3.15; CI 1.765–5.607; p < 0.001), and neoplastic brain disease (OR 3.63; CI 1.033–12.771; p < 0.05). Precipitating factors for delirium were acute renal failure (OR 6.79; CI 1.062–43.405; p < 0.05) and pressure sores (OR 3.66; CI 1.102–12.149; p < 0.05).

Our study identified several predisposing and precipitating risk factors for delirium in palliative care patients, some of which can be targeted early and modified to reduce symptom burden.

The hypoactive, hyperactive, and mixed subtypes of delirium differently impact patient management and prognosis, yet the evidence remains sparse. Therefore, we examined the outcome of varying management strategies in the subtypes of delirium.

In this observational cohort study, 602 patients were managed for delirium over 20 days with the following strategies: supportive care alone or in combination with psychotropics, single, dual, or triple+ psychotropic regimens. Cox regression models were calculated for time to remission and benefit rates (BRs) of management strategies.

Generally, the mixed subtype of delirium caused more severe and persistent delirium, and the hypoactive subtype was more persistent than the hyperactive subtype. The subtypes of delirium were similarly predictive for mortality (P = 0.697) and transfer to inpatient psychiatric care (P = 0.320). In the mixed subtype, overall, psychotropic drugs were administered more often (P = 0.016), and particularly triple+ regimens were administered more commonly compared to hypoactive delirium (P = 0.007). Patients on supportive care benefited most, whereas those on triple+ regimens did worst in terms of remission in all groups of hypoactive, hyperactive, and mixed subtypes (BR: 4.59, CI 2.01–10.48; BR: 4.59, CI 1.76–31.66; BR: 3.36, CI 1.73–6.52; all P < 0.05).

The mixed subtype was more persistent to management than the hypoactive and hyperactive subtypes. Delirium management remains controversial and, generally, supportive care benefited patients most. Psychopharmacological management for delirium requires careful choosing of and limiting the number of psychotropics.