Comprehensive geriatric assessment as an essential tool to register or update DNR codes in a tertiary care hospital.

PURPOSE: To investigate the prevalence of Do not Resuscitate (DNR) code registration in patients with a geriatric profile admitted to Antwerp University Hospital, a tertiary care hospital in Flanders, Belgium, and the impact of comprehensive geriatric assessment (CGA) on DNR code registration. PATIENTS AND METHODS: Retrospective analysis of a population of 543 geriatric patients (mean age 82.4 ± 5.19 years, 46.4% males) admitted to Antwerp University Hospital from 2018 to 2020 who underwent a CGA during admission. An association between DNR code registration status before and at hospital admission and age, gender, ethnicity, type of residence, clinical frailty score (CFS), cognitive and oncological status, hospital ward and stay on intensive care was studied. Admissions before and during the first wave of the pandemic were compared. RESULTS: At the time of hospital admission, a DNR code had been registered for 66.3% (360/543) of patients. Patients with a DNR code at hospital admission were older (82.7 ± 5.5 vs. 81.7 ± 4.6 years, p = 0.031), more frail (CFS 5.11 ± 1.63 vs. 4.70 ± 1.61, p = 0.006) and less likely to be admitted to intensive care. During the hospital stay, the proportion of patients with a DNR code increased to 77% before and to 85.3% after CGA (p < 0.0001). Patients were consulted about and agreed with the registered DNR code in 55.8% and 52.1% of cases, respectively. The proportion of patients with DNR codes at the time of admission or registered after CGA did not differ significantly before and after the start of the COVID-19 pandemic. CONCLUSION: After CGA, a significant increase in DNR registration was observed in hospitalized patients with a geriatric profile.

Combined ultrasound of m. quadriceps and diaphragm to determine the occurrence of sarcopenia and prolonged ventilation in a COVID-19 ICU cohort: The COVID-SARCUS trial.

OBJECTIVE: The aim of this study was to determine the development of sarcopenia in a COVID-19 intensive care unit population by sequential quadriceps and diaphragm ultrasound and its relationship with hospital outcomes. METHODS: We assessed muscle thickness, cross-sectional area, fascicle length, pennation angle, and echo intensity within 48 h after intubation, at days 5 and 10 and at discharge from the intensive care unit in 30 critically ill patients with confirmed COVID-19. RESULTS: A different evolution of muscle thickness of the diaphragm and m. rectus femoris was observed; the changes between the two muscles were not correlated (Pearson's χ2 3.91, P = 0.419). The difference in muscle thickness was linked to the outcome for both m. rectus femoris and diaphragm, with the best survival seen in the group with stable muscle thickness. The greatest loss of muscle thickness occurred between days 5 and 10. The echo intensity was higher in the patients with increased muscle thickness, who also had a worse prognosis. There was a correlation between cross-sectional area on day 5 and handgrip strength (r = 0.290, P = 0.010). Only 31% of patients were able to return to their preadmission residence without any additional rehabilitation. CONCLUSIONS: Muscle atrophy and decline in muscle strength appear in the earliest stages after admission to the intensive care unit and are related to functional outcome.

Bedside medication review with cognitive and depression screening by a clinical pharmacist as part of a comprehensive geriatric assessment in hospitalized older patients with polypharmacy: A pilot study.

BACKGROUND: Polypharmacy is highly prevalent in older patients with multimorbidity and is associated with increased risk of adverse drug events. This pilot study investigated the added value of a bedside medication review with cognitive and depression screening by a clinical pharmacist to identify potentially inappropriate medications (PIMs) and medication use issues in older patients with polypharmacy. METHODS AND RESULTS: In the period from September 2018 to March 2019, a clinical pharmacist took part in the comprehensive geriatric assessment of 37 older patients hospitalized at Antwerp University Hospital and conducted a medication review consisting of a record review, a bedside interview questionnaire covering medication use, evaluation of cognitive function (abbreviated MMSE), depression (GDS-4), and systematic check for possible PIMs (STOPP/START criteria). Patients were 83±4 years old and on a median of 12 home medications (range 5-20). The clinical pharmacist formulated an average of 7.7 recommendations to optimize medication use per patient, of which 89.9% were considered clinically relevant by the geriatrician. Only 2 out of 286 PIMs were discovered during routine electronic validation of medication prescriptions. Supervision of medication intake was absent in 75% of cognitively impaired patients, but advice to do so was implemented in 86.4% of cases. The multidisciplinary geriatric advice was communicated to the treating physician, who fully implemented 33.8% of the recommendations. CONCLUSIONS: Bedside medication review with cognitive and depression screening by a clinical pharmacist is useful to discover polypharmacy related problems and medication intake issues in a population of geriatric patients. Systematic screening for cognitive impairment and depression are needed to detect patients in need of support for correct medication use and therapy compliance.

Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people. Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout. At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS. This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population.

The Relationship Between Childhood Trauma and the Response to Group Cognitive-Behavioural Therapy for Chronic Fatigue Syndrome.

OBJECTIVE: To examine the relationship between childhood trauma and the response to group cognitive-behavioural therapy (GCBT) for chronic fatigue syndrome (CFS). METHODS: A single cohort study conducted in an outpatient university referral center for CFS including a well-documented sample of adult patients meeting the CDC criteria for CFS and having received 9 to 12 months of GCBT. A mixed effect model was adopted to examine the impact of childhood trauma on the treatment response in general and over time. The main outcome measures were changes in fatigue, as assessed with the Checklist Individual Strength (total score), and physical functioning, as gauged with the Short Form 36 Health Survey subscale, with the scales being completed at baseline, immediately after treatment completion and after 1 year. RESULTS: We included 105 patients with CFS. Childhood trauma was not significantly associated with the response to GCBT over time on level of fatigue or physical functioning. CONCLUSION: Childhood trauma does not seem to have an effect on the treatment response to dedicated GCBT for CFS sufferers over time. Therefore, in the allocation of patients to this kind of treatment, a history of childhood trauma should not be seen as prohibitive.

Assessing chronic fatigue syndrome: Self-reported physical functioning and correlations with physical testing.

The pathophysiology of chronic fatigue syndrome (CFS) remains unclear; no biomarkers have thus far been identified or physical tests designed to underpin its diagnosis. Assessment mainly uses Fukuda's criteria and is based on the exclusion of symptoms related to other diseases/syndromes, subjective self-reporting, and outcomes of self-report questionnaires. In order to improve the baseline assessment and progress evaluation of individuals suspected of CFS and using an association-oriented research strategy and a cross-correlational design, this study investigates possible associations between the performance on two physical tests, i.e. 'Timed Loaded Standing' (TLS), assessing trunk-arm endurance, and the 'Stops Walking with Eyes Closed while performing a secondary Cognitive Task' (SWECCT), measuring impaired automaticity of gait, and the results of two self-report questionnaires, the Checklist Individual Strength (CIS, total score and fatigue subscale score) and the physical functioning and vitality subscales of the Short Form Health Survey (SF-36) to gauge the participants' subjective feelings of fatigue and beliefs regarding their abilities to perform daily-life activities. Comparisons of the outcomes obtained in 27 female patients with a confirmed diagnosis of CFS revealed that trunk-arm endurance as measured with the TLS correlated with the SF-36 physical functioning subscale only (raw p value: 0.004). None of the other correlations were statistically significant. It is concluded that the TLS may have potential as an objective assessment tool to support the diagnosis and monitoring of treatment effects in CFS.

Scoring of Hypersomnolence and Fatigue in Patients With Obstructive Sleep Apnea Treated With a Titratable Custom-Made Mandibular Advancement Device.

STUDY OBJECTIVES: The objective of this study was to measure fatigue and hypersomnolence in patients with obstructive sleep apnea (OSA) treated with a mandibular advancement device (MAD), using Epworth Sleepiness Scale (ESS) for hypersomnolence and Checklist Individual Strength questionnaire (CIS20R) for fatigue. METHODS: This was a single-center, prospective cohort study. A total of 58 patients with OSA filled out ESS and CIS20R questionnaires at baseline and after 3 months of MAD treatment. A total of 39 full datasets were collected. Statistical analysis for reliability of the questionnaires, comparison between baseline and 3-month follow-up, correlation between the changes in the values of the two questionnaires, and changes in apnea-hypopnea index (AHI) were performed. RESULTS: CIS20R showed excellent reliability in this patient group at baseline and 3-month follow-up (Cronbach α = .97), ESS showed a marginally good reliability (Cronbach α = .82). The CIS20R (82/140) expressed high levels of fatigue at baseline, and ESS showed a normal level of daytime sleepiness. AHI, ESS, and CIS20R were significantly reduced under MAD treatment. A significant correlation between ESS and CIS20R was observed. No significant correlation between any of the questionnaires and the change in AHI was found. CONCLUSIONS: The CIS20R questionnaire results showed a high level of fatigue in the patients with OSA, and the questionnaire can be used to evaluate changes in fatigue due to MAD treatment after 3 months. The ESS failed to show similar characteristics. Therefore, a combination of ESS for hypersomnolence with CIS20R for fatigue is proposed for the follow-up of patients with OSA treated with MAD.

Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study in Patients and Healthy Subjects.

PURPOSE: Oxidative stress has been proposed as a contributor to pain in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). During incremental exercise in patients with ME/CFS, oxidative stress enhances sooner and antioxidant response is delayed. We explored whether oxidative stress is associated with pain symptoms or pain changes following exercise, and the possible relationships between oxidative stress and parasympathetic vagal nerve activity in patients with ME/CFS versus healthy, inactive controls. METHODS: The present study reports secondary outcomes from a previous work. Data from 36 participants were studied (women with ME/CFS and healthy controls). Subjects performed a submaximal exercise test with continuous cardiorespiratory monitoring. Levels of thiobarbituric acid-reactive substances (TBARSs) were used as a measure of oxidative stress, and heart rate variability was used to assess vagal activity. Before and after the exercise, subjects were asked to rate their pain using a visual analogic scale. FINDINGS: Significant between-group differences in pain at both baseline and following exercise were found (both, P < 0.007). In healthy controls, pain was significantly improved following exercise (P = 0.002). No change in oxidative stress level after exercise was found. Significant correlation between TBARS levels and pain was found at baseline (r = 0.540; P = 0.021) and after exercise (r = 0.524; P = 0.024) in patients only. No significant correlation between TBARS and heart rate variability at baseline or following exercise was found in either group. However, a significant correlation was found between exercise-induced changes in HRV and TBARS in healthy controls (r = -0.720; P = 0.001). IMPLICATIONS: Oxidative stress showed an association with pain symptoms in people with ME/CFS, but no exercise-induced changes in oxidative stress were found. In addition, the change in parasympathetic activity following exercise partially accounted for the change in oxidative stress in healthy controls. More research is required to further explore this link.

Influence of Morphine and Naloxone on Pain Modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia, and Controls: A Double-Blind, Randomized, Placebo-Controlled, Cross-Over Study.

BACKGROUND: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown. METHODS: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten chronic fatigue syndrome (CFS)/fibromyalgia (FM) patients, 11 rheumatoid arthritis (RA) patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/mL Naloxone) and placebo (2 mL Aqua) group. Pressure pain thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned pain modulation (CPM) efficacy and deep tissue pain pressure were assessed by adding ischemic occlusion at the opposite upper arm. RESULTS: Deep tissue pain pressure was lower and temporal summation higher in CFS/FM (P = 0.002 respectively P = 0.010) and RA patients (P = 0.011 respectively P = 0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (P time = 0.034). Accordingly, PPTs increased after placebo (P time = 0.015), and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, deep tissue pain, temporal summation or CPM in the control group. CONCLUSIONS: This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced deep tissue pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA.

Differential effects of childhood trauma subtypes on fatigue and physical functioning in chronic fatigue syndrome.

OBJECTIVE: There is wide consensus that childhood trauma plays an important role in the aetiology of chronic fatigue syndrome (CFS). The current study examines the differential effects of childhood trauma subtypes on fatigue and physical functioning in individuals suffering from CFS. METHODS: Participants were 155 well-documented adult, predominantly female CFS patients receiving treatment at the outpatient treatment centre for CFS of the Antwerp University Hospital in Belgium. Stepwise regression analyses were conducted with outcomes of the total score of the Checklist Individual Strength (CIS) measuring fatigue and the scores on the physical functioning subscale of the Medical Outcomes Short Form 36 Health Status Survey (SF-36) as the dependent variables, and the scores on the five subscales of the Traumatic Experiences Checklist (TEC) as the independent variables. RESULTS: The patients' fatigue (ß=1.38; p=0.025) and physical functioning scores (ß=-1.79; p=0.034) were significantly predicted by childhood sexual harassment. There were no significant effects of emotional neglect, emotional abuse, bodily threat, or sexual abuse during childhood. CONCLUSION: Of the childhood trauma subtypes investigated, sexual harassment emerged as the most important predictor of fatigue and poor physical functioning in the CFS patients assessed. These findings have to be taken into account in further clinical research and in the assessment and treatment of individuals coping with chronic fatigue syndrome.

The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People.

BACKGROUND: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post-exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS. OBJECTIVES: This study aims to examine the role of the autonomic nervous system in exercise-induced analgesia in healthy people and those with ME/CFS, by studying the recovery of autonomic parameters following aerobic exercise and the relation to changes in self-reported pain intensity. STUDY DESIGN: A controlled experimental study. SETTING: The study was conducted at the Human Physiology lab of a University. METHODS: Twenty women with ME/CFS- and 20 healthy, sedentary controls performed a submaximal bicycle exercise test known as the Aerobic Power Index with continuous cardiorespiratory monitoring. Before and after the exercise, measures of autonomic function (i.e., heart rate variability, blood pressure, and respiration rate) were performed continuously for 10 minutes and self-reported pain levels were registered. The relation between autonomous parameters and self-reported pain parameters was examined using correlation analysis. RESULTS: Some relationships of moderate strength between autonomic and pain measures were found. The change (post-exercise minus pre-exercise score) in pain severity was correlated (r = .580, P = .007) with the change in diastolic blood pressure in the healthy group. In the ME/CFS group, positive correlations between the changes in pain severity and low frequency (r = .552, P = .014), and between the changes in bodily pain and diastolic blood pressure (r = .472, P = .036), were seen. In addition, in ME/CHFS the change in headache severity was inversely correlated (r = -.480, P = .038) with the change in high frequency heart rate variability. LIMITATIONS: Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations. CONCLUSIONS: Reduced parasympathetic reactivation during recovery from exercise is associated with the dysfunctional exercise-induced analgesia in ME/CFS. Poor recovery of diastolic blood pressure in response to exercise, with blood pressure remaining elevated, is associated with reductions of pain following exercise in ME/CFS, suggesting a role for the arterial baroreceptors in explaining dysfunctional exercise-induced analgesia in ME/CFS patients.Key words: Aerobic exercise, aerobic power index, autonomic nervous system, exercise-induced analgesia, exercise-induced hypoalgesia, fibromyalgia, heart rate variability, stress-induced analgesia, pain.

A case of recurrent fever in an older man caused by Coxiella burnetii.

Q fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii. While it is mostly an asymptomatic infection, acute disease can manifest as fever associated with signs of pneumonia or hepatitis. Chronic Q fever develops in 1-5% of infected persons. Patients with a history of cardiac valve surgery, vascular prosthesis or vascular aneurysm, and to a lesser extent patients with pre-existing valvular disease, immune deficiencies, or renal insufficiency, are at highest risk. Most common manifestations are Q fever endocarditis and Q fever vascular infection. We present a case of chronic Q fever, followed by a summary of available literature.

Binocular Vision in Chronic Fatigue Syndrome.

INTRODUCTION AND PURPOSE: To compare binocular vision measurements between Chronic Fatigue Syndrome (CFS) patients and healthy controls. METHODS: Forty-one CFS patients referred by the Reference Centre for Chronic Fatigue Syndrome of the Antwerp University Hospital and forty-one healthy volunteers, matched for age and gender, underwent a complete orthoptic examination. Data of visual acuity, eye position, fusion amplitude, stereopsis, ocular motility, convergence, and accommodation were compared between both groups. RESULTS: Patients with CFS showed highly significant smaller fusion amplitudes (P < 0.001), reduced convergence capacity (P < 0.001), and a smaller accommodation range (P < 0.001) compared to the control group. CONCLUSION: In patients with CFS binocular vision, convergence and accommodation should be routinely examined. CFS patients will benefit from reading glasses either with or without prism correction in an earlier stage compared to their healthy peers. Convergence exercises may be beneficial for CFS patients, despite the fact that they might be very tiring. Further research will be necessary to draw conclusions about the efficacy of treatment, especially regarding convergence exercises. To our knowledge, this is the first prospective study evaluating binocular vision in CFS patients.

Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of an activity pacing self-management (APSM) intervention in improving performance of daily life activities in women with chronic fatigue syndrome (CFS). METHOD: A total of 33 women with CFS (age 41.1±11.2 yr) were randomly allocated to APSM (experimental group; n=16) or relaxation (control group; n=17). Main outcome measures included the Canadian Occupational Performance Measure (COPM; primary) and Checklist Individual Strength (CIS). RESULTS: COPM scores changed significantly over time in both groups (p=.03). The change in Satisfaction scores showed a significant difference in favor only of APSM (effect size=0.74 [0.11, 1.4]). CIS scores decreased significantly in the experimental group only (p<.01). CONCLUSION: APSM was found to be feasible and effective in optimizing participation in desired daily life activities in women with CFS. Replication in a larger sample with long-term follow-up is required.

Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma.

OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (GR) sensitivity. In addition, childhood trauma is considered a major risk factor for the syndrome. This study examines DNA methylation of the GR gene (NR3C1) in CFS and associations with childhood sexual and physical trauma. METHODS: Quantification of DNA methylation within the 1F promoter region of NR3C1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls by using Sequenom EpiTYPER. Further, we examined the association of NR3C1-1F promoter methylation with the outcomes of the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test in a subset of the study population. Mann-Whitney U tests and Spearman correlations were used for statistical analyses. RESULTS: Overall NR3C1-1F DNA methylation was lower in patients with CFS than in controls. After cytosine guanine dinucleotide (CpG)-specific analysis, CpG_1.5 remained significant after Bonferroni correction (adjusted p = .0014). Within the CFS group, overall methylation (ρ = 0.477, p = .016) and selective CpG units (CpG_1.5: ρ = 0.538, p = .007; CpG_12.13: ρ = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. There was no significant difference in NR3C1-1F methylation between traumatized and nontraumatized patients. CONCLUSIONS: We found evidence of NR3C1 promoter hypomethylation in female patients with CFS and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression). However, we found no evidence of an additional effect of childhood trauma on CFS via alterations in NR3C1 methylation.

Timed loaded standing in female chronic fatigue syndrome compared with other populations.

Patients with chronic fatigue syndrome (CFS), like patients with osteoporosis, have similar difficulties in standing and sitting. The aim of the study was to compare combined trunk and arm endurance among women with CFS (n = 72), women with osteoporosis (n = 30), nondisabled women (n = 55), and women from non-industrialized countries (n = 58) using the timed loaded standing (TLS) test. TLS measures how long a person can hold a 1 kg dumbbell in each hand in front of him or her with straight arms. TLS was higher in the industrialized nondisabled population than in the non-industrialized study population (p < 0.001) and in patients with osteoporosis (p = 0.002). TLS was lower in patients with CFS than in nondisabled controls (p < 0.001). After adjusting for age, body height, and weight, combined trunk and arm endurance was lower in CFS patients than in osteoporotic patients, even though the patients with osteoporosis were more than 25 yr older (p < 0.001) [corrected]. In CFS, TLS was lower than in the non-industrialized group (p = 0.02). Since only women were studied, external validity of the results is limited to adult female patients with CFS. TLS revealed a specific biomechanical weakness in CFS patients that can be taken into account from the onset of a rehabilitation program. We propose that influencing the quality, rather than the quantity, of movement could be used in the rehabilitation.

Reduced gait automaticity in female patients with chronic fatigue syndrome: Case-control study.

Patients with chronic fatigue syndrome (CFS) report difficulties walking for a prolonged period of time. This study compares gait automaticity between women with CFS and nondisabled controls. The "stops walking with eyes closed with secondary cognitive task" test is based on the classic "stops walking while talking" test but compares walking with eyes closed while performing a secondary cognitive task in a female CFS population (n = 34) and in female nondisabled controls (n = 38). When initiating gate, 23.5% of patients with CFS looked toward the ground compared with only 2.6% of nondisabled controls. After 7 m, subjects were asked to close their eyes, and after another 7 m, they were asked, "How much is 100 minus 7?" Of the patients with CFS, 55.9% stopped walking compared with 5.3% of nondisabled controls. Less automated walking was observed in patients with CFS than in nondisabled controls (p < 0.001). The test-retest reliability is moderate for global stopping. This simple test observed reduced gait automaticity in patients with CFS for the first time. Dual tasking could be helpful to address the functional limitations found in this particular study.