Fear of making a mistake: a prominent cause of stress for COVID-19 ICU staff-a mixed-methods study.

INTRODUCTION: The COVID-19 pandemic has had a profound effect on many domains of healthcare. Even in high-income countries such as Sweden, the number of patients has vastly outnumbered the resources in affected areas, in particular during the first wave. Staff caring for patients with COVID-19 in intensive care units (ICUs) faced a very challenging situation that continued for months. This study aimed to describe burnout, safety climate and causes of stress among staff working in COVID-19 ICUs. METHOD: A survey was distributed to all staff working in ICUs treating patients with COVID-19 in five Swedish hospitals during 2020 and 2021. The numbers of respondents were 104 and 603, respectively. Prepandemic data including 172 respondents from 2018 served as baseline. RESULTS: Staff exhaustion increased during the pandemic, but disengagement decreased compared with prepandemic levels (p<0.001). Background factors such as profession and work experience had no significant impact, but women scored higher in exhaustion. Total workload and working during both the first and second waves correlated positively to exhaustion, as did being regular ICU staff compared with temporary staff. Teamwork and safety climate remained unchanged compared with prepandemic levels.Respondents reported 'making a mistake' as the most stressful of the predefined stressors. Qualitative analysis of open-ended questions identified 'lack of knowledge and large responsibility', 'workload and work environment', 'uncertainty', 'ethical stress' and 'organization and teamwork' as major causes of stress. CONCLUSION: Despite large workloads, disengagement at work was low in our sample, even compared with prepandemic levels. High levels of exhaustion were reported by the ICU staff who carried the largest workload. Multiple significant causes of stress were identified, with fear of making a mistake the most significant stressor.

Does sleep deprivation increase the vulnerability to acute psychosocial stress in young and older adults?

Sleep loss and psychosocial stress often co-occur in today's society, but there is limited knowledge on the combined effects. Therefore, this experimental study investigated whether one night of sleep deprivation affects the response to a psychosocial challenge. A second aim was to examine if older adults, who may be less affected by both sleep deprivation and stress, react differently than young adults. 124 young (18-30 years) and 94 older (60-72 years) healthy adults participated in one of four conditions: i. normal night sleep & Placebo-Trier Social Stress Test (TSST), ii. normal night sleep & Trier Social Stress Test, iii. sleep deprivation & Placebo-TSST, iv. sleep deprivation & TSST. Subjective stress ratings, heart rate variability (HRV), salivary alpha amylase (sAA) and cortisol were measured throughout the protocol. At the baseline pre-stress measurement, salivary cortisol and subjective stress values were higher in sleep deprived than in rested participants. However, the reactivity to and recovery from the TSST was not significantly different after sleep deprivation for any of the outcome measures. Older adults showed higher subjective stress, higher sAA and lower HRV at baseline, indicating increased basal autonomic activity. Cortisol trajectories and HRV slightly differed in older adults compared with younger adults (regardless of the TSST). Moreover, age did not moderate the effect of sleep deprivation. Taken together, the results show increased stress levels after sleep deprivation, but do not confirm the assumption that one night of sleep deprivation increases the responsivity to an acute psychosocial challenge.

Cost-benefit assessment of using electronic health records data for clinical research versus current practices: Contribution of the Electronic Health Records for Clinical Research (EHR4CR) European Project.

INTRODUCTION: The widespread adoption of electronic health records (EHR) provides a new opportunity to improve the efficiency of clinical research. The European EHR4CR (Electronic Health Records for Clinical Research) 4-year project has developed an innovative technological platform to enable the re-use of EHR data for clinical research. The objective of this cost-benefit assessment (CBA) is to assess the value of EHR4CR solutions compared to current practices, from the perspective of sponsors of clinical trials. MATERIALS AND METHODS: A CBA model was developed using an advanced modeling approach. The costs of performing three clinical research scenarios (S) applied to a hypothetical Phase II or III oncology clinical trial workflow (reference case) were estimated under current and EHR4CR conditions, namely protocol feasibility assessment (S1), patient identification for recruitment (S2), and clinical study execution (S3). The potential benefits were calculated considering that the estimated reduction in actual person-time and costs for performing EHR4CR S1, S2, and S3 would accelerate time to market (TTM). Probabilistic sensitivity analyses using Monte Carlo simulations were conducted to manage uncertainty. RESULTS: Should the estimated efficiency gains achieved with the EHR4CR platform translate into faster TTM, the expected benefits for the global pharmaceutical oncology sector were estimated at €161.5m (S1), €45.7m (S2), €204.5m (S1+S2), €1906m (S3), and up to €2121.8m (S1+S2+S3) when the scenarios were used sequentially. CONCLUSIONS: The results suggest that optimizing clinical trial design and execution with the EHR4CR platform would generate substantial added value for pharmaceutical industry, as main sponsors of clinical trials in Europe, and beyond.

Decreased heart rate variability in children born with low birth weight.

BACKGROUND: Low birth weight (LBW) is associated with cardiovascular morbidity in adulthood. Imbalance in the autonomic nervous system (ANS) has been implicated as a mechanism behind the developmental programming of cardiovascular function. We hypothesized that deviations in the ANS function are seen in children born with LBW. METHODS: Eighty-six children were included: 31 born preterm (<32 wk gestational age), 27 born at term but small for gestational age (SGA), and 28 born at term with normal birth weight (control). Twenty-four-hour Holter-electrocardiogram monitoring was performed at an average age of 9 y. Heart rate variability results were analyzed using frequency and time domain methods. RESULTS: All frequency components and both time domain parameters tested were significantly lower in the preterm and SGA children compared with controls. The low frequency/high frequency ratio was not significantly different between children born with LBW and controls. CONCLUSION: The autonomic control appears to be affected in children born with LBW despite gestational age at birth. Decreased total power, as an estimation of the ANS's global activity, rather than the balance between parasympathetic and sympathetic modulation might be an early marker of cardiovascular disease later on in life for LBW born children.

Heart rate variability is related to self-reported physical activity in a healthy adolescent population.

This study investigated whether there is a relationship between heart rate variability (HRV) versus lifestyle and risk factors for cardiovascular disease in a population of healthy adolescents. HRV is as an index of tonic autonomic activity and in adults HRV is related to lifestyle and risk factors for cardiovascular disease, but it is not known if this is the case in adolescents. HRV was registered for 4 min in sitting position in 99 healthy adolescents (age range 15 years 11 months-17 years 7 months) and repeated after 6 months. On both occasions there were significant correlations (P < 0.05) between physical activity and HRV, with respective r values: high frequency (HF) 0.26, 0.30; low frequency power (LF) 0.35, 0.29 and the standard deviation of inter-beat intervals (SDNN) 0.28, 0.37. There was no significant interaction between first and second measurements. In contrast, there were no correlations to sleeping patterns, eating habits and smoking. Risk factors for cardiovascular disease [body mass index (BMI = weight (kg)/length in m(2)), systolic blood pressure and p-glucose] did not show any repeatable significant correlations to HRV. Multiple regression models showed that physical activity was a predictor for HF, LF and SDNN in both measurements. In conclusion HF, LF and SDNN were reproducible after 6 months and were related to physical activity on both occasions.

Long-term stability of heart rate variability in chronic stable angina pectoris, and the impact of an acute myocardial infarction.

BACKGROUND: Heart rate variability (HRV) reflects the balance between cardiac parasympathetic and sympathetic autonomic influences. Reduced HRV has adverse prognostic implications. The time course for changes in HRV over prolonged periods of time and the influence of an acute coronary event on HRV are not well established. METHODS: Heart rate variability was assessed in patients with chronic stable angina pectoris, who were followed for 3 years within the Angina Prognosis Study in Stockholm. Patients who suffered an acute myocardial infarction after the study were re-examined after this event. We assessed HRV by the simple geometric method differential index, and traditional time- and frequency-domain measurements of HRV. RESULTS: The differential index was essentially unchanged during the study (i.e. the ratio month 36/month 1 was 1.00 +/- 0.06, n = 261). Also most other time and frequency indices of HRV (SDNN, r-MSSD, SDNNIDX, total power, and VLF, LF, HF respectively; n = 63) remained largely unchanged; pNN50 and LF/HF were, however, less reproducible. In 21 patients with a subsequent acute myocardial infarction, SDNN, SDNNIDX, total power, LF and LF/HF were reduced following the event, whereas differential index, pNN50 and HF remained unchanged. CONCLUSIONS: Differential index and other indices of HRV are stable and reproducible in patients with chronic stable angina pectoris. High-frequency HRV (reflecting cardiac parasympathetic activity) and the differential index changed little following an acute coronary event, and may be suitable for predictions of the future risk of sudden death even in the presence of a recent acute coronary event.

Differential index: a simple time domain heart rate variability analysis with prognostic implications in stable angina pectoris.

OBJECTIVES: To examine the usefulness of time domain heart rate variability (HRV) measurements by a simple graphical method, the differential index (DI), in prognostic assessments of patients with chronic stable angina pectoris. METHODS: HRV measurements in the time domain by DI were compared to conventional measurements of standard deviation of all normal-to-normal intervals (SDNN), percent of differences between adjacent normal RR intervals >50 ms (PNN50) and square root of the mean of the sum of squares of differences between adjacent normal RR intervals (RMSSD) from 24-hour ambulatory electrocardiographic recordings in 678 patients in the Angina Prognosis Study in Stockholm. The patients received double-blind treatment with metoprolol or verapamil. Main outcome measures were cardiovascular death or non-fatal myocardial infarction during follow-up (median 40 months). RESULTS: Patients suffering cardiovascular death (n = 30) had lower DI, SDNN and PNN50 (all p < 0.001). In a multivariate Cox model, DI below median independently predicted cardiovascular death (p = 0.002), as did SDNN (p = 0.016) and PNN50 (p = 0.030), but not RMSSD (p = 0.10). The separation of survival curves was most pronounced and specificity was slightly better with DI. DI and PNN50 increased with metoprolol but not verapamil treatment. Short-term treatment effects were not related to prognosis. CONCLUSIONS: Low time domain HRV carries independent prognostic information regarding cardiovascular death in stable angina pectoris. The simple DI method provided equally good or better prognostic information than conventional, more laborious HRV methods.

Saliva testosterone and heart rate variability in the professional symphony orchestra after "public faintings" of an orchestra member.

Musicians are sensitive to changes in their work environment. A 2-year longitudinal study with repeated observations was performed in two professional symphony orchestras. A representative sample from each one of them was selected, 15 and 16 members respectively. In one of them a wind player fainted twice in front of the audience shortly preceding and coinciding with the start of the study. Changes in two indicators that reflect regenerative/anabolic and parasympathetic tone, saliva testosterone concentration (STC) and very low-frequency power (VLFP) in heart rate variability were followed in relation to this dramatic change. Saliva samples and 24-h ECG heart rate variability recordings were collected on five occasions every 6 months during a 2-year period. No changes were seen in the control orchestra whereas the levels showed a pronounced rise in the intervention orchestra during the first part of the study, starting from low levels. VLFP showed a similar pattern, with initially low and then rising level in the intervention orchestra and higher stable level in the other group. In the total study group, a rise in STC over the whole observation period was significantly correlated with increase in VLFP and also significantly correlated with a decrease in low/high-frequency power ratio in heart rate variability. The changes observed in the anabolic/regenerative STC and the parasympathetically influenced VLFP may reflect changes in the work environment associated with the faintings.

Circadian variation in heart-rate variability in localization-related epilepsy.

PURPOSE: Case-control studies of sudden unexpected death in epilepsy (SUDEP) have reported that SUDEP is more likely to occur during sleep and thus presumably during night hours. The circadian variation of heart-rate variability (HRV) might be of relevance to this risk. We examined night versus daytime HRV in patients with newly diagnosed and refractory localization-related epilepsy, assessing the effects of drug treatment and epilepsy surgery on the night/daytime HRV ratio. METHODS: We used spectral analysis to assess HRV and calculated the night-time (00.00-05.00)/daytime (07.30-21.30) ratio of HRV in 14 patients with newly diagnosed localization-related epilepsy before and during carbamazepine (CBZ) treatment and in 21 patients with temporal lobe epilepsy before and after epilepsy surgery. Both groups were compared with age- and sex-matched controls. RESULTS: No significant differences were found from controls in the night/daytime ratios of HRV whether compared before or after initiation of treatment with CBZ in newly diagnosed epilepsy patients. When patients were used as their own controls, night/daytime ratios of standard deviation of RR intervals (p = 0.04) and total power (p = 0.04) were significantly lower during treatment than before. Compared with those of controls, the night/daytime ratios were lower in epilepsy surgery patients before surgery [low-frequency power (p = 0.04); high-frequency power (p = 0.04)]. Night/daytime ratios did not change significantly after surgery. CONCLUSIONS: The HRV of the patients was more affected during night-time when the risk of SUDEP seems to be highest in such patients.

The role of premature atrial contractions as the main triggers of postoperative atrial fibrillation.

UNLABELLED: To better understand the pathogenesis of postoperative atrial fibrillation (AF), the mode of onset of AF after coronary artery bypass grafting was analyzed with respect to the autonomic balance, the heart rate (HR), and the presence of arrhythmias preceding the onset of sustained AF. METHOD: Holter recordings of 24 hours, obtained from the first postoperative morning until clinically documented sustained AF, were analyzed in 29 untreated patients and in 13 patients treated with thoracic epidural anesthesia (TEA), who all developed AF after coronary artery bypass grafting. The presence of arrhythmias, the HR, and the autonomic balance, assessed by heart rate variability in the frequency domain, were analyzed at predefined time intervals within the 3-hour period before AF onset. Supraventricular premature beats (SPBs) and ventricular premature beats triggering the onset of AF were also evaluated. RESULT: An SPB triggering the onset of AF can be identified in 21 (72.4%) of 29 untreated patients and in 12 (100%) of 12 TEA-treated patients in whom the recordings permitted such an analysis. The heart rate variability components analyzed during 5-minute periods for 30 minutes before AF onset did not differ significantly from those at corresponding times at the first postoperative day in either patient group. The HR during the 8 beats immediately before AF onset was lower in TEA-treated than in untreated patients. CONCLUSION: The finding of an SPB at the onset of postoperative AF in most of the patients and irrespective of changes in HR supports the hypothesis that postoperative AF is primarily triggered by latent focal atrial activity. The autonomic tone did not seem to be of major importance in the population studied.

Differential index, a novel graphical method for measurements of heart rate variability.

BACKGROUND: Commonly used methods to evaluate heart rate variability require extensive filtering of the registrations in order to exclude artefacts and ectopic beats. We developed and validated a novel graphical method for time-domain measurements of heart rate variability, the differential index, which does not require filtering and is simple to use. METHODS: The 24-h ambulatory long-term electrocardiogram recordings from 120 patients with angina pectoris and 49 control subjects were computerised without any filtering process. Sample density histograms of differences in the RR interval for successive beats were constructed and the widths of the histograms were used to obtain the differential index. For comparison, the same registrations were analysed by conventional methods. RESULTS: The differential index was most closely related (P<0.001) to conventional short-term time domain (e.g. percent of differences between adjacent normal RR intervals >50 ms, pNN50, r=0.81) and frequency-domain (e.g. high frequency power, r=0.84) components, but also to long-term time domain (e.g. standard deviation of all normal-to-normal RR intervals for all 5-min segments of the entire registration, SDNNIDX, r=0.72) and frequency-domain (e.g. low frequency power, r=0.64) components. CONCLUSION: The differential index method shows good agreement with established indices of heart rate variability. The insensitivity to recording artefacts and short-lasting disturbances of sinus rhythm make the differential index method particularly suited when data quality is imperfect. The simplicity of the method is valuable when large numbers of registrations are to be evaluated.

Vaccination of prostatectomized prostate cancer patients in biochemical relapse, with autologous dendritic cells pulsed with recombinant human PSA.

This study was conducted in prostate cancer patients in biochemical relapse after radical prostatectomy, to assess the feasibility, safety, and immunogenicity of therapeutic vaccination with autologous dendritic cells (DCs) pulsed with human recombinant prostate-specific antigen (PSA) (Dendritophage-rPSA). Twenty-four patients with histologically proven prostate carcinoma and an isolated postoperative rise of serum PSA (>1 ng/ml to 10 ng/ml) after radical prostatectomy were included. The patients received nine administrations of PSA-loaded DCs by combined intravenous, subcutaneous, and intradermal routes over 21 weeks. Postbaseline blood tests were performed at months 1, 3, 6, 9, and 12 (PSA levels), at months 6 and 12 (circulating prostate cancer cells), at month 6 (anti-PSA IgG and IgM antibodies), and at up to eight time points before, during, and after immunization (PSA-specific T cells). Circulating prostate cancer cells detected in six patients at baseline were undetectable at 6 months and remained undetectable at 12 months. Eleven patients had a postbaseline transient PSA decrease on one to three occasions, predominantly occurring at month 1 (7 patients) or month 3 (2 patients). Maximum PSA decrease ranged from 6% to 39%. PSA decrease on at least one occasion was more frequent in patients with low Gleason score ( p=0.016) at prostatectomy and with positive skin tests at study baseline ( p=0.04). PSA-specific T cells were detected ex vivo by ELISpot for IFN-gamma in 7 patients before vaccination and in 11 patients after vaccination. Of the latter 11 patients, 5 had detectable T cells both before and during the vaccination period, 4 only during the vaccination period, while 2 patients could for technical reasons not be assessed prevaccination. No induction of anti-PSA IgG or IgM antibodies was detected. There were no serious adverse events or otherwise severe toxicities observed during the trial. Immunization with Dendritophage-rPSA was feasible and safe in this cohort of patients. An immune response specific for PSA could be detected in some patients. A notable effect was the disappearance of circulating prostate cells in all patients who were RT-PCR positive before vaccination.

A new approach to the mouse arm syndrome.

OBJECTIVES: The study validates a new computer mouse concept. The tested device is a small mouse with a pivoting pen-shaped handle. The hypothesis behind the design is the assumptions that the pen grip requires less static tension than the normal mouse grip and that fine-motor, high precision tasks normally are done with finger movements with forearm at rest. METHODS: Four muscles were monitored with electromyography (EMG) during work with a new mouse and with a traditional mouse. RESULTS: EMG activity was significant lower, in M. pronator teres--46%, M. extensor digitorum--46%, M. trapezius--69%, and M. levator scapulae--82%, during work with the new mouse as compared to the traditional mouse. CONCLUSION: Altering the design of the computer mouse can significantly reduce muscular tension.

Does singing promote well-being?: An empirical study of professional and amateur singers during a singing lesson.

This study explored the possible beneficial effects of singing on well-being during a singing lesson. Eight amateur (2m, 6f, age 28-53 yrs) and eight professional (4m, 4f, age 26-49 yrs) singers who had been attending singing lessons for at least six months were included. Continuous ECG was recorded and computerized spectral analysis was performed. Serum concentrations of TNF-alpha, prolactin, cortisol, and oxytocin were measured before and 30 min after the lesson. Five visual analogue scales (VAS, sad-joyful, anxious-calm, worried-elated, listless-energetic, and tense-relaxed) were scored before and after the lesson. In addition, a semi-structured interview was performed. Heart rate variability analyses showed significant changes over time in the two groups for total power, and low and high frequency power. Power increased during singing in professionals, whereas there were no changes in amateurs. This indicates an ability to retain more "heart-brain connection." i.e., more cardio-physiological fitness for singing in professional singers, compared to amateur singers. Serum concentration of TNF-alpha increased in professionals after the singing lesson, whereas the concentration in amateurs decreased. Serum concentrations of prolactin and cortisol increased after the lesson in the group of men and vice versa for women. Oxytocin concentrations increased significantly in both groups after the singing lesson. Amateurs reported increasing joy and elatedness (VAS), whereas professionals did not. However, both groups felt more energetic and relaxed after the singing lesson. The interviews showed that the professionals were clearly achievement-oriented, with focus on singing technique, vocal apparatus and body during the lesson. The amateurs used the singing lessons as a means of self-actualization and self-expression as a way to release emotional tensions. In summary, in this study, singing during a singing lesson seemed to promote more well-being and less arousal for amateurs compared to professional singers, who seemed to experience less well-being and more arousal.

Autonomic denervation after the Maze procedure.

The Maze III procedure is a surgical operation for curative treatment of AF. The procedure is extensive, however, with multiple incisions in both atria, and its effects on autonomic regulation of the heart rhythm are not known. This study comprises 17 patients, 10 with paroxysmal AF and 7 with chronic AF, who had no concurrent cardiac disease known to affect heart rate variability (HRV). A 24-hour Holter recording was performed preoperatively and 2 months (early) and 7 months (late) after surgery, for analysis of HRV in the time and frequency domains. Early after the Maze procedure all HRV components were markedly reduced compared to baseline (mean +/- 1 SD): SDNN 73 +/- 13 versus 148 +/- 50 (ms), total power 168 +/- 126 versus 560 +/- 1567 (ms2), low frequency (LF) power 47 +/- 67 versus 826 +/- 677 (ms2), high frequency (HF) power 47 +/- 40 versus 678 +/- 666 (ms2), and LF:HF 1.22 +/- 0.9 versus 2.55 +/- 1.4. Late after the Maze procedure all variables were still reduced. Only total power increased significantly between early and late follow-up (168 +/- 126 vs 496 +/- 435 ms2). Late after Maze surgery, values of the different HRV components did not differ between the patients with paroxysmal AF and chronic AF. Early after the Maze procedure there is a marked decrease of all HRV components, which is maintained 7 months after surgery, a pattern consistent with denervation of the heart.

Carbamazepine affects autonomic cardiac control in patients with newly diagnosed epilepsy.

Previous studies indicate that epilepsy patients may have impaired autonomic cardiovascular control in the interictal state although it is unclear whether the observed reduction in cardiovascular responses is due to the epilepsy and the interictal epileptogenic discharges, or to the treatment with antiepileptic drugs. Spectral analysis of heart rate variability makes it possible to partly separate the sympathetic components, low frequency (LF), from the vagal components, high frequency (HF) of autonomic cardiac control. We used spectral analysis of heart rate variability to assess the effect of carbamazepine (CBZ) on autonomic cardiac control in patients with newly diagnosed epilepsy. Fifteen adult outpatients with newly diagnosed seizures/epilepsy underwent 24 h ambulatory EKG recordings before and after commencement of CBZ treatment. Total power as well as low frequency (LF), very low frequency (VLF) and high frequency (HF) power in heart rate variability was calculated. When analysing the full 24 h recordings, patients had significantly lower standard deviation of RR-intervals (P=0.0015), total power (P=0.0010), LF (P=0.0002), VLF (P=0.0025) and HF (P=0.0139) during treatment with CBZ than before. The results were very similar for daytime and night time recordings. Our observations demonstrate that CBZ may suppress both parasympathetic and sympathetic functions in newly diagnosed patients with epilepsy. The possible implications of our results for sudden unexpected death in epilepsy are discussed.

Evidence of decreased sympathetic function in children with psychosomatic symptoms.

We investigated cardiovascular autonomic function using power spectral analysis of heart rate variation and beat-to-beat finger arterial pressure at rest and while standing and correlated these findings with self-reported psychosomatic and psychosocial symptoms in 122 schoolchildren. Children with three or more psychosomatic and psychosocial symptoms (somatizers) were found to have significantly lower blood pressure than children without symptoms. Somatizers had the more decreased spectral power of the low frequency (LF) band of arterial pressure and RR intervals in the supine position. The high frequency (HF) power did not differ between the two groups. Somatizers showed a more marked reduction in systolic arterial pressure at the onset of standing than did subjects without symptoms but somatizers showed an identical response in systolic arterial pressure when compared to subjects without symptoms during the later stage of standing. The increases in the LF band of arterial pressure and LF/HF of RR intervals during standing were higher in somatizers. These results suggest that somatizers have decreased sympathetic modulation. We conclude that psychosomatic and psychosocial symptoms in children might be associated with low blood pressure and decreased sympathetic modulation.