A participatory and comprehensive intervention to improve violence prevention in two high-risk occupations: effect and process evaluation of a stepped wedge cluster randomised trial.

BACKGROUND: Work-related violence committed by clients, patients, and customers represents a major occupational health risk for employees that needs to be reduced. METHODS: We tested a comprehensive violence prevention intervention involving active participation of both employees and managers in the Prison and Probation Service (PPS) and on psychiatric wards in Denmark. We used a stepped wedge cluster randomised controlled trial design. We measured the degree of implementation of the intervention by registration of fidelity, reach, and dose and used a mixed-effects regression analysis to estimate the effects of the intervention. RESULTS: We recruited 16 work units for the intervention, but three work units dropped out. The average implementation rate was 73%. In the psychiatric wards, the intervention led to statistically significant improvements in the primary outcome (an increase in the degree to which managers and employees continuously work on violence prevention practices based on their registration and experiences), but none statistically significant improvements in any of the secondary outcomes. In the PPS units, the intervention did not lead to a statistically significant improvement in the primary outcome, but to statistically significant improvements in three secondary outcomes. CONCLUSION: Most work units were able to carry out the intervention as planned. The intervention showed mixed results regarding the primary outcome. Nevertheless, the results indicate improvements also in the sector where a change in the primary outcome was not achieved. The results point at that a participatory and comprehensive approach could be a viable way of working with violence prevention in high-risk workplaces. TRIAL REGISTRATION: ISRCTN86993466: 20/12/2017.

Intravenous MELAtonin for prevention of Postoperative Agitation and Emergence Delirium in children (MELA-PAED): A protocol and statistical analysis plan for a randomized clinical trial.

BACKGROUND: Emergence agitation and delirium in children remain a common clinical challenge in the post-anesthetic care unit. Preoperative oral melatonin has been suggested as an effective preventive drug with a favorable safety profile. The oral bioavailability of melatonin, however, is low. Therefore, the MELA-PAED trial aims to investigate the efficacy and safety of intraoperative intravenous melatonin for the prevention of emergence agitation in pediatric surgical patients. METHODS: MELA-PAED is a randomized, double-blind, parallel two-arm, multi-center, superiority trial comparing intravenous melatonin with placebo. Four hundred participants aged 1-6 years will be randomized 1:1 to either the intervention or placebo. The intervention consists of intravenous melatonin 0.15 mg/kg administered approximately 30 min before the end of surgery. Participants will be monitored in the post-anesthetic care unit (PACU), and the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) will be performed on days 1, 7, and 14 after the intervention. Serious Adverse Events (SAE) will be assessed up to 30 days after the intervention. RESULTS: The primary outcome is the incidence of emergence agitation, assessed dichotomously as any Watcha score >2 during the participant's stay in the post-anesthetic care unit. Secondary outcomes are opioid consumption in the post-anesthetic care unit and adverse events. Exploratory outcomes include SAEs, postoperative pain, postoperative nausea and vomiting, and time to awakening, to first oral intake, and to discharge readiness. CONCLUSION: The MELA-PAED trial investigates the efficacy of intravenous intraoperative melatonin for the prevention of emergence agitation in pediatric surgical patients. Results may provide further knowledge concerning the use of melatonin in pediatric perioperative care.

Intensive care nurses' experiences of caring for isolated COVID-positive patients during first wave of COVID-19.

Background: COVID-19 has fundamentally changed all fields of health care. Intensive care nurses have been at the forefront of the pandemic facing the massive impact of the disease, both professionally and personally. This study investigated nurses' experiences of caring for isolated COVID-19 positive patients in the intensive care department during the first wave of the COVID-19 pandemic. The study investigated how isolation affected the nurses themselves, how they related with their patients, and how isolation affected patient care in general. Methods: The study was performed at a 20-bed university hospital intensive care department in Copenhagen, Denmark. COVID-19 positive patients were isolated or cohort isolated. A dedicated nurse cared for each isolated patient and wore full personal protective equipment. The study is based on in-depth phenomenological interviews with intensive care nurses conducted in summer 2020. The interviews were structured according to the principles of "Phenomenologically Grounded Qualitative Research." The data included observations from within the isolated patient rooms. Findings: Six intensive care nurses participated in the study. The analysis documented following themes consistently reported by all nurses: (1) a general sense of uncanniness, (2) intense feelings of confinement and co-isolation, and (3) heightened senses of bodily objectification, including how nurses' experienced their patients and also themselves. Conclusion: This is the first Scandinavian phenomenological study to focus on mapping the experiences of intensive care nurses during the extreme circumstances of the first wave of the COVID-19 pandemic. Further studies may explore long-term effects, such as psychiatric morbidity or psychological functioning in these individuals.

Remimazolam for sedation: A protocol for a systematic review with meta-analysis, trial sequential analysis, and GRADE approach.

BACKGROUND: Procedural sedation aims to facilitate a successful diagnostic or therapeutic procedure. The pharmacokinetic properties and pharmacodynamic effects need to be taken into consideration when choosing the ideal sedative. Midazolam and propofol are frequently employed. However, they are associated with respiratory depression with increasing dosage. Also, midazolam has a potentially unpredictable pharmacodynamic response and propofol may cause hypotension and injection site pain. Remimazolam may provide a superior alternative due to its rapid pharmacodynamic profile and insignificant circulatory effects. METHODS: This protocol employs the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The review aims to assess the beneficial and harmful clinical effects of remimazolam versus placebo or other sedatives in adult patients requiring sedation in relation to a diagnostic or therapeutic procedure, or due to other circumstances. Three primary outcomes are identified: Sedation success rate, respiratory complications, and hemodynamic complications. Six secondary outcomes are identified: among these are quality of recovery and serious adverse events. All randomized trials are included. The search strategy includes six major biomedical databases. Literature screening and data extraction will be performed independently by two authors. Risk of systemic error will be assessed with Risk of Bias 2 Tool. Risk of random error will be assessed with trial sequential analysis. Heterogeneity will be evaluated by appropriate statistical tests. The certainty of the evidence will be judged using Grading of Recommendations Assessment, Development, and Evaluation. Meta-analysis will be carried out with Rstudio. A "Summary of Findings" table will be presented with our primary and secondary outcome results. DISCUSSION: The systematic review with up-to-date methodology outlined in this protocol investigates the clinical effects of remimazolam in relation to procedural sedation. The results may guide clinicians in the clinical use of remimazolam.

Experiences of isolation in patients in the intensive care unit during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, patients in the intensive care unit have been subjected to strict isolation precautions, and potentially long and complicated patient courses. The aim of the study is to provide an investigation of the experiences of isolation in COVID-19-positive patients in the ICU during the first phase of the COVID-19 pandemic in Denmark. METHODS: The study was performed in a 20-bed ICU at a university hospital in Copenhagen, Denmark. The study is based on a phenomenological framework, Phenomenologically Grounded Qualitative Research. This approach provides insights into the tacit, pre-reflective and embodied dimensions of the specific experience under investigation. Methods included a combination of in-depth structured interviews with ICU patients 6-12 months after ICU discharge, and observations from inside the isolated patient rooms. The descriptions of experiences gathered through the interviews were subjected to systematic thematic analysis. RESULTS: Twenty-nine patients were admitted to the ICU in the period 10 March and 19 May 2020. A total of six patients was included in the study. Themes consistently reported across all patients included (1) being objectified to degrees that implied self-alienation; (2) feeling a sense of being in captivity; (3) being in an experiential state of surrealism, and finally (4) experiencing extreme loneliness and intercorporeal deprivation. CONCLUSION: This study provided further insights into the liminal patient experiences of being isolated in the ICU due to COVID-19. Robust themes of experience were achieved through an in-depth phenomenological approach. Although, similarities in experiences compared to other patient groups exist, the precarious situation constituted by COVID-19 lead to significant intensifications across multiple parameters.

Crisis social support after work-related violence and threats and risk for depressive symptoms: a 3-months follow-up study.

INTRODUCTION: Employees working at psychiatric wards are at risk for work-related threats and violence that may impact their physical and mental health. Studies have found that crisis social support may mitigate these adverse health effects. PURPOSE: To examine the effects crisis social support on depressive symptoms 3 months after a violent or threating work incident and furthermore, to examine the effect of variations in prolonged social support on depressive symptoms during 3 months after a violent or threating incident. METHODOLOGY: After exposure to work-related violence and threats at work, the employees received a questionnaire within the first month and after 3 months. Right after the incident, 374 employees answered both the depression and crisis support items and were included in the analyses. 3 months later 276 employees answered both the depression and social support items. Prospective associations between crisis social support and depression were calculated using stepwise regressions and linear mixed models. RESULTS: Crisis social support at T1 was significantly and inversely associated with a lower level of depressive symptoms at T2, Std. Beta = - 012, t (3) = - 2.1, p = .040. Employees experiencing either a stable or increasing level of support from T1 to T2 had significantly lower levels of depressive symptoms compared to employees who experienced a decrease in support in the same period, mean differenceStable-Decreasing = 4.0 t (190) = 5.2, p = 0.006 and mean differenceIncreasing-Decreasing = 7.6, t (189) = 5.3, p < .001. CONCLUSION: The study results indicate that depressive symptoms following work-related violence or threats can be mitigated by prolonged social support. We recommend that organizations continue to offer crisis social support in the subsequent months, and not just immediately after a violent or threating incident.

Negative Acts as Risk Factor for Work-Related Violence and Threats from Clients towards Employees: A Follow-Up Study.

BACKGROUND: Work-related violence and threats are major problems in many occupations, especially within the human service sector, with consequences at multiple levels, including reduced physical and mental health, increased absenteeism, and reduced organizational commitment. It is, therefore, crucial to identify risk factors for work-related violence and threats. However, only a few studies have examined whether negative acts at work increase the risk of work-related violence and threats from clients toward employees. OBJECTIVE: To examine the associations between exposure to negative acts towards employees from colleagues, clients, or a combination of both, and the risk of work-related violence and threats perpetrated by clients towards employees in a longitudinal study. METHODS: Questionnaire data were collected in 2010, 2011, and 2015. In total, 5333 employees from special schools, psychiatric wards, eldercare, and the Prison and Probation Services participated in the first round of data collection in 2010. Negative acts were measured in 2010 using the Short Negative Acts Questionnaire, while work-related threats and violence were measured at all three-time points. The analyses were performed using multilevel logistic regression. RESULTS: Negative acts from clients and the combination of negative acts from both clients and colleagues were associated with later exposure to work-related violence and threats. The associations were observed after one year, and work-related threats were still present after four years. CONCLUSION AND IMPLICATIONS: Negative acts are associated with an increased risk of work-related violence and threats perpetrated by clients toward employees. Organizations may reduce the risk of work-related violence and threats by preventing negative acts.

Experiences of preventing violence in two high-risk sectors: A qualitative study of front-line workers.

BACKGROUND: Exposure to workplace violence is associated with physical and/or psychological trauma. Despite its significant impact, little is known about front-line workers' experiences of preventing workplace violence. OBJECTIVE: This study aimed to identify what workers identify as important to preventing workplace conflicts from escalating into violence. METHODS: We conducted seventeen qualitative focus-group interviews with fifty-eight workers at the Danish Prison and Probation Service and psychiatric hospitals. We applied thematic analysis to identify types of violence-prevention practices, and prerequisites for successfully preventing workplace violence. RESULTS: We identified two main categories of violence-prevention practices, and one main category of prerequisites for violence-prevention practices. Main category A), "the individual worker's violence-prevention practices" included the sub-categories, 1) identify the causes of workplace violence and potentially violent situations, 2) establish relationships, state rules, and set clear boundaries and 3) display empathy and communicate respectfully. Main category B), "collaborative practices for preventing workplace violence" included 4) communicate with co-workers, and share information and observations, 5) coordinate work, avoid being played off against colleagues, and support colleagues. Main category C), "prerequisites for violence-prevention practices" included 6) managing one's emotions, and 7) having sufficient time to do the job, and being a part of a stable team, whose members know each other and the inmates/patients". CONCLUSION: This study contributes to a better understanding of the interplay among individual, collaborative, and contextual aspects of preventing workplace violence. We believe that an increased understanding of the complexity of preventing workplace violence in high-risk sectors is useful when designing comprehensive violence-prevention strategies.

Workplace's Development of Activities and Action Plans to Prevent Violence From Clients in High-Risk Sectors.

INTRODUCTION: Interventions trying to prevent violence from clients towards employees tend to show limited effect on the risk or the frequencies of violent episodes, possibly due to a too-narrow focus on only one or a few preventive strategies. This study aimed to show what employees and line managers identify as key intervention areas for preventing violence and threats. METHODS: The study is based on data collected during a participatory intervention study aiming to improve violence prevention in Danish psychiatric units and prison and detention centers. In the intervention study, employees and line managers from 13 work units developed 293 suggestions and 92 action plans to prevent workplace violence. Through qualitative thematic analysis of the suggestions and action plans, we identified the main categories that work units viewed as important and realistic to work with to improve violence prevention. RESULTS: We identified 12 topics of violence prevention that work units considered relevant. Action plan topics used by more than half of the work units included: specific approaches to violence prevention (e.g., de-escalating techniques), communication between employees to transfer knowledge between shifts, and introduction to new employees and temporary workers. Topics used by three to five work units were: interdisciplinary corporation, communication and relational work, uniform approaches, organization of work, and staffing. Topics used rarely were: definition of violence and threats, policy and guidelines, support from colleagues and management, and engagement in violence prevention. For nine of the 12 topics, action plans were developed in both high-risk sectors. CONCLUSIONS: The violence prevention action plans developed by work units from two high-risk sectors indicate that workplaces estimate the prevention of client-induced workplace violence to require activities on many levels and cannot be solved by a single focused approach. This variety of preventive activities needs to be considered when designing violence prevention interventions.

The use of melatonin in Danish intensive care departments-A nationwide observational study.

BACKGROUND: Melatonin is widely employed as a hypnotic in various patient groups. In intensive care patients, melatonin seems to be increasingly used due to potential clinical effects and a favourable safety profile. OBJECTIVES: We aimed to investigate the extend of usage and clinical practice of melatonin therapy in intensive care departments in Denmark. DESIGN: Data from regional hospital pharmacies and the Danish Intensive Care Database were used to estimate defined daily dose and defined daily dose per 1000 ICU admission days. Also, related expenses in the period 2015-2019. Finally, a questionnaire describing the clinical practice of melatonin therapy was provided to all Danish intensive care departments. PRINCIPAL OBSERVATIONS: The usage of melatonin in intensive care departments in Denmark increased from 21,300 DDD (200.0 DDD per 1000 ICU admission days) in 2015 to 52,170 DDD (560.7 DDD per 1000 ICU admission days) in 2019. A total of 32 ICU departments participated in the study (97% of all Danish ICU departments). All included ICU departments employed melatonin as a hypnotic. Nineteen percent of included departments administered melatonin to all admitted patients, whereas 25% of departments rarely administered melatonin. Magistral melatonin 3-mg tablets was the most employed drug dose/formulation. Increased doses of melatonin were administered in selected patients. Melatonin was considered safe by prescribing clinicians. CONCLUSIONS: Melatonin is widely and increasingly used in Danish intensive care departments. The more than doubled usage of melatonin in the study period advocates for further studies employing validated outcomes of sleep and other patient-relevant outcomes. EDITORIAL COMMENT: This study documents that melatonin is frequently used as a hypnotic in Danish intensive care units during recent years despite a shortage of reliable evidence to support a recommendation to treat with melatonin in this context. These results support a need for conducting clinical trials to determine whether or not there is a beneficial effect of melatonin treatment in critically ill patients.

The association between pupils´ aggressive behaviour and burnout among Danish school teachers - the role of stress and social support at work.

BACKGROUND: Pupils´ aggressive behaviour towards teachers is a serious problem which is slowly gaining attention and has been found to be linked to burnout. However, prospective studies investigating the role of stress and social support from colleagues and supervisor are lacking. Therefore, the aims of the present study were 1. to investigate the association between pupils´ aggressive behaviour and burnout among Danish primary and lower secondary school teachers, 2. to investigate whether the association between pupils´ aggressive behaviour and burnout depends on the level and duration of stress, and 3. to investigate whether social support from colleagues or a supervisor at the work place has a mitigating effect on the association between pupils´ aggressive behaviour and burnout among teachers. METHODS: This study is a longitudinal study using data from 1198 teachers collected in two survey rounds at an interval of 1-year. Teacher-reported aggressive behaviour in pupils measured as harassment, threats, and violence towards teachers was collected at baseline. Burnout was measured at follow-up. The analyses were performed using multilevel logistic regression. RESULTS: Statistically significant associations between harassment, threats, or violence and burnout 1 year later were found (all ORs 1.6) after adjustment for potential confounders. After further adjustment for stress, the estimates attenuated to ORs between 1.4 and 1.5, and were also statistically significant. Pupils´ aggressive behaviour in combination with low support from colleagues increased the risk of burnout, whereas the risk of burnout increased among those experiencing pupils´ aggressive behaviour in combination with receiving high support from the supervisor. CONCLUSIONS: The results indicate associations between all three types of pupils´ aggressive behaviour and burnout among teachers in Danish primary and lower secondary schools. Stress explained only a minor part of the association between teachers' perceptions of pupils' aggressive behaviour and burnout in teachers, and the results regarding social support were conflicting. The results of this study emphasize the growing need for preventive initiatives directed towards pupils´ aggressive behaviour, and future research should focus on exploring in depth how to support and prevent burnout in teachers exposed to aggressive behaviour.

The Demand-Control Model and Pupils' Aggressive Behaviour towards Teachers: A Follow-Up Study.

PURPOSE: Pupils' aggressive behaviour towards teachers is a common phenomenon in schools across different countries. The purpose of this study is to test hypotheses that are central to the Job Demand-Control model as risk factors for pupils' aggressive behaviour towards teachers. METHOD: Questionnaire data were collected in 2018 and 2019 from teachers at 94 public schools in Denmark. In total, 1198 teachers participated in both rounds. Demands and social support at work were measured in 2018, and pupils' aggressive behaviour was measured in 2019. The analyses were performed using multivariate logistic regression analysis. RESULTS: Teachers were often exposed to pupils' aggressive behaviour during their work. High emotional work demands and low control were associated with increased risk of pupils' aggressive behaviour. No mitigating effect of high control was found on the association between emotional demands and risk for pupils' aggressive behaviour towards teachers. CONCLUSION: High emotional demands were strongly associated with the aggressive behaviour of pupils towards teachers. Job control over own work situation was not enough to lower the risk of aggressive behaviour under conditions in which teachers experience high emotional demands. Based on these results, we recommend that supervisors carefully balance teachers' emotional demands to their resources.

Work-related violence and organizational commitment among health care workers: does supervisor's support make a difference?

INTRODUCTION: Work-related threats and violence are major occupational hazards, with potentially serious consequences for both victims and the organization that employs them. Only a few studies have prospectively examined the mitigating effect of social support from supervisors on organizational commitment following exposure to work-related violence and threats. OBJECTIVE: This study aimed at examining the effect of immediate supervisor's support on affective commitment within 1, 3, 6 and 12 months after exposure to violence and threats. METHODS: After exposure to work-related violence and threats, the employees received a questionnaire within the first month and after 3, 6 and 12 months. Right after the incident, 398 employees filled out the questionnaire, and 138 employees answered the questionnaire at all four time points. Prospective associations and mean differences between groups were calculated using linear mixed models. RESULTS: Employees receiving very high levels of social support from supervisors immediately after being exposed to work-related violence or threats had a significantly higher level of organizational commitment across all four time points when compared to the group experiencing middle/low levels of support. Furthermore, at 1- and 3-month follow-up employees receiving very high levels of social support from supervisors following work-related violence and threats reported significantly higher levels of commitment than did the group with high levels of social support from supervisors. CONCLUSION: Organizations should enhance the availability of social support from supervisors for employees experiencing work-related violence and threats. Training of supervisors to be very much concerned about employees exposed to work-related violence may be of critical importance to both the health and work outcomes of employees.

Methodology and applicability of the human contact burn injury model: A systematic review.

The contact burn injury model is an experimental contact thermode-based physiological pain model primarily applied in research of drug efficacy in humans. The employment of the contact burn injury model across studies has been inconsistent regarding essential methodological variables, challenging the validity of the model. This systematic review analyzes methodologies, outcomes, and research applications of the contact burn injury model. Based on these results, we propose an improved contact burn injury testing paradigm. A literature search was conducted (15-JUL-2020) using PubMed, EMBASE, Web of Science, and Google Scholar. Sixty-four studies were included. The contact burn injury model induced consistent levels of primary and secondary hyperalgesia. However, the analyses revealed variations in the methodology of the contact burn injury heating paradigm and the post-burn application of test stimuli. The contact burn injury model had limited testing sensitivity in demonstrating analgesic efficacy. There was a weak correlation between experimental and clinical pain intensity variables. The data analysis was limited by the methodological heterogenicity of the different studies and a high risk of bias across the studies. In conclusion, although the contact burn injury model provides robust hyperalgesia, it has limited efficacy in testing analgesic drug response. Recommendations for future use of the model are being provided, but further research is needed to improve the sensitivity of the contact burn injury method. The protocol for this review has been published in PROSPERO (ID: CRD42019133734).

Can high workplace social capital buffer the negative effect of high workload on patient-initiated violence? Prospective cohort study.

BACKGROUND: High workload seems to increase the risk of patient-initiated workplace violence (patient-initiated violence). However, the temporal association between workload and violence remains uncertain. Understanding the interplay of factors in the psychosocial working environment and patient-initiated violence is important to future preventive initiatives. AIM: To assess whether a high workload increases the risk of patient-initiated violence, and whether intraorganizational relationships based on trust, reciprocity, justice and collaboration, known as workplace social capital, moderate this risk. METHOD: Baseline survey data on 1823 social educators was collected followed by 12 monthly surveys on patient-initiated violence exposure. Poisson regressions, in mixed models, were conducted to assess the risk of violence at four levels of workload. Further, moderation analyses were conducted to assess the moderating effects of three sub-types of workplace social capital. RESULTS: High and very high workload increased the risk of patient-initiated violence: RR = 1.5 [1.4-1.6], p < .001 and RR = 1.4 [1.3-1.4], p < .001. All three levels of workplace social capital had a moderating effect on the workload-violence association: Workload*Workplace social capital(co-worker): F (3, 16,712) = 3.4, p = .017, Workload*Workplace social capital(local management): F (3, 16,748) = 11.9, p < .001, Workload*Workplace social capital(general management): F (3, 16,556) = 5.5, p < .001. Only high Workplace social capital (co-workers) reduced the risk of violence at all levels of workload. Workplace social capital (general management) reduced the risk of violence at high, medium and low workload, and Workplace social capital (local management) reduced the risk of violence at medium and low workload. CONCLUSION: High workload clearly increases the risk of patient-initiated violence. A high workplace social capital appears to be a viable protective factor and should be investigated further in studies of patient-initiated violence prevention.

Depressive Symptoms Following Work-Related Violence and Threats and the Modifying Effect of Organizational Justice, Social Support, and Safety Perceptions.

Work-related threats and violence is a major occupational hazard and the consequences for victims may be a range of physical and psychological symptoms. The purpose of this study was to examine the associations between exposure to work-related violence and threats and subsequent risk for depression and to examine whether the associations were modified by social support, organizational justice and safety perceptions. Questionnaire data was collected in 2010, 2011 and in 2015. A total of 5,342 employees from special schools, psychiatric wards, eldercare and the Prison and Probation Services (PPS) participated in the first round in 2010. The analysis was performed by multivariate logistic regression. Staff exposed for work-related threats and violence had an increased risk for depression compared to non-exposed staff. The risk was highest for staff working in PPS. Compared to low levels, there were a tendency for high levels of social support, organizational justice and safety perception to attenuate the associations between work-related threats and violence and depression. However, none of the differences were statistically significant. Many employees working in human service sectors are exposed to work-related threats and violence which increases the risk for depression. The risk for depression following work-related threats and violence may be modified by social support, organizational justice and the perception of safety workplace. It is recommended that workplaces adopt an integrated organizational approach including both prevention of work-related threats and violence and intervention to modify the health consequences of work-related threats and violence.

Pharmacokinetics and Safety of Intravenous, Intravesical, Rectal, Transdermal, and Vaginal Melatonin in Healthy Female Volunteers: A Cross-Over Study.

INTRODUCTION: We aimed to investigate the pharmacokinetic properties and safety of melatonin administered by alternative routes of administration. METHODS: This study employed a cross-over design in healthy female volunteers. Twenty-five milligrams of melatonin was administered intravenously, intravesically, rectally, transdermally, and vaginally. Blood samples were collected at specified time points up to 24 h following intravenous, intravesical, rectal, and vaginal administration, and up to 48 h following transdermal administration. Plasma melatonin concentrations were determined by radioimmunoassay. Sedation was evaluated by a simple reaction-time test, and sleepiness was assessed by the Karolinska Sleepiness Scale. Adverse events were registered for each route of administration. RESULTS: Ten participants were included. We documented a mean (SD) time to maximal concentration of 51 (29) min for intravesical, 24 (20) min for rectal, 21 (8) h for transdermal, and 147 (56) min for vaginal administration. The mean (SD) elimination half-life was 47 (6) min for intravenous, 58 (7) min for intravesical, 60 (18) min for rectal, 14.6 (11.1) h for transdermal, and 129 (17) min for vaginal administration. The mean (SD) bioavailability was 3.6 (1.9)% for intravesical, 36.0 (28.6)% for rectal, 10.0 (5.7)% for transdermal, and 97.8 (31.7)% for vaginal administration. No significant changes in reaction times were observed following administration of melatonin by any of the administration routes. Increased tiredness was documented following transdermal administration only. No serious adverse effects were documented. CONCLUSION: Rectally and vaginally administered melatonin may serve as relevant alternatives to standard oral melatonin therapy. Transdermal delivery of melatonin displayed an extended absorption and can be applied if prolonged effects are intended. Intravesical administration displayed, as expected, a very limited bioavailability. Melatonin administered by these routes of administration was safe.

Characteristics, interventions, and longer term outcomes of COVID-19 ICU patients in Denmark-A nationwide, observational study.

BACKGROUND: Most data on intensive care unit (ICU) patients with COVID-19 originate in selected populations from stressed healthcare systems with shorter term follow-up. We present characteristics, interventions and longer term outcomes of the entire, unselected cohort of all ICU patients with COVID-19 in Denmark where the ICU capacity was not exceeded. METHODS: We identified all patients with SARS-CoV-2 admitted to any Danish ICU from 10 March to 19 May 2020 and registered demographics, chronic comorbidities, use of organ support, length of stay, and vital status from patient files. Risk factors for death were analyzed using adjusted Cox regression analysis. RESULTS: There were 323 ICU patients with confirmed COVID-19. Median age was 68 years, 74% were men, 50% had hypertension, 21% diabetes, and 20% chronic pulmonary disease; 29% had no chronic comorbidity. Invasive mechanical ventilation was used in 82%, vasopressors in 83%, renal replacement therapy in 26%, and extra corporeal membrane oxygenation in 8%. ICU stay was median 13 days (IQR 6-22) and hospital stay 19 days (11-30). Median follow-up was 79 days. At end of follow-up, 118 had died (37%), 15 (4%) were still in hospital hereof 4 in ICU as of 16 June 2020. Risk factors for mortality included male gender, age, chronic pulmonary disease, active cancer, and number of co-morbidities. CONCLUSIONS: In this nationwide, population-based cohort of ICU patients with COVID-19, longer term survival was high despite high age and substantial use of organ support. Male gender, age, and chronic co-morbidities, in particular chronic pulmonary disease, were associated with increased risk of death.

Cognitive impairments and recovery in patients with work-related stress complaints - four years later.

Patients on sick leave due to work-related stress often present with cognitive complaints. The primary aim of this prospective cohort study was to examine potential long-term consequences of previous ongoing work-related stress in terms of cognitive functioning four years after initial professional care seeking. We tested a group of patients with work-related stress complaints with a comprehensive neuropsychological test battery. Patients were examined at a department of occupational medicine and tested at baseline, one-year follow-up and four-year follow-up. At each time point, we compared the performance of patients with healthy controls matched pairwise on sex, age and length of education. This paper presents the results from the four-year follow-up. Patients improved on their neuropsychological test performance during the four years but the main improvements took place during the first year. At baseline, the main impairments in the patient group concerned executive function and mental speed. At four-year follow-up, patients displayed slightly lower scores on the neuropsychological tests relative to controls but only the difference on immediate memory was significant corresponding to a small effect size (Cohen's d). More than half of the patients who participated in the four-year follow-up reported that they felt only slightly or partially recovered. The level of work participation among the former patients improved considerably during the four-year follow-up period.Lay SummaryThis study examines the long-term consequences of work-related stress in terms of cognitive functioning and recovery four years after initial professional care seeking. After four years, patients continued to display significantly lower memory scores than controls but no other significant differences between the groups were found on neuropsychological tests. Levels of work participation among patients improved considerably over time, yet, more than half of the former patients who participated in the four-year follow-up did not feel completely recovered.