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Background: In Denmark, cost savings motivate mandatory biosimilar switches. In 2018, patients switched from originator to biosimilar adalimumab, that is, to GP2017 in Eastern and to SB5 in Western Denmark. However, concerns were raised about additional costs covering, that is, an increased number of outpatient visits due to patient education, treatment monitoring, and patient concerns. Objectives: To investigate whether the switch led to increased total healthcare costs, defined as costs related to in- and outpatient contacts in hospitals and the primary sector and use of prescription medicine (excluding biological treatment). Design: Observational cohort study with geographical cluster pseudo-randomization. Methods: Patients with rheumatoid arthritis, psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA), who switched were identified in the nationwide DANBIO registry. Total healthcare costs 9 months before and after the switch were captured from the National Patient and Prescription registries. The difference between pre- and post-switch costs was estimated by a generalized estimation equations (GEE) model. Results: Overall, 1316 patients switched to GP2017 (n = 621) or SB5 (n = 695). Total healthcare costs were mainly driven by hospital costs. The monthly fluctuations of hospital costs 9 months before and after the switch were largely similar or decreased. In the adjusted analyses (GEE), hospital costs decreased after the switch (by approximately 15%) for GP2017 switchers, especially PsA (estimate = 0.83; 95% CI 0.75–0.92) and AxSpA patients (estimate = 0.85; 0.77–0.93), with no significant changes for SB5 switchers. Conclusion: We found no increase in total healthcare costs in 9 months following a nationwide mandatory adalimumab originator to biosimilar switch. Our findings were strengthened by similar results for GP2017 and SB5., Background: In Denmark, cost savings motivate mandatory biosimilar switches. In 2018, patients switched from originator to biosimilar adalimumab, that is, to GP2017 in Eastern and to SB5 in Western Denmark. However, concerns were raised about additional costs covering, that is, an increased number of outpatient visits due to patient education, treatment monitoring, and patient concerns. Objectives: To investigate whether the switch led to increased total healthcare costs, defined as costs related to in- and outpatient contacts in hospitals and the primary sector and use of prescription medicine (excluding biological treatment). Design: Observational cohort study with geographical cluster pseudo-randomization. Methods: Patients with rheumatoid arthritis, psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA), who switched were identified in the nationwide DANBIO registry. Total healthcare costs 9 months before and after the switch were captured from the National Patient and Prescription registries. The difference between pre- and post-switch costs was estimated by a generalized estimation equations (GEE) model. Results: Overall, 1316 patients switched to GP2017 (n = 621) or SB5 (n = 695). Total healthcare costs were mainly driven by hospital costs. The monthly fluctuations of hospital costs 9 months before and after the switch were largely similar or decreased. In the adjusted analyses (GEE), hospital costs decreased after the switch (by approximately 15%) for GP2017 switchers, especially PsA (estimate = 0.83; 95% CI 0.75–0.92) and AxSpA patients (estimate = 0.85; 0.77–0.93), with no significant changes for SB5 switchers. Conclusion: We found no increase in total healthcare costs in 9 months following a nationwide mandatory adalimumab originator to biosimilar switch. Our findings were strengthened by similar results for GP2017 and SB5.

Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and bleeding events in all ICU patients with COVID-19 in Denmark during the first and second waves of the pandemic

Background: ICU admission due to COVID-19 may result in cognitive and physical impairment. We investigated the long-term cognitive and physical status of Danish ICU patients with COVID-19. Methods: We included all patients with COVID-19 admitted to Danish ICUs between March 10 and May 19, 2020. Patients were the contacted prospectively at 6 and 12 months for follow-up. Our primary outcomes were cognitive function and frailty at 6 and 12 months after ICU admission, estimated by the Mini Montreal Cognitive Assessment, and the Clinical Frailty Scale. Secondary outcomes were 6- and 12-month mortality, health-related quality of life (HRQoL) assessed by EQ-5D-5L, functional status (Barthel activities of daily living and Lawton–Brody instrumental activities of daily living), and fatigue (Fatigue Assessment Scale). The study had no information on pre-ICU admission status for the participants. Results: A total of 326 patients were included. The 6- and 12-month mortality was 37% and 38%, respectively. Among the 204 six-month survivors, 105 (51%) participated in the 6-month follow-up; among the 202 twelve-month survivors, 95 (47%) participated in the 12-month follow-up. At 6 months, cognitive scores indicated impairment for 26% (95% confidence interval [CI], 11.4–12.4) and at 12 months for 17% (95% CI, 12.0–12.8) of participants. Frailty was indicated in 20% (95% CI, 3.4–3.9) at 6 months, and for 18% (95% CI, 3.3–3.8) at 12 months. Fatigue was reported by 52% at 6 months, and by 47% at 12 months. For HRQoL, moderate, severe, or extreme health problems were reported by 28% at 6 months, and by 25% at 12 months. Conclusion: Long-term cognitive, functional impairment was found in up to one in four of patients surviving intensive care for COVID-19. Fatigue was present in nearly half the survivors at both 6 and 12 months. However, pre-ICU admission status of the patients was unknown.

Background: Characteristics and care of intensive care unit (ICU) patients with COVID-19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID-19 admitted to Danish ICUs in the first wave with those admitted later. Methods: Among all Danish ICU patients with COVID-19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis. Results: Among all hospitalised patients with COVID-19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID-19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave. Conclusions: After the first wave of COVID-19 in Denmark, a lower proportion of hospitalised patients with COVID-19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level.

The number of forensic psychiatric patients has steadily increased in many countries during the past 30 years. This increase has been especially pronounced in Denmark when viewed on a per capita basis. Explanations that consider the diversity of possible factors influencing the development are currently insufficient. Most forensic psychiatric patients suffer from psychotic conditions and are convicted under Section 16 of the Danish Penal Code. A smaller proportion is comprised of non-psychotic mentally-disordered offenders convicted under Section 69. In recent years, a hitherto unobserved increase has been seen in the use of treatment sanctions for the latter group. This article describes factors that may have contributed to this development during the period 2003-2013. This is a retrospective file-based study using comparative statistical analysis. The study utilizes 1,078 forensic psychiatric assessment reports concerning non-psychotic mentally-disordered offenders covering the years 2003, 2008, and 2013, together with statements from the Medico-Legal Council and all final verdicts. Results indicate a near doubling in the number of psychiatric sanctions given to non-psychotic mentally-disordered offenders. The total number of forensic psychiatric assessments required by the judicial authorities also increased, though not to the same extent. Geographical differences were found in, among other factors, requests from the police for forensic psychiatric assessments, psychiatric diagnoses and medical recommendations for the court. Interestingly, a significant decrease in the involvement of the Medico-Legal Council occurred during the 10-year study period.

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.

BACKGROUND: Rhabdomyolysis-induced acute kidney injury (AKI) is a common and serious condition. We aimed to summarise the available evidence on this topic and provide recommendations according to current standards for trustworthy guidelines.METHODS: This guideline was developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The following preventive interventions were assessed: (a) fluids, (b) diuretics, (c) alkalinisation, (d) antioxidants, and (e) renal replacement therapy. Exclusively patient-important outcomes were assessed.RESULTS: We suggest using early rather than late fluid resuscitation (weak recommendation, very low quality of evidence). We suggest using crystalloids rather than colloids (weak recommendation, low quality of evidence). We suggest against routine use of loop diuretics as compared to none (weak recommendation, very low quality of evidence). We suggest against use of mannitol as compared to none (weak recommendation, very low quality of evidence). We suggest against routine use of any diuretic as compared to none (weak recommendation, very low quality of evidence). We suggest against routine use of alkalinisation with sodium bicarbonate as compared to none (weak recommendation, low quality of evidence). We suggest against the routine use of any alkalinisation as compared to none (weak recommendation, low quality of evidence). We suggest against routine use of renal replacement therapy as compared to none (weak recommendation, low quality of evidence). For the remaining PICO questions, no recommendations were issued.CONCLUSION: The quantity and quality of evidence supporting preventive interventions for rhabdomyolysis-induced AKI is low/very low. We were able to issue eight weak recommendations and no strong recommendations.

Background: Intravenous administration of fluids is an essential part of critical care. While some fluid administration is likely beneficial, there is increasing observational evidence that the development of fluid overload is associated with increased mortality. There are no randomised trials to confirm this association in patients with acute kidney injury. We aim to perform a pilot trial to test the feasibility of forced fluid removal compared to standard care in patients with acute kidney injury and severe fluid overload, the FFAKI trial. Methods: Then FFAKI trial is a pilot, multicentre, randomised clinical trial recruiting adult intensive care patients with acute kidney injury and fluid overload, defined as more than 10% of ideal bodyweight. Patients are randomised with concealed allocation to either standard care or forced fluid removal with a therapeutic target of negative net fluid balance ≥1mL/kg/h. The safety of fluid removal is continually evaluated according to predefined criteria of hypoperfusion: lactate ≥4mmol/L, mean arterial pressure <50mmHg or mottling beyond the edge of the kneecaps. If patients fulfil one of these criteria, fluid removal is suspended until hypoperfusion has resolved. The primary outcome measure is fluid balance at 5days after randomisation and secondary outcomes include mean daily fluid balance, fluid balance at discharge from the intensive care unit, time to neutral fluid balance, number of serious adverse reactions and number of protocol violations. All patients are followed for 90days. Discussion: The FFAKI trial started in October 2015 and, when completed, will provide data to evaluate whether a large trial of forced fluid removal in critically ill patients is feasible. Our primary outcome will show if the experimental intervention leads to a clinically relevant difference in fluid balance, which could prove beneficial in intensive care patients with acute kidney injury. Trial registration: EudraCT, identifier: 2015-001

PURPOSE: The aim of this study was to assess associations between consecutive thrombelastography (TEG) profiles and standard coagulation tests and disease severity and mortality in patients with severe sepsis. MATERIALS AND METHODS: This was a prospective observational study of adults with severe sepsis admitted to the intensive care unit (ICU). Clinical scores/variables, infection, TEG, biochemistry, therapy, and overall mortality were recorded. RESULTS: Fifty patients (60% men, median age 62 years, 28-day mortality 24%) were included. At admission, 22%, 48%, and 30% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (maximum amplitude [MA]), respectively. Hypocoagulable patients had higher Sequential Organ Failure Assessment and disseminated intravascular coagulation scores compared with hypercoagulable patients and higher 28-day mortality compared with normocoagulable patients (all P <.05). Most patients (73%-91%) displayed a TEG MA comparable with the admission profile during the initial 4 ICU days or until death/discharge. Patients progressing to hypocoagulable MA had a high early mortality (80%) and hypocoagulable MA independently predicted 28-day mortality (adjusted odds ratio, 4.29 [95% confidence interval, 1.35-13.65], P = .014). In hypocoagulable and hypercoagulable patients, only fibrinogen (P = .041 and P <.001, respectively) contributed independently to clot strength, whereas both platelets (P <.001) and fibrinogen (P <.001) contributed independently to clot strength in normocoagulable patients. CONCLUSIONS: The ICU admission TEG MA remained constant for several days in patients with severe sepsis and hypocoagulable MA independently predicted 28-day mortality.

In a recent study we found no difference in the concentrations of luminal lactate in the rectum between nonsurvivors and survivors in early septic shock (

Previously, we observed that rectal luminal lactate was higher in non-survivors compared with survivors of severe sepsis or septic shock persisting >24 h. The present study was initiated to further investigate this tentative association between rectal luminal lactate and mortality in a larger population of patients in early septic shock.