The incidence of new and persistent benzodiazepine use after surgery.

BACKGROUND: It is possible that a portion of new and new persistent use of benzodiazepines is among individuals who start using the medications before or after surgery. We studied the incidence of new and new persistent benzodiazepine use among patients undergoing surgery. METHODS: Retrospective, single-center, population-based cohort of all individuals ≥18 years undergoing first surgery between January 2, 2006 and December 31, 2018 with a year of follow-up for filled medications. Benzodiazepine-naïve patients were defined as not filling a prescription from a year to 31 days before surgery. Patients with new use were naïve patients who filled a prescription between 30 days before and 14 days after surgery, and patients with new persistent use were patients with new use who filled a prescription between 15 days and a year after surgery. Patient and procedural characteristics and prescription filling patterns between the groups were compared. RESULTS: A total of 55,997 patients (32,136 women [57.4%]; median [interquartile range] age, 55 [39, 69] years) were included. The incidence of new use among naïve patients was 2.7% (95% confidence interval, 2.6%-2.8%; n = 1,311), and, of those, 43.7% (95% confidence interval, 41.0%-46.5%; n = 571) had new persistent benzodiazepine use. Approximately 10% of patients with new use filled a prescription for benzodiazepine in every 30-day window during the follow-up period. CONCLUSION: A small portion of surgical patients begin benzodiazepine use perioperatively, but subsequently half fill criteria for persistent use. This highlights the importance of identifying strategies to minimize both new use and the progression of new use into persistent use in surgical patients.

Development of a prognostic model of COVID-19 severity: a population-based cohort study in Iceland.

BACKGROUND: The severity of SARS-CoV-2 infection varies from asymptomatic state to severe respiratory failure and the clinical course is difficult to predict. The aim of the study was to develop a prognostic model to predict the severity of COVID-19 in unvaccinated adults at the time of diagnosis. METHODS: All SARS-CoV-2-positive adults in Iceland were prospectively enrolled into a telehealth service at diagnosis. A multivariable proportional-odds logistic regression model was derived from information obtained during the enrollment interview of those diagnosed between February 27 and December 31, 2020 who met the inclusion criteria. Outcomes were defined on an ordinal scale: (1) no need for escalation of care during follow-up; (2) need for urgent care visit; (3) hospitalization; and (4) admission to intensive care unit (ICU) or death. Missing data were multiply imputed using chained equations and the model was internally validated using bootstrapping techniques. Decision curve analysis was performed. RESULTS: The prognostic model was derived from 4756 SARS-CoV-2-positive persons. In total, 375 (7.9%) only required urgent care visits, 188 (4.0%) were hospitalized and 50 (1.1%) were either admitted to ICU or died due to complications of COVID-19. The model included age, sex, body mass index (BMI), current smoking, underlying conditions, and symptoms and clinical severity score at enrollment. On internal validation, the optimism-corrected Nagelkerke's R2 was 23.4% (95%CI, 22.7-24.2), the C-statistic was 0.793 (95%CI, 0.789-0.797) and the calibration slope was 0.97 (95%CI, 0.96-0.98). Outcome-specific indices were for urgent care visit or worse (calibration intercept -0.04 [95%CI, -0.06 to -0.02], Emax 0.014 [95%CI, 0.008-0.020]), hospitalization or worse (calibration intercept -0.06 [95%CI, -0.12 to -0.03], Emax 0.018 [95%CI, 0.010-0.027]), and ICU admission or death (calibration intercept -0.10 [95%CI, -0.15 to -0.04] and Emax 0.027 [95%CI, 0.013-0.041]). CONCLUSION: Our prognostic model can accurately predict the later need for urgent outpatient evaluation, hospitalization, and ICU admission and death among unvaccinated SARS-CoV-2-positive adults in the general population at the time of diagnosis, using information obtained by telephone interview.

HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2.

Memory T-cell responses following SARS-CoV-2 infection have been extensively investigated but many studies have been small with a limited range of disease severity. Here we analyze SARS-CoV-2 reactive T-cell responses in 768 convalescent SARS-CoV-2-infected (cases) and 500 uninfected (controls) Icelanders. The T-cell responses are stable three to eight months after SARS-CoV-2 infection, irrespective of disease severity and even those with the mildest symptoms induce broad and persistent T-cell responses. Robust CD4+ T-cell responses are detected against all measured proteins (M, N, S and S1) while the N protein induces strongest CD8+ T-cell responses. CD4+ T-cell responses correlate with disease severity, humoral responses and age, whereas CD8+ T-cell responses correlate with age and functional antibodies. Further, CD8+ T-cell responses associate with several class I HLA alleles. Our results, provide new insight into HLA restriction of CD8+ T-cell immunity and other factors contributing to heterogeneity of T-cell responses following SARS-CoV-2 infection.

Longitudinal changes in inflammatory biomarkers among patients with COVID-19: A nationwide study in Iceland.

OBJECTIVES: All SARS-CoV-2-positive persons in Iceland were prospectively monitored and those who required outpatient evaluation or were admitted to hospital underwent protocolized evaluation that included a standardized panel of biomarkers. The aim was to describe longitudinal changes in inflammatory biomarkers throughout the infection period of patients with COVID-19 requiring different levels of care. DESIGN: Registry-based study. SETTING: Nationwide study in Iceland. PATIENTS: All individuals who tested positive for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) from February 28 to December 31, 2020 in Iceland and had undergone blood tests between 5 days before and 21 days following onset of symptoms. MEASUREMENTS AND MAIN RESULTS: Data were collected from the electronic medical record system of Landspitali-The National University Hospital of Iceland. Data analyses were descriptive and the evolution of biomarkers was visualized using locally weighted scatterplot smoothing curves stratified by the worst clinical outcome experienced by the patient: outpatient evaluation only, hospitalization, and either intensive care unit (ICU) admission or death. Of 571 included patients, 310 (54.3%) only required outpatient evaluation or treatment, 202 (35.4%) were hospitalized, and 59 (10.3%) were either admitted to the ICU or died. An early and persistent separation of the mean lymphocyte count and plasma C-reactive protein (CRP) and ferritin levels was observed between the three outcome groups, which occurred prior to hospitalization for those who later were admitted to ICU or died. Lower lymphocyte count, and higher CRP and ferritin levels correlated with worse clinical outcomes. Patients who were either admitted to the ICU or died had sustained higher white blood cell and neutrophil counts, and elevated plasma levels of procalcitonin and D-dimer compared with the other groups. CONCLUSIONS: Lymphocyte count and plasma CRP and ferritin levels might be suitable parameters to assess disease severity early during COVID-19 and may serve as predictors of worse outcome.

Reconstruction of a large-scale outbreak of SARS-CoV-2 infection in Iceland informs vaccination strategies.

OBJECTIVES: The spread of SARS-CoV-2 is dependent on several factors, both biological and behavioural. The effectiveness of nonpharmaceutical interventions can be attributed largely to changes in human behaviour, but quantifying this effect remains challenging. Reconstructing the transmission tree of the third wave of SARS-CoV-2 infections in Iceland using contact tracing and viral sequence data from 2522 cases enables us to directly compare the infectiousness of distinct groups of persons. METHODS: The transmission tree enables us to model the effect that a given population prevalence of vaccination would have had on the third wave had one of three different vaccination strategies been implemented before that time. This allows us to compare the effectiveness of the strategies in terms of minimizing the number of cases, deaths, critical cases, and severe cases. RESULTS: We found that people diagnosed outside of quarantine (Rˆ=1.31) were 89% more infectious than those diagnosed while in quarantine (Rˆ=0.70) and that infectiousness decreased as a function of time spent in quarantine before diagnosis, with people diagnosed outside of quarantine being 144% more infectious than those diagnosed after ≥3 days in quarantine (Rˆ=0.54). People of working age, 16 to 66 years (Rˆ=1.08), were 46% more infectious than those outside of that age range (Rˆ=0.74). DISCUSSION: We found that vaccinating the population in order of ascending age or uniformly at random would have prevented more infections per vaccination than vaccinating in order of descending age, without significantly affecting the expected number of deaths, critical cases, or severe cases.

Therapeutics and COVID-19-A living WHO guideline: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the Living WHO guideline on therapeutics and COVID-19. This trustworthy continuously updated guideline serves as a highly useful decision aid for Nordic anaesthesiologists caring for patients with COVID-19.

A descriptive study of the surge response and outcomes of ICU patients with COVID-19 during first wave in Nordic countries.

BACKGROUND: We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. METHODS: Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. RESULTS: Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6%-6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%-85%) in all countries, the proportion of patients receiving renal replacement therapy (7%-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0%-85%). Crude ICU mortality ranged from 11% to 33%. CONCLUSION: There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.

Clinical spectrum of coronavirus disease 2019 in Iceland: population based cohort study.

OBJECTIVE: To characterise the symptoms of coronavirus disease 2019 (covid-19). DESIGN: Population based cohort study. SETTING: Iceland. PARTICIPANTS: All individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR) between 17 March and 30 April 2020. Cases were identified by three testing strategies: targeted testing guided by clinical suspicion, open invitation population screening based on self referral, and random population screening. All identified cases were enrolled in a telehealth monitoring service, and symptoms were systematically monitored from diagnosis to recovery. MAIN OUTCOME MEASURES: Occurrence of one or more of 19 predefined symptoms during follow-up. RESULTS: Among 1564 people positive for SARS-CoV-2, the most common presenting symptoms were myalgia (55%), headache (51%), and non-productive cough (49%). At the time of diagnosis, 83 (5.3%) individuals reported no symptoms, of whom 49 (59%) remained asymptomatic during follow-up. At diagnosis, 216 (14%) and 349 (22%) people did not meet the case definition of the Centers for Disease Control and Prevention and the World Health Organization, respectively. Most (67%) of the SARS-CoV-2-positive patients had mild symptoms throughout the course of their disease. CONCLUSION: In the setting of broad access to RT-PCR testing, most SARS-CoV-2-positive people were found to have mild symptoms. Fever and dyspnoea were less common than previously reported. A substantial proportion of SARS-CoV-2-positive people did not meet recommended case definitions at the time of diagnosis.

Humoral Immune Response to SARS-CoV-2 in Iceland.

BACKGROUND: Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. RESULTS: Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. CONCLUSIONS: Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

Nationwide Incidence and Outcomes of Patients With Coronavirus Disease 2019 Requiring Intensive Care in Iceland.

OBJECTIVES: To determine the nationwide demographics and hospital mortality of patients with severe acute respiratory syndrome coronavirus 2 infection requiring admission to the ICU for coronavirus disease 2019 in Iceland. DESIGN: Prospective observational study. SETTING: All ICUs in Iceland (Landspitali University Hospital and Akureyri Regional Hospital). PATIENTS: All patients admitted to the ICU for management of coronavirus disease 2019 between March 14, 2020, and April 13, 2020, with follow-up through May 5, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 27 patients were admitted to the ICU for coronavirus disease 2019 out of 1,788 severe acute respiratory syndrome coronavirus 2 positive cases, rendering an overall admission ratio of 1.5% (95% CI, 1.0-2.2%). The population rate of ICU admission for coronavirus disease 2019 was 7.4 (95% CI, 4.9-10.8) admissions per 100,000 individuals. The hospital mortality of patients admitted to the ICU was 15% (95% CI, 4-34%), and the mortality of patients receiving mechanical ventilation was 19% (95% CI, 4-46%). CONCLUSIONS: We report a lower overall ratio of ICU admissions for coronavirus disease 2019 among severe acute respiratory syndrome coronavirus 2 positive patients and a lower hospital mortality for patients treated in the ICU for coronavirus disease 2019 compared with initial reports from Italy and China. Our results could be explained by the early adoption of widespread testing and a successful national response to the pandemic.