Seroprevalence of SARS-CoV-2 Antibodies in Denmark: Results of Two Nationwide Population-Based Surveys, February and May 2021.

Background: Seroprevalence studies can be used to measure the progression of national COVID-19 epidemics. The Danish National Seroprevalence Survey of SARS-CoV-2 infections (DSS) was conducted as five separate surveys between May 2020 and May 2021. Here, we present results from the two last surveys conducted in February and May 2021. Methods: Persons aged 12 or older were randomly selected from the Danish Population Register and those having received COVID-19 vaccination subsequently excluded. Invitations to have blood drawn in local test centers were sent by mail. Samples were analyzed for whole Immunoglobulin by ELISA. Seroprevalence was estimated by sex, age and geography. Comparisons to vaccination uptake and RT-PCR test results were made. Results: In February 2021, we found detectable antibodies in 7.2% (95% CI: 6.3-7.9%) of the invited participants (participation rate 25%) and in May 2021 in 8.6% (95% CI: 7.6-9.5%) of the invited (participation rate: 14%). Seroprevalence did not differ by sex, but by age group, generally being higher among the <50 than 50+ year-olds. In May 2021, levels of seroprevalence varied from an estimated 13% (95% CI: 12-15%) in the capital to 5.2% (95% CI: 3.4-7.4%) in rural areas. Combining seroprevalence results with vaccine coverage, estimates of protection against infection in May 2021 varied from 95% among 65+ year-olds down to 10-20% among 12-40 year-olds. In March-May 2021, an estimated 80% of all community SARS-CoV-2 infections were diagnosed by RT-PCR and captured by surveillance. Conclusion: Seroprevalence estimates doubled during the 2020-21 winter wave of SARS-CoV-2 infections and then stabilized as vaccinations were rolled out. The epidemic affected large cities and younger people the most. Denmark saw comparatively low infections rates, but high test coverage; an estimated four out of five infections were detected by RT-PCR in March-May 2021.

Disability adjusted life years associated with COVID-19 in Denmark in the first year of the pandemic.

BACKGROUND: Burden of disease studies measure the public health impact of a disease in a society. The aim of this study was to quantify the direct burden of COVID-19 in the first 12 months of the epidemic in Denmark. METHODS: We collected national surveillance data on positive individuals for SARS-CoV-2 with RT-PCR, hospitalization data, and COVID-19 mortality reported in the period between 26th of February, 2020 to 25th of February, 2021. We calculated disability adjusted life years (DALYs) based on the European Burden of Disease Network consensus COVID-19 model, which considers mild, severe, critical health states, and premature death. We conducted sensitivity analyses for two different death-registration scenarios, within 30 and 60 days after first positive test, respectively. RESULTS: We estimated that of the 211,823 individuals who tested positive to SARS-CoV-2 by RT-PCR in the one-year period, 124,163 (59%; 95% uncertainty interval (UI) 112,782-133,857) had at least mild symptoms of disease. The total estimated disease burden was 30,180 DALYs (95% UI 30,126; 30,242), corresponding to 520 DALYs/100,000. The disease burden was higher in the age groups above 70 years of age, particularly in men. Years of life lost (YLL) contributed with more than 99% of total DALYs. The results of the scenario analysis showed that defining COVID-19-related fatalities as deaths registered up to 30 days after the first positive test led to a lower YLL estimate than when using a 60-days window. CONCLUSION: COVID-19 led to a substantial public health impact in Denmark in the first full year of the epidemic. Our estimates suggest that it was the the sixth most frequent cause of YLL in Denmark in 2020. This impact will be higher when including the post-acute consequences of COVID-19 and indirect health outcomes.

Prevalence of SARS-CoV-2 antibodies in Denmark: nationwide, population-based seroepidemiological study.

Seroprevalence studies have proven an important tool to monitor the progression of the coronavirus disease 2019 (COVID-19) pandemic. We present results of consecutive population-based seroprevalence surveys performed in Denmark in 2020. In spring, late summer and autumn/winter of 2020, invitation letters including a questionnaire covering symptoms were sent to representative samples of the population above 12 years and to parents of children below 18 years in the sample. Blood samples were analysed for total Ig and seroprevalence estimates per population segment were calculated and compared to other surveillance parameters. Based on 34 081 participants (participation rate 33%), seroprevalence estimates increased from 1.2% (95%CI: 0.3-1.9%) in May to 4.1% (95%CI: 3.1-4.9%) in December 2020. Seroprevalence estimates were roughly three times higher in those aged 12-29 years compared to 65 + and higher in metropolitan municipalities. By December 2020, 1.5% of the population had tested positive by RT-PCR. Infected individuals in older age groups were hospitalised several fold more often than in younger. Amongst seropositives, loss of taste/smell were the more specific symptoms, 32-56% did not report any symptoms. In more than half of seroconverted families, we did not see evidence of transmission between generations. Seroprevalence increased during 2020; adolescents were primarily infected in the autumn/winter. Denmark has a high per capita test rate; roughly one undiagnosed infection of SARS-CoV-2 were estimated to occur for each diagnosed case. Approximately half were asymptomatically infected. The epidemic appears to have progressed relatively modestly during 2020 in Denmark.

Catheter-related bloodstream infections in patients with intestinal failure receiving home parenteral support: risks related to a catheter-salvage strategy.

Background: In intestinal failure (IF) patients receiving home parenteral support (HPS), catheter-related bloodstream infections (CRBSIs) frequently result in replacement of their tunneled central venous catheters (CVCs), which may lead to future loss of central venous access. Objective: This observational study investigated the consequences of a catheter-salvage strategy related to CRBSIs. Design: All CRBSIs from 2002 to 2016 in the Copenhagen IF and microbiological databases were retrospectively analyzed. Catheter salvage was defined by successful antimicrobial therapy with a retained CVC at discharge. Re-occurrences of CRBSIs with the same microbial species and identical antibiogram were defined as a relapse (<30 d) or as a recurrent (30-100 d) infection. Cox regression analyses incorporated a frailty factor to account for recurrent events and overrepresentation by some patients. Cumulative incidence curves are presented with a competing risk model. Results: There were 2006 tunneled CVCs inserted in 715 adult HPS patients covering 2014.3 CVC years, with a CRBSI incidence rate of 1.83/1000 (n = 1350) and a mortality rate of 0.007/1000 CVC days (n = 5). The mean ± SD salvage rate was 55.3% ± 5.5%, varying according to infection type [monoinfections (62.9% ± 4.4%) and polyinfections (58.6% ± 17.3%)] and causative microorganism [coagulase-negative Staphylococci (CoNS) (68.1% ± 9.4%), Staphylococcus aureus (42.6% ± 17.5%), and Enterobacteriaceae (54.3% ± 16.7%)]. The overall risk of CRBSI relapse was 7.5%, and the risk of CRBSI recurrence was 7.3%. The HR for a subsequent CRBSI was 14% lower in a replaced than in a retained CVC (95% CI: 0.74, 0.99). The HR for a new CRBSI after catheter salvage was 36% higher after polyinfections than after monoinfections (95% CI: 1.03, 1.79). Enterobacteriaceae entailed an increased risk of CRBSI recurrence compared with CoNS (2.26; 95% CI; 1.08, 4.75) and S. aureus (4.45; 95% CI: 1.28, 15.5). Conclusions: High catheter-salvage rates related to CRBSIs were achievable and safe in HPS patients within a broad range of microorganisms but contributed to an increased risk of CRBSI relapse or recurrence.

Home Parenteral Nutrition in Adult Patients With Chronic Intestinal Failure: Catheter-Related Complications Over 4 Decades at the Main Danish Tertiary Referral Center.

BACKGROUND/AIMS: Catheter-related complications (CRCs) cause mortality and morbidity in patients dependent on parenteral support at home (HPN) due to intestinal failure (IF). This study describes the incidences of CRCs in an adult IF cohort over 40 years. It illustrates the evolution and consequences of CRCs, their association to demographic characteristics, and potential risk factors in an effort to provide the rationale for preventive precautions to the relevant patients with IF at risk. METHODS: All patients with IF discharged with HPN from 1970-2010 were included. Patient and treatment characteristics were extracted from the Copenhagen IF database. The incidences were given per 1000 central venous catheter (CVC) days. RESULTS: The 1715 CRCs occurred in 70% of the 508 patients with IF (56% of the 2191 CVCs). The incidence of catheter-related bloodstream infections (CRBSIs) was 1.43. Higher age, HPN administration by community home nurses, and prior CRBSIs significantly raised the hazard for CRBSIs. In the 1970s, catheters were generally replaced following CRBSIs, whereas catheter salvage was the norm in the 2000s. The incidences of mechanical complications, tunnel infections, and catheter-related venous thromboses were 0.80, 0.25, and 0.11, respectively. The overall CRC incidence was 2.58, decreasing the first 3 decades but peaking in the last (2.84). The deaths related to CRCs were low (0.018). CONCLUSION: Even in an experienced IF center of excellence, the incidence of CRCs increased over the 4 decades. This increase could be explained by the expansion of the indication of HPN to a more elderly and frail patient population.

Catheter-Related Bloodstream Infections in Adults Receiving Home Parenteral Nutrition: Substantial Differences in Incidence Comparing a Strict Microbiological to a Clinically Based Diagnosis.

BACKGROUND: A common complication in patients receiving home parenteral nutrition (HPN) is catheter-related bloodstream infections (CRBSIs). The CRBSI incidence has been advocated as an outcome parameter assessing the quality of care. This study aimed to illustrate how the use of different CRBSI definitions affects the reported incidence. MATERIALS AND METHODS: In an observational study based on the Copenhagen intestinal failure database, all clinically reported CRBSIs from 2002-2013 were compared with data from the affiliated microbiological database according to recommended CRBSI criteria. RESULTS: Clinically, 1034 CRBSIs were observed in 548 adults receiving HPN for 1410 catheter-years. Thus, the clinically assessed CRBSI incidence was 1.95/1000 catheter-days. However, based on the microbiological evaluation, only 47% of our episodes fulfilled the Centers for Disease Control and Prevention (CDC) and European Society for Clinical Nutrition (ESPEN) CRBSI criteria. Employing a catheter-salvaging strategy, 40% of the CRBSI diagnoses were supported by the paired blood culture positivity criteria and only 6% by a positive catheter tip. In 53%, CRBSIs were categorized as a clinical or "probable CRBSI" diagnosis. In 20% of all episodes, missing information/blood cultures hampered a CDC/ESPEN CRBSI diagnosis. Thereby, according to CDC/ESPEN CRBSI definitions, the incidence was 0.92/1000 days or 46% lower than clinically assessed. CONCLUSION: This study illustrates the practical and methodological challenges and great variability in reporting of the CRBSI incidence. Nonetheless, it is recommended as a marker of the quality of care. Consensus regarding CRBSI definitions is a prerequisite for a meaningful comparison of this important outcome parameter between HPN centers.

Effect of Liraglutide Treatment on Jejunostomy Output in Patients With Short Bowel Syndrome: An Open-Label Pilot Study.

BACKGROUND: An impaired hormonal "ileo-colonic brake" may contribute to rapid gastric emptying, gastric hypersecretion, high ostomy losses, and the need for parenteral support in end-jejunostomy short bowel syndrome (SBS) patients with intestinal failure (IF). Liraglutide, a glucagon-like peptide 1 receptor agonist, may reduce gastric hypersecretion and dampen gastric emptying, thereby improving conditions for intestinal absorption. MATERIALS AND METHODS: In an 8-week, open-label pilot study, liraglutide was given subcutaneously once daily to 8 end-jejunostomy patients, aged 63.4 ± 10.9 years (mean ± SD) and with small bowel lengths of 110 ± 66 cm. The 72-hour metabolic balance studies were performed before and at the end of treatment. Food intake was unrestricted. Oral fluid intake and parenteral support volume were kept constant. The primary end point was change in the ostomy wet weight output. RESULTS: Liraglutide reduced ostomy wet weight output by 474 ± 563 g/d from 3249 ± 1352 to 2775 ± 1187 g/d (P = .049, Student t test). Intestinal wet weight absorption tended to increase by 464 ± 557 g/d (P = .05), as did urine production by 765 ± 759 g/d (P = .02). Intestinal energy absorption improved by 902 ± 882 kJ/d (P = .02). CONCLUSION: Liraglutide reduced ostomy wet weight output in end-jejunostomy patients with SBS-IF and increased their intestinal wet weight and energy absorption. If larger, randomized, placebo-controlled studies confirm these effects, it adds to the hypothesis that many ileo-colonic brake hormones in conjunction may be involved in the process of intestinal adaptation. By identification of key hormones and addressing their potential synergistic effects, better treatments may be provided to patients with SBS-IF. This trial was registered at clinicaltrialsregister.eu as 2013-005499-16.

Taurolidine-citrate-heparin lock reduces catheter-related bloodstream infections in intestinal failure patients dependent on home parenteral support: a randomized, placebo-controlled trial.

Background: In patients with intestinal failure who are receiving home parenteral support (HPS), catheter-related bloodstream infections (CRBSIs) inflict health impairment and high costs.Objective: This study investigates the efficacy and safety of the antimicrobial catheter lock solution, taurolidine-citrate-heparin, compared with heparin 100 IE/mL on CRBSI occurrence.Design: Forty-one high-risk patients receiving HPS followed in a tertiary HPS unit were randomly assigned in a double-blinded, placebo-controlled trial. External, stratified randomization was performed according to age, sex, and prior CRBSI incidence. The prior CRBSI incidence in the study population was 2.4 episodes/1000 central venous catheter (CVC) days [95% Poisson confidence limits (CLs): 2.12, 2.71 episodes/1000 CVC days]. The maximum treatment period was 2 y or until occurrence of a CRBSI or right-censoring because of CVC removal. The exact permutation tests were used to calculate P values for the log-rank tests.Results: Twenty patients received the taurolidine-citrate-heparin lock and 21 received the heparin lock, with 9622 and 6956 treatment days, respectively. In the taurolidine-citrate-heparin arm, no CRBSIs occurred, whereas 7 CRBSIs occurred in the heparin arm, with an incidence of 1.0/1000 CVC days (95% Poisson CLs: 0.4, 2.07/1000 CVC days; P = 0.005). The CVC removal rates were 0.52/1000 CVC days (95% Poisson CLs: 0.17, 1.21/1000 CVC days) and 1.72/1000 CVC days (95% Poisson CLs: 0.89, 3.0/1000 CVC days) in the taurolidine-citrate-heparin and heparin arm, respectively, tending to prolong CVC survival in the taurolidine arm (P = 0.06). Costs per treatment year were lower in the taurolidine arm (€2348) than in the heparin arm (€6744) owing to fewer admission days related to treating CVC-related complications (P = 0.02).Conclusions: In patients with intestinal failure who are life dependent on HPS, the taurolidine-citrate-heparin catheter lock demonstrates a clinically substantial and cost-beneficial reduction of CRBSI occurrence in a high-risk population compared with heparin. This trial was registered at clinicaltrials.gov as NCT01948245.

Single-Center, Adult Chronic Intestinal Failure Cohort Analyzed According to the ESPEN-Endorsed Recommendations, Definitions, and Classifications.

BACKGROUND/AIMS: The objective of this study was to describe a clinically well-defined, single-center, intestinal failure (IF) cohort based on a template of definitions and classifications endorsed by the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: A cross-sectional, retrospective, adult IF cohort, receiving parenteral support (PS), was extracted from the Copenhagen IF database at the tertiary IF center, Copenhagen University Hospital, Rigshospitalet, Denmark. RESULTS: Rigshospitalet provided PS to 188 adult patients with IF on December 31, 2011. Six patients received only fluids and electrolytes, while 97% required parenteral energy (17 ± 12 kcal/kg/d). Although 92% of the cohort had undergone intestinal resection, only 53% were classified as patients with short bowel syndrome (SBS) according to the pathophysiological classification. In the remaining cohort, patients were distributed as 5% with intestinal fistula, 12% with intestinal dysmotility, 5% with mechanical obstruction, and 14% with mucosal diseases. Twelve percent had a combination of pathophysiological causes. The patients with SBS (n = 100) were subdivided according to bowel anatomy into group 1 (jejuno/ileostomy, n = 82), group 2 (jejuno-colonic-anastomosis, n = 16), and group 3 (jejuno-ileo-colonic-anastomosis, n = 2). When evaluating the cohort requirements for PS using the ESPEN chronic IF classification based on the need for fluid volume and energy, 53% of the patients with IF were distributed in the maximum categories. CONCLUSION: The orphan condition of IF with its large patient heterogeneity mandates establishment of uniform definitions and a harmonization of classifications. As illustrated, the ESPEN-endorsed definitions and classifications are well designed and may serve as a common uniform template to facilitate both intra- and intercenter comparisons between reference centers and thus outcome results.

Home Parenteral Nutrition in Adult Patients With Chronic Intestinal Failure: The Evolution Over 4 Decades in a Tertiary Referral Center.

BACKGROUND/AIMS: In Denmark, the public healthcare system ensures patients with intestinal failure (IF) the same rights for a life-saving treatment as patients with other organ failures. This study reports the epidemiological data from the largest Danish IF center. As one of the pioneering centers in treating IF with home parenteral nutrition (HPN), this study documents the HPN evolution and describes the demographics and outcome in one of the world's largest single-center cohorts. METHODS: We included patients with IF discharged with HPN from 1970-2010. Data were extracted according to European Society for Clinical Nutrition and Metabolism classifications from the Copenhagen IF database. RESULTS: Over the decades, we observed an exponential increase in the number of HPN patients. The 508 patients with IF collectively received HPN for 1751 years. While receiving HPN, 211 patients with IF (42%) died. Only 24 deaths were HPN related: sepsis (n = 10), liver disease (n = 12), central venous thrombosis (n = 1), and a complicated catheter placement (n = 1). The HPN-related mortality was as low as 0.014 deaths/HPN year. In the first decade, HPN was mainly provided to younger, intestinally resected adult patients with IF with inflammatory bowel disease (IBD), but numerically, they were subsequently outnumbered by elderly patients with IF with cancer or complications from non-IBD, noncancer abdominal surgery. Despite these demographic changes, the HPN-related mortality has decreased in the past decade. CONCLUSION: Evolving from being a rare, experimental treatment in the 1970s, HPN at present is safe with a low treatment-related mortality in the experienced center, despite HPN being more widely used in a more elderly population.

Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid-induced insulin resistance.

AIMS/HYPOTHESIS: We evaluated the insulinotropic properties of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in healthy individuals at risk of developing type 2 diabetes before and after glucocorticoid-induced insulin resistance. METHODS: Nineteen healthy, glucose tolerant, first-degree relatives of type 2 diabetic patients underwent OGTT and 7 mmol/l and 15 mmol/l glucose clamps with concomitant infusions of GLP-1, GIP or NaCl and a final infusion of arginine for determination of maximum beta cell capacity before and after treatment with dexamethasone. In addition, first-phase insulin responses were determined at 7 mmol/l and 15 mmol/l and second-phase insulin responses at 7 mmol/l. RESULTS: After dexamethasone treatment, all 19 participants had increased insulin resistance (HOMA-IR and insulin sensitivity index [M/I] values) and 2 h plasma glucose concentrations, while beta cell function indices generally increased according to the increased resistance. First-phase insulin responses induced by GLP-1 and GIP at 7 mmol/l and maximal beta cell secretory capacity did not differ before and after dexamethasone, while second-phase responses to 7 mmol/l and first-phase responses to 15 mmol/l glucose were reduced equally for both hormones. CONCLUSIONS/INTERPRETATION: Glucocorticoid-induced insulin resistance in individuals at risk of type 2 diabetes leads to a reduced insulinotropic effect of the incretin hormones. This reduction was not associated with a decrease in the maximal beta cell secretory capacity, indicating that the reduced incretin effect in the developing dysglycaemia of the present experimental model is due to a specific early reduction of the insulinotropic effects of the incretin hormones. TRIAL REGISTRATION: Clinicaltrials.gov NCT02235584.