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.

[First case of COVID-19 treated with tocilizumab in Iceland]. / Fyrsta meðferð með tocilizumab við COVID-19 hérlendis - sjúkratilfelli

A gentleman in his early fifties became ill with flu-like symptoms after vacationing abroad and was diagnosed with COVID-19 after returning to Iceland. A few days later he was admitted to the University Hospital, Landspitali, due to worsening respiratory symptoms and severe fatigue. A computed tomography scan of lthe lungs showed diffuse bilateral consolidations and ground glass changes. He developed respiratory failure and was transferred to the intensive care unit where he received further treatment, including tocilizumab (IL-6 receptor inhibitor). He subsequently showed clinical improvement and did not require endotracheal intubation.

Hepatocellular Jaundice due to Hydroxycut in Monozygotic Twins.

Liver injury associated with the use of a number of different of herbal and dietary supplements are increasingly recognized. It is though often unclear which of the sometimes multiple ingredients are responsible for the liver injury. Several case reports have been published on suspected liver injury due to Hydroxycut, which is a multi-ingredient supplement often used to induce weight loss. However, the hepatotoxic potential of Hydroxycut has though been disputed, and steatotic liver disease has also been implicated in patients who are found to have elevated liver enzymes while on Hydroxycut. We report clinically apparent liver injury with jaundice associated with the use of Hydroxycut in monozygotic twins with remarkably similar type of liver injury. Both had the genotype HLA-B 35:01 allele, a risk factor for green-tea extract induced liver injury, which is included in Hydroxycut.

Increased attendance rates and altered characteristics of sexual violence.

OBJECTIVE: To study the attendance rates and characteristics of sexual violence presented at emergency services for rape victims, over a 10-year period. DESIGN: Incidence study. SETTING: Rape Trauma Service, within an emergency department at a tertiary referral university hospital. POPULATION. The total female population in Iceland. METHODS: Medical records on visits were reviewed and systematically coded. Annual attendance rates were calculated over time as number of visits per 10 000 female inhabitants aged 13-49 years. Characteristics of sexual violence, perpetrators and victims were compared between 1998-2002 and 2003-2007. MAIN OUTCOME MEASURES: Annual attendance rates and characteristics of sexual violence. RESULTS: Of 1153 visits, 828 (71.8%) were due to severe sexual violence (penetration). Annual attendance rates of all sexual violence increased from 12.5 to 16.9 per 10 000 women aged 13-49 (p<0.01). Attendance rates due to severe sexual violence increased specifically among women aged 18-25 (p<0.01). The proportion of assaults involving multiple perpetrators increased from 13.9% in 1998-2002 to 18.9% in 2003-2007 (p=0.05). With time, a higher proportion of victims had seriously impaired consciousness due to alcohol consumption (p<0.01) and had used illegal drugs prior to assault (p<0.05). CONCLUSIONS: The findings point towards an increase in women's visits to specialized emergency services for rape victims, particularly in the age group 18-25 years. The increased role of multiple perpetrators, alcohol and illicit drugs in sexual violence calls for further attention.

Immediate surge in female visits to the cardiac emergency department following the economic collapse in Iceland: an observational study.

OBJECTIVE: To study potential changes in attendance at emergency departments (ED) in Reykjavík immediately following the swift economic meltdown in Iceland in October 2008. METHODS: Using electronic medical records of the National University Hospital in Reykjavík, a population-based register study was conducted contrasting weekly attendance rates at Reykjavík ED (cardiac and general ED) during 10-week periods in 2006, 2007 and 2008. The weekly number of all ED visits (major track), with discharge diagnoses, per total population at risk were used to estimate RR and 95% CI of ED attendance in weeks 41-46 (after the 2008 economic collapse) with the weekly average number of visits during weeks 37-40 (before the collapse) as reference. RESULTS: Compared with the preceding weeks (37-40), the economic collapse in week 41 2008 was associated with a distinct increase in the total number of visits to the cardiac ED (RR 1.26; 95% CI 1.07 to 1.49), particularly among women (RR 1.41; 95% CI 1.17 to 1.69) and marginally among men (RR 1.15; 95% CI 0.96 to 1.37). A similar increase was not observed in week 41 at the general ED in 2008 or in either ED in 2007 or 2006. In week 41 2008, visits with ischaemic heart disease as discharge diagnoses (ICD-10: I20-25) were increased among women (RR 1.79; 95% CI 1.01 to 3.17) but not among men (RR 1.07; 95% CI 0.71 to 1.62). CONCLUSION: The dramatic economic collapse in Iceland in October 2008 was associated with an immediate short-term increase in female attendance at the cardiac ED.

Determining SARS-CoV-2 non-infectivity state-A brief overview.

From the beginning of the COVID-19 pandemic, it has claimed over 6 million lives, and globally the pandemic rages with detrimental consequences, with the emergence of new more infectious and possibly virulent variants. A clinical obstacle in this battle has been to determine when an infected individual has reached a non-infectious state. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can be transmitted under diverse circumstances, and various rules and regulations, along with different testing methods, have been applied in an attempt to confine the transmission. However, that has proven to be a difficult task. In this review, we take together recently published data on infectivity and transmission of SARS-CoV-2 and have combined it with the clinical experience that physicians in Iceland have accumulated from the pandemic. In addition, we suggest guidelines for determining when patients with COVID-19 reach a non-infectious state based on a combination of clinical experience, scientific data, and proficient use of available tests. This review has addressed some of the questions regarding contagiousness and immunity against SARS-CoV-2.

Outpatient Use of Antimicrobials in Patients With Rheumatoid Arthritis Before and After Treatment With Tumor Necrosis Factor Inhibitors: A Nationwide Retrospective Cohort Study.

OBJECTIVE: The objective of this study was to investigate the effect of tumor necrosis factor α inhibitor (TNFi) initiation on the use of antimicrobials among biologic-naïve patients with rheumatoid arthritis (RA). METHODS: Information on all biologic-naïve patients with RA was extracted from ICEBIO, a nationwide registry. Each patient was matched on age, sex, and calendar time to five randomly selected individuals from the general population. All filled antimicrobial and glucocorticoid prescriptions in the 2 years before and after initiation of the first TNFi were extracted from the Prescription Medicines Register. Prescriptions were quantified by using the number of filled prescriptions (NP) and defined daily doses. RESULTS: We extracted information on 359 patients with RA and 1795 comparators. During the 24 months before initiating treatment with TNFi, patients with RA received more prescriptions for antimicrobials than their matched general population comparators (mean ± SD: 2.8 ± 3.4 vs 1.6 ± 2.7; P < 0.001). The 24-month mean NP for patients with RA increased to 3.5 ± 3.9 (P < 0.001) after initiating TNFi: antibiotics, 2.6 ± 3.2 to 3.2 ± 3.5 (P < 0.001); antivirals, 0.06 ± 0.5 to 0.16 ± 0.7 (P = 0.004); and antimycotics, 0.14 ± 0.5 to 0.22 ± 0.9 (P = 0.06). The 12-month mean NP was highest in the second year after TNFi initiation (1.9 ± 2.4). No association was found between NP and glucocorticoids, age, body mass index, or pre-TNFi Disease Activity Score 28-joint count and C-reactive protein. CONCLUSION: Patients with RA on TNFi are more commonly treated for infections in the outpatient settings than previously reported. Patients are prescribed more antimicrobials in the 2 years preceding TNFi initiation than the general population, and this use further increases after initiation of TNFi. In contrast to what is reported for infections requiring hospitalization, outpatient antimicrobial use remained elevated for at least 2 years.

Effect of booster vaccination against Delta and Omicron SARS-CoV-2 variants in Iceland.

By the end of July 2021, the majority of the Icelandic population had received vaccination against COVID-19. In mid-July a wave of SARS-CoV-2 infections, dominated by the Delta variant, spread through the population, followed by an Omicron wave in December. A booster vaccination campaign was initiated to curb the spread of the virus. We estimate the risk of infection for different vaccine combinations using vaccination data from 276,028 persons and 963,557 qPCR tests for 277,687 persons. We measure anti-Spike-RBD antibody levels and ACE2-Spike binding inhibitory activity in 371 persons who received one of four recommended vaccination schedules with or without an mRNA vaccine booster. Overall, we find different antibody levels and inhibitory activity in recommended vaccination schedules, reflected in the observed risk of SARS-CoV-2 infections. We observe an increased protection following mRNA boosters, against both Omicron and Delta variant infections, although BNT162b2 boosters provide greater protection against Omicron than mRNA-1273 boosters.

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.

Lessons from the past: familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918.

The pandemic influenza of 1918 (Spanish flu) killed 21-50 million people globally, including in Iceland, where the characteristics and spread of the epidemic were well documented. It has been postulated that genetic host factors may have contributed to this high mortality. We identified 455 individuals who died of the Spanish flu in Iceland during a 6-week period during the winter of 1918, representing >92% of all fatal domestic cases mentioned by historical accounts. The highest case fatality proportion was 2.8%, and peak excess mortality was 162/100,000/week. Fatality proportions were highest among infants, young adults, and the elderly. A genealogical database was used to study relatedness and relative risk (RR) of the fatal influenza victims and relatives of their unaffected mates. The significance of these RR computations was assessed by drawing samples randomly from the genealogical database matched for age, sex, and geographical distribution. Familial aggregation of fatalities was seen, with RRs for death ranging from 3.75 for first-degree relatives (P < 0.0001) to 1.82 (P = 0.005), 1.12 (P = 0.252), and 1.47 (P = 0.0001) for second- to fourth-degree relatives of fatal influenza victims, respectively. The RRs within the families of unaffected mates of fatal influenza victims were 2.95 (P < 0.0001), 1.27 (P = 0.267), 1.35 (P = 0.04), and 1.42 (P = 0.001), for first- to fourth-degree relatives, respectively. In conclusion, the risk of death from the Spanish flu was similar within families of patients who succumbed to the illness and within families of their mates who survived. Our data do not provide conclusive evidence for the role of genetic factors in susceptibility to the Spanish flu.

Pneumonia due to Mycobacterium cosmeticum in a renal transplant recipient.

A 69-year-old man renal transplant recipient for 4 years, presented with 4-day history of cough and dyspnoea. He was diagnosed with community-acquired pneumonia and treated accordingly. He deteriorated requiring intensive care unit admission and intubation. Mycobacterial culture from bronchoalveolar lavage grew colonies within 7 days of incubation while Mycobacterium tuberculosis PCR was negative. The antibiotic regimen was adjusted to cover for rapidly growing mycobacteria with imipenem, amikacin and clarithromycin. The final culture reported Mycobacterium cosmeticum He improved on the antibiotic regimen given which the organism turned to be sensitive to. We reported the second case with M. cosmeticum that fulfilled the diagnostic criteria for non-tuberculous mycobacterial lung infection. Improvement of patient's lung infection on appropriate antibiotics points to a causal relationship.

Antibiotic resistance among major pathogens compared to hospital treatment guidelines and antibiotic use in Nordic hospitals 2010-2018.

BACKGROUND: The Nordic countries have comparable nationwide antibiotic resistance surveillance systems and individual antibiotic stewardship programmes. The aim of this study was to assess antibiotic resistance among major pathogens in relation to practice guidelines for hospital antibiotic treatment and antibiotic use in Nordic countries 2010-2018. METHODS: Antibiotic resistance among invasive isolates from 2010-2018 and aggregated antibiotic use were obtained from the European Centre for Disease Prevention and Control. Hospital practice guidelines were obtained from national or regional guidelines. RESULTS: Antibiotic resistance levels among Escherichia coli and Klebsiella pneumoniae were similar in all Nordic countries in 2018 and low compared to the European mean. Guidelines for acute pyelonephritis varied; 2nd generation cephalosporin (Finland), 3rd generation cephalosporins (Sweden, Norway), ampicillin with an aminoglycoside or aminoglycoside monotherapy (Denmark, Iceland and Norway). Corresponding guidelines for sepsis of unknown origin were 2nd (Finland) or 3rd (Sweden, Norway, Iceland) generation cephalosporins, carbapenems, (Sweden) combinations of penicillin with an aminoglycoside (Norway, Denmark), or piperacillin-tazobactam (all Nordic countries). Methicillin-resistant Staphylococcus aureus rates were 0-2% and empirical treatment with anti-MRSA antibiotics was not recommended in any country. Rates of penicillin non-susceptibility among Streptococcus pneumoniae were low (<10%) except in Finland and Iceland (<15%), but benzylpenicillin was recommended for community-acquired pneumonia in all countries. CONCLUSION: Despite similar resistance rates among Enterobacteriaceae there were differences in practice guidelines for pyelonephritis and sepsis. National surveillance of antibiotic resistance can be used for comparison and optimization of guidelines and stewardship interventions to preserve the low levels of antibiotic resistance in Nordic countries.

Molecular benchmarks of a SARS-CoV-2 epidemic.

A pressing concern in the SARS-CoV-2 epidemic and other viral outbreaks, is the extent to which the containment measures are halting the viral spread. A straightforward way to assess this is to tally the active cases and the recovered ones throughout the epidemic. Here, we show how epidemic control can be assessed with molecular information during a well characterized epidemic in Iceland. We demonstrate how the viral concentration decreased in those newly diagnosed as the epidemic transitioned from exponential growth phase to containment phase. The viral concentration in the cases identified in population screening decreased faster than in those symptomatic and considered at high risk and that were targeted by the healthcare system. The viral concentration persists in recovering individuals as we found that half of the cases are still positive after two weeks. We demonstrate that accumulation of mutations in SARS-CoV-2 genome can be exploited to track the rate of new viral generations throughout the different phases of the epidemic, where the accumulation of mutations decreases as the transmission rate decreases in the containment phase. Overall, the molecular signatures of SARS-CoV-2 infections contain valuable epidemiological information that can be used to assess the effectiveness of containment measures.

[Opioid Induced Pituitary Dysfunction].

A 77-year-old woman with a history of anal squamous cell carcinoma was admitted because of malaise, diarrhea and nausea, in addition to back pain related to a verte- bral compression fracture. During the course of treatment, opioid therapy was initiated, following which the patient became progressively hypotensive and hyponatraemic and respiratory drive progressively decreased. Serum levels of cortisol, TSH and LH were decreased and prolactin slightly elevated, but a Synacthen test and brain MRI turned out normal, suggesting a diagnosis of opioid-induced pituitary dysfunction. The patient was given glucocorticoid replacement therapy with good results. Here we present a case of this serious but less well recognised side-effect of opioids.

Contamination of cooked peeled shrimp (Pandalus borealis) by Listeria monocytogenes during processing at two processing plants.

Listeria spp. and Listeria monocytogenes contamination was evaluated in cooked peeled shrimp (final or semifinal product, 82 samples) and the shrimp-processing environment (two plants, 613 samples) in eight surveys conducted from 1998 through 2001. Listeria was detected in 12.5% (78) of the 695 samples (11.2% of the samples were positive for L. monocytogenes), but none of the samples of final product contained Listeria. One hundred seventy-two L. monocytogenes isolates were characterized by pulsed-field gel electrophoresis. Cleavage with macrorestriction enzymes AscI and ApaI yielded 14 different pulsotypes in the plants; two types were dominant, one in each plant. Sixty-three of the 106 isolates in plant A and 43 of the 66 isolates in plant B were of the dominant types. Certain strains, mainly of serotypes 1/2c and 4b and pulsotypes 1A and 2H, were persistent for long periods in both plants. Adaptation of good hygienic practices in the processing plants, including strict rules concerning traffic of staff and equipment, and existing hygienic requirements appeared to be effective in preventing contamination between areas within plants and in the final product. The persistence of Listeria strains in these two processing plants indicates the importance of detecting the places in the processing environment (e.g., transporters, equipment, floors, and drains) where L. monocytogenes can survive so that cleaning and disinfection efforts can be directed to such niches.

Virulence of Listeria monocytogenes isolates from humans and smoked salmon, peeled shrimp, and their processing environments.

The virulence of 82 Listeria monocytogenes isolates from human cases and cold-smoked salmon, cooked peeled shrimp, and their production environments was assessed using the plaque-forming assay and a subcutaneous inoculation test in mice. These isolates were previously typed using serotyping and pulsed-field gel electrophoresis. The isolates from food-production environments were collected in several surveys over the period of 5 years. Sixty-eight (99.8%) of 69 isolates tested from food and food-processing environments were considered virulent while only one was avirulent. All clinical isolates (13) were highly virulent. The isolates were from raw materials, final products, and the production environment. This stresses the importance of hygiene in the processing environment as well as among personnel to avoid contamination of the final product.

HLA class II sequence variants influence tuberculosis risk in populations of European ancestry.

Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 × 10(-13)) and PTB (OR = 1.25, P = 5.8 × 10(-12)), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 × 10(-12))--both located between HLA-DQA1 and HLA-DRB1--and a missense variant encoding p.Ala210Thr in HLA-DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 × 10(-9), OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 × 10(-4)). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells.