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Children and adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are usually asymptomatic or have mild coronavirus disease (COVID-19) with low rates of hospitalization and death. Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe complication of SARS-CoV-2 infection. This paper reviews an excerpt of the literature on disease burden and complications following COVID-19 in children and adolescents aged 0-17 years, in addition to the effects and adverse drug reactions of BNT162b2 and mRNA-1273 vaccinations among children and adolescents aged 5-17 years.

BACKGROUND: The continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period.METHODS AND FINDINGS: A Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: -0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI

Introduction: In Denmark, physicians are legally obliged to report serious adverse drug reactions (ADRs), such as intracranial hemorrhage (ICH) following anticoagulant (AC) treatment, to the Danish Medicines Agency. We were therefore puzzled to discover a high number of reports concerning ICHs following treatment with the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin. This was surprising, as all DOACs have been found to be associated with a lower risk of ICH compared with warfarin in phase III randomized controlled trials. Objectives: The primary aim of the study was to estimate the level of underreporting of ICH as an ADR following treatment with warfarin, dabigatran, rivaroxaban, and apixaban. Methods: This observational study covered a 5-year period (2014–2018). Using nationwide registries held by the Danish Health Data Authority, the number of users, exposure time in person-years, and related ICH events for each of the study drugs were estimated. Data on ADR-ICH reports were extracted from the interactive ADR overviews held by the Danish Medicines Agency. Results: From 2014 to 2018, 97.0% of the identified warfarin-related ICH events were not reported as ADRs. For the DOACs, the level of underreporting ranged from 88.8 to 90.8%. Conclusion: We found a heavy and differentiated level of underreporting of ICH as an ADR following treatment with the four study drugs.

Tramadol is a commonly used opioid with a potential of addiction and abuse. Using Danish nationwide registers, we aimed to (1) characterise opioid poisonings; (2) assess the 30-day mortality following morphine, oxycodone, and mixed poisonings compared to tramadol poisonings; and (3) assess the development in tramadol poisonings during a 12-year period. Poisonings were identified from 2006 to 2017. A Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) along with 95% confidence intervals (CIs) for 30-day mortality following morphine, oxycodone or mixed poisonings compared to tramadol poisonings. We identified 7718 opioid poisonings among 6365 patients. The patients with a tramadol poisoning were younger and had less comorbidities than the patients with a morphine, oxycodone or mixed poisoning. Within 30 days, a total of 205 patients died. The 30-day mortality risk was higher following morphine (aHR 3.2, 95% CI 2.0-5.1), oxycodone (aHR 2.1, 95% CI 1.2-3.6) and mixed poisonings (aHR 1.6, 95% CI 1.0-2.7) compared to tramadol poisonings. The annual number of tramadol poisonings increased from 233 in 2006 to 501 in 2013 and declined to 348 in 2017. In conclusion, despite a lower mortality risk compared to other opioid poisonings, physicians should consider the poisoning and abuse risks when prescribing tramadol.

We aimed to characterize the in-hospital analgesic use among total hip or knee arthroplasty (THA or TKA) patients, and to identify possible drug-related challenges. We identified 15 263 patients operated with a THA or TKA between 1 January 2012 and 30 April 2016. The prevalence of analgesic users and patients with potential clinically relevant drug-drug interactions (DDIs), along with the prevalence of readmission among patients with vs. without a DDI, were calculated. A DDI was defined as the combination of (A) a diuretic, an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, and an non-steroidal anti-inflammatory Drug (NSAID); (B) warfarin and an NSAID; and (C) a benzodiazepine or a benzodiazepine-related drug and an opioid. The prevalence of analgesics administered in THA and TKA patients was 99.3% and 99.1% for paracetamol and 93.8% and 98.8% for opioids, respectively. The prevalence of patients who received interaction A, B or C was 8.4%, 2.5% and 40.7%, respectively. Patients with vs. without a DDI had a higher prevalence of 30-day readmission. In conclusion, most THA and TKA patients were administered paracetamol or opioids. The prevalence of 30-day readmission was higher in patients with than in patients without a potential clinically relevant DDI.

The aim of this study was to validate registration of pharmacological treatment in the Danish Hip Arthroplasty Register (DHR) and Danish Knee Arthroplasty Register (DKR). We conducted a population-based study in the Capital Region of Denmark, January 2012 to April 2016. Positive predictive value (PPV) and sensitivity were calculated with 95% confidence intervals (CI) for antithrombotic, antihemorrhagic and antibiotic treatment registered in the DHR and DKR using electronic health records as the reference standard. For the DHR, the PPV and sensitivity were 77.9% (95% CI: 77.2-78.6) and 99.6% (95% CI: 99.4-99.7) for antithrombotic treatment, 70.9% (95% CI: 70.1-71.7) and 97.4% (95% CI: 97.1-97.7) for antihemorrhagic treatment, and 82.9% (95% CI: 82.2-83.5) and 99.4% (95% CI: 99.3-99.5) for antibiotic treatment, respectively. For the DKR, the PPV and sensitivity were 80.6% (95% CI: 79.8-81.4) and 99.6% (95% CI: 99.4-99.7) for antithrombotic treatment, and 84.4% (95% CI: 83.7-85.1) and 100.0% (95% CI: 99.9-100.0) for antibiotic treatment, respectively. The PPV and sensitivity for overall pharmacological treatment registered in the DHR and DKR were generally high and acceptable for use in research.

Introduction: The aim of this study was to examine the prevalence and characteristics of tramadol users in Denmark, Norway and Sweden. Methods: Data from the national prescription databases comprising the entire population of Denmark, Norway and Sweden between 2007 and 2015 were used to assess prescription medicine use and sold amount (in defined daily doses (DDDs)) of tramadol, other opioids and non-steroidal anti-inflammatory drugs. Results: From 2007 to 2015 the prevalence of tramadol users increased in Denmark from 45 to 52 per 1,000 residents, and in Norway from 20 to 41 per 1,000 residents. In Sweden, the prevalence decreased from 36 to 17 per 1,000 residents. In comparison, the prevalence of other opioid users decreased in Denmark and Norway, but increased in Sweden. During the study period, there were more female than male tramadol users in all three countries, and the prevalence of tramadol users tended to increase with age. The average tramadol DDD per treated patient remained fairly constant in Norway, while it increased in Denmark and Sweden. In Denmark and Norway, women received a higher DDD than men. The amount of sold tramadol and other opioids combined per 1,000 residents was highest in Denmark. Conclusions: From 2007 to 2015, the prescription patterns of tramadol and other opioids differed between the three countries. Tramadol was generally used more frequently by women. Women received higher DDD then men in Norway and Denmark, but not in Sweden. The prevalence of tramadol users tended to increase with age in all countries.

In this narrative review of the real-world effectiveness and safety of pharmacological thromboprophylaxis following primary total hip and knee arthroplasty, a total of 12 non-interventional observational studies were included. Pharmacological thromboprophylaxis included warfarin, heparins, dabigatran, rivaroxaban, apixaban, acetylsalicylic acid, and fondaparinux. The absolute risks varied across the included studies. These variations can be explained by differences in patient populations, drug exposure, follow-up time, and definition of outcomes, which makes it a challenge to compare the risk estimates. These findings emphasize the need for a large population-based real-world study to provide comparable risk estimates associated with different pharmacological thromboprophylaxis.

A substantial proportion of cancer patients experience chemotherapy-induced nausea and vomiting (CINV) despite the use of antiemetic drugs. Prevalent genetic polymorphisms involved in antiemetic drug metabolism, drug transport and receptor pathways likely affect the effectiveness of antiemetics. Knowledge on which polymorphisms to integrate into individualised clinical care is needed. We did a systematic review evaluating the association between polymorphisms and effectiveness of antiemetics in cancer patients receiving moderately to highly emetogenic chemotherapy. Twenty studies n = 2331 evaluated eight polymorphisms in five candidate genes involved in 5-HT3 antagonist pathways. HTR3C C1214G increased the risk of acute chemotherapy-induced vomiting in the dominant model (odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.08–6.63). ABCB1 C3435T reduced the risk of acute CINV in the recessive model (OR = 0.60, 95 % CI: 0.44-0.81). Future studies should evaluate candidate genes that affect pharmacogenetics of other antiemetics beside 5-HT3 antagonists.

Astrid Blicher Schelde,1 Morten Schmidt,1,2 Morten Madsen,1 Søren Steen Nielsen,3 Jørgen Frøkiær,4,5 Christian Fynbo Christiansen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Cardiology, Regional Hospital West Jutland, Herning, Denmark; 3Department of Clinical Physiology and Nuclear Medicine, Aalborg University Hospital, Aalborg, Denmark; 4Department of Nuclear Medicine, Aarhus University Hospital, Skejby, Denmark; 5Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkCorrespondence: Astrid Blicher ScheldeDepartment of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, DenmarkTel +45 8716 7212Email astridblicher@hotmail.comBackground: Comorbidity is common among patients with myocardial infarction (MI). We examined whether comorbidity level modified the single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI)-based prediction of 5-year risk of MI and all-cause death in patients with MI.Methods: This cohort study included patients with prior MI having a SPECT MPI at Aarhus University Hospital, Denmark, 1999–2011. Using nationwide registries, we obtained information on comorbidity levels (low, moderate, and severe) and outcomes. We computed risk and hazard ratios (HRs) with 95% confidence intervals (CIs) for MI and all-cause death, comparing normal (no defects) versus abnormal scan (reversible and/or fixed defects) using Cox regression adjusting for sex, age, and comorbidity level.Results: We identified 1,192 patients with MI before SPECT MPI. The 5-year risk for patients with normal versus abnormal scans were 11.7% versus 18.3% for MI, and 8.0% versus 13.2% for all-cause death, respectively. The overall 5-year adjusted HR (aHR) of MI was 1.56 (95% CI: 1.09–2.21), 1.33 (95% CI: 0.82–2.15) with low comorbidity, 1.39 (95% CI: 0.68–2.83) with mode