Implications of Age for the Diagnostic and Prognostic Value of Cardiac Troponin T and I.

BACKGROUND: The influence of age on cardiac troponin is unclear and may vary between cardiac troponin T (cTnT) and I (cTnI). We aimed to compare the impact of age on the diagnostic and prognostic utility of cTnT and cTnI. METHODS: This Danish nationwide, register-based cohort study included patients with at least one cardiac troponin (cTn) measurement from 2009 through June 2022, stratified into decades of age. We used peak cTn concentration during admission, dichotomized as positive/negative and normalized to the 99th percentile. Receiver operating characteristics for myocardial infarction (MI) and logistic regression were used to estimate the odds ratio (OR) for mortality at 1 year. RESULTS: We included 541 817 patients; median age 66 years (interquartile range [IQR] 51-77) and 256 545 (47%) female. A total of 40 359 (7.4%) had an MI, and 59 800 (14.1%) patients died within 1 year of admission. The predictive ability of both cTns for MI were highest for patients 30 to 50 years. This was most pronounced for cTnT, the specificity of which fell from 83% among patients 40 to 49 years to 4% for patients ≥90 years. The prognostic ability of both cTns for 1-year mortality declined with age. cTnT had stronger prognostic ability for all age-groups; OR for a positive cTnT 28.4 (95% CI, 20.1-41.0) compared with 9.4 (95% CI, 5.0-16.7) for cTnI among patients <30 years. CONCLUSIONS: The predictive and prognostic ability of cTnT and cTnI declined with age. cTnT had a low specificity for MI in elderly patients. However, cTnT was the strongest prognostic marker among all age groups.

Prevalence and prognostic relevance of electrocardiographic abnormalities among patients with ANCA-associated vasculitis.

OBJECTIVES: Current guidelines provide limited evidence for cardiovascular screening in ANCA-associated vasculitis (AAV). This study aimed to investigate the prevalence of electrocardiogram (ECG) abnormalities and associations between no, minor or major ECG abnormalities with cardiovascular mortality in AAV patients compared with matched controls. METHOD: Using a risk-set matched cohort design, patients diagnosed with granulomatosis with polyangiitis or microscopic polyangiitis with digital ECGs were identified from Danish registers from 2000-2021. Patients were matched 1:3 to controls without AAV on age, sex, and year of ECG measurement. Associated hazards of cardiovascular mortality according to ECG abnormalities were assessed in Cox regression models adjusted for age, sex, and comorbidities, with subsequent computation of 5-year risk of cardiovascular mortality standardized to the age- and sex-distribution of the sample. RESULTS: A total of 1431 AAV patients were included (median age: 69 years, 52.3% male). Median follow-up was 4.8 years. AAV was associated with higher prevalence of left ventricular hypertrophy (17.5% vs 12.5%), ST-T deviations (10.1% vs 7.1%), atrial fibrillation (9.6% vs 7.5%), and QTc prolongation (5.9% vs 3.6%). Only AAV patients with major ECG abnormalities demonstrated significantly elevated risk of cardiovascular mortality [HR 1.99 (1.49-2.65)] compared with controls. This corresponded to a 5-year risk of cardiovascular mortality of 19.14% (16-22%) vs 9.41% (8-11%). CONCLUSION: Patients with AAV demonstrated a higher prevalence of major ECG abnormalities than controls. Notably, major ECG abnormalities were associated with a significantly increased risk of cardiovascular mortality. These results advocate for the inclusion of ECG assessment into routine clinical care for AAV patients.

Changes in mouse epidermal DNA methylation during development of squamous cell carcinoma in response to UVR.

Squamous cell carcinoma (SCC) is a common skin cancer, often caused by exposure to ultraviolet radiation (UVR). Recent studies have shown that changes in DNA methylation play a crucial role in the development of cancers. However, methylation patterns of SCC are not well characterised. Identifying biomarkers for the risk of developing SCC could be helpful for early detection and diagnosis and can potentially improve treatment and prevention strategies. This study aimed to investigate methylation changes in the epidermis of mice exposed to UVR for 24 weeks. We examined the DNA methylation levels of 260 199 CpGs using the Illumina Infinium Mouse Methylation BeadChip and studied the epidermis of UVR-exposed and unexposed mice every 4 weeks for 24 weeks (n = 39). We identified CpGs with large differences in methylation levels (ß-values) between UVR-exposed and unexposed mice. We also observed differences in the epigenetic age of these mice. We identified CpGs in Rev, Ipmk, Rad51b, Fgfr2, Fgfr3 and Ctnnb1 that may serve as potential biomarkers for SCC risk and could be helpful for the early detection and prevention of SCC. Further investigations are necessary to determine the biological functions and clinical significance of these CpGs.

The Danish Nationwide Electrocardiogram (ECG) Cohort.

The electrocardiogram (ECG) is a non-invasive diagnostic tool holding significant clinical importance in the diagnosis and risk stratification of cardiac disease. However, access to large-scale, population-based digital ECG data for research purposes remains limited and challenging. Consequently, we established the Danish Nationwide ECG Cohort to provide data from standard 12-lead digital ECGs in both pre- and in-hospital settings, which can be linked to comprehensive Danish nationwide administrative registers on health and social data with long-term follow-up. The Danish Nationwide ECG Cohort is an open real-world cohort including all patients with at least one digital pre- or in-hospital ECG in Denmark from January 01, 2000, to December 31, 2021. The cohort includes data on standardized and uniform ECG diagnostic statements and ECG measurements including global parameters as well as lead-specific measures of waveform amplitudes, durations, and intervals. Currently, the cohort comprises 2,485,987 unique patients with a median age at the first ECG of 57 years (25th-75th percentiles, 40-71 years; males, 48%), resulting in a total of 11,952,430 ECGs. In conclusion, the Danish Nationwide ECG Cohort represents a novel and extensive population-based digital ECG dataset for cardiovascular research, encompassing both pre- and in-hospital settings. The cohort contains ECG diagnostic statements and ECG measurements that can be linked to various nationwide health and social registers without loss to follow-up.

Preterm children born below 33-35 weeks of gestation have an increased risk of mathematical difficulties.

AIM: To investigate the association between gestational age (GA) and grade point averages by domains of language and mathematics at the end of lower secondary education. METHODS: A nationwide register-based study including all Danish children born in 1992-1997 who completed lower secondary education. Grades were evaluated by GA. Domain-specific differences in grades were investigated, and academic profiles were made. RESULTS: The study population comprised 319 796 children. For language, only minor differences in grades were observed. The grades in mathematics ranged from 7.02 (95% confidence interval [CI]: 7.00-7.04) at GA = 40 weeks to 5.86 (95% CI: 5.61-6.11) at GA <28 weeks. Grade differences showed lower grades in mathematics, compared to language, below GA 33-35 weeks. The academic profile of mathematical difficulties was more prevalent among GA <32 weeks. Average/high grades within both domains represented the predominant academic profile, constituting 68.8% at GA 39-41 weeks and 56.6% at GA <28 weeks. CONCLUSION: Only in mathematics decreasing GA was associated with lower grades. Increased mathematical difficulties were found below GA 33-35 weeks. The academic profile of mathematical difficulties was more prevalent among GA <32 weeks. However, the absolute differences in grades were small, and the predominant academic profile was average/high grades within both domains across all GA.

Poor socioeconomic outcomes: Completion of the final examination after lower secondary education mitigates risks associated with gestational age.

AIM: To investigate the influence of gestational age (GA) on the association between completion of the final examination after 10-11 years of basic education and education, financial independence and income in early adulthood. METHODS: A nationwide register-based study including individuals born in Denmark between 1990 and 1992. Completion of the examination was evaluated at age 18 and education, financial independence and income at age 28. RESULTS: Of 165 683 individuals included, 15.7%, 10.8% and 5.5% had low educational level, were not financially independent and had low income. For those who completed the examination odds ratio (OR) ranged from 1.03 at GA = 32-36 weeks to 1.25 at ≤27 weeks for low education, from 1.10 to 0.91 for not being financial independent and from 1.06 to 1.48 for low income. For those who did not complete the examination, OR increased from 7.55 at ≥37 weeks to 15.03 at ≤27 weeks for low education and from 4.68 to 15.31 for not being financial independent. For low income, OR was 2.57 and independent of GA. CONCLUSION: For individuals who completed the examination, the odds of poor socioeconomic outcomes were independent of GA. Individuals who did not complete the examination had increased odds of poor socioeconomic outcomes, particularly as GA decreased.

Five-year neurodevelopmental assessment of extremely preterm or extremely low birthweight infants: Association with school performance.

AIM: We investigated the associations between motor performance and IQ at 5 years of age and school difficulties and grade point averages (GPAs) at 18 years of age. Additionally, the accuracy of preschool IQ in predicting school difficulties was examined. METHODS: A nationwide follow-up study of children born in 1994-1995 who were <28 weeks of gestation or had a birthweight <1000 g. The Danish personal identification number was used to merge data from a national cohort study with population-based registries. Logistic regression analyses examined the associations between motor performance/IQ and school difficulties. Linear regression analyses and the area under the receiver operator curve (AUC) were used to examine the relationship between IQ and GPAs. RESULTS: The study population comprised 248 children, 37% were classified with school difficulties. Motor performance and IQ were associated with school difficulties. The odds of having school difficulties increased as IQ decreased, and the same pattern was observed for GPAs. IQ predicted school difficulties, with an AUC of 0.80 (confidence interval: 0.74-0.86). CONCLUSION: Preschool motor performance and IQ were associated with school difficulties. Additionally, IQ was linked to GPAs. As a screening tool, the predictive ability of preschool IQ for academic difficulties was moderate/high in this cohort.

Implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting.

BACKGROUND AND PURPOSE: Length of hospital stay after hip and knee arthroplasty is about 1 day in Denmark with few patients discharged on the day of surgery. Hence, a protocol for multicenter implementation of discharge on day of surgery has been instituted. We aimed to describe the implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting. METHODS: We performed a prospective multicenter study from 7 public hospitals across Denmark. Patients were screened using well-defined in- and exclusion criteria and were discharged on day of surgery when fulfilling functional discharge criteria. The study period was from September 2022 to February 2023 with variable start of implementation. Data from the same centers in a 6-month period before the COVID pandemic from July 2019 to December 2019 was used for baseline control. RESULTS: Of 2,756 primary hip and knee arthroplasties, 37% (95% confidence interval [CI] 35-39) were eligible (range 21-50% in centers) and 52% (range 24-62%) of these were discharged on day of surgery. 21% (CI 20-23) of all patients (eligible and non-eligible) were discharged on day of surgery with a range of 10-31% within centers. This was an additional 15% (CI 13-17, P < 0.001) compared with patients discharged in the control period (6% in 2019). CONCLUSION: We found it possible to perform outpatient hip and knee replacement in 21% of patients in a public healthcare setting, probably to be increased with further center experience.

Meningioma animal models: a systematic review and meta-analysis.

BACKGROUND: Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models-each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types. METHODS: We searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies. RESULTS: We included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92-96) for orthotopic and 95% (93-96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33-72) and heterotopic 82% (73-89)] and finally GEM revealed a TTR of 34% (26-43). CONCLUSION: This systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages). SYSTEMATIC REVIEW REGISTRATION: PROSPERO-ID CRD42022308833.

Retinal vessel dynamics analysis as a surrogate marker for raised intracranial pressure in patients with suspected idiopathic intracranial hypertension.

INTRODUCTION: Retinal vessel dynamics analysis has proven to be a viable, non-invasive surrogate marker for increased intracranial pressure. We aimed to test this method in patients with suspected idiopathic intracranial hypertension. METHODS: Patients with suspected idiopathic intracranial hypertension were prospectively enrolled for hand-held fundus-videography during diagnostic lumbar puncture. After extracting optic disc images, peripapillary arteriole-to-venule-ratios were measured using machine-learning algorithms with manual identification control. A general linear model was applied to arteriole-to-venule-ratios and corresponding lumbar opening pressures to estimate cerebrospinal fluid pressure. RESULTS: Twenty-five patients were included with a significant difference in arteriole-to-venule-ratio between patients with (n = 17) and without (n = 8) idiopathic intracranial hypertension (0.78 ± 0.10 vs 0.90 ± 0.08, p = 0.006). Arteriole-to-venule-ratio correlated inversely with lumbar opening pressure (slope regression estimate -0.0043 (95% CI -0.0073 to -0.0023), p = 0.002) and the association was stronger when lumbar opening pressure exceeded 15 mm Hg (20 cm H2O) (slope regression estimate -0.0080 (95% CI -0.0123 to -0.0039), p < 0.001). Estimated cerebrospinal fluid pressure predicted increased lumbar opening pressure >20 mm Hg (27 cm H2O) with 78% sensitivity and 92% specificity (AUC 0.81, p = 0.02). A stand-alone arteriole-to-venule-ratio measurement predicting lumbar opening pressure >20 mm Hg (27 cm H2O) was inferior with a 48% sensitivity and 92% specificity (AUC 0.73, p = 0.002). CONCLUSION: Retinal vessel dynamics analysis with the described model for estimating cerebrospinal fluid pressure is a promising non-invasive method with a high sensitivity and specificity for detecting elevated intracranial pressure at follow-up assessments of patients with confirmed idiopathic intracranial hypertension if initial lumbar opening pressure and arteriole-to-venule-ratio data are available.

All-cause mortality among Danish nursing home residents before and during the COVID-19 pandemic: a nationwide cohort study.

A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671-35,943), 34,801 (95% CI: 34,180-35,432), and 35,708 (95% CI: 35,085-36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620-38,929), 36,956 (95% CI: 36,323-37,600), 37,475 (95% CI: 36,838-38,122), and 38,536 (95% CI: 37,798-39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38-46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18-32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical.

Consequences of COVID-19-related lockdowns and reopenings on emergency hospitalizations in pediatric patients in Denmark during 2020-2021.

There is a considerable burden of children being hospitalized due to infectious diseases worldwide. The COVID-19 pandemic provided a unique opportunity to examine effects of worldwide efforts to control spread of infection. We aimed to investigate overall age-specific hospitalizations due to viral and bacterial infections and diseases triggered by respiratory tract infections during and after lockdown. This nationwide register-based observational study included children from 29 days to 17 years old hospitalized in all Danish pediatric emergency departments during the years 2015-2021. Main outcomes were ICD-10 diagnoses for infectious diseases and infection triggered illnesses. Fluctuations in hospitalization events were explored using figures with weekly events per 100,000. Total events followed a predictable pattern during 2015-2019. In 2020-2021, there was a drop in hospital encounters after lockdowns and surge after reopenings. In 2021, there was a surge of hospital encounters in the late summer due to respiratory syncytial virus infections and asthmatic bronchitis mostly in infants from 29 days to 2 years. For the infectious diseases, there was a dramatic decrease in events after lockdowns and immediate increase in cases that followed the same pattern of previous years after reopenings. Bacterial infections, like urinary tract infections, sepsis, and meningitis followed a steady pattern throughout all calendar-years. CONCLUSIONS: Nationwide efforts to minimize infectious disease spread like lockdowns have a preventative and period lasting effect but reopenings/reunions result in surges of infectious diseases. This might be due to children not getting immunized steadily thereby increasing the pool of possible hosts for potential viral infections. WHAT IS KNOWN: • There is a seasonal fluctuation in viral/respiratory infections in children with higher infection rates in the winter and lower rates in the summer. • RSV infection is a major source of concern. WHAT IS NEW: • Major lockdowns and reopenings disrupt the seasonal fluctuations which can result in high surges in infections that increases the burden of children emergency departments and the risk of serious complications.

Peripheral nerve-blocks and associations with length of stay and readmissions in fast-track total hip and knee arthroplasty.

BACKGROUND: Peripheral nerve blocks (PNB) have recently been recommended in total hip (THA) and knee (TKA) arthroplasty as they may reduce pain, morphine consumption, length of stay (LOS) and complications. However, whether PNBs are associated with early discharge within an enhanced recovery protocol including multimodal analgesia is uncertain. METHODS: An observational multicenter study from January to August 2017 in six Danish Arthroplasty Centers with established fast-track protocols. Prospective recording of preoperative characteristics and information on PNB, LOS and readmissions through the Danish National Patient Registry and medical records. Multiple logistic regression was used to investigate associations between PNB and a LOS >1 day, LOS >4 days, and 30-days readmissions. We also reported on mobilization, pain, opioid and fall-related complications leading to LOS >4 days or readmissions. RESULTS: A total of 2027 (58.6%) THA and 1432 (41.4%) TKAs with a median LOS of 1 day (IQR 1-2) and 5.3% (CI:4.6-6.1) 30-days readmission rate were identified. PNB was used in 40.7% (CI:38.2-43.3) of TKA and 2.7% (CI:2.0-3.5) of THA, but with considerable interdepartmental variation (0.0-89.0% for TKA). There was no association between PNB and LOS >1 day (OR:1.19 CI:0.82-1.72; p = .354), LOS >4 days (OR:1.4 CI:0.68-2.89; p = .359) or 30-days readmissions (OR:1.02 CI:0.63-1.65; p = .935) in TKA. Logistic regression in THA was not possible due to limited use of PNB. In TKA there were 12 (2.1% CI:1.2-3.6) with and 1 (0.1% CI:0.02-0.7) without a PNB, who had mobilization, pain or opioid-related complications, and 5 (0.9% CI:0.4-2.0) versus 4 (0.5% CI:0.2-1.2) who fell. Correspondingly, 2 (3.7% CI:1.0-12.6) and 11 (0.6% CI:0.3-1.0) of THA patients had these complications, while 0 (0.0% CI:0.0-6.6) and 17 (0.8% CI:0.5-1.3) fell. CONCLUSION: Routine use of peripheral nerve blocks was not associated with early discharge or 30-days readmissions in fast-track THA and TKA. Future studies should focus on benefits of PNB in high-risk patients.

"Visualization" of pain using cerebral 18F-FDG PET/CT following surgical treatment of lumbar disc herniation.

PURPOSE: We hypothesized that unilateral leg pain following surgical treatment of lumbar disc herniation (LDH) is associated with an increase in the glucose metabolism of the contralateral thalamus. METHODS: Patients scheduled for surgery due to LDH underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography less than two weeks prior to surgery. Their thalamic FDG uptake was measured and expressed as the mean and partial volume corrected mean standardized uptake values (SUVmean and cSUVmean). These measures were compared with patient-related outcome measures collected pre- and 1-year post-operatively: back and leg pain on a 0-100 VAS scale and health-related quality of life as measured by the EuroQol-5D (EQ-5D). RESULTS: Twenty-six patients (ten females) aged 49.7 ± 7.4 (mean ± SD) years were included. There was a significant correlation between painful body side and increased contralateral thalamic uptake of FDG, with regard to cSUVmean values. Correlation analyses including clinical parameters and cSUVmean indicated some association with 1-year change in EQ-5D. CONCLUSION: These preliminary data sustain the hypothesis that unilateral pain in patients with LDH is associated with increased glucose metabolism in the contralateral thalamus, suggesting a central role of thalamus in chronic pain perception.

Virtual magnetic resonance elastography predicts the intraoperative consistency of meningiomas.

BACKGROUND AND PURPOSE: Virtual magnetic resonance elastography (vMRE) is an experimental imaging modality designed to non-invasively predict the haptic properties of tissues. The modality is sensitive to tissue stiffness and fibrosis. Information about meningioma consistency prior to resection is of great interest in neurological surgery as the surgical plan and outcome may be affected by the tumor's stiffness. In this study, we assessed the ability of vMRE to predict the intraoperative consistency and mechanical heterogeneity of intracranial meningiomas. MATERIALS AND METHODS: We included 12 patients scheduled for meningioma resection, of which one patient was found to have a solitary fibrous tumor on histological examination. All participants underwent preoperative vMRE and intraoperative consistency grading. RESULTS AND CONCLUSIONS: Intraoperative qualitative consistency correlated positively with vMRE-based consistency assessment (odds ratio 5.63, 95% CI 1.12-28.30, p = 0.04) at b1000. Mechanically homogenous tumors had significantly lower ∆ mean stiffness than heterogeneous tumors (8.13 vs 18.07 kPa, p = 0.01). This study thus demonstrates a possible clinical application of vMRE in predicting the intraoperative consistency and mechanical heterogeneity of meningiomas.

Study protocol for discharge on day of surgery after hip and knee arthroplasty from the Center for Fast-track Hip and Knee Replacement.

BACKGROUND AND PURPOSE: Limited data exists on the implementation process and safety of discharge on the day of surgery after primary hip and knee arthroplasty in a multicenter setting. We report our study protocol on the investigation of the feasibility, safety, and socioeconomic aspects following discharge on day of surgery after hip and knee arthroplasty across 8 fast-track centers. PATIENTS AND METHODS: This is a study protocol for a prospective cohort study on discharge on day of surgery from the Center for Fast-track Hip and Knee Replacement. The collaboration includes 8 centers covering 40% of the primary hip and knee arthroplasty procedures undertaken in Denmark. All patients scheduled for surgery are screened for eligibility using well-defined inclusion and exclusion criteria. Eligible patients fulfilling discharge criteria will be discharged on day of surgery. We expect to screen 9,000 patients annually. Duration and outcome: Patients will be enrolled over a 3-year period from September 2022 and reporting of results will run continuously until December 2025. We shall report the proportion of eligible patients and patients discharged on day of surgery as well as limiting factors. Readmissions and complications within 30 days are recorded with real-time follow-up by research staff. Furthermore, patient-reported information on willingness to repeat discharge on day of surgery, contacts with the healthcare system, complications, and workability is registered 30 days postoperatively. EQ-5D, Oxford Knee Score, and Oxford Hip Score are completed preoperatively and after 3 months and 1 year. Finally, outcome data will be used in the development of a prediction model for successful discharge on the day of surgery.

Household Exposure to Severe Acute Respiratory Syndrome Coronavirus 2 and Association With Coronavirus Disease 2019 Severity: A Danish Nationwide Cohort Study.

BACKGROUND: Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severity of coronavirus disease 2019 (COVID-19) is likely associated with the infectious dose of SARS-CoV-2 exposure. We therefore aimed to assess the association between SARS-CoV-2 exposure within households and COVID-19 severity. METHODS: We performed a Danish, nationwide, register-based, cohort study including laboratory-confirmed SARS-CoV-2-infected individuals from 22 February 2020 to 6 October 2020. Household exposure to SARS-CoV-2 was defined as having 1 individual test positive for SARS-CoV-2 within the household. Cox proportional hazards models were used to estimate the association between "critical COVID-19" within and between households with and without secondary cases. RESULTS: From 15 063 multiperson households, 19 773 SARS-CoV-2-positive individuals were included; 11 632 were categorized as index cases without any secondary household cases; 3431 as index cases with secondary cases, that is, 22.8% of multiperson households; and 4710 as secondary cases. Critical COVID-19 occurred in 2.9% of index cases living with no secondary cases, 4.9% of index cases with secondary cases, and 1.3% of secondary cases. The adjusted hazard ratio for critical COVID-19 among index cases vs secondary cases within the same household was 2.50 (95% confidence interval [CI], 1.88-3.34), 2.27 (95% CI, 1.77-2.93) for index cases in households with no secondary cases vs secondary cases, and 1.1 (95% CI, .93-1.30) for index cases with secondary cases vs index cases without secondary cases. CONCLUSIONS: We found no increased hazard ratio of critical COVID-19 among household members of infected SARS-CoV-2 index cases.

COVID-19 infection and hospitalization risk according to vaccination status and DMARD treatment in patients with rheumatoid arthritis.

OBJECTIVES: The objectives of this study were to investigate the incidence of COVID-19 hospitalization in unvaccinated and vaccinated patients with RA compared with matched controls, and in patients with RA according to DMARD treatment. METHODS: This was a Danish nationwide matched-cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalization (Danish National Patient Register) and first-time positive SARS-CoV-2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PYs) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals. RESULTS: In total, 28 447 unvaccinated patients and 568 940 comparators had IRs for COVID-19 hospitalization of 10.4 (8.0-13.4) and 4.7 (4.3-5.1) per 1000 PYs, respectively (aHR 1.88, 1.44-2.46). When fully vaccinated, corresponding IRs were 0.9 (0.5-1.6) and 0.5 (0.4-0.6) per 1000 PYs (aHR 1.94, 1.03-3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09-1.57) for testing positive for SARS-CoV-2 and 1.09 (0.92-1.14) among vaccinated RA patients. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalization compared with conventional DMARD-treated patients. CONCLUSION: The incidence of COVID-19 hospitalization was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients.

The effects of preoperative focused cardiac ultrasound in high-risk patients: A randomised controlled trial (PREOPFOCUS).

BACKGROUND: Surgery is the third most common cause of mortality worldwide. Focused cardiac ultrasound (FOCUS) yields information on cardiac status and discloses the presence of unknown pathology. Preoperative FOCUS changes patient treatment, allowing for a patient-tailored anaesthesia. We hypothesised that preoperative FOCUS would reduce the proportion of patients who were either admitted to hospital for more than 10 days or who were dead within 30 days after high-risk, non-cardiac surgery. METHODS: This was a randomised, controlled, multi-center study. Patients ≥65 years of age, admitted for urgent orthopaedic- or abdominal surgery, scheduled for general- or neuraxial anaesthesia and with ASA 3/4 were eligible for inclusion. Patients were randomised in a 1:1 ratio to preoperative FOCUS or no preoperative FOCUS performed in accordance with a predefined protocol. Primary endpoint was the proportion of patients admitted more than 10 days or who were dead within 30 days. Secondary endpoints included major complications, days of admission and changes in anaesthesia handling. RESULTS: During the second COVID-19 wave the study monitoring committee terminated the study prematurely. We included 338 patients of which 327 were included in the final analysis. In the FOCUS group, 41/163 (25%) patients met the criteria for the primary endpoint versus 35/164 (21%) for the control group, adjusted odds ratio 1.37 (95% CI 0.86-2.30), p = .36. The proportions of patients who developed major complications did not differ significantly between groups. Length of hospital stay was 4 (3-8) days in the FOCUS group and 4 (3-7) days on the control group (adjusted p = .24). CONCLUSION: The routine availability of preoperative FOCUS assessment in this cohort does not appear to reduce the risk for hospitalisation exceeding 10 days or 30-day mortality, although study enrolment was prematurely terminated.

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

BACKGROUND: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both. OBJECTIVE: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures. DESIGN: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541). SETTING: Denmark, April and May 2020. PARTICIPANTS: Adults spending more than 3 hours per day outside the home without occupational mask use. INTERVENTION: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use. MEASUREMENTS: The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses. RESULTS: A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was -0.3 percentage point (95% CI, -1.2 to 0.4 percentage point; P = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23]; P = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection. LIMITATION: Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others. CONCLUSION: The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection. PRIMARY FUNDING SOURCE: The Salling Foundations.