Changes in vaccination uptake against pneumococcal disease, influenza, and coronavirus disease 2019 (COVID-19) before and after a Head and Neck cancer diagnosis.

BACKGROUND: Pneumonia is one of the main contributors to non-cancer mortality among patients with head and neck cancer (HNC). This study aimed to determine the vaccine uptake for pneumococcal polysaccharide and conjugate vaccines, quadrivalent influenza vaccines, and mRNA COVID-19 vaccines before and after an HNC diagnosis. Furthermore, the study investigated the timing of vaccination after a cancer diagnosis. MATERIALS & METHODS: This register based multicentre study included Danish patients ≥ 18y diagnosed with HNC between 2018 and 2021. The vaccine uptake was assessed by calculating cumulative incidence (CI), while the timing of vaccination after an HNC diagnosis was explored by calculating incidence rates of vaccination the first and second half year after a cancer diagnosis. RESULTS: The cumulative incidence of vaccine uptake for pneumococcal vaccines was estimated to be 8 % and 16 % one year before and after an HNC diagnosis, respectively. The CIs were 36 % and 38 % for quadrivalent influenza vaccines, respectively, whereas the CIs of vaccine uptake for mRNA COVID-19 vaccines were 60 % and 89 %. The IR of mRNA COVID-19 vaccinations the first half year after HNC diagnosis were 273 per 1000 person-months of follow-up (PMFU) and 111 per 1000 PMFU the second half year, respectively (IRR: 0.38, p < 0.001). Comparing the same periods, the IR of quadrivalent influenza vaccination was 28 per 1000 PMFU and 51 per 1000 PMFU (IRR: 1.95, 0 < 0.001). The IRs of pneumococcal vaccinations were 11 per 1000 PMFU and 14 per 1000 PMFU (IRR 1.28, p = 0.21). CONCLUSIONS: Although our study shows a significant increase in pneumococcal and COVID-19 vaccine uptake after HNC diagnosis, a gap remains in vaccine uptake before diagnosis, underscoring the need for increased awareness of vaccination options and recommendations. Our findings could serve as a reference for future recommendations.

Association of COVID-19 and Development of Type 1 Diabetes: A Danish Nationwide Register Study.

OBJECTIVE: To compare the incidence of type 1 diabetes (T1D) before and during the coronavirus disease 2019 (COVID-19) pandemic and determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with T1D development. RESEARCH DESIGN AND METHODS: All Danish residents aged <30 years free of diabetes from 2015 to 2021 were included. Individuals were followed from 1 January 2015 or birth until the development of T1D, the age of 30, the end of the study (31 December 2021), emigration, development of type 2 diabetes, onset of any cancer, initiation of immunomodulating therapy, or development of any autoimmune disease. We compared the incidence rate ratio (IRR) of T1D using Poisson regression models. We matched each person with a SARS-CoV-2 infection with three control individuals and used a cause-specific Cox regression model to estimate the hazard ratio (HR). RESULTS: Among 2,381,348 individuals, 3,579 cases of T1D occurred. The adjusted IRRs for T1D in each quarter of 2020 and 2021 compared with 2015-2019 were as follows: January-March 2020, 1.03 (95% CI 0.86; 1.23); January-March 2021, 1.01 (0.84; 1.22), April-June 2020, 0.98 (0.80; 1.20); April-June 2021, 1.34 (1.12; 1.61); July-September 2020, 1.13 (0.94; 1.35); July-September 2021, 1.21 (1.01; 1.45); October-December 2020, 1.09 (0.91; 1.31); and October-December 2021, 1.18 (0.99; 1.41). We identified 338,670 individuals with a positive SARS-CoV-2 test result and matched them with 1,004,688 control individuals. A SARS-2-CoV infection was not significantly associated with the risk of T1D development (HR 0.90 [95% CI 0.60; 1.35]). CONCLUSIONS: There was an increase in T1D incidence during April-June 2021 compared with April-June 2015-2019, but this could not be attributed to SARS-CoV-2 infection.

Prevalence and duration of anti-SARS-CoV-2 antibodies in healthcare workers.

INTRODUCTION: Knowledge of the seroprevalence and duration of antibodies against SARS-CoV-2 was needed in the early phases of the COVID-19 pandemic and is still necessary for policy makers and healthcare professionals. This information allows us to better understand the risk of reinfection in previously infected individuals. METHODS: We investigated the prevalence and duration of detectable antibodies against SARS-CoV-2 in sequentially collected samples from 379 healthcare professionals. RESULTS: SARS-CoV-2 seroprevalence at inclusion was 5.3% (95% confidence interval (CI): 3.3-8.0%) and 25% of seropositive participants reverted during follow-up. At the end of follow-up, the calculated probability of having detectable antibodies among former seropositive participants was 72.2% (95% CI: 54.2-96.2%). CONCLUSION: Antibodies against SARS-CoV-2 were detectable in a subset of infected individuals for a minimum of 39 weeks. FUNDING: The assays performed at Rigshospitalet were developed with financial support from the Carlsberg Foundation (CF20-0045) and the Novo Nordisk Foundation (NFF205A0063505 and NNF20SA0064201). TRIAL REGISTRATION: The study was registered with the Danish National Committee on Health Research Ethics (H-20022312).

Behavioral factors associated with SARS-CoV-2 infection.

OBJECTIVE: To study the association between behavioural factors and incidence rates of SARS-CoV-2 infection. DESIGN: Case-control web-based questionnaire study. SETTING: Questionnaire data were collected in the Capital Region of Denmark in December 2020 when limited restrictions were in place, while the number of daily SARS-CoV-2 cases increased rapidly. PARTICIPANTS: 8913 cases of laboratory-confirmed SARS-CoV-2 infection were compared with two groups of controls: (1) 34 063 individuals with a negative SARS-CoV-2 test from the same date (negative controls, NCs) and 2) 25 989 individuals who had never been tested for a SARS-CoV-2 infection (untested controls, UC). Controls were matched on sex, age, test date and municipality. EXPOSURE: Activities during the 14 days prior to being tested positive for SARS-CoV-2 or during the same period for matched controls and precautions taken during the entire pandemic. MAIN OUTCOMES AND MEASURES: SARS-CoV-2 infection incidence rate ratios (IRR). RESULTS: Response rate was 41.4% (n=93 121). Using public transportation, grocery shopping (IRR: NC: 0.52; UC: 0.63) and outdoor sports activities (NC: 0.75; UC: 0.96) were not associated with increased rate of SARS-CoV-2 infection. Most precautions, for example, using hand sanitizer (NC: 0.79; UC: 0.98), physical distancing (NC: 0.79; UC: 0.82) and avoiding handshakes (NC: 0.74; UC: 0.77), were associated with a lower rate of infection. Activities associated with many close contacts, especially indoors, increased rate of infection. Except for working from home, all types of occupation were linked to increased rate of infection. CONCLUSIONS: In a community setting with moderate restrictions, activities such as using public transportation and grocery shopping with the relevant precautions were not associated with an increased rate of SARS-CoV-2 infection. Exposures and activities where safety measures are difficult to maintain might be important risk factors for infection. These findings may help public health authorities tailor their strategies for limiting the spread of SARS-CoV-2.

Risk factors for fatigue and impaired function eight months after hospital admission with COVID-19.

INTRODUCTION: We aimed to evaluate post-COVID-19 fatigue, change in functional capacity and health-related quality of life (HRQoL) eight months after discharge from hospital due to COVID-19. METHODS: A total of 83 patients (35 women) admitted to the Copenhagen University Hospital - North Zealand Hospital, Denmark, for COVID-19 during the period from March to June 2020 were evaluated eight months after discharge using validated questionnaires quantifying fatigue, HRQoL and post-COVID-19 functional status. Follow-up data were correlated with measures of pre-COVID-19 status (anthropometrics, comorbidities) and measures of severity of the acute infection. RESULTS: A total of 22 (65%) women and 12 (26%) men reported excessive fatigue. In all, 20 women (67%) and 17 men (37%) reported decreased physical function. Female sex was associated with fatigue. Loss of physical function was associated with pre-COVID-19 presence of heart disease and absence of lung disease. Severity of the acute COVID-19 infection was not associated with fatigue or change in functional status. Fatigue and functional status were correlated with both generic HRQoL and lung disease-specific HRQoL. CONCLUSIONS: Female sex was associated with a higher risk of fatigue eight months after hospitalisation with COVID-19 infection. Regarding loss of functional capacity after COVID-19, we found an apparently protective effect of pre-COVID-19 lung disease. Our findings underscore the urgent need for further research and the importance of evaluating those recovering from COVID-19 for symptoms of excessive fatigue and change in functional capacity irrespective of the severity of the initial infection. FUNDING: none. TRIAL REGISTRATION: not relevant.

Evaluation of a novel heparin-iloprost-based antithrombotic formulation blood collection tube for clinical usage.

BACKGROUND: The objective of our study was to evaluate a single blood collection tube with a novel antithrombotic formulation to measure both hematological, biochemical, and d-dimer analytes. METHODS: Paired samples of gold standard blood tubes (EDTA, lithium heparin, sodium citrate) and a new antithrombotic formulation blood tube were collected from 187 patients. The new antithrombotic tube is a lithium heparin tube preloaded with a liquid form of prostacyclin analog. The novel tube was tested on seventeen hematological parameters and smears against EDTA, on fourteen biochemical parameters against lithium heparin and on d-dimer against sodium citrate. RESULTS: All correlation coefficients were close to 0.99. The Bland-Altman analyses presented a satisfactory correspondence for all analytes. All the hematological examinations demonstrated comparable results between EDTA and the novel formulation, except for platelet counts analyzed by impedance method, but not by fluorescence. We detected lower mean platelet volume with/without outliers (5.06%)/(5.13%) in the novel formulation and increased mean corpuscular hemoglobin concentration (2.55%). All the biochemistry analytes demonstrated comparable results between lithium heparin and the novel tube. d-dimer showed comparable results between citrated blood and the novel formulation after dilution correction. CONCLUSIONS: We describe a novel antithrombotic formulation tube with the potential to be introduced into clinical laboratories for simultaneous analysis of thirty-two blood analytes.

Effectiveness of Docetaxel for Metastatic Hormone-sensitive Prostate Cancer in Clinical Practice.

BACKGROUND: Addition of docetaxel to androgen deprivation therapy (ADT) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been proved to be effective with an overall survival (OS) benefit in phase III clinical trials. The effectiveness of docetaxel with ADT in the general patient population remains unknown. OBJECTIVE: The purpose of this study is to report the clinical experience in mHSPC patients treated with 3rd-weekly docetaxel plus ADT in routine practice at two Danish institutions. DESIGN SETTING AND PARTICIPANTS: A two-center retrospective study including consecutive mHSPC patients treated with 3rd-weekly docetaxel plus ADT was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes of interest were OS, and biochemical and clinical progression-free survival. RESULTS AND LIMITATIONS: A total of 173 consecutive patients with mHSPC who received docetaxel every 3rd week plus ADT between June 2015 and February 2018 were included. Most patients had high-volume disease (85%). All six planned docetaxel cycles were delivered in 149 cases (86%). Of the patients, 106 (61%) were alive at the last follow-up. At a median follow-up of 42 (37.8-58.6) mo, the median OS was 51.6 (41.5-56.3) mo. Castration-resistant prostate cancer (CRPC) developed in 46% within 1 yr, with a median time to CRPC of 15.6 (13.0-18.1) mo. Prostate-specific antigen nadir ≤0.2 ng/l was achieved in 15% of patients after 6 mo of ADT and in 19% after 12 mo. CONCLUSIONS: The effect of docetaxel for mHSPC patients treated in routine practice appears comparable with the overall efficacy reported in the literature. Selection of patients will influence the results in clinical practice and clinical studies. PATIENT SUMMARY: In this report, we looked at the clinical effectiveness of docetaxel combined with androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) in a Danish population. We found the effect of docetaxel treatment for mHSPC in the general population to be comparable with the overall efficacy reported in published studies.

Characteristics and early outcomes of patients hospitalised for COVID-19 in North Zealand, Denmark.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic associated with significant morbidity and mortality worldwide. Limited data are available describing the clinical presentation and outcomes of hospitalised COVID-19 patients in Europe. METHODS: This was a single-centre retrospective chart review of all patients with COVID-19 admitted to the North Zealand Hospital in Denmark between 1 March and 4 May 2020. Main outcomes include major therapeutic interventions during hospitalisation, such as invasive mechanical ventilation, as well as death. RESULTS: A total of 115 patients were included, including four infants. The median age of adults was 68 years and 40% were female. At admission, 55 (50%) patients had a fever, 29 (26%) had a respiratory rate exceeding 24 breaths/minute, and 78 (70%) received supplemental oxygen. The prevalence of co-infection was 13%. Twenty patients (18%) (median age: 64 years; 15% female) were treated in the intensive care unit. Twelve (10.4%) received invasive mechanical ventilation and three (2.6%) renal replacement therapy. Nine patients (8%) developed pulmonary embolism. Sixteen patients (14%) died. Among patients requiring mechanical ventilation (n = 12), seven (6.1%) were discharged alive, four (3.4%) died and one (0.9%) was still hospitalised. CONCLUSION: In this cohort of hospitalised COVID-19 patients, mortality was lower than in other Danish and European case series. FUNDING: none. TRIAL REGISTRATION: not relevant.

An updated review on primary signet-ring cell carcinoma of the urinary bladder and report of a case.

OBJECTIVE: The aim of the present study was to emphasize the critical importance of the clinician's awareness of signet-ring cell carcinoma (SRCC) of the urinary bladder, a rare and aggressive disease entity. MATERIALS AND METHODS: A review of the current literature was conducted and a classic case of advanced SRCC of the urinary bladder is reported, clearly demonstrating the severity of this disease and the imperative need for standardized recommendations for the diagnostic work-up and management of urinary bladder SRCC. RESULTS: The prognosis for patients with SRCC of the urinary bladder is poor, attributed to presentation at advanced stages following asymptomatic progression, inefficacy of multimodality therapy and possibly an aggressive underlying biological phenotype. Treatment options are limited and not well studied. CONCLUSION: Given the rarity of SRCC, multi-institutional clinical trials and international cooperation are mandatory to improve survival for patients with primary SRCC of the bladder.

Breast and ovarian cancers: a survey and possible roles for the cell surface heparan sulfate proteoglycans.

Tumor markers are widely used in pathology not only for diagnostic purposes but also to assess the prognosis and to predict the treatment of the tumor. Because tumor marker levels may change over time, it is important to get a better understanding of the molecular changes during tumor progression. Occurrence of breast and ovarian cancer is high in older women. Common known risk factors of developing these cancers in addition to age are not having children or having children at a later age, the use of hormone replacement therapy, and mutations in certain genes. In addition, women with a history of breast cancer may also develop ovarian cancer. Here, the authors review the different tumor markers of breast and ovarian carcinoma and discuss the expression, mutations, and possible roles of cell surface heparan sulfate proteoglycans during tumorigenesis of these carcinomas. The focus is on two groups of proteoglycans, the transmembrane syndecans and the lipid-anchored glypicans. Both families of proteoglycans have been implicated in cellular responses to growth factors and morphogens, including many now associated with tumor progression.

Syndecan-1 and syndecan-4 are independent indicators in breast carcinoma.

Syndecan proteoglycans may be key regulators of tumor invasion and metastasis because this four-member family of transmembrane receptors regulates cell adhesion, proliferation, and differentiation. Their expression can also serve as prognostic markers. In breast carcinomas, syndecan-1 overexpression correlates with poor prognosis and aggressive phenotype. Syndecan-4 is expressed in most breast carcinoma cell lines, but its role in malignancy is unclear. A possible relationship between syndecan-1 and syndecan-4 expression and established prognostic factors in breast carcinomas was examined. Duplicate samples of 114 benign and malignant breast disease cases were stained for the two syndecans. Clinicopathological information was available for all cases. Syndecan-1 was detected in 72.8% of cases, with significant association between its expression and histological tumor type (p<0.05) and high grade tumors (p<0.05). Syndecan-4 was expressed in 66.7% of cases; expression correlated significantly with positive estrogen (p<0.01) and progesterone (p<0.01) receptor status. Independent expression of the two syndecans was noted from an analysis of single and double positive cases. There was a statistical relationship between syndecan-1 presence in high-grade tumors and absence of syndecan-4, whereas syndecan-4 presence in cases positive for estrogen and progesterone receptor associated with syndecan-1 absence. These syndecans may, therefore, have distinct roles in regulating breast carcinoma cell behavior.