Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial.

BACKGROUND: The role of the neurokinin-1 (NK-1) receptor antagonists in the prevention of radiation-induced nausea and vomiting has not been established. The purpose of the GAND-emesis study was to investigate the efficacy and safety of fosaprepitant in combination with palonosetron and dexamethasone in the prevention of nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly cisplatin in patients with cervical cancer. METHODS: This investigator initiated, multinational, randomised, double-blind, placebo-controlled phase 3 trial, included women with cervical cancer scheduled to receive fractionated radiotherapy and weekly cisplatin 40 mg/m(2) for 5 weeks. Patients had to be naive to chemotherapy and radiotherapy. Patients were randomly assigned to receive either single doses of fosaprepitant 150 mg intravenously or placebo (saline) in combination with palonosetron 0·25 mg intravenously and dexamethasone 16 mg orally before cisplatin administration. Randomisation was done by the unmasked pharmacist, who used a list of six numbers (a block) provided in a sealed envelope. A web-based randomisation number generator was used to generate the full list of randomisation numbers that was split up in blocks of six numbers. All patients received oral dexamethasone 8 mg twice a day on day 2, 4 mg twice a day on day 3, and 4 mg once on day 4. The treatment was repeated for 5 weeks. The primary endpoint was the proportion of patients with sustained no emesis after 5 weeks of treatment. The modified intention-to-treat population (all patients who received study medication) was used for the statistical analyses. The study was registered with ClinicalTrials.gov, number NCT01074697. FINDINGS: Between June 15, 2010, and March 8, 2015, 246 patients from four countries consented to the study and were randomly assigned. Of these, 234 patients were eligible, having received study medication (118 received fosaprepitant, 116 received placebo). The proportion of patients with sustained no emesis at 5 weeks (competing risk analysis) was 48·7% (95% CI 25·2-72·2) for the placebo group compared with 65·7% (42·2-89·2) of patients for the fosaprepitant group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group compared with the placebo group (subhazard ratio 0·58 [95% CI 0·39-0·87]; p=0·008). Treatments were generally well tolerated with few grade 3 adverse events none of which were related to the study treatment; the most common grade 3 adverse event during the 5 weeks of treatment was diarrhoea (11 [9%] of 118 patients in the fosaprepitant group vs six [5%] of 116 patients in the placebo group). There was only one report of a grade 4 adverse event (neutropenia), in the fosaprepitant group. No deaths were recorded in either group. INTERPRETATION: To our knowledge, this is the first study to investigate safety and efficacy of a NK-1 receptor antagonist during 5 weeks of radiotherapy and concomitant weekly cisplatin. Patients receiving fosaprepitant in addition to palonosetron and dexamethasone were less likely to experience emesis and nausea compared with those receiving palonosetron and dexamethasone alone. Both treatments were safe and well tolerated. Further investigations in other radiotherapy settings are warranted. FUNDING: Private and hospital or university funding, unrestricted grants from Biovitrum and Helsinn Healthcare SA.

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.

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.

[Palliation of pain from bone metastases with radioactive isotopes]. / Palliation af smertegivende knoglemetastaser med radioaktive isotoper.

We summarise the physical and pharmacokinetic properties of the radionuclides used. The effect on pain from bone metastases caused by prostate cancer, breast cancer, and lung cancer is well documented. A review of the literature does not substantiate a clinically significant difference in the palliative effect produced by any of the radionuclides used. The effect achieved with nuclides is the same as that seen after external radiation. Radionuclides seem to reduce the number of new painful sites from bone metastases, and, as such, use of nuclides is expected to reduce the need for repeated external palliative radiation.

Squamous cell carcinoma of the nasal vestibule 1993-2002: a nationwide retrospective study from DAHANCA.

BACKGROUND: A retrospective nationwide study of cancer of the nasal vestibule was conducted to evaluate classification systems and prognostic factors for treatment outcome. METHODS: Patients treated between 1993 and 2002 at head and neck oncology centers in Denmark were included. RESULTS: The 5-year results were locoregional control 67%, overall survival 50%, cancer-specific survival 74%. Cancer-specific survival according to Wang classification was 83%, 63%, and 39% for T1, T2, T3, respectively (p < .000). Regarding T1 tumors, 5-year locoregional control for surgery, surgery + radiotherapy (RT), or RT was 94%, 87%, or 61%, respectively (p < .000). Fifty-four Gray in 18 fractions was found comparable with 66 Gy in 33 fractions regarding T1 tumors. CONCLUSION: This national survey is the largest series of nasal vestibule cancer ever published. Wang classification is more prognostic and easier to use than the Union Internationale Contre le Cancer 2002. Surgery or hypofractionated RT can be used for T1 lesions, whereas larger lesions should be treated with combined approach.