Can biopsies be omitted after normal colposcopy in women referred with low-grade cervical cytology? A prospective cohort study.

BACKGROUND: Controversy surrounds whether women with low-risk cytology screening results but a normal colposcopic assessment should have random biopsies taken. The aim of this study was to determine the yield of CIN2+ from one to four cervical biopsies in women with cytology of LSIL or ASCUS and a normal colposcopic impression. METHODS: Between January 2017 and September 2020, women over 18 years old referred for colposcopic examination due to either an abnormal smear (ASCUS+) or follow-up after previous cervical intraepithelial neoplasia (CIN) were invited to participate in the study. All study participants underwent colposcopic examination and had four biopsies taken. The biopsies were analyzed separately. RESULTS: In total, 1327 women with abnormal cervical cancer screening results or attending follow-up after a previous CIN diagnosis were enrolled in the study and examined by colposcopy. Of these, 173 were newly referred with cytology of LSIL or ASCUS and had a normal colposcopic impression and four adequate biopsies. Of these, 22.0% were diagnosed with CIN2+. When combining the results of the four biopsies, we found a 100% relative increase in CIN2+ cases compared to using only one biopsy (from 11.0% to 22.0%, P = 0.006). CONCLUSION: As we found CIN2+ from random cervical biopsies in 22.0% of women with cytology of LSIL or ASCUS who had a normal colposcopic impression, we advocate performing four random cervical biopsies at the squamocolumnar junction in such women. Trial registration NCT04249856, January 31 2020 (retrospectively registered).

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia: The COVID STEROID randomised, placebo-controlled trial.

BACKGROUND: In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID-19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low-dose hydrocortisone on patient-centred outcomes in adults with COVID-19 and severe hypoxia. METHODS: In this multicentre, parallel-group, placebo-controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID-19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/d) vs a matching placebo for 7 days or until hospital discharge. The primary outcome was the number of days alive without life support at day 28 after randomisation. RESULTS: The trial was terminated early when 30 out of 1000 participants had been enrolled because of external evidence indicating benefit from corticosteroids in severe COVID-19. At day 28, the median number of days alive without life support in the hydrocortisone vs placebo group were 7 vs 10 (adjusted mean difference: -1.1 days, 95% CI -9.5 to 7.3, P = .79); mortality was 6/16 vs 2/14; and the number of serious adverse reactions 1/16 vs 0/14. CONCLUSIONS: In this trial of adults with COVID-19 and severe hypoxia, we were unable to provide precise estimates of the benefits and harms of hydrocortisone as compared with placebo as only 3% of the planned sample size were enrolled. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04348305. European Union Drug Regulation Authorities Clinical Trials (EudraCT) Database: 2020-001395-15.