Background An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. Objective The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. Methods As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. Results The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. Conclusions Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider.

The purpose of this study is to provide evidence that empty follicle syndrome (EFS) is a result of an abnormality in the in-vivo biological activity of some batches of commercially available human chorionic gonadotrophin (HCG). This is a comparative study between six consecutive in-vitro fertilization (IVF) cases with EFS (study group) and 10 IVF pregnancy cycles (control group). Both groups received the same ovarian stimulation protocol consisting of leuprolide acetate and human menopausal gonadotrophin (HMG). An i.m. injection of 10,000 IU of HCG was administered once follicles had reached 18-20 mm and oestradiol/follicle > or = 16 mm was at least 900 pmol/l. Transvaginal aspiration was performed 36 h later. Plasma HCG prior to and 12 h after i.m. injection as well as the follicular fluid (FF) concentrations of oestradiol, progesterone, luteinizing hormone (LH) and HCG were determined in the study group and controls. The in-vitro biological activity of the batch of HCG used by the EFS cases and the control group was determined using a Leydig cell preparation from adult rats. Furthermore, the plasma clearance rate after i.v. injection of 5000 IU of HCG, from the same batches, was studied in three male volunteers. In the IVF cycles, no HCG was detected in plasma prior to the injection of commercial HCG. After 12 h, no HCG was detected in the study group compared to a mean of 207.5 IU/l (110-360) in controls. Mean FF concentration of LH, HCG, progesterone and oestradiol was 0.9 IU/l, 0 IU/l, 3.1 nmol/ml and 4.4 nmol/ml in EFS compared to 1.0, 98.3, 32.0 and 3.7 in pregnancy cycles. The in-vitro biological activity in both HCG batches was not significantly different; however, immunoreactive HCG used in EFS cases was undetectable in plasma of male volunteers as soon as 10 min after i.v. injection of 5000 IU of HCG. The endocrine abnormalities found in follicular fluids of EFS are not a consequence of an ovarian problem but the result of a lack of exposure to biologically active HCG. The rapid clearance of the drug after i.v. injection and the high affinity of desialylated HCG to liver cells suggest this to be a possible explanation for this infrequent but unfortunate event.

Ketoconazole, an imidazole derivative known to inhibit cytochrome P450-dependent adrenal enzymes was given to a patient with a functioning adrenal rest tumor of the liver in preparation for surgery. The drug was administered in a stepwise manner for 42 days starting with 400 mg and reaching 1 g the last 4 weeks of the trial. Clear clinical improvement was evident early in the trial and was associated with evidence of amelioration of her hypercortisolism and striking changes in serum and urinary levels of steroid hormones and metabolites. Sex steroids in serum and urine fell dramatically from the first day to the end of the trial. Urinary 17-ketosteroid excretion fell from a basal average of 139 mg/24 h to near normal levels within a week of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng/ml; serum 17 beta-estradiol fell likewise from 1096 to 150 pg/ml. In contrast, cortisol levels in serum and urine increased in the first 2 weeks of the trial and subsequently fell to values below the basal levels. Similarly, serum 17 alpha-OH-progesterone levels increased 63% above the basal levels by day 6 of the trial and declined afterwards. Nine months after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. We conclude that ketoconazole was effective in blocking tumoral steroidogenesis which resulted in clinical benefit.

Background Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. Methods ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. Results Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400–850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5–25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1–13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (− 93.3%) and to 0.06 for severe exacerbations (− 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0–10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. Conclusions We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463

This prospective study analyses the value of the beta-subunit of human chorionic gonadotrophin (beta-HCG) in 120 pregnancies obtained after in-vitro fertilization (IVF)--embryo transfer. Spontaneous conception cycles (n = 16) were also analysed allowing a comparison between these two forms of conception. Of the 120 clinical pregnancies, 48 started as single gestations and 50 started with two or more sacs. There were 14 clinical abortions and eight ectopic pregnancies. All subjects had blood samples taken under a fixed protocol on days 11, 14, 17, 20 and 23 after follicular aspiration. Weekly samples were obtained thereafter until day 60 from ovum retrieval. Transvaginal ultrasounds were performed at weekly intervals, starting on day 23 after follicular aspiration. In spontaneous conception cycles blood samples were obtained daily, starting on the day of follicular rupture. In spontaneous conception cycles and in IVF-embryo transfer conceptions, the doubling time (DT) of beta-HCG was 1.4 +/- 0.3 and 1.6 +/- 0.4 days respectively. This difference was not significant. In multigestations, the DT was 1.5 +/- 0.3 days. The absolute values of beta-HCG in early spontaneous gestations were significantly higher than in IVF-embryo transfer cycles, suggesting that the blastocyst implants with less cellular mass when initiated in vitro as compared with the in-vivo condition. The early prediction of ectopic pregnancy and spontaneous clinical abortion was analysed by the beta-HCG profile as well as the absolute values in comparison to normal pregnancies. Both parameters showed significant differences as early as the interval between days 11 and 23 from follicular aspiration.(ABSTRACT TRUNCATED AT 250 WORDS)