Constraints on primordial black holes.

We update the constraints on the fraction of the Universe that may have gone into primordial black holes (PBHs) over the mass range 10-5to 1050 g. Those smaller than ∼1015 g would have evaporated by now due to Hawking radiation, so their abundance at formation is constrained by the effects of evaporated particles on big bang nucleosynthesis, the cosmic microwave background (CMB), the Galactic and extragalacticγ-ray and cosmic ray backgrounds and the possible generation of stable Planck mass relics. PBHs larger than ∼1015 g are subject to a variety of constraints associated with gravitational lensing, dynamical effects, influence on large-scale structure, accretion and gravitational waves. We discuss the constraints on both the initial collapse fraction and the current fraction of the dark matter (DM) in PBHs at each mass scale but stress that many of the constraints are associated with observational or theoretical uncertainties. We also consider indirect constraints associated with the amplitude of the primordial density fluctuations, such as second-order tensor perturbations andµ-distortions arising from the effect of acoustic reheating on the CMB, if PBHs are created from the high-σpeaks of nearly Gaussian fluctuations. Finally we discuss how the constraints are modified if the PBHs have an extended mass function, this being relevant if PBHs provide some combination of the DM, the LIGO/Virgo coalescences and the seeds for cosmic structure. Even if PBHs make a small contribution to the DM, they could play an important cosmological role and provide a unique probe of the early Universe.

Clinical outcomes and adverse events in patients hospitalised with COVID-19, treated with off-label hydroxychloroquine and azithromycin.

AIMS: To assess clinical outcomes and adverse drug events in patients hospitalised with COVID-19 treated with off-label hydroxychloroquine (HCQ) and azithromycin (Az). METHODS: We performed a retrospective analysis of hospitalised patients who had a positive polymerase chain reaction test for SARS-CoV-2 and received HCQ plus Az or no targeted therapy. The primary end point was clinical improvement on day 7 defined as either hospital discharge or an improvement of 2 points on a 6-category ordinal scale. Secondary outcomes included mortality at day 28, intensive care admission, requirement for mechanical ventilation and incidence of adverse events. RESULTS: Data from a total of 134 patients were evaluated; 82 patients received HCQ/Az and 52 patients received no targeted therapy. Clinical improvement was seen in 26.8% of patients who received HCQ/Az but this was not significant. The rates of intensive care transfer and mechanical ventilation were higher in the treatment group, but these differences were not significant. Mortality at day 28 was significantly higher in the treatment group (P = .03). Hypoglycaemia elevated liver function tests and QT prolongation were monitored in both groups. The risk of QT prolongation was significantly higher in the treatment group. Treatment was stopped early in 6 (7.3%) patients due to adverse events. CONCLUSION: Although patients who received HCQ/Az were more severely ill the administration of these repurposed drugs did not result in clinical improvement and was associated with a significant increase in toxicity. This descriptive study highlights the importance of monitoring all repurposed agents for adverse events.

An electronic medical record reminder is independently associated with improved opportunistic influenza vaccination rates for older inpatients.

BACKGROUND: Influenza vaccination will have added importance this winter given the possibility of further waves of the COVID-19 pandemic. This study examines the impact of an electronic medical record (EMR) reminder on influenza vaccine uptake among eligible hospital inpatients. METHODS: We included a convenience sample of 750 adults (median age 77 years) who are eligible for influenza vaccination (⩾65 years and/or length of stay >30 days). A live electronic dashboard identified patients eligible for vaccination, prompting reminders sent to the clinical teams via the EMR. RESULTS: The EMR reminder was associated with almost a 50% higher likelihood of vaccination after adjusting for other covariates (odds ratio 1.48 (95% confidence interval 1.00-2.20); p = 0.048). DISCUSSION: Reminders sent to the clinical team via the EMR appear to be an effective means of increasing vaccine uptake and should be considered as part of this year's drive to vaccinate eligible patients in hospital.