Ann Robinson’s research reviews—29 October 2020

Ann Robinson reviews the latest research from the top medical journals

Tocilizumab doesn’t lower mortality in covid-19 related pneumonia

Tocilizumab joins a growing list of drugs that don’t seem to reduce mortality in covid-19. In this small randomised trial embedded in the CORUMINO-19 cohort—of hospitalised patients with moderate to severe pneumonia and covid-19 who needed oxygen but not intensive care—tocilizumab, an interleukin-6 receptor antibody, did not reduce mortality by day 28. There was possibly a small reduction in the need for ventilation and mortality at day 14 compared with normal care (24% v 36%). It is too soon to write off tocilizumab entirely; larger trials are needed to tease out subgroups that may benefit and to find out whether combining tocilizumab with corticosteroids and antiviral drugs gives better results. Even if 28 day mortality doesn’t fall, tocilizumab may prevent deterioration, keep some patients out of intensive care, and improve their long term health and quality of life as a result.

JAMA Intern Med doi:10.1001/jamainternmed.2020.6820

Lopinavir-ritonavir in patients admitted to hospital with covid-19

The UK RECOVERY trial has found that a combination of the antiviral drugs lopinavir and ritonavir did not reduce 28 day mortality, length of hospital stay, risk of progressing to invasive mechanical ventilation, or death among patients admitted to hospital with covid-19 compared with those who received usual care. The results held true across several subgroups including age, sex, and ethnicity, but the drug combination couldn’t be tested in intubated patients because of technical problems so we can’t be sure that they wouldn’t benefit. The dexamethasone and hydroxychloroquine groups in this trial have now been stopped, but azithromycin, tocilizumab, convalescent plasma, and REGN-CoV2 (a combination of two monoclonal antibodies against SARS-CoV-2 spike protein) are still being studied and others can be added, which is the beauty of this trial. The WHO Solidarity trial reported last week that none of the four repurposed drugs studied (remdesivir, interferon, hydroxychloroquine, and lopinavir-ritonavir) showed any significant impact on mortality or disease course, so there’s an urgent need for fresh candidates.

Lancet doi:10.1016/S0140-6736(20)32013-4

Consigning cervical cancer to history

The World Health Organization is trying to eliminate cervical cancer across the world. Human papillomavirus (HPV) vaccination rates are currently low in low and middle income countries, so effective screening and early-stage treatment remain essential if the WHO is to achieve its goal. This cross-sectional study based on self reported data in 55 low and middle income countries between 2005 and 2018 found a median level of 43.6% of women aged 30-49 years had ever had a cervical cancer screening test in their lifetime. This ranged massively from 0.3% in sub-Saharan Africa to 97.4% in Latin America and the Caribbean. Women in the highly populated countries of Indonesia, China, and India, and those living in poverty and rural areas were least likely to have had any cervical cancer screening tests. Relying on self reporting is always a limitation, but this study is a useful step in the long march towards wiping out cervical cancer globally.

JAMA doi:10.1001/jama.2020.16244

Steroids in prematurity; effective and safe in low income countries too

Antenatal corticosteroids have been shown to reduce mortality and complications of prematurity in high income countries, but they seem to have the opposite effect in low income countries. This well designed WHO study found fewer neonatal deaths among live born infants of women given antenatal intramuscular dexamethasone compared with placebo (19.5% v 23.5%), less severe respiratory distress and need for neonatal resuscitation, and lower stillbirth or neonatal death (25.7% v 29.2%). The researchers estimated that 1 in 25 women would need to be treated with dexamethasone to prevent one neonatal death. Dexamethasone was safe for mothers and their babies, with no increase in maternal infection or neonatal hypoglycaemia compared with placebo. The study covered a wide range of sites with different approaches to maternal and neonatal care, including the use of ultrasound scanning to assess gestational age which muddies the waters. Further study is needed into the best dosing regimens and safety profile of dexamethasone, and the role of tocolytic drugs that postpone delivery for long enough to allow the dexamethasone to be given.

N Engl J Med doi:10.1056/NEJMoa2022398

Preoperative anaemia: intravenous iron top-ups don’t help

Preoperative anaemia (haemoglobin <130 g/L for men or <120 g/L for women) is common and is associated with worse outcomes after surgery. Oral iron is often ineffective in surgical patients because iron transport and metabolism are disrupted by the presence of inflammation or chronic disease. Does intravenous iron work any better? A single 1000 mg dose of ferric carboxymaltose given 10-42 days before major elective abdominal surgery to correct the anaemia didn’t reduce mortality rates or the need for blood transfusions compared with placebo (29% v 28%) according to this well conducted UK study. These robust findings mean that current guidelines recommending preoperative iron therapy before major elective surgery need to be revisited and probably revised.

Lancet doi:10.1016/S0140-6736(20)31539-7

Ann Robinson is an NHS GP and health writer and broadcaster.