Cochrane Library Editorial - Anticholinergic drugs and dementia: time for transparency in the face of uncertainty
Would you choose a treatment option that might increase your risk of developing dementia?
Anticholinergic drugs (which contract smooth muscle, reduce heart rate, dilate blood vessels, and increase bodily secretions) are commonly used in clinical practice for the management of many conditions affecting older adults - for example for urinary incontinence and for treating depression. As a consequence, the cumulative anticholinergic exposure for older people taking medications for multiple health conditions can be underestimated. The sum of this exposure is called anticholinergic burden (ACB). Some anticholinergic drug adverse effects are short‐term and obvious (e.g. dry mouth, constipation) whereas others may be insidious and irreversible – one such concern related to long‐term ACB is a possible contribution to cognitive decline and dementia.
In a new Cochrane Library Editorial, Henry Woodford and Jennifer M Stevenson share their thoughts on the problems with current research and areas that lead to uncertainty around the ACB causality and risks. Given the uncertainty around ACB they call for the reduction of exposure, through fully informed shared decision‐making when anticholinergic medications are initiated, and regular medication review for older people using drugs with anticholinergic.
Co-Chair of Cochrane’s Governing Board and Director of the Cochrane Campbell Global Ageing Partnership Tracey Howe will present at an online event on Tuesday, 7 September, Enabling Knowledge for Healthy Ageing: Launching the UN Decade of Healthy Ageing Platform.
Tracey will speak at the event about knowledge sharing to foster healthy ageing, in the context of the launch of the online Platform for the UN Decade of Healthy Ageing. Of the event, Tracey said, “We are honoured to participate in this important event demonstrating how the Cochrane Campbell Global Ageing Partnership’s high-quality evidence contributes to decision making that fosters healthy ageing.”
All are invited to join to hear from a diverse array of speakers, which can be viewed here.
Can non-pharmacological measures prevent or reduce Covid-19 (SARS-CoV-2) infections in long term care facilities?
A recently published Cochrane review explores what measures can be taken in long-term care facilities to prevent COVID-19 outbreaks.
Can non-medicinal measures prevent or reduce SARS-CoV-2 infections in long term care facilities?
- Non-medicinal measures (e.g. visiting restrictions or regular testing) may prevent SARS-CoV-2 infections (causing COVID-19 disease) in residents and staff in long term care facilities, but we have concerns about the reliability of the findings.
- More high-quality studies on real-world experiences are needed, in particular.
- More research is also needed on measures in facilities where most residents and staff are vaccinated, as well as regions other than North America and Europe.
What are non-medicinal measures?
Non-medicinal measures are ways of preventing or reducing disease without using medicine, such as vaccines. These include controlling people's movements and contacts, using personal protective equipment (PPE), or regular testing for infection.
SARS-CoV-2 is very infectious. Elderly or disabled people, who live in care homes (long-term care facilities), are vulnerable to infection because they live in close contact with other people, with carers and visitors entering and leaving the facility. Due to age and underlying health conditions, care home residents have an increased risk of becoming seriously ill with COVID-19 and dying from the disease.
What did we want to find out?
We wanted to find out how effective non-medicinal measures are in preventing residents and staff in long-term care facilities from becoming infected with SARS-CoV-2 and in reducing the spread of the infection. We focused on all types of long-term care facilities for adults, such as nursing homes for the elderly and skilled nursing facilities for people living with disabilities.
What did we do?
We searched for studies that investigated the effects of non-medicinal measures in long-term care facilities. To be included, studies had to report how many infections, hospitalisations or deaths the measures prevented in residents or staff, or whether the measures prevented the introduction of the virus into the facilities or prevented outbreaks within facilities. We included any type of study, including observational studies that used ‘real-world’ data, or modelling studies based on assumed data from computer-generated simulations.
What did we find?
We found 22 studies, 11 observational and 11 modelling studies. All studies were conducted in North America or Europe.
There were four main types of measures.
- Entry regulation measures to prevent residents, staff or visitors introducing the virus into the facility. Measures included staff confining themselves with residents, quarantine for newly-admitted residents, testing new admissions, not allowing the admission of new residents, and preventing visitors from entering facilities.
- Contact-regulating and transmission-reducing measures to prevent people passing on the virus. Measures included wearing masks or PPE, social distancing, extra cleaning, reducing contact between residents and among staff, and placing residents and staff in care groups and limiting contact between groups.
- Surveillance measures designed to identify an outbreak early. Measures included regular testing of residents or staff regardless of symptoms, and symptom-based testing.
- Outbreak control measures to reduce the consequences of an outbreak. Measures included isolation of infected residents, and separating infected and non-infected residents or staff caring for them.
Some studies used a combination of these measures.
Entry regulation measures (4 observational studies; 4 modelling studies)
Most studies showed that such measures were beneficial, but some studies found no effects or unwanted effects, such as depression and delirium among residents in the context of visiting restrictions.
Contact-regulating and transmission-reducing measures (6 observational studies; 2 modelling studies)
Some measures may be beneficial, but often the evidence is very uncertain.
Surveillance measures (2 observational studies; 6 modelling studies)
Routine testing of residents and staff may reduce the number of infections, hospitalisations and deaths among residents, although the evidence on the number of deaths among staff was less clear. Testing more often, getting test results faster, and using more accurate tests were predicted to have more beneficial effects.
Outbreak control measures (4 observational studies; 3 modelling studies)
These measures may reduce the number of infections and the risk of outbreaks in facilities, but often the evidence is very uncertain.
Combination measures (2 observational studies; 1 modelling study)
A combination of different measures may be effective in reducing the number of infections and deaths.
What are the limitations of the evidence?
Our confidence in these results is limited. Many studies used mathematical prediction rather than real-world data, and we cannot be confident that the model assumptions are accurate. Most observational studies did not use the most reliable methods. This means we cannot be confident that the measure caused the effect, for example, that testing of residents reduced the number of deaths.
How up to date is this evidence?
This review includes studies published up to 22 January 2021.
Dr. Jan M Stratil, first author of the review, said, “Measures to prevent outbreaks of COVID-19 in long-term care facilities, such as restrictions on visiting, wearing masks, regular testing, and isolation of suspected cases were assessed in this Cochrane review. We found that some of these measures may prevent SARS-CoV-2 infections and their consequences for residents and staff, though we have concerns about the reliability of the findings.
More high-quality studies on real-world experiences are needed, in particular in facilities with high vaccination rates, as well as from regions other than North America and Europe. Also, it should be explored why the topic of COVID-19 in long-term care facilities, despite the very high disease burden, received relative little attention by the research community.”
Cochrane Convenes will bring together key thought leaders from around the world to discuss the COVID-19 evidence response and develop recommendations to help prepare for and respond to future global health emergencies.
In this interview, we talk to Jeremy Grimshaw, a member of the Cochrane Convenes steering group, about what he hopes will come out of the event.
Why do you think it is important to hold Cochrane Convenes now?
The COVID-19 pandemic has presented one of the greatest stress tests society has faced in a century. It has been a huge success for research in the way we have rapidly been able to understand the virus, how to address it and develop vaccines, but one challenge that arose during this very rapid period is that it has been hard for decision makers to make sense of the production of research. Evidence synthesis and systematic reviews are critical when the evidence base is evolving at speed.
COVID-19 has tested the evidence synthesis world and prompted innovation, methodological developments, improvements in producing rapid evidence syntheses and greater global collaboration. But it has also revealed fragility in the system: the challenge of co-ordination and duplication of effort, questionable quality in some systematic reviews, and the fact that evidence synthesis can become redundant quickly. We must address these challenges so that those involved in the production and use of evidence are better positioned in the future.
Cochrane Convenes offers a great opportunity to learn from the innovation and look at the weaknesses and tackle these as a global community of evidence producers and users.
Tell us about your involvement and the Global Commission on Evidence to Address Societal Challenges.
Shortly after the pandemic started, I was a co-lead of COVID-END, an umbrella network of over 50 evidence synthesis organisations which came together to encourage co-ordination and collaboration across the evidence community. We saw COVID-END as time limited and that capturing learnings and experiences over the course of the pandemic would have useful applications in the longer term.
In parallel to Cochrane Convenes, COVID-END has set up a Global Commission on Evidence to Address Societal Challenges. This independent commission draws on expertise in decision making from across the world, from health and non-health sectors with a few members from the evidence synthesis research community. Our aim is to create a high-level roadmap that will stimulate further development of the evidence system. Cochrane has been part of COVID-END from the start and we see the commission and Cochrane Convenes as parallel highly complementary activities.
We hope during the Cochrane Convenes meeting we can road test some of the ideas coming out of the commission.
What do you hope will come from Cochrane Convenes?
Cochrane’s leadership is important in this space because it is the preeminent evidence synthesis organisation. It made a fantastic contribution to the pandemic response, which has only furthered its position in the evidence community, so it is well placed to pull together a group to think about the implications not only for its work but also the broader evidence community. Cochrane Convenes is a powerful signal to kick off and accelerate the start of discussions and debates about what we as an evidence community need to do differently to improve the evidence response in ‘normal’ times, as well as when we are faced with a health emergency. It will also help inform Cochrane’s future strategy, which others will take note of.
Which challenges do you think are critical for the evidence community to address in this forum?
How we co-ordinate evidence synthesis is critical. Even before the pandemic, there was inappropriate duplication of systematic reviews and then gaps where there are none. We need to establish how there can be a global stock of preferably living systematic reviews that decision makers can draw on when they need to, managed through a co-ordinated flow of relevant and timely synthesis. This will raise issues about the conduct and timeliness of evidence synthesis which will prompt questions about infrastructure and securing funding for synthesis activities.
Healthcare systems, governments, clinicians and patients should see evidence as one of the key tools in helping them make informed decisions and start to incorporate evidence as a routine part of their decision making. We need prompts for decision makers to consider evidence in their processes and to reflect on how we provide evidence to the decision makers in friendly and understandable formats. This is about closing the gap between the producers and users of evidence. We need to ask how we support evidence intermediary organisations that can act as the link between suppliers of evidence and those who use it. There are pockets of excellence around the world and the ambition is to make this the norm so evidence always informs key decisions.
Who would you like to see in attendance, and why?
National, organisational, professional and citizen views are critical and the more of those views Cochrane Convenes can bring together the better. Cochrane is full of great science, but it needs to improve the conversations it has externally – and listen and understand other perspectives. Decision makers could also do better to understand how evidence syntheses can support what they are interested in.
This is an example of COVID enabling the convening of rooms in a way that would not have happened before. After the pandemic we have an opportunity to look at how global communities and societies function together and how evidence used in decision making will help us all maximise global goods and citizen wellbeing.
- Visit the Cochrane Convenes website
- Visit the COVID-END website
- Visit the Global Commission on Evidence to Address Societal Challenges website
Monday, August 30, 2021
'SARS‐CoV‐2‐neutralising monoclonal antibodies for treatment of COVID‐19' from Cochrane Haematology published today in the Cochrane Library.
- We do not know whether antibodies (the body’s natural defence against disease) made in a laboratory and all the same as one another (monoclonal) and designed to target COVID-19, are an effective treatment for COVID-19 because we assessed only six studies exploring different treatments in different types of patients.
- We identified 36 ongoing studies that will provide more evidence when completed.
- We will update this review regularly as more evidence becomes available.
We spoke to Nina Kreuzberger, Research Associate, who explained this review to us:
“In the rush to treat COVID patients, treatments have been used that are not yet supported by mature data. SARS-CoV-2 neutralising monoclonal antibodies (mAbs) are being used and bought widely, although their value is still under question. Multiple monoclonal antibodies or antibody cocktails, such as bamlanivimab, bamlanivimab with etesevimab, casirivimab with imdevimab, sotrovimab, and regdanvimab, have been investigated in one study each.
In non-hospitalised patients, mAbs may reduce the rate of hospitalisation or death, but effects on mortality alone, adverse events, serious adverse events and quality of life are uncertain or vary per substance due to small sample sizes, or are completely lacking. Data on bamlanivimab in hospitalised patients show little to no effect on mortality and hospital discharge, but may increase the occurrence of adverse events. Similarly, casirivimab with imdevimab has probably no effect on mortality and hospital discharge, data on adverse effects are lacking. These studies suggest that it would be valuable to take a look at subgroups of patients based on serostatus.
We know there are 36 ongoing studies and look forward to updating this review to get a clearer picture on the benefits of this treatment soon.”
What are ‘monoclonal’ antibodies?
Antibodies are made by the body as a defence against disease. However, they can also be produced in a laboratory from cells taken from people who have recovered from a disease.
Antibodies that are designed to target only one specific protein – in this case, a protein on the virus that causes COVID-19 – are ‘monoclonal’. They attach to the COVID-19 virus and stop it from entering and replicating in human cells, which helps to fight the infection. Monoclonal antibodies have been used successfully to treat other viruses. They are thought to cause fewer unwanted effects than convalescent plasma, which contains a variety of different antibodies.
What did we want to find out?
We wanted to know if COVID-19 specific monoclonal antibodies are an effective treatment for COVID-19. We looked at whether they:
- reduced the number of deaths from any cause;
- improved symptoms or made them worse;
- increased admissions to hospital; and
- caused any serious or other unwanted effects.
What did we do?
We searched for studies that investigated one or more monoclonal antibodies to treat people with confirmed COVID-19 compared with placebo (sham treatment), another treatment or no treatment. Studies could take place anywhere globally and include participants of any age, gender or ethnicity, with mild, moderate or severe COVID-19.
We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and size.
What did we find?
We found six active studies including a total of 17,495 people. Four studies investigated non-hospitalised people with no symptoms or mild COVID-19. Two studies investigated hospitalised people with moderate to severe COVID-19. Studies took place across the world. Three studies were funded by pharmaceutical companies. The monoclonal antibodies they studied were bamlanivimab, etesevimab, casirivimab and imdevimab, sotrovimab, regdanvimab. We did not identify data for mortality at 60 days and quality of life.
Non-hospitalised people, with no symptoms or mild COVID-19 (four studies)
One study investigated different doses of bamlanivimab (465 people), compared to placebo.
We don’t know whether bamlanivimab:
- increases or reduces the number of deaths because no participants died within 30 days of treatment;
- causes more or fewer serious unwanted effects because there were few events.
Bamlanivimab may reduce the number of admissions to hospital within 30 days of treatment compared to placebo.
- May cause slightly fewer unwanted effects than placebo.
- We did not find data for improved symptoms or worsened symptoms.
One study investigated a combination of bamlanivimab and etesevimab (1035 people), compared to placebo.
- Bamlanivimab and etesevimab may reduce the number of deaths and admissions to hospital.
- May cause slightly more unwanted effects.
- May cause more serious unwanted effects.
For treatment with bamlanivimab alone or in combination with etesevimab we did not find data for improved symptoms or worsened symptoms.
One study (phase 1/2 with 799 people) investigated different doses of casirivimab combined with imdevimab, compared to placebo.
- Casirivimab combined with imdevimab may reduce the number of hospital admissions or death.
- We don't know whether casirivimab and imdevimab causes more unwanted (grades 3 and 4) and serious unwanted effects than placebo because there were too few deaths to allow us to make a judgment.
- We did not find data for the number of people who died at day 30 and development of severe symptoms.
- We did not include results from phase 3 (5607 people) of this study, because of high risk of bias, as it was not clear which participants were included in the analysis.
One study (583 people) investigated sotrovimab, compared to placebo.
We don't know whether sotrovimab:
- increases or reduces the number of deaths and people requiring invasive mechanical ventilation or dying, because there were too few deaths to allow us to make a judgment.
- Sotrovimab may reduce the number of people requiring oxygen, unwanted (grades 3 to 4) and serious unwanted effects;
- may have little or no effect on unwanted effects (all grades).
Another study (327 people) investigated different doses of regdanvimab (40 mg/kg and 80 mg/kg), compared to placebo.
- Regdanvimab at either dose may reduce the number of admissions to hospital or death.
- May increase unwanted events (grades 3 to 4).
- Regdanvimab at a dose of 80 mg/kg may reduce unwanted effects (all grades) and 40 mg/kg may have little to no effect.
- We don't know whether regdanvimab increases or decreases the number of deaths, requirement for invasive mechanical ventilation, and serious unwanted effects, because there were too few events to allow us to make a judgment.
Hospitalised people with moderate to severe COVID-19 (2 studies)
One study (314 people) investigated bamlanivimab compared to placebo.
- We don’t know whether bamlanivimab increases or decreases the number of deaths due to any cause up to 30 or 90 days after treatment because there were too few deaths to allow us to make a judgment (6 deaths with bamlanivimab and 4 deaths with placebo in 314 people).
- Bamlanivimab may slightly increase the development of severe COVID-19 symptoms five days after treatment and the number of people with unwanted effects.
- Bamlanivimab may have little to no effect on time until discharge from hospital.
- We don’t know whether bamlanivimab causes serious unwanted effects by day 30 because the study was small and reported few serious unwanted effects.
Another study (9785 people) investigated casirivimab combined with imdevimab, compared to standard of care.
- Casirivimab combined with imdevimab has probably little to no effect on the number of deaths, requirement for invasive mechanical ventilation or death, and hospital discharge alive.
- We did not find data for unwanted and serious unwanted effects.
What are the limitations of the evidence?
Our confidence in the evidence is low because we found only six studies, and they did not report everything we were interested in, such as the number of deaths within 60 days and quality of life. We found 36 ongoing studies. When they are published, we will add their results to our review. These results are likely to change our conclusions and will also help us understand how new variants affect how well monoclonal antibodies work.
How up to date is this evidence?
The evidence is up to date to 17 June 2021.
The Governing Board voted unanimously to re-appoint Catherine Marshall for a second term as Co-Chair from September 2021 until September 2023. Catherine will continue to work alongside fellow Co-Chair, Tracey Howe.
The Governing Board is responsible for setting Cochrane's strategic direction and overseeing the work of the Chief Executive Officer, Editor in Chief, and Central Executive Team, which leads, coordinates and supports all the operational work across Cochrane Groups to deliver the organization's strategic goals.
Outside Cochrane, Catherine is a Health Sector consultant based in New Zealand specialising in policy, evidence-based healthcare, consumer engagement guideline development and implementation. She is currently Co-Chair of the Partnership Advisory Group with the Guidelines International Network (G-I-N) and is an Honorary Patron of G-IN and previously Vice Chair of G-I-N's board of trustees for 9 years.
Catherine has a long history in guideline development and was the inaugural Chief Executive of the New Zealand Guidelines Group, which often relied on evidence from the Cochrane Library. Catherine is also a prominent health consumer advocate, working on the development of health consumer legislation in New Zealand and as a former member of the NZ Stronger Consumer Voices Alliance and the NZ Health and Disability Non-Government Organisation Council. In 2018, she helped organize and participate in the consumer programs for the Cochrane Colloquium in Edinburgh. She is currently Co-Chair of the wellington Free Ambulance Consumer Council.
Of her appointment, Catherine says, “I continue to be been deeply impressed by the strength of Cochrane and the talent of the people who contribute to the collaboration. The work of the Collaboration during the pandemic has been phenomenal - and it has been wonderful to see our work applied and valued during a time of global emergency. I am strongly committed to continuing to building a vibrant and trusted organisation that will have a strong future, expanding our reach around the globe and finding new ways Cochrane advice can inform health decisions.”
Cochrane Library Special Collections provide a round-up of up-to-date Cochrane evidence on a specific topic. This Special Collection has been created to highlight evidence-based interventions to reduce stillbirth and improve care for families after stillbirth and in a subsequent pregnancy, identify women at increased risk of stillbirth, and improve knowledge of causes of and contributors to stillbirth.
Stillbirth is a major public health problem with an enormous global mortality burden and psychosocial impact on women, families, communities, and health systems. Despite the scale of the problem and potential for prevention, stillbirth has been largely neglected in global public health. While there has been some improvement in the global stillbirth rate over the past 20 years, much more needs to be done. Efforts to ensure optimal care throughout the COVID-19 pandemic are critical, particularly for disadvantaged populations.
Topics of the Special collection include:
- Preventing stillbirth
- Novel approaches for identifying women at increased risk of stillbirth
- Improving care after stillbirth and in subsequent pregnancies
- Improving knowledge of causes of and contributors to stillbirth
A special Evidently Cochrane blog post for maternity care providers and families has also been published. Dr Aleena Wojcieszek, clinical epidemiologist, science communicator, and honorary research fellow at the Australian Centre of Research Excellence in Stillbirth (Stillbirth CRE), and Ms Susannah Hopkins Leisher, mom to stillborn son Wilder Daniel (13 July 1999), PhD student in epidemiology at Columbia University, and chair of the International Stillbirth Alliance, look at an overview of Cochrane evidence on antenatal interventions to prevent stillbirth and perinatal death. This review is included in the Special Collection.
- Read the Special Collection
- Read the Evidently Cochrane blog: Preventing stillbirth: What’s the latest evidence?
Tuesday, August 24, 2021
Cochrane is delighted to launch a Russian translation of MECIR (Methodological Expectations for Cochrane Intervention Reviews) from Cochrane Russia.
This is the third translation of Cochrane’s methods guidance since the launch of version 6 of the Cochrane Handbook for Systematic Reviews of Interventions (see this Cochrane Editorial for more details about the Handbook’s launch). It is another important milestone in supporting the engagement of people with different native languages in Cochrane Reviews.
Access the Russian translation of MECIR.
Ensuring that Cochrane Reviews represent the highest possible quality is critical if they are to inform decision making in clinical practice and health policy. MECIR are Standards that guide the conduct and reporting of Cochrane Intervention Reviews; they are essentially the ‘how-to’ guide for Cochrane Reviews and are drawn from the Cochrane Handbook for Systematic Reviews of Interventions. All Standards are tagged as ‘mandatory’ or ‘highly desirable’. Mandatory Standards should always be met unless an appropriate justification for not doing so can be provided. Highly desirable Standards should generally be implemented but justification for not implementing them is unnecessary.
The development of MECIR has been a collaborative effort over the years, involving review authors, editors and methodologists from all corners of our community. We are thrilled that this collaboration now includes Cochrane Translation Teams.
Professor Liliya Eugenevna Ziganshina, Director of Cochrane Russia, said “At Cochrane Russia we are happy and privileged to contribute to the translation of Cochrane MECIR Standards. This has been a fascinating experience, a learning opportunity and empowering exercise for all involved! The uptake of Cochrane review Plain Language Summaries in Russia has been growing recently, especially in the new pandemic reality. Appreciation and respect of Cochrane as the global research community and its work in multilingual changing world is high in Russia. We hope that the Russian version of MECIR will contribute to higher quality of research output, to review and methods training in Russia, and to overall better understanding and use of Cochrane reviews in Russia and beyond."
Post written by Judith Deppe (Multi-language Programme Manager, Cochrane) and Ella Flemyng (Methods Implementation Manager, Cochrane)
Location: Radcliffe Primary Care Building, Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG
Pay grade: £29,176 - £32,817 p.a.
Start date: Jan 2022
Length: Funded for 18 months in the first instance
Closing date: 12.00 midday on 7 Sept 2021
Interviews: week commencing 13 Sept 2021
Applications are invited for a research assistant to work as part of a team with Dr. Jamie Hartmann-Boyce and Dr Nicola Lindson from Cochrane Tobacco Addiction group on an evidence synthesis project on the impact of e-cigarette use and availability on smoking in young people.
They wish to appoint an enthusiastic candidate with knowledge of systematic reviewing and/or addiction research. You will conduct screening, data extraction, and quality assessment for the review. The ideal candidate will have experience of conducting a systematic review, will hold an MSc or above in a health-related discipline (or be close to completing an MSc), and have a working knowledge of epidemiological statistics and a high level of attention to detail.
Featured review: What are the benefits and risks of beds, mattresses and overlays for preventing and treating pressure ulcers?
Are corticosteroids (anti-inflammatory medicines) given orally or by injection an effective treatment for people with COVID-19?
- Corticosteroids (anti-inflammatory medicines) given orally or by injection (systemic) are probably effective treatments for people hospitalised with COVID-19. The authors don’t know whether they cause unwanted effects.
- The authors don’t know which systemic corticosteroid is the most effective. They found no evidence about people without symptoms or with mild COVID-19 who were not hospitalised.
- They found 42 ongoing studies and 16 completed studies that have not published their results. The authors will update this review when we find new evidence.
What are corticosteroids?
Corticosteroids are anti-inflammatory medicines that reduce redness and swelling. They also reduce the activity of the immune system, which defends the body against disease and infection. Corticosteroids are used to treat a variety of conditions, such as asthma, eczema, joint strains and rheumatoid arthritis.
Systemic corticosteroids can be swallowed or given by injection to treat the whole body. High doses of corticosteroids taken over a long time may cause unwanted effects, such as increased appetite, difficulty sleeping and mood changes.
Why are corticosteroids possible treatments for COVID-19?
COVID-19 affects the lungs and airways. As the immune system fights the virus, the lungs and airways become inflamed, causing breathing difficulties. Corticosteroids reduce inflammation, so may reduce the need for breathing support with a ventilator (a machine that breathes for a patient). Some patients’ immune systems overreact to the virus causing further inflammation and tissue damage; corticosteroids may help to control this response.
What did we want to find out?
The authors wanted to know whether systemic corticosteroids are an effective treatment for people with COVID-19 and whether they cause unwanted effects.
They were interested in:
- deaths from any cause up to 14 days after treatment, or longer if reported;
- whether people got better or worse after treatment, based on their need for breathing support;
- quality of life;
- unwanted effects and infections caught in hospital.
What did the authors do?
They searched for studies that investigated systemic corticosteroids for people with mild, moderate or severe COVID-19. People could be any age, sex or ethnicity.
Studies could compare:
- corticosteroids plus usual care versus usual care with or without placebo (sham medicine);
- one corticosteroid versus another;
- corticosteroids versus a different medicine;
- different doses of a corticosteroid; or
- early versus late treatment.
They compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did they find?
The team found 11 studies with 8075 people. About 3000 people received corticosteroids, mostly dexamethasone (2322 people). Most studies took place in high-income countries.
They also found 42 ongoing studies, and 16 completed studies that have not yet published their results.
Ten studies compared corticosteroids plus usual care versus usual care with or without placebo. Only one study compared two corticosteroids. The studies included only hospitalised people with confirmed or suspected COVID-19. No studies looked at non-hospitalised people, different doses or timing, or provided information about quality of life.
Corticosteroids plus usual care compared to usual care with or without placebo (10 studies)
- Corticosteroids probably reduce the number of deaths from any cause slightly, up to 60 days after treatment (9 studies, 7930 people).
- One study (299 people) reported that people on a ventilator at the start of the study were ventilation-free for more days with corticosteroids than with usual care, so corticosteroids may improve people’s symptoms.
- Four studies (427 people) reported whether people not on a ventilator at the start of treatment later needed to be put on a ventilator, but we could not pool the studies’ results, so we are unsure if people’s symptoms get worse with corticosteroids or usual care.
- The authors don’t know if corticosteroids increase or reduce serious unwanted effects (2 studies, 678 people), any unwanted effects (5 studies, 660 people), or infections caught in hospital (5 studies, 660 people).
Methylprednisolone versus dexamethasone (1 study, 86 people)
- The authors don’t know whether the corticosteroid methylprednisolone reduces the number of deaths from any cause compared to dexamethasone in the 28 days after treatment.
- The authors don’t know if methylprednisolone worsens people’s symptoms compared to dexamethasone, based on whether they needed ventilation in the 28 days after treatment.
- The study did not provide information about anything else we were interested in.
What are the limitations of the evidence?
The authors are moderately confident in the evidence about corticosteroids’ effect on deaths from any cause. However, their confidence in the other evidence is low to very low, because studies did not use the most robust methods, and the way results were recorded and reported differed across studies. The author team did not find any evidence on quality of life and there was no evidence from low-income countries or on people with mild COVID-19 or no symptoms, who were not hospitalised.
This evidence is up to date to 16 April 2021.
Lead authors explain the evidence
Lead Cochrane Haematology authors Carina Wagner from University of Cologne and Mirko Griesel from University of Leipzig Medical Centre said,
“Corticosteroids given orally or by injection probably have a small benefit in the treatment of people hospitalised with COVID-19, however we don’t know whether they also cause unwanted effects.
At this stage we don’t know which systemic corticosteroid is the most effective and we found no evidence about people without symptoms or with mild COVID-19 who were not hospitalised. We found 42 ongoing studies and 16 completed studies that have not yet published their results. We will update this review when we find new evidence about this treatment which is relatively low cost and available in large parts of the world.”
- Read the full review on the Cochrane Library
- Visit the Cochrane Haematology website
- See all the Cochrane COVID-19 resources
Tuesday, August 17, 2021
What can individuals do, especially those with long-term breathing problems, to avoid the effects of air pollution?
This recently published Cochrane review explores this question, and we sat down with the lead author of the review to discuss the review findings.
Tell us about this Cochrane review…What did you find out?
The main thing that we found out from this review is that we are really lacking evidence on the importance of different interventions to reduce the impact of air pollution on the health of individuals with lung conditions. As well as finding very few studies covering the topic to include in the review, the ones that were found all used different methods, which meant that it was difficult to combine them and derive conclusions from them. This was disappointing, but certainly not unexpected.
Can individuals looking to protect themselves from air pollution take anything from this review?
People living with chronic conditions (such as asthma and COPD) have real concerns about being exposed to air pollution and often ask what they can do to ensure that they protect themselves most effectively. Common questions we receive at the European Lung Foundation are about how to commute to work while avoiding exposure and the best time to exercise or go out walking. There are lots of common-sense suggestions and advice that we can provide them with, but it would be much more beneficial to have evidence-based recommendations. These evidence-based recommendations are also needed for healthcare professionals to ensure that they can best advise their patients when they see them regularly in their clinics.
There is little from this review that can really add to what we would already advise, but some studies did reinforce the tips we would currently give: for example using a mask or a lower pollution cycle route may reduce some of the physiological impacts from air pollution.
Given the studies you found and the challenge this presented in drawing any conclusions, what could helpfully happen next?
This review should be a call to action to individuals working in the field to carry out more studies looking at the health outcomes of people living with chronic conditions when using specific interventions to reduce exposure to air pollution – such as changing routes, using air quality indexes, masks etc. Larger and longer studies that recruit participants with pre-existing chronic conditions and that include patient-important outcomes (such as exacerbations, hospital admissions, quality of life and adverse events) are urgently needed.
In this recently published Cochrane review, authors explored the effects of treating COVID-19 with remdesivir, an antiviral medication.
First author Kelly Ansems said "Based on the current evidence, we are moderately certain, that remdesivir has little or no effects on mortality in adults hospitalised with COVID-19, but we cannot validly assess potential differences in its effect depending on initial disease severity due to incompleteness of the current available study data. Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID-19 research."
- For adults hospitalised with COVID-19, remdesivir probably has little or no effect on deaths from any cause up to 28 days after treatment compared with placebo (sham treatment) or usual care.
- The review authors are uncertain whether remdesivir improves or worsens patients’ condition, based on whether they needed more or less help with breathing.
- Researchers should agree on key outcomes to be used in COVID-19 research, and future studies should investigate these areas. This would allow future updates of this review to draw more certain conclusions about the use of remdesivir to treat COVID-19.
What is remdesivir?
Remdesivir is a medicine that fights viruses. It has been shown to prevent the virus that causes COVID-19 (SARS-CoV-2) from reproducing. Medical regulators have approved remdesivir for emergency use to treat people with COVID-19.
What did authors want to find out?
The authors of this review wanted to know if remdesivir is an effective treatment for people in hospital with COVID-19 and if it causes unwanted effects compared to placebo or usual care.
People with COVID-19 are given different kinds of breathing support, depending on how severe their breathing difficulties are. The authors used the types of breathing support people received as a measure of the success of remdesivir in treating COVID-19. Types of breathing support included:
- for severe breathing difficulties: invasive mechanical ventilation, when a breathing tube is put into patients’ lungs, and a machine (ventilator) breathes for them. Patients are given medicine to make them sedated whilst they are on a ventilator.
- for moderate to severe breathing difficulties: non-invasive mechanical ventilation through a mask over the nose and/or mouth, or a helmet. Air or oxygen is pushed through the mask. Patients are generally awake for this treatment.
- for moderate breathing difficulties: oxygen via a mask or prongs that sit in the nostrils. Patients can still breathe room air.
The authors were interested in the following outcomes:
- deaths from any cause in the 28 days after treatment;
- whether patients got better after treatment, measured by how long they spent on mechanical ventilation or oxygen;
- whether patients’ condition worsened so that they needed oxygen or mechanical ventilation;
- quality of life;
- any unwanted effects; and
- serious unwanted effects.
What did the authors do?
They searched for studies that investigated remdesivir to treat adults with COVID-19 compared to placebo or standard care. Patients were hospitalised with COVID-19 and could be of any gender or ethnicity.
They compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did they find?
They found 5 studies with 7452 people hospitalised with COVID-19. Of these, 3886 people were given remdesivir. The average age of patients was 59 years. Studies took place around the world, mainly in high- and upper-middle-income countries.
The included studies compared remdesivir to placebo or usual care in people hospitalised with COVID-19 for up to 28 days.
Deaths from any cause
Remdesivir probably makes little or no difference to deaths from any cause (4 studies, 7142 people). In 1000 people, 8 fewer die with remdesivir compared to placebo or standard care.
Did patients get better with remdesivir?
- Remdesivir may have little or no effect on the length of time patients spent on invasive mechanical ventilation (2 studies, 1298 people).
- The authors do not know whether remdesivir increases or decreases time on supplemental oxygen (3 studies, 1691 people).
Did patients get worse with remdesivir?
- Authors do not know whether patients are more or less likely to need any mechanical ventilation (invasive or non-invasive) with remdesivir (3 studies, 6696 people).
- Patients may be less likely to need invasive mechanical ventilation (2 studies, 1159 people).
- Authors do not know whether patients are more or less likely to need non-invasive mechanical ventilation (1 study, 573 people).
- Authors do not know whether patients are more or less likely to need oxygen by mask or nasal prongs (1 study, 138 people).
Quality of life
None of the included studies reported quality of life.
- Authors do not know whether remdesivir leads to more or fewer unwanted effects of any level (3 studies, 1674 people).
- Patients are probably less likely to experience serious unwanted effects with remdesivir than with placebo or standard care (3 studies, 1674 people). In 1000 people, 63 fewer would experience a serious unwanted effect compared to placebo or standard care.
What are the limitations of the evidence?
The authors of this review are moderately confident in the evidence for deaths from any cause and serious unwanted effects; however, their confidence in the other evidence is limited because studies used different methods to measure and record their results, and the review authors did not find many studies for some of the outcomes of interest.
How up-to-date is this evidence?
The evidence is current to 16 April 2021.
Deadline for submissions: 24 September
Nominations are open for the 2021 Cochrane-REWARD prize, which recognizes initiatives that have potential to reduce research waste.
An estimated $170 billion of research funding is wasted each year because its outcomes cannot be used . The waste occurs during 5 stages of research production: question selection, study design, research conduct, publication, and reporting [2,3]. Much of this waste appears to be avoidable or remediable, but there are few proposed solutions.
The Cochrane-REWARD prize was established in 2017 to stimulate and promote research in this area.Cochrane is now calling for nominations for the 2021 prize.
This year, the prize committee especially encourages submissions related to tackling COVID-19 research waste.
The COVID-19 pandemic has seen research published at an unprecedented scale, and it is likely that many of the existing research waste issues have been amplified . However, there are also notable examples of efforts to reduce waste and we are keen to highlight some of these.
All nominations will be assessed using the following criteria:
- The nominee has addressed at least one of the 5 stages of waste (questions, design, conduct, publication, reporting) in health research;
- The nominee has pilot or more definitive data showing the initiative can lower waste;
- The initiative can be scaled up;
- The estimated potential reduction in research waste that the initiative might achieve.
Nominations for the 2021 prize should be submitted by 24 September 2021. Two prizes will be awarded (a 1st prize of £1500 and a 2nd prize of £1000), but other shortlisted candidates will also be highlighted to help disseminate good ideas.
The winners of the 2021 prize will be announced in a virtual ceremony later in the year, where they will also be given the opportunity to present about their work.
- More information on the prize and how to submit a nomination.
- Read about the previous winners of the Cochrane-REWARD prize.
- Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Lancet. 2009 Jul 4;374(9683):86-9.
- Macleod MR, Michie S, Roberts I, et al. Biomedical research: increasing value, reducing waste. Lancet. 2014 Jan 11;383(9912):101-4.
- Glasziou P, Altman DG, Bossuyt P, et al. Reducing waste from incomplete or unusable reports of biomedical research. Lancet. 2014 Jan 18;383(9913):267-76.
- Glasziou, P and Chalmers, I. Research waste is still a scandal—an essay by Paul Glasziou and Iain Chalmers. BMJ. 2018 Nov 12;363:k4645
- Glasziou P, Sanders S and Hoffmann T. Waste in covid-19 research BMJ. 2020 May 12;369:m1847.
The Cochrane Methods team has defined a programme of work to improve the quality and impact of Cochrane reviews in public health with the support of the Methods Executive, Methods Groups and Public Health and Health Systems Network. The programme has been designed to foster collaboration between Methods Groups and Cochrane Review Group (CRG) Networks and to support the ongoing response to COVID-19. It focuses on producing high-priority public health reviews and delivering user-friendly resources to improve the planning, conduct and reporting of methods within them.
Why focus on public health?
Public health reviews, especially those relating to COVID-19, are often highly scrutinised and have wide-ranging impacts on policy and global health outcomes. However, public health reviews typically address complex questions and use a range of complex methods that are considered non-standard in Cochrane, and existing guidance is not always being applied accurately or consistently. In the Cochrane context, public health reviews are defined as those that include diverse sources of evidence (e.g., not solely RCTs), complex interventions that are delivered at the population level (e.g., policies rather than drugs or treatments), exposures that cannot be delivered in randomized controlled trials (e.g. studying the effects of a chemical or viral exposure), and outcomes that measure something other than efficacy (e.g., harms, process outcomes, implementation or costs).
How will the programme support review production?
The programme of work is based on the premise that high-quality, timely review production requires expert methodological support and pragmatic resources that help authors and editors translate Handbook guidance into practice. The topics and approach have been designed to bring CRGs and Methods Groups together to ensure the projects and their outputs are designed with the needs of Cochrane editors and authors in mind.
Though the focus is on public health reviews, the challenges faced within them are often encountered in other topic areas, such as choosing when and how to include non-randomised studies of interventions, assessing bias in non-randomized studies of interventions, planning a useful synthesis in light of complexity and heterogeneity, incorporating qualitative evidence, and reporting results when a meta-analysis has not been possible. By tackling the challenges in a COVID-priority area, the aim will be to develop, adapt and apply the tools more widely across Cochrane. The Methods Support Unit plays an important role in bridging the gap between CRGs and Methods Groups and will be embedded in the projects to support capacity-building.
What has happened so far?
The Cochrane Methods team mapped the most frequently cited challenges from two recent methods surveys of CRGs by methodological area and listed possible projects to address them. The projects were then shortlisted considering extent of author and CRG need, potential for impact, and the anticipated time and resources required to deliver a useful output. The projects have been refined with Cochrane’s Methods Executive and project teams are now being brought together. Each has been designed to deliver a practical tool or decision aid for editors or authors by the end of 2021 that harnesses existing theory so that it can be more easily applied.
- Project 1: Preferred and accepted risk of bias tools for assessing bias in non-randomised studies of interventions
- Project 2: Practical guidance to frame public health intervention review questions, define outcomes and choose appropriate study designs
- Project 3: Standard terminology to help authors describe different study designs appropriately and consistently
- Project 4: Practical conduct and reporting guidance for assessing risk of bias in non-randomised studies of interventions and/or ROBINS-I
- Project 5: Practical tools to implement SWiM reporting guidance to improve pre-specification and presentation of findings
In addition to the projects, plans are underway to deliver a suite of learning resources around qualitative evidence synthesis, and to house a bank of exemplar reviews showcasing best practice. A Methods Symposium will also take place in October 2021 covering a range of methodological challenges relating to public health reviews and complex interventions. The symposium will be followed by a methods implementation surgery led by the Methods Support Unit and aimed at CRGs in November 2021 to discuss the outputs that were developed and how they can support editors and authors.
How can I get involved?
Each project will be encouraged to use Task Exchange to call for volunteers across the community to provide feedback on the first draft of the tools and resources being developed. Those interested in getting involved are encouraged to create a profile or contact the Methods Team directly to enquire about other ways to contribute.
- Introduction to a collection of articles in the American Journal of Public Health describing the issues in more detail, coordinated by Lisa Bero, Senior Editor of the Cochrane Public Health and Health Systems network
- Priority review topics guiding Cochrane’s ongoing response to COVID-19
World Evidence-Based Healthcare Day will take place again this year on 20 October – learn more on the website
On World Evidence-Based Healthcare (EBHC) Day, seven leaders in evidence-based healthcare spotlight the global impact of evidence on healthcare research, policy, practice and health outcomes.
Today JBI, Cochrane, Campbell Collaboration, GIN, the Institute for Evidence-Based Healthcare, the Centre for Evidence-based Health Care and NICE launch the World EBHC Day 2021 campaign, ‘the role of evidence in an infodemic’.
The 2021 campaign supports the infodemic management efforts of the World Health Organization (WHO) by exploring the role of evidence in an infodemic, in particular promoting access to trustworthy, evidence-informed health information.
“The COVID-19 pandemic has highlighted the importance of developing rapid evidence-informed responses and ensuring the best available evidence is accessible, transparent and understood. The rapid response of the global evidence community has been important and necessary. However, it has been accompanied by the exponential production of misinformation which has contributed to the creation of a global infodemic,” explains Bianca Pilla, World EBHC Day Committee Chair.
The overabundance of information and the distribution of misinformation is amplified through social media and spreads like a virus, making it hard for people to find trustworthy, evidence-based guidance when they need it.
“Never before has there been a more urgent need for a coordinated, evidence-based approach to mitigating the harm caused by an infodemic and the spread of health misinformation. COVID-19 misinformation is harming communities and individuals,” says Dr Sylvie Briand, Director of the WHO Department of Global Infectious Hazard Preparedness.
The World EBHC Day campaign in 2021 responds to the WHO’s call for action. Guided by infodemiologist Gunther Eysenbach’s work on infodemic management and the WHO’s infodemic management framework, JBI, together with the organising partners of World EBHC Day, provide a platform for the global evidence community to share their experiences, stories and collective wisdom.
WHO has produced a public health research agenda which recognises that infodemic management is an emerging and evolving field of research and practice, and that transdisciplinary synthesis is required to develop the field.
“The infodemic has been a major challenge to achieving an evidence-informed response to COVID-19,” says Dr Karla Soares-Weiser, Editor in Chief of the Cochrane Library. “This year’s World EBHC Day will be a timely opportunity for the evidence community to come together and explore our role in the responding to the current infodemic, as well as to consider how we can prepare for future infodemics.”
World EBHC Day calls on individuals and organisations in healthcare around the world to take action as we lead up to World EBHC Day on 20 October. Visit worldebhcday.org and contribute to a global response for infodemic management.
About World Evidence-Based Healthcare Day 2021
World Evidence-Based Healthcare (EBHC) Day is held on 20 October each year. It is a global initiative that raises awareness of the need for better evidence to inform healthcare policy, practice and decision making in order to improve health outcomes globally. It is an opportunity to participate in debate about global trends and challenges, but also to celebrate the impact of individuals and organisations worldwide, recognising the work of dedicated researchers, policymakers and health professionals in improving health outcomes.
Location: De Montfort University - Faculty of Health and Life Sciences. Leicester, UK
Salary: Part-time, 0.3 FTE, 11.1 hours per week
Contract type: 13 month fixed Term Contract
Closes: 8 August
The purpose of the role is to assist the principal investigator in all phases of the NIHR-funded study: ‘Cochrane Review of Interventions for Hyperhidrosis’. Key duties will include searching and selection of studies, data extraction, assessment of risk of bias, and data analysis and interpretation. You will also contribute to study outputs.
They are looking for someone with a PhD in Bioscience or Healthcare related discipline or equivalent experience. You will have experience of conducting high quality systematic reviews and meta-analysis. The ability to explain complex knowledge to a range of audiences is essential, along with excellent verbal and written communication skills. Good organisations skills and the ability to work well in a team are also required.
Featured review: Compression bandages or stockings versus no compression for treating venous leg ulcers
The existing expectations for RoB 2 that were set out in November 2020 have been revisited and kept in place after results of a Cochrane-funded study were released. The study was initiated to underpin methods policy and implementation plans with data about the usability of RoB 2 compared with the study-based Cochrane risk of bias tool for RCTs, and its impact on efficiency and review quality. The work was led by Bernd Richter and Bianca Hemmingsen from the Cochrane Metabolic and Endocrine Disorders Group and looked at inter-reliability across domains, time-taken to perform assessments, usability issues, and consequences for analysis results and interpretation.
The decision to keep the current expectations in place means that uptake of RoB 2 to assess randomised controlled trials is encouraged but there will still be the option to use the study-based Cochrane risk of bias tool, providing it is applied in a way that allows for differences in bias across outcomes to be captured. Reviews using RoB 2 should be prepared and edited in RevMan Web to take advantage of functionality that has been designed to store and present assessments clearly. Authors wishing to adopt RoB 2 after the protocol has been published, including switching to the tool for a review update, should make the decision with editorial staff and consult the resources available in the Starter Pack for reporting guidance.