Featured Review: Drugs for correcting the basic defect in the most common cystic fibrosis-causing gene variant
Read this recently published Cochrane review about CFTR correctors, a therapy for cystic fibrosis targeted at specific variants (most commonly F508del)
In this review, the authors looked at drugs (or drug combinations) for correcting the basic defect in the most common cystic fibrosis (CF)-causing gene variant (F508del) and assessed their impact on outcomes important to people with Cystic Fibrosis, e.g. survival, quality of life (QoL), lung function and safety.
Professor Kevin Southern, lead author of this review, has been involved in the care of children with CF for over 30 years, and has a deep appreciation of the impact of this condition on the young people and their families. "It has been great to work with the team to produce this comprehensive review, which clearly identifies the positive impact that triple therapy has on the well being of people with CF. The benefits identified in trials will prove to be transformational for young adults with CF like Freya Miao (pictured here with her glass of milk to take this therapy), who can now focus on maintaining good health as they move through adult life."
He continued, "The review concludes that people with CF with one or two F508del gene variants will benefit from this intervention. In some countries, people with this gene variant are not able to access this important new therapy because of both funding and regulatory issues, and this represents a significant inequality that needs to be addressed.”
The CF gene makes a protein that helps salts move across cells in many parts of the body; over 80% of people with Cystic Fibrosis have at least one copy of F508del, meaning they make a full length of this protein, but it can not move through the cell correctly. Laboratory experiments suggest that if this protein reaches the cell wall, it may be able to function, restore salt movement, and correct the chronic problems that people with Cystic Fibrosis experience. The authors examined several agents for correcting F508del. Their original review showed that while single drugs alone were not effective, they were when combined with other drugs. This updated review includes single, dual (corrector plus potentiator), and triple therapies (two different correctors plus one potentiator).
The authors included 19 studies (2959 children and adults) lasting between 1 day and 24 weeks (with an extension of two studies up to 96 weeks). Eight studies (344 participants) compared monotherapy: 4PBA, CPX, lumacaftor, cavosonstat and FDL169) to placebo (dummy treatment containing no active medicine), six studies (1840 participants) compared dual therapy (lumacaftor-ivacaftor or tezacaftor-ivacaftor) to placebo. Five studies (775 participants) assessed triple therapy (elexacaftor-tezacaftor-ivacaftor or VX-659-tezacaftor-ivacaftor); only the combination with elexacaftor progressed beyond early studies. In 14 studies, participants had two copies of F508del, in two studies participants had one F508del variant and one different variant, while in three studies participants had either two copies of F508del or one copy of F508del and one different variant.
Monotherapy versus control
These studies did not report any deaths or clinically relevant improvements in QoL scores. There was insufficient evidence to show an effect on lung function. All studies reported side effects, but it is difficult to assess their relevance due to the range of effects and the small number of participants in the studies.
Dual therapy versus control
Neither the lumacaftor-ivacaftor or tezacaftor-ivacaftor studies in people with two copies of F508del reported any deaths and there were improvements in QoL and lung function. Pulmonary exacerbation (a flare-up of symptoms) rates were also lower. Neither combination therapy was linked to severe side effects, although people starting treatment with lumacaftor-ivacaftor experienced shortness of breath for one to two weeks, this usually stopped without further treatment. More concerningly, in longer studies some people taking lumacaftor-ivacaftor experienced a rise in blood pressure; two people (out of over 500) even stopped lumacaftor-ivacaftor treatment because of high blood pressure. These side effects were not reported for tezacaftor-ivacaftor. Tezacaftor-ivacaftor therapy has not yet been assessed in children with CF under 12 years old.
Triple therapy versus control
No deaths were reported in the three studies. Triple therapies improved QoL scores and lung function, with no difference in the number or severity of side effects; there was a longer time until the next pulmonary exacerbation. There is high-quality evidence that elexacaftor-tezacaftor-ivacaftor therapy is clinically effective with few side effects for pwCF with one or two F508del variants aged 12 years or older. Further RCTs are required in children (under 12 years) and those with more severe respiratory function. The side effect profile of elexacaftor-tezacaftor-ivacaftor therapy seems to be similar to tezacaftor-ivacaftor, but we need to collect information over the longer term.
Quality of the evidence
The overall quality of the evidence varied from low to high. There were generally few details about study design, so we could not make clear judgements on potential biases. We had fewer concerns with the larger more recent studies. In 10 studies, some results were not analysed or reported. Some findings were based on studies that were too small to show important effects and for nine studies the results may not be applicable to all pwCF due to the age (i.e. only adults or only children studied) or an unusual design (pwCF received monotherapy and then combination therapy).
Behind The Numbers is a podcast aimed at disseminating research, news, & educational resources pertaining to Epidemiology and Biostatistics. Led by Gabriele Zitikyte, MSc Epidemiology student and executive member of the Canadian Society of Epidemiology and Biostatistics (CSEB)-uOttawa chapter, the podcasts feature interviews and discussions that highlight different areas within epidemiology.
Recently, they spoke to Dr. Adrienne Stevens, the Managing Director of Cochrane Canada. Dr. Stevens expands on the differences between rapid reviews and systematic reviews, as well as the many ways that Cochrane is doing its part in combatting COVID-19 by continuing to promote evidence-informed health decision making. Dr. Stevens covers the Cochrane work on rapid review methodology to other Cochrane COVID-10 projects, such as the COVID-19 Recommendations Map.
- You can listen to the Behind The Numbers episode on iTunes or Spotify
- Learn more about the COVID-19 Recommendations Map
- Read the Cochrane Library Supplement
- Read all the Cochrane resources and news on COVID-19
The Membership team in Cochrane's People Services Department are delighted to announce a new version of our Join Cochrane pages that lay out all the varied ways people can get involved with Cochrane’s work. At the heart of the new content are:
- Clear benefits of Cochrane Membership
- New involvement pathways for patients and carers and for students
The pages also showcase the fantastic Membership badges, which are available for to download from the Cochrane Account portal.
This week, the total number of Cochrane Members and Supporters hit the 100,000 mark. This impressive figure reflects the fact that we encourage anyone interested in our work to create a Cochrane Account, which unlocks access to free resources such as Cochrane Evidence Essentials and opportunities to contribute as part of Cochrane Crowd, the Cochrane Consumer Network, or on our volunteer hub, Cochrane TaskExchange.
Many of those who join as Supporters, will progress to earn Membership. Testimonies from Cochrane Members who share their experiences of getting involved, show the real value of Cochrane Membership as a reward for contributing to our work.
Thanks to our amazing translation teams, most of whom are volunteers, these pages are available in different languages - and the translators will have earned Membership points for their hard work!
We would like to thank the Web Team, and the Knowledge Translation Department, for their help in preparing these pages and their translated versions.
Tell us about this Cochrane Review
This is an interesting time for the treatment of airways diseases. Traditionally we've thought of these as coming under two main headings, asthma and chronic obstructive pulmonary disease (COPD), plus a handful of other rarer conditions such as bronchiectasis. Characteristically asthma caused variation in lung function tests such as peak flow or FEV1, either over time or with medication whereas COPD is defined by lung function that didn't improve ("fixed airflow obstruction"). Basing diagnosis on one dimension of the disease process (how quickly someone come blow air out of their lungs) obviously misses many other aspects of these conditions including the symptoms that impact people on a day to day basis.
In the clinic, we come across many different disease traits, for example
- Wheeze/airflow obstruction
- Cough, either daytime or disturbing sleep overnight
- Sputum production, either intermittent or continuous
- Frequent "exacerbations" or flare ups of symptoms
- Structural changes in the lungs seen on CT scans
- Persistent breathlessness and exercise intolerance
- Association of symptoms with exposures at work or elsewhere
Why was it important to do this systematic review?
People may experience any of these and other traits regardless of whether their "official" label is asthma or COPD (or something else). Identifying the traits present in a particular individual at a particular time is what the pragmatic physician does to help agree a personalised treatment plan with an individual patient. This presents a problem for someone trying to be "evidence based" as trials have mostly lumped participants into broad but heterogenous groups based on diagnostic labels.
Why is this review important for people living with COPD and the clinicians treating them?
We've tried in this review to look at what are considered "asthma" treatments (anti IL5 drugs) in individuals with COPD who nonetheless may have traits that might respond to these drugs. We'd planned specific subgroup analyses looking at those with raised levels of particular biomarkers such as peripheral blood eosinophil counts that might define certain traits. The included trials were somewhat of a disappointment, mostly taking all comers rather than targeting groups who theoretically might respond. These were "lumper" trials, looking for(and on the whole failing to find) a modest benefit in a whole population. As you might have gathered, I think we need to split these groups down and personalise our treatments.
What can people living with COPD and clinicians treating them take from this evidence?
Should people living with COPD or their clinicians be racing to start anti-IL5 drugs? No. However this is hopefully just a start. In the future, I'd like to see a person with an airways disease (be it labelled asthma or COPD) be able to choose the evidence based treatments that work for their particular set of problems and avoid the therapies that aren't relevant to their manifesting disease traits. There is clearly a challenge to us systematic reviewers. How do we collect evidence when the diagnostic labels used in trials don't capture the breadth of the experience of those living with the conditions?
Today, the COVID-19 Recommendations Map launches, offering policymakers, healthcare practitioners, researchers and the general public - anywhere in the world - a comprehensive catalogue of critically appraised evidence.
This global collaborative effort from Cochrane Canada, McMaster University’s WHO Collaborating Centre for Infectious Diseases and an international consortium of researchers spanning six continents have developed this living map of the latest evidence-based recommendations for the prevention and care of COVID-19.
The project brought together Cochrane groups from across the world including Cochrane Germany, Cochrane Canada, Cochrane South Africa, and Cochrane Iberoamerica.
“The fast-evolving COVID-19 pandemic has thrown up the challenge of rapidly developing, appraising, disseminating and updating multiple guidelines. To meet this challenge, the international team we have assembled will provide evidence-based recommendations that can be accessed by anyone and applied in virtually any setting across the globe.”
Supporting healthcare decision-making in Canada and around the world, especially when time is of the essence, is the primary goal of Cochrane Canada and its many partners on this project, said Cochrane Canada’s Managing Director, Dr. Adrienne Stevens.
“Collectively, we have mobilized quickly to get this work underway. Our hope is that by providing access to these recommendations and their underlying evidence, we are reducing waste in research by capitalizing on efforts already put forth. Knowing what exists can also help inform decisions on what additional guidelines should be undertaken, effectively steering the use of research dollars on COVID-19.”
Funding for the living map was provided by the Canadian Institutes of Health Research (CIHR).
Members of the public, health professionals and researchers know that there is ‘information overload’ about the COVID-19 pandemic, with lots of mistrust and misinformation. Cochrane US wanted to help people find trustworthy evidence about COVID-19 in the US by leveraging the strengths of the members of the new US Network.
Cochrane US created a comprehensive online repository to share COVID-19 research, projects and guidelines from trustworthy sources. This is a living resource that they add to and update in real-time and offer free on their website. They also included videos about systematic reviews, Plain Language Summaries of evidence, and other easy-to-understand resources.
Read more about the work that Cochrane US did to address information needs during the COVID-19 pandemic in this short case story.
Research about COVID-19 is growing fast during the pandemic. Healthcare professionals, journalists, policy-makers and people with an interest wanted simple summaries of the latest evidence in Portuguese to help inform their decisions.
To meet this need, Cochrane Portugal produced regular newsletters in the Portuguese language. They included short summaries about new COVID-19 research from around the world and shared the newsletters through their mailing list and on their website.
People are busy so they made sure that every newsletter was not longer than one page and took less than seven minutes to read. They focused on high-quality studies that were relevant in clinical practice and wrote the newsletters in a non-technical way so they could be used by people who were not doctors. Newsletters were sent out twice a week.
Cochrane Portugal received funding from the Institute for Evidence Based Healthcare at the University of Lisbon School of Medicine.
Published on the Cochrane Library is a new editorial, 'COVID‐19: working together and making a difference for decision‐makers'. The editorial outlines Cochrane's agile response to the situation and the many lessons learned.
It also introduces the special supplement to the 'Collaborating in response to COVID‐19: editorial and methods initiatives across Cochrane.' The The supplement collects examples of initiatives for coordinating and preparing for evidence synthesis, facilitating and developing methods for evidence synthesis, organizing collaborative approaches for evidence synthesis and publication, and ensuring evidence informs guidelines and practice.
- Read the Cochrane Library Editorial
- Read the Cochrane Library Supplement
- Read the Cochrane vs. COVID-19 case studies
- Read all the Cochrane resources and news on COVID-19
Thursday, December 10, 2020
Cochrane has expanded its response to COVID-19 by publishing two rapid scoping reviews about care bundles in the intensive care unit (ICU) and measures implemented in schools to contain the SARS-CoV-2 virus. Both reviews were commissioned by the World Health Organisation to inform their guidance. The reviews serve as exemplars for how similar research could be published by Cochrane beyond the pandemic.
Cochrane does not ordinarily publish scoping reviews, which differ from systematic reviews in important ways. Rather than summarise the results of studies to assess the effect of an intervention or accuracy of a diagnostic test, the purpose of a scoping review is to identify the amount and type of evidence relating to a given topic. Scoping reviews can play an important role for researchers and decision makers by mapping and characterizing an evidence base to highlight gaps or inform the design of a further systematic review.
Scoping reviews follow many of the same steps of a systematic review including pre-specification of methods, and a systematic approach to identify, sift and present the evidence. They generally have a broader scope than a systematic review and, given that the objective is not to assess effectiveness or safety, there is usually no critical appraisal of studies, synthesis of their outcome data, or application of established GRADE methods.
The reviews followed a set of interim recommendations set by the Cochrane Editorial and Methods Department (EMD), which were based on existing conduct and reporting standards and guidance.[refs 1,2,3] Areas for development have been highlighted that would be needed to ensure quality and consistency on a wider scale, but the reviews serve as an important proof of concept that we hope to build upon in the future to continue meeting the diverse needs of stakeholders.
Declan Devane, Director of Cochrane Ireland and one of the authors of the ICU care bundles scoping review commented “I think it critical that Cochrane respond to the evidence synthesis needs of health decision makers. Like much of the recent COVID-19 evidence response, this scoping review was only possible in the time available because of the commitment of a team of clinicians and methodologists who were supported flexibly and iteratively by Cochrane. Processes were adapted and flexed to meet commissioners needs resulting in a good experience for all concerned. The learning from our experience will help inform future scoping review processes. I believe firmly that the relevance and value of Cochrane will depend on its ability to respond innovatively, and promptly, to decision-maker needs. This is another example that shows we can.”
A range of initiatives are underway to reflect on what has been achieved by the Cochrane community during the pandemic, including the Cochrane COVID-19 supplement that published this week. The Central Executive Team is considering whether and how new review and article types should be pursued beyond the pandemic situation to meet user needs and accommodate innovation in evidence synthesis. A web-based survey will be circulated in January to invite Cochrane staff and members to share their views.
- PRISMA extension for Scoping Reviews explanatory paper (Tricco, AC, Lillie, E, Zarin, W, O'Brien, KK, Colquhoun, H, Levac, D, Moher, D, Peters, MD, Horsley, T, Weeks, L, Hempel, S et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018,169(7):467-473.)
- JBI Manual for Evidence Synthesis. Chapter 11: Scoping Reviews (Peters MDJ, Godfrey C, McInerney P, Munn Z, Tricco AC, Khalil, H. Chapter 11: Scoping Reviews (2020 version). In: Aromataris E, Munn Z (Editors). JBI Manual for Evidence Synthesis, JBI, 2020.)
- Lockwood et al 2019 practical guidance (Lockwood C, Borgess dos Santos K, Pap R. Practical guidance for knowledge synthesis: scoping review methods. Asian Nursing Research. 2019,13(5):287-94.)
People experiencing homelessness are more likely to use tobacco, and face many problems that make it difficult for them to quit. Health problems caused by using tobacco are among the leading causes of death among this group of people, so there is a need to find new ways to reduce tobacco use in people experiencing homelessness. Healthcare guidance says that treatment to quit tobacco smoking should include some form of counseling or support, plus medicines designed to help people stop smoking. However, this treatment is often not provided or used among people experiencing homelessness. This review looked at whether systems designed to help adults experiencing homelessness to get treatments to quit tobacco, and treatments designed to help adults experiencing homelessness to quit tobacco lead to more use of treatments and more people quitting tobacco use. The authors also looked at whether treatments to help adults experiencing homelessness to quit tobacco changed their use of other drugs and their mental health
The study included 10 studies involving 1634 participants. One of these studies is still being carried out, but the other nine have been completed. All participants were tobacco smokers, aged 18 years or older, and had experienced homelessness. Most participants were recruited from places within the community, such as homeless shelters, but some were also recruited from healthcare clinics. All studies offered participants some form of counseling support to quit smoking, and eight of these studies also offered stop‐smoking medicines. The treatments tested in the included studies were: e‐cigarettes, text‐message support, rewards for stopping smoking, more intensive counseling support, treatments focused on other lifestyle challenges plus smoking, and cognitive behavioral therapy. The evidence is up to date to January 2020.
There was not enough information to decide whether stop‐smoking treatments targeted specifically at people experiencing homelessness made them more likely to quit smoking than standard treatment to stop smoking. There was also not enough information to determine whether these treatments affected the mental health or drug use of people experiencing homelessness.
Quality of evidence
The authors judged all of the information included in this review to be either of low or of very low quality. This is because the studies included in this review were small, and there were problems with how some of the included studies were carried out. This means it is difficult to know whether these interventions help people who experience homelessness to quit smoking. The findings of this review are very likely to change as new studies are completed.
Featured Review: Antenatal corticosteroids for accelerating fetal lung maturation in women at risk of preterm birth
The Cochrane review about antenatal steroids in reducing risk of infant mortality and morbidity is an important one in Cochrane's history. Cochrane's logo is based on the forest plot from the original publication in 1982. This review has recently been updated and lead author, Fiona Stewart, tells us how the logo might look now, base on the current data.
What does this update tell us?
Our overall findings can be summed up like this: antenatal steroids given to women at risk of preterm birth reduce the risk of infant mortality and morbidity. In other words, babies are more likely to survive and less likely to have serious illness, such as respiratory distress syndrome and intraventricular haemorrhage (bleeding in the brain). The evidence also suggests that there is probably little risk of death or infection in the mothers who receive the steroids.
What is different to the last version?
In the last version of the review, the authors identified a distinct lack of evidence from low- and middle-resource countries. Since then the World Health Organisation has organised two large randomised controlled trials to address precisely this gap and one of those trials is now included in this latest update. This means we now have a much better idea of the benefits and risks of antenatal corticosteroids in a wide range of settings where there are different levels of healthcare service provision.
Another important difference from the last version is that we have taken into account the trustworthiness of the evidence, in addition to the standard methods that we use to assess risk of bias and to rate the overall certainty of evidence. We used a set of criteria, developed by the Cochrane Pregnancy and Childbirth group, to assess whether each trial in the review can demonstrate its trustworthiness in terms of research governance and feasibility of results. Where we had concerns about a trial’s trustworthiness we contacted the study authors for further information. Where our concerns were not resolved or where we did not receive any response, we did not include those trials in our analysis.
The Cochrane logo is based on the forest plot of the first publication of this review. Each horizontal line represents the results of one study, while the diamond represents the combined result - our best estimate of whether the treatment is effective or harmful. The diamond sits clearly to the left of the vertical line representing “no difference”; therefore the evidence indicates that the treatment is beneficial. Would this update to the review change the forest plot that the logo is based on?
The Cochrane logo represents what the forest plot would have looked like in 1982, had a meta-analysis been carried out using the trial evidence that was available at the time for the outcome of neonatal mortality. Now, decades later, we have substantially more evidence and if the logo was created from scratch now we wouldn’t be able to fit enough horizontal lines in it to illustrate the number of trials we now have included in the analysis! Most importantly, the diamond at the bottom would still be in the same place because the analysis in the logo and the analysis in our update both show that antenatal steroids reduce the risk of neonatal death compared to placebo or no treatment.
What can clinicians/and or mothers take from this evidence?
Clinicians and mothers can be confident that there is high-certainty evidence to support the use of antenatal steroids for women at risk of preterm birth, no matter where you are in the world since the evidence is consistent across high-, middle- and lower-resource settings. The evidence also demonstrated that giving antenatal steroids to mum is safe and does not result in any long-term harm to their babies. However it is important that they are only given to women considered at high risk of preterm birth because appropriate timing is very important to ensure maximum benefit.
Will this review be updated again?
Yes, the review will be updated to include the results of trials that are still ongoing. There are still a few remaining questions; firstly, whether antenatal steroids have the same benefits in different gestational age ranges. The majority of the evidence in the review comes from trials where the women were very preterm (approximately 28-34 weeks). We would like to know if the effect of corticosteroids compared with placebo is similar at the later preterm period (approximately 34-36 weeks). We know of at least one large trial – ACTION-II, organised by the WHO – which is investigating antenatal corticosteroids compared with placebo in women at 34-36 weeks. We anticipate being able to include the results from that trial, and four smaller trials that are ongoing, in another update in a year or so. Secondly, we are interested in the effects of antenatal steroids in particular groups for whom there is currently limited evidence; for instance, women with medical problems in pregnancy such as diabetes, or women who are carrying more than one child.
Wearing Cochrane evidence: a personal story of impact
Rebecca Selby, a mum of four, shares how this Cochrane Review has impacted her family.
- Read the updated review
- Learn more about Cochrane Pregnancy and Childbirth
- Read a personal impact story: “Wearing Cochrane evidence”
- Watch “What is a Systematic Review?”
- Read about the history and meaning of the Cochrane logo
New Cochrane Systematic Review shows that knee replacement surgery using a tourniquet increases the risk of serious complications, and causes additional pain after surgery
What are the benefits and risks of using a tourniquet in knee replacement surgery?
Senior author Mr Peter Wall, Consultant Orthopaedic Surgeon from Warwick Clinical Trials Unit and University Hospitals Coventry and Warwickshire NHS Trust, summarized:
The evidence indicates that knee replacement surgery performed with a tourniquet increases the risk of serious complications needing additional healthcare, many of which might be avoided if a tourniquet is not used. Most people do very well after knee replacement, but like any major surgery, there are risks and use of a tourniquet may exacerbate these.
Why is this question important?
Knee replacement is a common operation that involves replacing a damaged, worn, or diseased knee with an artificial joint made of metal and plastic. Most surgeons prefer to carry out knee replacement surgery with the aid of a tourniquet ‐ a tight band placed around the thigh that restricts blood flow to the knee. Potential benefits of using a tourniquet include limiting blood loss during surgery and making it easier to conduct the operation. However, a tourniquet may increase the risk of pain and complications for patients after surgery.
How did the authors identify and evaluate the evidence?
First, they searched for relevant, robust studies in the medical literature. They then compared the results and summarised the evidence from all studies. Finally, they assessed how certain the evidence was. To do this, they considered factors such as the way studies were conducted, study size, and consistency of findings across studies. Based on these assessments, they categorised the evidence as being of very low, low, moderate, or high certainty.
What did they find?
They found 41 studies that involved 2819 people (944 men and 1777 women) who were randomly assigned to have surgery with a tourniquet, or surgery without. This type of study, known as a randomised controlled trial, provides the most robust evidence about the effects of a treatment.
Studies were conducted in hospitals in Australia, Asia, Europe, and the USA. Each study involved between 20 and 166 people who were between 58 and 84 years of age. They were followed for between one day and two years after surgery.
Five studies were publicly funded, and one study received funding from a medical equipment manufacturing company. The other 35 studies did not receive specific funding or did not state who funded them.
The studies provided low to moderate evidence that:
- Pain on the first day after surgery is probably worse with a tourniquet. On average, on a scale of 0 to 10 (higher scores = worse pain), people operated on with a tourniquet rated their pain as 5.81. People operated on without a tourniquet rated their pain as 4.56 (average difference: 1.25 points);
- Knee function one year after surgery is probably similar with or without a tourniquet. On average, on a scale of 0 to 100 (higher scores = better functioning), people operated on with a tourniquet rated their knee function as 89.74. People operated on without a tourniquet rated their knee function as 90.03 (average difference: 0.29 points);
- Satisfaction with treatment may be similar with or without a tourniquet. Six months after the operation, 94% of people operated on with or without a tourniquet were 'extremely' or 'very' satisfied with their treatment;
- There may be little or no difference in health‐related quality of life with or without a tourniquet. On average, on a scale of 0 to 100 (higher scores = better quality of life), people operated on with a tourniquet rated their quality of life as 54.64. People who had surgery without a tourniquet rated their quality of life as 56.17 (average difference: 1.53 points); and
- Serious adverse events such as blood clots in the leg or lung, infection, or re‐operation other than to replace the artificial joint are probably more likely to occur with a tourniquet. Five per cent of people operated on with a tourniquet reported serious adverse events compared to 2.9% of people operated on without a tourniquet.
We do not know if using a tourniquet affects chances of needing a second operation to replace an artificial joint because available evidence is of very low certainty.
No studies investigated the effects of surgery with a tourniquet on people’s ability to process thoughts (cognitive function).
What does this mean?
Knee replacement with a tourniquet is probably slightly less beneficial, and is associated with greater risks, than surgery without a tourniquet.
How up‐to‐date is this review?
Evidence in this Cochrane Review is current to March 2020.
Featured Review: Helping families secure a step‐up to emergency care for patients with a life-threatening condition
A life‐threatening condition is a medical emergency. The faster a person secures the right medical care, the better their chances of surviving. When patients and their families know the signs of a life‐threatening medical emergency and how best to communicate concerns around a deterioration in health, they can act quickly to seek emergency care and work with staff to ensure a timely response.
Increasing patient and family involvement
Education and coaching are available to help patients and their families, and healthcare professionals work together to make sure patients and families can secure emergency care when needed. These strategies focus on:
- helping patients and their families to notice changes in a patient's condition and tell healthcare staff about them;
- empowering patients and families to feel confident about arranging for urgent or emergency care;
- healthcare staff giving patients and families a chance to talk about their concerns, and actively listening to them during an emergency consultation; and
- training healthcare staff to respond appropriately when patients and their families raise concerns about a patient's condition.
Why we did this Cochrane Review
We wanted to find out if education and coaching strategies could help patients and families to recognise when changes in a health condition are life‑threatening and act to help secure emergency care.
What did we do?
We searched for studies that tested strategies to involve and empower patients and their families in seeking emergency care for a life‐threatening medical condition. We also included studies where the strategy included a component targeted at enabling staff response.
We looked for studies in which the strategies people received were decided at random. This type of study usually gives the most reliable evidence about the effects of a strategy.
Search date: we included evidence published up to 21 October 2019.
What we found
We found nine relevant studies in different healthcare settings in which 436,684 patients and family members took part. Seven of the strategies studied involved face‐to‐face education or coaching sessions for patients and families, and two involved education programmes aimed at healthcare staff as well as patients and their families. All strategies had an educational part and an engagement part (for example, self‐monitoring; using action plans); two strategies additionally focused on communication skills and using shared language.
All studies compared usual care against receiving strategies to increase involvement of patients and their families in seeking emergency care. In four studies, people in the usual care group also received information or educational strategies. The studies varied in design and in their assessments, making it difficult to compare all their results.
We did not find any studies that looked at patients', or their families', satisfaction with care, or what they thought of their involvement in seeking emergency care.
What are the results of our review?
Compared with usual care, strategies to improve involvement in securing emergency care:
- may help patients and their families to know which danger signs to look for, and to know the right action to take (4 studies; 3086 people);
- probably have little to no effect on stillbirth in pregnancy (1 study; 409,175 people); and
- probably do not increase anxiety levels in patients and their families (1 study; 2,597 people).
We are uncertain if the strategies affected:
- peoples' confidence in recognising and reporting worsening in a health condition (2 studies; 217 people); or
- the time between the start of life‐threatening symptoms and receiving emergency treatment (4 studies; 27,023 people).
Our confidence in our results
We are moderately confident about the effect of the strategies on anxiety levels and on stillbirth, although these results might change with further evidence. We are less confident about our other findings, which are likely to change with further evidence. Some of the studies we compared had small numbers of people taking part, so their results may have been unreliable.
Strategies to help patients and their families to secure emergency care may improve their knowledge about life‐threatening conditions, and probably don't increase their anxiety more than usual care
Early in the COVID-19 pandemic, primary care doctors (general practitioners) and nurses had many questions. Cochrane Belgium wanted to create clear answers to primary care clinicians’ most frequent questions about COVID-19, based on scientific evidence, making the answers relevant to Belgium.
A university collected questions that were relevant to primary care in Belgium. Masters students studying medicine worked in pairs to draft answers in the Dutch language. Cochrane Belgium checked and validated each of these rapid answers to make sure they were accurate, consistent and evidence-based. They also developed criteria to assess each of the answers.
Author interview: the role of cognitive behavioural therapy for anxiety disorders in children and adolescents
In this short interview, Postdoctoral Researcher and lead author Tessa Reardon tells us about this recently published review.
What does this Cochrane review tell us about the role of cognitive behavioural therapy for anxiety disorders in children and adolescents?
Our review shows the key role cognitive behaviour therapy (CBT) plays in the treatment of anxiety disorders in children and adolescents. CBT is the most frequently evaluated treatment for these disorders. Indeed, this review includes 88 studies which is more than twice as many studies as the previous Cochrane review on this topic. Encouragingly, our findings reinforce previous conclusions that CBT is more effective than no treatment for anxiety disorders in children and adolescents. We didn’t find evidence that CBT is superior to alternative treatments, but few studies have compared CBT to alternative treatments so we are still not sure about this. The review also tells us most about the short-term benefits of CBT, and we still know relatively little about the extent to which these benefits continue in the medium to longer term.
What can CBT practitioners take from this evidence?
CBT practitioners can be reassured by the evidence of an advantage of CBT compared to waiting lists and no treatment. CBT can be provided in a range of different ways, for example, practitioners can work one-to-one with children, deliver group sessions, work with parents, deliver brief or longer treatments. Importantly, we did not find clear evidence that one way of providing CBT is more effective than another. A particular challenge facing practitioners and services is the very limited access to CBT for children and adolescents with anxiety disorders, and our findings suggest that practitioners can deliver relatively brief CBT interventions, without a negative impact on short-term outcomes.
Nevertheless, CBT practitioners cannot be complacent. This review suggests that about half of children and adolescents will recover from their primary anxiety disorder following a CBT intervention and this means that the other half do not recover. As researchers, we now need to focus on identifying how we can improve these recovery rates and what these children and young people who do not benefit from current CBT interventions need.
What can parents/carers of children and adolescents with anxiety disorders learn from this review?
Parents and carers can also be reassured that lots of studies have now evaluated CBT, and this review shows that CBT works well for many children and young people with anxiety disorders. However, it is equally important that parents and carers are aware that not all children and adolescents benefit from CBT, and some may need alternative support.
The extent to which parents are involved in CBT programmes for children and adolescents varies considerably – from little to no involvement, through to parent-led approaches where therapists support parents to apply CBT skills and strategies in their child’s daily life. We did not find evidence that one way of providing CBT is consistently better than another, but, not surprisingly, the parent-led approach has typically been tested with primary and preschool aged children, rather than teenagers.
The global pandemic has bought about concerns about increasing anxiety among children and adolescents - what can this review tell us about the role of CBT as treatment during this time?
Before the pandemic, anxiety disorders were common among children and adolescents, with concerns about increasing prevalence rates, particularly among adolescents. The pandemic has increased these concerns even further. Before the pandemic, we also knew that only a small minority of children and adolescents with anxiety disorders were accessing CBT, and the pandemic will have meant that even fewer children who may benefit from CBT are receiving it. Maximising the efficiency of CBT delivery is more important than ever to help ensure that children and adolescents can access effective treatment when they need it. Reducing the amount of therapist contact time involved in treatment and online delivery are both ways to potentially improve treatment efficiency. Encouragingly, this review indicates that CBT involving less than 10 hours of clinical contact can achieve similar outcomes to much longer treatments. Online delivery was beyond the scope of this review, but there is growing evidence that online CBT is also effective for children and adolescents with anxiety disorders.
It is with the deepest disappointment that we must confirm that as a result of the continued global spread and impact of COVID-19 (Coronavirus), we have taken the decision to cancel the Global Evidence Summit (GES 2), due to be hosted in Prague between 5-8 October 2021.
The Global Organizing Committee (comprising four partners: Cochrane, JBI, GIN and Campbell) concluded, with the agreement of our local host - CEBHC-KT and Masaryk University, that the most appropriate decision is to cancel the Summit in Prague in its entirety for 2021 and postpone it until 2 – 6 October 2023.
As global leaders in evidence-informed healthcare, the partners take very seriously our responsibility and duty of care to our communities in the face of continuing risks associated with the spread of the coronavirus for the foreseeable future.
However, we are committed to working together, along with additional organizations to present the second annual World EBHC Day on the 20 October, 2021. This 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. The inaugural World EBHC Day that took place on 20 October 2020 was a great success. The intention for 2021 is to build on this year’s work and continue to celebrate the impact of individuals and organizations worldwide, recognizing the work of dedicated researchers, policymakers and health professionals in improving health outcomes.
Thursday, November 26, 2020
The cancellation of the second Global Evidence Summit is extremely disappointing news for all of us and we would like to thank the huge amount of people, including our local hosts, who have been working so hard on the preparations. We are in no doubt that we will be able to build successfully on the work accomplished so far to ensure that when GES 2 does go ahead in October 2023 in Prague it will be everything we anticipated: a world-class scientific event and a memorable gathering of the evidence-based medicine community in the historical capital of Bohemia.
We thank you for your ongoing support and commitment to the Global Evidence Summit and will look forward to meeting again for this unique event in 2023.
We hope that you all remain safe and well during these extraordinary times.
With our very best wishes,
Director, CEBHC-KT (Czech Cochrane, JBI and GRADE centres), Chair of the GES Scientific Committee and Local Organizing Committee
Executive Director, Joanna Briggs Institute
CEO, Guidelines International Network
CEO, The Campbell Collaboration
Cochrane Library Editor in Chief to present at Brigham and Women's Hospital Surgical Grand Rounds on 2 December
Dr. Karla Soares-Weiser, Editor in Chief of the Cochrane Library, will present at Brigham and Women's Hospital Surgical Grand Rounds on December 2, 2020, as part of the Professional Fulfillment Virtual Series. In the presentation, titled "Leadership, systematic reviews, and COVID: An international perspective", Dr. Soares-Weiser will reflect on her professional trajectory, Cochrane and its mission, and how Cochrane has confronted the COVID-19 pandemic.
All are welcome to join this presentation on December 2, 2020 from 8:15-9:15 am EST (check the time in your time zone). Please click the following link to access the Grand Rounds webinar: https://partners.zoom.us/j/81328907313Thursday, November 26, 2020
On 26th November 2020, the World Health Organization (WHO) launched their guidelines on physical activity and sedentary behaviour. This Special Collection curated by the Cochrane Campbell Global Ageing Partnership includes associated relevant topics addressing healthy ageing, aligning with the concerted global action of the Decade of Healthy Ageing (2020 to 2030). The WHO defines healthy ageing as “the process of developing and maintaining the functional ability that enables wellbeing in older age”. Functional ability includes people meeting their basic needs, being mobile, continuously learning and growing, building and maintaining relationships, and participating in society.
Older age can be accompanied by a greater risk of developing chronic non-communicable diseases, and associated functional limitations. People aged 60 years old and over account for nearly 25% of the disease burden arising from these conditions. However, being free of disease or health conditions is not a requirement for healthy ageing and many older adults have health conditions that can be well managed and therefore have little impact on their quality of life.
Physical activity plays a critical role in promoting healthy ageing, and evidence from epidemiological studies has determined that it is strongly associated with healthier ageing. Regular and adequate levels of physical activity have multiple health and wellbeing benefits and can prevent, or even reverse, some effects of chronic conditions across a lifespan. Popular ways to be active are through walking, cycling, dancing, and engaging in hobbies. Any other physical activity that is performed during leisure time, or during work, can have also have health benefits.
This years’ United Nations International Day of Older Persons focused on how the COVID-19 pandemic affects how ageing is addressed. The impact of quarantine, often in isolation, at home will have a substantial deconditioning effect, affecting millions of older people. Physical inactivity has been shown to be associated with noncommunicable diseases and higher mortality, and activity is now more important than ever, given COVID-19 restrictions.
This Special Collection brings together a selection of Cochrane Reviews assessing the benefits of physical activity interventions on activity levels, physical function, and symptoms. The reviews synthesize evidence regarding the general population, or groups of people who have specific health conditions. A future Special Collection will focus on specific exercise interventions.
China was the first country to identify COVID-19, but people didn’t know much about the virus in the early stages of the pandemic. To address this need for information, Cochrane China used the mobile telephone social media app WeChat to find out what doctors, nurses and members of the public wanted to know about COVID-19 and to share evidence with them.
Specifically, Cochrane China used WeChat to: advertise a survey to find out what doctors and nurses wanted to know about preventing and treating COVID-19, to invite volunteers to help them find evidence and translate it, and to keep in touch with people who were interested in their ongoing work.
- Learn more about what Cochrane China achieved by harnessing the power of social media during a pandemic, and what they learned in the process in this short case study.
Cochrane First Aid vs COVID-19: Making sure COVID-19 evidence is available in people’s preferred language
Cochrane published a rapid review about whether cleaning hands with ash reduces the spread of COVID-19 and other infectious diseases in areas where soap is not widely available. It was important to get this evidence out widely, so Cochrane First Aid translated the rapid review findings into six languages.
Cochrane First Aid worked with volunteers, and partnered with a number of organizations, to help to share evidence about handwashing with ash with lay people who educate the public in low-income countries. They also created a Blogshot (short visual summary) and used social media and their newsletter to share this review with a wide audience.
- Learn more about how Cochrane First Aid made sure this evidence was available to people in their preferred language in this short case study.