Key messages

• Early treatment of meticillin-resistant Staphylococcus aureus (MRSA) (a type of bacteria which are resistant to some antibiotics) infection in people with cystic fibrosis (CF) seems possible, but we are unsure about the effectiveness of current routine treatment.

• Longer-term implications of treatment are not clear.

• Research is needed to assess MRSA infection and treatment in the age of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (drugs that fix the broken protein made by the CF gene so salt and water can move correctly across cells and help move mucus from the lungs).

What is cystic fibrosis (CF)?

CF is an inherited condition which causes thick mucus to build up in the lungs and other organs. It is very difficult for people with CF to cough up this thick mucus, making it an ideal breeding ground for germs (including MRSA), and making them more prone to chest infections. CF worsens over time. Although there is currently no cure, many people with CF can lead active and full lives.

What is MRSA and how is it treated?

MRSA (meticillin-resistant Staphyloccocus aureus) are bacteria which cause infection that is treated with antibiotics. However, MRSA are resistant to some types of antibiotics, making the infection hard to treat. They are sometimes called 'superbugs' and infection with MRSA is particularly worrying for people with CF, as it is thought that MRSA can cause more damage than other bacteria which are not resistant to antibiotics.

MRSA is usually treated with a combination of antibiotics, taken orally (by mouth) or inhaled, alongside decontamination treatment (antibiotic creams applied to the skin and nasal cavities).

What did we want to find out?

We wanted to know whether treatment with antibiotics:

• can get rid of MRSA infection in the lungs of children or adults with CF;

• does not cause infection with other resistant bacteria;

• does not cause unwanted effects.

What did we do?

We looked for studies that investigated antibiotics (oral or inhaled) to treat MRSA infections in people with CF.

• Studies had to compare antibiotic treatment with either no treatment, placebo (sham treatment) or other type of antibiotics.

• People had to have CF and current infection with MRSA.

What did we find?

We found five studies which recruited 410 people with CF and a diagnosed MRSA infection. Studies took place in Italy or North America and lasted from eight weeks to six months. People in the studies (equal numbers of males and females) were young (average age ranged from 11 to 25 years).

Oral antibiotics compared to no treatment (2 studies, 106 people)

One group of people with CF were treated with oral antibiotics (trimethoprim, sulfamethoxazole and rifampicin or co-trimoxazole and rifampicin), plus decontamination treatment; the other group received no treatment.

• Oral antibiotics may clear MRSA. One trial stopped early due to clear benefits of antibiotics, but some people cleared the infection with no treatment. In six months, there was no difference between groups in the number of people who still had MRSA.

• Antibiotics may increase lung function.

• There may be little to no difference between groups in quality of life, frequency of flare-ups of the disease (although one study reported fewer people taking antibiotics were admitted to hospital in the first six months), unwanted effects of treatment, or changes in weight.

Inhaled antibiotics compared to placebo (2 studies, 251 people)

Both studies compared a standard dose of vancomycin (an inhaled antibiotic) to placebo (a dummy drug) and one study also compared a standard dose of vancomycin to a high dose.

• Inhaled antibiotics probably make no difference to lung function compared to placebo (2 studies), but results from one study indicated that inhaled antibiotics probably lead to a small increase after 20 weeks.

• A standard dose of vancomycin probably makes no difference to the frequency of flare-ups compared to placebo (2 studies);

• One study reported a longer time to the next flare-up with the lower dose of vancomycin;

• One study reported a decrease in MRSA bacteria levels with a higher dose of vancomycin for up to one month;

• Neither study reported any differences in quality of life or unwanted effects.

Oral plus inhaled antibiotics compared to oral antibiotics plus placebo (1 study, 25 people)

One study compared a combination of oral plus inhaled antibiotics to inhaled antibiotics plus placebo.

• We are uncertain if either treatment made any difference to MRSA clearance;

• There may be few or no differences between groups in lung function, quality of life or unwanted effects;

• The study did not report changes in weight or frequency of flare-ups.

What are the limitations of the evidence?

Our confidence in the results ranged from high to very low. This was due to potential issues with the trial designs (people knew which treatment they were receiving), or because there were small numbers of people in each trial and many of them dropped out.

How up to date is this evidence?

This review updates our previous review published in 2022. The evidence is current to 28 April 2026.

Key messages

• Nicotine electronic cigarettes (e-cigarettes) can help people to stop smoking for at least six months. They work better than nicotine replacement therapy, and probably better than e-cigarettes without nicotine.

• E-cigarettes may work better than no support, or behavioural support alone, and may not be associated with serious unwanted effects.

• However, we still need more evidence, particularly about the effects of newer types of e-cigarettes that have better nicotine delivery than older types, as better nicotine delivery might help more people quit smoking.

What are e-cigarettes?

E-cigarettes or 'vapes' are handheld devices that work by heating a liquid that usually contains nicotine and flavourings. E-cigarettes allow users to inhale nicotine in a vapour rather than smoke. Because they do not burn tobacco, regulated e-cigarettes do not expose users to the same levels of chemicals that can cause diseases in people who smoke conventional cigarettes.

Using an e-cigarette is commonly known as 'vaping'. Many people use e-cigarettes to help them to stop smoking tobacco. Here we focus primarily on e-cigarettes containing nicotine.

What did we want to find out?

Stopping smoking lowers the risk of many diseases. Many people find it difficult to stop smoking. We wanted to find out if using e-cigarettes could help people to stop smoking, and if people using them for this purpose experience any unwanted effects.

What did we do?

We searched for studies that looked at the use of e-cigarettes for stopping smoking in people of any age.

We were interested in:

· how many people stopped smoking for at least six months; and

· how many people had unwanted effects, reported after at least one week of use.

What did we find?

We found 80 studies including 29,861 adults who smoked. Most studies took place in the USA (40 studies) and the UK (16). Most studies compared nicotine e-cigarettes with:

• nicotine replacement therapy (e.g. patches or gum);

• medicines to help people stop smoking (varenicline and cytisine);

• e-cigarettes without nicotine;

• heated tobacco (products that heat tobacco to a high enough temperature to release vapour, without burning it or producing smoke; these differ from e-cigarettes because they heat tobacco leaf/sheet);

• oral nicotine pouches (pouches that contain no tobacco but release nicotine when kept in the mouth);

• other types of nicotine-containing e-cigarettes (e.g. pod devices, newer devices);

• advice or counselling (behavioural support); or

• no support for stopping smoking.

What are the results of our review?

• More people stop smoking for at least six months with e-cigarettes than with nicotine replacement therapy (11 studies; 4114 people);

• People may be more likely to stop smoking for at least six months with e-cigarettes with nicotine than e-cigarettes without nicotine (7 studies, 1918 people);

• Nicotine e-cigarettes may help more people to stop smoking than behavioural support only or no support (11 studies, 7214 people);

• For every 100 people using nicotine e-cigarettes to stop smoking, 8 to 10 might successfully stop, compared with only 6 of 100 people using nicotine-replacement therapy, 6 of 100 using e-cigarettes without nicotine, or 5 of 100 people having no support or behavioural support only;

• We are uncertain if there is a difference between how many unwanted effects occur using nicotine e-cigarettes compared with nicotine replacement therapy, no support or behavioural support only (although non-serious unwanted effects were more common in groups receiving nicotine e-cigarettes compared to no support or only behavioural support);

• Studies comparing nicotine e-cigarettes to nicotine replacement therapy reported low numbers of unwanted effects, including serious unwanted effects. Compared to nicotine e-cigarettes, there is probably no difference in how many:

  • serious unwanted effects occur in people using nicotine replacement therapy;

  • non-serious unwanted effects occur in people using non-nicotine e-cigarettes.

What are the limitations of the evidence?

• We are confident in the evidence that nicotine e-cigarettes help more people to stop smoking than nicotine replacement therapy, but we need more evidence about e-cigarettes without nicotine.

• Studies comparing nicotine e-cigarettes with behavioural or no support also showed higher quit rates in people using nicotine e-cigarettes, but we are more uncertain of the data because the people in the studies were aware of each treatment they were getting.

• Most of our results for the unwanted effects could change when more evidence becomes available, as there were often few cases of effects reported with unclear results.

How up to date is the evidence?

This review updates our previous review published in 2025. We will update it again when new evidence becomes available. The evidence is up to date to 1 January 2026.

Key messages

• Taking blood from the umbilical cord or placenta instead of directly from babies born too soon (preterm) likely reduces retinopathy of prematurity, an eye disease that can affect vision, and may reduce complications such as brain bleeding (intraventricular hemorrhage) and bronchopulmonary dysplasia, a type of lung disease.

• We do not know if returning blood after testing or using strict rules to limit blood tests help to minimize blood sampling and the complications associated with it.

• We need large, high-quality studies that follow babies until they are at least three years old to better understand what methods work best and how they affect longer-term development. Future studies should investigate newer approaches, such as taking tiny amounts of blood for testing or using non-blood body fluids, such as saliva and urine, as well as the methods described here.

Why is minimizing blood sampling from babies born too early important?

Babies born before 37 weeks of pregnancy (known as 'preterm') often need many blood tests while they are in hospital. Because these babies are very small, repeated blood sampling can remove a large amount of their total blood volume. This can lead to the need for blood transfusions.

Several methods have been studied to reduce blood loss, such as using blood from the umbilical cord or placenta at birth, using very small blood samples, returning blood to the baby after testing, or following strict rules to limit how often blood is taken. It remains unclear which of these methods is effective and safe.

What did we want to find out?

We wanted to find out whether different strategies to reduce blood sampling in preterm babies:

• improves their survival;

• reduces physical or mental developmental issues, including blindness, deafness, and cerebral palsy (a lifelong condition that affects movement, posture, and muscle control), at 18 months of age and older;

• reduces serious complications, including retinopathy of prematurity (an eye disease that can affect vision), brain bleeding (intraventricular hemorrhage), and bronchopulmonary dysplasia, a type of lung disease.

What did we do?

We searched for studies that compared different blood-saving strategies with the usual care given to preterm babies. We compared and summarized the results of the studies and rated our confidence in the evidence, based on how the studies were designed and how many babies were involved.

What did we find?

We found five studies involving 365 very preterm babies (born more than three months before the due date). Two studies were conducted in India, two in the USA, and one in Israel. The smallest study included 20 babies, and the largest, 102.

One study received funding from the government, a charity telethon, and a technology company. The author of another study was also an owner of the company that made and supplied the blood-returning device used in the study. The three remaining studies either did not provide funding details or stated that there were no conflicts of interest.

Main results

None of the studies reported results for physical or mental developmental issues (including blindness, deafness, and cerebral palsy) when the babies were 18 months of age or older.

Using blood from the umbilical cord or placenta at birth, instead of taking blood directly from the baby:

• may reduce brain bleeding during the first week of life: about 12 fewer babies in every 100 may have severe brain bleeding (from 2 to 16 fewer babies; 2 studies, 160 babies);

• may reduce bronchopulmonary dysplasia: about 13 fewer babies in every 100 may develop this lung condition (from 25 fewer to 4 more babies; 2 studies, 152 babies);

• probably reduces retinopathy of prematurity requiring treatment before hospital discharge: about 19 fewer babies in every 100 are likely to develop retinopathy of prematurity (from 6 to 27 fewer babies; 2 studies, 152 babies).

We do not know if using blood from the umbilical cord or placenta improves babies' survival rates.

We also do not know if (1) devices that return blood into the baby's bloodstream after testing, or (2) following strict rules to limit blood sampling make any difference to:

• survival rates;

• serious complications (including retinopathy of prematurity, brain bleeding, and bronchopulmonary dysplasia).

Only one small study looked at each of these approaches.

What are the limitations of the evidence?

We are moderately confident that using umbilical cord or placenta blood significantly reduces the number of babies who develop retinopathy of prematurity – our confidence was reduced because relatively few babies were studied. We have little to no confidence in the evidence on survival and other serious complications (brain bleeding and bronchopulmonary dysplasia) because the studies were very small, and in some cases, the results varied.

We are not confident in the evidence for (1) devices that return blood into the baby's bloodstream and (2) following strict rules to limit blood sampling because:

• too few studies investigated these methods;

• the number of babies included was small;

• we had concerns about these studies' methods, reporting of results, or both.

How up to date is this evidence?

The evidence is current to September 2025.

Key messages

• Hearing aids probably cause a large improvement in the ability of adults with mild to moderate hearing loss to take part in everyday life and to listen to other people. They may slightly improve everyday health-related well-being but may make little to no difference to loneliness.

• It is unclear whether hearing aids result in a difference in working memory (the ability to hold information in your mind for a short time and act on it) or cause unwanted effects, such as pain or over-exposure to noise, as there was very limited evidence to help us answer this question.

• We need better and longer studies that report the effects of hearing aids separately for different age groups, sexes, levels of hearing loss, types of hearing aids, social and financial situations, and races and ethnicities.

What is mild to moderate hearing loss?

Hearing loss is very common, with most people affected having mild to moderate hearing loss.

• Mild hearing loss means soft sounds are harder to hear and may result in difficulties listening in noisy backgrounds.

• Moderate hearing loss means speech may not be clear and conversations can be difficult to hear, in quiet as well as noisy backgrounds.

The most common causes of hearing loss are ageing and noise exposure.

How is hearing loss managed?

Hearing aids are the most common technology used to help people with mild to moderate hearing loss and are in widespread use. Hearing aids make sounds louder and aim to make them clearer, so they are easier to hear. This is particularly important for hearing speech. The overall goal of hearing aids is to reduce the impact of hearing loss and improve a person's ability to take part in everyday life.

What did we want to find out?

We wanted to find out if hearing aids were better than other options, such as no hearing aids, placebo (dummy) hearing aids, or education programmes, to improve:

• a person's ability to take part in everyday situations;

• unwanted effects such as pain or those caused by over-exposure to noise;

• well-being related to general health, such as physical and social well-being;

• the ability to listen to other people;

• mental health – we were most interested in loneliness; and

• the ability to think, remember, and learn (cognition) – we were most interested in working memory (holding information in the mind for a short time and acting on it).

What did we do?

We searched for studies that looked at hearing aids for adults with mild to moderate hearing loss compared to other options. We compared and summarised the studies, and then rated our confidence in the evidence based on factors such as study methods, size and duration.

What did we find?

We found 16 studies involving 2261 adults with mild to moderate hearing loss. Their average age was between 58 and 83 years. The studies lasted between four weeks and three years and took place in the USA, Europe, Brazil, Hong Kong, and Australia.

• Hearing aids probably cause a large improvement in the ability of adults with mild to moderate hearing loss to take part in everyday situations (8 studies, 1683 people).

• It is unclear if hearing aids cause unwanted effects. Only one study reported two cases of people feeling pain or discomfort with hearing aids; no studies reported unwanted effects from over-exposure to noise.

• Hearing aids may slightly improve general well-being related to health (4 studies, 1558 people), and probably cause a large improvement in the ability to listen to other people (5 studies, 622 people).

• Hearing aids may result in little or no difference in loneliness (2 studies, 907 people).

• Their effects on working memory are unclear (3 studies, 910 people).

The evidence from this review supports the usual practice of offering hearing aids to adults with mild to moderate hearing loss who seek help for their hearing difficulties.

What are the limitations of the evidence?

There were several limitations. It is often difficult to hide whether someone is wearing hearing aids in a study as they are usually visible. This may affect the accuracy of the results. Studies of three months or less may not be long enough to measure the full range of effects from hearing aids. Some effects may only become evident over a longer period. Studies measured the effects of hearing aids differently, which made them difficult to compare.

How up to date is this review?

This is an update of a review first published in 2017. We last searched for evidence in August 2024. We also included published evidence from existing and ongoing studies up to 18 May 2026.

Key messages

• When a pregnant woman has been given the medicine oxytocin into a vein to start or progress labour, stopping the oxytocin once she is in active labour, rather than continuing oxytocin until the baby is delivered, may make little or no difference to whether a caesarean section (delivery through cut in the tummy) is needed, and it seems to be safe for both mother and baby.

• Stopping the oxytocin when active labour begins may help avoid excessive contractions and reduce unnecessary exposure to medication, but it may mean that labour lasts longer, although the result for duration of labour was very uncertain.

• Decisions about whether to continue or stop oxytocin should be discussed with healthcare professionals and take into account the clinical situation (including labour progress, contractions, current condition of woman and baby), the monitoring that is available, and the woman’s preferences.

What is oxytocin?

In pregnant women, when near the time to deliver their baby ('term', which is after 37 weeks of pregnancy), artificial oxytocin is a medicine that is used to start the womb (uterus) contractions needed for labour or to make them stronger. It is often given through a drip into a vein. Once active labour is established (which is when the cervix has opened (dilated) at least 4 cm and contractions are happening regularly), it is thought that the body produces enough natural oxytocin to keep labour progressing. Continuing to give artificial oxytocin once a woman is in active labour may make contractions too frequent or too strong, which may cause stress to the baby and potentially increase the likelihood of a woman needing to have a caesarean section (cut across the tummy to get the baby out).

What did we want to find out?

We wanted to know whether stopping oxytocin once labour is active decreases the risk of caesarean, and whether it has any benefits or harms for mothers or babies.

What did we do?

We looked for studies that compared the two approaches in women with a term singleton pregnancy (that is, one baby, not having twins or triplets) who were receiving oxytocin for induction or to speed up labour, so that we could find out whether it is better to:

• stop oxytocin once the active phase of labour begins, or

• continue oxytocin until birth?

We searched for evidence up to 17 November 2025. We combined study results where possible to give us the maximum information. We assessed how trustworthy each study is and how confident we can be in the results, based on factors such as the size of the studies, whether they were well designed and carried out, and how precise their results were.

What did we find?

We included nine studies involving 4814 women. The studies took place in hospitals in Denmark, France, India, Iran, Israel, Thailand, Turkey, and the USA. The studies used several different definitions of active labour.

Main results

Stopping oxytocin during the active phase of labour:

• may make little or no difference to the number of caesarean births (8 studies, 4710 women);

• makes little or no difference to the number of instrumental births (5 studies, 3776 women); and

• may reduce the risk of contractions that are too frequent or too strong (called uterine tachysystole or hyperstimulation) (3 studies, 1371 women); but

• labour was about 35 minutes longer on average when oxytocin was stopped, though this result was very uncertain (8 studies, 4141 women).

In addition, during the active phase of labour, there is:

• no clear difference between continuation and discontinuation of oxytocin for Apgar scores (a quick assessment of how well a baby is doing after birth) (5 studies, 2096 women);

• no clear difference between continuation and discontinuation of oxytocin for signs of reduced oxygen supply to the baby before birth, measured by testing the blood from the umbilical cord after birth (6 studies 4086 women); and

• probably little to no difference between continuation and discontinuation of oxytocin in admission to the neonatal unit (7 studies, 4606 women).

What are the limitations of the evidence?

The reliability of the evidence varied a lot. We were sure about the results for instrumental births, Agpar scores, and reduced oxygen supply to the baby before birth, and quite sure about the results for neonatal unit admission. We were a little unsure about the results for caesarean section and uterine hyperstimulation, and very unsure about the results for the duration of the active phase of labour. Some reasons for uncertainty were that:

• study participants knew which group they were in, that is, whether oxytocin was continued or stopped, and this may have affected the results;

• studies used different definitions for the measures they reported, such as the active phase of labour, uterine tacysystole, and uterine hyperstimulation; and

• how long the pregnant women were in labour varied across the studies.

How up to date is this evidence?

The evidence is up to date to 17 November 2025.

Key messages

• Vaccines are a well-researched method of preventing dengue. Most research focuses on whether the vaccines work and are safe. There is less information about how vaccines are offered to people and whether people's behaviour changes when they have been vaccinated.

• Other common areas of research are community education, such as teaching school children about mosquitoes, and changes to the environment, for example, removing areas where mosquitoes might live. Most of this research examines the effects of these methods on mosquitoes. Less research looks at the methods' effects on the spread of the disease.

• This evidence gap map highlights where evidence exists and where important critical gaps remain. Critical gaps include: understanding the type of people who were included in the studies; and how the various methods were used. We need more evidence in these areas to help people make decisions on preventing dengue.

What is dengue, and why is prevention important?

Dengue is a disease caused by a virus that is carried by a specific type of mosquito called 'Aedes'. Dengue spreads when these mosquitoes bite people. It causes flu-like symptoms, leading to more serious illness in about one in 20 people and sometimes even death. In 2023, there were over 6.5 million dengue cases and more than 7300 dengue-related deaths worldwide. Most people who get dengue live in low- and middle-income countries, where health systems may have few resources to prevent dengue. Dengue has spread recently, as a warming climate and changing rainfall patterns have created more areas in which mosquitoes can live.

What did we want to find out?

We wanted to find out what evidence about dengue prevention is available and where important gaps remain. Our goal was to map the evidence that is available for each method of preventing dengue, and see whether some methods and ways of measuring results have been studied more than others. This should tell us where to focus future research efforts to provide the right information for people working to prevent dengue. This evidence gap map does not aim to assess how well any method works.

What did we do?

We searched for evidence on dengue prevention. The evidence could be from ‘primary studies’, where new evidence is gathered directly from a source, for example by comparing two methods, or from ‘systematic reviews’, which combine and analyse the results from more than one primary study. We then mapped the evidence according to:

• the type of prevention method (for example, vaccines, community education, environmental management);

• what the evidence measured (effects on mosquitoes, spread of the disease, behavioural effects, how it was implemented, safety, costs);

• the study design; and

• the countries where the studies took place.

As our aim was to map the number and type of studies available, we did not assess how well the studies were designed and conducted, or how confident we could be in their results. However, where we found large reviews that summarised several studies, we rated our confidence in the evidence and assessed how useful the reviews could be for people making decisions about dengue control.

We asked doctors and people working to control dengue to help us:

• inform decisions about which prevention methods and measurements of impact to include;

• identify additional studies;

• ensure the gap map was usable and relevant; and

• prioritise gaps identified from the map.

What did we find?

We found 550 studies that took place in many different countries, mostly in low- and middle-income areas. We found that there were many more studies for some methods than others. The studies also measured different things. For example, some looked at the number of people getting dengue and some looked at changes in behaviour.

• Vaccines were a commonly researched method, with 99 studies and 4 reviews, mainly focusing on how well the vaccines worked and if they were safe.

• Other methods — particularly community education (187 studies) and environmental management (83 studies) — were mostly assessed by studies measuring effects on mosquitoes or changes in people's behaviour, with far fewer assessing dengue cases, severe disease, or implementation outcomes (these are measures relating to how much and how well a method is use).

• Very few of the studies about interventions other than vaccines measured harms or costs, limiting the relevance of the evidence for real-world programme planning.

• Useful evidence summaries were available for some methods but not for others. We found several reviews of some methods (e.g. vaccines) but other methods only had outdated or low-quality reviews, even though the methods had been tested in many research studies.

What are the limitations of the evidence?

The studies did not give much information about the types of people they included or how the different methods were used. This limits our ability to understand how well current research addresses unfair differences in the health of different groups of people (health inequities) and to support government decisions about dengue control in different parts of the world.

How up to date is this evidence?

The evidence is up to date to August 2025.

Key messages

• During an operation to widen one or both of the main blood vessels of the neck (carotid endarterectomy), there is probably little or no difference between the use of man-made (synthetic) and natural (biological) patches to close the repair in terms of the risk of stroke or death up to 80 months after the operation. There may be little or no difference between the patches in the risk of stroke on one side of the body (ipsilateral stroke), stroke of any type, or the blood vessel being blocked or narrowing again by more than half its width (arterial occlusion or re-stenosis greater than 50%) up to 80 months after the operation.

• The evidence is very uncertain about the effect of synthetic compared with biological patches on the risk of a stroke on one side of the body or a rupture of the artery (bleeding from the patch repair) during the operation or within 30 days, or a leak from artery repair causing a small blood-filled bulge (pseudoaneurysm formation) up to 80 months after the operation.

• Larger studies with longer follow-up are needed so that we can know for sure whether synthetic and biological patches have similar results, or whether one type is safer or more effective than the other.

What is carotid endarterectomy?

Carotid endarterectomy is an operation to remove fatty build-up from one or both of the main blood vessels (carotid arteries) in the neck. Fatty build-up can narrow the artery or block blood flow to the brain, causing a stroke. Removing it helps reduce this risk. After the artery is opened and cleaned, surgeons often sew in a patch to widen the artery and strengthen the repair.

What patches are used in carotid endarterectomy?

Patches can be made from natural (biological) materials, such as a vein from the patient's own body (autologous vein) or tissue from a cow's heart (bovine pericardium), or from man-made (synthetic) materials, such as PTFE (polytetrafluoroethylene) or Dacron. Different patch materials may affect healing and the risk of infection, blood clots, or the artery narrowing again. These problems may increase the risk of stroke.

What did we want to find out?

We wanted to find out whether the choice of patch material affects the results of surgery, especially the risks of stroke, artery-related complications, and death, and longer-term effects.

What did we do?

We searched for studies that compared different patch materials in people undergoing carotid endarterectomy. We combined patches made using human veins or bovine pericardium into one category (biological patches), and all man-made materials into another category (synthetic patches). We 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 we find?

From our updated searches, we identified one new study, as well as some long-term results from studies included in previous versions of the review. In total, the review includes 15 studies involving 4971 participants, mainly men in their sixties. The studies were conducted in North America, Europe, and Australia.

Main results

Twelve studies (with 2021 carotid endarterectomy procedures) contributed results to our main comparison of synthetic and biological patches.

The evidence is very uncertain about the effects of synthetic versus biological patches on:

• stroke on one side of the body during the operation or within 30 days (5 studies, 797 participants);

• a rupture of the artery during the operation or within 30 days (6 studies, 1068 participants);

• a leak from artery repair causing a small blood-filled bulge up to 80 months after the operation (5 studies, 980 participants).

The use of synthetic patches instead of biological patches may result in little or no difference in:

• stroke on one side of the body up to 53 months after the operation (5 studies, 971 participants);

• stroke of any type up to 53 months after the operation (7 studies, 1167 participants);

• blocking of the artery or narrowing again by more than half the width up to 80 months after the operation (9 studies, 1431 participants).

The use of synthetic patches instead of biological patches probably results in little or no difference in:

• stroke or death up to 80 months after the operation (6 studies, 1115 participants).

What are the limitations of the evidence?

We do not know for sure if synthetic and biological patches give similar results for people undergoing carotid endarterectomy, or if one type works better or is safer than the other. We are uncertain because:

• many of the studies were small;

• there were problems with how some studies were carried out and how they reported their results;

• some important complications were rare, which makes it difficult to detect any difference in risk between patch types.

How up to date is the evidence?

This is an update of a review originally published 30 years ago and last updated in 2021. The evidence is current to 30 April 2025.

Key messages

• In people with alpha 1 antitrypsin deficiency, delivering additional alpha 1 antitrypsin through a drip into a vein (intravenous augmentation therapy) may lead to a slight increase in the number of exacerbations (worsening of lung disease) people experience each year, but may have little or no effect on the number of people who die. We are unsure whether intravenous augmentation therapy has any effect on the number of people who have serious unwanted events like hospitalisation or permanent damage. Delivering additional alpha 1 antitrypsin through a breathing mask (inhaled augmentation therapy) may have little or no effect on the number of people who have serious unwanted events, and we are unsure whether this treatment has any effect on exacerbations.

• Our review included few studies, and we have little confidence in the evidence.

What is alpha 1 antitrypsin deficiency (AATD)?

Alpha 1 antitrypsin (AAT) is a protein that helps protect our organs against damage from our body's own enzymes. AAT deficiency (AATD) is a genetic disease where people do not produce enough AAT. It can lead to lung damage and chronic obstructive pulmonary disease (COPD; a long-term condition that makes it hard to breathe). Symptoms of AATD include shortness of breath, cough, and wheeze. Smokers with AATD have a higher risk of developing severe lung disease. AATD can also lead to liver problems. Some people with AATD can stay healthy throughout their lives.

What is alpha 1 antitrypsin augmentation therapy?

AAT augmentation therapy aims to raise AAT levels in the bloodstream and lungs using AAT protein taken from the blood of healthy donors. AAT augmentation therapy may help protect lung tissue from damage and slow lung disease progression. It can be given through a drip into a vein (intravenous), injected under the skin (subcutaneous), or inhaled through a breathing mask.

What did we want to find out?

We wanted to find out if topping up AAT levels in people with AATD could reduce the number of exacerbations (worsening of the disease), the number of people who die, and the number of people who have serious unwanted events like hospitalisation or permanent damage. Our review focused on the results that were most important to people with the disease.

What did we do?

We searched for studies that compared AAT augmentation therapy given by any route (intravenous, subcutaneous, or inhaled) against AAT augmentation therapy delivered by another route, a dummy treatment (placebo), or no treatment. We compared and summarised the results and rated our confidence in the evidence based on factors such as study methods and sizes.

What did we find?

We found six studies with 524 participants. Four studies looked at intravenous AAT augmentation therapy, and the other two looked at inhaled AAT augmentation therapy. All six compared AAT augmentation therapy with placebo. The studies were conducted in high-income countries across Europe, North America, and Australia. The smallest study had five participants, and the largest had 180 participants.

Main results

Intravenous AAT augmentation therapy versus placebo

• Intravenous AAT augmentation therapy may lead to a slight increase in the number of exacerbations people experience each year. The evidence shows a rate of 1960 yearly exacerbations for every 1000 people receiving intravenous AAT augmentation therapy, compared with 1420 yearly exacerbations for every 1000 people receiving placebo (290 more exacerbations in the AAT group).

• Intravenous AAT augmentation therapy may have little or no effect on the number of people who die compared with placebo.

• We do not know whether people who receive intravenous AAT augmentation therapy are any more likely to have one or more serious unwanted events than those who receive placebo.

Inhaled AAT augmentation therapy versus placebo

• We do not know whether inhaled AAT augmentation therapy has any effect on the number of exacerbations people experience each year compared with placebo.

• No studies reported deaths.

• Inhaled AAT augmentation therapy may make little or no difference to the number of people who have one or more serious unwanted events compared with placebo.

What are the limitations of the evidence?

We have little confidence in the evidence because few studies were available, the studies we found included few participants, and the results only covered some of the people we were interested in.

How up to date is this evidence?

We included evidence published up to August 2025.

Key messages

• Brain–computer interface (BCI) training may slightly improve arm movement, but may make little to no difference to leg movement. We are very uncertain whether it helps with everyday activities.

• Compared with a 'sham' (fake) BCI, BCI training may make little to no difference to movement or everyday activities.

• Larger, well-designed studies are needed to confirm the true benefits and harms of BCI training.

What is a brain-computer interface (BCI)?

A brain–computer interface (BCI) is a technology that creates a direct link between the brain and an external device. It usually uses sensors placed on the scalp to detect brain signals when a person imagines or attempts a movement.

How is BCI used after stroke?

After a stroke, people often experience muscle weakness or loss of movement. BCI training reads the brain signals produced when a person intends to move, and turns them into real-time feedback. For example, when the patient thinks about moving their hand, the BCI detects this and triggers a robotic glove to move their hand, or delivers electrical stimulation to the muscles. This feedback happens at the same moment as the person's effort, which is thought to help "rewire" the brain and promote recovery of movement.

What did we want to find out?

We wanted to find out whether BCI training is better than conventional therapy, other active treatments, or a sham (fake) BCI at improving arm and leg movement, and the ability to carry out everyday activities in people with stroke. We also wanted to find out if BCI training is linked to any unwanted effects.

What did we do?

We searched for studies looking at the effects of BCI training in adults who had had a stroke and had difficulty moving as a result. The people in these studies had had either type of stroke (one caused by a blocked blood vessel or one caused by bleeding in the brain), and most were in the months following their stroke, once their condition had stabilised. We then compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as the methods used and the number of people studied.

What did we find?

We found 43 studies involving 1628 adults who had had a stroke. Here is what the evidence suggests:

• When BCI training was compared with conventional therapy, it may give arm movement a small boost (10 studies, 611 people), but may make little to no difference to leg movement (1 study, 64 people). We cannot tell whether it helps with everyday activities (5 studies, 282 people), as the evidence is very uncertain.

• When compared with other active treatments, BCI training may give balance a small boost (6 studies, 165 people), but may make little to no difference to leg movement (4 studies, 130 people). For arm movement (14 studies, 331 people) and everyday activities (5 studies, 163 people), we are not confident enough to say either way.

• When it was compared with a fake or 'sham' BCI, which looks and feels like the real thing but does not give genuine brain-signal feedback, BCI training did not seem to make much difference to arm (9 studies, 279 people) or leg movement (3 studies, 106 people), or to everyday activities (1 study, 28 people).

We also looked at a few other things, such as muscle tightness, muscle strength, and overall recovery of the nervous system. The evidence on these was too uncertain for us to draw conclusions.

We also wanted to know about unwanted effects, but many studies simply did not mention them. In the studies that did, the effects were usually mild, such as sore muscles or feeling tired. Because so few studies reported this properly, we cannot be sure whether BCI training carries any extra risk.

What are the limitations of this evidence?

We have little to very little confidence in the evidence, for several reasons:

• Most of the studies were small and involved only a few people.

• Many were carried out in ways that could have influenced their results. For example, the people taking part often knew which treatment they were receiving.

• The findings also varied widely from one study to another.

• Finally, some studies that found no benefit may not have been published, which could make BCI training appear more helpful than it really is.

How up to date is this evidence?

The evidence is up to date to October 2025.

Key messages

• Only one study looked at whether giving medicines that stimulate breathing, like caffeine, to babies born a few weeks early can help prevent or reduce problems with low oxygen levels or breathing. This means that we have very little evidence about their use.

• Caffeine may help reduce the number of times late preterm babies have low oxygen levels, but we do not know if it reduces the need for breathing (respiratory) support (such as ventilators); and we are not sure if caffeine causes unwanted effects.

• More research is needed to know if medicines that stimulate breathing are helpful and safe for babies born a few weeks early. We found some studies that will be published soon that will help to update the evidence.

How old are late preterm babies?

Babies born a few weeks early, between 34 and 36 weeks of pregnancy, are called ‘late preterm’. These babies are not as fully developed as babies born at full term (after 37 weeks, or 8.5 months), and their lungs and other organs may be weaker.

What is intermittent hypoxemia?

Sometimes, a person's oxygen levels can drop for short periods of time (a condition called intermittent hypoxia). When this happens, it is difficult to breathe. Breathing difficulties can cause long-term problems by damaging the brain.

What are methylxanthines?

Methylxanthines are medicines which make breathing easier by relaxing the muscles we use to breathe. Caffeine is the most commonly used type of methylxanthine because it has fewer unwanted effects than other types.

What did we want to find out?

Although methylxanthines like caffeine are often used, successfully, to treat breathing problems in very early (premature) babies (born before 32 weeks of pregnancy), they are used less often in late preterm babies, and it is not clear if this treatment can help them. We wanted to know if methylxanthines are better than no treatment or a dummy treatment (placebo) for preventing or treating problems with low oxygen levels or breathing in late preterm babies. We also wanted to know if these medicines cause any unwanted effects.

What did we do?

We searched for studies that compared methylxanthines with placebo or no treatment in late preterm babies. We looked for studies that measured:

• how often babies had low oxygen levels;

• whether they needed help to breathe;

• how long they stayed in the hospital;

• if the treatment had any unwanted effects;

• if the babies survived until leaving the hospital.

We looked at the results of the only study we found. We summarized the results, and rated our confidence in the evidence based on factors such as the number of babies in the study (study size), and methods used when conducting the study.

What did we find?

We found one study from New Zealand with 132 late preterm babies. The study compared different doses of caffeine with a placebo and had the following results.

• Caffeine may reduce the number of times babies have low oxygen levels over one week from starting treatment.

• It is not clear if caffeine helps with other problems, like needing help to breathe, or improves the chances of being able to leave hospital earlier or surviving until leaving the hospital.

• It is not clear if caffeine causes unwanted effects.

• The study did not report on other important outcomes, like long-term development or the number of times a baby stopped breathing (apnea).

We found no studies that looked at using methylxanthines to treat, rather than prevent, breathing problems in these babies.

What are the limitations of the evidence?

The biggest limitation is that we only found one study. This means we cannot be sure about the results. The study did not report on all the outcomes we wanted to know about, and some results were not clear. Our confidence in these findings is very low because they are based on only one small study, and we had some concerns about how the study was carried out and reported. Future research may change these results.

How up to date is this evidence?

The evidence is current to December 2025. There are five studies in progress and when they are complete, their results may help us better understand if methylxanthines are helpful and safe for late preterm babies.

What are the long-term benefits and risks of different types of weight loss surgery (also called metabolic and bariatric surgery) to treat obesity and type 2 diabetes in adults?Key messages

• In people with obesity and type 2 diabetes, gastric (stomach) bypass (i.e. Roux-en-Y gastric bypass and one-anastomosis gastric bypass) may be most beneficial for improving body weight, waist circumference, type 2 diabetes status and long-term blood sugar levels at least five years after surgery, but for one-anastomosis gastric bypass, we are very uncertain about the results.

• It is unclear whether the different surgical procedures have an effect on risks such as serious unwanted health effects and death from any cause at least five years after surgery.

• Larger and well-designed studies may help reduce the existing uncertainties and increase our confidence in the findings.

What are obesity and type 2 diabetes?
Obesity is a condition with too many fat deposits that can damage health. In type 2 diabetes, the body has difficulty controlling blood sugar levels because the hormone insulin does not work properly. Type 2 diabetes often occurs in people with obesity, and both conditions increase the risk of premature death and other health problems, such as cardiovascular disease.

How are obesity and type 2 diabetes treated?

Lifestyle interventions such as nutrition, exercise, and behavioural programmes, along with medicines, are often used first for weight loss and improvement of diabetes status. When these do not work well, metabolic and bariatric surgery may be considered as an additional treatment option. There are a number of different types of bariatric surgery:

• gastric (stomach) banding;

• gastric sleeve (removal of a part of the stomach);

• Roux-en-Y gastric bypass (RYGB);

• one-anastomosis gastric bypass, or mini-gastric bypass;

• gastric plication (folding to make the stomach smaller);

• biliopancreatic diversion with duodenal switch.

What did we want to find out?

• Which of the different types of surgery are the safest and most beneficial ones by comparing them with each other and with lifestyle and medication therapy regarding their long-term (at least 5 years follow-up) benefits and risks.

• Whether these surgical procedures improve body weight, waist circumference, type 2 diabetes status, long-term blood sugar levels, and quality of life at least five years after surgery.

• Whether surgery affects serious unwanted health effects, death from any cause, and type 2 diabetes complications over this period.

What did we do?
We searched for studies involving people with obesity and type 2 diabetes. We included studies that compared at least two different surgical procedures, or surgery with lifestyle and medication treatment. We summarised and compared all treatments using a method called network meta-analysis, and we rated our confidence in the results based on factors such as study methods and sample size.

What did we find?
We found 18 studies, including 15,282 people with obesity and type 2 diabetes. In 13 of these studies (including 911 people), participants were assigned randomly to two or more treatment groups. This is the best way to ensure that groups of people are similar. Five studies (with 14,371 people) used ‘real-life’ observational data. The studies investigated surgical procedures such as gastric band, gastric sleeve, Roux-en-Y gastric bypass, one-anastomosis gastric bypass, and gastric plication. We found that:

• Roux-en-Y gastric bypass, may improve body weight and likely reduce waist circumference compared with lifestyle and medication treatment in the long term.

• One-anastomosis gastric bypass and, to a lesser extent, gastric sleeve, may also improve body weight and waist circumference, but we are very uncertain about the results.

• Roux-en-Y gastric bypass, one-anastomosis gastric bypass, gastric sleeve, and gastric band may improve type 2 diabetes status, but we are very uncertain about the results.

• It is unclear whether the types of surgery have an effect on serious unwanted health effects or death from any cause.

• Roux-en-Y gastric bypass may reduce type 2 diabetes complications in the long term compared to non-surgical treatments, but we are very uncertain about the results.

• Roux-en-Y gastric bypass may improve blood sugar levels compared to non-surgical treatments.

• One-anastomosis gastric bypass and gastric sleeve may also improve blood sugar levels, but we are very uncertain about the results.

• RYGB and SG may lead to a greater increase in health-related quality of life than non-surgical treatments, but again, we are very uncertain about the results.

What are the limitations of the evidence?
Our confidence in the evidence is often low to very low because the studies included only small numbers of people, and the results for some outcomes, especially serious unwanted health effects, death from any cause, and type 2 diabetes complications, were based on very few events. Moreover, for several surgical procedures, there were not enough studies to be certain about the outcomes. It is important to note that rating our confidence in findings was based only on studies in which participants were randomly assigned to groups and did not include observational studies.

How up to date is this evidence?
This evidence is up to date as of June 2024.

Key messages

• Any type of physical activity may slightly reduce body weight, waist size, and body fat percentage in adolescents with obesity, compared to no physical activity.

• We do not know if physical activity has an effect on other measures of weight, body size, or health problems due to obesity, compared to no physical activity.

• We need larger, longer-lasting, and better-quality studies to be more certain about the effects of physical activity on adolescents with obesity.

What is obesity?

Obesity is when a person has too much body fat, which can harm their health. Worldwide, obesity amongst adolescents (aged 10 to 19 years) has tripled since 1990, and more than 300 million children and adolescents may be living with obesity by 2050.

Obesity during childhood and adolescence can negatively affect physical and mental health, and may increase the risk of having cancer, liver disease, or kidney disease in adulthood.

Weight loss is the best way to reduce the health risks caused by obesity. This is usually done through lifestyle changes such as doing more physical activity (e.g. swimming, running, weight-lifting) and eating healthier foods, or with surgery or medication.

What did we want to find out?

We wanted to find out if, compared to no physical activity, physical activity helps adolescents with obesity:

• lose weight and reduce their BMI (the 'body mass index' is used to check if someone is a healthy weight; their weight is divided by their height multiplied by itself), BMI z-score (how someone's BMI compares to BMIs of others of the same age and sex), waist size, and body fat percentage;

• lower their blood sugar levels and insulin resistance (insulin is a hormone that helps to control blood sugar levels).

We also wanted to find out if one type of physical activity was better than another type at producing these effects, and if the physical activity programmes led to any unwanted, harmful events.

What did we do?

We searched for studies that compared participating in physical activity (such as doing aerobic exercise, weight-lifting, or playing football) to:

• no physical activity;

• another type of physical activity (for example, high-intensity exercise compared to moderate-intensity exercise).

The adolescents needed to do the physical activities for at least 12 weeks. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and number of participants.

What did we find?

We found 30 studies including 1508 adolescents. The studies were small: the smallest included only 21 adolescents and the largest, 106. Just under half of the adolescents involved were female (46%). Their average age ranged from 10 years to nearly 17 years. The studies took place in 15 countries: 5 in Tunisia; 4 each in China and Iran; 3 in Brazil; 2 each in Canada, Spain, and the USA; and 1 each in Australia, Estonia, India, Mexico, South Korea, Sweden, Taiwan, and Thailand.

Most studies lasted 12 or 13 weeks; the longest study lasted 32 weeks.

We organised the studies' results into two broad comparisons:

• any type of physical activity (e.g. aerobic exercise, active video-gaming) compared to no physical activity (22 studies);

• one type of physical activity compared to another type (17 studies).

Main resultsPhysical activity versus no physical activity

Compared to no physical activity, any type of physical activity may slightly reduce:

• body weight: adolescents in the active groups weighed on average 1.88 kg less (17 studies, 749 adolescents);

• waist size: in the active groups, adolescents' average waist size was 2.88 cm smaller (10 studies, 476 adolescents);

• body fat percentage: in the active groups, adolescents' average body fat percentage was 2.96% lower (9 studies, 313 adolescents).

We are very uncertain about the effect of any type of physical activity on:

• BMI;

• BMI z-score;

• blood sugar levels;

• insulin resistance;

• unwanted, harmful events.

One type of physical activity versus another type

We are very uncertain about the effect of one type of physical activity compared with another on any of the points we were interested in.

What are the limitations of the evidence?

We have limited confidence in the evidence because:

• the studies were small;

• the types of physical activities varied;

• the studies' reporting of their methods and findings was poor;

• some studies did not report all their results;

• no studies reported on unwanted, harmful events.

The studies comparing two different types of physical activity were quite varied, which meant we were mostly unable to combine their results to produce strong evidence. Therefore, we do not know whether one type of physical activity is better than another.

How up to date is this evidence?

This evidence is current to December 2025.

Key messages

• This updated review assessed special solutions (culture media) that are important for helping embryos develop in assisted reproduction technology (ART) treatments used for women who cannot get pregnant naturally. Currently, we do not know which culture medium gives the best chance of giving birth to a live baby. One study showed that an embryo culture medium called G5 probably leads to more live births than one called HTF, but the other studies did not show clear differences in success rates between different culture media.

• The evidence is limited because the studies tested different culture media and their results could not be combined. Many studies had weaknesses, such as small numbers of people taking part. More, well-designed studies are needed to find out which embryo culture medium works best.

What is an embryo culture medium?

A woman who cannot get pregnant naturally may use assisted reproductive technology (ART) treatments, such as IVF (in vitro fertilization), in which eggs are fertilized by sperm outside the body. Supporting the embryo this creates to develop (culture) is a very important part of IVF treatment. The embryo is placed in a special solution called an embryo culture medium. This medium provides nutrients and helps the embryo grow in the laboratory until it is transferred to the womb (uterus) or frozen for later use. There are many different embryo culture media.

Why is there no agreement about which culture medium works best?

There is currently no clear agreement on which type of embryo culture medium gives the best chances of having a live baby. The available research does not give enough reliable information to clearly choose one culture medium over another. This makes it difficult for doctors and patients to know which option to use.

What did we want to find out?

We wanted to know whether different types of human embryo culture media affect the chances of having a baby or an ongoing pregnancy (pregnancy confirmed by heartbeat on ultrasound) for women undergoing IVF treatments.

What did we do?

We searched for studies that compared different embryo culture media available for use during IVF treatments. We looked at the results of studies for all the measurements we think are important. We considered the reliability of each study based on how it was designed and conducted. We made a judgement about how certain we were about the evidence for each important measure.

What did we find?

We found 26 relevant studies, eight of which evaluated the most important measures, such as live birth or ongoing pregnancy. Another five studies are in progress, and there are 60 studies that we have not been able to include because they are only published as short summaries without enough information. It was not possible to combine any of the studies' results because no two studies compared the same culture media.

Main results

Eight studies (3315 women) of the 26 studies included in the review reported live birth or ongoing pregnancy.

Most studies did not find a clear difference between the culture media they compared. However, the two largest studies did find some differences that could be important.

One study showed that there was probably a 6% higher chance of having a live birth with G5 compared to HTF (836 women). Another study showed that there may be a 6% higher chance of having a live birth with EmbryoAssist plus GM-CSF (with low HSA (a low concentration of a protein in the blood called albumin)) compared to a version of EmbyroAssist without the GM-CSF (743 women), but we are very uncertain about this result, especially because the treatment was changed during the study.

The same studies found differences in ongoing pregnancy rates. One suggested that G5 probably increases the chance of ongoing pregnancy compared with HTF (836 women). The other suggested that EmbryoAssist plus GM-CSF (low HSA) may increase the chance of ongoing pregnancy compared with EmbryoAssist without GM-CSF (743 women), but we are very uncertain about this result.

The evidence is very limited and unclear, and we could not combine results from different studies. Further well-designed studies are needed to confirm the findings and determine if any specific culture medium improves treatment success.

What are the limitations of the evidence?

• Many studies included only a small number of women.

• Some studies had problems with how they were designed.

• A few studies assigned eggs or embryos (rather than women) to the groups being compared, or transferred embryos from different study groups to the same woman.

• Most studies did not clearly describe the ingredients in the culture media.

• Many studies did not report all important measures.

Overall, the evidence was mostly very uncertain because:

• the studies could not be combined with each other;

• the studies' results were not precise; and

• the studies' results were not always worked out in the right way.

How up to date is the evidence?

This review updates one published in 2015. The evidence is current to 28 August 2025.

Key messages

• Given as maintenance treatment (long-term treatment to keep symptoms under control) in people with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), subcutaneous immunoglobulin (SCIg) compared to placebo (dummy treatment) probably reduces the number of people who experience a worsening in disability. In addition, the average loss of grip strength and average worsening in disability score are probably lower among people receiving SCIg maintenance treatment compared with those receiving placebo. There is probably a higher risk of local side effects (affecting the injection site), but no difference in systemic side effects (affecting other parts of the body), in people treated with SCIg compared to those treated with placebo.
• We need more and better studies to investigate the benefits of SCIg given as induction treatment (short-term therapy) or maintenance treatment. In particular, there is a need for studies comparing SCIg maintenance treatment with other medicines, such as intravenous immunoglobulin (antibodies given through a vein).

What is chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)?

CIDP is a rare disorder of the nerves that leads to gradually progressive sensory symptoms and weakness in arms and legs. CIDP is a disorder in which the body's own immune system presumably attacks the nerves (an autoimmune disease). If left untreated, people with CIDP can become severely disabled.

How is CIDP treated?

Treatment for CIDP can be divided into short-term (induction) treatment and long-term (maintenance) treatment. Most people with CIDP will require long-term treatment. The aim of induction treatment is to improve disability, whereas the goal of maintenance treatment is to keep the condition stable and prevent disability from worsening. One of the preferred treatments for both induction and maintenance treatment is intravenous immunoglobulins (IVIg). This treatment consists of purified antibodies collected from donated blood and given through a drip into a vein. Immunoglobulins can also be given by injection directly under the skin (subcutaneously). Unlike IVIg, subcutaneous immunoglobulin (SCIg) treatment does not require hospitalisation or an intravenous line.

What did we want to find out?

We wanted to know if SCIg induction treatment is better for increasing the probability of an improvement in disability, and if SCIg maintenance treatment is better for reducing the risk of worsening in disability, compared with placebo (dummy treatment) or other treatments (such as IVIg). We also wanted to know if SCIg treatment is better than placebo or other treatments for improving change in grip strength and change in disability score, and whether SCIg treatment has any side effects.

What did we do?

We searched for studies that evaluated SCIg as induction treatment or maintenance treatment compared with placebo or other treatments. We compared and summarised the results of the studies for both the induction and maintenance treatment groups, and rated our confidence in the evidence.

What did we find?

We found four studies that involved 360 people with CIDP. Most participants were men (62%), and the average age was 55 years. The studies involved people from all over the world. The smallest study involved 20 people and the largest 172. One study compared SCIg to IVIg as induction treatment. The other three compared SCIg with placebo as maintenance treatment. Studies lasted from 10 weeks to 26 weeks. All studies were partly or entirely funded by pharmaceutical companies.

Main results

We found no studies comparing SCIg to placebo as induction treatment.

The study comparing SCIg to IVIg provided very few data. There may be no difference in change in disability score after five weeks in people who receive SCIg induction treatment and those who receive IVIg induction treatment.

Compared with placebo, SCIg maintenance treatment probably reduces the number of people who experience a worsening in disability. In addition, the average loss of grip strength and average worsening in disability score are probably lower in people receiving SCIg maintenance treatment compared with those receiving placebo. SCIg maintenance treatment probably leads to more local side effects (affecting the injection site) than placebo treatment. There is probably no difference in systemic side effects (affecting other parts of the body) with SCIg maintenance treatment compared to placebo. Side effects were mostly mild in the studies, but some were more serious.

We found no studies comparing SCIg maintenance treatment to other treatments.

What are the limitations of the evidence?

In the induction treatment group, we have little confidence in the evidence because the study enroled few participants, and they were aware of the treatment they received. In the maintenance treatment group, we are only moderately confident in the evidence, because the number of included participants was relatively small.

How up to date is this evidence?

The evidence is up-to-date to July 2025.

Key messages

• Some immune-checkpoint inhibitor combinations help people with extensive-stage SCLC live longer than standard chemotherapy alone.

• Not all combinations of immunotherapy are equally effective or safe.

• More research is needed on quality of life and long-term treatment effects, and several immune-checkpoint inhibitor combinations are now important first-line treatment options.

This summary is written for people living with extensive-stage small cell lung cancer (SCLC), their families, caregivers, and anyone looking for clear and accessible information about treatment options.

What is extensive-stage small cell lung cancer (extensive-stage SCLC)?

SCLC is a fast-growing type of lung cancer. It is usually divided into two stages: limited and extensive. In extensive-stage disease, cancer has already spread widely in the lungs or to other parts of the body. Most people with extensive-stage SCLC are treated with a combination of chemotherapy drugs, usually platinum and etoposide, often referred to as 'PE chemotherapy'. But cancer often comes back quickly.

Immune-checkpoint inhibitors are a type of cancer treatment that helps the immune system recognise and attack cancer cells. They work differently from chemotherapy and have become important in treating several types of cancer.

What did we want to find out?

We wanted to find out whether combining immune-checkpoint inhibitors with standard chemotherapy improves survival and other outcomes for people with extensive-stage SCLC. We also wanted to know how safe these treatments are and whether they affect quality of life.

What did we do?

We looked for high-quality studies that compared different immune-checkpoint inhibitor treatments with chemotherapy alone in people with extensive-stage SCLC. We combined the results using a method called network meta-analysis (NMA). This method lets us compare many treatments at the same time, even when some treatments were not directly compared in the same study. NMA works by linking results across different trials. For example, if Study 1 compared Treatment A with Treatment B, and Study 2 compared Treatment B with Treatment C, we can estimate how Treatment A might compare with Treatment C — even though they were never tested against each other. This approach helps build a more complete picture of how all treatments compare overall and which options may be more helpful.

What did we find?

We found 14 studies, with 7541 people contributing data on overall survival, the main outcome of interest. Most of the studies tested whether adding immune-checkpoint inhibitors to platinum-etoposide chemotherapy could improve outcomes.

• Among the evaluated regimens, we found the lowest estimated risk of death with platinum-etoposide chemotherapy combined with benmelstobart plus anlotinib or serplulimab, and we also found improvements in survival with durvalumab or adebrelimab.

• Other combinations, such as those including ipilimumab, probably do not improve survival and may increase side effects. Some treatments, including serplulimab or certain combination immunotherapies, were also linked with more side effects than standard chemotherapy.

• For progression-free survival (the time before the cancer gets worse), some treatments delayed cancer worsening, but these effects did not always match improvements in overall survival.

• Only a few treatments improved response rates (shrinking or eliminating tumours), and this did not always match the improvements in survival.

• There was not enough useful information about quality of life to help people and clinicians make informed decisions.

What are the limitations of the evidence?

Some studies included only a small number of people or were conducted in limited regions, which may affect how well the results apply to everyone. Also, not all studies reported results in the same manner. Few studies reported on patient experiences or long-term effects. Because few studies directly compared different immune-checkpoint inhibitor combinations with each other, we need more head-to-head trials to be certain about which treatments work best. People may wish to discuss with their healthcare team how these results apply to their own situation, including side effects, expected benefits, and how treatment may affect day-to-day quality of life.

How up to date is this evidence?

This review includes evidence available up to December 2025.

Review question

We aimed to find out if it is effective and safe to stop antidepressants for people with depression or anxiety who have been taking them for six months or longer.

We compared different approaches for stopping long-term antidepressants versus continuation. We looked at benefits (e.g. successful discontinuation rate) and harms, such as return of the depressive or anxiety episode (relapse), side effects, and withdrawal symptoms (i.e. symptoms people experience when stopping an antidepressant).

Background

Antidepressants are widely used for depression and anxiety. Guidelines recommend that an antidepressant should be continued for at least six months after people start to feel better, and for at least two years if they have had two or more periods of depression. Many people take antidepressants for much longer, and as they can cause unpleasant side effects, long-term use puts people at risk of harm that may outweigh the benefits.

Study characteristics

Our search up until January 2020 found 33 studies, which included 4995 adult participants. Most people in these studies had recurrent depression (two or more episodes of depression before stopping antidepressants), and most were recruited from specialist mental healthcare services. In 13 studies, the antidepressant was stopped abruptly; in 18 studies, the antidepressant was stopped gradually over several weeks ("tapering"); in four studies, psychological therapy support was also offered; and in one study, stopping was prompted by a letter to the GP with guidance on tapering. Most tapering schemes lasted four weeks or less.

Key results

We found very low-certainty evidence suggesting that abrupt stopping may lead to higher risk of relapse and there was insufficient evidence of its effect on occurrence of side effects compared to continuation of the antidepressant.

We found very low-certainty evidence suggesting that "tapering" over a few weeks may lead to higher risk of a return and again may have little or no effect on side effects compared to continuation.

We found evidence of very low to low certainty to suggest that stopping the antidepressant in combination with providing preventive cognitive therapy (PCT), or MBCT, was possible for 40% to 75% of participants in the group tapering the antidepressant and may show no difference in effects on relapse.

We found low-certainty evidence suggesting that a prompt letter and guidance on tapering sent to the GP may have no effect on the number of people who stop their antidepressant.

We were unable to draw conclusions about withdrawal symptoms after abrupt or gradual stopping of an antidepressant, as this generally was not assessed.

None of the studies used very slow tapering schemes beyond a few weeks, tapered liquid forms of antidepressants, or used tapering strips (to allow tapering with very low doses).

None of the identified studies investigated stopping combined with providing supportive therapy such as online support or self-help therapy.

Certainty of evidence

Overall, the certainty of evidence was low to very low. This means we have limited or little confidence in the results, and new research is likely to change our conclusions. The main reasons for this assessment of evidence certainty were that trials did not distinguish between symptoms of relapse of depression and symptoms of withdrawal. Also, most studies used no tapering or very "rapid" tapering schedules (four weeks or less), and nearly all studies included people with recurrent depression (more than two episodes).

Conclusions

We found few studies that examined stopping long-term antidepressants. We are uncertain if the approaches for stopping long-term antidepressants studied to date are effective and safe in people with recurrent depression. People should discuss with their doctor when they want to stop their antidepressant.

Future studies should include people in primary care with only one or no earlier episodes of depression, older people, and people taking antidepressants for anxiety. Studies should taper antidepressants slowly while taking care to distinguish withdrawal symptoms from relapse.

Key messages

- Using balloons that coat the inside of blood vessels with medicines (drug-eluting) to treat peripheral arterial disease led to better results in terms of whether a person received more than one treatment for the same artery during the study (target lesion revascularization), whether a treated artery became narrowed again (binary restenosis), and the difference in millimeters between the treated segment and how narrow it was on follow-up (late lumen loss).

- There was no difference between drug-eluting balloons and uncoated, plain balloon angioplasty in amputation, amputation-free survival, death, change in a way of measuring disease severity (the ankle-brachial index), quality of life scores, or walking ability.

What is peripheral arterial disease of the lower legs, and what are drug-eluting balloons?

Peripheral arterial disease of the lower legs is a condition where blood supply to the lower legs is not as good as it should be because of blockages in the blood vessels (tubes that carry blood around the body). It affects many people. In its most serious form, it can lead to pain, infections, and amputation due to poor blood flow. People with peripheral arterial disease are usually first treated with medicines and habit changes, including strategies to stop smoking and a walking program to improve their general health, which in turn can improve their condition. However, medicines and habit changes do not work for all people, and some may need an operation. This operation can be traditional open surgery or a less invasive procedure known as angioplasty, which uses a balloon to open the blockages in the arteries. A new type of angioplasty, known as drug-eluting balloon angioplasty, is a promising alternative to traditional balloon angioplasty for treating peripheral arterial disease. Unlike traditional plain balloons, drug-eluting balloons also coat the inside of the blood vessels with medicines that are used to treat cancer (chemotherapy), such as paclitaxel, in hopes of stopping the worsening of peripheral arterial disease even after surgery and preventing or delaying its complications.

What did we want to find out?

The goal of this review was to find out how drug-eluting balloon angioplasty compares with plain balloon angioplasty for treating peripheral arterial disease of the lower legs.

What did we do?

We combined 31 studies (clinical trials) that randomly assigned 5292 participants having an angioplasty for peripheral arterial disease to either receive drug-eluting balloon angioplasty or plain balloon angioplasty. The studies included thigh and leg arteries above and below the knee. The studies were carried out in Europe, the USA, China, Singapore, Jordan, Japan, and New Zealand, and all used drug-eluting balloons with the drug paclitaxel. Participants were followed up for up to five years after surgery.

What did we find?

At up to five years, there were better results for drug-eluting balloons based on an indicator of whether a person received more than one treatment to the same artery during the period covered by the study (target lesion revascularization). At up to two years, there were also better results for binary restenosis, which happens when a treated artery becomes narrowed again after being previously treated. At up to six months, there were better results in terms of the difference in millimeters between the treated segment and how narrow it was on follow-up (late lumen loss). There was no evidence of a difference between drug-eluting balloon and uncoated angioplasty in amputation, amputation-free survival, death, change in the ankle-brachial index (a measure of disease severity), quality of life scores, or walking ability.

What are the limitations of the evidence?

There were differences in the way that participants were given anti-clotting medication to be taken by mouth after surgery. Other concerns included various studies reporting results for the same outcome that differed more than would be expected, and results that showed both an important difference as well as no difference between treatments. This meant that we had to lower our confidence in the evidence. Our confidence in the evidence was low for the outcome target lesion revascularization and moderate for amputation, binary restenosis, death, and change in the ankle-brachial index.

How up to date is this evidence?

This review updates our previous review from 2016. The evidence is up to date to March 2023.

Key messages

• Swallowing therapy may improve swallowing in stroke survivors following a recent stroke, but no one therapy is effective overall.

• Severity of swallowing problems is probably improved by electrical stimulation of the outside of the neck and brain, nerve stimulation and combined therapies. Acupuncture probably reduces swallowing problems at the end of the trial and increases swallowing safety; medication probably reduces chest infections; and electrical stimulation of the inside of the neck probably reduces the number of people needing a breathing tube at the end of the study.

• Future studies should be larger and of better quality.

Why do people who have had a stroke need swallowing therapy?

People who have had a stroke often have difficulty chewing and swallowing saliva, and food and drink (called 'dysphagia'). It can affect up to 80% of stroke survivors and can lead to:

• choking and chest infections, due to inhaling not swallowing saliva and food;

• malnutrition and weight loss, which might mean slower recovery;

• poor quality of life;

• long stays in hospital; and

• increased risk of death or being sent to a care home.

Many people's swallowing improves without treatment, but between 15% and 51% of people will still have problems swallowing around two weeks after their stroke.

What is swallowing therapy?

Swallowing therapy aims to speed up recovery of swallowing function and reduce the negative effects of swallowing problems on health and well-being.

There are many types of swallowing therapy; we looked at the following:

• acupuncture;

• swallowing exercises;

• medication;

• stimulating the neck with electrical pulses (NMES: outside; PES: inside), or the brain with electrical (tDCS) or magnetic pulses (TMS, TBS);

• physical stimulation with cold, sour flavours or fizzy drinks;

• nerve stimulation; and

• combinations of these therapies.

What did we want to find out?

We wanted to assess the effectiveness of swallowing therapies to improve swallowing in stroke survivors up to six months after their stroke. We were interested in:

• how bad (severity) their swallowing problems were after treatment;

• the number of people who had swallowing problems at the end of the trial;

• how safe their swallowing was;

• whether chest infections or pneumonia were reduced due to improved swallowing; and

• the number of people dependent on a breathing tube.

What did we do?

We searched for studies that investigated different swallowing therapies for adults with swallowing problems after a stroke. Studies had to compare a therapy with usual care, no treatment, or a placebo treatment (that is, an inactive treatment that seems like a real treatment). Usual care could be any treatments or combinations of treatments, but had to be the same for all the people in the studies.

We read the studies carefully and recorded what they found. We also judged how much we could trust the results by looking at how big the trials were and how well they were done.

What did we find?

We found 181 studies with 11,500 people.

• Severity of swallowing problems after treatment: acupuncture, swallowing exercises and medication may reduce swallowing problems but the evidence is very uncertain. Physical stimulation and magnetic brain stimulation (TBS, TMS) may reduce, and NMES, tDCS, nerve stimulation and combined therapies probably reduce swallowing problems. PES may make little to no difference.

• Number of people with swallowing problems at the end of treatment: acupuncture probably results, and physical stimulation and tDCS may result in fewer people with swallowing problems at the end of treatment. We are not sure about the effects of swallowing exercises and NMES. Medication may, and PES and combined therapies probably make little to no difference.

• Safety of swallowing: acupuncture and TMS probably improve, and swallowing exercises and PES may improve swallowing safety. TBS may improve swallowing safety, and NMES and tDCS may have little to no effect on swallowing safety, but the evidence is very uncertain.

• Chest infections or pneumonia: medications probably reduce, and acupuncture, swallowing exercises, PES and physical stimulation may reduce the number of chest infections or pneumonia. We are unsure about the effects of NMES. Combined therapies probably do not reduce the number of chest infections or pneumonia.

• Need for a breathing tube: PES probably reduces the number of people dependent on a breathing tube. We are very uncertain about the effects of swallowing exercises.

What are the limitations of the evidence?

Many of the studies were small and of poor quality. This makes it harder to trust the results. In the future, studies should use more reliable methods, and they should be larger so we can be more confident in the results. Many of the swallowing therapies involved different methods of delivery, so it is still not clear which approach is most effective for each type of therapy.

How up to date is this evidence?

The evidence is current to July 2025. This is an update of the review originally published in 1999 and updated in 2012 and 2018.

Key messages

• Any benefits in terms of pregnancy chances of full bladder, removing mucus from the cervix, or afterloading (loading the embryo into the catheter after it has been placed in the uterus) are unclear, and information on unwanted effects was rarely reported.

• Further larger and well-designed studies are needed to improve our confidence in the evidence on the effects of preparation techniques before embryo transfer.

What is in vitro fertilisation and embryo transfer?

In vitro fertilisation (IVF) is a type of fertility treatment. An egg is fertilised by sperm in a laboratory, and the resulting embryo is placed in the uterus (womb) to develop as normal. The embryo is transferred through a tube (catheter) that is inserted into the vagina and through the neck of the womb (cervix) into the uterus. This is the last step in the IVF process and is the most likely to go wrong. Only one-third of transfers result in pregnancy.

Clinicians use various techniques to improve the success of embryo transfer. For example, inserting the catheter may be easier if the woman has a full bladder, or if doctors clear away any mucus from the cervix. The type of catheter used, positioning the catheter first and then putting the embryo in the catheter (called ‘afterloading’), or carrying out a practice procedure may also help.

What did we want to find out?

We wanted to find out the effects of preparation techniques before embryo transfer on live birth rate, unwanted effects, pregnancy rate, pregnancy loss rate, and difficulty of transfer.

What did we do?

We searched for studies comparing preparation techniques before embryo transfer with no special preparation techniques in women with infertility having IVF. We compared and summarised the results of the studies and rated our confidence in the evidence using structured methods and standard tools, based on factors such as study methods and sizes.

What did we find?

We found 11 studies involving a total of 2524 women with infertility who were undergoing embryo transfer. The studies were conducted in Canada, the USA, Argentina, Brazil, Belgium, Greece, Italy, the Netherlands, Spain, the UK, Turkey, and Japan. Six of these studies looked at techniques including:

• adjusting bladder fullness;

• cleaning the mucus from the cervix; and

• afterloading.

Main resultsEmbryo transfer under a full bladder versus an empty bladder

We are very uncertain about the effect of a full bladder versus an empty bladder on pregnancy rate, pregnancy loss rate, and difficulty of transfer.

• Live birth rate: not reported

• Pregnancy rate (2 studies, 273 women)

• Pregnancy loss rate (1 study, 131 women)

• Difficulty of transfer (1 study, 142 women)

Removing mucus versus no mucus removal

• Live birth rate: one study reported 52 live births per 220 cycles in the mucus removal group and 42 live births per 205 cycles in the no-mucus removal group.

• Pregnancy rate: there may be little to no difference between groups in pregnancy rate (1 study, 97 women). A second study reported 65 pregnancies per 220 cycles in the mucus removal group and 63 pregnancies per 205 cycles in the no-mucus removal group.

• Pregnancy loss rate: one study reported 15/220 cycles in the mucus removal group and 20/205 cycles in the no-mucus removal group.

• Difficulty of transfer: not reported

Embryo afterloading versus direct embryo transfer

• Live birth rate: not reported

• Pregnancy rate: there may be little to no difference between groups in pregnancy rate (2 studies, 654 women).

• Pregnancy loss rate: there may be little to no difference between groups in pregnancy loss rate (1 study, 352 women).

• Difficulty of transfer: we are very uncertain about the effect of embryo afterloading versus direct embryo transfer on difficulty of transfer: one study reported that afterloading may reduce the difficulty of transfer (352 women), while a second study reported there was no difficulty of transfer for both groups.

What are the limitations of the evidence?

We have little to very low confidence in the evidence. The available research is limited, and most studies were small in size and old. This means we cannot be sure which, if any, of these individual preparation techniques (e.g. full bladder, mucus removal, afterloading) are effective or safe, so the findings should be interpreted with caution. More high-quality research is needed to find out whether any of these preparation techniques truly improve IVF outcomes and to better understand their possible unwanted effects.

How up to date is this evidence?

This review is an update of our previous review published in 2009, with literature searches conducted up to October 2025.

Key messages

• Based on three included studies, we found that checking more often might help people keep their blood sugar under better control over time, although the evidence is very uncertain.

• Future studies are needed looking at the best way for people with type 1 diabetes to check their blood sugar at home, including how often to check, when to check, and what target numbers to aim for, so they and their doctors have clear guidance.

• People wanting to know how often to check their blood sugar should talk to their healthcare provider, as the best choice may depend on the patient's specific needs.

What is type 1 diabetes?

Type 1 diabetes is a lifelong condition that occurs when the body can no longer make insulin. Insulin is a hormone that turns food into energy and manages the level of sugar in your blood. People with type 1 diabetes need to take insulin every day. Many also check their blood sugar regularly, which can help them decide on insulin doses and manage food, exercise, and daily activities more safely. People with type 1 diabetes typically check their blood sugar 4 to 10 times a day.

Guidelines offer different advice about how to check blood sugar. It remains unclear which approach works best, especially where test supplies or other resources are limited.

What did we want to find out?

We wanted to find out what kind of blood sugar checking works best for adults with type 1 diabetes in everyday life. This includes how many times a day people may need to check their blood sugar, what times of day checking is most useful, and what blood sugar range they should try to stay within. We also wanted to know whether different ways of checking blood sugar affect people’s health and daily well-being.

What did we do?

We looked for studies that compared different ways of checking blood sugar in adults aged 18 years and older with type 1 diabetes. This included how often people checked their blood sugar, what times of day they checked it, and the blood sugar levels they were trying to reach. We 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 we find?

We found three studies involving 16,481 adults with type 1 diabetes. All three studies only looked at how often people checked their blood sugar. No studies provided evidence about the best times of day to check blood sugar or the best blood sugar targets to use.

• In one study (123 people), people who checked their blood sugar more carefully throughout the day may have had slightly lower blood sugar levels after nine months than those receiving usual care according to standard diabetes guidelines, but the evidence is very uncertain.

• In the other two studies (16,358 people), which followed people for up to two years, those who checked their blood sugar more often tended to have better blood sugar control. Those who checked most often had the lowest blood sugar levels. However, this evidence is very uncertain.

The studies we found all pointed in the same direction, suggesting a benefit with more frequent checking.

No study reported effects on:

• low blood sugar events;

• diabetic ketoacidosis, a life-threatening complication of diabetes that can occur when there is a lack of insulin;

• long-term diabetes complications; or

• quality of life

People who are considering how often to check their blood sugar should discuss this with their healthcare provider, as the best choice may depend on individual circumstances.

What are the limitations of the evidence?

We have very low confidence in the evidence. The studies were few, small, or had problems with their methods. Because of this, we still do not know how often adults with type 1 diabetes should check their blood sugar, the best times of day to check it, or what blood sugar levels they should aim for.

How up to date is this evidence?

The evidence is current to January 2026.