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.

What are international travel-related control measures?

International travel control measures are methods to manage international travel to contain the spread of COVID-19. Measures include:

- closing international borders to stop travellers crossing from one country to another;

- restricting travel to and from certain countries, particularly those with high infection levels;

- screening or testing travellers entering or leaving a country if they have symptoms or have been in contact with an infected person;

- quarantining newly-arrived travellers from another country, that is, requiring travellers to stay at home or in a specific place for a certain time.

What did we want to find out?

We wanted to find out how effective international travel-related control measures are in containing the COVID-19 pandemic.

What we did

We searched for studies on the effects of these measures on the spread of COVID-19. Studies had to report how many cases these measures prevented or detected, or whether they changed the course of the pandemic. The studies could include people of any age, anywhere. They could be of any design including those that used ‘real-life’ data (observational studies) or hypothetical data from computer-generated simulations (modelling studies).

This is the first update of our review. This update includes only studies on COVID-19, published up to 13 November 2020.

What we found

We found 62 studies. Most (49 studies) were modelling studies; only 13 used real-life data (observational studies). Studies took place across the world and at different times during the pandemic. Levels of COVID-19 within countries varied.

Most studies compared current travel-related control measures with no travel-related controls. However, some modelling studies also compared current measures against possible measures, for example, to see what might happen if controls were more or less relaxed or were combined with other measures.

Main results

Below we summarise the findings of some outcomes.

Travel restrictions reducing or stopping cross-border travel (31 modelling studies)

Most studies showed that travel restrictions reducing or stopping cross-border travel were beneficial, but this beneficial effect ranged from small to large. Additionally, some studies found no effect. Studies also predicted that these restrictions would delay the outbreak, but the delay ranged from one day to 85 days in different studies.

Screening at borders (13 modelling studies and 13 observational studies)

These studies assessed screening at borders, including screening people with symptoms or who had potentially been exposed to COVID-19, or testing people, before or after they travelled.

For screening based on symptoms or potential exposure to COVID-19, modelling studies found that screening reduced imported or exported cases and delayed outbreaks. Modelling studies predicted that 1% to 53% of cases would be detected. Observational studies reported a wide range of cases detected, from 0% to 100%, with the majority of studies reporting less than 54% of cases detected.

For screening based on testing, studies reported that testing travellers reduced imported or exported cases, and cases detected. Observational studies reported that the proportion of cases detected varied from 58% to 90%. This variation might be due to the timing of testing.

Quarantine (12 modelling studies)

All studies suggested that quarantine may be beneficial, but the size of this effect ranged from small to large in the different studies. Modelling studies, for example, predicted that quarantine could lead to between 450 and over 64,000 fewer cases in the community. Differences in effects may depend on how long people were quarantined for and how well they followed the rules.

Quarantine and screening at borders (7 modelling studies and 4 observational studies)

For quarantine and screening at borders, most studies suggested some benefit, however the size of this effect differed between studies. For example, observational studies reported that between 68% and 92% of cases would be detected. Differences in effects may depend on how long people were quarantined for and how often they were tested while in quarantine.

How reliable are these results?

Our confidence in these results is limited. Most studies were based on mathematical predictions (modelling), so we lack real-life evidence. Further, we were not confident that models used correct assumptions, so our confidence in the evidence on travel restrictions and quarantine, in particular, is very low. Some studies were published quickly online as ‘preprints’. Preprints do not undergo the normal rigorous checks of published studies, so we are not certain how reliable they are. Also, the studies were very different from each other and their results varied according to the specification of each travel measure (e.g. the type of screening approach), how it was put into practice and enforced, the amount of cross-border travel, levels of community transmission and other types of national measures to control the pandemic.

What this means

Overall, international travel-related control measures may help to limit the spread of COVID-19 across national borders. Restricting cross-border travel can be a helpful measure. Screening travellers only for symptoms at borders is likely to miss many cases; testing may be more effective but may also miss cases if only performed upon arrival. Quarantine that lasts at least 10 days can prevent travellers spreading COVID-19 and may be more effective if combined with another measure such as testing, especially if people follow the rules.

Future research needs to be better reported. More studies should focus on real-life evidence, and should assess potential benefits and risks of travel-related control measures to individuals and society as a whole.

Key messages

• Antifibrinolytics help prevent bleeding by stopping blood clots from breaking down too quickly. Tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) are two antifibrinolytic medications.

• Compared to placebo (an inactive 'dummy' medicine), TXA probably makes little or no difference to the number of people with thrombocytopenia and blood disorders who experience moderate or worse than moderate bleeding. It may make little or no difference to the number who experience severe, life-threatening bleeding, or dangerous blood clots in the blood vessels (thromboembolism).

• We do not know if EACA helps because there was a lack of data.

What are haematological disorders?

Haematological (i.e. blood) disorders are conditions that affect the blood and blood-forming organs (such as bone marrow). They disrupt the blood's normal functions of oxygen transport, clotting, and immunity. Some of these blood disorders are not cancer and may cause problems like anaemia or sickle cell anaemia. Others are cancers of the blood, such as leukaemia, lymphoma, and myeloma.

How are haematological disorders treated?

People with haematological (blood) cancers and other blood disorders are frequently at risk of severe or life-threatening bleeding from having low platelet counts (thrombocytopenia). When the number of platelets in the blood is low, the blood does not clot as it should, so people may bruise or bleed more easily. This may be from bone marrow failure due to an underlying blood disorder, but also from the toxic effect of treatment (chemotherapy) on the bone marrow.

People with low platelets may be given platelet transfusions: that is, receive platelets from donated blood to help prevent bleeding. These transfusions carry risks, ranging from mild reactions such as fevers, to more serious or even life-threatening consequences. These include infections transmitted to the patient from the transfused platelets, despite stringent attempts to prevent this.

What did we want to find out?

Clearly, ways to safely prevent bleeding in people with thrombocytopenia whilst also minimising exposure to transfused platelets would be welcome. One possible way of achieving these goals is the use of antifibrinolytics (also known as lysine analogues): tranexamic acid (TXA) and epsilon aminocaproic acid (EACA).

These medications help to stabilise the clots that form after bleeding, therefore reducing the chances of further bleeding as well as the need for transfusing platelets. There may be risks associated with the use of TXA and EACA: the most important is the increased risk of forming unwanted blood clots (such as deep vein thrombosis (DVT)), which could be potentially life-threatening.

We wanted to find out if TXA and EACA are better than placebo (an inactive 'dummy' medicine) or no medication at reducing the number of people who:

• experienced moderate bleeding or worse;

• experienced severe or life-threatening bleeding;

• experienced any type of thromboembolism (dangerous blood clots);

• died.

We also wanted to find out if TXA or EACA caused any serious unwanted, harmful effects.

What did we do?

We searched for studies that compared TXA or EACA with placebo or no treatment in people with haematological (blood) disorders who have a low platelet count and would usually be treated with platelet transfusions. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and the number of participants involved.

What did we find?

We found eight studies with a total of 1041 participants. Six studies compared TXA to placebo, one compared EACA to no EACA, and one compared EACA to standard platelet transfusion. Seven studies were in adults and one was in children. Five studies were funded by governments, universities, or other non-pharmaceutical organisations; one study received funding from a pharmaceutical company; and the remaining two studies did not provide information about funding.

Main results

In people with haematological disorders who have a low platelet count, tranexamic acid (TXA) compared to placebo:

• probably makes little or no difference to the number who experience moderate or worse than moderate bleeding;

• may make little or no difference to the number who experience severe, life-threatening bleeding, or dangerous blood clots in the blood vessels (thromboembolism).

There was not enough evidence to reach conclusions about the effect of TXA on the risk of death or the risk of serious side effects.

The two studies that looked at epsilon aminocaproic acid (EACA) did not report enough information to allow us to analyse their results.

What are the limitations of the evidence?

In general, we have little to no confidence in the evidence because there were too few studies to be certain about the results of our outcomes. In addition, some of the events we were looking for (e.g. death, dangerous blood clots) happened in very few people, which makes the results uncertain. These limitations mean it is difficult to draw firm conclusions about the effectiveness and safety of antifibrinolytic medications.

How current is this evidence?

The evidence is current to January 2025. This is an update of a review last published in 2016.

Background

Some infectious diseases are spread by airborne droplets from coughs and sneezes, which can infect people who touch contaminated skin or surfaces. Washing hands with soap and water may prevent these diseases from spreading. People with no soap may use other materials like ash, mud, soil with or without water, or water alone, to clean their hands. Hand cleaning with ash (the solid remains from cooking stoves and fires) might work by rubbing away or inactivating the virus or bacteria. However, chemicals in the ash could also damage the skin.

If ash is an effective hand cleanser, it could reduce the spread of coronavirus (COVID-19) and other infectious diseases in low-income areas where soap is not widely available.

What did we want to find out?

We wanted to know whether people who use ash for hand cleaning are more or less likely to catch infectious diseases than people who use soap, water, mud or soil, or who do not clean their hands. We also wanted to know whether using ash causes unwanted effects, like sore hands or a rash.

Our methods

We looked for studies that examined hand cleaning with ash compared with soap, mud, soil, water only or no hand cleaning. To answer our questions, the studies could include adults and children and take place anywhere.

COVID-19 is spreading rapidly, so we needed to answer this question quickly. This meant we shortened some steps of the normal Cochrane Review process. We could not find the full texts of five potentially relevant studies, or contact study authors for additional data. Although we searched several databases we may have missed some studies. We plan to include all relevant information in a future version of the review.

Results

We identified 14 studies that assessed ash for hand cleaning. Only one small study directly compared people chosen at random to use ash or soap or other materials (randomised studies produce the best evidence). The studies included people of all ages and mainly took place in low-income, rural communities. Six studies provided information to help answer our question.

One study investigated children who had been to hospital with diarrhoea compared with children who had not. Study authors looked at the hand washing area in the children’s houses to see how they cleaned their hands. They found that families that used ash for hand cleaning made a similar number of hospital visits for children with diarrhoea as those families that used soap.

Another study investigated whether women with unusual vaginal itching or discharge were more likely to clean their hands with ash than women who had not experienced such symptoms. They found that women who used ash and water for hand cleaning were as likely to experience vaginal itching or discharge as those women who used soap.

Four studies measured bacteria on hands after using ash, soap, water, mud or no hand cleaning. We are uncertain about the effect of ash compared with other materials for hand cleaning on bacteria on people’s hands because the studies used unreliable methods and their results were unclear.

None of the studies provided information about the severity of infectious diseases, whether people used ash or another material consistently, the number of deaths, or unwanted effects due to hand cleaning with ash.

Certainty of the evidence

Our certainty (confidence) in the evidence was limited because we found few studies; those we did find had unreliable methods and different kinds of participants, and none of the studies we found reliably examined whether participants got infections.

Conclusion

We are uncertain whether hand cleaning with ash compared with hand cleaning with soap, water, mud, soil or no hand cleaning stops or reduces the spread of viral or bacterial infections. We do not know if hand cleaning with ash causes unwanted effects.

Search date

This review includes evidence published up to 26 March 2020.

Key messages

• Vitamin B12 supplementation reduces the risk of vitamin B12 deficiency, and probably improves vitamin B12 levels in children less than 12 years of age, compared to placebo (a substance that looks the same as the intervention/treatment but does not contain any active ingredient) (that is, children who did not take vitamin B12 supplements).

• Vitamin B12 supplements, with other micronutrients (important vitamins and minerals the body needs in small amounts to function), may result in little to no difference in vitamin B12 deficiency or total vitamin B12 levels, compared to children who received the same supplements without vitamin B12.

• The impact of vitamin B12 supplements on other health outcomes in children is less clear.

What is vitamin B12?

Vitamin B12 is an important nutrient that helps make red blood cells and keep the body's cells and nerves healthy. Vitamin B12 deficiency is an important public health problem, including in children and in resource-poor settings. Lower vitamin B12 levels in children have been linked to anaemia (lower haemoglobin levels), and poorer growth, development, and cognition (a child's ability to gain knowledge through thought, understanding, and the senses).

What did we want to find out?

We wanted to find out if taking vitamin B12 supplements would improve the nutrition and health of children less than 12 years of age.

What did we do?

We searched for studies that looked at the effects of vitamin B12 compared to placebo (a substance that looks the same as the intervention/treatment but does not contain any active ingredient), no intervention, or the same supplements without vitamin B12. We summarised the results of the studies and our confidence in the evidence, based on information such as how the study was done.

What did we find?

We included 16 studies involving 4083 children less than 12 years of age (2 days to 11 years). Nine studies, including 2391 children, had data that we could analyse. The studies were conducted in 10 countries around the world. In most studies, the outcomes were assessed immediately after the intervention from five weeks to 31 months, with one study assessing outcomes after nine years. Vitamin B12 supplements were provided from 28 days to 31 months in amounts from 0.9 to 150 micrograms a day.

Supplementation with vitamin B12 alone versus placebo

There may be little to no difference in height/length, cognition (for example, attention), or development (for example, motor skill development). Children who received vitamin B12 supplements had less vitamin B12 deficiency, and probably had higher vitamin B12 levels, compared to placebo. There may be little to no difference between groups in anaemia. No studies provided data on any unwanted (adverse) effects.

Vitamin B12 alone versus no intervention

The evidence is very uncertain for height/length. No studies reported data we could analyse for other outcomes.

Vitamin B12 and other micronutrients, compared to supplements with the same supplement without vitamin B12

There may be little to no difference between groups for height/length, cognition (for example, attention), or development (for example, motor skill development). Children who received vitamin B12 supplementation (with other nutrients) may have little to no difference in vitamin B12 deficiency, vitamin B12 levels, anaemia, or any unwanted effects.

What are the limitations of the evidence?

The small number and the size of studies were limitations of this review. Few studies reported on health outcomes, including growth, cognition, development, anaemia, or any adverse effects. The different ages of children, and differences in the amount of vitamin B12 and when the outcomes were measured, are also limitations of this review.

How up to date is this evidence?

The evidence is up to date as of 23 September 2025.

Key messages

• We found four breast cancer risk prediction models that had been tested enough times to evaluate in detail. These were the Gail, Tyrer-Cuzick, BOADICEA, and BRCAPRO models.

• The BOADICEA model was one of the more reliable tools for estimating future breast cancer risk in women with a family history of the disease, meaning it may help them and their doctors to decide on treatment.

• Further research is needed to improve the accuracy of existing prediction models in distinguishing between women with a family history of breast cancer who will and will not develop the disease.

Why is it helpful to be able to predict a woman’s risk of breast cancer?

Women who have a history of breast cancer in their family have a higher likelihood of developing breast cancer themselves during their lifetime. In clinics, a woman's chance of developing breast cancer in a given time period is often estimated using statistical tools known as breast cancer risk prediction models.

Being able to estimate the risk of developing breast cancer accurately for a woman with a family history of breast cancer helps doctors and the woman decide how to manage or reduce her risk of breast cancer. Management may include:

• regular imaging with mammograms or magnetic resonance imaging (MRI; a type of scan that creates detailed pictures of the breast tissue) to detect breast cancer at an early stage;

• taking risk-reducing medications; or

• in some cases, surgical removal of both breasts to prevent breast cancer.

Currently, it is not clear which of the available breast cancer risk prediction models works best in women with a family history of breast cancer.

What did we want to find out?

We wanted to:

• identify breast cancer risk prediction models that have been developed or tested (or both) in women with a family history of breast cancer; and

• assess how accurately they predict future risk of developing breast cancer in these women.

What did we do?

We searched for studies that developed or tested these models. We looked at how accurately the models predicted breast cancer risk, focusing on:

• whether the predicted number of breast cancer cases was similar to the number that actually occurred (calibration); and

• whether the model could distinguish between women who did and did not develop breast cancer (discrimination).

When enough studies assessed the same model, we combined their results statistically.

What did we find?

We identified 12 models that estimate future breast cancer risk that had been tested in studies where all or most women had a family history of breast cancer. The models were tested using information from as few as 134 women to as many as 130,058. Most of the women lived in North America, Europe, or Australia, with a small number from Asia.

The studies were funded by governments (25 studies), universities (24), non-profit organisations (21), and industry (3). Six studies did not report funding sources, and some received funding from more than one source.

We were able to combine results from several studies for four models: the Gail, Tyrer-Cuzick, BOADICEA, and BRCAPRO models.

Calibration: was the predicted number of breast cancer cases similar to the actual number?

• The Gail and BOADICEA models accurately estimated the numbers of women in the included studies who would develop breast cancer in a given timeframe:

  • for every 100 breast cancers Gail predicted would occur, about 106 actually occurred in reality;

  • for every 100 breast cancers BOADICEA predicted, about 98 actually occurred.

• The Tyrer-Cuzick model estimated that more women in the studies would develop breast cancer than actually did. For every 100 breast cancers it predicted, only about 86 actually occurred.

• The BRCAPRO model estimated that fewer women in the studies would develop breast cancer than actually did. For every 100 breast cancers it predicted, about 144 actually occurred.

Discrimination: how well did the models distinguish between women who develop and do not develop breast cancer?

• All four models were moderately accurate in distinguishing between women who would and would not develop breast cancer in a given timeframe, but none did a great job.

• The Tyrer-Cuzick (version 8), BOADICEA, and BRCAPRO models correctly distinguished women who would develop breast cancer from those who would not about 64 to 65 times out of 100.

• The Gail model performed slightly less well, correctly distinguishing women who would develop breast cancer 61 times out of 100.

What are the limitations of the evidence?

We rated the quality of most studies included in our review as poor or unclear, which means we cannot be confident that these results are reliable. Our confidence was reduced for several reasons, including:

• in some studies, too few women developed breast cancer, making it harder to judge how accurate the prediction models were;

• not all studies reported the model performance information we sought;

• some studies had missing information or did not explain how they handled missing information.

How up to date is this evidence?
The review includes studies published up to December 2024.

Key messages

• There is little difference in how long women with advanced (stage IIIC/IV) epithelial ovarian cancer (EOC) survive, whether they have chemotherapy or surgery first. There is probably little difference in how long it takes for EOC to return after treatment.

• Giving chemotherapy prior to surgery probably reduces serious risks of surgery; probably halves the risk of needing bowel removal during surgery; and probably results in a large reduction in needing a stoma (where the bowel is diverted through the abdominal wall into a bag to collect the contents).

• Giving chemotherapy prior to surgery is an alternative to surgery followed by chemotherapy in women with advanced EOC. Decisions about which treatment to have first depend on patient preference, how well the woman is at time of diagnosis, the risks of surgery, and the amount and spread of disease.

What is epithelial ovarian cancer, and how is it treated?

Ovarian cancer is the eighth most common cancer worldwide in women. Around 90% of ovarian cancers are epithelial ovarian cancer (EOC), arising from the surface of the ovary or lining of fallopian tubes. Most women with EOC are diagnosed when their cancer is at a late stage, and their disease has spread throughout the abdominal cavity (stage IIIC/IV). Although survival rates have improved over the last 30 years, only four in every 10 women with EOC are alive 10 years after diagnosis.

Treatment for ovarian cancer involves a combination of surgery and chemotherapy. Surgery aims to remove as much visible cancer as possible. However, surgery alone is unlikely to cure EOC, and most women will also need chemotherapy. Chemotherapy uses platinum-based medications to treat cells that cannot be removed by surgery or cannot be seen.

Traditionally, chemotherapy is given after surgery. However, chemotherapy can be given before surgery and then followed by the remaining cycles of chemotherapy, as usual.

Why is this important?

Women with advanced EOC may be too unwell at diagnosis to have surgery, or may require extensive surgery to remove all visible disease. Giving chemotherapy before surgery may shrink the cancer prior to surgery, so that women become well enough to undergo surgery or need less extensive surgery.

What did we want to find out?

We wanted to find out if giving chemotherapy before surgery was better than doing surgery first and then giving chemotherapy. We were interested in how many women with EOC:

• were alive 48 months after diagnosis;

• had no EOC 24 months after treatment;

• died following surgery;

• had unwanted effects due to surgery;

• needed to have their bowel diverted through the abdominal wall into a bag to collect bowel contents (a 'stoma'), or to have part of the bowel removed (a 'bowel resection'); and

• saw an improvement in their quality of life.

What did we do?

We searched for studies that investigated chemotherapy followed by surgery compared with surgery followed by chemotherapy in women diagnosed with advanced EOC. 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 seven studies with 2650 women with stage III/IV EOC that compared the effects of giving an initial chemotherapy treatment followed by surgery then chemotherapy as normal, with surgery followed by chemotherapy. Studies took place worldwide, in 20, mainly high-income countries.

Giving chemotherapy before surgery:

• makes little or no difference to the number of women still alive after 48 months (5 studies, 2380 women);

• probably makes little or no difference to the number of women who remained disease-free after 24 months (5 studies, 2380 women);

• reduces deaths due to surgery (5 studies, 2201 women);

• probably reduces the risk of severe unwanted effects of surgery (3 studies, 1094 women);

• probably results in a large reduction in the risk of needing a stoma (3 studies, 1291 women), or a bowel resection (5 studies, 2237 women);

• may slightly improve quality of life 6 months after treatment, but the results are uncertain (3 studies, 559 women).

What are the limitations of the evidence?

We are confident that chemotherapy before surgery makes no difference to overall survival and reduces deaths due to surgery. We are less confident in the rest of the evidence for several reasons. It was clear which treatment women received, which might change the results. Although the studies only enrolled women with advanced EOC (stage IIIC/IV), and many had extensive disease, later studies only enrolled women when the surgeons thought they could remove all of the visible disease with surgery. We could only analyse results from five of the seven studies. We will add results from further studies when they are available.

How up-to-date is the evidence?

The evidence is current to 9 October 2025.

Key messages

• We are unsure about the effects of rocking premature babies to stimulate their inner ear and brain (vestibular stimulation) on death compared to no stimulation; there may be little to no difference in weight gain.

• We identified too few studies to report on the effects of vestibular stimulation on physical or mental development, such as learning difficulties, cerebral palsy, or blindness. No studies compared one type of vestibular stimulation with another, so it is unclear which types of vestibular stimulation are most effective.

• Future studies should be bigger, use more robust methods, and define and report their research more clearly.

What is the vestibular system?

The vestibular system is a sensory system within the inner ear and the brain. It controls balance and physical coordination. It helps us maintain our posture when standing, sitting or walking; it helps our brains to process what we see and hear. It is vital to navigate the day-to-day world. Like other organs and sensory systems, the vestibular system develops while we are in the womb.

What is vestibular stimulation?

Vestibular stimulation involves body movements such as rocking, swinging, rolling, turning and bouncing. In the womb, babies receive this type of stimulation through the mother's movements. After birth, babies receive this type of stimulation when they are held and fed, washed and changed, played with, and moved around onto their tummies or sides. Premature babies, born before nine months of pregnancy, may not receive as much of this type of stimulation as babies born at nine months because they may be quite small and fragile, or ill and in an incubator. This may affect their physical and mental development. For example, they may develop breathing problems, not gain weight, or be deaf or blind.

What did we want to find out?

We wanted to find out if stimulating the vestibular systems of hospitalized, premature babies by gently rocking, repositioning, swinging in a hammock, or laying on a waterbed or on an air mattress could be helpful and safe for their short-term and long-term well-being. Specifically, we wanted to find out if vestibular stimulation might:

• decrease the number of babies who develop physical or mental delays at 18 to 24 months of age;

• increase infants' weight gain;

• reduce death in babies during hospitalization after birth.

What did we do?

We searched for studies set in neonatal intensive care units that compared:

• any type of vestibular stimulation to no vestibular stimulation;

• one type of vestibular stimulation to another. For example, hammock swinging compared to waterbed rocking.

We compared and summarized the results of the studies and rated our confidence in the evidence based on factors such as the size of the study (number of babies) and the methods of the study.

What did we find?

We found 4 studies with 196 premature infants. Three studies took place in the USA and 1 in Canada. Healthcare professionals carried out vestibular stimulation in all studies. The studies investigated different types of vestibular stimulation.

• One study evaluated vestibular stimulation with an air mattress swinging back and forth in a regular rhythm.

• One study evaluated vestibular stimulation with a waterbed swinging back and forth in a regular rhythm.

• One study evaluated rocking.

• One study evaluated stimulation with a rocking chair (VestibuGlide).

No studies provided evidence about disabilities such as cerebral palsy, delayed physical or mental development, blindness or deafness. We did not find any studies that directly compared different types of vestibular stimulation.

Main resultsVestibular stimulation compared to no intervention

It is very uncertain whether vestibular stimulation, compared to no stimulation, has any effect on death (1 study, 122 babies).

Three studies (169 babies) investigated weight gain, but they all defined it differently and measured it over different periods, so we could not combine their results. We don't know whether vestibular stimulation makes any difference to weight gain compared to no stimulation.

What are the limitations of the evidence?

We have little confidence in these results, as the few studies we found were not well-designed and included few babies. Several studies did not report on outcomes or lacked data that we were interested in.

How up-to-date is this evidence?

The evidence is current up to 26 October 2025.

Key messagesAlbumin versus no intervention

• We are very uncertain about the effects of albumin on death due to any cause, unwanted serious events, complications of cirrhosis (advanced liver damage), and severe infection.

• We are very uncertain whether albumin may reduce kidney damage.

Albumin versus other intravenous fluids (such as synthetic colloids or saline solutions)

• We are very uncertain about the effects of albumin on death due to any cause, on kidney damage, or whether albumin increases serious unwanted effects or reduces septic shock.

• More larger studies are required where the people and investigators are not aware of the treatments being used. These studies should include children. They also need to investigate differences in the albumin used and compare it with other types of intravenous fluids.

What is cirrhosis of the liver?

Cirrhosis is scarring of the liver, which develops over time. Complications of cirrhosis may include the appearance of fluid in the tummy, impaired brain function, or yellowing of the skin. People with liver cirrhosis are prone to bacterial (tiny germs that can make you sick) infections. Complications of advanced cirrhosis are frequent and can lead to death. If treated on time, complications and death can be reduced.

What did we want to find out?

To assess the benefits and risks of human albumin (a protein found in the blood), in addition to antibiotics, in people with liver cirrhosis and bacterial infections compared to no intervention, placebo (dummy pill), or other intravenous fluids (sterile products given within the vein to increase or retain the volume of fluid in the organ system responsible for transporting blood through vessels to and from all parts of the body (that is, the circulatory system).

What did we do?

We searched for studies that tested albumin in people of any age with cirrhosis and infections. We collected and summarised the data needed for our analysis. We studied, among others, how similar the study participants were, whether all participants completed the studies, and what kind of data were reported and how they were measured. We rated our confidence in the evidence based on factors like the study methods used to conduct the studies. We rated the certainty of evidence in the studied outcomes (that is, the results collected at the longest time point) as very low or low.

What did we find?

We found 11 studies with 1273 adults with an average age of 54 years (no children). All the people involved received antibiotics. Albumin was administered through a vein. In eight studies, albumin was compared with no treatment. In three studies, albumin was compared with different types of intravenous fluids. Five studies included 388 people with cirrhosis and an infection of the peritoneum (a membrane that lines the inside of the tummy), called spontaneous bacterial peritonitis. Four studies included 477 people with cirrhosis and infections in various body parts, like the lungs, urinary tract (where urine is produced), and skin. Two studies enroled 408 people with cirrhosis who had infections in different body areas along with dangerously low blood pressure due to a severe infection.

One trial was conducted in eight European countries, and ten were conducted in India, Spain, China, France, Egypt, and Taiwan. The studies took place in a clinic or university hospital. About half the studies were short-term, lasting for up to one month, and the other half lasted for three months.

Ten studies were either free from for-profit support or did not report the sources of support, and one declared partial private support, delivering albumin vials.

Main results

We identified problems in the way the studies were performed, which reduced the certainty of the results.

Albumin versus no intervention
It is either uncertain or very uncertain whether albumin affects death due to any cause, unwanted serious events, complications of cirrhosis, and septic shock (that is, decreased blood pressure in severe infection with organ damage). It is very uncertain whether albumin may reduce the risk of kidney damage. The studies did not report data on well-being.

Albumin versus other intravenous fluids

It is very uncertain whether albumin affects death due to any cause or kidney damage, or whether albumin may increase serious unwanted events. It is uncertain whether albumin may reduce septic shock. The studies did not report data on well-being or on other complications of cirrhosis.

For both comparisons, we could not assess the effect of albumin regarding the site of infection.

What are the limitations of the evidence?

We are very unconfident of the evidence because there were problems with the design and conduct of the studies, and the data for a meaningful analysis of the studied outcomes were insufficient or lacking. Therefore, we cannot be sure of the effects of albumin compared with no intervention, or compared with other intravenous fluid.

How up-to-date is this evidence?

The evidence is up-to-date to 20 August 2025.

Key messages

• Compared with trapeziectomy (removal of the bone at the base of the thumb), trapeziectomy with LRTI (replacing the ligament and strengthening the joint with tendon from the forearm) may provide little to no benefit in pain, function, joint imaging or unwanted effects from 3 to 54 months after treatment.

• We don't know the best surgery to treat osteoarthritis of the thumb. More research is required in this area.

What is thumb osteoarthritis?

Osteoarthritis is a disease of the joints, sometimes called 'wear and tear disease'. Osteoarthritis at the base of the thumb (trapeziometacarpal joint) may cause pain, stiffness and weakness in the thumb. This can affect how well the thumb moves, how strong the grip is and how well someone can do routine things at home or at work.

Although many people suffer from this condition, its effects on how you feel cannot be measured with X-rays. Therefore, osteoarthritis of the thumb is treated based on its effects instead of what is seen on X-rays.

For many people, these effects are very small, and treatment is not necessary. Certain jobs and hobbies can worsen it, especially if the person needs to pinch and grip a lot.

How is thumb osteoarthritis treated?

Osteoarthritis in the thumb can be treated using:

• non-surgical approaches, like splinting or anti-inflammatory medication

• steroid injections

• surgery - often used when the first two methods do not work

There are many types of surgery, but they all aim to reduce pain and increase function (or reduce disability). Most surgeries begin by removing the trapezium bone at the base of the thumb (trapeziectomy) and then reconstructing or securing the joint using ligaments or tendons taken from elsewhere in the body, from a donor, or artificial ones. The most common procedure is trapeziectomy with ligament reconstruction and tendon interposition (LRTI). This involves reconstructing the ligament that holds the bones between the thumb and index finger together and filling the space left behind by the removed bone with spare tendon from the forearm to support the thumb. Other surgeries include leaving the space left behind by the trapeziectomy open on purpose to fill up with scar tissue (haematoma distraction) or replacing the joint entirely with artificial joints (arthroplasty).

What did we want to find out?

For people with thumb osteoarthritis, we wanted to find the best surgical methods to:

• reduce pain, disability, unwanted events, and treatment failure (leading to more surgery), and

• improve quality of life.

We also wanted to see the effects of different methods on people's satisfaction with their treatment and what the joint looked like in an X-ray.

What did we do?
We searched for studies that compared different surgical methods for thumb osteoarthritis. People in the studies could be any age or sex, have severe or mild osteoarthritis, and be anywhere in the world. We compared and summarised the results and rated our confidence in the evidence.

What did we find?

We found 25 studies with 1591 people, mostly women. The studies used various surgical procedures. The most widely used was trapeziectomy with LRTI. Studies followed people for 12 to 120 months.

No studies included placebo surgery (surgery without aiming to correct the arthritis) or sham surgery (fake surgery) as a comparison.

Main results

Compared with trapeziectomy, trapeziectomy with LRTI may provide little to no benefit in pain, function, joint imaging or unwanted effects between 3 and 54 months after treatment (4 studies; 421 participants).

Pain measured on a 0 to 100 scale (0 is no pain) was 2.8 points better with trapeziectomy with LRTI.

• People who had trapeziectomy with LRTI rated their pain as 23.2 points.

• People who had trapeziectomy rated their pain as 26 points.

Physical function measured on a 0 to 100 scale (0 is best function) was 0.01 points worse with trapeziectomy with LRTI.

Unwanted effects: after trapeziectomy with LRTI, 66 more people per 1000 had unwanted effects at the end of follow-up.

• 133 per 1000 people reported an unwanted event with trapeziectomy with LRTI.

• 67 per 1000 people reported an unwanted event with trapeziectomy.

Joint imaging: distance between the scaphoid bone (bone in the wrist) and first metacarpal (bone in the hand connecting your wrist to your thumb) was 0.1 mm worse with trapeziectomy with LRTI compared to trapeziectomy.

Studies did not report people's overall satisfaction with treatment, treatment failure or quality of life.

What are the limitations of the evidence?

We have little confidence in the evidence that trapeziectomy with LRTI reduces pain, improves function, or results in more people reporting unwanted effects, as the studies were small, and the surgical procedures varied considerably across studies.

We are uncertain if any surgery has benefits compared to no surgery, non-surgical therapies or placebo surgery, as we found no studies that assessed these comparisons. Further research is likely to change the estimates of these results.

How up-to-date is this evidence?

This is an update of a review first published in 2005. The evidence is current to 19 May 2025.

Key messages

• Compared to a saline placebo (an inactive sterile water injection), Botox-A may provide a slight short-term improvement in pain (6%) which does not extend to the long term. People may report treatment success (20%) in both the short and long term. There may be no improvement in people's ability to carry out everyday activities, or in health-related well-being. There may be a 16% higher chance of mild unwanted effects such as soreness at the injection site, muscle fatigue, general soreness, or headache lasting up to three weeks.

• Manufacturers of Botox A funded some of the research, which may have influenced the studies and overestimated the benefit of this treatment.

• Future studies should be larger, use better methods and last longer. The studies should be independently funded.

What is Botox-A?

Botox-A is a neurotoxin (chemical substance) that temporarily weakens or paralyses certain muscles or blocks certain nerves. It is injected into trigger points. Trigger points are defined as very sensitive knots within taut bands of skeletal muscles that can produce pain felt in a different body region other than where the problem is, also known as referred pain.

Botox-A might help persistent neck pain by reducing muscle tension and spasm, and related pain signals.

People might experience unwanted effects that are mild and short-lived, such as small areas that are sore or tender. Rare events like severe allergic reaction that leads to death can occur.

What did we want to find out?

For people with persisting neck pain, we wanted to find out if Botox-A was better than a saline placebo (inactive sterile water) injection at improving:

• pain;

• physical function (ability to carry out everyday activities);

• health-related well-being;

• how successful people felt their treatment was;

• patient satisfaction.

Neck pain may include symptoms originating from the neck that are felt in the head, upper back, and arm. Neck pain could be with or without associated myofascial pain (sensitive knots with taut muscle bands), degenerative changes (wear and tear changes), whiplash-associated disorders, and headaches stemming from the neck.

We also wanted to know if Botox-A caused any unwanted effects.

What did we do?

We searched for studies that looked at Botox-A medical injections compared to a placebo. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods, varied treatment doses, how similar the studies' results were, and how big the studies were.

What did we find?

We found 16 studies with 855 people with persistent neck pain (associated myofascial pain, whiplash-associated disorders, or headaches stemming from the neck). They were aged 18 to 80 years and more than half (64%) were women. Most studies lasted from 3 to 12 weeks; only two studies lasted 24 weeks or longer. They took place in pain management clinics in hospitals, surgery departments, and universities in North and Central America, Europe, the Middle East, and Asia. Most studies reported short-term results (up to three months). The total Botox-A dose ranged from 10 to 400 units, administered across 1 to 10 trigger points.

Main results

In people with persistent neck pain treated with Botox-A compared with placebo:

• there may be a slight short-term improvement in pain (6%; 12 studies, 393 people), but these changes may not make a real difference in daily life. The observed improvement in pain may not be sustained in the long term;

• there may be little to no benefit for daily physical function (2%; 3 studies, 76 people) or health-related well-being, but we are not confident in this evidence;

• there may be a small improvement in both in the short term (20%; 1 study, 19 people) and long term (20%; 1 study, 31 people) for participant-reported treatment success;

• the risk of mild unwanted effects such as injection site soreness, muscle fatigue, muscle soreness, or general headache may be 16% higher when compared to placebo. These unwanted effects may last up to three weeks.

No studies evaluated patient satisfaction.

What are the limitations of the evidence?

Our confidence in the evidence is limited for several reasons.

• Most of the evidence was short-term, so we don’t know what the long-term effects are.

• Most studies were funded by pharmaceutical companies, so they may overstate the benefits of Botox-A.

• The methods used in several studies likely introduced sources of error, including how they divided people into treatment groups and the possibility that people in the studies knew which treatment they were getting.

• Studies used different doses of Botox-A, which makes it difficult to compare their results.

Future studies should be independently funded, use more robust methods and present long-term results.

How up to date is this evidence?

The evidence is up to date to March 2026. This review updates the previous version published in 2011 with 10 new studies. We now find a potentially slight improvement in pain.

Key messages

• Lowering the body temperature of donors in the intensive care unit before retrieving organs may not improve how soon the organ starts to work in the recipient.

• Lowering the body temperature of donors may not reduce the number of organs that could be used for transplant or cause any safety problems (such as heart issues).

• One-year survival of the transplanted organ was only reported by three of the four studies. Quality of life and heart disease for the recipients at 12 months were not reported in any of the studies. Key organ-related measures at 12 months (e.g. heart: heart function; pancreas: the need for insulin) were not reported.

What is solid organ transplantation?

Solid organ transplantation is a surgical procedure where a solid organ (kidney, heart, liver, lung or pancreas) is transferred from one person - the donor - to another person - the recipient. It is the optimal treatment for people living with end-stage organ failure. However, there remains a shortage of optimal organs for donation. Many organs come from people who are brain dead (where a person has permanent and irreversible loss of brain function) in an intensive care unit. The process of brain death is known to cause significant injury to organs. Therefore, efforts to optimise the care of these donors should be maximised to achieve the best outcomes and graft function in the transplant recipients.

Why lower the body temperature of donors, and how is it done?

Lowering the body temperature of donors to below normal core temperature (< 35.5°C) may slow the body's processes, helping to keep the organs healthier until they are retrieved and transplanted. This can take place in the intensive care unit between brain death and organ donation. Lowering the body temperature may be achieved by allowing donors to spontaneously cool to the target temperature, using fans, ice packs, or specific external cooling systems to promote the lowering of the body temperature of the donor, or bladder irrigation, invasive cooling lines or temperature-controlled humidified gases used during ventilation to achieve the desired core temperature. The degree of therapeutic hypothermia can also be classified as mild (34.0°C to 35.5°C), moderate (32.0°C to 33.9°C), moderately deep (30.0°C to 31.9°C) and deep (< 30°C).

What did we want to find out?

We wanted to see whether lowering the body temperature of donors makes organs healthier and improves outcomes for recipients after an organ transplant. We were interested in:

• how soon donated organs started working;

• whether the transplant was successful;

• whether the recipient survived (and for how long).

What did we do?

We searched for studies that assessed whether lowering the body temperature of donors was effective and if it caused unwanted effects. Donors in the studies had to have irreversible loss of all functions of the entire brain or irreversible loss of the capacity for consciousness and an irreversible loss of the ability to breathe. Recipients had to be receiving solid organs such as kidney, heart, liver, lung or pancreas. Studies could be set anywhere in the world.

What did we find?

We found four studies with 2096 donors that looked at the effect of lowering the body temperature of donors prior to transplantation. Two studies looked at kidney transplantation, and two studies looked at multiple solid organs (kidney, liver, lung, heart, pancreas). Studies were undertaken in the USA and France.

Kidney transplantation

Lowering the body temperature of donors compared to keeping them at normal body temperature:

• may not reduce the time it takes for transplanted kidneys to start working (4 studies, 3015 recipients);

• may make no difference to survival of the transplanted kidney one year after transplant (3 studies, 2075 recipients);

• may make no difference to how many kidney recipients survived for a year after transplant (1 study, 526 recipients).

Other organs

Lowering the body temperature of donors compared to keeping them at normal body temperature:

• may not reduce the time for transplanted lungs to start to work (1 study, 99 recipients);

• may not reduce the time for transplanted livers to start to work (1 study, 262 recipients);

• is unlikely to reduce the number of organs available for transplant (4 studies, 4265 recipients).

Lowering the body temperature of donors compared with keeping them at normal body temperature may not cause any problems with the donors (such as heart issues) (3 studies, 2015 donors).

What are the limitations of the evidence?

The small number of studies investigated, and the donor organs transplanted were the major limitations of this review. One-year survival of the transplanted organ was only reported by three studies. Quality of life and heart disease for the recipients at 12 months were not reported in any of the studies. Key organ-related measures at 12 months (e.g. heart: heart function; pancreas: the need for insulin) were not reported. Most studies focused on kidney donors and recipients, with very little information for other solid organs.

How up to date is this evidence?

The review is current to September 2025.

Key messages

• Compared to standard dental screw implants placed after building up the jawbone, longer screws placed in the cheekbone were less likely to fail and allowed working replacement teeth to be fitted much sooner, but led to more complications.

• Drilling the holes that receive the implant screws can be done with a standard rotary (spinning) tool or a vibrating tool that 'shaves' the bone (piezoelectric surgery). There may be little or no difference between the two methods in terms of how durable the implants or replacement teeth are, or the risk of complications, but rotary drills are probably faster.

• Few studies have looked at these issues. We need more and bigger studies to have more confidence about the benefits and risks.

What happens when people have no or few natural teeth?

When teeth are lost, the surrounding bone can gradually shrink because it is no longer stimulated by chewing. The amount of bone loss varies from person to person. It can be so severe that people are unable to wear removable dentures comfortably. This can make eating and speaking difficult and may affect confidence, well-being, and social relationships. Dental implants can help address these problems.

What are dental implants, and how do they help?

Standard dental implants are short screws (0.5 to 2 cm long) placed into the jawbone which act like artificial tooth roots. Dentists can attach permanent ('fixed') teeth to them, or removable or semi-removable dentures.

Cheekbone implants ('zygomatic implants') are longer: about 3 to 5 cm. They are used when the upper jawbone has shrunk so much that there is not enough bone left to hold standard implants securely. Cheekbone implants almost always support fixed teeth, not removable dentures.

With cheekbone implants, fixed teeth can often be placed on the same day as the implants. This is because they avoid the need for jawbone grafting, which is when a surgeon adds new bone (or bone-like material) to the jaw so it can support an implant. Bone grafting is complex, expensive, and time-consuming. It may require several surgeries and take more than a year before replacement teeth can be fitted.

Cheekbone implant screws can be placed using rotary drills or piezoelectric surgery, which uses sound vibrations to cut bone and may be less traumatic. Cheekbone dental implants can lead to complications, and the potential benefits need to be weighed against these risks.

What did we want to find out?

We wanted to find out if, compared to standard implants in grafted jawbone, cheekbone implants led to fewer:

• replacement teeth failures – where the teeth break or loosen;

• implant failures – where the implant screws become unstable;

• complications.

We also wanted to find out:

• which type of implant led to higher satisfaction and faster rehabilitation;

• which method for implant site preparation was faster for surgeons and preferred by people undergoing treatment.

What did we do?

We searched for studies that compared:

• cheekbone implants to standard implants in grafted jawbone in people with severe bone loss in the upper jaw; or

• different ways to prepare the cheekbone implant site.

We compared and summarised the study results, and rated our confidence in the evidence, based on factors such as study methods.

What did we find?

We found two small studies that followed participants for three years. They were both carried out in Europe. One compared cheekbone implants to standard implants in grafted bone, and involved 71 people. The other compared piezoelectric surgery to rotary drills for preparing the implant site, and involved 20 people.

Main results

After three years, compared to standard implants in grafted jawbone, cheekbone implants:

• may have led to fewer replacement teeth failures: for every 100 people treated, about 12 fewer people with cheekbone implants had problems with their replacement teeth;

• probably had fewer implant failures: for every 100 people treated, about 22 fewer people with cheekbone implants had problems;

• probably led to more complications: roughly four-fifths of people with cheekbone implants had complications, compared to about half of the people with standard implants.

We do not know which procedure left people more satisfied. However, people who received cheekbone implants probably received their new teeth much sooner – in a little more than 1 day – than those with standard implants, where it typically took 444 days before replacement teeth could be fitted.

In the study that compared two methods (piezoelectric surgery versus rotary drills) for preparing the implant sites, after three years, there may be little or no difference between them in terms of:

• replacement teeth failures;

• implant failures;

• complications;

• people's preference.

However, rotary drills probably made implant placement faster by more than 9 minutes.

What are the limitations of the evidence?

Our confidence in the evidence ranged from very low to moderate. We found only two studies testing these approaches, and they involved few people. More well-designed studies are needed to identify the best methods.

How up to date is this evidence?

The evidence is current to November 2025.

Key messages

• Giving adults smaller amounts of red blood cells during a blood transfusion may not make any difference to their risk of dying, how long they stay in hospital, or any unwanted treatment effects, compared with giving larger amounts of red blood cells, but the evidence from some studies is unclear.

• At the same time, it may reduce the amount of blood given for one transfusion, which saves money and means that more blood is available for other people who need a transfusion.

• We did not find enough information to know whether it is better to give children or babies who need a transfusion larger or smaller amounts of red blood cells.

What is a blood transfusion?

Many people in hospital do not have enough healthy red blood cells to carry oxygen around their body, which can make them tired, weak, and short of breath. This is called anemia, and it can be treated in several different ways. Sometimes, people may need to have extra blood added to their own (a blood transfusion). Red blood cells are an important part of the extra blood. However, there is not much information available for doctors about the amount of red blood cells (the ‘red blood cell volume’) that should be given.

The volume of red blood cells in the blood can be measured in units (e.g. one unit of red blood cells) for adults. For babies and children, doctors give a certain amount depending on how much the child weighs. For example, they might give 20 mL of red blood cells for every kg the child weighs (20 mL/kg). Because blood transfusion involves some risks and there is a limited amount of blood available, doctors have been recommended to give the smallest effective amount to adults. Currently, it is recommended that one unit of red blood cells (rather than two units) is given to adults in hospital who are not bleeding and whose condition is not changing quickly. In children and newborns, there is no recommended standard amount for transfusion.

What did we want to find out?

We wanted to find out if it is safe to give a smaller amount of red blood cells to adults, children and newborns in hospital who need a blood transfusion. We looked at whether people stayed in hospital longer, had any unwanted effects from the treatment, any problems with their heart, breathing or other body systems, if they started bleeding again, and how many red blood cells were given.

What did we do?

We searched for studies that compared two different volumes of red blood cell transfusion for people in hospital. For example, two units of red blood cells compared with one unit of red blood cell for adults, or 20 mL/kg compared with 10 mL/kg for children. We compared and summarized 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 12 studies that involved 5478 people. Nine studies included a total of 1945 adults; one included women needing a blood transfusion after childbirth and the others included people who needed a blood transfusion because of blood cancer. One study included 3199 anemic children aged two months to 12 years, and two studies included a total of 334 newborn babies born before 32 weeks of pregnancy.

In adults, when comparing one unit of red blood cells to two units of red blood cells for a single blood transfusion, there may be no increased risk of dying, no increase in length of hospital stay, and no increase in any unwanted effects of the transfusion, blood clots (thrombosis) or starting to bleed again. However, the evidence is unclear.

What are the limitations of the evidence?

We have little confidence in most of the evidence we found because there were not enough studies to be certain about the results. In some of the studies, it is possible that people were aware of which treatment patients were getting. People in some of the studies were not randomly placed into the different treatment groups. This means that differences between the groups could be due to differences between people rather than between the treatments.

How up to date is this evidence?

The evidence is current to August 2025.

Key messages

• Non-medicinal measures (e.g. visiting restrictions or regular testing) may prevent SARS-CoV-2 infections (causing COVID-19 disease) in residents and staff in long term care facilities, but we have concerns about the reliability of the findings.

• More high-quality studies on real-world experiences are needed, in particular.

• More research is also needed on measures in facilities where most residents and staff are vaccinated, as well as regions other than North America and Europe.

What are non-medicinal measures?

Non-medicinal measures are ways of preventing or reducing disease without using medicine, such as vaccines. These include controlling people's movements and contacts, using personal protective equipment (PPE), or regular testing for infection.

SARS-CoV-2 is very infectious. Elderly or disabled people, who live in care homes (long-term care facilities), are vulnerable to infection because they live in close contact with other people, with carers and visitors entering and leaving the facility. Due to age and underlying health conditions, care home residents have an increased risk of becoming seriously ill with COVID-19 and dying from the disease.

What did we want to find out?

We wanted to find out how effective non-medicinal measures are in preventing residents and staff in long-term care facilities from becoming infected with SARS-CoV-2 and in reducing the spread of the infection. We focused on all types of long-term care facilities for adults, such as nursing homes for the elderly and skilled nursing facilities for people living with disabilities.

What did we do?

We searched for studies that investigated the effects of non-medicinal measures in long-term care facilities. To be included, studies had to report how many infections, hospitalisations or deaths the measures prevented in residents or staff, or whether the measures prevented the introduction of the virus into the facilities or prevented outbreaks within facilities. We included any type of study, including observational studies that used ‘real-world’ data, or modelling studies based on assumed data from computer-generated simulations.

What did we find?

We found 22 studies, 11 observational and 11 modelling studies. All studies were conducted in North America or Europe.

There were four main types of measures.

1.Entry regulation measures to prevent residents, staff or visitors introducing the virus into the facility. Measures included staff confining themselves with residents, quarantine for newly-admitted residents, testing new admissions, not allowing the admission of new residents, and preventing visitors from entering facilities.

2. Contact-regulating and transmission-reducing measures to prevent people passing on the virus. Measures included wearing masks or PPE, social distancing, extra cleaning, reducing contact between residents and among staff, and placing residents and staff in care groups and limiting contact between groups.

3. Surveillance measures designed to identify an outbreak early. Measures included regular testing of residents or staff regardless of symptoms, and symptom-based testing.

4. Outbreak control measures to reduce the consequences of an outbreak. Measures included isolation of infected residents, and separating infected and non-infected residents or staff caring for them.

Some studies used a combination of these measures.

Main results

Entry regulation measures (4 observational studies; 4 modelling studies)

Most studies showed that such measures were beneficial, but some studies found no effects or unwanted effects, such as depression and delirium among residents in the context of visiting restrictions.

Contact-regulating and transmission-reducing measures (6 observational studies; 2 modelling studies)

Some measures may be beneficial, but often the evidence is very uncertain.

Surveillance measures (2 observational studies; 6 modelling studies)

Routine testing of residents and staff may reduce the number of infections, hospitalisations and deaths among residents, although the evidence on the number of deaths among staff was less clear. Testing more often, getting test results faster, and using more accurate tests were predicted to have more beneficial effects.

Outbreak control measures (4 observational studies; 3 modelling studies)

These measures may reduce the number of infections and the risk of outbreaks in facilities, but often the evidence is very uncertain.

Combination measures (2 observational studies; 1 modelling study)

A combination of different measures may be effective in reducing the number of infections and deaths.

What are the limitations of the evidence?

Our confidence in these results is limited. Many studies used mathematical prediction rather than real-world data, and we cannot be confident that the model assumptions are accurate. Most observational studies did not use the most reliable methods. This means we cannot be confident that the measure caused the effect, for example, that testing of residents reduced the number of deaths.

How up to date is this evidence?

This review includes studies published up to 22 January 2021.

Key messages

• Current care for preterm infants (babies born early) who are at risk of respiratory distress syndrome (lung problems causing breathing difficulties) usually involves an intervention called continuous positive airway pressure (CPAP). In these infants, giving surfactant (a coating for the lungs to make breathing easier) as a preventive measure may make little or no difference to the risk of chronic lung disease (needing long-term oxygen support), and probably slightly increases the risk of death, compared with giving surfactant only to those babies who actually develop breathing problems.

• In contrast, for preterm infants not receiving CPAP, giving surfactant preventively reduces the risk of death and may slightly reduce the risk of pneumothorax (lung injury), compared to giving surfactant only if and when breathing problems develop.

• In our view, giving all preterm infants CPAP at birth and then giving surfactant only to those who have symptoms of breathing problems may be the best approach to managing the risk of respiratory distress syndrome.

What is a preterm infant?

A preterm infant is a baby who is born early, having spent less than 37 weeks in the womb.

What is surfactant?

Surfactant is a mixture of fats and proteins produced by the body that coats the inside of the alveoli (tiny air sacs in the lungs) and helps the lungs work properly. Some preterm infants are born before their lungs produce enough surfactant, which makes it difficult for their lungs to stay open and get enough oxygen. This is called respiratory distress syndrome (RDS). Surfactant replacement therapy can be used to replace the missing surfactant.

What did we want to find out?

We wanted to know whether to give surfactant to preterm babies, preventively, that is, immediately after birth before any breathing problems occur ('prophylactic surfactant'), or only if the baby has symptoms ('selective surfactant').

Studies conducted 30 years ago suggested that preterm infants who were intubated (breathing tube placed in the airway, down the throat, and into the lungs) and were treated with prophylactic surfactant (before breathing problems occurred) had fewer RDS complications such as chronic lung disease or pneumothorax.

Newer studies, however, suggest that a better treatment approach may be using breathing support (i.e. continuous positive airway pressure (CPAP)) through a mask or nose prongs placed on the baby’s face, and applying surfactant only if breathing problems develop. This avoids putting tubes into the windpipe and giving medicines that may be unnecessary.

What did we do?

We searched for studies that tested the prophylactic versus selective use of surfactant. We combined results for infant mortality (death) within the first 28 days of life (the neonatal period) and the development of more severe lung disease that may require long-term oxygen supplementation (chronic lung disease). We looked at whether results varied if preterm babies were given CPAP to support their breathing at birth or if their mothers had received medication, such as steroids, which help the baby’s lungs mature during the prenatal period.

What did we find?

We identified 10 relevant studies that involved 3151 babies.

When considering all studies together, prophylactic surfactant probably results in little to no difference in the risk of chronic lung disease (CLD) compared to selective use of surfactant (5 studies, 1874 babies) and may slightly reduce the risk of pneumothorax (8 studies, 3094 babies). It may make little to no difference to the risk of moderate-to-severe neurodevelopmental impairment (problems with brain development) (1 study, 976 babies).

Studies where infants received CPAP showed that prophylactic use of surfactant probably slightly increases the risk of mortality compared to its selective use as a treatment once RDS symptoms have developed, and it may make little to no difference to the risk of CLD. The evidence for pneumothorax is very uncertain.

In contrast, studies where infants did not receive CPAP showed that prophylactic use of surfactant reduces mortality risk compared with giving surfactant selectively after RDS develops, and it may reduce the risk of pneumothorax slightly. The evidence for CLD is very uncertain.

In our view, the review findings favor early stabilization of breathing with CPAP for all preterm infants at risk of developing RDS and then selective use of surfactant for preterm infants showing RDS symptoms.

What are the limitations of the evidence?

People running the studies and families of babies taking part may have known which treatment was being given, which may have influenced measurements.

Not all studies provided information about everything of interest. For example, some studies did not measure longer-term infant development.

The studies did not provide enough reliable information for us to understand the effects of the age of the babies (born before 28 weeks or closer to their due date), mothers receiving steroids before giving birth, or different methods of giving the surfactant.

How up to date is this evidence?

This review updates a previous 2012 Cochrane review. The evidence is current to 31 January 2025.