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.

Key messages

• In people with hip osteoarthritis (a condition where the cartilage cushioning the hip joint wears down, causing pain and stiffness), exercise compared with dummy treatment may have little to no effect on pain, but may improve joint function slightly. Compared with no treatment, usual care, or limited education, exercise probably leads to small improvements in pain and joint function, although these may not be noticeable in daily life. Adding exercise to another treatment probably has little to no effect on pain and joint function.

• We are unsure if exercise leads to more unwanted events than dummy treatment or no treatment/usual care in people with hip osteoarthritis. When added to another treatment, exercise probably reduces the risk of unwanted events slightly.

• We need more and better-designed studies that focus specifically on people with hip osteoarthritis to draw more solid conclusions about the effects of exercise.

What is hip osteoarthritis?

Hip osteoarthritis occurs when the cartilage cushioning the hip joint wears down. It is a common, long-lasting condition. People with hip osteoarthritis often experience joint pain and stiffness. They may have difficulty performing everyday activities such as climbing stairs and getting up from a chair.

How might exercise help?

Exercise aims to improve muscle strength, joint movement, and self-belief in the capacity to perform certain activities. These effects should reduce pain and disability, helping people to better manage their symptoms. Exercise programmes vary considerably, with a wide range of different exercise types, intensities, and delivery methods.

What did we want to find out?

We wanted to know whether exercise reduces pain and improves joint function and well-being for people with hip osteoarthritis. We also wanted to know if people in the studies who exercised were more likely to report treatment success and less likely to drop out of the study or have unwanted events.

What did we do?

We searched for studies that assessed the effects of exercise in adults with hip osteoarthritis. Exercise programmes had to be land-based, planned, structured, and repetitive. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and how consistent the results were across the studies.

What did we find?

We found 18 studies with 1368 adults. Participants were mostly women (63%) and aged between 53 years and 74 years. Studies took place in Australia, Canada, Denmark, Finland, Germany, Ireland, Italy, the Netherlands, New Zealand, Norway, Sweden, and the USA. Exercise programmes lasted between two and 52 weeks. Most studies measured results immediately after the exercise programme; some studies also reported longer-term results.

Exercise compared with dummy treatment (2 studies, 123 adults)

• Exercise may have little to no effect on pain.

• Exercise may improve joint function slightly. On a scale of 0 to 100, where a 13-point difference is a meaningful change, people who exercised scored 7.4 points better than those on dummy treatment.

• No studies reported well-being or treatment success.

• People who exercise may be no more likely to stop treatment.

• We are unsure if there are more unwanted events with exercise.

Exercise compared with no treatment, usual care, or limited education (10 studies, 494 adults)

• Exercise probably improves pain and joint function, but only slightly. On a scale of 0 to 100, people who exercised scored 7.2 points better for pain (where a 12-point difference is a meaningful change) and 8.8 points better for joint function (where a 13-point difference is a meaningful change), compared with people receiving no treatment, usual care, or education.

• Exercise probably has little to no effect on well-being.

• People who exercise may be no more likely to report treatment success or to stop treatment.

• We are unsure if there are more unwanted events with exercise.

Exercise plus another treatment compared with the other treatment alone (7 studies, 751 adults)

• Exercise probably has little to no effect on pain, joint function, well-being, or whether people stop treatment.

• Exercise may have little to no effect on whether people report treatment success.

• People who exercise probably have slightly fewer unwanted events.

What are the limitations of the evidence?

Because the studies included people with different levels of hip pain and disability, the results are likely to apply to most adults with hip osteoarthritis. However, there were very few younger adults in the studies, so the findings may not apply as well to younger people.

In most studies, people knew whether they were receiving exercise, and pain and physical function were self-reported. This may make exercise appear more effective than it really is.

We are moderately confident in some of the results and less confident in others. This is because many studies were small, and the results varied across the studies. Further research may change the results.

How up to date is this evidence?

This review updates our previous review published in 2014. The evidence is up to date to February 2025.

Key messages

• When types of minimally invasive glaucoma surgery that act on Schlemm's canal (called SC-MIGS) are compared with non-minimally invasive (conventional) glaucoma surgeries, there may be little to no difference in the proportion of people who are medication-free in the short, medium, or long term.

• More people may be medication-free in the short term after SC-MIGS compared with cataract surgery alone; however, there may be a higher risk of bleeding.

• SC-MIGS may reduce eye pressure more than laser treatment.

What is open-angle glaucoma?

Open-angle glaucoma is a common eye condition in which there is damage to the optic nerve, which usually progresses slowly over many years. 'Open-angle' means that the eye's natural drainage channels are not blocked but do not drain fluid effectively. This can increase pressure in the eye and damage the optic nerve, causing vision loss, often affecting the peripheral vision before the central vision. Some people develop glaucoma despite normal eye pressure and require further pressure-lowering treatment.

How is open-angle glaucoma treated?

Treatment includes eye drops, laser treatment, and surgery. Surgery is usually used if eye drops or laser treatment has not worked.

Standard surgery usually involves bypassing the drainage channels of the eye to improve fluid drainage. It may be performed under local anaesthetic (while the patient is awake) or general anaesthetic (while the patient is asleep). Complications, such as bleeding in the eye or very low eye pressure, can occur, and some people may need repeat surgery.

One alternative to standard surgical procedures is minimally invasive glaucoma surgery. Some of these procedures act on a part of the drainage network of the eye called Schlemm's canal.

What did we want to find out?

We wanted to find out whether these types of minimally invasive glaucoma surgery that specifically act on Schlemm's canal (called SC-MIGS below) help improve outcomes and whether they cause any harmful or unwanted effects in people with open-angle glaucoma. We were particularly interested in:

• the likelihood of people not needing eye drops;

• the likelihood of progressive visual field loss (loss of central or side areas of vision);

• changes in eye pressure;

• changes in the number of eye drops used following surgery;

• any unwanted effects or side effects.

What did we do?

We searched for studies that compared SC-MIGS to other types or combinations of surgery, or to laser treatment. 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 10 studies that involved 639 people (639 eyes). People in the studies were men and women aged between 41 and 74 years. The studies took place in Italy, Japan, India, the USA and Latin America, Poland, Canada, and China. The studies compared:

• SC-MIGS with conventional glaucoma surgery;

• SC-MIGS plus cataract surgery with cataract surgery alone;

• SC-MIGS with types of minimally invasive glaucoma surgery that don’t act on Schlemm’s canal;

• one type of SC-MIGS with another type of SC-MIGS;

• SC-MIGS with laser procedures.

SC-MIGs versus standard glaucoma surgery (3 studies, 99 people)

There may be no difference between SC-MIGS and standard glaucoma surgery in the likelihood of people not needing eye drops to control their glaucoma, having progressive visual field loss, or in the average change in eye pressure, number of eye drops people used following surgery, or unwanted effects.

SC-MIGS plus cataract surgery versus cataract surgery alone (2 studies, 132 people)
People may be less likely to need eye drops to control their glaucoma, average change in eye pressure may be greater, but there may be more risk of bleeding with SC-MIGS plus cataract surgery compared with cataract surgery alone.

SC-MIGS versus types of minimally invasive glaucoma surgery that don’t act on Schlemm’s canal (2 studies, 238 people)
There may be no difference between these two treatments in how likely people are not to need eye drops to control their glaucoma, number of eye drops used following surgery, or need for further surgery.

One type of SC-MIGS versus another type of SC-MIGS (2 studies, 140 people)
There is likely no difference between one type of SC-MIGS and another in any of the things we wanted to find out.

SC-MIGS versus laser procedures (1 study, 30 people)
Eye pressure may be reduced more, but there may be more risk of bleeding with SC-MIGS compared with laser procedures.

What are the limitations of the evidence?

Our confidence in the evidence is very limited because there were not many studies, and they did not include many people. The studies did not use the best methods, so their results may not be reliable. Also, the studies each focused on a small group of people of the same ethnicity or nationality, so we don’t know how their findings will apply to different groups of people.

How up to date is this evidence?

The evidence is up to date as of October 2025.

Key messages

• Transfusing platelets (giving blood cells that form clots to stop bleeding) at higher platelet count levels (when there is less risk of bleeding) does not seem to decrease death or bleeding.

• Transfusing at a lower platelet level likely reduces platelet transfusions without increasing the risk of death or bleeding.

• Future studies are needed to know the exact platelet count at which babies should be given platelets based on their individual risks for bleeding.

What are platelets?

Platelets are blood cells that form clots to stop bleeding. A low platelet level (platelet level on a blood test of less than 150,000 platelets per microliter) is known as thrombocytopenia. Thrombocytopenia is common in premature or sick newborn babies and can increase their risk of bleeding.

How is thrombocytopenia treated?

Thrombocytopenia is commonly treated by giving platelets from donated blood. Platelets are given directly into a vein in a procedure called a transfusion. However, platelet transfusion itself may increase the risk of death and other harms, and experts in the field differ about whether a platelet transfusion should be done when babies' platelets are lower versus when they are higher.

What did we want to find out?

We wanted to find out if it is better to give platelets when platelet levels are higher compared to when they are lower in babies with thrombocytopenia. We wanted to know the effects of transfusion on death and bleeding, and on babies' development.

What did we do?

We searched for studies that looked at giving platelet transfusions to babies with thrombocytopenia. 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 three studies (856 babies) that compared different platelet levels for treatment with a platelet transfusion. Two studies took place in high-income countries (the USA, Canada, the UK, Ireland, and the Netherlands), and one in a lower-middle-income country (India). One study looked at whether it was better to give a platelet transfusion when the platelets in babies were just a little low (mild thrombocytopenia) compared to if the platelets were low (moderate thrombocytopenia) (mild thrombocytopenia range). Another study looked at whether it was better to give a platelet transfusion when the platelets were just low (moderate thrombocytopenia) compared to if the platelets were very low (severe thrombocytopenia) (moderate thrombocytopenia range). The third study looked at whether it was better to give a platelet transfusion when the platelets were very low (severe thrombocytopenia) compared to if the platelets were extremely low (very severe thrombocytopenia) (severe thrombocytopenia range).

We found no difference between lower and higher platelet levels in death:

• mild thrombocytopenia range (1 study, 152 babies);

• moderate thrombocytopenia range (1 study, 44 babies);

• severe thrombocytopenia range (1 study, 656 babies).

We found no difference between lower and higher platelet levels in bleeding:

• mild thrombocytopenia range (not reported);

• moderate thrombocytopenia range (1 study, 44 babies);

• severe thrombocytopenia range (1 study, 658 babies).

We found that transfusing at a lower platelet level likely reduces platelet transfusions without increasing the risk of death or bleeding:

• mild thrombocytopenia range (1 study, 152 babies);

• moderate thrombocytopenia range (not reported);

• severe thrombocytopenia range (1 study, 659 babies).

What are the limitations of the evidence?

We have only moderate to very low confidence in the evidence. Our confidence is limited because the people doing the studies knew which treatment they were giving, and we only found three studies, all of which differed in the platelet levels studied. The studies also differed in whether they included babies who were already bleeding. The largest study did not include babies with bleeding.

How up-to-date is this evidence?

The evidence is current to June 2025.

Key messages

• In children and adolescents with neurological impairment, we are very uncertain about the effect of adding an antireflux procedure (fundoplication) on symptoms of gastro-esophageal reflux, death, and major surgical complications (perforation or peritonitis), when compared to gastrostomy alone or gastro-jejunal tubes.

• The addition of an antireflux procedure when performing a gastrostomy may result in little to no difference in the number of hospitalizations for respiratory disease (pneumonia).

• Further research is necessary. Better designed observational studies could help to improve our confidence in the evidence.

Why treat gastro-esophageal reflux in children with neurological impairment?

Because of damage to their central nervous system, children with neurological impairment are prone to vomiting and feeding difficulties, and are at increased risk of dying from lower respiratory tract infections, such as pneumonia. The treatment of gastro-esophageal reflux (where the stomach acid frequently flows back into the esophagus [food pipe] and causes heartburn) aims to prevent these symptoms and complications.

How is gastro-esophageal reflux that doesn't get better with medicine treated in these children?

The two most common procedures used to treat or prevent the consequences of gastro-esophageal reflux (antireflux procedures) in children with neurological impairment are fundoplication, where the stomach is wrapped around the lower esophageal sphincter, and the placement of a gastro-jejunal tube, which passes a feeding tube from the stomach into the small intestine (jejunum). These procedures differ in their surgical risks: fundoplication is more complex, requires more anesthesia (sedation), and involves a longer recovery period. Gastro-jejunal tubes are easier to place but require continuous feeding, which may increase caregiving needs and reduce the quality of life of children and their families.

What did we want to find out?

We wanted to find out if a fundoplication or passing of a gastro-jejunal tube is better than a gastrostomy (feeding tube entered directly into the stomach) alone to improve symptoms of gastro-esophageal reflux and number of deaths.

We also wanted to know if fundoplication caused more major surgical complications, and if antireflux procedures could prevent respiratory morbidity (pneumonia) in the long term.

What did we do?

We searched for studies comparing the two antireflux procedures (fundoplication or gastro-jejunal tubes) versus gastrostomy alone or versus each other in children and adolescents with neurological impairment.

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 11 studies involving a total of 3122 children with neurological impairment. The children were followed up for between 9 months and 12 years.

Main results

Gastrostomy plus fundoplication compared to gastrostomy alone for gastro-esophageal reflux

• We are very uncertain about the effect on symptoms of gastro-esophageal reflux (3 studies, 180 children), death (3 studies, 415 children), major surgical complications within the first 30 days after surgery (3 studies, 412 children), and emergency department visits after surgery (1 study, 130 children).

• Gastrostomy plus fundoplication may result in little to no difference in number of hospitalizations for respiratory disease (pneumonia) (1 study, 2054 children).

• No studies looked at child's quality of life for this comparison. Length of stay after surgery was reported but not compared for gastrostomy plus fundoplication versus gastrostomy alone.

Gastro-jejunal tubes compared to gastrostomy alone for gastro-esophageal reflux

• We are very uncertain about the effect on death (1 study, 50 children) and child's quality of life (1 study, 50 children).

• No studies looked at symptoms of gastro-esophageal reflux, major surgical complications, length of stay after surgery, number of hospitalizations for respiratory disease (pneumonia), or number of emergency department visits after surgery for this comparison.

Gastrostomy plus fundoplication compared to gastro-jejunal tubes for gastro-esophageal reflux

• We are very uncertain about the effect on symptoms of gastro-esophageal reflux (3 studies, 1531 children), death (3 studies, 418 children), and major surgical complications during the first 30 days after surgery (2 studies, 190 children).

• Gastrostomy plus fundoplication may result in little to no difference in number of hospitalizations for respiratory disease (pneumonia) (1 study, 228 children).

• No studies looked at number of emergency department visits after surgery or child's quality of life for this comparison. Length of stay after surgery was reported but not compared for gastrostomy plus fundoplication versus gastro-jejunal tubes.

What are the limitations of the evidence?

We have little to very low confidence in the evidence. There were many problems with the methods of the included studies, such as incomplete reporting, differences among the participants in each group, and small study sizes that prevented the recording of events that don't occur very often during the follow-up period. Also, the included studies did not report all the outcomes we were interested in.

How up-to-date is this evidence?

The evidence is current to September 2024.

Key words: neurological impairment, children, adolescents, gastrostomy, tubes, fundoplication, gastro-jejunal, gastro-esophageal reflux disease, gastro-oesophageal reflux, GERD.

Key messages

• A common treatment for inflammatory arthritis is a medicine that alters the immune system and so reduces inflammation (DMARDs). Stopping DMARD treatment around the time of surgery to treat an affected joint may increase people's risk of experiencing a flare (worsening symptoms), but may make no difference to their likelihood of developing an infection or experiencing an unwanted event after the operation.

• More studies are needed to assess the effects of stopping or continuing DMARDs on disease activity, function, and quality of life.

What is inflammatory arthritis?

Inflammatory arthritis (including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis) is a chronic (persistent) condition that causes abnormal inflammation in the joints, ligaments (connective tissue), and tendons (which attach muscle to bone), resulting in pain, stiffness, swelling, and loss of function. It is a progressive disease that, if uncontrolled, may result in irreversible joint damage, significantly impaired function and quality of life, and inability to work.

How is inflammatory arthritis treated?

Inflammatory arthritis is treated with medicines called 'disease-modifying anti-rheumatic drugs' or 'DMARDs' that control the inflammation, thus reducing symptoms (pain, swelling, or stiffness) and preventing joint damage.

However, since DMARDs alter the immune system, they may also increase the risk of infection, including surgical site infections.

What did we want to find out?

We aimed to find out about the benefits and risks of stopping compared to continuing DMARDs around the time of surgery in people with inflammatory arthritis. We were interested in:

• flare (worsening symptoms or increased disease activity)

• infections after surgery

• infection in the artifical (prosthetic) joint

• disease activity score (from questionnaires)

• function (measured by questionnaire)

• unwanted events (such as wound problems or complications from surgery)

What did we do?

We searched for studies that investigated the effects of stopping or continuing DMARDs around the time of surgery. People in the studies had to be adults with inflammatory arthritis. They could be undergoing any type of surgery except for emergency or unplanned surgery.

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

What did we find?

We found three studies with 306 people. All had rheumatoid arthritis and had been taking conventional synthetic (man-made) DMARDs for more than 10 years. They were all undergoing planned orthopaedic surgery, that is, surgery on bones, joints and tendons. Their average age was 56 years, and 83% were women. Studies were conducted in France, the UK and Japan. One trial reported receiving funding from a foundation unrelated to commercial purposes and two studies did not report funding sources.

Main results

Compared with continuation of DMARDs during surgery:

• discontinuation may increase the risk of flare: 37% more people had a flare or worsening of the underlying disease activity when stopping DMARDs during surgery compared to those who continued with DMARDs (2 studies, 224 people). Out of 100 people who continued DMARDs, none reported a flare, compared to 37 out of 100 people who stopped DMARDs;

• discontinuation may have little or no effect on postoperative infections: 0% fewer people had postoperative infections when stopping DMARDs (3 studies, 306 people). Out of 100 people who continued DMARDs, 3 had postoperative infections compared to 3 out of 100 people who stopped with continuation of DMARDs.

• only one study (64 people) reported postoperative joint infections, with no infections in people who continued or stopped DMARDs.

• discontinuation may have little or no effect on total unwanted events, such as problems with the wound (3 studies, 306 people) or serious unwanted events, such as need for further surgery or procedures (2 studies, 242 people); 9% more people reported an unwanted event and 2% more people reported a serious unwanted event when stopping DMARDs.

What are the limitations of the evidence?

We have little confidence in the evidence because we found only three studies, and people in the studies were aware of which treatment they were getting. This may affect their reporting of disease flare, unwanted events and serious unwanted events, but it probably does not affect how they reported postoperative infections. None of the studies measured prosthetic joint infections, disease activity and function, so we don't know the effect of stopping DMARDs around the time of surgery on them. We only found studies on one type of DMARD.

How up to date is this evidence?

The evidence is up-to-date to 24 March 2025.

Editorial note: This is a living systematic review. We search for new evidence approximately yearly and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Key messages

• Cyclosporine A (CsA) eye drops, including Restasis, Cequa, and other newer versions, may improve some signs and symptoms of dry eye compared with their "vehicle" (inactive eye drops containing no CsA) or artificial tears. However, we have only moderate or low confidence in these results.

• People who used CsA eye drops were slightly more likely to stop treatment due to unwanted effects, but overall, few people withdrew from studies for this reason.

• We need higher-quality, longer-lasting studies that look at the benefits and harms of CsA eye drops in people with dry eye disease of varying seriousness.

What is dry eye disease?

The eye's surface is moist and covered with a thin film of tears. When problems arise with the tear film, people can develop a common condition known as dry eye disease. People with dry eye may have eye discomfort (such as a feeling of grittiness), burning sensations, light sensitivity, and blurred or fluctuating vision, which can affect driving and reading and lower their quality of life.

Some people develop dry eye disease because of another health condition or as a result of eye treatment, while in others, the cause is unknown. Many cases of dry eye are linked to health conditions that cause inflammation (swelling and irritation) in and around the eyes.

What are cyclosporine A (CsA) eye drops?

CsA eye drops are anti-inflammatory medicines that aim to reduce eye surface inflammation, improve tear production, and prevent eye surface damage. CsA eye drops come in different strengths, typically ranging from 0.05% (lower strength) to 2% (higher strength).

What did we want to find out?

We wanted to find out whether CsA eye drops work better than eye drops containing all the same ingredients except cyclosporine ('vehicle eye drops' or just 'vehicle'), artificial tears, or another type or strength of CsA to improve:

• dry eye symptoms;

• eye surface health;

• tear production;

• how well tears stay on the eye (tear film stability).

We also wanted to find out whether people using CsA eye drops were more likely to stop using them because of unwanted effects than those using vehicle, artificial tears, or CsA drops of a different type or strength.

What did we do?

We searched for studies comparing CsA eye drops with vehicle, artificial tears, or another CsA formulation or strength. We compared and summarized the results of these studies and rated our confidence in the evidence based on factors such as study methods and the number of people in the studies.

What did we find?

We found 58 studies involving 10,225 people with dry eye disease. China, South Korea, and the USA contributed 35 of the 58 studies (60%). Participants were typically around 53 years old. Women made up about 80% of participants overall, though proportions varied across studies from 46% to 100%. Pharmaceutical companies funded or sponsored nearly half of the studies. Non-profit organizations supported 10 studies, six studies had no external funding, and 14 studies did not report funding sources.

We grouped the studies into six groups based on CsA strength and the comparison treatments. Here, we focus on three groups with the most data.

Main results

Comparison 1

Compared to vehicle, artificial tears, or both, using CsA 0.05% eye drops for three months may have slightly improved people's:

• dry eye symptoms (13 studies, 1396 people);

• eye surface health (7 studies, 1355 people).

Results for tear production and tear film stability were inconsistent, preventing us from drawing firm conclusions.

Comparison 2

People using CsA eye drops of different strengths and types may have had slightly better tear production than those using CsA 0.05% eye drops after three months, but the difference between groups was small (5 studies, 572 people). We are uncertain about the effects on:

• dry eye symptoms;

• eye surface health;

• tear film stability.

Comparison 3

Compared to vehicle, artificial tears, or both, using CsA 0.1% eye drops for three months:

• probably improved eye surface health slightly (7 studies, 2940 people);

• may have improved tear production slightly (3 studies, 735 people).

Results for dry eye symptoms were inconsistent, preventing us from drawing firm conclusions. We are uncertain about the effect of CsA 0.1% on tear film stability.

Stopping treatment due to unwanted effects

Compared with people using vehicle eye drops or artificial tears, those using CsA 0.05% or 0.1% were slightly more likely to stop treatment due to unwanted effects. Overall, only a few people stopped treatment because of unwanted effects.

What are the limitations of the evidence?

We have little confidence in the evidence for dry eye symptoms, eye surface health, tear production, and tear film stability because study results were often inconsistent or too uncertain to determine the true size of the effect. Many studies gave unclear or few details about their methods. However, we are moderately confident in the evidence about stopping treatment.

How up to date is this evidence?

The evidence is current to March 2026.

Key messages

• Venepuncture (inserting a needle into a vein) may be less painful than heel lance (using a special device to puncture the skin) for newborn babies when having a blood sample taken, with or without sugar water for pain relief, and may reduce the need for more than one skin puncture when no sugar water is given for pain relief.

• We don’t know which procedure, venepuncture or heel lance, is more painful for newborn babies when sugar is used for pain relief.

• We need better designed and larger studies that fully report their results to show which method is better for babies.

Why do we take blood samples from newborn babies?

In most countries, a blood sample from newborn babies is needed for routine screening tests. Blood samples may also be needed for other blood tests to diagnose and manage diseases, such as jaundice or low blood sugar (hypoglycemia). However, taking blood from babies is painful. Untreated pain in newborn babies may affect their physical growth and brain development. A sweet, sugar solution (such as sucrose) can be given to babies before the procedure, which helps to reduce the pain. It is difficult to measure pain in babies, but we rely on things like facial expressions, crying, and changes in heart rate to assess their pain.

How are blood samples taken?Venepuncture

Venepuncture is a method of taking a blood sample where a person uses a needle to directly puncture the vein. The person who performs this must be well-trained to help ensure they successfully take a blood sample. This technique is often used when 1 mL or more of blood is required, and to prevent repeated punctures to the skin and associated complications (such as skin infections) from heel lance.

Heel lance

Heel lance is the standard way of taking a blood sample from newborn babies in hospitals worldwide. It is commonly used when the blood sample required is less than 1 mL. It does not require special training or expertise for successful use. The procedure involves making a small puncture (between 1 mm and 2 mm deep) on the heel of the foot using a lancet, which is usually an automatic device. Following the puncture, the infant's heel is squeezed to collect the required blood sample, which causes further pain.

What did we want to find out?

We wanted to find out:

• whether venepuncture is less painful than heel lance for newborn babies; and

• which procedure works best first time, so a second skin puncture is not needed.

What did we do?

We searched for studies that compared venepuncture and heel lance for taking blood samples in newborn babies. The studies needed to measure pain responses and the number of skin punctures needed for a successful sample. They also needed to record whether babies were given sugar solution as pain relief. Babies in the studies had to be healthy and born at full term. 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 included eight studies involving 826 full-term newborn babies. Three studies took place in Sweden, and one each in Japan, Malaysia, Nepal, Spain, and the UK.

When no sweet-tasting solution was given:

• venepuncture probably causes less pain compared to heel lance (6 studies, 488 babies); and

• venepuncture probably reduces the need for more than one skin puncture compared to heel lance (6 studies, 397 babies).

When a sweet-tasting solution was given:

• venepuncture may cause less pain compared to heel lance (3 studies, 170 babies); and

• we are uncertain about the effect of venepuncture compared to heel lance on the need for more than one skin puncture (2 studies, 110 babies).

What are the limitations of the evidence?

Our confidence in the evidence was limited, and ranged from moderate to very low. This is because all the studies had limitations in how they were carried out. These included issues with how babies were assigned to each group, how the studies reported their results, and the number of babies included in the studies. In addition, the people doing the procedures knew which sampling method each baby received, which could have influenced how the studies assessed pain.

How up to date is this evidence?

This review updates our 2011 Cochrane review. The evidence is up to date to July 2025.

Key messages

• Most children with growth-plate pain (apophysitis) get better over time. Whether treatment for apophysitis affects short-term pain, physical function, and participation in sport is uncertain.

• It is uncertain whether any treatment is better or worse than any other. The studies were mostly small and had problems with their design. The studies did not always measure unwanted effects from a treatment, and none measured whether any children withdrew from studies because of unwanted effects.

• The evidence is limited. Most studies included more boys than girls, and included children who were more active than average. The children often knew which treatment they were receiving, which may have influenced the results.

What is apophysitis?

During puberty, children sometimes develop pain in the growth plates in their hips, knees, and feet. This pain is usually caused by irritation of the growth plate from repeated stress over time rather than from a single event. The pain is usually short-term and has limited impact on a child's life. However, sometimes the pain can make children limp, play less sport, or be less physically active. The conditions are called different names based on the location of the growth, but are commonly known as 'apophysitis' or 'lower limb apophyseal injuries'.

How is apophysitis treated?

Many different healthcare professionals treat apophysitis, including general practitioners or physicians, physiotherapists, and podiatrists. Many treatments are used, including exercises, medicines, strapping, braces, or devices put in shoes like foot orthoses or heel lifts. Regardless of treatment, apophysitis usually gets better on its own, but in some cases, the pain can last for a long time.

What did we want to find out?

We wanted to find out which treatments reduce pain effectively and to understand how safe these treatments are. We wanted to know which treatments improve how children function physically and take part in sport. We also wanted to know if one treatment worked better than another.

What did we do?

We searched for studies that tested the different types of treatments for apophysitis in the hip, knee, and foot. We did not search for any treatments that involved surgery.

We combined results from studies that tested the same treatments and used similar methods to measure effectiveness. We rated our level of certainty about this evidence.

What did we find?

We found 10 studies that involved 654 children whose average age ranged from 10.3 to 13.3 years. Seven studies focused on heel pain (calcaneal apophysitis), and three focused on pain in the front of the knee (traction apophysitis of the tibial tubercle).

Main results

• One study (23 children) compared a medicine called dexamethasone to a placebo (fake treatment). We are very uncertain whether dexamethasone reduces pain, improves physical function, or helps children return to sport in the short term. Two studies (74 children) reported unwanted effects of medicines, but the evidence was also very uncertain.

• One study (21 children) compared dexamethasone to usual care. We are very uncertain whether dexamethasone reduces pain, improves physical function, or helps children return to sport in the short term. One study (30 children) reported unwanted effects, but the evidence was also very uncertain.

• One study (22 children) compared Kinesio tape to a placebo. We are very uncertain whether Kinesio tape improves pain or physical function in the short term. The study did not report on participation in sport or unwanted effects.

• One study (124 children) compared foot orthoses to heel lifts. It found that there is probably little to no difference between them in terms of pain or physical function in the short term. The study did not report on participation in sport. One study (101 children) reported that there were no unwanted effects.

• One study (43 children) compared heel cushioning to a heel strap. We are very uncertain whether heel cushioning improves physical function or causes any unwanted effects in the short term. The study did not report on participation in sport.

• None of the studies reported whether any children withdrew from the studies because of unwanted effects.

What are the limitations of this research?

• In most studies, the children and carers knew which treatments they were receiving, which may have influenced how they reported improvements. This may affect how reliable the results are.

• Apophysitis often improves on its own as children continue to grow and the growth-plates close, so it is difficult to know if any improvements are due to treatments or natural recovery over time.

• There were many more boys than girls in the studies, and most participants were very physically active. It is unlikely that the condition impacts boys and girls differently, but we are unsure if our findings can be applied to children who are less physically active.

• Finally, most studies had only a small number of participants. This means we cannot be confident in the results and cannot know whether the findings would apply to a wider group of children with apophysitis.

How up to date is this evidence?

The evidence is current to 4 January 2025.