Key messages

• For making symptoms go away (remission), ustekinumab works slightly better than placebo (sham treatment). Adalimumab plus immune system drugs, guselkumab and upadacitinib probably work slightly better than placebo, while vedolizumab and natalizumab probably work only a little better than placebo.

• For stopping symptoms coming back (preventing active disease) within one to two years of remission, adalimumab probably works slightly better than placebo.

• In the short term (about one year), compared to placebo, upadacitinib, ustekinumab and vedolizumab probably lead to fewer people stopping treatment due to unwanted effects. We can’t be sure about unwanted effects of biologics in the long term based on the existing evidence.

What is Crohn's disease?

Crohn's disease is a life-long (chronic) inflammatory disease that can affect any part of the gut. Common symptoms include bloody poo (stool or faeces), diarrhoea, stomach ache, fever, weight loss, fatigue and others. When someone is experiencing symptoms of Crohn's, they are said to have 'active' disease, and when their symptoms are under control, then they are said to be 'in remission'. We don't know what exactly causes Crohn's, but it could be related to a combination of genes, immune system malfunction, 'bad' gut bacteria and environmental reasons. There is no known cure, but the symptoms are usually managed with medications, such as steroids, immune system medications and, if necessary, surgery.

What are biologics?

At the turn of the century, a new category of medications called biologics, or advanced treatments, became available and started being widely used for the treatment of Crohn's. These are new and different treatments that target parts of the immune system more specifically than the older treatments, and they are thought to be better and have fewer unwanted effects. They can be delivered through a vein (intravenous), under the skin or sometimes orally.

What did we want to find out?

We wanted to find out whether all the biologics (medications that target specific parts of the immune system) or advanced treatments that are being used (or have been tested) can treat Crohn's, whether they have unwanted effects and how they compare to each other. The things we looked for were whether a medication can make symptoms go away, improve symptoms or make the gut look healed during a colonoscopy (examination inside the colon), as well as whether these medications have unwanted effects in the short term (up to one to two years) and long term (longer than two years).

What did we do?

We searched for studies that compared biologics with any other medical treatment or a placebo (a sham treatment) for adults with Crohn’s disease. People in the studies could be men or women. They could have had Crohn’s disease for any length of time and have used any medication for their Crohn’s disease. We summarised the findings and assessed how confident we could be in the results, based on how the studies were designed and carried out.

What did we find?

We included 94 studies with 27,476 people, with about equal numbers of men and women. Most people were around 30 to 40 years old, but they ranged from older adolescents to people in their sixties. Severity in the induction studies was moderate to severe. In the maintenance studies, some people were in remission and some had responded to previous therapy and still had some symptoms. Most induction studies followed people for three to six months and maintenance studies for about one year.

Main results

• There were 66 induction studies, involving 20,653 people, and 22 maintenance studies, involving 6823 people.

• For making symptoms go away (remission), ustekinumab works slightly better than placebo (sham treatment). Adalimumab plus immune system drugs, guselkumab and upadacitinib probably work slightly better than placebo, while vedolizumab and natalizumab probably work only a little better than placebo. Risankizumab, BI695501 (a medication that resembles adalimumab), a combination of infliximab with immune system medications, and filgotinib may also work, but we are less certain about them.

• We are uncertain whether other medications work or not, compared to placebo.

• For stopping symptoms coming back (preventing active disease) within one to two years of remission, adalimumab probably works slightly better than placebo.

• In the short term (about one year), compared to placebo, upadacitinib, ustekinumab and vedolizumab probably lead to fewer people stopping treatment due to unwanted effects. Other medications like risankizumab, certolizumab and filgotinib could be similar to placebo too, but we're less certain about them.

• We can’t be sure about unwanted effects of biologics in the long term based on the existing evidence.

What are the limitations of the evidence?

The included studies had people with very different characteristics between them, such as mixes of people who have or have not used biologics or advanced treatments before, people with more or less serious disease, and people using or not using other treatments at the same time. When these characteristics of people are not similar across the studies, it can make it difficult to be sure of the results.

The information we have is mainly around clinical symptoms, and information from colonoscopies or microscope examination was limited. There were also some issues with the way the included studies were carried out and the quality of the methods they used.

How up to date is this review?

This review is up to date to June 2025.

Key messages

- Audit and feedback in healthcare is when a health professional's performance is evaluated and compared to professional standards (audit). Then the health professionals are given the results of the comparison (feedback), with the hope that it might help them improve their performance.

- Audit and feedback helps to improve health professional performance a little to a moderate amount. It works best when it shows health professionals how they compare to top performers, focuses on important areas for improvement, and includes tips for making changes. Audit and feedback can be even more helpful when combined with other supports like reminders or extra training.

- Future research should focus on finding the best ways to improve audit and feedback interventions.

What is meant by audit and feedback in healthcare?

Audit and feedback is often used in healthcare organisations to improve healthcare professionals’ performance. In an audit and feedback process, an individual’s professional practice or performance is measured and then compared to professional standards or targets. In other words, their professional performance is “audited”. During the "feedback", the results of this comparison are then provided to health professionals. The aim of this process is to encourage healthcare professionals to take action or make changes to follow standards.

What did we do?

We searched for all the studies in which healthcare professionals were randomised to receive audit and feedback and in which the results on professional practice were measured.

What did we find?

We found 292 studies that met the requirements. We found that audit and feedback is often used together with other strategies to improve quality of care, such as educational meetings or reminders. Most studies measured the effect of audit and feedback on doctors, although some studies measured the effect on nurses or pharmacists. Audit and feedback was used to influence their performance in different areas, including the proper use of prescription treatments or test-ordering.

The exact way that audit and feedback was delivered varied widely across the studies. Sometimes health professionals were given feedback verbally, other times in writing, on an electronic dashboard or through multiple modes. In some studies, this feedback was given to them by the researchers responsible for the study, while in other studies, feedback was given by supervisors or colleagues. In some studies, health professionals were given feedback only once, while others were given feedback monthly. Sometimes, they were also given or supported to create an action plan with suggestions or advice about how to improve their performance.

Main results: What happens when health professionals are audited and provided with feedback?

The effect of using audit and feedback varied widely across the included studies, but most often it achieves small-to-moderate improvements in quality of care.

Audit and feedback may be most effective when recipients can see how their own performance compares to their high-performing peers, when it helps the health professional to identify and take action on high-priority clinical issues, and when it focuses on areas where health professionals have substantial room for improvement. Other features of audit and feedback that are associated with greater effects are when it involves measurement of the individual recipient's practice (rather than their team or organisation); comes from a respected peer with an existing relationship to the recipient; includes multiple modalities (e.g., verbal and written); and features an action plan with advice for improvement.

In addition, the effect of audit and feedback may change when combined with other strategies that support improved quality of care, such as education or reminders.

What are the limitations of the evidence?

The quality of the evidence is moderate and further research is needed to confirm the features of audit and feedback that are most likely to achieve the greatest effects in different situations.

How up to date is this evidence?

This review updates our previous review. The evidence analysed is up-to-date to June 2020.

Key messages

• There is some very limited evidence to inform decision-making, but this is very uncertain.

• There are worries that people with cystic fibrosis (CF) and nontuberculous mycobacteria (NTM) might not live as long after transplant as those with CF without NTM, but we found no clear evidence about how NTM affects survival after lung transplant.

• Future studies are needed to show the effects of NTM in people with CF undergoing lung transplant on survival, the risk of later developing NTM disease, and organ rejection.

What is cystic fibrosis?

Cystic fibrosis (CF) is a common, inherited condition where mucus is not cleared well from the lungs. This leads to infection and a steady loss of lung function. People with CF may be considered for a lung transplant if their lung function is poor and rapidly declining. Transplant may improve a person's quality and duration of life.

What are nontuberculous mycobacteria?

Nontuberculous mycobacteria (NTM) are germs commonly found in the environment and cause lung disease in people with CF, which can be difficult to treat. NTM infection is thought to lead to worse outcomes for people undergoing lung transplant. Whilst guidelines recommend testing and treating people with CF for NTM before lung transplant, NTM infection should not be a reason not to transplant.

What did we want to find out?

We wanted to know the effects of NTM on lung transplant in people with CF.

What did we do?

We searched for studies of people with CF (of any age) with or without NTM lung infection who were being considered for lung transplant. We also looked for studies of people with CF and NTM who either did or did not undergo a lung transplant. Our main outcomes of interest were survival, post-transplant NTM infection, time to rejection of the transplanted lungs, and quality of life; additional outcomes of interest were lung function, flare-ups of disease, weight and height.

What did we find?

We included four studies reporting on 388 adults, three with fewer than 15 relevant participants each and one larger one. Mycobacterium abscessus was the most common NTM infection identified. All four studies compared people with CF and NTM infection to people with CF and no NTM infection undergoing lung transplant. All studies reported on survival and post-transplant NTM infection; two studies reported on organ rejection; and one commented on lung function in general. We are very uncertain of the effects of lung transplant on any of the outcomes listed below.

Main results

Survival

The three smaller studies all reported similar length of survival between people with CF and NTM infection and those without NTM at transplant. The larger study found that people with CF who had NTM infection when transplanted survived longer than those with no NTM infection at transplant. This study also reported that the five people who had post-transplant NTM infection survived longer on average than the 141 participants without NTM infection post-transplant.

Post-transplant NTM infection

The largest study found that seven out of 18 participants who had NTM infection at transplant continued to have infection post-transplant and four developed NTM disease (long-term infection); 10 of the 89 participants who did not have NTM infection at transplant went on to develop it after transplant (but none had NTM disease). There were 39 people transplanted for whom there was no information on NTM infection status at transplant; three of these people had NTM infection post-transplant, and one developed NTM disease. The remaining small studies reported that NTM was found post-transplant in three out of 13 participants in one study (four were positive before transplant); one out of five participants in a second study (all of whom were positive before transplant); and two out of nine participants in the third study (five participants had NTM disease at the time of transplant).

Time to rejection

One study reported that none of the five NTM-positive CF transplant recipients experienced organ rejection, with the risk of rejection appearing similar between the NTM and the non-NTM group. The second study only stated that three out of five transplant recipients with NTM disease were reported to have chronic organ rejection.

Lung function

One study (9 participants) reported that two out of the four participants who were NTM-negative at transplant had poor or deteriorating lung function, one at eight months and one at five years post-transplant.

What are the limitations of the evidence?

None of the studies we found reported any data we could analyse. The studies did not make any adjustments to allow for age, additional treatments, or any variation in severity of disease in the people they reported on. The characteristics of the people in the comparator groups were not always clear. For these reasons, we have very low confidence in the available evidence.

How up-to-date is this evidence?

The evidence is current to 17 February 2026.

Key messages

• The available evidence is limited, and we don't yet know the best way to organize rehabilitation services across health systems.
• Using different providers (such as specialist physiotherapists) may make little to no difference to health outcomes. Telerehabilitation (rehabilitation via video calls or apps) may offer similar results to usual in-person rehabilitation for independence in everyday activities, well-being, depression, arm function, and mobility, but more research is needed.
• Most studies come from high-income countries, so findings may not apply everywhere. More research is needed in diverse settings.

What are delivery arrangements?

Delivery arrangements are about the practical side of rehabilitation: who helps you, when and where you get help, and how services are organized to make sure your care is smooth and effective. This can include things like how quickly you can get an appointment or start treatment; whether it's a doctor, nurse, therapist, or another trained professional providing treatment; the conditions and support for the people delivering your care; how different healthcare providers coordinate with each other so your care feels joined up; and whether you receive rehabilitation in a hospital, clinic, or at home, or through telerehabilitation (where therapy is delivered through video calls or apps).

What did we want to find out?

We wanted to understand:

• the best ways health systems can organize rehabilitation services (things like who provides care, how quickly people get appointments, and whether technology like telerehabilitation helps recovery);
• what research exists worldwide on how rehabilitation services are organized and delivered;
• how this information can guide health system stakeholders when making decisions about rehabilitation; and
• whether new kinds of research and policies are needed to improve rehabilitation services.

What did we do?

This project was part of a larger study on rehabilitation and health policy. We searched three large research databases for systematic reviews (collections of evidence from many individual studies) on how rehabilitation services are delivered.

What did we find?

We found 25 systematic reviews. Of those, just five had results we could use for this project. They covered studies conducted mainly in high-income countries in Europe, the Americas, and the Western Pacific. The reviews involved different populations, including older adults and people recovering from stroke.

Main results

• When care is given by health professionals other than doctors (such as specialist physiotherapists), there is no evidence of a meaningful difference in health outcomes compared with care provided by doctors.
• We found no reliable evidence about whether receiving care in hospitals, clinics, or at home makes a difference. A few studies looked at rehabilitation delivered at home compared with usual in-person care, finding similar results for both approaches, but the number of studies was small, and the evidence is not strong enough to draw solid conclusions.
• For people recovering from stroke, doing rehabilitation at home by video or phone may produce similar results to in-person rehabilitation for independence in everyday activities, well-being, depression, arm function, and mobility, but more research is needed.

What are the limitations of the evidence?

Many of the reviews had some research weaknesses, so our confidence in the results is limited. Where the review authors had formally assessed their confidence in the evidence, they mostly gave low-confidence ratings. This means future studies could change our findings. Nearly all studies were done in high-income countries. There was no evidence from Africa, South‑East Asia, or the Eastern Mediterranean, so results may not apply everywhere.

How up to date is this evidence?
The evidence is current to 17 November 2024.

Key messages

• The effects of three weight-reducing medicines (orlistat, phentermine/topiramate and naltrexone/bupropion) on death rates and cases of heart disease are unclear for people with hypertension (high blood pressure) due to a lack of reliable evidence. There is no information about these measures for the medicines semaglutide and tirzepatide.

• Taking phentermine/topiramate or naltrexone/bupropion probably causes more unwanted events in people with hypertension than taking a placebo (inactive 'dummy' medicine). Taking orlistat probably causes an increase in the number of serious unwanted effects compared to taking a placebo. We did not find any information about side effects for people with hypertension taking semaglutide or tirzepatide.

• Long-term studies are needed to assess the effects of medicines used for weight management on death rates and heart and blood vessel problems in people with hypertension. It is also important that results for people with hypertension be provided by authors of any completed study that included people with and without hypertension.

What is high blood pressure (hypertension)?

Blood pressure is a measure of the force that your heart uses to pump blood around your body. It is usually given as two numbers: the pressure when your heart pushes blood out (systolic pressure), and the pressure when your heart rests between beats (diastolic pressure). Blood pressure is considered to be high when systolic pressure is over 140 and/or diastolic pressure is over 90. The risk of developing high blood pressure (hypertension) increases with age.

Why is hypertension a problem?

Hypertension can increase the risk of developing serious health problems, such as heart attack or stroke. Lowering blood pressure in people with hypertension reduces the number of people who develop diseases of the heart and blood vessels (cardiovascular diseases), which leads to fewer deaths and cardiovascular problems.

Is there a link between being overweight and hypertension?

Being overweight is associated with increased blood pressure. Hypertension treatment guidelines recommend maintaining a healthy weight and losing weight when needed. Some people may take medicine specifically to help reduce their weight.

What did we want to find out?

We wanted to find out if weight-loss medicines could reduce the negative effects of hypertension on people's health.

What did we do?

We updated a systematic review. We looked for studies on how weight-loss medicines affect people with hypertension. We wanted to know how many people experienced unwanted events (e.g. side effects), how many developed heart disease or stroke, and if any died.

We looked for studies called 'randomised controlled trials', which usually give the most reliable evidence about the effects of a treatment. We rated how certain we were about the evidence, taking into account how the studies were done, how many people took part and whether results were consistent. All studies compared a weight-loss medicine with a placebo, which is a 'dummy' medicine, one that looks like the same medicine but is inactive.

What did we find?

We added two new studies of medicines recently approved for weight reduction, so, in total, this updated review includes eight studies. They involved around 13,000 people with hypertension (average age 46 to 62 years). Three studies were conducted in the USA, three in European countries and two were multinational. The studies lasted between six and 48 months. Pharmaceutical companies funded seven of the eight studies.

For people with hypertension, three drugs that are approved to help people lose weight over time (orlistat, phentermine/topiramate and naltrexone/bupropion) may make little to no difference to how many people die or how many people have heart problems, but we are very uncertain about the results. People taking orlistat, phentermine/topiramate and naltrexone/bupropion probably have more serious unwanted events than those taking placebo. However, there may be little to no difference in unwanted events in general between orlistat and placebo, and little to no difference in serious unwanted events between phentermine/topiramate and placebo, but we are very uncertain about these results. The most common unwanted events were digestive problems (for orlistat, phentermine/topiramate), and dry mouth and skin tingling or numbness (for naltrexone/bupropion).

The studies that investigated semaglutide or tirzepatide did not present information on the number of deaths, heart problems or safety issues in people with hypertension.

What are the limitations of the evidence?

We are not confident in the evidence regarding overall deaths and heart problems for orlistat, phentermine/topiramate or naltrexone/bupropion, or regarding serious unwanted events for phentermine/topiramate, because of our concerns about how the studies were conducted and the low number of the events. We are not confident in the evidence about all unwanted events for orlistat because of our concerns about how the studies were conducted and because the results were inconsistent across different studies. We have more confidence in the evidence regarding serious unwanted events for orlistat and naltrexone/bupropion, and regarding all unwanted events for phentermine/topiramate or naltrexone/bupropion, but we do not have high certainty about these because of our concerns about how some of the studies were conducted.

How up to date is this evidence?

We included evidence published up to 22 April 2024.

Key messages

• Compared to regular human insulin, five faster-acting insulin analogues may offer similar benefits in controlling blood glucose levels.

• Compared to regular human insulin, some of them (ultra-rapid lispro, fast-acting aspart and aspart) may reduce the risk of severe complications such as episodes of low blood glucose.

• The evidence about mild diabetes complications, quality of life and adherence to treatment was unclear.

What is type 1 diabetes?

Type 1 diabetes is a condition in which a person's blood sugar (glucose) level becomes too high because the pancreas cannot produce any insulin to control the levels of glucose.

How is the condition treated?

People with type 1 diabetes have to inject insulin to control their glucose levels and stay well. Faster-acting insulin analogues are modified versions of human insulin that are designed to act more quickly after injection than regular human insulin. Examples include insulin lispro, insulin aspart, insulin glulisine, fast-acting insulin aspart (FIAsp) and ultra-rapid lispro insulin (URLi). They can be injected immediately before meals and lead to lower blood sugar levels after food intake.

What did we want to find out?

We wanted to compare the effects of long-term treatment with fast (and very fast)-acting insulin analogues to regular human insulin or another fast-acting insulin in people with type 1 diabetes on multiple daily injections. We wanted to find out about the effects on blood sugar control, episodes of low blood sugar, low blood sugar at nighttime, a serious complication (diabetic ketoacidosis), quality of life and adherence to treatment.

What did we find?

We found 15 studies where people were randomly put into one of two or more treatment groups. The studies compared the faster-acting insulin analogues to regular human insulin and involved 6335 participants. The people in the included studies were monitored (called follow-up) for between 24 and 52 weeks.

Main results

According to our analyses, five faster-acting insulin analogues may be similar to regular human insulin in terms of short-term (defined as less than one year) glycaemic control, as measured by HbA1c (which reflects average blood sugar levels over the past two to three months). We are uncertain about the effects on control of fasting blood glucose levels, mild or moderate episodes of low blood sugar (called hypoglycaemia), severe or serious episodes of low blood sugar at nighttime (called nocturnal hypoglycaemia), or adherence to the insulin treatment. However, they may be better, especially regarding severe hypoglycaemia or a very dangerous complication with high blood sugar and urine ketones (acids) called diabetic ketoacidosis.

We found no clear evidence for mild or moderate hypoglycaemia at nighttime or health-related quality of life (which is physical, mental, emotional and social health). We also did not find any data for long-term follow-up (defined as longer than one year).

What are the limitations of the evidence?

We have limited confidence in the evidence, mainly because most of the studies were carried out in an unblinded way (where healthcare professionals and participants know which treatment they received). There was also a moderate number of dropouts (more than 5% but less than 20% of the participants did not continue the treatment until the end of the study) and there was not enough study detail provided, so that we can't be confident in all the studies. Furthermore, several studies showed inconsistencies in the reporting of their methods and results.

How up to date is this evidence?

This evidence is current as of May 2025.

Key messages

• There is no clear evidence showing that any particular frequency of changing a person's position (repositioning) or any particular position (e.g. tilting the bed to a 30-degree angle) works better than any other to prevent bedsores (pressure injuries) in adults in hospital or care homes.

• Some repositioning frequencies and positions may reduce the costs of care, but this evidence is limited and uncertain.

• This is the second update of a review published in 2014. Research is still limited. Most studies are small and not well designed.

What are bedsores?

Bedsores (also called pressure injuries, pressure ulcers, pressure sores, decubitus ulcers) happen when people are not able to move much, or spend a lot of time sitting or lying down, such as elderly people or those who are very ill. When a body part presses against a mattress or chair for a long time, the skin rubs over bony parts of the body, like the heels, tailbone, hips, back, and the back of the head. Blood flow is reduced and skin and tissue break down.

How are bedsores prevented?

Changing a person's position can improve blood flow to areas that press against the bed or other surfaces, and it can have other benefits, such as increased comfort and mental well-being. The approaches used to prevent bedsores include:

• repositioning: moving or turning someone regularly, for example, every 2, 3, or 4 hours;

• position: placing someone in different positions, for example, raising the head of the bed or tilting the body;

• micromovement: frequent, small position changes made for people who cannot move (e.g. during surgery); and

• specially adapted mattresses and dressings.

What did we want to find out?

We wanted to know:

• which repositioning approaches (e.g. frequencies (how regularly someone is moved) and positions) are best for preventing bedsores;

• their effects on healthcare costs; and

• their effects on health-related quality of life, pain, and patient satisfaction.

What did we do?

We searched for studies that involved adults without bedsores who were receiving care in any hospital, long-term, or aged healthcare facility. The studies investigated which approaches to repositioning were most effective for preventing bedsores.

We summarised the findings and assessed our confidence in the results, based on how the studies were designed and conducted.

What did we find?

We found three new studies published since the 2020 version of the review. This 2026 updated review includes 11 studies and two cost evaluations.

The studies took place in China, Belgium, North America, Iran, and the UK. Most studies were in hospitals (intensive care units, operating theatres, wards); three were in nursing homes. The studies involved 4462 adults aged 18 to 90 years.

Repositioning

• We combined results from four studies comparing different repositioning frequencies. It is unclear whether changing a patient’s position every 2 versus 4 hours, every 2 versus 3 hours, every 3 versus 4 hours, or every 4 versus 6 hours makes any difference to the chance of developing bedsores (4 studies, 2175 people).

• One study tested a device worn by patients that electronically tracks their position and feeds that information back to nurses. Nurses in one group got visual reminders from the sensor to turn the patient every two hours, while nurses in the other group did not get reminders and turned patients based on their own judgement. The visual warnings provided by the device probably reduce the chance of getting bedsores (1 study, 1312 people).

Position

• The effect of 30° tilt, 3-hourly repositioning overnight compared to 90° tilt, 6-hourly repositioning overnight on developing bedsores is unclear (2 studies, 252 people).

• Raising the head of the bed by 30° compared to 45° may have no effect on bedsores (1 study, 80 people), but the evidence is unclear.

• Lying face down (prone) with 'lung recruitment manoeuvres' (a procedure to help open up the lungs) may result in more bedsores than lying face up (1 study, 116 people).

Micromovement

• Micromovement may reduce bedsores (2 studies, 477 people).

Cost-effectiveness

• One study estimated that repositioning costs are lower per resident per day with 4-hourly compared to 2-hourly repositioning, mostly due to reduced nursing time.

• Another study estimated that repositioning every 3 hours with a 30-degree tilt costs less than standard care (repositioning every 6 hours with a 90-degree tilt).

Other measures

• No studies reported the other measures we were interested in.

What are the limitations of the evidence?

Our confidence in the evidence is low or very low. Most studies were small or poorly designed. Information about cost-effectiveness was very limited. Health-related quality of life, pain, and patient satisfaction were not reported at all.

As the evidence does not show the best way to prevent pressure injuries, how often to change someone's position should be based on the person's medical condition, personal preferences, comfort, and how much they can move themselves.

How up to date is this review?

This is an update of a review published in 2014 and updated in 2020. The evidence is current to 7 August 2025.

Key messages

• Taking an oral (by mouth) iron preparation may increase iron stores in the blood compared to not taking an oral iron preparation.

• The higher iron in the blood meant more people could donate that otherwise may have been deferred (stopped from donating because of low iron levels).

• More people taking iron tablets may experience unwanted effects like gut problems while taking the tablets, at least initially, compared to people not taking iron tablets.

What is iron supplementation, and how can it help with blood donation?

Low iron is a common cause of deferral (stopped from donating) in people wishing to donate blood. If iron removed from the body through blood donation is not replaced, then donors may become iron deficient. All donors are screened at each visit for low iron levels. Iron can usually be replenished through a healthy diet, but it may take a long time. Iron supplementation using tablets or injections may reduce this time and help donors return to being able to donate much sooner.

What did we want to find out?

We wanted to find out if giving iron tablets or an injection of iron to potential blood donors would improve the iron stores in their blood, and reduce the chance of them being deferred (stopped) from donating because they had too little iron in their blood.

What did we do?

We searched for studies that compared giving iron supplements (as tablets, an injection, or an infusion (into a vein)) with getting no iron supplementation, as well as comparing different types of iron and different doses of iron. 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 8 new studies, for a total of 38 studies (7475 people). Iron was most commonly given as daily tablets (orally), with only five studies looking at other methods (injections or infusions directly into the blood).

• Iron tablets may increase the iron stored in the blood when taken over a few weeks or months compared to not taking iron tablets. This probably allowed more people to donate at their next attempt (lower deferral rates) (7 studies, 1647 people for deferral).

• More people taking iron tablets experienced unwanted effects, mostly gut problems such as stomach pain, constipation (hard stools), and diarrhoea (loose watery stools), compared to those not taking iron tablets (8 studies, 2641 people).

• There was no difference in non-gut problems (like headaches) between people who took iron tablets and those who didn't, and those that took the iron tablets found they had less "weakness" than those not taking the tablets.

What are the limitations of the evidence?

Our confidence in the evidence ranged from high to very low. In cases where our confidence was limited, this was because some of the studies were very old or very small (not many people were studied), and sometimes the studies did not report on everyone they said they would, and it was possible that people in the studies knew which treatment they were getting. We wanted to look at how different types of iron or different doses worked differently, as well as the impact on men and women separately, and whether they already had low iron stores in their blood, but not all studies gave us this information, so the answers are not as clear as we would like.

How up-to-date is the evidence?

This review updates our previous review, last published in 2014. The evidence is current to January 2025.

Key messages

• Compared with placebo (dummy treatment), antibiotics may reduce back pain slightly and may have some beneficial effect in improving disability in the short term in people with low back pain linked to damaged vertebral endplates (the layer between the disc and the vertebra) and disc rupture. It is unclear if antibiotics increase the risk of unwanted events and serious unwanted events compared with placebo.

• We need more high-quality, long-term studies to confirm the benefits and harms of antibiotics. Future studies should explore different types of antibiotics, alternative ways to deliver them (like injections), and populations in various world regions to account for antibiotic resistance.

What are low back pain and radicular pain?

Low back pain is pain or discomfort in the area between the bottom of the ribs and the crease under the buttocks. Lumbar radicular pain, sometimes known as sciatica or radiculopathy, refers to pain that radiates down the leg from the lower back. The most common cause of radicular pain is irritation of a nerve root in the lumbar spine (the bottom five vertebrae). Low back and radicular pain can seriously limit the ability of people to work, enjoy hobbies, and stay independent.

How are low back pain and radicular pain treated?
There are many treatments available for low back pain and radicular pain, including education, self-care, painkillers, and physiotherapy. Some studies have suggested that low back pain and radicular pain may stem from an infection in a spinal disc caused by the bacteria Cutibacterium acnes (C. acnes), which is commonly found on human skin and is best known for its role in acne. For this reason, some experts think that antibiotic treatment for C. acnes (e.g. penicillin) could improve low back pain, radicular pain, or both.

What did we want to find out?

We wanted to find out if antibiotics were better than placebo (dummy treatment) or other treatments for reducing pain and back-related disability, and whether these antibiotics had any unwanted effects, in people with low back pain, radicular pain, or both.

What did we do?

We searched for studies that investigated antibiotics compared with placebo in people with low back pain, radicular pain, or both. 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 included three studies with 402 people (mostly women); the average ages ranged between 45 years and 51 years. The studies took place in Denmark, Belgium, and Norway.

Main results

Compared with placebo, antibiotics may improve back pain slightly after 12 to 14 weeks in people with low back pain linked to disc rupture and damage to the vertebral endplate (the layer between the disc and the vertebra). Two studies measured this outcome in 255 participants. On average, people who had antibiotics rated their pain as 50.6 out of 100, compared with 59 out of 100 among those who had placebo.

Compared with placebo, antibiotics may result in a small to moderate improvement in back-related disability after 12 to 14 weeks in people with low back pain linked to disc rupture and damage to the vertebral endplate (2 studies, 255 participants). On average, people who had antibiotics rated their back-related disability as 45.2 out of 100, compared with 55.7 out of 100 among those who had placebo (2 studies, 255 participants).

We don't know if people taking antibiotics are more likely to experience any unwanted effects compared with those taking placebo (2 studies, 262 participants). In the studies, 76 out of every 100 people taking antibiotics reported having unwanted effects, compared with 49 out of 100 people taking placebo, but we are very uncertain about these results.

We don't know if people taking antibiotics are more likely to experience serious unwanted effects compared with those taking placebo (2 studies, 262 participants). In the studies, three out of every 100 people taking antibiotics reported serious unwanted effects, compared with two out of every 100 people taking placebo, but we are very uncertain about these results.

The unwanted effects reported by people taking antibiotics included abdominal pain, diarrhoea, increased flatulence or burping, rash, and fungal infection.

What are the limitations of the evidence?

We have little confidence in the evidence for the effects of antibiotics on back pain and back-related disability, and we are not confident in the evidence related to unwanted effects and serious unwanted effects. The main issues were that the results varied widely, and the studies tested only one type of antibiotic in people from a single region (Scandinavia).

How up to date is this evidence?

The evidence is current to 26 August 2025.

Key messages

• In people with stomach cancer, there may be little to no difference in survival and the chance of the cancer coming back whether the spleen is removed or kept during surgery to remove the stomach. We are unsure about the effects of removing or keeping the spleen on death shortly after surgery.

• Removing the stomach and the spleen probably leads to more people having complications after the operation. However, we are very uncertain whether removing the spleen changes the chance of needing another operation, or the length of hospital stay. We found no evidence about quality of life.

• Future studies should investigate people with tumors in different locations and at different stages of severity. They should look at quality of life and unwanted effects.

What is stomach cancer?

Stomach cancer is a disease in which the cells forming the inner lining of the stomach become abnormal and start to divide uncontrollably, forming a mass called a tumor.

How is stomach cancer managed?

Stomach cancer in the upper third of the stomach is often treated by performing an operation to remove the stomach (total gastrectomy). Removing the spleen at the same time as the stomach also removes the lymph nodes near the spleen. The more lymph nodes that can be removed, the more accurately doctors can judge what stage a cancer has reached, which can indirectly improve survival by identifying people who can benefit from additional therapies. The routine surgical removal of the spleen during total gastrectomy is controversial: it may potentially benefit people in terms of survival; conversely, it is also possible that it may have no benefits and may be associated with unwanted effects.

What did we want to find out?

We wanted to find out if removing the spleen during surgery for stomach cancer is better or worse than leaving it in place. We looked at the effects on survival, chance of cancer coming back, death shortly after surgery, complications after surgery, need for another operation, length of hospital stay, and quality of life.

What did we do?

We searched for studies that compared removing the spleen versus keeping the spleen during total gastrectomy. Studies could take place anywhere, and be published at any time and in any language. We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and study sizes.

What did we find?

We found five studies with 1002 adults undergoing surgery for stomach cancer. The studies were conducted in Asia and South America and were published between 1985 and 2017. On average, the proportion of women in the studies was between 20% and 30%. Four studies with 908 participants reported the tumor stage. Three studies with 736 participants reported the tumor depth and type. The studies reported the following outcomes: survival, chance of cancer coming back, death shortly after surgery, complications after surgery, need for another operation, and length of hospital stay.

Main results

Compared with keeping the spleen, removing the spleen during surgery for stomach cancer probably leads to more people having complications after surgery. It is unclear if removing the spleen has an effect on death shortly after surgery, the chance of needing another operation, or the length of hospital stay. Removing the spleen may make little to no difference to survival and the chance of cancer coming back. None of the studies reported quality of life.

What are the limitations of the evidence?

We are not confident in the evidence because it is possible that people in the studies were aware of what treatment they were getting, and not all the studies provided data about everything that we were interested in. In addition, some studies did not clearly report how they were conducted, and there are not enough studies to be certain about the results of our outcomes.

How up to date is this evidence?

The evidence is current to February 2025.

Key messages

• Choosing to fix the patch with glue or a self-sticking patch compared to using stitches, tacks, or staples may make little to no difference to the risk of long-term pain and the hernia coming back.

• Fixing the patch with glue or a self-sticking patch may reduce the risk of blood collecting under the skin compared with using stitches, tacks, or staples.

• We generally have little or very little confidence in the results, meaning the results should be interpreted carefully.

What is a groin hernia?

A groin hernia happens when abdominal content, like part of the intestine or fat, pushes through a weak spot in the groin. A hernia causes a bulge and sometimes pain. Groin hernias are common and typically require surgery as they do not go away without surgery.

How is a groin hernia treated?

A groin hernia can be treated by a keyhole operation where surgeons make small cuts in the abdomen and use special tools to fix the groin hernia from inside the abdomen. Surgeons place a patch over the weak area in the groin to support it. The patch can be attached using glue or special self-sticking patches (named ‘non-penetrating patch fixation’ in this review) or using sharp tools like stitches, tacks, or staples (named ‘penetrating patch fixation’ in this review).

What did we want to find out?

We wanted to find out whether non-penetrating or penetrating patch fixation was more effective in reducing pain, preventing the hernia from coming back, and avoiding other problems during and after surgery.

What did we do?

We looked for studies where adults with groin hernias were randomly assigned to non-penetrating or penetrating patch fixation during keyhole surgery. We combined the results of these studies and assessed how trustworthy the evidence was.

What did we find?

We found 35 studies involving 4329 adults. About half of the participants had non-penetrating patch fixation, and the other half had penetrating patch fixation. Most participants were men aged between 37 and 66 years. The most common type of hernia was a first-time-occurring hernia on one side of the groin. Most studies compared fixing the patch with glue compared to using staples or tacks. The studies were of varying size, with between 30 and 600 people each, and follow-up time varied from a few days up to 56 months after surgery. Most of the included studies were from Asia or Europe.

What are the main results?

Non-penetrating patch fixation may make little to no difference to the risk of long-term pain and the hernia coming back after surgery. Non-penetrating patch fixation may reduce the risk of blood collecting under the skin in the groin compared with penetrating patch fixation, but we are not confident in this evidence. We do not know if the type of patch fixation has an effect on short-term pain, infections of the patch, how long the surgery takes, or if it prolongs how quickly people return to normal activities.

What are the limitations of the evidence?

A limitation is that we have little confidence in the evidence. This is mainly due to studies not reporting all relevant information or because there are not enough studies to be certain about the results of the outcomes.

How up to date is this evidence?

The evidence is up to date to 14 November 2024.

Key messages

• Blue light-supported resection (surgical removal) of the bladder may have little to no effect on the chance of cancer returning in people at low risk (risk for cancer returning), but may reduce the chance for those at medium and high risk.

• Blue light-supported resection of the bladder probably has little to no effect on the chance of cancer getting worse in people at low risk (for cancer getting worse) or medium risk, but may reduce the chance for those at high risk.

Why is a special visualization method (blue light) used during resection of the bladder?

In people who might have bladder cancer, the possible tumor is cut from the inner bladder wall using a special instrument inserted through the tube that carries urine from the bladder to outside the body (the urethra) into the bladder. However, it is sometimes difficult to tell what is normal bladder tissue and what is cancer. In order to see the tumor better and remove it completely, a liquid (contrast agent) is put into the bladder through a thin tube (catheter). During surgery, a special light is used to make the cancer cells light up red.

What did we want to find out?

We wanted to find out if using blue light-enhanced resection of the bladder is better than using white light during bladder surgery for people with non-muscle (superficial) invasive bladder cancer. We looked at whether it affects:

• the time it takes for cancer to return (recurrence);

• the time it takes for cancer to get worse (progression);

• whether people lived for longer;

• serious complications during surgery;

• mild complications during surgery;

• and if it had any unwanted effects.

What did we do?

We searched for studies which randomly assigned people with bladder cancer to have either blue light-enhanced resection of the bladder or white light-based resection of the bladder. We compared and summarized the results of these studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We identified 17 studies comparing the use of blue light-enhanced resection of the bladder to white light-based resection of the bladder. These studies involved a total of 4890 participants in the review. Blue light-enhanced resection of the bladder may have little to no effect on the risk of recurrence in people at low risk, but may reduce the risk of recurrence in those at medium and high risk. Blue light supported resection of the bladder probably has little to no effect on the risk of progression in people at low risk, may have little or no effect on the risk of progression in people at medium risk, but may reduce the risk of progression in those at high risk. We also found that blue light may have little to no effect on the number of mild or serious surgical complications, the risk of death from bladder cancer over time, any unwanted effects and mild surgical complications.

What are the limitations of the evidence?

The most significant limitations of the evidence considered in this review stem from the quality of the included studies. In some studies, the treatments were not delivered exactly as planned, making it harder to compare the groups fairly. Other studies had missing information, and the amount or reasons for missing data differed between treatment groups, which could affect the results. In addition, some studies may have reported only selected outcomes while leaving out others, creating a risk that the findings do not provide a complete picture of the intervention's effects.

How up to date is this evidence?

This review updates our previous review. The evidence is up to date to March 2026.

Key messages

• Telepharmacy may help people take their medicines as prescribed, and may reduce both systolic blood pressure (the pressure in your arteries when your heart beats) and diastolic blood pressure (the pressure between heartbeats). It probably makes little or no difference to blood sugar control (HbA1c).

• We are very uncertain about its effects on patients’ satisfaction with care. Telepharmacy may affect medicine‐related problems (such as side effects or interactions), but findings varied because some interventions aimed to detect more problems while others aimed to reduce harms from medicines. No studies reported the number of deaths or unwanted effects from telepharmacy, so potential harms remain uncertain.

• Studies did not show consistent effects on quality of life, hospital admissions, hospital emergency department visits, or healthcare costs. Most studies involved only a few people or had limitations, and the studies varied in delivery and content.

What is telepharmacy?

Telepharmacy is the use of phone calls, video calls, mobile apps, or other electronic communication to provide pharmacy services without meeting in person. It can include advice about medicines, help with taking medicines as prescribed, and monitoring of health. Telepharmacy can make it easier for people to get support from a pharmacist, especially if they live far from a clinic or have difficulty travelling. It may also help pharmacists detect medicine‐related problems and adjust treatments when needed.

What are long-term health conditions?

Long-term health conditions, sometimes called chronic conditions, are health problems that can usually be controlled but not cured. They last for three months or longer, and may get worse over time. People with long-term conditions often require ongoing care. Examples include diabetes, high blood pressure, asthma, and heart disease. These conditions can affect a person’s quality of life and may lead to serious complications if not well managed. People with long‐term conditions often need regular check‐ups, tests, and support to take their medicines correctly.

What did we want to find out?

We wanted to find out whether telepharmacy, compared with usual care, helps people take their medicines as prescribed, and improves patients’ satisfaction with care, medicine‐related problems, asthma control, blood pressure, and blood sugar control (measured using the HbA1c test) in people with long‐term conditions in outpatient settings. We also looked at other possible effects, such as quality of life, admissions to hospital, emergency department visits, and healthcare costs.

What did we do?

We searched for studies that compared pharmacist‐led telepharmacy with usual care for people with long-term conditions in outpatient settings. We included high-quality studies, known as randomised controlled trials. We summarised the results and rated our confidence in the evidence, considering factors such as study design, number of participants, and consistency of results.

What did we find?

We found 21 trials including 5440 people, which were performed in different countries and settings (e.g. pharmacy, hospital). Most trials compared telepharmacy with usual face-to-face care for people with long‐term conditions in outpatient settings. In the included studies, usual care generally referred to standard face-to-face care without additional telepharmacy support. Most studies lasted 12 months or less.

In people with long-term conditions in outpatient settings, compared with usual care:

• telepharmacy may improve how well people take their medicines as prescribed (10 studies, 2978 people), that is, as instructed by their healthcare providers;

• the evidence is very uncertain about whether telepharmacy improves patients’ satisfaction with their care (3 studies, 422 people);

• telepharmacy may affect problems such as medicine side effects or interactions (5 studies, 547 people), but findings varied because some studies aimed to detect more problems while other studies aimed to reduce harms;

• telepharmacy may reduce systolic blood pressure (the pressure in your arteries when your heart beats) and diastolic blood pressure (the pressure between heartbeats) (5 studies, 1254 people); but

• telepharmacy probably makes little or no difference to blood sugar control (HbA1c levels) (5 studies, 1771 people).

No studies reported the number of deaths or unwanted effects from telepharmacy, so potential harms remain uncertain. We have more confidence in some findings (such as blood sugar control) than in others (such as patients' satisfaction with their care). For some outcomes, future research could change what we know.

What are the limitations of the evidence?

Our confidence in the findings was reduced because many studies involved only a few people, had problems with how they were carried out, or produced results that did not always agree. Evidence about problems caused by medicines came only from descriptions given by patients, as we were unable to group and analyse data from different studies. The studies used telepharmacy interventions that varied in their content, and how or how often they were given, which may have influenced the results.

How up to date is this evidence?

The evidence is up to date to December 2025.

Key messages

• Current evidence does not allow firm conclusions regarding the safety of treatment with insulin-like growth factor-1, a protein that helps blood vessels in the retina of the eye grow normally, in premature babies born before term and weighing less than 1500 grams.

• Current evidence does not allow firm conclusions regarding the effect of insulin-like growth factor-1 treatment for prevention of retinopathy of prematurity, a disease in premature babies where blood vessels in the back of the eye do not grow normally.

• So far, studies of insulin-like growth factor-1 in preterm infants may not detect important benefits or side effects.

What are retinopathy of prematurity and insulin-like growth factor-1?

Retinopathy of prematurity is a common disease in babies born prematurely with a birth weight less than 1500 grams. It is caused when blood vessels in the back of the eye do not grow normally. Retinopathy of prematurity can cause vision problems or blindness.

Insulin-like growth factor-1 is a protein that helps blood vessels in the retina of the eye grow normally during pregnancy. When babies are born too early, they may not have enough insulin-like growth factor-1 in their bodies and this may cause blood vessels in the retina to grow abnormally, leading to the development of retinopathy of prematurity.

How is retinopathy of prematurity treated?

Currently, retinopathy of prematurity is treated with lasers that burn the retina in the back of the baby's eye to stop stimulation of the abnormal blood vessels that may damage vision, or with medications that are injected into the eye to temporarily stop the abnormal blood vessels from continuing to grow and damage vision.

What did we want to find out?

We wanted to find out if giving insulin-like growth factor-1 to premature babies prevents or treats retinopathy of prematurity. We also wanted to find out if giving insulin-like growth factor-1 to premature babies causes any serious side effects or problems, or had an effect on any other medical issues caused by prematurity, like brain bleeding or lung disease of prematurity.

What did we do?

We searched for research studies that compared treatment with insulin-like growth factor-1 either to a placebo (a ‘dummy’ or sham treatment) or to standard care, which is usual neonatal intensive care unit (NICU) care that does not normally include giving insulin-like growth factor-1, in premature babies who were at risk of developing retinopathy of prematurity. We compared and summarized the results of the studies and rated our confidence in the evidence based on study methods and size.

What did we find?

We included two studies with a total of 140 premature babies. The included studies tested insulin-like growth factor-1 treatment in premature babies and followed their outcomes through five to six years of age.

We found that the results of current studies do not allow for a definite conclusion regarding its efficacy for preventing or treating retinopathy of prematurity. The results of current studies also do not allow for a definite conclusion regarding the safety of insulin-like growth factor-1 treatment in premature babies, including harmful effects or death.

What are the limitations of the evidence?

Our confidence in the evidence is very low, and the results of further research could differ from the results of this review. Two main factors reduced our confidence in the evidence. First, we only identified two studies of insulin-like growth factor-1 treatment in premature infants and not many infants participated in them. This means there may not have been enough participants who received treatment to determine whether it actually made a difference. Second, the studies we found had problems with their design or the way they were conducted, which may affect the accuracy of their results.

How up to date is this evidence?

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

Key messages

• In people with mild memory and thinking problems (mild cognitive impairment (MCI)) or mild dementia due to Alzheimer's disease, laboratory-produced medicines (anti-amyloid monoclonal antibodies) that target and remove potentially damaging build-ups of amyloid proteins in the brain, probably result in little to no difference in the decline in memory functioning and thinking ability, or in how severe dementia symptoms are, compared with placebo (sham treatment) 18 months after the start of treatment.

• Anti-amyloid monoclonal antibodies probably cause more brain swelling and tiny (micro) bleeds than placebo. They do not increase other serious unwanted effects or deaths compared with placebo.

• Successful removal of amyloid proteins from the brain does not seem to be associated with clinically meaningful improvements in people with MCI or mild dementia due to Alzheimer’s disease. Future research on disease-modifying treatments for Alzheimer’s disease should focus on other treatments.

What is Alzheimer’s disease?

In Alzheimer’s disease, brain cells die following the build-up of proteins (called amyloid plaques). Alzheimer’s disease affects people’s memory and thinking abilities. Symptoms are usually mild to begin with and do not interfere with everyday life. This is called ‘mild cognitive impairment’ (MCI). Over time, it can progress to mild dementia, where memory and thinking difficulties are serious enough to interfere with everyday activities. About 15% of people with MCI will develop dementia due to Alzheimer’s disease within two years. It is the most common form of dementia among older people.

What are anti-amyloid monoclonal antibodies?

Antibodies are made by the body as a defence against disease. They can also be produced in a laboratory for use as a medical treatment. Anti-amyloid antibodies are designed to target the amyloid proteins that cause plaques due to Alzheimer’s disease, and remove them from the brain. They are ‘monoclonal’ because they only target amyloid proteins. Removing amyloid proteins from the brain may slow the progression of Alzheimer’s disease.

What did we want to find out?

We wanted to know if anti-amyloid monoclonal antibodies are an effective medicine for people with MCI or mild dementia due to Alzheimer’s disease. We evaluated whether they slowed down:

• the decline in memory and thinking;

• the decline in ability to manage everyday activities; and

• the worsening of dementia symptoms.

We also wanted to know if they caused any unwanted effects.

What did we do?

We searched for studies that investigated one or more anti-amyloid monoclonal antibodies to treat people with MCI or mild dementia due to Alzheimer’s disease, compared with placebo (sham treatment that does not contain any medicine but looks identical to the medicine being tested and is delivered in the same way).

We summarised the results of the studies, and rated our confidence in the evidence, considering aspects such as study sizes and methods.

What did we find?

We found 17 studies that were carried out in different countries and involved 20,342 people. The average age across studies was from 70 to 74 years. All studies were funded by companies that produced the anti-amyloid monoclonal antibodies.

Main results

After 18 months of treatment, anti-amyloid monoclonal antibodies:

• may make little to no difference to how bad people’s dementia symptoms are (9 studies, 8053 people);

• probably make little to no difference in the decline in memory and thinking ability (13 studies, 9895 people) or the ability to manage everyday activities (3 studies, 3478 people);

• may result in a small improvement in more complex everyday tasks, such as shopping, managing finances, taking medication, and using transportation (1 study, 1252 people);

• probably result in a small increase in the occurrence of brain swelling. For every 1000 people using monoclonal antibodies, 119 developed brain swelling compared with only 12 of 1000 people using placebo (11 studies, 13,595 people);

• may result in a small increase in microbleeds in the brain (3 studies, 4308 people);

• do not increase other serious unwanted effects as defined by the study authors (9 studies, 11,904 people); and

• do not increase deaths from any cause (7 studies, 9733 people).

What are the limitations of the evidence?

Our confidence in the evidence is limited for two reasons. Firstly, people who received monoclonal antibodies had more brain swelling and microbleeds than people receiving placebo. However, most studies did not separate people with symptoms of brain swelling and microbleeds from those in whom these effects were only visible with a scan. This reporting gap leaves patients without the information they need to understand the seriousness of potential unwanted effects. Secondly, the results came from studies that did not last very long. These are important limitations in the evidence for people with Alzheimer’s disease, who need to know the longer-term benefits and unwanted effects of medicines.

We found six ongoing studies. The review's conclusions may change as new results become available.

How up to date is this evidence?

The evidence is current to 7 August 2025.

Key messages

• Children with low language proficiency (LLP) (difficulties) may meet problems with speaking, understanding language, and literacy (ability to read) as they grow older. They also have psychological and social difficulties later in life, but the evidence is less certain for these outcomes than for learning outcomes.

• It is unclear whether early language skills affect later independence and participation in everyday life, as the evidence is very limited and uncertain.

• We need more long-term, high-quality studies with large samples and comparison groups to understand which children are most affected and how early language difficulties affect later outcomes, particularly independence and participation in daily life, where current evidence is limited.

Low language proficiency in children

Children with LLP have difficulties with speaking, understanding, or using language in early childhood. These difficulties can affect how children learn to read, communicate with others, and take part in everyday activities at school and at home. For some children, early language difficulties improve over time. For others, they continue as children grow older and may affect later learning, social relationships, and independence.

What did we want to find out?
We wanted to see whether children with low language skills at ages four to eight years old continue to have problems with language, reading, and quality of life as they grow up.

What did we do?
We searched for studies of children between the ages of four and eight years who were identified as having LLP. These children either scored below average on language tests or had a clinical diagnosis. We analysed outcomes related to language and reading, as well as five areas of quality of life:

• psychological well-being (mental health)

• physical health

• independence

• social relationships (making friends)

• participation in everyday life such as work and community life

We combined the results of the studies using statistical methods (meta-analysis) and took into account that some outcomes were related to each other.

What did we find?

We found 80 studies (that took place in North America or Europe) which followed children with LLP into adolescence or adulthood and reported outcomes from 15 different groups of children (cohorts), with about 28,800 children in total.

Children with LLP are likely to continue:

• having difficulties with language and reading into adolescence and adulthood.

These difficulties were noticeable and consistent across studies. Children with LLP may also be at higher risk of:

• mental health problems, such as depression or anxiety

• difficulties with making friends

• less independence in daily life

We do not have enough evidence to know whether they have problems with physical health.

What are the limitations of the evidence?

Some studies in this review had limitations that affect how confident we can be in the results.

• We are highly confident that children with LLP have difficulties with literacy (ability to read) when growing up.

• We are moderately confident that children with LLP have difficulties with language when growing up, because some of the children in the studies dropped out. However, our results were generally consistent.

• We are moderately confident that children with LLP experience more mental health problems (e.g. problems with making friends) and a lack of participation in everyday life when growing up. Our confidence is only moderate because of small studies (for participation) or variation between studies. Generally, patterns were consistent but further evidence may change our results.

• We have low confidence that children with LLP have difficulties with becoming independent when growing up, because of very few studies. Further evidence is likely to change our results.

• We are not confident that children with LLP have difficulties with physical health when growing up. The evidence is very uncertain.

The way low language proficiency was described and measured sometimes varied between studies. Some outcomes — especially physical health, independence, and participation in daily life — were only reported in a few studies. Some studies were small or included only certain groups of children. Important factors, such as non-verbal IQ or other health conditions, were not always reported. The results also varied between studies, which means that not all children with LLP are affected in the same way. Overall patterns are consistent, but some findings should be interpreted carefully.

How up to date is this evidence?

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

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