• Telling people what treatment they will receive – rather than them not being told – improves recruitment.

• Telephoning people who don't respond to an initial postal invitation to join a trial improves recruitment when the initial recruitment rate is low.

• Tailored, user-tested information leaflets, sending letters about the importance of research, or providing a link to videos make little or no difference to recruitment.

Research trials compare different approaches, such as treatments, programmes, or ways of delivering services. In health care, trials are essential to test new medicines and devices on human volunteers (‘trial participants’) to make sure they are safe and effective. However, finding and keeping trial participants is challenging. About half of all trials fail to recruit the number of people they need on time. Strategies to boost recruitment include changing trial methods and improving information for potential participants and how they are invited to take part.

We wanted to find out which strategies encouraged more people to join research trials, and whether they:

• were good value for money (cost-effective);

• made any difference to whether people stayed in the trial until the end (retention); and

• had any effect on the diversity of the people and places involved.

We searched for studies that tested different recruitment strategies embedded within research trials. Potential participants were chosen by chance to receive different recruitment approaches, and the studies measured how many people joined the trial.

We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as methods and the number of people participating.

We found 91 studies, each involving between 37 and 30,000 participants, mostly conducted in the UK (46 studies) and USA (23 studies). All were in healthcare trials. Nearly all (99%) were carried out in high-income countries. Most studies gave little information about the people they recruited.

The studies tested 65 different recruitment strategies ranging from changes to trial methods to how people were approached and informed about taking part. Participants had different health concerns (e.g. cancer, surgery).

We are confident in the evidence for only 5 of the 65 strategies investigated, and we focus on these below.

Trial procedures

• Potential participants are more likely to join an ‘open-label’ trial, where they know their treatment, than a ‘blinded’ trial, where they do not know which treatment they will receive (3 trials, 9004 participants).

• For every 100 people invited, an open-label trial recruits 10 more participants.

• The trials involved mostly women in the UK and Estonia.

• There was no information about cost-effectiveness and retention.

Telephone reminders

• Telephoning people who have not responded to a postal invite improves recruitment (2 trials, 1450 people).

• Six more people take part if 100 people are called.

• Participants were aged 58 years on average and lived in Canada and Norway.

• There was no information on cost-effectiveness or retention.

Letters about the importance of research

• Sending letters about the importance of research before the trial invitation does not significantly improve recruitment (2 trials, 5376 participants).

• One more person joins if 100 people are sent a letter.

• This small gain was not good value, costing 2.08 pounds sterling (GBP) per additional participant recruited.

• The trials involved mostly older white people in the UK and Ireland.

QR code or link to videos alongside printed information leaflets

• Providing a QR code or link to videos alongside a printed information leaflet makes no difference to recruitment (7 trials, 11,612 participants) or retention (5 trials, 7403 participants).

• There is zero change per 100 people.

• This strategy was not cost-effective (GBP 0.78 more).

• The trials involved people in the UK.

Information leaflets

• Information leaflets developed with input from people similar to those being recruited make no difference compared to standard leaflets (6 trials, 27,805 participants).

• Both types of leaflet result in 7 in 100 people joining the trial.

• The trials involved people in the UK, mostly older women in one trial.

• There was no information on cost-effectiveness or retention.

• Our confidence in all but the five strategies above is limited because they were tested in only one trial, the trials testing them had problems with their methods, or the results were very uncertain.

• We found cost information for only 8 strategies, and retention information for only 15 trials.

• Few trials reported information about participants' age, sex, gender, education level, and income level, so we are not sure how effective the strategies would be for different people.

• Most trials (75%) were carried out in the UK or USA, so our findings may not apply to healthcare systems in other parts of the world. We screened all non-English studies, none were eligible.

This review updates our 2018 review. The evidence is current to February 2023.

• It is unclear if medicines used to prevent bone loss (bisphosphonates) lower the risk of breaking a hip, backbone (spine), or other bones in men.

• These medicines probably do not cause more unwanted effects or serious health problems than dummy treatment (placebo) in men.

• Other medicines (parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) analogues, denosumab, and romosozumab) appear to show similar results, except we are very uncertain about the effects of PTH/PTHrP analogues on unwanted effects.

Bone loss (osteoporosis) is when bones become thin, fragile, and break (fracture) easily. Fractures commonly occur in the hip, backbone (spine), and other bones. These fractures often happen in older people after a fall from a standing height or less. Such fractures can lead to long-lasting pain, loss of independence, disability, and in some cases even death. Osteoporosis in men usually starts later in life and progresses more slowly than in women. Other risk factors for fractures such as balance, muscle strength, co-existing conditions, medications, and fall direction may also differ between men and women.

Doctors often use bone-strengthening medicines to help prevent fractures caused by minor falls or injuries. Common medicines include bisphosphonates (zoledronic acid, alendronate, risedronate, ibandronate), parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP) analogues, denosumab, or romosozumab. Most research on these medicines has been done in women, especially after menopause. Much less is known about the effects of these treatments in men who are at risk of fracture.

We wanted to find out if these medicines reduce fractures of the hip, spine, or other bones, and if they cause unwanted effects in men at risk of fracture.

We searched for studies where men at risk of fracture were given bisphosphonates, PTH/PTHrP analogues, denosumab, or romosozumab compared with dummy treatment (placebo) or other treatments. 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.

We found 17 studies (4132 participants). The average age of participants ranged from 52 to 73 years. Two studies were conducted in Germany, four in the USA, one in Turkey, one in Taiwan, and nine studies were multinational.

Compared with placebo, at up to two years:

• 0.1% less people had a hip fracture when taking bisphosphonates, but the evidence is very uncertain (4 studies, 1635 people):

  • 0.2% of people had a hip fracture with bisphosphonate;

  • 0.3% of people had a hip fracture with placebo.

• 0.4% less people had symptomatic spine fractures when taking bisphosphonates, but the evidence is very uncertain (5 studies, 1876 people):

  • 0.4% of people had a symptomatic spine fracture with bisphosphonate;

  • 0.8% of people had a symptomatic spine fracture with placebo.

• 0.5% less people had other (not hip or spine) fractures when taking bisphosphonates, but the evidence is very uncertain (6 studies, 2043 people):

  • 1.6% of people had other fractures with bisphosphonate;

  • 2.1% of people had other fractures with placebo.

Bisphosphonates probably do not increase the risk of unwanted effects. 4.2% more people experienced unwanted effects with bisphosphonates compared to those taking a placebo (7 studies, 2548 people):

• 74.6% of people experienced unwanted effects with bisphosphonate;

• 70.4% of people experienced unwanted effects with placebo.

1.2% less people withdrew from the study because of unwanted effects with bisphosphonate compared to those taking a placebo, but the evidence is very uncertain (7 studies, 2548 people):

• 2.5% of people withdrew from the study because of unwanted effects with bisphosphonate;

• 3.7% of people withdrew from the study because of unwanted effects with placebo.

Bisphosphonates probably do not increase the risk of serious unwanted effects (6 studies, 2457 people). 1.4% less people experienced serious unwanted events with bisphosphonates compared to those taking a placebo:

• 27.2% of people experienced serious unwanted effects with bisphosphonate;

• 28.6% of people experienced serious unwanted effects with placebo.

Disability was not measured in any trial.

We found similar results for PTH or PTHrP analogues (4 studies, 569 people), denosumab (1 study, 240 people), and romosozumab (1 study, 244 people) compared with placebo.

We have very low confidence in the effect of bisphosphonates on preventing fractures as there were few trials; the follow-up time was usually short (mostly two years or less); and there were few people with fractures in both study groups.

We have only moderate confidence in the effect of bisphosphonates on unwanted effects or serious unwanted effects because it was not clear if all studies had fully reported every event. We have very low confidence in the effect of bisphosphonates on study withdrawals due to unwanted effects, because in some studies it was not clear whether people withdrew because of unwanted effects or for other reasons.

The evidence is current to October 2025.

• People with stroke can safely take part in programmes of exercise that involve aerobic fitness training.

• Aerobic fitness training may improve fitness, reduce disability, increase walking speed, and improve balance at the end of the programme, but it is unclear if these are noticeable improvements.

• There is not enough evidence about the effects of aerobic training and further research is needed.

A stroke occurs when the blood supply to part of the brain is interrupted, leading to damage in specific areas of the brain. The impact of stroke can be life-changing and varies depending on the severity of damage and where it occurs in the brain. As well as affecting the ability to move, stroke can impact thinking, feeling, and behaviour. These effects can persist throughout life after stroke. One physical impact of stroke is reduced aerobic fitness and muscle strength, which make physical activity and getting back to everyday activities more difficult. Low aerobic fitness could also be a risk for having another stroke.

After a stroke, many patients receive rehabilitation, for example, from a physiotherapist or other health professional, to help them overcome difficulties with everyday activities. Rehabilitation often includes different types of exercise. One type is aerobic (or 'cardiorespiratory') training, which involves continuous exercise that increases heart rate, which may increase the stamina needed for repetitive activities like walking.

We wanted to find out if aerobic fitness training is beneficial at any time after stroke (whether in hospital or after going home). Specifically, we wanted to know whether aerobic training after stroke:

• is safe;

• improves physical fitness and movement (including walking and balance);

• changes how people feel (including depression and quality of life); and

• reduces the risk of another stroke.

We searched for studies that tested an aerobic training exercise programme for people after a stroke compared to usual care, no programme or a non-exercise programme. We only included studies if the exercise programme being tested was based only on aerobic training; we excluded studies that involved other types of exercise, such as muscle strength training.

We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors like study methods and the number of people involved.

We found 53 studies involving 2672 people with stroke. Most of the study participants could walk. Thirty-seven of the studies were conducted in high-income countries. The average age of study participants was 61.9 years. Most studies took place either within three months of a stroke (19 studies) or at least six months after a stroke (29 studies). In 28 studies, the people in the aerobic exercise groups received more attention than those in the control groups.

In 49 studies, exercise sessions lasted between 20 and 60 minutes; in 48 studies, exercise frequency was 3 to 5 days a week. The programme was less than 12 weeks in 37 studies. Exercise intensity was reported as maximal heart rate, heart rate reserve (based on resting heart rate), or participants' ratings of perceived exertion.

Sixteen of the 53 studies followed up the people taking part in the studies. The length of follow-up ranged between 12 weeks and 12 months after the programme started. One study planned a six-month follow-up but did not report it.

• Aerobic exercise does not affect the number of deaths at the end of the programme (36 studies, 1563 participants) or at follow-up (10 studies, 713 participants).

• Aerobic exercise does not affect the number of second strokes at the end of the programme (8 studies, 544 participants) and probably does not affect them at follow-up (4 studies, 412 participants).

• We are very uncertain about the results for blood pressure at the end of the programme (9 studies, 535 participants) or at follow-up (3 studies, 155 participants).

• Aerobic exercise may cause small improvements in balance (18 studies, 772 participants), disability (17 studies, 1073 participants), aerobic fitness (13 studies, 608 participants) and comfortable walking speed (16 studies, 647 participants) at the end of the programme, but it is unclear if these changes are large enough to be meaningful for people with stroke. The results at follow-up are unclear; the aerobic fitness benefit may continue but may not be large enough to be meaningful for people with stroke (5 studies, 237 participants).

• Most studies involved people who could walk; little is known about the many people with stroke who have more limited mobility.

• Most studies took place in high-income countries; little is known about people with stroke in other countries.

• There are many uncertainties and not enough evidence about the effects of aerobic training. Further research is needed.

This review is one of three that update a previous single review on fitness training for stroke. The evidence is based on searches run up to April 2025.

° Many NTCP models have been developed to predict unwanted effects following radiotherapy in head and neck cancer patients but most of them have not been sufficiently externally validated, that is, tested with patients who were not involved in the original model developmental study, to know how well they really predict the unwanted effects.

° For models tested in two or more studies in addition to their original model development studies, the quality of testing and reporting of their results was generally poor, so it is difficult to know how useful they might be.

° More and better designed studies are required to investigate this issue in the area of head and neck cancer.

The likelihood of having unwanted effects as a result of radiotherapy can be calculated by using so-called NTCP models. NTCP models calculate the risk of radiation-induced side effects based on information from the patient, their disease, and their treatment.

Radiotherapy is the mainstay of treatment of patients with head and neck cancer. However, radiotherapy exposes healthy, sometimes crucial, parts of the head and neck region to radiation. This may result in damage to these normal organs, e.g. disturbed saliva production, which may have important consequences for the quality of life of head and neck cancer patients treated with radiotherapy. To reach an optimal balance between tumour control and preventing radiation-induced side effects, normal tissue complication probability (NTCP) models can be helpful. These models predict the risk of radiation-induced side effects based on information from the patient, their disease, and their treatment. There have been a substantial number of NTCP models for patients with head and neck cancer. We wanted to find out what the quality of study design, conduct, and analysis (i.e. risk of bias) is, and how well these models can predict the risk of radiation-induced side effects.

We searched for studies that developed and/or validated NTCP models in patients with head and neck cancer.

In most of the 617 models developed from 162,527 patients in 152 identified articles, the quality of the models was not sufficient; and it has not been investigated how well they perform in new patients for 78% of these models. For the remaining 22% of the models, 193 external validations were found in 48,852 patients from 39 articles. There were only ten models with two or more external validations. The models were able to distinguish patients with and without the outcome well, but it was often unclear whether their predictions were in line with what was observed, because the latter was not always assessed and/or reported. Overall, the quality of most of these studies was low.

The evidence is current to 8th January 2024.

• Iodine supplementation improves thinking ability (cognitive function) slightly and may have little to no effect on growth (weight) in children and adolescents. None of the studies reported unwanted effects.

• Iodine supplementation likely reduces the occurrence of insufficient production of thyroid hormones (hypothyroidism), and risk of infant death (mortality) in places with high infant mortality rates. We are unsure about its effect on reducing enlargement of the thyroid gland (goitre).

• Future studies should focus on areas or populations in which lack of iodine could be a problem, and include children of lower socioeconomic levels. They should look at higher doses of iodine given during longer periods of treatment and follow-up times.

Iodine is a mineral used to make thyroid hormones, which are required for the normal development of the body and brain. Given its role in human development, it is especially important that children receive enough iodine. Lack of iodine (iodine deficiency) in children can lead to delayed growth and development of the central nervous system, intellectual disability, infant death, and enlargement of the thyroid gland (goitre).

The primary sources of iodine in the diet are iodised salt, seafood, grains from iodine-rich soils, and dairy products. Iodine supplementation can be given as combined iodine and plant-based oil (iodised oil), which is injected into a muscle only once or yearly, or as potassium iodide tablets, capsules, or drops, given in a low dose daily or weekly.

We wanted to know whether iodine supplementation results in fewer children and adolescents having iodine deficiency disorders compared with placebo (dummy treatment). We also wanted to know if receiving iodine supplementation was associated with any unwanted effects.

We searched for studies comparing iodine supplementation to placebo in children and adolescents at risk of iodine deficiency. 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.

We found eight studies (2528 people) that looked at the effects of preventive iodine supplementation in children and adolescents. The studies were conducted between 1982 and 2009 mainly in low‐income environs in Albania, Bangladesh, Colombia, Indonesia, Malawi, New Zealand, and Tanzania. The studies compared iodine supplementation by mouth (oral) (alone or with iron in one study) versus placebo.

• Iodine supplementation results in a slight increase in thinking ability (cognitive function) compared to placebo (1 study, 166 people).

• Iodine supplementation may result in little to no difference in children's weight compared to placebo (3 studies, 658 people).

• Iodine supplementation likely results in a large reduction in insufficient production of thyroid hormones (hypothyroidism) compared to placebo (1 study, 264 people).

• No study reported unwanted effects related to iodine or quality of life.

• Iodine supplementation likely reduces death due to any cause compared to placebo (1 study, 617 people).

• The evidence is very uncertain about the effect of iodine supplementation on the reduction of goitre (2 studies, 432 people). One study did not use robust methods. We removed it from our analyses and found that iodine likely results in a large reduction in goitre (1 study, 230 people).

• The evidence is very uncertain about the effect of iodine plus iron on weight (1 study, 146 people).

• No study reported cognitive function, hypothyroidism, unwanted effects, quality of life, death due to any cause, or goitre.

Our confidence in the evidence ranged from high to very low. In cases where our confidence was limited, this was because:

• it is possible that people in the studies knew which treatment they were getting;

• the studies were done in different types of people;

• there are not enough studies to be certain about the results.

The evidence is current to May 2025.

• HoLEP and the standard prostate operation (TURP) may relieve urinary symptoms and improve quality of life to a similar degree and with similar serious complications in the first year after surgery.

• HoLEP probably lowers the need for a blood transfusion compared to TURP, prostatectomy (removal of the prostate) and laser ablation (using a laser beam to destroy prostate tissue). For every 1000 men treated, about 36 fewer would need one.

• We don’t have enough evidence yet to say whether HoLEP is better for very large prostates or for people who take certain blood-thinning medicines.

The prostate is a small gland found only in men. It’s a non-cancerous condition where the prostate grows bigger as men get older, which can block urine flow. This is like a pipe getting narrower and harder to pee through.

Treatments include lifestyle changes, medicines, and surgeries. For a long time, the most common surgery was called transurethral resection of the prostate (TURP). In TURP, a doctor uses a small tool inserted through the urethra (the pee tube) to scrape away the extra prostate tissue. Today, doctors also use lasers to do this job. One type of laser surgery is called HoLEP.

We wanted to know how HoLEP compares with other surgical options in terms of relief of symptoms, quality of life, and safety (unwanted effects).

We searched for studies where doctors compared HoLEP with other prostate surgeries. We looked at how well each surgery worked, how safe it was, and how quickly men recovered. We then summed all the results and assessed the reliability of each study.

We found 52 studies involving 6242 men who had prostate surgery. This summary focuses on studies comparing HoLEP with TURP — the standard prostate operation — in the first year after surgery, because this is the comparison the one most relevant to men choosing between operations. The average age of the men ranged from 65 to 74 years, and the average prostate size in the studies ranged from 30 cc to 142 cc. Studies took place in 11 countries.

• Symptoms and quality of life: HoLEP may relieve urinary symptoms (14 studies, 1666 people) and improve quality of life (6 studies, 876 people) to a similar extent as TURP. Any difference we found was too small to matter to men.

• Serious complications: HoLEP may have similar serious complications (10 studies, 1147 people) compared with TURP.

• Repeat surgery and erectile function: These are probably similar after both operations.

• Ejaculation: No study reported what happened to ejaculation after either operation, even though this matters a great deal to many men.

• Blood transfusion: HoLEP probably lowers the chance of needing a blood transfusion compared to most other surgeries. About 44 in every 1000 men need a transfusion after TURP, compared with about 8 in every 1000 after HoLEP (15 studies, 1755 people).

• We also compared HoLEP with other laser operations, other enucleation techniques, and open surgery, and examined results beyond one year. These results are reported in the full review.

• Study quality: Most studies had design problems — for example, it is impossible to mask surgeons and very challenging to mask patients as to which operation was performed, which can affect how results are measured and reported. Only a few studies had pre-registered plans, so some results may have been selectively reported. For these reasons, our confidence in many findings is low or very low.

• Short follow-up: Most studies only followed patients for up to 12 months. We do not know whether the benefits of HoLEP hold up over longer periods, or whether repeat surgery rates differ substantially in the long run.

• No study reported on ejaculatory function for any comparison. Given that roughly three out of four men experience retrograde ejaculation (dry orgasm) after HoLEP, this is an important gap. Data on urinary leakage (incontinence) after surgery were also not consistently reported.

• Surgeon experience: Most surgeons in the included studies were highly experienced with HoLEP. Actual results may differ where surgeons are still learning: complication rates continue to fall with experience, settling only after about 350 operations.

• Limited evidence for certain patient groups: We could not perform the planned analyses for men with very large prostates (≥ 80 mL) or those taking blood-thinning medicines, because too few studies included these patients. These are precisely the groups in whom HoLEP may offer the greatest advantage, so this is a particularly important gap.

• Fewer studies for some comparisons: Most evidence compared HoLEP with TURP; we are less certain about comparisons with laser ablation, alternative enucleation techniques, or open surgery.

This review is up-to-date to April 08, 2026.

• In adults with chronic hepatitis B, thymosin-alpha1 may reduce death from any cause and serious unwanted effects. We are less sure about its effects on well-being, hepatitis B-related illness or death, non-serious unwanted effects and liver health.

• Future studies should use more robust methods and include more people.

Chronic hepatitis B is caused by infection with the hepatitis B virus (HBV). HBV attacks the liver, making it become inflamed – red, painful, and swollen. HBV infection can be short-term (acute) or long-term (chronic). Chronic HBV infection is when the condition lasts for more than six months. If not successfully treated, it may progress to chronic hepatitis, cirrhosis and other liver diseases, liver failure, cancer, and death.

Thymosin-alpha 1 is a substance made by a small gland in the chest called the thymus, which helps the body fight infections and disease. It may stop HBV from replicating and boost the body's immune system, helping it fight the virus. It is given as an injection under the skin.

We wanted to know whether, in people with chronic hepatitis B, thymosin-alpha 1 is an effective treatment given alone, or with an additional treatment (called standard, regular, or supportive treatment), compared with placebo (dummy treatment) no treatment or the same additional treatment.

We were interested in whether thymosin-alpha 1:

• caused death for any reason

• caused serious unwanted effects (any event that led to death, disability or hospitalisation)

• improved people's well-being

• reduced HBV-related illness

• reduced risk of dying from chronic HBV infection

• reduced the risk of non-serious unwanted effects (events less serious than those above), and

• improved liver health.

We searched for studies that investigated thymosin-alpha 1 for people with chronic hepatitis B. Studies could include additional treatments as long as everyone in the study got the same additional treatment. Otherwise, people not receiving thymosin-alpha 1 received placebo or no treatment.

Studies could take place anywhere in the world. People in the studies could be men or women, and receive treatment by injection anywhere on the body and at any dose.

We found 10 studies involving 1349 adults with chronic hepatitis B. The studies investigated thymosin-alpha 1, given alone or with an additional treatment, compared with placebo (2 studies), no treatment (2 studies) or the same additional treatment (6 studies). The additional treatments were standard treatments for chronic HBV infection, including interferon, peginterferon, lamivudine, and tenofovir or entecavir.

The smallest study included 12 people, and the largest 690. The studies were funded by universities, the pharmaceutical industry, national bodies or research grants.

Thymosin-alpha 1 may:

• reduce the risk of death from any cause; in three studies, 14 of 460 people (3%) who received thymosin-alpha 1 died, compared with 26 of 447 people (5.8%) who received the control intervention from 6 months to 24 months after treatment;

• result in a small reduction in serious unwanted events; in five studies, 54 of 534 people (10.1%) who received thymosin-alpha 1 experienced a serious unwanted event, compared with 70 of 522 people (13.4%) who received the control intervention from 6 months to 24 months after treatment.

We are less certain that thymosin-alpha 1 may:

• make no difference to people's well-being five years after treatment (1 study, 161 people);

• make no difference to HBV-related illnesses. In three studies, 33 of 433 people (7.6%) who received thymosin-alpha 1 and 37 of 421 people (8.8%) who received the control intervention developed HBV-related illness from 6 to 24 months after treatment;

• reduce the risk of dying from chronic HBV. In three studies, 14 of 460 people (3%) who received thymosin-alpha 1 died from chronic HBV, compared with 26 of 447 people (5.8%) who received the control intervention up to 24 months after treatment;

• reduce the risk of non-serious unwanted effects; in five studies, 16 of 151 people (10.6%) who received thymosin-alpha 1 experienced a non-serious unwanted effect, compared with 32 of 149 people (21.5%) who received the control intervention from 12 months to 24 months after treatment;

• make no difference to improved liver health. In two studies, based on changes seen in liver samples, 146 of 358 people (40.8%) who received thymosin-alpha 1 had improved liver health compared with 163 of 344 people (47.4%) who received the control intervention from 12 months to 24 months after treatment.

All 10 studies had problems with design and methods. Overall, we have little confidence in the results because only a few studies provided information on the outcomes we were interested in, results varied across studies, and many studies included a small number of participants.

The evidence is current to June 2026.

• The effects of hormone therapy on women’s long-term health differ depending on whether they take combined hormone therapy (both oestrogen and progestogen) or oestrogen alone.
• We suggest using caution when considering the results of this review, given the evolution in the doses and methods for taking hormone therapy over time. Findings summarised here come from studies that gave hormone therapy as tablets taken by mouth.
• Future studies could explore the long-term effects of hormone therapy in women who are under 50 years, or whose ovaries have stopped working because of medical treatment.

Menopause occurs naturally (usually between 44 and 55 years) when the ovaries stop releasing eggs and reduce (almost stop) hormone production. Menopause is diagnosed when these changes lead to 12 consecutive months without a menstrual period. Menopause also occurs after surgery to remove both ovaries, and does not require this 12-month timeframe.

Perimenopause is the transitional phase before menopause, when hormone levels decline and periods become irregular. It may last several years and causes symptoms like hot flushes, night sweats and mood changes.

Lower hormone levels may affect women's heart, blood vessels and bones, increasing the risk of high cholesterol, weight and fat changes, high blood pressure, diabetes, heart disease, stroke, osteoporosis and reduced strength or mobility.

Hormone therapy uses oestrogen, with or without another hormone called progestogen, to relieve menopause symptoms. Women without a womb (uterus) can take oestrogen alone, while those with a womb need both (oestrogen and progestogen) to protect against cancer of the womb lining (endometrial cancer).

Oestrogen may be given orally or through the skin (transdermally), and progestogen may be given orally, through the vagina (transvaginally) or by using an intrauterine device (T-shaped device inside the womb). Combined hormone therapy can be taken daily or cyclically (oestrogen is given daily and progestogen is given for part of the month, producing withdrawal vaginal bleeds).

We wanted to find out if long-term use of hormone therapy affects women’s health in the long term.

We searched for studies that compared menopausal women taking hormone therapy for at least one year to those taking an inactive 'dummy' medicine (placebo). 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.

We found 24 studies involving 45,660 participants. Most data came from two large, high-quality studies conducted during the 1990s and reported in the early 2000s. The results presented below are drawn from one of those studies. We present full results in the main review.

Based on evidence from one study in 16,608 women that measured outcomes at roughly 5.5 years of follow-up, combined continuous hormone therapy probably:

• made little or no difference to the risk of having a heart attack or developing lung cancer;
• increased the chance of developing breast cancer (from about 19 to 24 women in every 1000);
• reduced the risk of bone fractures (from about 111 to 87 women in every 1000).

Combined continuous hormone therapy may have increased the chances of having:

• a stroke (from about 13 to 18 women in every 1000);
• a blood clot in a vein (from about 10 to 20 women in every 1000);
• gallbladder disease requiring surgery (from about 16 to 27 women in every 1000).

Based on evidence from one study in 10,739 women who had undergone a hysterectomy (surgery to remove the womb) that measured outcomes at 7 years of follow-up, oestrogen-only hormone therapy probably:

• made little or no difference to the risk of having a heart attack, a blood clot in a vein, or developing breast cancer;
• reduced the chance of having a bone fracture (from about 141 to 103 women in every 1000);
• increased the chance of having a stroke (from about 24 to 32 women in every 1000) and gallbladder disease requiring surgery (from about 27 to 47 women in every 1000).

Oestrogen-only hormone therapy may have made little or no difference to the risk of developing lung cancer.

We did not have enough data to assess the risk of long-term hormone therapy use in women younger than 50 years.

Only about 30% of the women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for hot flushes and night sweats. In addition, hormone therapy has changed over time, with new ways to take it, different hormone types, and updated doses. The study providing most of the data gave women hormone therapy in pill form, which may have different risks to the types currently used in clinical practice.

The evidence is current to September 2024.

Magnesium sulphate given to women at risk of preterm birth for protecting their babies' brains reduces cerebral palsy, and the combined outcome of death or cerebral palsy, in their children up to two years of age, when compared with placebo.

Future research in this area should focus on the effects of treatment:

• on children when they are adolescents and adults; and

• for different groups of women at risk of preterm birth, and with different ways of giving magnesium sulphate.

Magnesium sulphate is a common medicine used across the world for different complications in pregnancy.

Babies born early (preterm, before 37 weeks of pregnancy) have a higher risk of complications including death and disabilities, such as cerebral palsy. In recent years, magnesium sulphate has been given to women who are likely to have their babies preterm (because of spontaneous preterm labour, or a medical indication to plan an induction of labour or caesarean birth early) to help protect their babies' brains and prevent these complications.

We wanted to find out if magnesium sulphate is better than placebo (a 'dummy' treatment that does not contain any medicine but appears identical to the medicine being tested) at protecting the brains of babies likely to be born preterm.

We were interested in the effect of magnesium sulphate on important outcomes, including: death (of the babies, or later as children), cerebral palsy, and major 'neurodevelopmental disability' (which might include serious outcomes like cerebral palsy, blindness, deafness, or global cognitive or intellectual impairment). We were also interested in the effect on important outcomes for women, including serious complications of magnesium sulphate (death, respiratory or cardiac arrest), and stopping treatment because of side effects.

We searched for studies that looked at whether magnesium sulphate caused benefits or harms for women and their preterm babies when compared to placebo or no treatment. We compared and summarised results and rated our confidence in the evidence, based on factors such as study methods and sizes.

We found six studies involving 5917 women at less than 34 weeks of pregnancy and their 6759 babies. The studies were all conducted in high-income countries. The included studies compared magnesium sulphate with placebo.

Compared with placebo, magnesium sulphate in women at risk of having their babies preterm:

• reduces cerebral palsy (evidence from 6 studies with 6107 children) and the combined outcome of death or cerebral palsy (6 studies, 6481 children) for children up to two years of age;

• probably makes little to no difference in death (6 studies, 6759 children), major neurodevelopmental disability (1 study, 987 children), or the combined outcome of death or major neurodevelopmental disability (3 studies, 4279 children), for children up to two years of age;

• may make little to no difference in the above-mentioned outcomes for children at early school age;

• may make little to no difference in serious complications of treatment for women (4 studies, 5300 women), but probably increases women stopping treatment because of side effects (3 studies, 4736 women).

We are confident in our finding that magnesium sulphate reduces cerebral palsy, and the combined outcome of death or cerebral palsy, in children up to two years of age.

We have little confidence in the evidence for outcomes of children at school age, as studies could not provide data for all children, and there are not yet enough studies/data to be certain about the results.

We have little confidence in our finding that magnesium sulphate makes little to no difference in serious complications of treatment for women, as there was only one complication reported in one study. We have moderate confidence in our findings that magnesium sulphate probably increases women stopping treatment because of side effects, as the findings differed across studies, probably because of different decision-making processes for stopping treatment.

The results of further research for the outcomes in which we have limited confidence could differ from the results of this review.

The evidence is current to 17 March 2023.

• Multisensory stimulation (the stimulation of more than one sense at a time) may support growth in preterm infants by increasing weight gain before discharge from the hospital. However, it is unclear whether it improves longer-term developmental outcomes or reduces the risk of death, as the available evidence is limited and uncertain.

• When compared with stimulation of a single sense (touch alone), it is uncertain whether multisensory stimulation is better than touch alone at increasing weight gain during the intervention.

Multisensory stimulation means giving premature babies experiences that activate two or more of their senses. The senses involved and the types of stimulation used include the sense of:

• hearing — a parent’s voice, singing, or calming music;

• touch — massage or passive movements;

• smell and taste — a mother’s scent or breast milk;

• balance — gentle rocking or changing the baby's position;

• sight — soft, cycled lighting and simple shapes, colors, or moving patterns.

During the newborn period, the brain grows very quickly. Providing positive sensory experiences at this time may help premature babies in several ways, such as supporting their memory, helping them regulate emotions, and improving early learning and development.

We wanted to find out whether multisensory stimulation compared with single‑sense stimulation or standard care helps premature babies survive, grow, stay healthy, and develop well. Specifically, we wanted to find out whether multisensory stimulation might:

• reduce the number of babies with severe developmental problems at 18 to 24 months' age, such as cerebral palsy, delay in development, limitations in mental abilities, blindness, or deafness;

• reduce the number of babies who die during the newborn period or before hospital discharge;

• increase the amount of weight the infants gained by the time they left the hospital.

We also looked at other important measures of the babies’ health, including:

• how long they stayed in the hospital or in the neonatal intensive care unit (NICU);

• how long it took before they could feed fully by mouth;

• how many days they needed breathing support.

We searched for studies in which multisensory stimulation began before the baby was discharged from the hospital after birth, and which compared multisensory stimulation with:

• no intervention or standard care;

• single-sense stimulation.

We 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 enrolled) and the methods used.

We included 19 studies (1544 premature babies). Eighteen of these studies compared multisensory stimulation with standard care, and one study compared multisensory stimulation with a single‑sense intervention (touch only).

In 10 studies, the main goal was to examine how multisensory stimulation affects babies’ brain and behavioral development.

The remaining nine studies focused on weight gain during the intervention, weight gain prior to hospital discharge, length of stay in the NICU, total length of hospital stay, time until the baby could feed fully by mouth, number of days the baby needed breathing support, or a combination of these measures.

We also found 13 ongoing studies and 4 studies that have not yet been fully assessed. They may give us more useful information in the future.

None of the studies that compared multisensory stimulation with no intervention reported on the critical outcome major developmental disability at 18 to 24 months' corrected age. Only one study assessed a related outcome, cerebral palsy at 12 months. Because this study was very small, the evidence is very uncertain about whether multisensory stimulation modifies the risk of cerebral palsy.

Multisensory stimulation may result in little or no difference in death before hospital discharge, although it was reported in only one large study. It may increase total weight gain prior to discharge, but the observed effect is small, and its clinical significance remains uncertain.

Compared with single-sense stimulation (touch), we could not tell whether multisensory stimulation helped babies gain more weight during the intervention. The only study we found comparing a multi- to single-sensory intervention did not report the critical outcomes, such as major developmental problems at 18 to 24 months' corrected age, death during the first hospital stay, or total weight gain prior to discharge.

We have limited confidence in these findings because many of the studies were small or not well-designed. Several studies did not report the outcomes we were most interested in or did not provide enough data for us to analyze. Because of these limitations, the true effects of multisensory stimulation may be different from what we found.

The evidence is up-to-date to 28 November 2025.

• In adults with long-lasting (chronic) low back pain, lower-back (lumbar) supports used on their own without additional treatment may not reduce pain or disability.

• In adults with chronic low back pain, pain may be slightly reduced when lumbar supports are used with pain medication compared to using the pain medication on its own. We do not know their effect on disability. We do not know if adding education and exercise to lumbar supports is any better than education and exercise on its own, or whether adding physiotherapy to lumbar supports has any benefit over physiotherapy on its own.

• More research is needed, particularly amongst older adults and people living in low-income and middle-income countries.

Low back pain is pain in the lower part of the back, which may also spread to one or both legs. When symptoms last longer than 12 weeks, it is considered long‐lasting and is referred to as chronic low back pain, which is a common cause of disability impacting people's quality of life across the world. It is estimated to be the leading cause of the need for rehabilitation, making it expensive in terms of healthcare costs and lost working hours.

Lumbar supports include braces, belts, and general supports that help stabilise or support the lower back. Some are made of hard plastic to limit movement. Others are softer, allowing for some movement but still providing support during movement.

Other assistive devices are items that help people with disabilities move around more easily. They include wheelchairs, mobility scooters, tricycles, crutches, walking sticks/canes, and walking frames/walkers.

We wanted to know whether lumbar supports and other assistive devices for adults with chronic low back pain help to reduce pain and disability, and improve health-related quality-of-life. We were also interested in the safety of the treatments, whether people receiving them felt they were helpful, whether they reduced painkiller use and falls, and their effects on anxiety, depression, and taking part in social activities.

We searched for studies where people with chronic low back pain received either a specific back pain treatment or 'usual care' (e.g. painkillers, general physiotherapy, education) or no treatment, and the results of the groups were compared with each other. We combined the results of similar studies and assessed how certain we were about the evidence.

We found eight studies with 501 men and women aged from 25 to 78 years. They had had chronic low back pain for between one and five years. All the studies investigated lumbar supports (for example, braces, corsets). Five of the studies took place in low- and middle-income countries (Bangladesh, Iran, Turkey) and three in high-income countries (Japan, USA).

• Lumbar supports alone, compared to getting no treatment, may have little to no effect on pain and disability after three months (1 study, 107 participants).

• Lumbar supports plus pain medication may result in a small reduction in pain intensity after three to four weeks compared with pain medication alone, but the evidence is very uncertain for disability (2 studies, 149 participants).

• We are very uncertain about the effect of adding lumbar supports to exercise and education (i.e. teaching about the structure and movement of the lower back, how it functions in daily activities, common conditions that can lead to low back pain, and different treatment options to help manage and relieve symptoms) on pain and disability after six weeks, when compared to exercise and education alone (1 study, 24 or 25 participants).

• We are very uncertain about the effect of combining lumbar supports with general physiotherapy (including ultrasound, low-intensity electrical current, heat, exercises to improve flexibility and increase strength) on pain and disability after four weeks, when compared to general physiotherapy alone (1 study, 41 participants).

• Overall, we have limited confidence in the results, and our conclusions might change after further studies are done.

• The most important limitation was that study participants and healthcare providers knew what treatment they were getting. Even though this is impossible to prevent in these types of studies, it may have affected how participants felt about their pain or disability and how they rated it.

• None of the studies reported on the unwanted effects of the treatments.

• The characteristics of the study participants were not usually reported in detail. It is difficult to know how the results should be applied to the broader group of patients with chronic low back pain.

• No studies tested mobility devices like walking aids or wheelchairs, even though these treatments are often prescribed and could potentially affect pain and disability. This gap in the evidence is especially significant for older adults and individuals with disabilities.

This evidence is current to January 2025.

Many people suffer from depression and anxiety. These problems can make people feel sad, scared and even suicidal, and can affect their work, their relationships and their quality of life. Depression and anxiety can occur because of personal, financial, social or health problems.

‘Collaborative care’ is an innovative way of treating depression and anxiety. It involves a number of health professionals working with a patient to help them overcome their problems. Collaborative care often involves a medical doctor, a case manager (with training in depression and anxiety), and a mental health specialist such as a psychiatrist. The case manager has regular contact with the person and organises care, together with the medical doctor and specialist. The case manager may offer help with medication, or access to a ‘talking therapy’ to help the patient get better.

Collaborative care has been tested with patients in a number of countries and health care systems, but it is not clear whether it should be recommended for people with depression or anxiety.

In this review we found 79 randomised controlled trials (RCTs) (90 comparisons) including 24,308 patients worldwide, comparing collaborative care with routine care or alternative treatments (such as consultation-liaison) for depression and anxiety. There were problems with the methods in some of the studies. For example, the methods used to allocate patients to collaborative care or routine care were not always free from bias, and many patients did not complete follow-up or provide information about their outcomes. Most of the studies focused on depression and the evidence suggests that collaborative care is better than routine care in improving depression for up to two years. A smaller number of studies examined the effect of collaborative care on anxiety and the evidence suggests that collaborative care is also better than usual care in improving anxiety for up to two years. Collaborative care increases the number of patients using medication in line with current guidance, and can improve mental health related quality of life. Patients with depression and anxiety treated with collaborative care are also more satisfied with their treatment.

• Taking antibiotics one hour before dental implant placement probably reduces the risk of early implant failure under routine conditions. This benefit is mainly based on studies using a single dose of amoxicillin taken before surgery, most often 2 g one hour before implant placement. Based on the available evidence, about 19 people would need to receive antibiotics to prevent one person from having an early implant failure.

• We do not know whether taking antibiotics for longer periods, taking them before or after surgery, or using other antibiotics other than amoxicillin provides additional benefit. Evidence about unwanted effects is uncertain because they were rare and not always reported.

• Future studies are needed to better understand the effects of giving antibiotics around the time of dental implant surgery, especially when an implant is placed immediately after a tooth is removed. Studies should compare a single dose of antibiotics given before surgery with longer or repeated treatment. It would also be useful to compare commonly used antibiotics, such as amoxicillin and clindamycin.

Dental implants are used to replace missing teeth and support crowns, bridges, or dentures. During implant placement, bacteria can be introduced into the surgical site. If the site around an implant becomes infected, treatment is difficult and removal of the implant is often required.

Antibiotics are sometimes given before or after surgery to reduce the risk of infection. However, they can also cause unwanted effects, ranging from mild symptoms to severe allergic reactions. Also, their widespread use contributes to antibiotic resistance, where bacteria change and grow so that the antibiotics that used to effectively treat them no longer work. For these reasons, the routine use of antibiotics for dental implant placement remains controversial.

We wanted to know whether taking antibiotics around the time of dental implant placement:

• reduces implant failures and artificial teeth failures;

• reduces postoperative infections;

• causes unwanted effects.

We wanted to know if the effects of antibiotics differed according to:

• antibiotics compared to placebo (dummy treatment) or no antibiotics;

• different doses or different durations of the same antibiotic;

• the same dosage of the same antibiotic given at different times;

• different antibiotics.

We searched for studies in which adults receiving dental implants without the addition of bone tissue (bone augmentation procedures) were assigned by chance to receive either antibiotics or no antibiotics, or to receive different antibiotic regimens. 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.

We found 15 studies including a total of 2874 people. The studies were conducted in Europe (Italy, Spain, Belgium, Ireland, and Sweden), the USA, Canada, Brazil, Iran, and Saudi Arabia, and were published between 2008 and 2024.

• People who received antibiotics one hour before dental implant placement were probably less likely to experience early implant failure than those who received placebo or no antibiotics (10 studies, 1919 people). This means that about 80 out of 1000 people without antibiotics experienced implant failure, compared with about 27 out of 1000 people who received antibiotics.

• Antibiotics probably reduce artificial teeth failures (9 studies, 1864 people) and postoperative infections (10 studies, 1919 people).

• There may be little to no difference between taking a single dose of antibiotics and taking multiple doses in implant failures (5 studies, 760 people) or postoperative infections (5 studies, 760 people).

• The evidence for artificial teeth failures is very uncertain.

• The evidence is very uncertain for implant failures, artificial teeth failures, and postoperative infections.

• There may be little to no difference in implant failures, artificial teeth failures, and postoperative infections between amoxicillin and clindamycin (1 study, 81 people).

Unwanted effects were rare and inconsistently reported. Most were mild (such as diarrhoea), but one severe allergic reaction requiring hospital admission was reported. Because few people experienced unwanted effects, we cannot reliably rule out rare but serious harms.

Our confidence in the evidence ranged from moderate to very low because some studies had problems with their methods, and in many cases, the evidence was based on small numbers of events.

This review is current to 19 November 2025.

• If healthcare workers feel they have good support from managers, receive IPC training, and are told about IPC guidelines in a clear and helpful way, they are better able to follow the guidance.

• If there is not enough space where they work, they are too busy, do not have enough personal protective equipment (PPE) and other supplies, or if patients do not follow advice, then it is more difficult for healthcare workers to follow the IPC guidelines.

• Healthcare workers who want to protect themselves, their families, and their patients tend to try to follow the guidelines as much as possible, but the quality and fit of the PPE they have can make it more difficult.

• More research is needed on training, communication and education to make it easier for healthcare workers to follow guidelines, on developing systems to minimise patient contact, and on providing appropriate PPE to enable them to be prepared for pandemics.

COVID‐19 is a respiratory infectious disease that spread worldwide in 2020. During the COVID-19 pandemic, healthcare workers needed to prevent the virus from spreading the disease to other patients, themselves, or people in the public. Infection prevention and control (IPC) guidelines are used to give healthcare workers information about using personal protective equipment (PPE) like masks, gloves, and gowns; separating patients with COVID-19; and stricter cleaning routines. However, some factors make it easier for healthcare workers to follow these guidelines, while others make it harder.

We wanted to find out:

• what made it easier and what made it harder for healthcare workers to follow IPC guidelines for COVID-19;

• compare our findings with our existing Cochrane review, published in 2020, to see what was similar and what was different about COVID-19 compared to other respiratory infectious diseases.

We searched for studies that looked at healthcare workers’ views and experiences of following IPC guidelines for COVID‐19.

• Guidelines could be local, national, or international, for any healthcare setting.

• Studies could take place in hospitals, long-term care places or community health care.

• Healthcare workers could include either clinical or support staff working in the above places.

We then looked for themes (important elements) that came from the data:

• Organisational: supporting safety, communication and training;

• Environmental: workspace, ventilation, facilities, availability of PPE;

• Individual: knowledge, attitudes, use of PPE.

We rated our confidence in each study and each finding based on the quality of their methods.

We found 170 studies. To make it easier to handle the data, we selected 26 studies that best represented all the studies. They explored the views and experiences of nurses, doctors, and other healthcare workers dealing with COVID-19 in hospitals and nursing places where people live and receive care.

Several factors influence how well healthcare workers follow IPC guidelines. They reported that:

• it was easier to follow guidelines when they had support from their managers and when guidelines were communicated in a clear and accessible way.

• it was more difficult to follow guidelines if they were very busy, short-staffed, or if patients and visitors refused to wear masks and keep social distancing.

• training was very important. However, they did not all have the chance to attend IPC training.

• they need enough space, PPE and other supplies, hand-washing stations, and showers to follow the IPC guidelines.

• those with good knowledge and attitude towards IPC were more likely to follow the guidelines.

• healthcare workers worried about infecting themselves and other people, but some worried less once people started being vaccinated.

• PPE was uncomfortable to wear for long periods and, if it did not fit properly or was of poor quality, it was more difficult for them to practice IPC.

Many factors affect healthcare workers’ willingness and ability to follow IPC guidelines. For the public and patients attending healthcare settings, this review highlights that there will be better adherence to infection prevention and control in places where staff are supported, trained, and have adequate supplies. However, it is important to note that many of the challenges (e.g. crowded spaces) are structural and not the fault of individual staff.

Our review includes a set of questions based on our findings to help healthcare providers plan, implement, or manage IPC strategies to ensure their workers follow IPC guidelines for diseases like COVID-19, which can spread worldwide and affect many people at once.

We were very confident of some of the evidence, but mainly our confidence in the evidence was limited. This was because no studies explored mental health and issues for children, meaning we are not sure how our findings apply to these groups. Also, the data from the studies were mostly collected at the peak of the pandemic (in 2020), so we have no way of knowing whether IPC guideline practices, training, and PPE evolved at later stages.

This review updates (and extends) our previous review (2020). The evidence is up-to-date to April 2024.

• Physical exercise training may help increase heart and lung function (cardiorespiratory fitness) in people with spinal cord injury up to 6 weeks after training stopped.

• The effects of physical exercise training are unclear on the ability to perform everyday activities, well-being, mood, and any unwanted effects.

• In the future, researchers should focus on large, well-designed studies that address issues that are important to people with spinal cord injury.

The spinal cord is a bundle of nerves and fibres that runs from the brain down the centre of the spine. It carries signals between the brain and parts of the body. A spinal cord injury (as a result of an accident or medical condition) disrupts these signals. This can cause loss of muscle function or movement (paralysis) or weakness, loss of feeling, and issues with basic body functions like bladder and bowel control, sexual function, and blood pressure regulation. The exact location of the injury determines how much of the body is affected. Injuries in the neck can affect the whole body; injuries in the back may only affect the trunk and legs. People with spinal cord injury find everyday tasks and movement difficult. Some need a wheelchair to move about and rely on help from others for daily tasks.

Cardiorespiratory fitness is how well your heart, lungs, and blood vessels work together to supply oxygen to your body during physical activities. The benefits of good cardiorespiratory fitness on general health, daily life, mood and well-being are widely accepted for non-disabled people, but can be challenging to achieve in people who find it hard or impossible to move their limbs. However, people with spinal cord injury may also benefit from good cardiovascular fitness, meaning they could lead more active lives with more independence and better well-being.

We wanted to know whether physical exercise training (compared to no training) improved cardiorespiratory fitness in people with spinal cord injury. We also looked at its effects on:

• functional fitness (the ability to perform daily activities, like push a wheelchair or walk a certain distance);

• well-being:

• mood (depression and anxiety); and

• unwanted effects due to training, such as death, hospitalisation, falls, stroke or heart attack, pain, or injury.

We searched for studies that compared physical exercise training to no training in adults with spinal cord injury. They could have had their injury for any length of time, and it could be from any cause. Training could last for any time and be of any intensity but had to be planned, structured and repetitive, and intended to improve cardiorespiratory fitness. It could include cycling, rowing, walking or swimming. It could take place in hospital, in the community or at home.

We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as the design and size of studies.

We found 17 studies with a total of 505 people. There were between 10 and 68 people in each study, with a mix of neck and back injuries. They had an average age of 27 to 57 years, and 71% were men. Twelve studies took place in Europe or North America. Training sessions:

• focused on arms only or arms and legs

• typically consisted of using an arm ergometer (stationary arm bike), rowing, wheelchair propulsion, robotic gait training (machine-based, supported walking)

• happened two to five times a week

• ran for between 6 weeks and 9 months, and

• lasted between 30 minutes and 2 hours.

All studies examined the effects of physical exercise up to six weeks after the training had stopped (short-term) and only one study for longer than 6 weeks (long-term).

In the short-term, physical exercise training may help improve cardiorespiratory fitness in people with spinal cord injury (15 studies, 337 participants).

It is unclear whether physical exercise training:

• increases functional fitness (3 studies, 67 people)

• improves well-being (2 studies, 49 people)

• reduces depression and anxiety (1 study, 23 people)

• increases unwanted events (4 studies, 141 people)

Our confidence in the evidence is low or very low for several reasons. Most studies were small and not high quality. For example, many studies failed to present all the data that they collected, failed to provide a plan at the start of the study on how they would analyse the data, and failed to keep most of the participants in the study. Few studies included our most important points of interest for this review.

The evidence is current to 9 December 2025.

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

• Longer-term implications of treatment are not clear.

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

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

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

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

We wanted to know whether treatment with antibiotics:

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

• does not cause infection with other resistant bacteria;

• does not cause unwanted effects.

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

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

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

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

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

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

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

• Antibiotics may increase lung function.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

We were interested in:

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

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

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

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

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

• e-cigarettes without nicotine;

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

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

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

• advice or counselling (behavioural support); or

• no support for stopping smoking.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

• improves their survival;

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

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

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

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

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

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

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

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

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

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

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

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

• survival rates;

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

Only one small study looked at each of these approaches.

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

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

• too few studies investigated these methods;

• the number of babies included was small;

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

The evidence is current to September 2025.

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

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

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

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

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

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

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

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

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

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

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

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

• the ability to listen to other people;

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

• continue oxytocin until birth?

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

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

Stopping oxytocin during the active phase of labour:

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

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

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

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

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

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

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

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

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

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

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

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

The evidence is up to date to 17 November 2025.