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Lavita AI 17

Can non-pharmacological treatments reduce the frequency of attacks in vestibular migraine?

Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. These unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of interventions have been used, or proposed to be used, as prophylaxis for this condition, to help reduce the frequency of the attacks. Many of these interventions include dietary, lifestyle or behavioural changes, rather than medication. OBJECTIVES: To assess the benefits and harms of non-pharmacological treatments used for prophylaxis of vestibular migraine.

Search methods:

Trial registration:

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Does higher dose caffeine have a significant impact on mortality and major neurodevelopmental disability in preterm infants?

Very preterm infants often require respiratory support and are therefore exposed to an increased risk of bronchopulmonary dysplasia (chronic lung disease) and later neurodevelopmental disability. Caffeine is widely used to prevent and treat apnea (temporal cessation of breathing) associated with prematurity and facilitate extubation. Though widely recognized dosage regimes have been used for decades, higher doses have been suggested to further improve neonatal outcomes. However, observational studies suggest that higher doses may be associated with harm.

To determine the effects of higher versus standard doses of caffeine on mortality and major neurodevelopmental disability in preterm infants with (or at risk of) apnea, or peri-extubation.

High-dose caffeine strategies in preterm infants may have little or no effect on reducing mortality prior to hospital discharge or side effects. We are very uncertain whether high-dose caffeine strategies improves major neurodevelopmental disability, duration of hospital stay or seizures. No studies reported the outcome mortality or major neurodevelopmental disability in children aged 18 to 24 months and 3 to 5 years. High-dose caffeine strategies probably reduce the rate of bronchopulmonary dysplasia. Recently completed and future trials should report long-term neurodevelopmental outcome of children exposed to different caffeine dosing strategies in the neonatal period. Data from extremely preterm infants are needed, as this population is exposed to the highest risk for mortality and morbidity. However, caution is required when administering high doses in the first hours of life, when the risk for intracranial bleeding is highest. Observational studies might provide useful information regarding potential harms of the highest doses.

NOT ENOUGH INFORMATION

LOW

miscellaneous

Do interventions for the prevention and treatment of PDA in preterm infants have significant effects?

Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non-pharmacological, pharmacological, and surgical approaches have been explored to prevent or treat a PDA.

To summarise Cochrane Neonatal evidence on interventions (pharmacological or surgical) for the prevention of PDA and related complications, and interventions for the management of asymptomatic and symptomatic PDA in preterm infants.

This overview summarised the evidence from 16 Cochrane Reviews of RCTs regarding the effects of interventions for the prevention and treatment of PDA in preterm infants. Prophylactic indomethacin reduces severe IVH, but does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability. Prophylactic ibuprofen probably marginally reduces severe IVH (moderate-certainty evidence), while the evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH. All available prostaglandin inhibitor drugs appear to be effective in symptomatic PDA closure compared to no treatment (high-certainty evidence for indomethacin; moderate-certainty evidence for ibuprofen; low-certainty evidence for early administration of acetaminophen). Oral ibuprofen appears to be more effective in PDA closure than IV ibuprofen (moderate-certainty evidence). High dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (moderate-certainty evidence). There are currently two ongoing reviews, one on fluid restriction for symptomatic PDA, and the other on invasive management of PDA in preterm infants.

SUPPORTED

MEDIUM

cardiovascular system

Do opioids provide benefits in reducing procedural pain in neonates compared to placebo or other interventions?

Neonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures. Options for pain management include opioids, non-pharmacological interventions, and other drugs. Morphine, fentanyl, and remifentanil are the opioids most often used in neonates. However, negative impact of opioids on the structure and function of the developing brain has been reported.

To evaluate the benefits and harms of opioids in term or preterm neonates exposed to procedural pain, compared to placebo or no drug, non-pharmacological intervention, other analgesics or sedatives, other opioids, or the same opioid administered by a different route.

Compared to placebo, opioids probably reduce pain score assessed with PIPP/PIPP-R scale during the procedure; may reduce NIPS during the procedure; and may result in little to no difference in DAN one to two hours after the procedure. The evidence is very uncertain about the effect of opioids on pain assessed with other pain scores or at different time points. No studies reported if any harms occurred. The evidence is very uncertain about the effect of opioids on episodes of bradycardia or hypotension. Opioids may result in an increase in episodes of apnea. No studies reported parent satisfaction with care provided in the NICU. The evidence is very uncertain about the effect of opioids on any outcome when compared to non-pharmacological interventions or to other analgesics. We identified no studies comparing opioids to other opioids or comparing different routes of administration of the same opioid.

SUPPORTED

LOW

cognitive, mental, and mental health

Did the review investigate the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability?

Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature.

To determine the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability. Potentially assessed regimens might include: different doses of the same opioid, different routes of administration of the same opioid, continuous infusion versus bolus administration, or 'as needed' administration versus 'as scheduled' administration.

limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. we are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. only one small study reported on morphine infusion with parent- or nurse-controlled analgesia.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Did the McKenzie method show effectiveness in treating (sub)acute non-specific low back pain?

There is widespread agreement amongst clinicians that people with non-specific low back pain (NSLBP) comprise a heterogeneous group and that their management should be individually tailored. One treatment known by its tailored design is the McKenzie method (e.g. an individualized program of exercises based on clinical clues observed during assessment).

To evaluate the effectiveness of the McKenzie method in people with (sub)acute non-specific low back pain.

Based on low- to very low-certainty evidence, the treatment effects for pain and disability found in our review were not clinically important. Thus, we can conclude that the McKenzie method is not an effective treatment for (sub)acute NSLBP.

REFUTED

LOW

musculoskeletal system and dermatology

Do pharmacological interventions provide a large or medium effect on pain intensity for non-specific low back pain compared to placebo?

Pharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological interventions for LBP published in the Cochrane Library, is limited by lack of a comprehensive overview.

To summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non-specific LBP.

We found no high- or moderate-certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate-certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high-certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low- and high-certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate-certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low-certainty evidence that NSAIDs and very low- to high-certainty evidence that opioids may provide a small effect on pain. For safety, we found low-certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low-certainty evidence that opioids may increase the risk of adverse events.

REFUTED

LOW

musculoskeletal system and dermatology

Does nebulised hypertonic saline solution (≥ 3%) have significant effects in infants with acute bronchiolitis?

Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and updated in 2010, 2013, and 2017.

To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis.

Nebulised hypertonic saline may modestly reduce length of stay amongst infants hospitalised with acute bronchiolitis and may slightly improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation amongst outpatients and ED patients. Nebulised hypertonic saline seems to be a safe treatment in infants with bronchiolitis with only minor and spontaneously resolved adverse events, especially when administered in conjunction with a bronchodilator. The certainty of the evidence was low to very low for all outcomes, mainly due to inconsistency and risk of bias.

SUPPORTED

LOW

respiratory system

Do non-opioid analgesics have an effect on neonates exposed to procedural pain compared to placebo or no drug, non-pharmacological intervention, other analgesics, or different routes of administration?

Neonates are an extremely vulnerable patient population, with 6% to 9% admitted to the neonatal intensive care unit (NICU) following birth. Neonates admitted to the NICU will undergo multiple painful procedures per day throughout their stay. There is increasing evidence that frequent and repetitive exposure to painful stimuli is associated with poorer outcomes later in life. To date, a wide variety of pain control mechanisms have been developed and implemented to address procedural pain in neonates. This review focused on non-opioid analgesics, specifically non-steroidal anti-inflammatory drugs (NSAIDs) and N-methyl-D-aspartate (NMDA) receptor antagonists, which alleviate pain through inhibiting cellular pathways to achieve analgesia. The analgesics considered in this review show potential for pain relief in clinical practice; however, an evidence summation compiling the individual drugs they comprise and outlining the benefits and harms of their administration is lacking. We therefore sought to summarize the evidence on the level of pain experienced by neonates both during and following procedures; relevant drug-related adverse events, namely episodes of apnea, desaturation, bradycardia, and hypotension; and the effects of combinations of drugs. As the field of neonatal procedural pain management is constantly evolving, this review aimed to ascertain the scope of non-opioid analgesics for neonatal procedural pain to provide an overview of the options available to better inform evidence-based clinical practice. OBJECTIVES: To determine the effects of non-opioid analgesics in neonates (term or preterm) exposed to procedural pain compared to placebo or no drug, non-pharmacological intervention, other analgesics, or different routes of administration.

Search methods:

the two small included studies comparing ketamine versus either placebo or fentanyl, with very low-certainty evidence, rendered us unable to draw meaningful conclusions. the evidence is very uncertain about the effect of ketamine on pain score during the procedure compared with placebo or fentanyl. we found no evidence on nsaids or studies comparing different routes of administration. future research should prioritize large studies evaluating non-opioid analgesics in this population. as the studies included in this review suggest potential positive effects of ketamine administration, studies evaluating ketamine are of interest. furthermore, as we identified no studies on nsaids, which are widely used in older infants, or comparing different routes of administration, such studies should be a priority going forward.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Can intraocular anti-VEGF medications, alone or with conventional therapy, effectively reduce intraocular pressure in neovascular glaucoma?

Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG.

To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more types of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG.

Anti-VEGFs as an adjunct to conventional treatment could help reduce IOP in NVG in the short term (four to six weeks), but there is no evidence that this is likely in the longer term. Currently available evidence regarding the short- and long-term effectiveness and safety of anti-VEGFs in achieving control of IOP, visual acuity, and complete regression of new iris vessels in NVG is insufficient. More research is needed to investigate the effect of these medications compared with, or in addition to, conventional surgical or medical treatment in achieving these outcomes in NVG.

NOT ENOUGH INFORMATION

LOW

sensory organs

Does chest physiotherapy show efficacy in infants younger than 24 months old with acute bronchiolitis?

Acute bronchiolitis is the leading cause of medical emergencies during winter months in infants younger than 24 months old. Chest physiotherapy is sometimes used to assist infants in the clearance of secretions in order to decrease ventilatory effort. This is an update of a Cochrane Review first published in 2005 and updated in 2006, 2012, and 2016.

To determine the efficacy of chest physiotherapy in infants younger than 24 months old with acute bronchiolitis. A secondary objective was to determine the efficacy of different techniques of chest physiotherapy (vibration and percussion, passive exhalation, or instrumental).

We found low-certainty evidence that passive slow expiratory technique may result in a mild to moderate improvement in bronchiolitis severity when compared to control. This evidence comes mostly from infants with moderately acute bronchiolitis treated in hospital. The evidence was limited with regard to infants with severe bronchiolitis and those with moderately severe bronchiolitis treated in ambulatory settings. We found high-certainty evidence that conventional techniques and forced expiratory techniques result in no difference in bronchiolitis severity or any other outcome. We found high-certainty evidence that forced expiratory techniques in infants with severe bronchiolitis do not improve their health status and can lead to severe adverse effects. Currently, the evidence regarding new physiotherapy techniques such as RRT or instrumental physiotherapy is scarce, and further trials are needed to determine their effects and potential for use in infants with moderate bronchiolitis, as well as the potential additional effect of RRT when combined with slow passive expiratory techniques. Finally, the effectiveness of combining chest physiotherapy with hypertonic saline should also be investigated.

NOT ENOUGH INFORMATION

LOW

respiratory system

Does the use of bubble CPAP versus other pressure sources reduce treatment failure and associated morbidity and mortality in preterm infants with respiratory distress?

Several types of pressure sources, including underwater bubble devices, mechanical ventilators, and the Infant Flow Driver, are used for providing continuous positive airway pressure (CPAP) to preterm infants with respiratory distress. It is unclear whether the use of bubble CPAP versus other pressure sources is associated with lower rates of CPAP treatment failure, or mortality and other morbidity. OBJECTIVES: To assess the benefits and harms of bubble CPAP versus other pressure sources (mechanical ventilators or Infant Flow Driver) for reducing treatment failure and associated morbidity and mortality in newborn preterm infants with or at risk of respiratory distress.

Search methods:

given the low level of certainty about the effects of bubble cpap versus other pressure sources on the risk of treatment failure and most associated morbidity and mortality for preterm infants, further large, high-quality trials are needed to provide evidence of sufficient validity and applicability to inform context- and setting-relevant policy and practice.

NOT ENOUGH INFORMATION

LOW

respiratory system

Do antidepressants show efficacy in treating depressive symptoms in adults with cancer?

Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have a negative impact in terms of quality of life, compliance with anticancer treatment, suicide risk and possibly the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results.

To evaluate the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage).

Despite the impact of depression on people with cancer, the available studies were few and of low quality. This review found a potential beneficial effect of antidepressants against placebo in depressed participants with cancer. However, the certainty of evidence is very low and, on the basis of these results, it is difficult to draw clear implications for practice. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which drug to prescribe may be based on the data on antidepressant efficacy in the general population of people with major depression, also taking into account that data on people with other serious medical conditions suggest a positive safety profile for the SSRIs. Furthermore, this update shows that the usage of the newly US Food and Drug Administration-approved antidepressant esketamine in its intravenous formulation might represent a potential treatment for this specific population of people, since it can be used both as an anaesthetic and an antidepressant. However, data are too inconclusive and further studies are needed. We conclude that to better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.

SUPPORTED

LOW

cancer

Do conditional and unconditional cash transfer social protection interventions have perceived and experienced health outcomes by their recipients?

It is well known that poverty is associated with ill health and that ill health can result in direct and indirect costs that can perpetuate poverty. Social protection, which includes policies and programmes intended to prevent and reduce poverty in times of ill health, could be one way to break this vicious cycle. Social protection, particularly cash transfers, also has the potential to promote healthier behaviours, including healthcare seeking. Although social protection, particularly conditional and unconditional cash transfers, has been widely studied, it is not well known how recipients experience social protection interventions, and what unintended effects such interventions can cause. OBJECTIVES: The aim of this review was to explore how conditional and unconditional cash transfer social protection interventions with a health outcome are experienced and perceived by their recipients. SEARCH METHODS: We searched Epistemonikos, MEDLINE, CINAHL, Social Services Abstracts, Global Index Medicus, Scopus, AnthroSource and EconLit from the start of the database to 5 June 2020. We combined this with reference checking, citation searching, grey literature and contact with authors to identify additional studies. We reran all strategies in July 2022, and the new studies are awaiting classification.

Selection criteria:

our findings highlight the impact of the sociocultural context on the functioning and interaction between the individual, family and cash transfer programmes. even where the goals of a cash transfer programme are explicitly health-related, the outcomes may be far broader than health alone and may include, for example, reduced stigma, empowerment and increased agency of the individual. when measuring programme outcomes, therefore, these broader impacts could be considered for understanding the health and well-being benefits of cash transfers.

SUPPORTED

MEDIUM

miscellaneous

Does adding breast ultrasonography to mammography for breast cancer screening improve the detection of breast cancer for women at average risk?

Screening mammography can detect breast cancer at an early stage. Supporters of adding ultrasonography to the screening regimen consider it a safe and inexpensive approach to reduce false-negative rates during screening. However, those opposed to it argue that performing supplemental ultrasonography will also increase the rate of false-positive findings and can lead to unnecessary biopsies and treatments.

To assess the comparative effectiveness and safety of mammography in combination with breast ultrasonography versus mammography alone for breast cancer screening for women at average risk of breast cancer.

Based on one study in women at average risk of breast cancer, ultrasonography in addition to mammography leads to more screening-detected breast cancer cases. For women with dense breasts, cohort studies more in line with real-life clinical practice confirmed this finding, whilst cohort studies for women with non-dense breasts showed no statistically significant difference between the two screening interventions. However, the number of false-positive results and biopsy rates were higher in women receiving additional ultrasonography for breast cancer screening. None of the included studies analysed whether the higher number of screen-detected cancers in the intervention group resulted in a lower mortality rate compared to mammography alone. Randomised controlled trials or prospective cohort studies with a longer observation period are needed to assess the effects of the two screening interventions on morbidity and mortality.

NOT ENOUGH INFORMATION

LOW

cancer

Are mechanical methods for third-trimester induction of labor as effective and safe as pharmacological methods?

Mechanical methods were the first methods developed to ripen the cervix and induce labour. During recent decades they have been substituted by pharmacological methods. Potential advantages of mechanical methods, compared with pharmacological methods may include reduction in side effects that could improve neonatal outcomes. This is an update of a review first published in 2001, last updated in 2012.

To determine the effectiveness and safety of mechanical methods for third trimester (> 24 weeks' gestation) induction of labour in comparison with prostaglandin E2 (PGE2) (vaginal and intracervical), low-dose misoprostol (oral and vaginal), amniotomy or oxytocin.

Low- to moderate-quality evidence shows mechanical induction with a balloon is probably as effective as induction of labour with vaginal PGE2. However, a balloon seems to have a more favourable safety profile. More research on this comparison does not seem warranted. Moderate-quality evidence shows a balloon catheter may be slightly less effective as oral misoprostol, but it remains unclear if there is a difference in safety outcomes for the neonate. When compared to low-dose vaginal misoprostol, low-quality evidence shows a balloon may be less effective, but probably has a better safety profile. Future research could be focused more on safety aspects for the neonate and maternal satisfaction.

NOT ENOUGH INFORMATION

LOW

sexual and reproductive health

Does zinc supplementation prevent mortality and morbidity and promote growth in children aged 6 months to 12 years?

Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The effectiveness of preventive zinc supplementation in reducing prevalence of zinc deficiency needs to be assessed.

To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years.

Even though we included 16 new studies in this update, the overall conclusions of the review remain unchanged. Zinc supplementation might help prevent episodes of diarrhea and improve growth slightly, particularly in children aged 6 months to 12 years of age. The benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high.

SUPPORTED

MEDIUM

nutrition and dietary supplements

Do psychological interventions improve adherence to inhaled therapies in people with cystic fibrosis?

Adherence to treatment, including inhaled therapies, is low in people with cystic fibrosis (CF). Although psychological interventions for improving adherence to inhaled therapies in people with CF have been developed, no previous published systematic review has evaluated the evidence for efficacy of these interventions.

The primary objective of the review was to assess the efficacy of psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (CF). The secondary objective was to establish the most effective components, or behaviour change techniques (BCTs), used in these interventions.

Due to the limited quantity of trials included in this review, as well as the clinical and methodological heterogeneity, it was not possible to identify an overall intervention effect using meta-analysis. Some moderate-certainty evidence suggests that psychological interventions (compared with usual care) probably improve adherence to inhaled therapies in people with CF, without increasing treatment-related adverse events, anxiety and depression (low-certainty evidence). In future review updates (with ongoing trial results included), we hope to be able to establish the most effective BCTs (or 'active ingredients') of interventions for improving adherence to inhaled therapies in people with CF. Wherever possible, investigators should make use of the most objective measures of adherence available (e.g. data-logging nebulisers) to accurately determine intervention effects. Outcome reporting needs to be improved to enable combining or separation of measures as appropriate. Likewise, trial reporting needs to include details of intervention content (e.g. BCTs used); duration; intensity; and fidelity. Large trials with a longer follow-up period (e.g. 12 months) are needed in children with CF. Additionally, more research is needed to determine how to support adherence in 'under-served' CF populations.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does controlling blood pressure levels among diabetics have a significant effect on the prevention of diabetic retinopathy?

Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Concurrent blood pressure control has been advocated for this purpose, but individual studies have reported varying conclusions regarding the effects of this intervention.

To summarize the existing evidence regarding the effect of interventions to control blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs.

Hypertension is a well-known risk factor for several chronic conditions for which lowering blood pressure has proven to be beneficial. The available evidence supports a modest beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to five years, particularly for hypertensive type 2 diabetics. However, there was a paucity of evidence to support such intervention to slow progression of diabetic retinopathy or to affect other outcomes considered in this review among normotensive diabetics. This weakens any conclusion regarding an overall benefit of intervening on blood pressure in diabetic patients without hypertension for the sole purpose of preventing diabetic retinopathy or avoiding the need for treatment for advanced stages of diabetic retinopathy.

SUPPORTED

MEDIUM

cardiovascular system

Does skin-sparing mastectomy effectively and safely treat breast cancer?

Skin-sparing mastectomy (SSM) is a surgical technique that aims to maximize skin preservation, facilitate breast reconstruction, and improve cosmetic outcomes. Despite its use in clinical practice, the benefits and harms related to SSM are not well established.

To assess the effectiveness and safety of skin-sparing mastectomy for the treatment of breast cancer.

Based on very low-certainty evidence from observational studies, it was not possible to draw definitive conclusions on the effectiveness and safety of SSM for breast cancer treatment. The decision for this technique of breast surgery for treatment of DCIS or invasive breast cancer must be individualized and shared between the physician and the patient while considering the potential risks and benefits of available surgical options.

NOT ENOUGH INFORMATION

LOW

cancer

Do inhaled corticosteroids used as monotherapy provide benefits compared to placebo for people with stable COPD?

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much uncertainty. COPD clinical guidelines currently recommend selective use of ICS. ICS are not recommended as monotherapy for people with COPD, and are only given in combination with long-acting bronchodilators due to greater efficacy of combination therapy. Incorporating and critiquing newly published placebo-controlled trials into the monotherapy evidence base may help to resolve ongoing uncertainties and conflicting findings about their role in this population.

To evaluate the benefits and harms of inhaled corticosteroids, used as monotherapy versus placebo, in people with stable COPD, in terms of objective and subjective outcomes.

This systematic review updates the evidence base for ICS monotherapy with newly published trials to aid the ongoing assessment of their role for people with COPD. Use of ICS alone for COPD likely results in a reduction of exacerbation rates of clinical relevance, probably results in a reduction in the rate of decline of FEV

SUPPORTED

MEDIUM

respiratory system

Does methylphenidate have beneficial effects for children and adolescents with ADHD?

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on benefits and harms is uncertain. This is an update of our comprehensive systematic review on benefits and harms published in 2015.

To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD.

The majority of our conclusions from the 2015 version of this review still apply. Our updated meta-analyses suggest that methylphenidate versus placebo or no-intervention may improve teacher-rated ADHD symptoms and general behaviour in children and adolescents with ADHD. There may be no effects on serious adverse events and quality of life. Methylphenidate may be associated with an increased risk of adverse events considered non-serious, such as sleep problems and decreased appetite. However, the certainty of the evidence for all outcomes is very low and therefore the true magnitude of effects remain unclear. Due to the frequency of non-serious adverse events associated with methylphenidate, the blinding of participants and outcome assessors is particularly challenging. To accommodate this challenge, an active placebo should be sought and utilised. It may be difficult to find such a drug, but identifying a substance that could mimic the easily recognised adverse effects of methylphenidate would avert the unblinding that detrimentally affects current randomised trials. Future systematic reviews should investigate the subgroups of patients with ADHD that may benefit most and least from methylphenidate. This could be done with individual participant data to investigate predictors and modifiers like age, comorbidity, and ADHD subtypes.

SUPPORTED

LOW

cognitive, mental, and mental health

Can weight-loss interventions improve overall survival and reduce adverse events in overweight or obese women with endometrial cancer?

This is an updated version of the original Cochrane Review published in Issue 2, 2018. Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival, as well as a reduction in the risk of cardiovascular disease, which is a frequent cause of death in endometrial cancer survivors.

To evaluate the benefits and harm of weight-loss interventions, in addition to standard management, on overall survival and the frequency of adverse events in women with endometrial cancer who are overweight or obese compared with any other intervention, usual care, or placebo.

Trial registration:

NOT ENOUGH INFORMATION

LOW

cancer

Is high-dose opioid use effective and safe for chronic non-cancer pain?

This overview was originally published in 2017, and is being updated in 2022. Chronic pain is typically described as pain on most days for at least three months. Chronic non-cancer pain (CNCP) is any chronic pain that is not due to a malignancy. Chronic non-cancer pain in adults is a common and complex clinical issue, for which opioids are prescribed by some physicians for pain management. There are concerns that the use of high doses of opioids for CNCP lacks evidence of effectiveness, and may increase the risk of adverse events.

To describe the evidence from Cochrane Reviews and overviews regarding the efficacy and safety of high-dose opioids (defined as 200 mg morphine equivalent or more per day) for CNCP.

There is a critical lack of high-quality evidence, in the form of Cochrane Reviews, about how well high-dose opioids work for the management of CNCP in adults, and regarding the presence and severity of adverse events. No evidence-based argument can be made on the use of high-dose opioids, i.e. 200 mg morphine equivalent or more daily, in clinical practice. Considering that high-dose opioids have been, and are still being used in clinical practice to treat CNCP, knowing about the efficacy and safety of these higher doses is imperative.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does exercise-based rehabilitation benefit people with pulmonary hypertension compared to usual care or no exercise-based rehabilitation?

Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation.

To evaluate the benefits and harms of exercise-based rehabilitation for people with PH compared with usual care or no exercise-based rehabilitation.

In people with PH, supervised exercise-based rehabilitation may result in a large increase in exercise capacity. Changes in exercise capacity remain heterogeneous and cannot be explained by subgroup analysis. It is likely that exercise-based rehabilitation increases HRQoL and is probably not associated with an increased risk of a serious adverse events. Exercise training may result in a large reduction in mean pulmonary arterial pressure. Overall, we assessed the certainty of the evidence to be low for exercise capacity and mean pulmonary arterial pressure, and moderate for HRQoL and adverse events. Future RCTs are needed to inform the application of exercise-based rehabilitation across the spectrum of people with PH, including those with chronic thromboembolic PH, PH with left-sided heart disease and those with more severe disease.

SUPPORTED

LOW

respiratory system

Does anti-VEGF treatment improve the effectiveness and safety of treatment for proliferative diabetic retinopathy?

Proliferative diabetic retinopathy (PDR) is an advanced complication of diabetic retinopathy that can cause blindness. It consists of the presence of new vessels in the retina and vitreous haemorrhage. Although panretinal photocoagulation (PRP) is the treatment of choice for PDR, it has secondary effects that can affect vision. Anti-vascular endothelial growth factor (anti-VEGF), which produces an inhibition of vascular proliferation, could improve the vision of people with PDR.

To assess the effectiveness and safety of anti-VEGFs for PDR and summarise any relevant economic evaluations of their use.

Anti-VEGFs ± PRP compared with PRP alone probably increase visual acuity, but the degree of improvement is not clinically meaningful. Regarding secondary outcomes, anti-VEGFs ± PRP produce a regression of new vessels, reduce vitreous haemorrhage, and may reduce the need for vitrectomy compared with eyes that received PRP alone. We do not know if anti-VEGFs ± PRP have an impact on the incidence of adverse events and they may have little or no effect on patients' quality of life. Carefully designed and conducted clinical trials are required, assessing the optimal schedule of anti-VEGFs alone compared with PRP, and with a longer follow-up.

SUPPORTED

LOW

sensory organs

Can personally tailored activities improve psychosocial outcomes for people with dementia in long-term care facilities?

People with dementia who are being cared for in long-term care settings are often not engaged in meaningful activities. We wanted to know whether offering them activities which are tailored to their individual interests and preferences could improve their quality of life and reduce agitation. This review updates our earlier review published in 2018.

∙ To assess the effects of personally tailored activities on psychosocial outcomes for people with dementia living in long-term care facilities. ∙ To describe the components of the interventions. ∙ To describe conditions which enhance the effectiveness of personally tailored activities in this setting.

Offering personally tailored activities to people with dementia in long-term care may slightly reduce agitation. Personally tailored activities may result in little to no difference in quality of life rated by proxies, but we acknowledge concerns about the validity of proxy ratings of quality of life in severe dementia. Personally tailored activities probably have little or no effect on negative affect, and we are uncertain whether they have any effect on positive affect or mood. There was no evidence that interventions were more likely to be effective if based on one theoretical model rather than another. We included three new studies in this updated review, but two studies were pilot trials and included only a small number of participants. Certainty of evidence was predominately very low or low due to several methodological limitations of and inconsistencies between the included studies. Evidence is still limited, and we remain unable to describe optimal activity programmes. Further research should focus on methods for selecting appropriate and meaningful activities for people in different stages of dementia.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does the postnatal administration of phenobarbital in preterm infants at risk of developing IVH result in little to no difference in the incidence of IVH compared to control?

Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood in the newborn flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. It has been suggested that phenobarbital stabilises blood pressure and may protect against free radicals. This is an update of a review first published in 2001 and updated in 2007 and 2013.

To assess the benefits and harms of the postnatal administration of phenobarbital in preterm infants at risk of developing IVH compared to control (i.e. no intervention or placebo).

The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH (any grade or severe) compared with control (i.e. no intervention or placebo). The evidence is very uncertain about the effects of phenobarbital on ventricular dilation or hydrocephalus and on neurodevelopmental impairment. The evidence suggests that phenobarbital results in little to no difference in death before discharge and all deaths during the study period compared with control. Since 1993, no randomised studies have been published on phenobarbital for the prevention of IVH in preterm infants, and no trials are ongoing. The effects of postnatal phenobarbital might be assessed in infants with both neonatal seizures and IVH, in both randomised and observational studies. The assessment of benefits and harms should include long-term outcomes.

SUPPORTED

LOW

cognitive, mental, and mental health

Did the study investigate the views and experiences of consumers and health providers of formal partnership approaches to improve health services?

Partnering with consumers in the planning, delivery and evaluation of health services is an essential component of person-centred care. There are many ways to partner with consumers to improve health services, including formal group partnerships (such as committees, boards or steering groups). However, consumers' and health providers' views and experiences of formal group partnerships remain unclear. In this qualitative evidence synthesis (QES), we focus specifically on formal group partnerships where health providers and consumers share decision-making about planning, delivering and/or evaluating health services. Formal group partnerships were selected because they are widely used throughout the world to improve person-centred care. For the purposes of this QES, the term 'consumer' refers to a person who is a patient, carer or community member who brings their perspective to health service partnerships. 'Health provider' refers to a person with a health policy, management, administrative or clinical role who participates in formal partnerships in an advisory or representative capacity. This QES was co-produced with a Stakeholder Panel of consumers and health providers. The QES was undertaken concurrently with a Cochrane intervention review entitled Effects of consumers and health providers working in partnership on health services planning, delivery and evaluation.

1. To synthesise the views and experiences of consumers and health providers of formal partnership approaches that aimed to improve planning, delivery or evaluation of health services. 2. To identify best practice principles for formal partnership approaches in health services by understanding consumers' and health providers' views and experiences.

Successful formal group partnerships with consumers require health providers to continually reflect and address power imbalances that may constrain consumers' participation. Such imbalances may be particularly acute in recruitment procedures, meeting structure and content and decision-making processes. Formal group partnerships were perceived to improve the physical environment of health services, the person-centredness of health service culture and health service design and delivery. Implementing the best practice principles may help to address power imbalances, strengthen formal partnering, improve the experiences of consumers and health providers and positively affect partnership outcomes.

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Is there evidence on the effectiveness of therapeutics for mpox infection in humans?

Mpox was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on 23 July 2022, following the identification of thousands of cases in several non-endemic countries in previous months. There are currently no licenced therapeutics for treating mpox; however, some medications may be authorized for use in an outbreak. The efficacy and safety of possible therapeutic options has not been studied in humans with mpox. There is a need to investigate the evidence on safety and effectiveness of treatments for mpox in humans; should any therapeutic option be efficacious and safe, it may be approved for use around the world.

There are two parts to this Cochrane Review: a review of evidence from randomized controlled trials (RCTs), and a narrative review of safety data from non-randomized studies. Randomized controlled trials review To systematically review the existing evidence on the effectiveness of therapeutics for mpox infection in humans compared to: a) another different therapeutic for mpox, or b) placebo, or c) supportive care, defined as the treatment of physical and psychological symptoms arising from the disease. Non-randomized studies review To assess the safety of therapeutics for mpox infection from non-randomized studies (NRS).

Randomized controlled trials review This review found no evidence from randomized controlled trials concerning the efficacy and safety of therapeutics in humans with mpox. Non-randomized studies review Very low-certainty evidence from non-randomized studies indicates no serious safety signals emerging for the use of tecovirimat in people with mpox infection. In contrast, very low-certainty evidence raises a safety signal that brincidofovir may cause liver injury. This is also suggested by indirect evidence from brincidofovir use in smallpox. This warrants further investigation and monitoring. This Cochrane Review will be updated as new evidence becomes available to assist policymakers, health professionals, and consumers in making appropriate decisions for the treatment of mpox.

NOT ENOUGH INFORMATION

LOW

immune system and infections

Is botulinum toxin therapy effective in the treatment of strabismus compared with alternative conservative or surgical treatment options?

The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison with other treatment options for strabismus.

The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin.

It remains unclear whether botulinum toxin may be an alternative to strabismus surgery as an independent treatment modality among certain types of strabismus because we found only low and very low-certainty evidence in this review update. Low-certainty evidence suggests that strabismus surgery may be preferable to botulinum toxin injection to improve or correct strabismus when types of strabismus and different age groups are combined. We found low-certainty evidence suggesting botulinum toxin may have little to no effect on achievement of binocular single vision compared with surgery in children with acquired or infantile esotropia. We did not find sufficient evidence to draw any meaningful conclusions with respect to need for additional surgery, quality of life, and serious adverse events. We identified three ongoing trials comparing botulinum toxin with conventional surgeries in the varying types of strabismus, whose results will provide relevant evidence for our stated objectives. Future trials should be rigorously designed, and investigators should analyze outcome data appropriately and report adequate information to provide evidence of high certainty. Quality of life and cost-effectiveness should be examined in addition to clinical and safety outcomes.

NOT ENOUGH INFORMATION

LOW

sensory organs

Do oral Class I and III antiarrhythmic drugs reduce the risk of recurrence of atrial tachyarrhythmias after catheter ablation for atrial fibrillation?

Recurrence of atrial tachyarrhythmias (ATa) following catheter ablation for atrial fibrillation (AF) is a common problem. Antiarrhythmic drugs have been used shortly after ablation in an attempt to maintain sinus rhythm, particularly Class I and III agents. However, it still needs to be established if the use of Class I or III antiarrhythmic medications, or both, reduce the risk of recurrence of ATa.

To assess the effects of oral Class I and III antiarrhythmic drugs versus control (standard medical therapy without Class I or III antiarrhythmics, or placebo) for maintaining sinus rhythm in people undergoing catheter ablation for AF.

We found evidence to suggest that the use of Class I and/or III antiarrhythmics up to 3 months after ablation is associated with a reduced recurrence of ATa 0 to 6 months after ablation, which may not persist beyond 6 months, and an immediate reduction in hospitalisation for ATa 0 to 3 months after ablation. The evidence suggests there is no difference in rates of all-cause mortality, thromboembolic events, or myocardial infarction between Class I and/or III antiarrhythmics versus control.

SUPPORTED

MEDIUM

cardiovascular system

Do different corticosteroid treatment regimens affect mortality, pulmonary morbidity, and neurodevelopmental outcome in very low birth weight infants?

Systematic reviews showed that systemic postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants. However, corticosteroids have also been associated with an increased risk of neurodevelopmental impairment. It is unknown whether these beneficial and adverse effects are modulated by differences in corticosteroid treatment regimens related to type of steroid, timing of treatment initiation, duration, pulse versus continuous delivery, and cumulative dose.

To assess the effects of different corticosteroid treatment regimens on mortality, pulmonary morbidity, and neurodevelopmental outcome in very low birth weight infants.

The evidence is very uncertain about the effects of different corticosteroid regimens on the outcomes mortality, pulmonary morbidity, and long term neurodevelopmental impairment. Despite the fact that the studies investigating higher versus lower dosage regimens showed that higher-dosage regimens may reduce the incidence of death or neurodevelopmental impairment, we cannot conclude what the optimal type, dosage, or timing of initiation is for the prevention of BPD in preterm infants, based on current level of evidence. Further high quality trials would be needed to establish the optimal systemic postnatal corticosteroid dosage regimen.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does exercise plus standard care show benefits compared to standard care alone in adults with cancer receiving radiation therapy alone?

Radiation therapy (RT) is given to about half of all people with cancer. RT alone is used to treat various cancers at different stages. Although it is a local treatment, systemic symptoms may occur. Cancer- or treatment-related side effects can lead to a reduction in physical activity, physical performance, and quality of life (QoL). The literature suggests that physical exercise can reduce the risk of various side effects of cancer and cancer treatments, cancer-specific mortality, recurrence of cancer, and all-cause mortality.

To evaluate the benefits and harms of exercise plus standard care compared with standard care alone in adults with cancer receiving RT alone.

There is little evidence on the effects of exercise interventions in people with cancer who are receiving RT alone. While all included studies reported benefits for the exercise intervention groups in all assessed outcomes, our analyses did not consistently support this evidence. There was low-certainty evidence that exercise improved fatigue in all three studies. Regarding physical performance, our analysis showed very low-certainty evidence of a difference favouring exercise in two studies, and very low-certainty evidence of no difference in one study. We found very low-certainty evidence of little or no difference between the effects of exercise and no exercise on quality of life or psychosocial effects. We downgraded the certainty of the evidence for possible outcome reporting bias, imprecision due to small sample sizes in a small number of studies, and indirectness of outcomes. In summary, exercise may have some beneficial outcomes in people with cancer who are receiving RT alone, but the evidence supporting this statement is of low certainty. There is a need for high-quality research on this topic.

NOT ENOUGH INFORMATION

LOW

cancer

Do non-pharmacological interventions provide benefits for persistent postural-perceptual dizziness (PPPD)?

Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing and with visual stimulation. The condition was only recently defined and therefore the prevalence is currently unknown. However, it is likely to include a considerable number of people with chronic balance problems. The symptoms can be debilitating and have a profound impact on quality of life. At present, little is known about the optimal way to treat this condition. A variety of medications may be used, as well as other treatments, such as vestibular rehabilitation. OBJECTIVES: To assess the benefits and harms of non-pharmacological interventions for persistent postural-perceptual dizziness (PPPD). SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 November 2022.

Selection criteria:

further work is necessary to determine whether any non-pharmacological interventions may be effective for the treatment of pppd and to assess whether they are associated with any potential harms. as this is a chronic disease, future trials should follow up participants for a sufficient period of time to assess whether there is a persisting impact on the severity of the disease, rather than only observing short-term effects.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does antibiotic therapy provide benefits in the management of acute bacterial conjunctivitis?

Acute bacterial conjunctivitis is an infection of the conjunctiva and is one of the most common ocular disorders in primary care. Antibiotics are generally prescribed on the basis that they may speed recovery, reduce persistence, and prevent keratitis. However, many cases of acute bacterial conjunctivitis are self-limited, resolving without antibiotic therapy. This Cochrane Review was first published in The Cochrane Library in 1999, then updated in 2006, 2012, and 2022.

To assess the benefits and side effects of antibiotic therapy in the management of acute bacterial conjunctivitis.

The findings of this update suggest that the use of topical antibiotics is associated with a modestly improved chance of resolution in comparison to the use of placebo. Since no evidence of serious side effects was reported, use of antibiotics may therefore be considered to achieve better clinical and microbiologic efficacy than placebo. Increasing the proportion of participants with clinical cure or increasing the speed of recovery or both are important for individual return to work or school, allowing people to regain quality of life. Future studies may examine antiseptic treatments with topical antibiotics for reasons of cost and growing antibiotic resistance.

SUPPORTED

MEDIUM

sensory organs

Do medical interventions effectively manage traumatic hyphema?

Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications.

To assess the effectiveness of various medical interventions in the management of traumatic hyphema.

We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.

NOT ENOUGH INFORMATION

LOW

miscellaneous

Do different devices as adjuncts to trabeculectomy have benefits on IOP control in eyes with glaucoma compared to standard trabeculectomy?

Glaucoma is an optic neuropathy that leads to visual field defects and vision loss. It is the second leading cause of irreversible blindness in the world. Treatment for glaucoma aims to reduce intraocular pressure (IOP) to slow or prevent further vision loss. IOP can be lowered with medications, laser, or incisional surgery. Trabeculectomy is a surgical approach which lowers IOP by shunting aqueous humor to a subconjunctival bleb. Device-modified trabeculectomy techniques are intended to improve the durability and safety of this bleb-forming surgery. Trabeculectomy-modifying devices include the Ex-PRESS, the XEN Gel Stent, the PreserFlo MicroShunt, as well as antifibrotic materials such as Ologen, amniotic membrane, expanded polytetrafluoroethylene (ePTFE) membrane, Gelfilm and others. However, the comparative effectiveness and safety of these devices are uncertain.

To evaluate the benefits and harms of different devices as adjuncts to trabeculectomy on IOP control in eyes with glaucoma compared to standard trabeculectomy.

Use of an Ex-PRESS plus trabeculectomy may produce greater IOP reduction at one-year follow-up than standard trabeculectomy; however, due to potential biases and imprecision in effect estimates, the certainty of evidence is low. PreserFlo MicroShunt may be inferior to standard trabeculectomy in lowering IOP. However, PreserFlo MicroShunt may prevent postoperative hypotony and bleb leakage. Overall, device-modified trabeculectomy appears associated with a lower risk of cataract surgery within five years compared with standard trabeculectomy. Due to various limitations in the design and conduct of the included studies, the applicability of this evidence synthesis to other populations or settings is uncertain. Further research is needed to determine the effectiveness and safety of other devices in subgroup populations, such as people with different types of glaucoma, of various races and ethnicity, and with different lens types (e.g. phakic, pseudophakic).

NOT ENOUGH INFORMATION

LOW

sensory organs

Do pharmacological interventions, specifically SSRIs and SNRIs, provide benefits for persistent postural-perceptual dizziness (PPPD)?

Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing and with visual stimulation. The condition was only recently defined and therefore the prevalence is currently unknown. However, it is likely to include a considerable number of people with chronic balance problems. The symptoms can be debilitating and have a profound impact on quality of life. At present, little is known about the optimal way to treat this condition. A variety of medications may be used, as well as other treatments, such as vestibular rehabilitation. OBJECTIVES: To evaluate the benefits and harms of pharmacological interventions for persistent postural-perceptual dizziness (PPPD). SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 November 2022.

Selection criteria:

At present, there is no evidence from placebo-controlled randomised trials regarding pharmacological treatments - specifically SSRIs and SNRIs - for PPPD. Consequently, there is great uncertainty over the use of these treatments for this condition. Further work is needed to establish whether any treatments are effective at improving the symptoms of PPPD, and whether their use is associated with any adverse effects.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Do environmental interventions effectively reduce falls in older people living in the community?

Falls and fall-related injuries are common. A third of community-dwelling people aged over 65 years fall each year. Falls can have serious consequences including restricting activity or institutionalisation. This review updates the previous evidence for environmental interventions in fall prevention.

To assess the effects (benefits and harms) of environmental interventions (such as fall-hazard reduction, assistive technology, home modifications, and education) for preventing falls in older people living in the community.

We found high-certainty evidence that home fall-hazard interventions are effective in reducing the rate of falls and the number of fallers when targeted to people at higher risk of falling, such as having had a fall in the past year and recently hospitalised or needing support with daily activities. There was evidence of no effect when interventions were targeted to people not selected for risk of falling. Further research is needed to examine the impact of intervention components, the effect of awareness raising, and participant-interventionist engagement on decision-making and adherence. Vision improvement interventions may or may not impact the rate of falls. Further research is needed to answer clinical questions such as whether people should be given advice or take additional precautions when changing eye prescriptions, or whether the intervention is more effective when targeting people at higher risk of falls. There was insufficient evidence to determine whether education interventions impact falls.

SUPPORTED

HIGH

musculoskeletal system and dermatology

Does lens extraction provide better outcomes compared to LPI in the treatment of APAC?

Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the absence of timely intervention. Laser peripheral iridotomy (LPI) has been the standard of care thus far. However, LPI does not eliminate the long-term risk of chronic angle closure glaucoma and other associated sequelae. There has been increasing interest in lens extraction as the primary treatment for the spectrum of primary angle closure disease, and it is as yet unclear whether these results can be extrapolated to APAC, and whether lens extraction provides better long-term outcomes. We therefore sought to evaluate the effectiveness of lens extraction in APAC to help inform the decision-making process. OBJECTIVES: To assess the effect of lens extraction compared to LPI in the treatment of APAC.

Search methods:

Low certainty evidence suggests that early lens extraction may produce more favorable outcomes compared to initial LPI in terms of IOP control. Evidence for other outcomes is less clear. Future high-quality and longer-term studies evaluating the effects of either intervention on the development of glaucomatous damage and visual field changes as well as health-related quality of life measures would be helpful.

NOT ENOUGH INFORMATION

LOW

sensory organs

Does induction of labor for suspected fetal macrosomia affect the way of giving birth and maternal or perinatal morbidity?

Women with a suspected large-for-dates fetus or a fetus with suspected macrosomia (birthweight greater than 4000 g) are at risk of operative birth or caesarean section. The baby is also at increased risk of shoulder dystocia and trauma, in particular fractures and brachial plexus injury. Induction of labour may reduce these risks by decreasing the birthweight, but may also lead to longer labours and an increased risk of caesarean section.

To assess the effects of a policy of labour induction at or shortly before term (37 to 40 weeks) for suspected fetal macrosomia on the way of giving birth and maternal or perinatal morbidity.

Induction of labour for suspected fetal macrosomia has not been shown to alter the risk of brachial plexus injury, but the power of the included studies to show a difference for such a rare event is limited. Also antenatal estimates of fetal weight are often inaccurate so many women may be worried unnecessarily, and many inductions may not be needed. Nevertheless, induction of labour for suspected fetal macrosomia results in a lower mean birthweight, and fewer birth fractures and shoulder dystocia. The observation of increased use of phototherapy in the largest trial, should also be kept in mind. Findings from trials included in the review suggest that to prevent one fracture it would be necessary to induce labour in 60 women. Since induction of labour does not appear to alter the rate of caesarean delivery or instrumental delivery, it is likely to be popular with many women. In settings where obstetricians can be reasonably confident about their scan assessment of fetal weight, the advantages and disadvantages of induction at or near term for fetuses suspected of being macrosomic should be discussed with parents. Although some parents and doctors may feel the evidence already justifies induction, others may justifiably disagree. Further trials of induction shortly before term for suspected fetal macrosomia are needed. Such trials should concentrate on refining the optimum gestation of induction, and improving the accuracy of the diagnosis of macrosomia.

NOT ENOUGH INFORMATION

LOW

sexual and reproductive health

Does dose-escalated radiotherapy improve outcomes for localized and locally advanced prostate cancer?

Treatments for clinically localized prostate cancer include radical prostatectomy, external beam radiation therapy, brachytherapy, active surveillance, hormonal therapy, and watchful waiting. For external beam radiation therapy, oncological outcomes may be expected to improve as the dose of radiotherapy (RT) increases. However, radiation-mediated side effects on surrounding critical organs may also increase.

To assess the effects of dose-escalated RT in comparison with conventional dose RT for curative treatment of clinically localized and locally advanced prostate cancer.

Compared to conventional dose RT, dose-escalated RT probably results in little to no difference in time to death from prostate cancer, time to death from any cause, time to distant metastasis, and RT toxicities (except overall late GI toxicity). While dose-escalated RT may increase overall late GI toxicity, it may result, or probably results, in little to no difference in physical and mental quality of life, respectively.

NOT ENOUGH INFORMATION

MEDIUM

cancer

Does planned hospital birth reduce maternal or perinatal mortality, morbidity, or any other critical outcome for low-risk pregnant women?

Observational studies of increasingly better quality and in different settings suggest that planned hospital birth in many places does not reduce mortality and morbidity but increases the frequency of interventions and complications. Euro-Peristat (part of the European Union's Health Monitoring Programme) has raised concerns about iatrogenic effects of obstetric interventions, and the World Health Organization (WHO) has raised concern that the increasing medicalisation of childbirth tends to undermine women's own capability to give birth and negatively impacts their childbirth experience. This is an update of a Cochrane Review first published in 1998, and previously updated in 2012.

To compare the effects of planned hospital birth with planned home birth attended by a midwife or others with midwifery skills and backed up by a modern hospital system in case a transfer to hospital should turn out to be necessary. The primary focus is on women with an uncomplicated pregnancy and low risk of medical intervention during birth. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, WHO ICTRP, and conference proceedings), ClinicalTrials.gov (16 July 2021), and reference lists of retrieved studies.

this review shows that for selected, low-risk pregnant women, the evidence from randomised trials to support that planned hospital birth reduces maternal or perinatal mortality, morbidity, or any other critical outcome is uncertain. as the quality of evidence in favour of home birth from observational studies seems to be steadily increasing, it might be just as important to prepare a regularly updated systematic review including observational studies as described in the cochrane handbook for systematic reviews of interventions as to attempt to set up new rcts. as women and healthcare practitioners may be aware of evidence from observational studies, and as the international federation of gynecology and obstetrics and the international confederation of midwives collaboratively conclude that there is strong evidence that out-of-hospital birth supported by a registered midwife is safe, equipoise may no longer exist, and randomised trials may now thus be considered unethical or hardly feasible.

NOT ENOUGH INFORMATION

LOW

cancer

Does parathyroidectomy provide more benefits than harms in adults with primary hyperparathyroidism compared to simple observation or medical therapy?

Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and postmenopausal women. While most people with PHPT are asymptomatic at diagnosis, symptomatic disease can lead to hypercalcaemia, osteoporosis, renal stones, cardiovascular abnormalities and reduced quality of life. Surgical removal of abnormal parathyroid tissue (parathyroidectomy) is the only established treatment for adults with symptomatic PHPT to prevent exacerbation of symptoms and to be cured of PHPT. However, the benefits and risks of parathyroidectomy compared to simple observation or medical therapy for asymptomatic and mild PHPT are not well established.

To evaluate the benefits and harms of parathyroidectomy in adults with PHPT compared to simple observation or medical therapy.

In accordance with the literature, our review findings suggest that parathyroidectomy, compared to simple observation or medical (etidronate) therapy, probably results in a large increase in cure rates of PHPT (with normalisation of serum calcium and parathyroid hormone levels to laboratory reference values). Parathyroidectomy, compared with observation, may have little or no effect on serious adverse events or hospitalisation for hypercalcaemia, and the evidence is very uncertain about the effect of parathyroidectomy on other short-term outcomes, such as BMD, all-cause mortality and quality of life. The high uncertainty of evidence limits the applicability of our findings to clinical practice; indeed, this systematic review provides no new insights with regard to treatment decisions for people with (asymptomatic) PHPT. In addition, the methodological limitations of the included studies, and the characteristics of the study populations (mainly comprising white women with asymptomatic PHPT), warrant caution when extrapolating the results to other populations with PHPT. Large-scale multi-national, multi-ethnic and long-term RCTs are needed to explore the potential short- and long-term benefits of parathyroidectomy compared to non-surgical treatment options with regard to osteoporosis or osteopenia, urolithiasis, hospitalisation for acute kidney injury, cardiovascular disease and quality of life.

NOT ENOUGH INFORMATION

LOW

endocrine system and hormones

Does spinal cord stimulation (SCS) provide sustained clinical benefits for people with low back pain?

Spinal cord stimulation (SCS) is a surgical intervention used to treat persistent low back pain. SCS is thought to modulate pain by sending electrical signals via implanted electrodes into the spinal cord. The long term benefits and harms of SCS for people with low back pain are uncertain.

To assess the effects, including benefits and harms, of SCS for people with low back pain.

Data in this review do not support the use of SCS to manage low back pain outside a clinical trial. Current evidence suggests SCS probably does not have sustained clinical benefits that would outweigh the costs and risks of this surgical intervention.

REFUTED

MEDIUM

musculoskeletal system and dermatology

Did the study find a difference in drug effects between an experimental drug and an active placebo versus a standard placebo control intervention?

An estimated 60% of pharmacological randomised trials use placebo control interventions to blind (i.e. mask) participants. However, standard placebos do not control for perceptible non-therapeutic effects (i.e. side effects) of the experimental drug, which may unblind participants. Trials rarely use active placebo controls, which contain pharmacological compounds designed to mimic the non-therapeutic experimental drug effects in order to reduce the risk of unblinding. A relevant improvement in the estimated effects of active placebo compared with standard placebo would imply that trials with standard placebo may overestimate experimental drug effects.

We aimed to estimate the difference in drug effects when an experimental drug is compared with an active placebo versus a standard placebo control intervention, and to explore causes for heterogeneity. In the context of a randomised trial, this difference in drug effects can be estimated by directly comparing the effect difference between the active placebo and standard placebo intervention.

We did not find a statistically significant difference between active and standard placebo control interventions in our primary analysis, but the result was imprecise and the CI compatible with a difference ranging from important to irrelevant. Furthermore, the result was not robust, because two sensitivity analyses produced a more pronounced and statistically significant difference. We suggest that trialists and users of information from trials carefully consider the type of placebo control intervention in trials with high risk of unblinding, such as those with pronounced non-therapeutic effects and participant-reported outcomes.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Do systemic opioid analgesics in neonates who underwent surgery have benefits on all-cause mortality, pain, and significant neurodevelopmental disability compared to no intervention, placebo, non-pharmacological interventions, different types of opioids, or other drugs?

Neonates may undergo surgery because of malformations such as diaphragmatic hernia, gastroschisis, congenital heart disease, and hypertrophic pyloric stenosis, or complications of prematurity, such as necrotizing enterocolitis, spontaneous intestinal perforation, and retinopathy of prematurity that require surgical treatment. Options for treatment of postoperative pain include opioids, non-pharmacological interventions, and other drugs. Morphine, fentanyl, and remifentanil are the opioids most often used in neonates. However, negative impact of opioids on the structure and function of the developing brain has been reported. The assessment of the effects of opioids is of utmost importance, especially for neonates in substantial pain during the postoperative period.

To evaluate the benefits and harms of systemic opioid analgesics in neonates who underwent surgery on all-cause mortality, pain, and significant neurodevelopmental disability compared to no intervention, placebo, non-pharmacological interventions, different types of opioids, or other drugs.

Limited evidence is available on opioid administration for postoperative pain in newborn infants compared to either placebo, other opioids, or paracetamol. We are uncertain whether tramadol reduces mortality compared to placebo; none of the studies reported pain scores, major neurodevelopmental disability, cognitive and educational outcomes in children older than five years old, retinopathy of prematurity, or intraventricular hemorrhage. We are uncertain whether fentanyl reduces mortality compared to tramadol; none of the studies reported pain scores, major neurodevelopmental disability, cognitive and educational outcomes in children older than five years old, retinopathy of prematurity, or intraventricular hemorrhage. We are uncertain whether morphine reduces pain compared to paracetamol; none of the studies reported major neurodevelopmental disability, cognitive and educational outcomes in children more than five years old, all-cause mortality during initial hospitalization, retinopathy of prematurity, or intraventricular hemorrhage. We identified no studies comparing opioids versus non-pharmacological interventions.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Is intermittent phototherapy as effective as continuous phototherapy?

Phototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been proposed as an equally effective alternative with practical advantages of improved maternal feeding and bonding. The effectiveness of intermittent phototherapy compared with continuous phototherapy is unknown.

To assess the safety and effectiveness of intermittent phototherapy compared with continuous phototherapy.

the available evidence detected little or no difference between intermittent and continuous phototherapy with respect to rate of decline of bilirubin. continuous phototherapy appears to be more effective in preterm infants, however, the risks of continuous phototherapy and the potential benefits of a slightly lower bilirubin level are unknown. intermittent phototherapy is associated with a decrease in the total number of hours of phototherapy exposure. there are theoretical benefits to intermittent regimens but there are important safety outcomes that were inadequately addressed. large, well designed, prospective trials are needed in both preterm and term infants before it can be concluded that intermittent and continuous phototherapy regimens are equally effective.

NOT ENOUGH INFORMATION

LOW

miscellaneous

Does ultrasound guidance improve arterial line placement compared to traditional techniques in children and adolescents?

In arterial line cannulation in children and adolescents, traditional methods of locating the artery include palpation and Doppler auditory assistance. It is unclear whether ultrasound guidance is superior to these methods. This is an update of a review originally published in 2016.

To evaluate the benefits and harms of ultrasound guidance compared with traditional techniques (palpation, Doppler auditory assistance) for assisting arterial line placement at all potential sites in children and adolescents.

We identified moderate-certainty evidence that ultrasound guidance for arterial cannulation compared with palpation or Doppler auditory assistance improves first-attempt success rate, second-attempt success rate and overall success rate. We also found moderate-certainty evidence that ultrasound guidance reduces the incidence of complications, the number of attempts to successful cannulation and the duration of the cannulation procedure.

SUPPORTED

HIGH

cardiovascular system

Can ataluren and similar compounds improve clinically important outcomes in people with CF with class I mutations?

Cystic fibrosis (CF) is a common, life-shortening, genetic disorder in populations of Northern European descent caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces, and the mutation most notably affects the airways. In the lungs of people with CF, the defective protein compromises mucociliary clearance and makes the airway prone to chronic infection and inflammation, damaging the structure of the airways and eventually leading to respiratory failure. In addition, abnormalities in the truncated CFTR protein lead to other systemic complications, including malnutrition, diabetes and subfertility. Five classes of mutation have been described, depending on the impact of the mutation on the processing of the CFTR protein in the cell. In class I mutations, premature termination codons prevent the production of any functional protein, resulting in severe CF. Therapies targeting class I mutations aim to enable the normal cellular mechanism to read through the mutation, potentially restoring the production of the CFTR protein. This could, in turn, normalise salt transport in the cells and decrease the chronic infection and inflammation that characterises lung disease in people with CF. This is an update of a previously published review.

To evaluate the benefits and harms of ataluren and similar compounds on clinically important outcomes in people with CF with class I mutations (premature termination codons).

Trial registration:

NOT ENOUGH INFORMATION

LOW

respiratory system

Can ultrasound and shock wave therapy effectively reduce the time to healing of acute fractures in adults?

The morbidity and socioeconomic costs of fractures are considerable. The length of time to healing is an important factor in determining a person's recovery after a fracture. Ultrasound may have a therapeutic role in reducing the time to union after fracture by stimulating osteoblasts and other bone-forming proteins. This is an update of a review previously published in February 2014. OBJECTIVES: To assess the effects of low-intensity ultrasound (LIPUS), high-intensity focused ultrasound (HIFUS) and extracorporeal shockwave therapies (ECSW) as part of the treatment of acute fractures in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase (1980 to March 2022), Orthopaedic Proceedings, trial registers and reference lists of articles.

Selection criteria:

We were uncertain of the effectiveness of ultrasound and shock wave therapy for acute fractures in terms of patient-reported outcome measures (PROMS), for which few studies reported data. It is probable that LIPUS makes little or no difference to delayed union or non-union. Future trials should be double-blind, randomised, placebo-controlled trials recording validated PROMs and following up all trial participants. Whilst time to union is difficult to measure, the proportion of participants achieving clinical and radiographic union at each follow-up point should be ascertained, alongside adherence with the study protocol and cost of treatment in order to better inform clinical practice.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Does trunk training after stroke improve various aspects of physical function and quality of life?

Previous systematic reviews and randomised controlled trials have investigated the effect of post-stroke trunk training. Findings suggest that trunk training improves trunk function and activity or the execution of a task or action by an individual. But it is unclear what effect trunk training has on daily life activities, quality of life, and other outcomes.

To assess the effectiveness of trunk training after stroke on activities of daily living (ADL), trunk function, arm-hand function or activity, standing balance, leg function, walking ability, and quality of life when comparing with both dose-matched as non-dose-matched control groups.

There is evidence to suggest that trunk training as part of rehabilitation improves ADL, trunk function, standing balance, walking ability, upper and lower limb function, and quality of life in people after stroke. Core-stability, selective-, and unstable-trunk training were the trunk training approaches mostly applied in the included trials. When considering only trials with a low risk of bias, results were mostly confirmed, with very low to moderate certainty, depending on the outcome.

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Is pharmacological treatment beneficial for central sleep apnoea in adults?

The term central sleep apnoea (CSA) encompasses diverse clinical situations where a dysfunctional drive to breathe leads to recurrent respiratory events, namely apnoea (complete absence of ventilation) and hypopnoea sleep (insufficient ventilation) during sleep. Studies have demonstrated that CSA responds to some extent to pharmacological agents with distinct mechanisms, such as sleep stabilisation and respiratory stimulation. Some therapies for CSA are associated with improved quality of life, although the evidence on this association is uncertain. Moreover, treatment of CSA with non-invasive positive pressure ventilation is not always effective or safe and may result in a residual apnoea-hypopnoea index.

To evaluate the benefits and harms of pharmacological treatment compared with active or inactive controls for central sleep apnoea in adults.

There is insufficient evidence to support the use of pharmacological therapy in the treatment of CSA. Although small studies have reported positive effects of certain agents for CSA associated with heart failure in reducing the number of respiratory events during sleep, we were unable to assess whether this reduction may impact the quality of life of people with CSA, owing to scarce reporting of important clinical outcomes such as sleep quality or subjective impression of daytime sleepiness. Furthermore, the trials mostly had short-term follow-up. There is a need for high-quality trials that evaluate longer-term effects of pharmacological interventions.

NOT ENOUGH INFORMATION

LOW

respiratory system

Can different agents prevent severe kidney disease, treat established severe kidney disease, and prevent recurrent episodes of IgA vasculitis-associated kidney disease?

IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel vasculitis is characterised by palpable purpura, abdominal pain, arthritis or arthralgia and kidney involvement. This is an update of a review first published in 2009 and updated in 2015.

To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo, no treatment or any other agent for (1) the prevention of severe kidney disease in people with IgAV with or without kidney involvement at onset, (2) the treatment of established severe kidney disease (macroscopic haematuria, proteinuria, nephritic syndrome, nephrotic syndrome with or without acute kidney failure) in IgAV, and (3) the prevention of recurrent episodes of IgAV-associated kidney disease.

There are no substantial changes in conclusions from this update compared with the initial review or the previous update despite the addition of five studies. From generally low to moderate certainty evidence, we found that there may be little or no benefit in the use of corticosteroids or antiplatelet agents to prevent persistent kidney disease in children with IgAV in participants with no or minimal kidney involvement at presentation. We did not find any studies which evaluated corticosteroids in children presenting with IgAV and nephritic and/or nephrotic syndrome, although corticosteroids are recommended in such children in guidelines. Though heparin may be effective in reducing proteinuria, this potentially dangerous therapy is not justified to prevent serious kidney disease when few children with IgAV develop severe kidney disease. There may be no benefit of cyclophosphamide compared with no specific treatment or corticosteroids. While there may be no benefit in the efficacy of MMF or tacrolimus compared with IV cyclophosphamide in children or adults with IgAV and severe kidney disease, adverse effects, particularly infections, may be lower in MMF or tacrolimus-treated children. Because of small patient numbers and events leading to imprecision in results, it remains unclear whether cyclosporin, MMF or leflunomide have any role in the treatment of children with IgAV and severe kidney disease. We did not identify any studies which evaluated corticosteroids.

NOT ENOUGH INFORMATION

LOW

renal and urinary system

Does splinting have significant benefits for people with carpal tunnel syndrome?

Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve causing pain and numbness and tingling typically in the thumb, index and middle finger. It sometimes results in muscle wasting, diminished sensitivity and loss of dexterity. Splinting the wrist (with or without the hand) using an orthosis is usually offered to people with mild-to-moderate findings, but its effectiveness remains unclear.

To assess the effects (benefits and harms) of splinting for people with CTS.

There is insufficient evidence to conclude whether splinting benefits people with CTS. Limited evidence does not exclude small improvements in CTS symptoms and hand function, but they may not be clinically important, and the clinical relevance of small differences with splinting is unclear. Low-certainty evidence suggests that people may have a greater chance of experiencing overall improvement with night-time splints than no treatment. As splinting is a relatively inexpensive intervention with no plausible long-term harms, small effects could justify its use, particularly when patients are not interested in having surgery or injections. It is unclear if a splint is optimally worn full time or at night-time only and whether long-term use is better than short-term use, but low-certainty evidence suggests that the benefits may manifest in the long term.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Do lifestyle and dietary interventions show benefits for Ménière's disease?

Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Lifestyle or dietary modifications (including reducing the amount of salt or caffeine in the diet) are sometimes suggested to be of benefit for this condition. The underlying cause of Ménière's disease is unknown, as is the way in which these interventions may work. The efficacy of these different interventions at preventing vertigo attacks, and their associated symptoms, is currently unclear.

To evaluate the benefits and harms of lifestyle and dietary interventions versus placebo or no treatment in people with Ménière's disease.

The evidence for lifestyle or dietary interventions for Ménière's disease is very uncertain. We did not identify any placebo-controlled RCTs for interventions that are frequently recommended for those with Ménière's disease, such as salt restriction or caffeine restriction. We identified only two RCTs that compared a lifestyle or dietary intervention to placebo or no treatment, and the evidence that is currently available from these studies is of low or very low certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analyses of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.

NOT ENOUGH INFORMATION

LOW

sensory organs

Can intratympanic corticosteroids benefit people with Ménière's disease?

Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Corticosteroids are sometimes administered directly into the middle ear to treat this condition (through the tympanic membrane). The underlying cause of Ménière's disease is unknown, as is the way in which this treatment may work. The efficacy of this intervention in preventing vertigo attacks, and their associated symptoms, is currently unclear.

To evaluate the benefits and harms of intratympanic corticosteroids versus placebo or no treatment in people with Ménière's disease.

The evidence for intratympanic corticosteroids in the treatment of Ménière's disease is uncertain. There are relatively few published RCTs, which all consider the same type of corticosteroid (dexamethasone). We also have concerns about publication bias in this area, with the identification of two large RCTs that remain unpublished. The evidence comparing intratympanic corticosteroids to placebo or no treatment is therefore all low- or very low-certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area, and enable meta-analysis of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits. Finally, we would also highlight the responsibility that trialists have to ensure results are available, regardless of the outcome of their study.

NOT ENOUGH INFORMATION

LOW

sensory organs

Is intratympanic aminoglycosides more effective than placebo or no treatment for Ménière's disease?

Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Aminoglycosides are sometimes administered directly into the middle ear to treat this condition. The aim of this treatment is to partially or completely destroy the balance function of the affected ear. The efficacy of this intervention in preventing vertigo attacks, and their associated symptoms, is currently unclear.

To evaluate the benefits and harms of intratympanic aminoglycosides versus placebo or no treatment in people with Ménière's disease.

the evidence for the use of intratympanic gentamicin in the treatment of ménière's disease is very uncertain. this is primarily due to the fact that there are few published rcts in this area, and all the studies we identified enrolled a very small number of participants. as the studies assessed different outcomes, using different methods, and reported at different time points, we were not able to pool the results to obtain more reliable estimates of the efficacy of this treatment. more people may report an improvement in vertigo following gentamicin treatment, and scores of vertigo symptoms may also improve. however, the limitations of the evidence mean that we cannot be sure of these effects. although there is the potential for intratympanic gentamicin to cause harm (for example, hearing loss) we did not find any information about the risks of treatment in this review. consensus on the appropriate outcomes to measure in studies of ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analysis of the results. this must include appropriate consideration of the potential harms of treatment, as well as the benefits.

NOT ENOUGH INFORMATION

LOW

sensory organs

Are progestin-containing IUDs effective for emergency contraception compared to copper-containing IUDs or dedicated oral hormonal methods?

The copper intrauterine device (Cu-IUD) is a highly effective method of contraception that can also be used for emergency contraception (EC). It is the most effective form of EC, and is more effective than other existing oral regimens also used for EC. The Cu-IUD provides the unique benefit of providing ongoing contraception after it is inserted for EC; however, uptake of this intervention has been limited. Progestin IUDs are a popular method of long-acting, reversible contraception. If these devices were also found to be effective for EC, they would provide a critical additional option for women. These IUDs could not only provide EC and ongoing contraception, but additional non-contraceptive benefits, including a reduction in menstrual bleeding, cancer prevention, and pain management.

To examine the safety and effectiveness of progestin-containing IUDs for emergency contraception, compared with copper-containing IUDs, or compared with dedicated oral hormonal methods.

this review is limited in its ability to provide definitive evidence regarding the lng-iud's equivalence, superiority, or inferiority to the cu-iud for ec. only one study was identified in the review, which had possible risks of bias related to randomization and rare outcomes. additional studies are needed to provide definitive evidence related to the effectiveness of the lng-iud for ec.

NOT ENOUGH INFORMATION

LOW

sexual and reproductive health

Do systemic pharmacological interventions provide benefits for Ménière's disease?

Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. A number of pharmacological interventions have been used in the management of this condition, including betahistine, diuretics, antiviral medications and corticosteroids. The underlying cause of Ménière's disease is unknown, as is the way in which these treatments may work. The efficacy of these different interventions at preventing vertigo attacks, and their associated symptoms, is currently unclear.

To evaluate the benefits and harms of systemic pharmacological interventions versus placebo or no treatment in people with Ménière's disease.

The evidence for systemic pharmacological interventions for Ménière's disease is very uncertain. There are few RCTs that compare these interventions to placebo or no treatment, and the evidence that is currently available from these studies is of low or very low certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analyses of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.

NOT ENOUGH INFORMATION

LOW

sensory organs

Did surgical interventions show clear benefits over placebo or no treatment for Ménière's disease?

Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. First-line treatments often involve dietary or lifestyle changes, medication or local (intratympanic) treatments. However, surgery may also be considered for people with persistent or severe symptoms. The efficacy of different surgical interventions at preventing vertigo attacks, and their associated symptoms, is currently unclear.

To evaluate the benefits and harms of surgical interventions versus placebo or no treatment in people with Ménière's disease.

we are unable to draw clear conclusions about the efficacy of these surgical interventions for ménière's disease. we identified evidence for only two of our five proposed comparisons, and we assessed all the evidence as low- or very low-certainty. this means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. many of the outcomes that we planned to assess were not reported by the studies, such as the impact on quality of life, and adverse effects of the interventions. consensus on the appropriate outcomes to measure in studies of ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analyses of the results. this must include appropriate consideration of the potential harms of treatment, as well as the benefits.

NOT ENOUGH INFORMATION

LOW

sensory organs

Are there identifiable risk factors for the development of proliferative diabetic retinopathy and high-risk characteristics proliferative diabetic retinopathy in people with diabetes and diabetic retinopathy?

Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most serious complication of DR and can lead to total (central and peripheral) visual loss. PDR is characterised by the presence of abnormal new blood vessels, so-called "new vessels," at the optic disc (NVD) or elsewhere in the retina (NVE). PDR can progress to high-risk characteristics (HRC) PDR (HRC-PDR), which is defined by the presence of NVD more than one-fourth to one-third disc area in size plus vitreous haemorrhage or pre-retinal haemorrhage, or vitreous haemorrhage or pre-retinal haemorrhage obscuring more than one disc area. In severe cases, fibrovascular membranes grow over the retinal surface and tractional retinal detachment with sight loss can occur, despite treatment. Although most, if not all, individuals with diabetes will develop DR if they live long enough, only some progress to the sight-threatening PDR stage. OBJECTIVES: To determine risk factors for the development of PDR and HRC-PDR in people with diabetes and DR.

Search methods:

Antecedentes:

SUPPORTED

MEDIUM

endocrine system and hormones

Is positive pressure therapy more beneficial than placebo or no treatment for Ménière's disease?

Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. It is often treated with medication, but different interventions are sometimes used. Positive pressure therapy is a treatment that creates small pressure pulses, generated by a pump that is attached to tubing placed in the ear canal. It is typically used for a few minutes, several times per day. The underlying cause of Ménière's disease is unknown, as is the way in which this treatment may work. The efficacy of this intervention at preventing vertigo attacks, and their associated symptoms, is currently unclear.

To evaluate the benefits and harms of positive pressure therapy versus placebo or no treatment in people with Ménière's disease.

the evidence for positive pressure therapy for ménière's disease is very uncertain. there are few rcts that compare this intervention to placebo or no treatment, and the evidence that is currently available from these studies is of low or very low certainty. this means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. consensus on the appropriate outcomes to measure in studies of ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analyses of the results. this must include appropriate consideration of the potential harms of treatment, as well as the benefits.

NOT ENOUGH INFORMATION

LOW

sensory organs

Do different methods for informing people of a diagnosis of ALS/MND have measurable effects on knowledge, understanding, coping, and adjustment?

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), causes increasing physical impairment and disability. People with ALS/MND face huge physical challenges, and the diagnosis can be a source of great psychological distress for both people with ALS/MND and their carers. In such a context, how news of the diagnosis is broken is important. At present, there are no systematic reviews of methods for informing people with ALS/MND of their diagnosis.

To examine the effects and effectiveness of different methods for informing people of a diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), including effects on the person's knowledge and understanding of their disease, its treatment, and care; and on coping and adjustment to the effects of ALS/MND, its treatment, and care.

There are no RCTs that evaluate different communication strategies for breaking the bad news for people diagnosed with ALS/MND. Focused research studies are needed to assess the effectiveness and efficacy of different communication methods.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does the specific technique used for PD catheter insertion result in lower rates of PD catheter dysfunction and post-procedure complications?

Peritoneal dialysis (PD) relies on the optimal functionality of the flexible plastic PD catheter present within the peritoneal cavity to enable effective treatment. As a result of limited evidence, it is uncertain if the PD catheter's insertion method influences the rate of catheter dysfunction and, thus, the quality of dialysis therapy. Numerous variations of four basic techniques have been adopted in an attempt to improve and maintain PD catheter function. This review evaluates the association between PD catheter insertion technique and associated differences in PD catheter function and post-PD catheter insertion complications OBJECTIVES: Our aims were to 1) evaluate if a specific technique used for PD catheter insertion has lower rates of PD catheter dysfunction (early and late) and technique failure; and 2) examine if any of the available techniques results in a reduction in post-procedure complication rates including postoperative haemorrhage, exit-site infection and peritonitis.

Search methods:

The available studies show that the evidence needed to guide clinicians in developing their PD catheter insertion service is lacking. No PD catheter insertion technique had lower rates of PD catheter dysfunction. High-quality, evidence-based data are urgently required, utilising multi-centre RCTs or large cohort studies, in order to provide definitive guidance relating to PD catheter insertion modality.

NOT ENOUGH INFORMATION

LOW

renal and urinary system

Do interventions for slowing myopia progression in children show comparative efficacy?

Myopia is a common refractive error, where elongation of the eyeball causes distant objects to appear blurred. The increasing prevalence of myopia is a growing global public health problem, in terms of rates of uncorrected refractive error and significantly, an increased risk of visual impairment due to myopia-related ocular morbidity. Since myopia is usually detected in children before 10 years of age and can progress rapidly, interventions to slow its progression need to be delivered in childhood.

To assess the comparative efficacy of optical, pharmacological and environmental interventions for slowing myopia progression in children using network meta-analysis (NMA). To generate a relative ranking of myopia control interventions according to their efficacy. To produce a brief economic commentary, summarising the economic evaluations assessing myopia control interventions in children. To maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE; Embase; and three trials registers. The search date was 26 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of optical, pharmacological and environmental interventions for slowing myopia progression in children aged 18 years or younger. Critical outcomes were progression of myopia (defined as the difference in the change in spherical equivalent refraction (SER, dioptres (D)) and axial length (mm) in the intervention and control groups at one year or longer) and difference in the change in SER and axial length following cessation of treatment ('rebound'). DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. We assessed bias using RoB 2 for parallel RCTs. We rated the certainty of evidence using the GRADE approach for the outcomes: change in SER and axial length at one and two years. Most comparisons were with inactive controls.

Studies mostly compared pharmacological and optical treatments to slow the progression of myopia with an inactive comparator. Effects at one year provided evidence that these interventions may slow refractive change and reduce axial elongation, although results were often heterogeneous. A smaller body of evidence is available at two or three years, and uncertainty remains about the sustained effect of these interventions. Longer-term and better-quality studies comparing myopia control interventions used alone or in combination are needed, and improved methods for monitoring and reporting adverse effects.

NOT ENOUGH INFORMATION

LOW

sensory organs

Does peri-operative tranexamic acid have an effect on operative parameters in patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis?

Chronic rhinosinusitis, with or without nasal polyps, can have a major impact on a person's quality of life. Treatment is usually conservative and may include nasal saline, intranasal corticosteroids, antibiotics or systemic corticosteroids. If these treatments fail endoscopic sinus surgery can be considered. During surgery, visibility of the surgical field is important for the identification of important anatomic landmarks and structures that contribute to safety. Impaired visualisation can lead to complications during surgery, inability to complete the operation or a longer duration of surgery. Different methods are used to decrease intraoperative bleeding, including induced hypotension, topical or systemic vasoconstrictors or total intravenous anaesthesia. Another option is tranexamic acid, an antifibrinolytic agent, which can be administered topically or intravenously.

To assess the effects of peri-operative tranexamic acid versus no therapy or placebo on operative parameters in patients with chronic rhinosinusitis (with or without nasal polyps) who are undergoing functional endoscopic sinus surgery (FESS).

There is moderate-certainty evidence to support the beneficial value of topical or intravenous tranexamic acid during endoscopic sinus surgery with respect to surgical field bleeding score. Low- to moderate-certainty evidence suggests a slight decrease in total blood loss during surgery and duration of surgery. Whilst there is moderate-certainty evidence that tranexamic acid does not lead to more immediate significant adverse events compared to placebo, there is no evidence regarding the risk of serious adverse events more than 24 hours after surgery. There is low-certainty evidence that tranexamic acid may not change postoperative bleeding. There is not enough evidence available to draw robust conclusions about incomplete surgery or surgical complications.

SUPPORTED

MEDIUM

respiratory system

Can anti-fibrinolytic and haemostatic drugs and agents effectively reduce bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe blood loss?

Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion.

To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss.

Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Did probiotics and synbiotics show efficacy in treating functional abdominal pain disorders in children?

Functional abdominal pain is pain occurring in the abdomen that cannot be fully explained by another medical condition and is common in children. It has been hypothesised that the use of micro-organisms, such as probiotics and synbiotics (a mixture of probiotics and prebiotics), might change the composition of bacterial colonies in the bowel and reduce inflammation, as well as promote normal gut physiology and reduce functional symptoms.

To assess the efficacy and safety of probiotics in the treatment of functional abdominal pain disorders in children.

The results from this review demonstrate that probiotics and synbiotics may be more efficacious than placebo in achieving treatment success, but the evidence is of low certainty. The evidence demonstrates little to no difference between probiotics or synbiotics and placebo in complete resolution of pain. We were unable to draw meaningful conclusions about the impact of probiotics or synbiotics on the frequency and severity of pain as the evidence was all of very low certainty due to significant unexplained heterogeneity or imprecision. There were no reported cases of serious adverse events when using probiotics or synbiotics amongst the included studies, although a review of RCTs may not be the best context to assess long-term safety. The available evidence on adverse effects was of very low certainty and no conclusions could be made in this review. Safety will always be a priority in paediatric populations when considering any treatment. Reporting of all adverse events, adverse events needing withdrawal, serious adverse events and, particularly, long-term safety outcomes are vital to meaningfully move forward the evidence base in this field. Further targeted and appropriately designed RCTs are needed to address the gaps in the evidence base. In particular, appropriate powering of studies to confirm the safety of specific strains not yet investigated and studies to investigate long-term follow-up of patients are both warranted.

SUPPORTED

LOW

digestive system and metabolism

Do ESAs effectively and safely treat anaemia in adults with CKD?

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anaemia in people with chronic kidney disease (CKD). However, their use has been associated with cardiovascular events. This is an update of a Cochrane review first published in 2014.

To compare the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs against each other, placebo, or no treatment) to treat anaemia in adults with CKD.

Antecedentes:

NOT ENOUGH INFORMATION

LOW

endocrine system and hormones

Can antenatal dietary supplementation with myo-inositol prevent gestational diabetes?

Gestational diabetes with onset or first recognition during pregnancy is an increasing problem worldwide. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. Myo-inositol is one of the intracellular mediators of the insulin signal and correlates with insulin sensitivity in type 2 diabetes. The potential beneficial effect of improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes. This is an update of a review first published in 2015.

To assess if antenatal dietary supplementation with myo-inositol is safe and effective, for the mother and fetus, in preventing gestational diabetes.

Evidence from seven studies shows that antenatal dietary supplementation with myo-inositol during pregnancy may reduce the incidence of gestational diabetes, hypertensive disorders of pregnancy and preterm birth. Limited data suggest that supplementation with myo-inositol may not reduce the risk of a large-for-gestational-age infant. The current evidence is based on small studies that were not powered to detect differences in outcomes such as perinatal mortality and serious infant morbidity. Six of the included studies were conducted in Italy and one in Ireland, which raises concerns about the lack of generalisability to other settings. There is evidence of inconsistency among doses of myo-inositol, the timing of administration and study population. As a result, we downgraded the certainty of the evidence for many outcomes to low or very low certainty. Further studies for this promising antenatal intervention for preventing gestational diabetes are encouraged and should include pregnant women of different ethnicities and varying risk factors. Myo-inositol at different doses, frequency and timing of administration, should be compared with placebo, diet and exercise, and pharmacological interventions. Long-term follow-up should be considered and outcomes should include potential harms, including adverse effects.

SUPPORTED

LOW

nutrition and dietary supplements

Can factors influence the organization and delivery of in-person home-based rehabilitation and home-based telerehabilitation for people needing rehabilitation?

To increase people's access to rehabilitation services, particularly in the context of the COVID-19 pandemic, we need to explore how the delivery of these services can be adapted. This includes the use of home-based rehabilitation and telerehabilitation. Home-based rehabilitation services may become frequently used options in the recovery process of patients, not only as a solution to accessibility barriers, but as a complement to the usual in-person inpatient rehabilitation provision. Telerehabilitation is also becoming more viable as the usability and availability of communication technologies improve.

To identify factors that influence the organisation and delivery of in-person home-based rehabilitation and home-based telerehabilitation for people needing rehabilitation.

This synthesis identified several factors that can influence the successful implementation of in-person home-based rehabilitation and telerehabilitation services. These included factors that facilitate implementation, but also factors that can challenge this process. Healthcare providers, program planners and policymakers might benefit from considering these factors when designing and implementing programmes.

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MEDIUM

musculoskeletal system and dermatology

Is antibiotic treatment effective for chronic pulmonary infection in children and young people living with a neurodisability?

'Neurodisability' refers to a group of conditions that result primarily from a neurological problem (e.g. cerebral palsy), neuromuscular problem (e.g. a muscular dystrophy) or developmental problems (e.g. developmental impairment, Down syndrome). Children and young people with these conditions may have similar problems with mobility, feeding and airway clearance. Chest and breathing problems (including pulmonary infections) are commonly experienced by children and young people with neurodisabilities and are often a cause for them requiring hospital care. For those who are unable to completely clear their airway of secretions, or have frequent infections, pulmonary infections may not be able to be completely eradicated and therefore become chronic. It is unclear what treatment is best for children and young people in this position.

To assess the effectiveness and adverse effects of antibiotic treatment for chronic pulmonary infection in children and young people living with a neurodisability, including quality-of-life measures, effects on hospitalisation and healthcare contacts.

The findings of this systematic review highlight a lack of evidence in the antibiotic treatment of chronic pulmonary infection in children and young people up to the age of 18 living with a neurodisability. Further research examining this topic is therefore required.

NOT ENOUGH INFORMATION

LOW

respiratory system

Do educational support interventions improve school engagement and academic achievement in children and adolescents with chronic health conditions?

Chronic health conditions in children and adolescents can have profound impacts on education, well-being and health. They are described as non-communicable illnesses that are prolonged in duration, do not resolve spontaneously, and rarely cured completely. Due to variations in the definition of chronic health conditions and how they are measured prevalence estimates vary considerably and have been reported to be as high as 44% in children and adolescents. Of young people with a chronic health condition, an estimated 5% are affected by severe conditions characterised by limitations to daily activities impacting their ability to attend school. School attendance is important for academic and social skill development as well as well-being. When children and adolescents are absent from school due to a chronic health condition, school engagement can be affected. Disengagement from school is associated with poorer academic achievement, social-emotional functioning and career choices. Education support services for children and adolescents with chronic health conditions aim to prevent disengagement from school, education and learning during periods where their illness caused them to miss school. However, there is limited evidence on the effectiveness of educational support interventions at improving school engagement and educational/learning outcomes for children and adolescents with chronic health conditions.

To describe the nature of educational support interventions for children and adolescents with a chronic health condition, and to examine the effectiveness of these interventions on school engagement and academic achievement.

This review has demonstrated the infancy of quality research on the effectiveness of education support interventions for children and adolescents with chronic health conditions. At best, we can say that we are uncertain whether education support interventions improve either academic achievement or school engagement. Of the secondary outcomes, we are also uncertain whether education support interventions improve transition back to school, or school re-entry. However, we suggest there is some evidence that education support may slightly improve mental health, measured as self-esteem. Given the current state of the evidence of the effectiveness of education support interventions for children and adolescents with chronic health conditions, we highlight some important implications for future research in this field to strengthen the evidence that can inform effective practice and policy.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does combined mechanical and oral antibiotic bowel preparation prevent complications in elective colorectal surgery?

The success of elective colorectal surgery is mainly influenced by the surgical procedure and postoperative complications. The most serious complications include anastomotic leakages and surgical site infections (SSI)s, which can lead to prolonged recovery with impaired long-term health. Compared with other abdominal procedures, colorectal resections have an increased risk of adverse events due to the physiological bacterial colonisation of the large bowel. Preoperative bowel preparation is used to remove faeces from the bowel lumen and reduce bacterial colonisation. This bowel preparation can be performed mechanically and/or with oral antibiotics. While mechanical bowel preparation alone is not beneficial, the benefits and harms of combined mechanical and oral antibiotic bowel preparation is still unclear.

To assess the evidence for the use of combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery.

Based on moderate-certainty evidence, our results suggest that MBP+oAB is probably more effective than MBP alone in preventing postoperative complications. In particular, with respect to our primary outcomes, SSI and anastomotic leakage, a lower incidence was demonstrated using MBP+oAB. Whether oAB alone is actually equivalent to MBP+oAB, or leads to a reduction or increase in the risk of postoperative complications, cannot be clarified in light of the low- to very low-certainty evidence. Similarly, it remains unclear whether omitting preoperative bowel preparation leads to an increase in the risk of postoperative complications due to limited evidence. Additional RCTs, particularly on the comparisons of MBP+oAB versus oAB alone or nBP, are needed to assess the impact of oAB alone or nBP compared with MBP+oAB on postoperative complications and to improve confidence in the estimated effect. In addition, RCTs focusing on subgroups (e.g. in relation to type and location of colon resections) or reporting side effects of the intervention are needed to determine the most effective approach of preoperative bowel preparation.

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MEDIUM

digestive system and metabolism

Do behavioural and cognitive-behavioural interventions reduce outwardly directed aggressive behavior in people with intellectual disability?

Outwardly directed aggressive behaviour in people with intellectual disabilities is a significant issue that may lead to poor quality of life, social exclusion and inpatient psychiatric admissions. Cognitive and behavioural approaches have been developed to manage aggressive behaviour but the effectiveness of these interventions on reducing aggressive behaviour and other outcomes are unclear. This is the third update of this review and adds nine new studies, resulting in a total of 15 studies in this review.

To evaluate the efficacy of behavioural and cognitive-behavioural interventions on outwardly directed aggressive behaviour compared to usual care, wait-list controls or no treatment in people with intellectual disability. We also evaluated enhanced interventions compared to non-enhanced interventions.

There is moderate-certainty evidence that cognitive-behavioural approaches such as anger management and PBS may reduce outwardly directed aggressive behaviour in the short term but there is less certainty about the evidence in the medium and long term, particularly in relation to other outcomes such as quality of life. There is some evidence to suggest that combining more than one intervention may have cumulative benefits. Most studies were small and there is a need for larger, robust randomised controlled trials, particularly for interventions where the certainty of evidence is very low. More trials are needed that focus on children and whether psychological interventions lead to reductions in the use of psychotropic medications.

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MEDIUM

cognitive, mental, and mental health

Did administration of vitamin D or its hydroxylated metabolites reduce the risk of severe asthma exacerbations and improve asthma symptom control?

Since the previous Cochrane Review on this topic in 2016, debate has continued surrounding a potential role for vitamin D in reducing risk of asthma exacerbation and improving asthma control. We therefore conducted an updated meta-analysis to include data from new trials completed since this date.

To evaluate the effectiveness and safety of administration of vitamin D or its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control.

In contrast to findings of our previous Cochrane Review on this topic, this updated review does not find evidence to support a role for vitamin D supplementation or its hydroxylated metabolites to reduce risk of asthma exacerbations or improve asthma control. Participants with severe asthma and those with baseline 25(OH)D concentrations < 25 nmol/L were poorly represented, so further research is warranted here. A single study investigating effects of calcidiol yielded positive results, so further studies investigating effects of this metabolite are needed.

REFUTED

MEDIUM

respiratory system

Does endovascular therapy plus conventional medical treatment increase the risk of short-term stroke and death in people with symptomatic intracranial artery stenosis?

Intracranial artery stenosis (ICAS) is an arterial narrowing in the brain that can cause stroke. Endovascular therapy (ET) and conventional medical treatment (CMT) may prevent recurrent ischaemic stroke caused by ICAS. However, there is no consensus on the best treatment for people with ICAS.

To evaluate the safety and efficacy of endovascular therapy plus conventional medical treatment compared with conventional medical treatment alone for the management of symptomatic intracranial artery stenosis.

This review provides moderate-certainty evidence that ET plus CMT compared with CMT alone increases the risk of short-term stroke and death in people with recent symptomatic severe ICAS. This effect was still apparent at long-term follow-up but appeared to be due to the early risks of ET; therefore, there may be no clear difference between the interventions in terms of their effects on long-term stroke and death. The impact of delayed ET intervention (more than three weeks after a qualifying event) warrants further study.

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MEDIUM

cardiovascular system

Does digital technology improve adherence to inhaled therapies and health status in adults and children with CF?

Improved understanding and treatment of cystic fibrosis (CF) has led to longer life expectancy, which is accompanied by an increasingly complex regimen of treatments. Suboptimal adherence to the treatment plan, in the context of respiratory disease, has been found to be associated with poorer health outcomes. With digital technology being more accessible, it can be used to monitor adherence to inhaled therapies via chipped nebulisers, mobile phone apps and web-based platforms. This technology can allow monitoring of adherence as well as clinical outcomes, and allow feedback to both the person with CF and their healthcare team.

To assess the effects of using digital technology to monitor adherence to inhaled therapies and health status in adults and children with CF.

Digital monitoring plus tailored support via an online platform probably improves adherence to inhaled therapies and reduces treatment burden (but without a corresponding change in QoL) in the medium term (low- and moderate-certainty evidence). In a shorter time frame, technological enhancement of inhaling antibiotics may improve adherence to treatment (low-certainty evidence). There may be little or no effect on lung function with either intervention, and online monitoring probably makes no difference to pulmonary exacerbations. Future research should assess the effect of digital technology on adherence in both children and adults. Consideration of adherence to the total treatment regimen is also important, as an improvement in adherence to inhaled therapies could come at the cost of adherence to other parts of the treatment regimen.

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MEDIUM

respiratory system

Does convalescent plasma transfusion effectively treat people with COVID-19?

Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required.

To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach.

For the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have low certainty evidence for our primary outcomes. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.

REFUTED

HIGH

immune system and infections

Do different methods for treating dental and orthodontic complications in people with thalassaemia show varying effectiveness?

Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life-long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence-based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.

To assess different methods for treating dental and orthodontic complications in people with thalassaemia.

Although the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review. This review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.

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LOW

miscellaneous

Is ACBT more clinically effective than other airway clearance therapies in CF?

People with cystic fibrosis (CF) experience chronic airway infections as a result of mucus buildup within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review.

To compare the clinical effectiveness of ACBT with other airway clearance therapies in CF.

There is little evidence to support or reject the use of the ACBT over any other airway clearance therapy and ACBT is comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of ACBT on outcomes important for people with cystic fibrosis such as quality of life and preference.

NOT ENOUGH INFORMATION

LOW

respiratory system

Does erythromycin before endoscopy improve outcomes in adults with acute upper gastrointestinal haemorrhage?

Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH.

To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo.

We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.

NOT ENOUGH INFORMATION

LOW

digestive system and metabolism

Does corticosteroid injection provide benefits for carpal tunnel syndrome compared to no treatment or placebo?

Carpal tunnel syndrome (CTS) is a very common clinical syndrome manifested by signs and symptoms of irritation of the median nerve at the carpal tunnel in the wrist. Direct and indirect costs of CTS are substantial, with estimated costs of two billion US dollars for CTS surgery in the USA in 1995 alone. Local corticosteroid injection has been used as a non-surgical treatment for CTS many years, but its effectiveness is still debated.

To evaluate the benefits and harms of corticosteroids injected in or around the carpal tunnel for the treatment of carpal tunnel syndrome compared to no treatment or a placebo injection.

Local corticosteroid injection is effective for the treatment of mild and moderate CTS with benefits lasting up to six months and a reduced need for surgery up to 12 months. Where serious adverse events were reported, they were rare.

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MEDIUM

musculoskeletal system and dermatology

Do treatments for acute non-arteritic CRAO have significant effects?

Acute non-arteritic central retinal artery occlusion (CRAO) occurs as a sudden interruption of the blood supply to the retina and typically results in severe loss of vision in the affected eye. Although many therapeutic interventions have been proposed, there is no generally agreed upon treatment regimen.

To assess the effects of treatments for acute non-arteritic CRAO.

the current research suggests that proposed interventions for acute non-arteritic crao may not be better than observation or treatments of any kind such as eyeball massage, oxygen inhalation, tube expansion, and anticoagulation, but the evidence is uncertain. large, well-designed rcts are necessary to determine the most effective treatment for acute non-arteritic crao.

NOT ENOUGH INFORMATION

LOW

sensory organs

Do physical interventions effectively interrupt or reduce the spread of acute respiratory viruses?

Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review last published in 2020. We include results from studies from the current COVID-19 pandemic.

To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses.

The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions. There were additional RCTs during the pandemic related to physical interventions but a relative paucity given the importance of the question of masking and its relative effectiveness and the concomitant measures of mask adherence which would be highly relevant to the measurement of effectiveness, especially in the elderly and in young children. There is uncertainty about the effects of face masks. The low to moderate certainty of evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of RCTs did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness, and although this effect was also present when ILI and laboratory-confirmed influenza were analysed separately, it was not found to be a significant difference for the latter two outcomes. Harms associated with physical interventions were under-investigated. There is a need for large, well-designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, as well as the impact of adherence on effectiveness, especially in those most at risk of ARIs.

NOT ENOUGH INFORMATION

LOW

respiratory system

Does implantation with trifocal IOL improve visual acuity compared to bifocal IOL during cataract surgery for people with presbyopia?

Presbyopia occurs when the lens of the eyes loses its elasticity leading to loss of accommodation. The lens may also progress to develop cataract, affecting visual acuity and contrast sensitivity. One option of care for individuals with presbyopia and cataract is the use of multifocal or extended depth of focus intraocular lens (IOL) after cataract surgery. Although trifocal and bifocal IOLs are designed to restore three and two focal points respectively, trifocal lens may be preferable because it restores near, intermediate, and far vision, and may also provide a greater range of useful vision and allow for greater spectacle independence in individuals with presbyopia.

To assess the effectiveness and safety of implantation with trifocal versus bifocal IOLs during cataract surgery among people with presbyopia.

We found low-certainty of evidence that compared with bifocal IOL, implantation of trifocal IOL may improve uncorrected intermediate visual acuity at one year. However, there was no evidence of a difference between trifocal and bifocal IOL for uncorrected distance visual acuity, uncorrected near visual acuity, and best-corrected visual acuity at one year. Future research should include the comparison of both trifocal IOL and specific bifocal IOLs that correct intermediate visual acuity to evaluate important outcomes such as contrast sensitivity, quality of life, and vision-related adverse effects.

NOT ENOUGH INFORMATION

LOW

sensory organs

Does calcium and vitamin D supplementation improve bone mineral density in premenopausal women?

Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life.

To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo.

Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful.

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MEDIUM

nutrition and dietary supplements

Do antithrombotic drugs affect major adverse cardiovascular events for people with intracerebral haemorrhage?

This is an update of the Cochrane Review last published in 2017. Survivors of stroke due to intracerebral haemorrhage (ICH) are at risk of major adverse cardiovascular events (MACE). Antithrombotic (antiplatelet or anticoagulant) treatments may lower the risk of ischaemic MACE after ICH, but they may increase the risk of bleeding.

To determine the overall effectiveness and safety of antithrombotic drugs on MACE and its components for people with ICH.

We did not identify beneficial or hazardous effects of short-term prophylactic dose parenteral anticoagulation and long-term oral antiplatelet therapy after ICH on important outcomes. Although there was a significant reduction in MACE and all major occlusive vascular events after long-term treatment with therapeutic dose oral anticoagulation for atrial fibrillation after ICH, the pooled estimates were imprecise, the certainty of evidence was only moderate, and effects on other important outcomes were uncertain. Large RCTs with a low risk of bias are required to resolve the ongoing dilemmas about antithrombotic treatment after ICH.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Does hIVIG therapy provide benefits for people with COVID-19?

Hyperimmune immunoglobulin (hIVIG) contains polyclonal antibodies, which can be prepared from large amounts of pooled convalescent plasma or prepared from animal sources through immunisation. They are being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). This review was previously part of a parent review addressing convalescent plasma and hIVIG for people with COVID-19 and was split to address hIVIG and convalescent plasma separately.

To assess the benefits and harms of hIVIG therapy for the treatment of people with COVID-19, and to maintain the currency of the evidence using a living systematic review approach.

We included data from five RCTs that evaluated hIVIG compared to standard therapy, with participants with moderate-to-severe disease. As the studies evaluated different preparations (from humans or from various animals) and doses, we could not pool them. hIVIG prepared from humans may have little to no impact on mortality, and clinical improvement and worsening. hIVIG may increase grade 3-4 adverse events. Studies did not evaluate quality of life. RBD-specific polyclonal F(ab´)

NOT ENOUGH INFORMATION

LOW

immune system and infections

Do sanitation interventions effectively prevent diarrhoeal disease?

Diarrhoea is a major contributor to the global disease burden, particularly amongst children under five years in low- and middle-income countries (LMICs). As many of the infectious agents associated with diarrhoea are transmitted through faeces, sanitation interventions to safely contain and manage human faeces have the potential to reduce exposure and diarrhoeal disease.

To assess the effectiveness of sanitation interventions for preventing diarrhoeal disease, alone or in combination with other WASH interventions.

There is evidence that sanitation interventions are effective at preventing diarrhoea, both for young children and all age populations. The actual level of effectiveness, however, varies by type of intervention and setting. There is a need for research to better understand the factors that influence effectiveness.

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MEDIUM

digestive system and metabolism

Does remdesivir have a significant effect on clinical outcomes in patients treated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection?

Remdesivir is an antiviral medicine approved for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19). This led to widespread implementation, although the available evidence remains inconsistent. This update aims to fill current knowledge gaps by identifying, describing, evaluating, and synthesising all evidence from randomised controlled trials (RCTs) on the effects of remdesivir on clinical outcomes in COVID-19.

To assess the effects of remdesivir and standard care compared to standard care plus/minus placebo on clinical outcomes in patients treated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Based on the available evidence up to 31 May 2022, remdesivir probably has little or no effect on all-cause mortality or in-hospital mortality of individuals with moderate to severe COVID-19. The hospitalisation rate was reduced with remdesivir in one study including participants with mild to moderate COVID-19. It may be beneficial in the clinical course for both hospitalised and non-hospitalised patients, but certainty remains limited. The applicability of the evidence to current practice may be limited by the recruitment of participants from mostly unvaccinated populations exposed to early variants of the SARS-CoV-2 virus at the time the studies were undertaken. Future studies should provide additional data on the efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups.

NOT ENOUGH INFORMATION

LOW

immune system and infections

Is IVIG effective in treating and preventing cardiac consequences of Kawasaki disease?

Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry tongue, red eyes (bulbar conjunctival injection), rash, redness, swollen hands and feet or skin peeling; and enlarged cervical lymph nodes. High fevers and systemic inflammation characterise the acute phase. Inflammation of the coronary arteries causes the most serious complication of the disease, coronary artery abnormalities (CAAs). The primary treatment is intravenous immunoglobulin (IVIG) and acetylsalicylic acid (ASA/aspirin), with doses and regimens differing between institutions. It is important to know which regimens are the safest and most effective in preventing complications.

To evaluate the efficacy and safety of IVIG in treating and preventing cardiac consequences of Kawasaki disease.

The included RCTs investigated a variety of comparisons, and the small number of events observed during the study periods limited detection of effects. The certainty of the evidence ranged from moderate to very low due to concerns related to risk of bias, imprecision, and inconsistency. The available evidence indicated that high-dose IVIG regimens are probably associated with a reduced risk of CAA formation compared to ASA or medium- or low-dose IVIG regimens. There were no clinically significant differences in incidence of adverse effects, which suggests there is little concern about the safety of IVIG. Compared to ASA, high-dose IVIG probably reduced the duration of fever, but there was little or no difference detected in the need for additional treatment. Compared to medium- or low-dose IVIG, there may be reduced duration of fever and reduced need for additional treatment. We were unable to draw any conclusions regarding acute coronary syndromes, mortality, or length of hospital stay, or for the comparison IVIG versus prednisolone. Our findings are in keeping with current guideline recommendations and evidence from long-term epidemiology studies.

SUPPORTED

LOW

cardiovascular system

Is surgical treatment more effective than non-surgical treatment for patellar dislocation?

Patellar (knee cap) dislocation occurs when the patella disengages completely from the trochlear (femoral) groove. It affects up to 42/100,000 people, and is most prevalent in those aged 20 to 30 years old. It is uncertain whether surgical or non-surgical treatment is the best approach. This is important as recurrent dislocation occurs in up to 40% of people who experience a first time (primary) dislocation. This can reduce quality of life and as a result people have to modify their lifestyle. This review is needed to determine whether surgical or non-surgical treatment should be offered to people after patellar dislocation.

To assess the effects (benefits and harms) of surgical versus non-surgical interventions for treating people with primary or recurrent patellar dislocation.

We are uncertain whether surgery improves outcome compared to non-surgical management as the certainty of the evidence was very low. No sufficiently powered trial has examined people with recurrent patellar dislocation. Adequately powered, multicentre, randomised trials are needed. To inform the design and conduct of these trials, expert consensus should be achieved on the minimal description of both surgical and non-surgical interventions, and the pathological variations that may be relevant to both choice of these interventions.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Do medication review interventions in hospitalised adult patients affect all-cause mortality, hospital readmissions, emergency department contacts, and health-related quality of life?

A medication review can be defined as a structured evaluation of a patient's medication conducted by healthcare professionals with the aim of optimising medication use and improving health outcomes. Optimising medication therapy though medication reviews may benefit hospitalised patients.

We examined the effects of medication review interventions in hospitalised adult patients compared to standard care or to other types of medication reviews on all-cause mortality, hospital readmissions, emergency department contacts and health-related quality of life.

Medication reviews in hospitalised adult patients likely reduce hospital readmissions and may reduce emergency department contacts. The evidence suggests that mediation reviews may have little to no effect on mortality, while the effect on health-related quality of life is very uncertain. Almost all trials included elderly polypharmacy patients, which limits the generalisability of the results beyond this population.

SUPPORTED

MEDIUM

miscellaneous

Can individuals with a single unprovoked epileptic seizure be accurately estimated for the risk of further seizures at subsequent time points?

Epilepsy is clinically defined as two or more unprovoked epileptic seizures more than 24 hours apart. Given that, a diagnosis of epilepsy can be associated with significant morbidity and mortality, it is imperative that clinicians (and people with seizures and their relatives) have access to accurate and reliable prognostic estimates, to guide clinical practice on the risks of developing further unprovoked seizures (and by definition, a diagnosis of epilepsy) following single unprovoked epileptic seizure.

1. To provide an accurate estimate of the proportion of individuals going on to have further unprovoked seizures at subsequent time points following a single unprovoked epileptic seizure (or cluster of epileptic seizures within a 24-hour period, or a first episode of status epilepticus), of any seizure type (overall prognosis). 2. To evaluate the mortality rate following a first unprovoked epileptic seizure.

Despite the limitations of the data (moderate-certainty of evidence), mainly relating to clinical and methodological heterogeneity we have provided summary estimates for the likely risk of seizure recurrence at six months, one year and two years for both children and adults. This provides information that is likely to be useful for the clinician counselling patients (or their parents) on the probable risk of further seizures in the short-term whilst acknowledging the paucity of long-term recurrence data, particularly beyond 10 years.

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MEDIUM

cognitive, mental, and mental health

Do corticosteroids provide benefits in managing cancer-related fatigue in adults with advanced cancer?

Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality of life (QoL). CRF has a highly variable clinical presentation, likely due to a complex interaction of multiple factors. Corticosteroids are commonly used to improve CRF, but the benefits are unclear and there are significant adverse effects associated with long-term use. With the increasing survival of people with metastatic cancer, the long-term effects of medications are becoming increasingly relevant. Since the impact of CRF can be immensely debilitating and can negatively affect QoL, its treatment warrants further review.

To determine the benefits and harms of corticosteroids compared with placebo or an active comparator in adults with advanced cancer and CRF.

There is insufficient evidence to support or refute the use of systemic corticosteroids in adults with cancer and CRF. We included four small studies that provided very low-certainty of evidence for the efficacy of corticosteroids in the management of CRF. Further high-quality randomised controlled trials with larger sample sizes are required to determine the effectiveness of corticosteroids in this setting.

NOT ENOUGH INFORMATION

LOW

cancer

Does neoadjuvant treatment improve outcomes for stage III or stage IV melanoma?

Cutaneous melanoma is amongst the most aggressive of all skin cancers. Neoadjuvant treatment is a form of induction therapy, given to shrink a cancerous tumour prior to the main treatment (usually surgery). The purpose is to improve survival and surgical outcomes. This review systematically appraises the literature investigating the use of neoadjuvant treatment for stage III and IV cutaneous melanoma.

To assess the effects of neoadjuvant treatment in adults with stage III or stage IV melanoma according to the seventh edition American Joint Committee on Cancer (AJCC) staging system.

We are uncertain if neoadjuvant treatment increases OS or TTR compared with no neoadjuvant treatment, and it may be associated with a slightly higher rate of AEs. There is insufficient evidence to support the use of neoadjuvant treatment in clinical practice. Priorities for research include the development of a core outcome set for neoadjuvant trials that are adequately powered, with validation of pathological and radiological responses as intermediate endpoints, to investigate the relative benefits of neoadjuvant treatment compared with adjuvant treatment with immunotherapies or targeted therapies.

NOT ENOUGH INFORMATION

LOW

cancer

Do steroid implants show superior efficacy and safety in treating chronic non-infectious uveitis?

Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of treatment for all subtypes of non-infectious uveitis. They can be administered orally, topically with drops, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation.

To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis.

our confidence is limited that local corticosteroid implants are superior to sham therapy or standard-of-care therapy in reducing the risk of uveitis recurrence. we demonstrated different effectiveness on bcva relative to comparators in people with non-infectious uveitis. nevertheless, the evidence suggests that these implants may increase the risk of cataract progression and iop elevation, which will require interventions over time. to better understand the efficacy and safety profiles of corticosteroid implants, we need future trials that examine implants of different doses, used for different durations. the trials should measure core standard outcomes that are universally defined, and measured at comparable follow-up time points.

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sensory organs