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Lavita AI 13

Do psychosocial interventions have effects on mental health and well-being for survivors of rape, sexual assault, or sexual abuse experienced during adulthood?

Exposure to rape, sexual assault and sexual abuse has lifelong impacts for mental health and well-being. Prolonged Exposure (PE), Cognitive Processing Therapy (CPT) and Eye Movement Desensitisation and Reprocessing (EMDR) are among the most common interventions offered to survivors to alleviate post-traumatic stress disorder (PTSD) and other psychological impacts. Beyond such trauma-focused cognitive and behavioural approaches, there is a range of low-intensity interventions along with new and emerging non-exposure based approaches (trauma-sensitive yoga, Reconsolidation of Traumatic Memories and Lifespan Integration). This review presents a timely assessment of international evidence on any type of psychosocial intervention offered to individuals who experienced rape, sexual assault or sexual abuse as adults.

To assess the effects of psychosocial interventions on mental health and well-being for survivors of rape, sexual assault or sexual abuse experienced during adulthood.

Our review suggests that survivors of rape, sexual violence and sexual abuse during adulthood may experience a large reduction in post-treatment PTSD symptoms and depressive symptoms after experiencing a psychosocial intervention, relative to comparison groups. Psychosocial interventions do not seem to increase dropout from treatment or adverse events/effects compared to controls. However, the number of dropouts and study attrition were generally high, potentially missing harms of exposure to interventions and/or research participation. Also, the differential effects of specific intervention types needs further investigation. We conclude that a range of behavioural and CBT-based interventions may improve the mental health of survivors of rape, sexual assault and sexual abuse in the short term. Therefore, the needs and preferences of individuals must be considered in selecting suitable approaches to therapy and support. The primary outcome in this review focused on the post-treatment period and the question about whether benefits are sustained over time persists. However, attaining such evidence from studies that lack an active comparison may be impractical and even unethical. Thus, we suggest that studies undertake head-to-head comparisons of different intervention types; in particular, of novel, emerging therapies, with one-year plus follow-up periods. Additionally, researchers should focus on the therapeutic benefits and costs for subpopulations such as male survivors and those living with complex PTSD.

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Do the experiences and perceptions of children with chronic non-cancer pain and their families inform the design and delivery of health and social care services, interventions, and future research?

Chronic non-cancer pain in childhood is widespread, affecting 20% to 35% of children and young people worldwide. For a sizeable number of children, chronic non-cancer pain has considerable negative impacts on their lives and quality of life, and leads to increased use of healthcare services and medication. In many countries, there are few services for managing children's chronic non-cancer pain, with many services being inadequate. Fourteen Cochrane Reviews assessing the effects of pharmacological, psychological, psychosocial, dietary or physical activity interventions for managing children's chronic non-cancer pain identified a lack of high-quality evidence to inform pain management. To design and deliver services and interventions that meet the needs of patients and their families, we need to understand how children with chronic non-cancer pain and their families experience pain, their views of services and treatments for chronic pain, and which outcomes are important to them.

1. To synthesise qualitative studies that examine the experiences and perceptions of children with chronic non-cancer pain and their families regarding chronic non-cancer pain, treatments and services to inform the design and delivery of health and social care services, interventions and future research. 2. To explore whether our review findings help to explain the results of Cochrane Reviews of intervention effects of treatments for children's chronic non-cancer pain. 3. To determine if programme theories and outcomes of interventions match children and their families' views of desired treatments and outcomes. 4. To use our findings to inform the selection and design of patient-reported outcome measures for use in chronic non-cancer pain studies and interventions and care provision to children and their families. The review questions are: 1. How do children with chronic non-cancer pain and their families conceptualise chronic pain? 2. How do children with chronic non-cancer pain and their families live with chronic pain? 3. What do children with chronic non-cancer pain and their families think of how health and social care services respond to and manage their child's chronic pain? 4. What do children with chronic non-cancer pain and their families conceptualise as 'good' chronic pain management and what do they want to achieve from chronic pain management interventions and services?

We had high or moderate confidence in the evidence contributing to most review findings. Further research, especially into families' experiences of treatments and services, could strengthen the evidence for low or very low confidence findings. Future research should also explore families' experiences in low- to middle-income contexts; of pain treatments including opioid use in children, which remains controversial; and of social care services. We need development and testing of family-centred interventions and services acceptable to families. Future trials of children's chronic non-cancer pain interventions should include family-centred outcomes.

NOT ENOUGH INFORMATION

MEDIUM

cognitive, mental, and mental health

Does caffeine have a significant advantage over other methylxanthines in preterm infants at risk of apnea, with apnea, or in the peri-extubation phase?

Methylxanthines, including caffeine, theophylline, and aminophylline, work as stimulants of the respiratory drive, and decrease apnea of prematurity, a developmental disorder common in preterm infants. In particular, caffeine has been reported to improve important clinical outcomes, including bronchopulmonary dysplasia (BPD) and neurodevelopmental disability. However, there is uncertainty regarding the efficacy of caffeine compared to other methylxanthines.

To assess the effects of caffeine compared to aminophylline or theophylline in preterm infants at risk of apnea, with apnea, or in the peri-extubation phase.

Although caffeine has been shown to improve important clinical outcomes, in the few studies that compared caffeine to other methylxanthines, there might be little to no difference in mortality, bronchopulmonary dysplasia, and duration of hospital stay. The evidence is very uncertain about the effect of caffeine compared to other methylxanthines on long-term development and side effects. Although caffeine or other methylxanthines are widely used in preterm infants, there is little direct evidence to support the choice of which methylxanthine to use. More research is needed, especially on extremely preterm infants born before 28 weeks of gestation. Data from four ongoing studies might provide more evidence on the effects of caffeine or other methylxanthines.

NOT ENOUGH INFORMATION

LOW

miscellaneous

Does advising a delayed prescription of antibiotics in respiratory tract infections affect duration and/or severity of clinical outcomes, antibiotic use, antibiotic resistance, and patient satisfaction?

Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010, 2013 and 2017.

To evaluate the effects on duration and/or severity of clinical outcomes (pain, malaise, fever, cough and rhinorrhoea), antibiotic use, antibiotic resistance and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections.

For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%; moderate-certainty evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (30% versus 93%). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (13% versus 27%). Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with RTIs, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delayed antibiotics. Where clinicians are not confident in not prescribing antibiotics, delayed antibiotics may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, while maintaining patient safety and satisfaction levels. Further research into antibiotic prescribing strategies for RTIs may best be focused on identifying patient groups at high risk of disease complications, enhancing doctors' communication with patients to maintain satisfaction, ways of increasing doctors' confidence to not prescribe antibiotics for RTIs, and policy measures to reduce unnecessary antibiotic prescribing for RTIs.

NOT ENOUGH INFORMATION

MEDIUM

immune system and infections

Do psychological interventions reduce symptoms of depression in adults and adolescents with congenital heart disease?

Despite improvements in medical care, the quality of life of adults and adolescents with congenital heart disease remains strongly affected by their condition, often leading to depression. Psychotherapy, cognitive behavioural therapy, and other talking therapies may be effective in treating depression in both adults and young adults with congenital heart disease. The aim of this review was to assess the effects of treatments, such as psychotherapy, cognitive behavioural therapies, and talking therapies for treating depression in this population.

To evaluate the effects (both harms and benefits) of psychological interventions for reducing symptoms of depression in adolescents (aged 10 to 17 years) and adults with congenital heart disease. Psychological interventions include cognitive behavioural therapy, psychotherapy, or 'talking/counselling' therapy for depression.

Psychological interventions may reduce depression in adults with congenital heart disease compared to usual care. However, the certainty of the evidence is low. Further research is needed to establish the role of psychological interventions in this population, defining the optimal duration, method of administration, and number of sessions required to obtain the greatest benefit.

SUPPORTED

LOW

cognitive, mental, and mental health

Did newborn infants receiving positive pressure ventilation with a nasal interface in the delivery room have reduced mortality and morbidity compared to using a face mask, laryngeal mask airway, or another type of nasal interface?

The Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) makes practice recommendations for the care of newborn infants in the delivery room (DR). ILCOR recommends that all infants who are gasping, apnoeic, or bradycardic (heart rate < 100 per minute) should be given positive pressure ventilation (PPV) with a manual ventilation device (T-piece, self-inflating bag, or flow-inflating bag) via an interface. The most commonly used interface is a face mask that encircles the infant's nose and mouth. However, gas leak and airway obstruction are common during face mask PPV. Nasal interfaces (single and binasal prongs (long or short), or nasal masks) and laryngeal mask airways (LMAs) may also be used to deliver PPV to newborns in the DR, and may be more effective than face masks.

To determine whether newborn infants receiving PPV in the delivery room with a nasal interface compared to a face mask, laryngeal mask airway (LMA), or another type of nasal interface have reduced mortality and morbidity. To assess whether safety and efficacy of the nasal interface differs according to gestational age or ventilation device.

Nasal interfaces were found to offer comparable efficacy to face masks (low- to very low-certainty evidence), supporting resuscitation guidelines that state that nasal interfaces are a comparable alternative to face masks for providing respiratory support in the DR. Resuscitation with a nasal interface may reduce the rate of intubation in the DR when compared with a face mask. However, the evidence is very uncertain. This uncertainty is attributed to the use of a new ventilation system in the nasal interface group in two of the five trials. As such, it is not possible to differentiate separate, specific effects related to the ventilation device or to the interface in these studies.

SUPPORTED

LOW

respiratory system

Can vaccination effectively prevent herpes zoster in older adults?

Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of ageing is associated with a reduction in cellular immunity, and this predisposes older adults to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. Two types of herpes zoster vaccines are currently available. One of them is the single-dose live attenuated zoster vaccine (LZV), which contains the same live attenuated virus used in the chickenpox vaccine, but it has over 14-fold more plaque-forming units of the attenuated virus per dose. The other is the recombinant zoster vaccine (RZV) which does not contain the live attenuated virus, but rather a small fraction of the virus that cannot replicate but can boost immunogenicity. The recommended schedule for the RZV is two doses two months apart. This is an update of a Cochrane Review first published in 2010, and updated in 2012, 2016, and 2019.

To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.

Trial registration:

SUPPORTED

MEDIUM

immune system and infections

Does vitamin D supplementation provide benefits as a treatment for IBD?

Vitamin D possesses immunomodulatory properties and has been implicated in the pathogenesis and severity of inflammatory bowel disease (IBD). Animal studies and emerging epidemiological evidence have demonstrated an association between vitamin D deficiency and worse disease activity. However, the role of vitamin D for the treatment of IBD is unclear.

To evaluate the benefits and harms of vitamin D supplementation as a treatment for IBD.

There may be fewer clinical relapses when comparing vitamin D with placebo, but we cannot draw any conclusions on differences in clinical response, quality of life, or withdrawals, due to very low-certainty evidence. When comparing high and low doses of vitamin D, there were no data for clinical response, but there may be no difference in relapse for CD. We cannot draw conclusions on the other outcomes due to very low certainty evidence. Finally, comparing vitamin D (all doses) to supplemental-dose vitamin D, there were no data on clinical relapse or response, and we could not draw conclusions on other outcomes due to very low certainty evidence or missing data. It is difficult to make any clear recommendations for future research on the basis of the findings of this review. Future studies must be clear on the baseline populations, the purpose of vitamin D treatment, and, therefore, study an appropriate dosing strategy. Stakeholders in the field may wish to reach consensus on such issues prior to new studies.

NOT ENOUGH INFORMATION

LOW

digestive system and metabolism

Can pharmacological interventions during lumbar puncture in newborn infants reduce pain and discomfort compared to no intervention or placebo?

Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an assistant using a strict aseptic technique; it is important to monitor the infant during all the steps of the procedure. Without adequate analgesia, LP can cause considerable pain and discomfort. As newborns have increased sensitivity to pain, it is crucial to adequately manage the procedural pain of LP in this population.

To assess the benefits and harms, including pain, discomfort, and success rate, of any pharmacological intervention during lumbar puncture in newborn infants, compared to placebo, no intervention, non-pharmacological interventions, or other pharmacological interventions.

The evidence is very uncertain about the effect of topical anesthetics (lidocaine) compared to no anesthesia on successful lumbar puncture on first attempt, the number of attempts per lumbar puncture, episodes of bradycardia, episodes of desaturation, and occurrence of apnea. Compared to placebo, topical anesthetics (lidocaine or EMLA) may reduce pain assessed with the NFCS score. One ongoing study will assess the effects of systemic treatment.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does IVF improve pregnancy outcomes compared to other fertility treatments?

In vitro fertilisation (IVF) is a treatment for unexplained subfertility but is invasive, expensive, and associated with risks.

To evaluate the effectiveness and safety of IVF versus expectant management, unstimulated intrauterine insemination (IUI), and IUI with ovarian stimulation using gonadotropins, clomiphene citrate (CC), or letrozole in improving pregnancy outcomes.

IVF may improve LBR over unstimulated IUI. Data should be interpreted with caution as overall evidence quality was low.

SUPPORTED

LOW

sexual and reproductive health

Did prebiotics show benefits for improving health outcomes in people with CF?

Cystic fibrosis (CF) is a multisystem disease; the importance of growth and nutritional status is well established given their implications for lung function and overall survivability. Furthermore, it has been established that intestinal microbial imbalance and inflammation are present in people with CF. Oral prebiotics are commercially available substrates that are selectively utilised by host intestinal micro-organisms and may improve both intestinal and overall health.

To evaluate the benefits and harms of prebiotics for improving health outcomes in children and adults with CF.

This review did not find any evidence for the use of prebiotics in people with CF. Until such evidence is available, it is reasonable for clinicians to follow any local guidelines and to discuss the use of dietary prebiotics with their patients. Large and robust RCTs assessing the dietary prebiotics of inulin or galacto-oligosaccharides or fructo-oligosaccharides, or any combination of these, are needed. Such studies should be of at least 12 months in duration and assess outcomes such as growth and nutrition, gastrointestinal symptoms, pulmonary exacerbations, lung function, inflammatory biomarkers, hospitalisations, intestinal microbial profiling, and faecal short-chain fatty acids. Trials should include both children and adults and aim to be adequately powered to allow for subgroup analysis by age.

REFUTED

LOW

respiratory system

Does autoinflation have a beneficial effect on otitis media with effusion in children?

Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and mechanical treatment. Autoinflation is a self-administered technique, which aims to ventilate the middle ear and encourage middle ear fluid clearance by providing a positive pressure of air in the nose and nasopharynx (using a nasal balloon or other handheld device). This positive pressure (sometimes combined with simultaneous swallow) encourages opening of the Eustachian tube and may help ventilate the middle ear.

To assess the efficacy (benefits and harms) of autoinflation for the treatment of otitis media with effusion in children.

All the evidence we identified was of low or very low certainty, meaning that we have little confidence in the estimated effects. However, the data suggest that autoinflation may have a beneficial effect on OME-specific quality of life and persistence of OME in the short term, but the effect is uncertain for return to normal hearing and adverse effects. The potential benefits should be weighed against the inconvenience of regularly carrying out autoinflation, and the possible risk of ear pain.

SUPPORTED

LOW

sensory organs

Did ECMO improve mortality compared to conventional cardiopulmonary support in critically ill adults?

Extracorporeal membrane oxygenation (ECMO) may provide benefit in certain populations of adults, including those with severe cardiac failure, severe respiratory failure, and cardiac arrest. However, it is also associated with serious short- and long-term complications, and there remains a lack of high-quality evidence to guide practice. Recently several large randomized controlled trials (RCTs) have been published, therefore, we undertook an update of our previous systematic review published in 2014.

To evaluate whether venovenous (VV), venoarterial (VA), or ECMO cardiopulmonary resuscitation (ECPR) improve mortality compared to conventional cardiopulmonary support in critically ill adults.

In this updated systematic review, which included four additional RCTs, we found that ECMO was associated with a reduction in day-90 to one-year all-cause mortality, as well as three times increased risk of bleeding. However, the certainty of this result was only low to moderate, limited by a low number of small trials, clinical heterogeneity, and indirectness across studies.

SUPPORTED

LOW

cardiovascular system

Does silicone hydrogel SCL have a better effect on comfort, dry eye test results, and adverse events compared to hydrogel SCL?

Ocular discomfort is the leading cause of permanent discontinuation of soft contact lens (SCL) wear. Silicone hydrogel and hydrogel materials are the two major categories of SCLs, with silicone hydrogel materials being newer and more breathable than hydrogel materials. Whether comfort is associated with SCL material is controversial despite numerous studies. Similarly, the difference between these materials in terms of safety outcomes (e.g. frequency of microbial keratitis) is unclear.

To evaluate the comparative effectiveness and safety of silicone hydrogel compared with hydrogel SCLs on self-reported comfort, dry eye test results, and adverse events in SCL-wearing adults 18 years of age or older.

The overall evidence for a difference between all included silicone hydrogel and hydrogel SCLs was of very low certainty, with most trials at high overall risk of bias. The majority of studies did not assess comfort using a validated instrument. There was insufficient evidence to support recommending one SCL material over the other. For extended wear, hydrogel SCL may have a lower risk of adverse events at 52 weeks compared to silicon hydrogel. Future well-designed trials are needed to generate high certainty evidence to further clarify differences in SCL material comfort and safety.

NOT ENOUGH INFORMATION

LOW

sensory organs

Does pravastatin have a dose-related effect on LDL cholesterol?

A detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available.

Primary objective To assess the pharmacology of pravastatin by characterizing the dose-related effect and variability of the effect of pravastatin on the surrogate marker: low-density lipoprotein (LDL cholesterol). The effect of pravastatin on morbidity and mortality is not the objective of this systematic review. Secondary objectives • To assess the dose-related effect and variability of effect of pravastatin on the following surrogate markers: total cholesterol; high-density lipoprotein (HDL cholesterol); and triglycerides. • To assess the effect of pravastatin on withdrawals due to adverse effects.

Pravastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. This review did not provide a good estimate of the incidence of harms associated with pravastatin because of the lack of reporting of adverse effects in 48.4% of the randomized placebo-controlled trials.

SUPPORTED

MEDIUM

cardiovascular system

Can ovulation prediction methods for timing intercourse improve conception in couples trying to conceive?

Many factors influence fertility, one being the timing of intercourse. The 'fertile window' describes a stage in the cycle when conception can occur and is approximately five days before to several hours after ovulation. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile window to increase the likelihood of conception. Methods of predicting ovulation include urinary hormone measurement (luteinising hormone (LH) and oestrogen), fertility awareness-based methods (FABM) (including tracking basal body temperatures, cervical mucus monitoring, calendar charting/tracking apps), and ultrasonography. However, there are potentially negative aspects associated with ovulation prediction, including stress, time consumption, and cost implications of purchasing ovulation kits and app subscriptions. This review considered the evidence from randomised controlled trials (RCTs) evaluating the use of timed intercourse (using ovulation prediction) on pregnancy outcomes.

To evaluate the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive.

The new evidence presented in this review update shows that timed intercourse using urine ovulation tests probably improves live birth and pregnancy rates (clinical or positive urine pregnancy tests but not yet confirmed by ultrasound) in women under 40, trying to conceive for less than 12 months, compared to intercourse without ovulation prediction. However, there are insufficient data to determine the effects of urine ovulation tests on adverse events, clinical pregnancy, time to pregnancy, and quality of life. Similarly, due to limited data, we are uncertain of the effect of FABM on pregnancy outcomes, adverse effects, and quality of life. Further research is therefore required to fully understand the safety and effectiveness of timed intercourse for couples trying to conceive. This research should include studies reporting clinically relevant outcomes such as live birth and adverse effects in fertile and infertile couples and utilise various methods to determine ovulation. Only with a comprehensive understanding of the risks and benefits of timed intercourse can recommendations be made for all couples trying to conceive.

SUPPORTED

MEDIUM

sexual and reproductive health

Does cryotherapy in the acute phase after TKR have a significant effect on blood loss, pain, transfusion rate, range of motion, knee function, adverse events, and withdrawals due to adverse events?

Total knee replacement (TKR) is a common intervention for people with end-stage symptomatic knee osteoarthritis, resulting in significant improvements in pain, function and quality of life within three to six months. It is, however, acutely associated with pain, local oedema and blood loss. Post-operative management may include cryotherapy. This is the application of low temperatures to the skin surrounding the surgical site, through ice or cooled water, often delivered using specialised devices. This is an update of a review published in 2012.

To evaluate the effect of cryotherapy in the acute phase after TKR (within 48 hours after surgery) on blood loss, pain, transfusion rate, range of motion, knee function, adverse events and withdrawals due to adverse events.

The certainty of evidence was low for blood loss, pain and range of motion, and very low for transfusion rate, function, total adverse events and withdrawals from adverse events. We are uncertain whether cryotherapy improves transfusion rate, function, total adverse events or withdrawals from adverse events. We downgraded evidence for bias, indirectness, imprecision and inconsistency. Hence, the potential benefits of cryotherapy on blood loss, pain and range of motion may be too small to justify its use. More well-designed randomised controlled trials focusing especially on clinically meaningful outcomes, such as blood transfusion, and patient-reported outcomes, such as knee function, quality of life, activity level and participant-reported global assessment of success, are required.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Can antioxidant vitamin and mineral supplements slow down the progression of AMD in people with AMD?

Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review.

To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD.

Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.

SUPPORTED

MEDIUM

sensory organs

Does higher versus lower fractions of inspired oxygen have clear effects on various health outcomes in adult ICU patients?

This is an updated review concerning 'Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit'. Supplementary oxygen is provided to most patients in intensive care units (ICUs) to prevent global and organ hypoxia (inadequate oxygen levels). Oxygen has been administered liberally, resulting in high proportions of patients with hyperoxemia (exposure of tissues to abnormally high concentrations of oxygen). This has been associated with increased mortality and morbidity in some settings, but not in others. Thus far, only limited data have been available to inform clinical practice guidelines, and the optimum oxygenation target for ICU patients is uncertain. Because of the publication of new trial evidence, we have updated this review.

To update the assessment of benefits and harms of higher versus lower fractions of inspired oxygen (FiO

In adult ICU patients, it is still not possible to draw clear conclusions about the effects of higher versus lower oxygenation strategies on all-cause mortality, SAEs, quality of life, lung injuries, myocardial infarction, stroke, and sepsis at maximum follow-up. This is due to low or very low-certainty evidence.

NOT ENOUGH INFORMATION

LOW

respiratory system

Does machine perfusion technology provide superior clinically relevant outcomes compared to traditional static cold storage in people undergoing liver transplantation?

Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box).

To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation.

In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.

SUPPORTED

HIGH

digestive system and metabolism

Do different smoking cessation pharmacotherapies and e-cigarettes have comparative benefits, harms, and tolerability when used to help people stop smoking tobacco?

Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies.

To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco.

The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.

SUPPORTED

HIGH

respiratory system

Does shift schedule adaptation affect sleep quality, sleep duration, and sleepiness among shift workers?

Shift work is associated with insufficient sleep, which can compromise worker alertness with ultimate effects on occupational health and safety. Adapting shift work schedules may reduce adverse occupational outcomes.

To assess the effects of shift schedule adaptation on sleep quality, sleep duration, and sleepiness among shift workers.

Forward and faster rotation may reduce sleepiness during shifts, and may make no difference to sleep quality, but the evidence is very uncertain. Very low-certainty evidence indicated that sleep duration off-shift decreases with faster rotation. Low-certainty evidence indicated that on-duty workweeks with shift duration limited to 16 hours increases sleep duration, with moderate-certainty evidence for minimal reductions in sleepiness. Changes in shift duration and compression of workweeks had no effect on sleep or sleepiness, but the evidence was of very low-certainty. No evidence is available for other shift schedule changes. There is a need for more high-quality studies (preferably RCTs) for all shift schedule interventions to draw conclusions on the effects of shift schedule adaptations on sleep and sleepiness in shift workers.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does platinum-based chemotherapy improve long-term outcomes in early triple-negative breast cancer?

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with shorter survival and a higher likelihood of the cancer returning. In early TNBC, platinum-based chemotherapy has been shown to improve pathological complete response (pCR); however, its effect on long-term survival outcomes has not been fully elucidated and recommendations to include platinum chemotherapy are not consistent in international guidelines.

To evaluate the benefits and harms of platinum-based chemotherapy as adjuvant and neoadjuvant treatment in people with early triple-negative breast cancer.

Platinum-based chemotherapy using carboplatin in the adjuvant or neoadjuvant setting improves long-term outcomes of DFS and OS in early TNBC, with no evidence of differences by subgroup. This was at the cost of more frequent chemotherapy delays and dose reductions, and greater haematological toxicity, though serious adverse events including neuropathy, febrile neutropenia or treatment-related death were not increased. These findings support the use of platinum-based chemotherapy for people with early TNBC. The optimal dose and regimen are not defined by this analysis, but there is a suggestion that similar relative benefits result from the addition of carboplatin to either anthracycline-free regimens or those containing anthracycline agents.

SUPPORTED

MEDIUM

cancer

Does cell salvage effectively minimize the need for allogeneic red blood cell transfusion in adults undergoing elective or non-urgent surgery?

Concerns regarding the safety and availability of transfused donor blood have prompted research into a range of techniques to minimise allogeneic transfusion requirements. Cell salvage (CS) describes the recovery of blood from the surgical field, either during or after surgery, for reinfusion back to the patient.

To examine the effectiveness of CS in minimising perioperative allogeneic red blood cell transfusion and on other clinical outcomes in adults undergoing elective or non-urgent surgery.

In some types of elective surgery, cell salvage may reduce the need for and volume of allogeneic transfusion, alongside evidence of no difference in adverse events, when compared to no cell salvage. Further research is required to establish why other surgeries show no benefit from CS, through further analysis of the current evidence. More large RCTs in under-reported specialities are needed to expand the evidence base for exploring the impact of CS.

SUPPORTED

MEDIUM

miscellaneous

Can multivariable prognostic models accurately quantify the risk of clinical disease progression, worsening, and activity in adults with MS?

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects millions of people worldwide. The disease course varies greatly across individuals and many disease-modifying treatments with different safety and efficacy profiles have been developed recently. Prognostic models evaluated and shown to be valid in different settings have the potential to support people with MS and their physicians during the decision-making process for treatment or disease/life management, allow stratified and more precise interpretation of interventional trials, and provide insights into disease mechanisms. Many researchers have turned to prognostic models to help predict clinical outcomes in people with MS; however, to our knowledge, no widely accepted prognostic model for MS is being used in clinical practice yet.

To identify and summarise multivariable prognostic models, and their validation studies for quantifying the risk of clinical disease progression, worsening, and activity in adults with MS.

The current evidence is not sufficient for recommending the use of any of the published prognostic prediction models for people with MS in clinical routine today due to lack of independent external validations. The MS prognostic research community should adhere to the current reporting and methodological guidelines and conduct many more state-of-the-art external validation studies for the existing or newly developed models.

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cognitive, mental, and mental health

Did the systematic review find similar sensitivity and precision in the search filters for retrieving reports of systematic reviews in MEDLINE and Embase?

Bibliographic databases provide access to an international body of scientific literature in health and medical sciences. Systematic reviews are an important source of evidence for clinicians, researchers, consumers, and policymakers as they address a specific health-related question and use explicit methods to identify, appraise and synthesize evidence from which conclusions can be drawn and decisions made. Methodological search filters help database end-users search the literature effectively with different levels of sensitivity and specificity. These filters have been developed for various study designs and have been found to be particularly useful for intervention studies. Other filters have been developed for finding systematic reviews. Considering the variety and number of available search filters for systematic reviews, there is a need for a review of them in order to provide evidence about their retrieval properties at the time they were developed.

To review systematically empirical studies that report the development, evaluation, or comparison of search filters to retrieve reports of systematic reviews in MEDLINE and Embase.

Studies reporting the development, evaluation, or comparison of search filters to retrieve reports of systematic reviews in MEDLINE showed similar sensitivity and precision, with one filter showing higher levels of specificity. For Embase, filters showed variable sensitivity and precision, with limited information about how the filter was produced, which leaves us uncertain about their performance assessments. Newer filters had limitations in their methods or scope, including very focused subject topics for their gold standards, limiting their applicability across other topics. Our findings highlight that consensus guidance on the conduct of search filters and standardized reporting of search filters are needed, as we found highly heterogeneous development methods, accuracy assessments and outcome selection. New strategies adaptable across interfaces could enhance their usability. Moreover, the performance of existing filters needs to be evaluated in light of the impact of reporting guidelines, including the PRISMA 2009, on how systematic reviews are reported. Finally, future filter developments should also consider comparing the filters against a common reference set to establish comparative performance and assess the quality of systematic reviews retrieved by strategies.

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cognitive, mental, and mental health

Do music and vocal interventions improve physiological and neurodevelopmental outcomes in preterm infants compared to standard care?

Preterm birth interferes with brain maturation, and subsequent clinical events and interventions may have additional deleterious effects. Music as therapy is offered increasingly in neonatal intensive care units aiming to improve health outcomes and quality of life for both preterm infants and the well-being of their parents. Systematic reviews of mixed methodological quality have demonstrated ambiguous results for the efficacy of various types of auditory stimulation of preterm infants. A more comprehensive and rigorous systematic review is needed to address controversies arising from apparently conflicting studies and reviews.

We assessed the overall efficacy of music and vocal interventions for physiological and neurodevelopmental outcomes in preterm infants (< 37 weeks' gestation) compared to standard care. In addition, we aimed to determine specific effects of various interventions for physiological, anthropometric, social-emotional, neurodevelopmental short- and long-term outcomes in the infants, parental well-being, and bonding.

Music/vocal interventions do not increase oxygen saturation during and probably not after the intervention compared to standard care. The evidence suggests that music and voice do not increase infant development (BSID) or reduce parental state-trait anxiety. The intervention probably does not reduce respiratory rate in preterm infants. However, music/vocal interventions probably reduce heart rates in preterm infants during the intervention, and this beneficial effect is even stronger after the intervention, demonstrating that music/vocal interventions reduce heart rates in preterm infants post-intervention. We found no reports of adverse effects from music and voice. Due to low-certainty evidence for all other outcomes, we could not draw any further conclusions regarding overall efficacy nor the possible impact of different intervention types, frequencies, or durations. Further research with more power, fewer risks of bias, and more sensitive and clinically relevant outcomes are needed.

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cognitive, mental, and mental health

Does fortification of condiments and seasonings with iron alone or iron plus other micronutrients have a positive impact on iron deficiency, anaemia, and health-related outcomes in the general population?

Anaemia affects approximately 1.8 billion people worldwide; over 60% of anaemia cases globally are due to iron deficiency (ID). Iron deficiency and anaemia contribute to the global burden of disease and affect physical and cognitive development in children, and work productivity and economic well-being in adults. Fortification of food with iron, alone or in combination with other nutrients, is an effective intervention to control ID. Condiments and seasonings are ideal food vehicles for iron fortification in countries where they are commonly used.

To determine the effects and safety of condiment and seasoning fortification with iron alone or iron plus other micronutrients on iron deficiency, anaemia, and health-related outcomes in the general population.

We are uncertain whether consuming iron-fortified condiments/seasonings reduces anaemia, improves haemoglobin concentration, or improves ferritin concentration. It may reduce ID. Findings about ferritin should be interpreted with caution since its concentrations increase during inflammation. Consuming condiments/seasonings fortified with iron plus other micronutrients may reduce anaemia, and we are uncertain whether this will improve haemoglobin concentration or ferritin concentration. More studies are needed to determine the true effect of iron-fortified condiments/seasonings on preventing anaemia and improving health. The effects of this intervention on other health outcomes like malaria incidence, growth and development are unclear.

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nutrition and dietary supplements

Do specific factors influence a person's decision to participate in a vaccine trial during a pandemic or epidemic?

The World Health Organization declared the COVID-19 pandemic on 11 March 2020. Vaccine development and deployment were swiftly prioritised as a method to manage and control disease spread. The development of an effective vaccine relies on people's participation in randomised trials. Recruitment to vaccine trials is particularly challenging as it involves healthy volunteers who may have concerns around the potential risks and benefits associated with rapidly developed vaccines.

To explore the factors that influence a person's decision to participate in a vaccine trial in the context of a pandemic or epidemic.

This review identifies many of the factors that influence a person's decision to take part in a vaccine trial, and these reflect findings from reviews that examine trials more broadly. However, we also recognise some factors that become more important in connection with a vaccine trial in the context of a pandemic or epidemic. These factors include the potential stigma of taking part, the possible adverse effects of a vaccine, the added motivation for helping society, the role of community leaders in trial dissemination, and the level of trust placed in governments and companies developing vaccines. These specific influences need to be considered by trial teams when designing, and communicating about, vaccine trials in the context of a pandemic or epidemic.

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immune system and infections

Does sucrose effectively relieve pain from heel lance in neonates?

Sucrose has been examined for calming and pain-relieving effects in neonates for invasive procedures such as heel lance.

To assess the effectiveness of sucrose for relieving pain from heel lance in neonates in terms of immediate and long-term outcomes SEARCH METHODS: We searched (February 2022): CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and three trial registries.

Sucrose compared to control probably results in a reduction of PIPP scores 30 and 60 seconds after single heel lances (moderate-certainty evidence). Evidence is very uncertain about the effect of sucrose compared to NNS, breastfeeding, laser acupuncture, facilitated tucking, and the effect of sucrose + NNS compared to NNS in reducing pain. Sucrose compared to glucose, expressed breast milk, and skin-to-skin care shows little to no difference in pain scores. Sucrose combined with other nonpharmacologic interventions should be used with caution, given the uncertainty of evidence.

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MEDIUM

miscellaneous

Did interventions for fatigue in people receiving dialysis, including pharmacological and non-pharmacological approaches, have a significant effect on reducing fatigue?

Fatigue is a common and debilitating symptom in people receiving dialysis that is associated with an increased risk of death, cardiovascular disease and depression. Fatigue can also impair quality of life (QoL) and the ability to participate in daily activities. Fatigue has been established by patients, caregivers and health professionals as a core outcome for haemodialysis (HD).

We aimed to evaluate the effects of pharmacological and non-pharmacological interventions on fatigue in people with kidney failure receiving dialysis, including HD and peritoneal dialysis (PD), including any setting and frequency of the dialysis treatment.

Exercise, aromatherapy, massage and acupressure may improve fatigue compared to placebo, standard care or no intervention. Pharmacological and other non-pharmacological interventions had uncertain effects on fatigue or fatigue-related outcomes in people receiving dialysis. Future adequately powered, high-quality studies are likely to change the estimated effects of interventions for fatigue and fatigue-related outcomes in people receiving dialysis.

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renal and urinary system

Does different strategies of follow-up in women with epithelial ovarian cancer following completion of primary treatment have potential effects?

This is an update of a previous Cochrane Review, last updated in 2014. Ovarian cancer is the eighth most common cancer and seventh most common cause of death due to cancer in women worldwide. Traditionally, most women who have been treated for cancer undergo long-term follow-up in secondary care. However, it has been suggested that the use of routine review may not be effective in improving survival, or health-related quality of life (HRQOL), or relieving anxiety. In addition, traditional follow-up may not be cost-effective.

To compare the potential effects of different strategies of follow-up in women with epithelial ovarian cancer, following completion of primary treatment.

Limited evidence from one trial suggests that routine surveillance with CA125 in asymptomatic women and treatment at CA125-defined relapse does not seem to offer survival advantage when compared to treatment at symptomatic relapse. However, this study pre-dates the use of PARPi maintenance treatment and the increased use of secondary cytoreductive surgery, so the results may be limited in their applicability to current practice. Limited evidence from one trial suggests that individualised nurse-led follow-up may improve HRQOL in women with ovarian cancer following completion of primary treatment. Large RCTs are needed to compare different types of follow-up, looking at survival, HRQOL, psychological effects, and cost as outcomes.

NOT ENOUGH INFORMATION

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cancer

Does the efficacy and safety of high-dose dexamethasone, moderate-dose dexamethasone, low-dose dexamethasone, hydrocortisone, and placebo in preventing BPD, death, and other relevant morbidities differ?

Despite considerable improvement in outcomes for preterm infants, rates of bronchopulmonary dysplasia (BPD) remain high, affecting an estimated 33% of very low birthweight infants, with corresponding long-term respiratory and neurosensory issues. Systemic corticosteroids can address the inflammation underlying BPD, but the optimal regimen for prevention of this disease, balancing of the benefits with the potentially meaningful risks of systemic corticosteroids, continues to be a medical quandary. Numerous studies have shown that systemic corticosteroids, particularly dexamethasone and hydrocortisone, effectively treat or prevent BPD. However, concerning short and long-term side effects have been reported and the optimal approach to corticosteroid treatment remains unclear.

To determine whether differences in efficacy and safety exist between high-dose dexamethasone, moderate-dose dexamethasone, low-dose dexamethasone, hydrocortisone, and placebo in the prevention of BPD, death, the composite outcome of death or BPD, and other relevant morbidities, in preterm infants through a network meta-analysis, generating both pairwise comparisons between all treatments and rankings of the treatments.

While early treatment with moderate-dose dexamethasone or late treatment with high-dose dexamethasone may lead to the best effects for survival without BPD, the certainty of the evidence is low. There is insufficient evidence to guide this therapy with regard to plausible adverse long-term outcomes. Further RCTs with direct comparisons between systemic corticosteroid treatments are needed to determine the optimal treatment approach, and these studies should be adequately powered to evaluate survival without major neurosensory disability.

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respiratory system

Did psychosocial interventions effectively reduce antipsychotic medication use in care home residents?

Antipsychotic medications are regularly prescribed in care home residents for the management of behavioural and psychological symptoms of dementia (BPSD) despite questionable efficacy, important adverse effects, and available non-pharmacological interventions. Prescription rates are related to organisational factors, staff training and job satisfaction, patient characteristics, and specific interventions. Psychosocial intervention programmes aimed at reducing the prescription of antipsychotic drugs are available. These programmes may target care home residents (e.g. improving communication and interpersonal relationships) or target staff (e.g. by providing skills for caring for people with BPSD). Therefore, this review aimed to assess the effectiveness of these interventions, updating our earlier review published in 2012.

To evaluate the benefits and harms of psychosocial interventions to reduce antipsychotic medication use in care home residents compared to regular care, optimised regular care, or a different psychosocial intervention.

All included interventions were complex and the components of the interventions differed considerably between studies. Interventions and intervention components were mostly not described in sufficient detail. Two studies found evidence that the complex psychosocial interventions may reduce antipsychotic medication use. In addition, one study showed that medication review might have some impact on antipsychotic prescribing rates. There were no important adverse events. Overall, the available evidence does not allow for clear generalisable recommendations.

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cognitive, mental, and mental health

Does elective neck dissection of clinically negative neck nodes at the time of removal of the primary oral cavity tumor lead to increased survival and reduced locoregional recurrence?

Surgery is a common treatment option in oral cavity cancer (and less frequently in oropharyngeal cancer) to remove the primary tumour and sometimes neck lymph nodes. People with early-stage disease may undergo surgery alone or surgery plus radiotherapy, chemotherapy, immunotherapy/biotherapy, or a combination of these. Timing and extent of surgery varies. This is the third update of a review originally published in 2007.

To evaluate the relative benefits and harms of different surgical treatment modalities for oral cavity and oropharyngeal cancers.

We found moderate-certainty evidence based on five trials that elective neck dissection of clinically negative neck nodes at the time of removal of the primary oral cavity tumour is superior to therapeutic neck dissection, with increased survival and disease-free survival, and reduced locoregional recurrence. There was moderate-certainty evidence from one trial of no difference between positron emission tomography (PET-CT) following chemoradiotherapy versus planned neck dissection in terms of overall survival or locoregional recurrence. The evidence for each of the other seven comparisons came from only one or two studies and was assessed as low or very low-certainty.

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cancer

Does prenatal exposure to certain anti-seizure medications affect the prevalence of major congenital malformations in the child?

Prenatal exposure to certain anti-seizure medications (ASMs) is associated with an increased risk of major congenital malformations (MCM). The majority of women with epilepsy continue taking ASMs throughout pregnancy and, therefore, information on the potential risks associated with ASM treatment is required.

To assess the effects of prenatal exposure to ASMs on the prevalence of MCM in the child.

Exposure in the womb to certain ASMs was associated with an increased risk of certain MCMs which, for many, is dose-dependent.

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cognitive, mental, and mental health

Does exercise therapy for acute non-specific low back pain in adults have a clinically relevant effect on pain or functional status in the short term?

Low back pain (LBP) is the leading cause of disability globally. It generates considerable direct costs (healthcare) and indirect costs (lost productivity). The many available treatments for LBP include exercise therapy, which is practised extensively worldwide.

To evaluate the benefits and harms of exercise therapy for acute non-specific low back pain in adults compared to sham/placebo treatment or no treatment at short-term, intermediate-term, and long-term follow-up.

Exercise therapy compared to sham/placebo treatment may have no clinically relevant effect on pain or functional status in the short term in people with acute non-specific LBP, but the evidence is very uncertain. Exercise therapy compared to no treatment may have no clinically relevant effect on pain or functional status in the short term in people with acute non-specific LBP, but the evidence is very uncertain. We downgraded the certainty of the evidence to very low for inconsistency, risk of bias concerns, and imprecision (few participants).

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musculoskeletal system and dermatology

Did lay health workers' treatment of severe wasting in children lead to similar or slightly poorer outcomes compared to treatment by health professionals?

Since the early 2010s, there has been a push to enhance the capacity to effectively treat wasting in children through community-based service delivery models and thus reduce morbidity and mortality.

To assess the effectiveness of identification and treatment of moderate and severe wasting in children aged five years or under by lay health workers working in the community compared with health providers working in health facilities.

Identification and treatment of severe wasting in children who do not require inpatient care by LHWs, compared with treatment by health professionals, may lead to similar or slightly poorer outcomes. We found only two RCTs, and the evidence from non-randomised studies was of very low certainty for all outcomes due to serious risks of bias and imprecision. No studies included children aged under 6 months. Future studies must address these methodological issues.

NOT ENOUGH INFORMATION

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nutrition and dietary supplements

Do remotely-delivered psychological therapies provide benefits for the management of chronic pain in adults?

Chronic pain (pain lasting three months or more) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Common types (excluding headache) include back pain, fibromyalgia, and neuropathic pain. Access to traditional face-to-face therapies can be restricted by healthcare resources, geography, and cost. Remote technology-based delivery of psychological therapies has the potential to overcome treatment barriers. However, their therapeutic effectiveness compared to traditional delivery methods requires further investigation.

To determine the benefits and harms of remotely-delivered psychological therapies compared to active control, waiting list, or treatment as usual for the management of chronic pain in adults.

Currently, evidence about remotely-delivered psychological therapies is largely limited to Internet-based delivery of CBT. We found evidence that remotely-delivered CBT has small benefits for pain intensity (moderate certainty) and functional disability (moderate to low certainty) in adults experiencing chronic pain. Benefits were not maintained at follow-up. Our appraisal of quality of life and adverse events outcomes post-treatment were limited by study numbers, evidence certainty, or both. We found limited research (mostly low to very low certainty) exploring other psychological therapies (i.e. ACT). More high-quality studies are needed to assess the broad translatability of psychological therapies to remote delivery, the different delivery technologies, treatment longevity, comparison with active control, and adverse events.

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cognitive, mental, and mental health

Does breastfeeding or supplemental breast milk reduce procedural pain in neonates?

Pain in the neonate is associated with acute behavioural and physiological changes. Cumulative pain is associated with morbidities, including adverse neurodevelopmental outcomes. Studies have shown a reduction in changes in physiological parameters and pain score measurements following pre-emptive analgesic administration in neonates experiencing pain or stress. Non-pharmacological measures (such as holding, swaddling and breastfeeding) and pharmacological measures (such as acetaminophen, sucrose and opioids) have been used for analgesia. This is an update of a review first published in 2006 and updated in 2012.

The primary objective was to evaluate the effectiveness of breastfeeding or supplemental breast milk in reducing procedural pain in neonates. The secondary objective was to conduct subgroup analyses based on the type of control intervention, gestational age and the amount of supplemental breast milk given.

Moderate-/low-certainty evidence suggests that breastfeeding or supplemental breast milk may reduce pain in neonates undergoing painful procedures compared to no intervention/positioning/holding or placebo or non-pharmacological interventions. Low-certainty evidence suggests that moderate concentration (20% to 33%) glucose/sucrose may lead to little or no difference in reducing pain compared to breastfeeding. The effectiveness of breast milk for painful procedures should be studied in the preterm population, as there are currently a limited number of studies that have assessed its effectiveness in this population.

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sexual and reproductive health

Is one surgical approach to hysterectomy for benign gynaecological conditions more effective and safe than another?

Currently, there are five major approaches to hysterectomy for benign gynaecological disease: abdominal hysterectomy (AH), vaginal hysterectomy (VH), laparoscopic hysterectomy (LH), robotic-assisted hysterectomy (RH) and vaginal natural orifice hysterectomy (V-NOTES). Within the LH category we further differentiate the laparoscopic-assisted vaginal hysterectomy (LAVH) from the total laparoscopic hysterectomy (TLH) and single-port laparoscopic hysterectomy (SP-LH).

To assess the effectiveness and safety of different surgical approaches to hysterectomy for women with benign gynaecological conditions.

Among women undergoing hysterectomy for benign disease, VH appears to be superior to AH. When technically feasible, VH should be performed in preference to AH because it is associated with faster return to normal activities, fewer wound/abdominal wall infections and shorter hospital stay. Where VH is not possible, LH has advantages over AH including faster return to normal activities, shorter hospital stay, and decreased risk of wound/abdominal wall infection, febrile episodes or unspecified infection, and transfusion. These advantages must be balanced against the increased risk of ureteric injury and longer operative time. When compared to LH, VH was associated with no difference in time to return to normal activities but shorter operative time and shorter hospital stay. RH and V-NOTES require further evaluation since there is a lack of evidence of any patient benefit over conventional LH. Overall, the evidence in this review has to be interpreted with caution as adverse event rates were low, resulting in low power for these comparisons. The surgical approach to hysterectomy should be discussed with the patient and decided in the light of the relative benefits and hazards. Surgical expertise is difficult to quantify and poorly reported in the available studies and this may influence outcomes in ways that cannot be accounted for in this review. In conclusion, when VH is not feasible, LH has multiple advantages over AH, but at the cost of more ureteric injuries. Evidence is limited for RH and V-NOTES.

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sexual and reproductive health

Do pharmacological treatments provide significant benefits for infants and children with gastro-oesophageal reflux (GOR)?

Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary and secondary care, affecting approximately 50% of infants under three months old. The natural history of GOR in infancy is generally of a self-limiting condition that improves with age, but older children and children with co-existing medical conditions can have more protracted symptoms. The distinction between gastro-oesophageal reflux disease (GORD) and GOR is debated. Current National Institute of Health and Care Excellence (NICE) guidelines define GORD as GOR causing symptoms severe enough to merit treatment. This is an update of a review first published in 2014.

To assess the effects of pharmacological treatments for GOR in infants and children.

There is very low-certainty evidence about symptom improvements and changes in pH indices for infants. There are no summary data for endoscopic changes. Medications may or may not provide a benefit (based on very low-certainty evidence) for infants whose symptoms remain bothersome, despite nonmedical interventions or parental reassurance. If a medication is required, there is no clear evidence based on summary data for omeprazole, esomeprazole (in neonates), H₂antagonists, and alginates for symptom improvements (very low-certainty evidence). Further studies with longer follow-up are needed. In older children with GORD, in studies with summary data extracted, there is very low-certainty evidence that PPIs (rabeprazole and pantoprazole) may or may not improve GORD outcomes. No robust data exist for other medications. Further RCT evidence is required in all areas, including subgroups (preterm babies and children with neurodisabilities).

NOT ENOUGH INFORMATION

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digestive system and metabolism

Does hormone therapy affect sexual function in perimenopausal and postmenopausal women?

The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints. This review is an update of a review first published in 2013.

We aimed to assess the effect of hormone therapy on sexual function in perimenopausal and postmenopausal women.

Hormone therapy treatment with estrogen alone probably slightly improves the sexual function composite score in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), and in unselected postmenopausal women, especially in the lubrication, pain, and satisfaction domains. We are uncertain whether estrogen combined with progestogens improves the sexual function composite score in unselected postmenopausal women. Evidence regarding other hormone therapies (synthetic steroids and SERMs) is of very low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest the beneficial effects of synthetic steroids (for example tibolone) or SERMs alone or combined with estrogen on sexual function. More studies that evaluate the effect of estrogen combined with progestogens, synthetic steroids, SERMs, and SERMs combined with estrogen would improve the quality of the evidence for the effect of these treatments on sexual function in perimenopausal and postmenopausal women.

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endocrine system and hormones

Do red flags have diagnostic accuracy in screening for vertebral fracture in people with low back pain?

Low back pain is a common presentation across different healthcare settings. Clinicians need to confidently be able to screen and identify people presenting with low back pain with a high suspicion of serious or specific pathology (e.g. vertebral fracture). Patients identified with an increased likelihood of having a serious pathology will likely require additional investigations and specific treatment. Guidelines recommend a thorough history and clinical assessment to screen for serious pathology as a cause of low back pain. However, the diagnostic accuracy of recommended red flags (e.g. older age, trauma, corticosteroid use) remains unclear, particularly those used to screen for vertebral fracture.

To assess the diagnostic accuracy of red flags used to screen for vertebral fracture in people presenting with low back pain. Where possible, we reported results of red flags separately for different types of vertebral fracture (i.e. acute osteoporotic vertebral compression fracture, vertebral traumatic fracture, vertebral stress fracture, unspecified vertebral fracture).

The available evidence suggests that only a few red flags are potentially useful in guiding clinical decisions to further investigate people suspected to have a vertebral fracture. Most red flags were not useful as screening tools to identify vertebral fracture in people with low back pain. In primary care, 'older age' was informative for 'unspecified vertebral fracture', and 'trauma' and 'corticosteroid use' were both informative for 'unspecified vertebral fracture' and 'osteoporotic vertebral fracture'. In secondary care, 'older age' was informative for 'osteoporotic vertebral fracture' and 'trauma' was informative for 'unspecified vertebral fracture'. In tertiary care, 'presence of contusion/abrasion' was informative for 'vertebral compression fracture'. Combinations of red flags were also informative and may be more useful than individual tests alone. Unfortunately, the challenge to provide clear guidance on which red flags should be used routinely in clinical practice remains. Further research with primary studies is needed to improve and consolidate our current recommendations for screening for vertebral fractures to guide clinical care.

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musculoskeletal system and dermatology

Do specific psychological therapies show clear benefits for severe and enduring anorexia nervosa?

Anorexia nervosa is a psychological condition characterised by self-starvation and fear or wait gain or other body image disturbance. The first line of treatment is specific psychological therapy; however, there is no consensus on best practice for treating people who develop severe and enduring anorexia nervosa (SEAN). Notably, there is no universal definition of SEAN.

To evaluate the benefits and harms of specific psychological therapies for severe and enduring anorexia nervosa compared with other specific therapies, non-specific therapies, no treatment/waiting list, antidepressant medication, dietary counselling alone, or treatment as usual.

This review reports evidence from one trial that evaluated CBT-SEAN versus SSCM-SE. There was very low-certainty evidence of little or no difference in clinical improvement and treatment non-completion between the two therapies. There is a need for larger high-quality trials to determine the benefits of specific psychological therapies for people with SEAN. These should take into account the duration of illness as well as participants' previous experience with evidence-based psychological therapy for anorexia nervosa.

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cognitive, mental, and mental health

Does MHFA training have a significant impact on mental health and well-being, mental health service usage, and adverse effects in the communities where it is delivered?

The prevalence of mental health problems is high, and they have a wide-ranging and deleterious effect on many sectors in society. As well as the impact on individuals and families, mental health problems in the workplace negatively affect productivity. One of the factors that may exacerbate the impact of mental health problems is a lack of 'mental health literacy' in the general population. This has been defined as 'knowledge and beliefs about mental disorders, which aid their recognition, management, or prevention'. Mental Health First Aid (MHFA) is a brief training programme developed in Australia in 2000; its aim is to improve mental health literacy and teach mental health first aid strategies. The course has been adapted for various contexts, but essentially covers the symptoms of various mental health disorders, along with associated mental health crisis situations. The programmes also teach trainees how to provide immediate help to people experiencing mental health difficulties, as well as how to signpost to professional services. It is theorised that improved knowledge will encourage the trainees to provide support, and encourage people to actively seek help, thereby leading to improvements in mental health. This review focuses on the effects of MHFA on the mental health and mental well-being of individuals and communities in which MHFA training has been provided. We also examine the impact on mental health literacy. This information is essential for decision-makers considering the role of MHFA training in their organisations.

To examine mental health and well-being, mental health service usage, and adverse effects of MHFA training on individuals in the communities in which MHFA training is delivered.

We cannot draw conclusions about the effects of MHFA training on our primary outcomes due to the lack of good quality evidence. This is the case whether it is compared to no intervention, to an alternative mental health literacy intervention, or to an active control. Studies are at high risk of bias and often not sufficiently large to be able to detect differences.

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cognitive, mental, and mental health

Does adding a LABA or LAMA to ICS therapy show better efficacy and safety compared to doubling the dose of ICS in adolescents and adults with uncontrolled asthma on medium-dose ICS?

Inhaled corticosteroids (ICS) are the mainstay treatment for persistent asthma. Escalating treatment is required when asthma is not controlled with ICS therapy alone, which would include, but is not limited to, adding a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA) or doubling the dose of ICS.

To assess the efficacy and safety of adding a LABA or LAMA to ICS therapy versus doubling the dose of ICS in adolescents and adults whose asthma is not well controlled on medium-dose (MD)-ICS using a network meta-analysis (NMA), and to provide a ranking of these treatments according to their efficacy and safety.

The review findings suggest that MD- or HD-ICS/LABA and MD-ICS/LAMA reduce moderate to severe asthma exacerbations and increase the odds of ACQ responders compared to MD-ICS whereas HD-ICS probably does not. The evidence is generally stronger for MD- and HD-ICS/LABA than for MD-ICS/LAMA primarily due to a larger evidence base. There is no evidence to suggest that ICS/LABA, ICS/LAMA, or HD-ICS/LABA reduces severe asthma exacerbations or SAEs compared to MD-ICS. MD-ICS/LAMA likely reduces all-cause AEs and results in a slight reduction in treatment discontinuation due to AEs compared to MD-ICS. The above findings may assist in deciding on a treatment option during the stepwise approach of asthma management. Longer-term safety of higher than medium-dose ICS needs to be addressed in phase 4 or observational studies given that the median duration of included studies was six months.

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respiratory system

Can topical repellents alone or in combination with other interventions effectively reduce the incidence of malaria in high- and non-high-risk populations living in endemic areas?

Insecticide-based interventions, such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS), remain the backbone of malaria vector control. These interventions target mosquitoes that prefer to feed and rest indoors, but have limited capacity to prevent transmission that occurs outdoors or outside regular sleeping hours. In low-endemicity areas, malaria elimination will require that these control gaps are addressed, and complementary tools are found. The use of topical repellents may be particularly useful for populations who may not benefit from programmatic malaria control measures, such as refugees, the military, or forest goers. This Cochrane Review aims to measure the effectiveness of topical repellents to prevent malaria infection among high- and non-high-risk populations living in malaria-endemic regions.

To assess the effect of topical repellents alone or in combination with other background interventions (long-lasting insecticide-treated nets, or indoor residual spraying, or both) for reducing the incidence of malaria in high- and non-high-risk populations living in endemic areas.

There is insufficient evidence to conclude that topical repellents can prevent malaria in settings where other vector control interventions are in place. We found the certainty of evidence for all outcomes to be low, primarily due to the risk of bias. A protective effect was suggested among high-risk populations, specially refugees, who might not have access to other standard vector control measures. More adequately powered clinical trials carried out in refugee camps could provide further information on the potential benefit of topical repellents in this setting. Individually randomized studies are also likely necessary to understand whether topical repellents have an effect on personal protection, and the degree to which diversion to non-protected participants affects overall transmission dynamics. Despite this, the potential additional benefits of topical repellents are most likely limited in contexts where other interventions are available.

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immune system and infections

Is paracetamol or NSAIDs, alone or combined, more effective than placebo or no treatment in relieving pain in children with AOM?

Acute otitis media (AOM) is one of the most common childhood infectious diseases. Pain is the key symptom of AOM and central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management. This is an update of a review first published in 2016.

Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs as compared with paracetamol in children with AOM.

Despite explicit guideline recommendations on the use of analgesics in children with AOM, the current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in children with AOM is limited. Paracetamol and ibuprofen as monotherapies may be more effective than placebo in relieving short-term ear pain in children with AOM. The evidence is very uncertain for the effect of ibuprofen versus paracetamol on relieving short-term ear pain in children with AOM, as well as for the effectiveness of ibuprofen plus paracetamol versus paracetamol alone, thereby preventing any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Do blue-light filtering lenses improve visual performance, provide macular protection, and improve sleep quality in adults?

'Blue-light filtering', or 'blue-light blocking', spectacle lenses filter ultraviolet radiation and varying portions of short-wavelength visible light from reaching the eye. Various blue-light filtering lenses are commercially available. Some claims exist that they can improve visual performance with digital device use, provide retinal protection, and promote sleep quality. We investigated clinical trial evidence for these suggested effects, and considered any potential adverse effects.

To assess the effects of blue-light filtering lenses compared with non-blue-light filtering lenses, for improving visual performance, providing macular protection, and improving sleep quality in adults.

This systematic review found that blue-light filtering spectacle lenses may not attenuate symptoms of eye strain with computer use, over a short-term follow-up period, compared to non-blue-light filtering lenses. Further, this review found no clinically meaningful difference in changes to CFF with blue-light filtering lenses compared to non-blue-light filtering lenses. Based on the current best available evidence, there is probably little or no effect of blue-light filtering lenses on BCVA compared with non-blue-light filtering lenses. Potential effects on sleep quality were also indeterminate, with included trials reporting mixed outcomes among heterogeneous study populations. There was no evidence from RCT publications relating to the outcomes of contrast sensitivity, colour discrimination, discomfort glare, macular health, serum melatonin levels, or overall patient visual satisfaction. Future high-quality randomised trials are required to define more clearly the effects of blue-light filtering lenses on visual performance, macular health and sleep, in adult populations.

REFUTED

LOW

sensory organs

Do prophylactic anticoagulants result in little or no difference in outcomes compared to placebo or no treatment in non-hospitalised people with COVID-19?

The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare systems worldwide. Multiple reports on thromboembolic complications related to COVID-19 have been published, and researchers have described that people with COVID-19 are at high risk for developing venous thromboembolism (VTE). Anticoagulants have been used as pharmacological interventions to prevent arterial and venous thrombosis, and their use in the outpatient setting could potentially reduce the prevalence of vascular thrombosis and associated mortality in people with COVID-19. However, even lower doses used for a prophylactic purpose may result in adverse events such as bleeding. It is important to consider the evidence for anticoagulant use in non-hospitalised people with COVID-19.

To evaluate the benefits and harms of prophylactic anticoagulants versus active comparators, placebo or no intervention, or non-pharmacological interventions in non-hospitalised people with COVID-19.

We found low- to moderate-certainty evidence from five RCTs that prophylactic anticoagulants result in little or no difference in major bleeding, DVT, need for hospitalisation, or adverse events when compared with placebo or no treatment in non-hospitalised people with COVID-19. Low-certainty evidence indicates that prophylactic anticoagulants may result in little or no difference in all-cause mortality when compared with placebo or no treatment, but moderate-certainty evidence indicates that prophylactic anticoagulants probably reduce the incidence of VTE and PE. Low-certainty evidence suggests that comparing different doses of the same prophylactic anticoagulant may result in little or no difference in need for hospitalisation or adverse events. Prophylactic anticoagulants may result in little or no difference in risk of VTE, hospitalisation, or adverse events when compared with antiplatelet agents (low-certainty evidence). Given that there were only short-term data from one study, these results should be interpreted with caution. Additional trials of sufficient duration are needed to clearly determine any effect on clinical outcomes.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Does hyperbaric oxygen therapy (HBOT) benefit late radiation tissue injury (LRTI) compared to regimens that exclude HBOT?

This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy.

To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT.

These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

SUPPORTED

LOW

cancer

Do hydrogel dressings have a significant effect on healing donor site wounds following split-thickness skin grafts?

Donor site wounds of split-thickness skin grafts can be a major cause of morbidity. Choosing the appropriate dressing for these wounds is crucial to successful healing. Various types of dressing are available, including hydrogel dressings. A review of current evidence is required to guide clinical decision-making on the choice of dressing for the treatment of donor sites of split-thickness skin grafts.

To assess the effects of hydrogel dressings on donor site wounds following split-thickness skin grafts for wound healing.

There is insufficient evidence to determine the effect of hydrogel dressings on donor site wounds of split thickness skin grafts compared with other types of dressings. There is a need for adequately powered and well-designed RCTs, with adequate sample sizes, types of populations and subgroups, types of interventions, and outcomes, that compare hydrogel dressings with other treatment options in the treatment of donor site wounds of split-thickness skin grafts.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Is ICSI more effective and safer than c-IVF in couples with males presenting with normal total sperm count and motility?

Starting over 40 years ago, in vitro fertilisation (IVF) has become the cornerstone for fertility treatment. Since then, in 1992, Palermo and colleagues successfully applied the technique intracytoplasmic sperm injection (ICSI) to benefit couples where conventional in vitro fertilisation (c-IVF) and sub-zonal insemination (SUZI) proved unsuccessful. After this case report, ICSI has become the treatment of choice for couples with severe male factor subfertility. Over time, ICSI has been used in the treatment of couples with mild male and even unexplained infertility. This review is an update of the review, first published in 1999, comparing ICSI with c-IVF for couples with males presenting with normal total sperm count and motility.

To evaluate the effectiveness and safety of ICSI relative to c-IVF in couples with males presenting with normal total sperm count and motility.

The current available studies that compare ICSI and c-IVF in couples with males presenting with normal total sperm count and motility, show neither method was superior to the other, in achieving live birth, adverse events (multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity), also alongside secondary outcomes, clinical pregnancy, viable intrauterine pregnancy or miscarriage.

NOT ENOUGH INFORMATION

LOW

sexual and reproductive health

Does enteral tube feeding, including percutaneous endoscopic gastrostomy, improve survival, nutritional status, and quality of life in people with ALS compared to oral feeds without enteral tube feeding?

Maintaining adequate nutrition is critical for people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND). Enteral tube feeding is offered to people experiencing difficulty swallowing (dysphagia) to prevent weight loss and aspiration pneumonia. Among the types of enteral tube feeding, percutaneous endoscopic gastrostomy (PEG) is the typical procedure offered to people with ALS and will be mainly discussed here.

To examine the effectiveness of percutaneous endoscopic gastrostomy or other enteral tube feeding in people with ALS, compared to oral feeds without enteral tube feeding on: 1. survival; 2. nutritional status; 3. quality of life. To examine the incidence of minor and major complications of percutaneous endoscopic gastrostomy (PEG) and other enteral tube feeding procedures in people with ALS.

There are no RCTs or quasi-RCTs to indicate whether enteral tube feeding is effective compared to continuation of oral feeding for any of the outcome measures. Such RCTs are very unlikely to be performed for ethical reasons. RCTs evaluating the effect of different enteral tube insertion techniques and timings of tube placement on survival and quality of life of people with ALS dysphagia are feasible and warranted.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Did the treatments for bullous pemphigoid have significant effects?

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.

To assess the effects of treatments for bullous pemphigoid.

Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.

SUPPORTED

MEDIUM

musculoskeletal system and dermatology

Do implementation interventions improve adherence to evidence-based recommendations in acute stroke units?

There is a growing body of research evidence to guide acute stroke care. Receiving care in a stroke unit improves access to recommended evidence-based therapies and patient outcomes. However, even in stroke units, evidence-based recommendations are inconsistently delivered by healthcare workers to patients with stroke. Implementation interventions are strategies designed to improve the delivery of evidence-based care.

To assess the effects of implementation interventions (compared to no intervention or another implementation intervention) on adherence to evidence-based recommendations by health professionals working in acute stroke units. Secondary objectives were to assess factors that may modify the effect of these interventions, and to determine if single or multifaceted strategies are more effective in increasing adherence with evidence-based recommendations.

We are uncertain whether a multifaceted implementation intervention compared to no intervention improves adherence to evidence-based recommendations in acute stroke settings, because the certainty of evidence is very low.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Did pharmacological interventions for pain and sedation management have a significant impact on preventing GMH-IVH in ventilated preterm infants?

Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) may contribute to neonatal morbidity and mortality and result in long-term neurodevelopmental sequelae. Appropriate pain and sedation management in ventilated preterm infants may decrease the risk of GMH-IVH; however, it might be associated with harms.

To summarize the evidence from systematic reviews regarding the effects and safety of pharmacological interventions related to pain and sedation management in order to prevent GMH-IVH in ventilated preterm infants.

None of the reported studies had an impact on aGMH-IVH, sIVH, ACND, or MND. The certainty of the evidence ranged from moderate to very low. Large RCTs of rigorous methodology are needed to achieve an optimal information size to assess the effects of pharmacological interventions for pain and sedation management for the prevention of GMH-IVH and mortality in preterm infants. Studies might compare interventions against either placebo or other drugs. Reporting of the outcome data should include the assessment of GMH-IVH and long-term neurodevelopment.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Can pharmacological interventions effectively prevent neurological impairment, stroke, and death in asymptomatic carotid stenosis?

Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this disease. It is caused by atherosclerosis; that is, the build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis is more likely to occur in people with several risk factors, such as diabetes, hypertension, hyperlipidaemia, and smoking. As this damage can develop without symptoms, the first symptom can be a fatal or disabling stroke, known as ischaemic stroke. Carotid stenosis leading to ischaemic stroke is most common in men older than 70 years. Ischaemic stroke is a worldwide public health problem.

To assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis in preventing neurological impairment, ipsilateral major or disabling stroke, death, major bleeding, and other outcomes.

Although there is no high-certainty evidence to support pharmacological intervention, this does not mean that pharmacological treatments are ineffective in preventing ischaemic cerebral events, morbidity, and mortality. High-quality RCTs are needed to better inform the best medical treatment that may reduce the burden of carotid stenosis. In the interim, clinicians will have to use other sources of information.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Did the topical ophthalmic anesthetics prove to be effective and safe in reducing ocular pain in persons with corneal abrasions?

Despite potential analgesic benefits from topical ophthalmic amides and esters, their outpatient use has become of concern because of the potential for abuse and ophthalmic complications.

To assess the effectiveness and safety of topical ophthalmic anesthetics compared with placebo or other treatments in persons with corneal abrasions.

Despite topical anesthetics providing excellent pain control in the intraoperative setting, the currently available evidence provides little or no certainty about their efficacy for reducing ocular pain in the initial 24 to 72 hours after a corneal abrasion, whether from unintentional trauma or surgery. We have very low confidence in this evidence as a basis to recommend topical anesthetics as an efficacious treatment modality to relieve pain from corneal abrasions. We also found no evidence of a substantial effect on epithelial healing up to 72 hours or a reduction in ocular complications when we compared anesthetics alone or with NSAIDs versus placebo.

REFUTED

LOW

sensory organs

Can fibrin-based haemostatic agents reduce intraoperative blood loss in adults undergoing liver resection?

Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use.

To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection.

The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.

REFUTED

LOW

cancer

Does dance movement therapy have beneficial effects on dementia?

Dementia is a syndrome of acquired cognitive impairment which is severe enough to interfere with independent living. Over the course of the illness, people with dementia also experience changes in emotions, behaviour and social relationships. According to Alzheimer's Disease International, dementia affects approximately 55 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia, including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. A growing literature highlights the capacity of the arts and has embodied practices to address this complexity. Dance movement therapy (DMT) is an embodied psychological intervention that can address complexity and thus may be useful for people with dementia, but its effectiveness remains unclear.

To assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement) SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register of the International Clinical Trials Registry Portal until 8 December 2022.

This review included one RCT with a low risk of bias. Due to the low certainty of the evidence, the true effects of DMT as an intervention for dementia may be substantially different from those found. More RCTs are needed to determine with any confidence whether DMT has beneficial effects on dementia.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Is the inverted internal limiting membrane flap technique more effective than conventional internal limiting membrane peeling for treating large macular holes?

Macular hole (MH) is a full-thickness defect in the central portion of the retina that causes loss of central vision. According to the usual definition, a large MH has a diameter greater than 400 µm at the narrowest point. For closure of MH, there is evidence that pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling achieves better anatomical outcomes than standard PPV. PPV with ILM peeling is currently the standard of care for MH management; however, the failure rate of this technique is higher for large MHs than for smaller MHs. Some studies have shown that the inverted ILM flap technique is superior to conventional ILM peeling for the management of large MHs.

To evaluate the clinical effectiveness and safety of pars plana vitrectomy with the inverted internal limiting membrane flap technique versus pars plana vitrectomy with conventional internal limiting membrane peeling for treating large macular holes, including idiopathic, traumatic, and myopic macular holes.

We found low-certainty evidence from four small RCTs that PPV with the inverted ILM flap technique is superior to PPV with ILM peeling with respect to BCVA gains at three or more months after surgery. We also found moderate-certainty evidence that the inverted ILM flap technique achieves more overall and type 1 MH closures. There is a need for high-quality multicenter RCTs to ascertain whether the inverted ILM flap technique is superior to ILM peeling with regard to anatomical and functional outcomes. Investigators should use the standard logMAR charts when measuring BCVA to facilitate comparison across trials.

SUPPORTED

LOW

musculoskeletal system and dermatology

Does high flow nasal cannula oxygen therapy have a significant impact on the safety and efficacy of respiratory support in term infants compared to other forms of non-invasive respiratory support?

Respiratory failure or respiratory distress in infants is the most common reason for non-elective admission to hospitals and neonatal intensive care units. Non-invasive methods of respiratory support have become the preferred mode of treating respiratory problems as they avoid some of the complications associated with intubation and mechanical ventilation. High flow nasal cannula (HFNC) therapy is increasingly being used as a method of non-invasive respiratory support. However, the evidence pertaining to its use in term infants (defined as infants ≥ 37 weeks gestational age to the end of the neonatal period (up to one month postnatal age)) is limited and there is no consensus of opinion regarding the safety and efficacy HFNC in this population.

To assess the safety and efficacy of high flow nasal cannula oxygen therapy for respiratory support in term infants when compared with other forms of non-invasive respiratory support.

When compared with CPAP, HFNC may result in little to no difference in treatment failure. HFNC may have little to no effect on the duration of respiratory support, but the evidence is very uncertain. HFNC likely results in little to no difference in the length of stay at the intensive care unit. HFNC may reduce the incidence of nasal trauma and abdominal overdistension, but the evidence is very uncertain. When compared with LFNC, HFNC may reduce treatment failure slightly. HFNC may have little to no effect on the duration of respiratory support, length of stay at the ICU, or hospital length of stay, but the evidence is very uncertain. There is insufficient evidence to enable the formulation of evidence-based guidelines on the use of HFNC for respiratory support in term infants. Larger, methodologically robust trials are required to further evaluate the possible health benefits or harms of HFNC in this patient population.

NOT ENOUGH INFORMATION

LOW

respiratory system

Do prostaglandins provide benefits in adults undergoing liver transplantation compared with placebo or standard care?

Prostaglandins are naturally occurring lipids that are synthesised from arachidonic acid. Multiple studies have evaluated the benefits of prostaglandins in reducing ischaemia reperfusion injury after liver transplantation. New studies have been published since the previous review, and hence it was important to update the evidence for this intervention.

To evaluate the benefits and harms of prostaglandins in adults undergoing liver transplantation compared with placebo or standard care.

Eleven trials evaluated prostaglandins in adult liver transplanted recipients. Based on low-certainty evidence, prostaglandins may reduce all-cause mortality up to one month; may cause little to no difference in serious adverse events, liver retransplantation, early allograft dysfunction, primary non-function of the allograft, and length of hospital stay; and may have a large reduction in the development of acute kidney injury requiring dialysis. We do not know the effect of prostaglandins on adverse events considered non-serious. We lack adequately powered, high-quality trials evaluating the effects of prostaglandins for people undergoing liver transplantation.

NOT ENOUGH INFORMATION

LOW

digestive system and metabolism

Can interventions such as red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors prevent or reduce kidney complications or chronic kidney disease in people with sickle cell disease?

Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017.

To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination.

We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.

NOT ENOUGH INFORMATION

LOW

cancer

Do second language (L2) vocabulary interventions have immediate and long-term effects on vocabulary and social-emotional well-being in L2 learners up to six years of age?

Second language (L2) learners are a heterogeneous group. Their L2 skills are highly varied due to internal factors (e.g. cognitive development) and external factors (e.g. cultural and linguistic contexts). As a group, their L2 vocabulary skills appear to be lower than their monolingual peers. This pattern tends to persist over time and may have negative consequences for social interaction and inclusion, learning, and academic achievement.

To examine the immediate and long-term effects of second language (L2) vocabulary interventions targeting L2 learners up to six years of age on vocabulary and social-emotional well-being. To examine the associations between L2 vocabulary interventions and the general characteristics of L2 learners (e.g. age, L2 exposure, and L1 skills).

Findings from this review suggest that, compared to standard care, vocabulary interventions may benefit children's L2 vocabulary learning but have little to no effect on their listening comprehension, though the evidence is uncertain. Vocabulary interventions probably improve the children's storytelling skills slightly. Due to the limited number of studies that met our inclusion criteria and the very low- to moderate-certainty evidence as a result of inconsistency and imprecision, implications for practice should be considered with caution. This review highlights the need for more high-quality trials (e.g. RCTs) of vocabulary interventions for L2 learners, particularly studies of learners outside the USA.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Did the use of expanded polytetrafluoroethylene (ePTFE)-covered stents decrease shunt dysfunction in people with liver cirrhosis?

Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used procedure for management of uncontrolled upper gastrointestinal bleeding and refractory ascites in people with liver cirrhosis. However, nearly half of the people experience shunt dysfunction and recurrent symptoms within one year of the procedure. Expanded polytetrafluoroethylene (ePTFE)-covered stents are assumed to decrease shunt dysfunction by approximately 20% to 30%.

To evaluate the benefits and harms associated with the use of expanded polytetrafluoroethylene (ePTFE)-covered stents versus bare stents in transjugular intrahepatic portosystemic shunts (TIPSs) for managing people with liver cirrhosis.

Based on the small number of trials with insufficient sample size and events, and study limitations, we assessed the overall certainty of evidence in the predefined outcomes as low or very low. Therefore, we are uncertain which of the two interventions (ePTFE-covered stents or bare stents of the same diameter and ePTFE-covered stents versus bare stents of different stent diameters) is effective for the evaluated outcomes. None of the four trials reported data on health-related quality of life, and data on complications were either missing or rarely reported. We lack high-quality trials to evaluate the role of ePTFE-covered stents for TIPS for managing people with liver cirrhosis.

NOT ENOUGH INFORMATION

LOW

digestive system and metabolism

Does apnoeic oxygenation before intubation in adults reduce the incidence of hypoxaemia, morbidity, and mortality?

Apnoeic oxygenation is the delivery of oxygen during the apnoeic phase preceding intubation. It is used to prevent respiratory complications of endotracheal intubation that have the potential to lead to significant adverse events including dysrhythmia, haemodynamic decompensation, hypoxic brain injury and death. Oxygen delivered by nasal cannulae during the apnoeic phase of intubation (apnoeic oxygenation) may serve as a non-invasive adjunct to endotracheal intubation to decrease the incidence of hypoxaemia, morbidity and mortality.

To evaluate the benefits and harms of apnoeic oxygenation before intubation in adults in the prehospital, emergency department, intensive care unit and operating theatre environments compared to no apnoeic oxygenation during intubation.

There was some evidence that oxygenation during the apnoeic phase of intubation may improve the lowest recorded oxygen saturation. However, the differences in oxygen saturation were unlikely to be clinically significant. This did not translate into any measurable effect on the incidence of hypoxaemia or severe hypoxaemia in a group of predominately critically ill people. We were unable to assess the influence on hospital length of stay; however, there was a reduction in ICU stay in the apnoeic oxygenation group. The mechanism for this is unclear as there was little to no difference in first pass success or adverse event rates.

NOT ENOUGH INFORMATION

LOW

respiratory system

Does extracorporeal shock wave lithotripsy have different effects compared to percutaneous nephrolithotomy or retrograde intrarenal surgery for treating kidney stones?

Nephrolithiasis is a common urological disease worldwide. Extracorporeal shock wave lithotripsy (ESWL) has been used for the treatment of renal stones since the 1980s, while retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) are newer, more invasive treatment modalities that may have higher stone-free rates. The complications of RIRS and PCNL have decreased owing to improvement in surgical techniques and instruments. We re-evaluated the best evidence on this topic in an update of a Cochrane Review first published in 2014.

To assess the effects of extracorporeal shock wave lithotripsy compared with percutaneous nephrolithotomy or retrograde intrarenal surgery for treating kidney stones.

ESWL compared with PCNL may have lower three-month success rates, may have a similar effect on QoL, and probably leads to fewer complications. ESWL compared with RIRS may have lower three-month success rates, but the evidence on QoL outcomes and complication rates is very uncertain. These findings should provide valuable information to aid shared decision-making between clinicians and people with kidney stones who are undecided about these three options.

SUPPORTED

MEDIUM

urinary system

Does perioperative glycaemic control for people with diabetes undergoing surgery reduce all-cause mortality?

People with diabetes mellitus are at increased risk of postoperative complications. Data from randomised clinical trials and meta-analyses point to a potential benefit of intensive glycaemic control, targeting near-normal blood glucose, in people with hyperglycaemia (with and without diabetes mellitus) being submitted for surgical procedures. However, there is limited evidence concerning this question in people with diabetes mellitus undergoing surgery.

To assess the effects of perioperative glycaemic control for people with diabetes undergoing surgery.

High-certainty evidence indicates that perioperative intensive glycaemic control in people with diabetes undergoing surgery does not reduce all-cause mortality compared to conventional glycaemic control. There is low-certainty evidence that intensive glycaemic control may reduce the risk of cardiovascular events, but cause little to no difference to the risk of infectious complications after the intervention, while it may increase the risk of hypoglycaemia. There are no clear differences between the groups for the other outcomes. There are uncertainties among the intensive and conventional groups regarding the optimal glycaemic algorithm and target blood glucose concentrations. In addition, we found poor data on health-related quality of life, socio-economic effects and weight gain. It is also relevant to underline the heterogeneity among studies regarding clinical outcomes and methodological approaches. More studies are needed that consider these factors and provide a higher quality of evidence, especially for outcomes such as hypoglycaemia and infectious complications.

REFUTED

HIGH

endocrine system and hormones

Do combined oral contraceptive pills provide benefits for the management of primary dysmenorrhoea?

Dysmenorrhoea (painful menstrual cramps) is common and a major cause of pain in women. Combined oral contraceptives (OCPs) are often used in the management of primary dysmenorrhoea, but there is a need for reporting the benefits and harms. Primary dysmenorrhoea is defined as painful menstrual cramps without pelvic pathology.

To evaluate the benefits and harms of combined oral contraceptive pills for the management of primary dysmenorrhoea.

OCPs are effective for treating dysmenorrhoea, but they cause irregular bleeding, and probably headache and nausea. Long-term effects were not covered in this review. Continuous use of OCPs was probably more effective than the standard regimen but safety should be ensured with long-term data. Due to lack of data, we are uncertain whether NSAIDs are better than OCPs for treating dysmenorrhoea.

SUPPORTED

MEDIUM

sexual and reproductive health

Does tubeless percutaneous nephrolithotomy (PNL) provide better outcomes compared to standard PNL for the treatment of kidney stones in adults?

Percutaneous nephrolithotomy (PNL) is the standard of care for removing large kidney stones (> 2 cm). Once the procedure is complete, different exiting strategies exist to manage the percutaneous tract opening, including placement of an external nephrostomy tube, placement of an internal ureteral stent, or no external or internal tube. The decision to place or not place a tube is handled differently among clinicians and may affect patient outcomes.

To assess the effects of tubeless PNL (with ureteral stenting), totally tubeless PNL (without ureteral stenting or nephrostomy), and standard PNL (nephrostomy only) for the treatment of kidney stones in adults.

When comparing tubeless to standard PNL with regard to the predefined primary outcomes of this review, there may be little difference in early postoperative pain, while we are very uncertain of the effect on SAEs. People treated with tubeless PNL may benefit from a reduced length of stay compared to standard PNL. When comparing totally tubeless to standard PNL, early postoperative pain and severe adverse events may be reduced with totally tubeless PNL. The certainty of evidence by outcome was mostly very low (range: moderate to very low) for the comparison of tubeless to standard PNL and low (range: moderate to very low) for the comparison of totally tubeless to standard PNL. The most common reasons for downgrading the certainty of the evidence were study limitations, inconsistency, and imprecision. We did not find randomized trial evidence for other comparisons. Overall, further and higher-quality studies are needed to inform clinical practice.

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urinary system

Do interventions to prevent and reduce the use of physical restraints for older people in long-term care have significant effects?

Physical restraints (PR), such as bedrails and belts in chairs or beds, are commonly used for older people receiving long-term care, despite clear evidence for the lack of effectiveness and safety, and widespread recommendations that their use should be avoided. This systematic review of the efficacy and safety of interventions to prevent and reduce the use of physical restraints outside hospital settings, i.e. in care homes and the community, updates our previous review published in 2011.

To evaluate the effects of interventions to prevent and reduce the use of physical restraints for older people who require long-term care (either at home or in residential care facilities) SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid Sp), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register, the International Clinical Trials Registry Portal, on 3 August 2022.

Organisational interventions aimed to implement a least-restraint policy probably reduce the number of residents with at least one PR and probably largely reduce the number of residents with at least one belt. We are uncertain whether simple educational interventions reduce the use of physical restraints, and interventions providing information about residents' fall risk may result in little to no difference in the use of physical restraints. These results apply to long-term care institutions; we found no studies from community settings.

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MEDIUM

cognitive, mental, and mental health

Does superficial endovenous ablation improve the healing and recurrence of venous leg ulcers and the quality of life of people with venous ulcer disease?

Venous leg ulcers (VLUs) are a serious manifestation of chronic venous disease affecting up to 3% of the adult population. This typically recalcitrant and recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The longstanding mainstay treatment for VLUs is compression therapy. Surgical removal of incompetent veins reduces the risk of ulcer recurrence. However, open surgery is an unpopular option amongst people with VLU, and many people are unsuitable for it. The efficacy of the newer, minimally-invasive endovenous techniques has been established in uncomplicated superficial venous disease, and these techniques can also be used in the management of VLU. When used with compression, endovenous ablation aims to further reduce pressure in the veins of the leg, which may impact ulcer healing.

To determine the effects of superficial endovenous ablation on the healing and recurrence of venous leg ulcers and the quality of life of people with venous ulcer disease.

Endovenous ablation of superficial venous incompetence in combination with compression improves leg ulcer healing when compared with compression alone. This conclusion is based on high-certainty evidence. There is moderate-certainty evidence to suggest that it is probably cost-effective at one year and low certainty evidence of unclear effects on recurrence and complications. Further research is needed to explore the additional benefit of endovenous ablation in ulcers of greater than six months duration and the optimal modality of endovenous ablation.

SUPPORTED

HIGH

musculoskeletal system and dermatology

Can hyaluronic acid (and its derivatives) promote the healing of chronic wounds?

Hyaluronic acid is synthesised in plasma membranes and can be found in extracellular tissues. It has been suggested that the application of hyaluronic acid to chronic wounds may promote healing, and the mechanism may be due to its ability to maintain a moist wound environment which helps cell migration in the wound bed.

To evaluate the effects of hyaluronic acid (and its derivatives) on the healing of chronic wounds.

There is currently insufficient evidence to determine the effectiveness of hyaluronic acid dressings in the healing of pressure ulcers or foot ulcers in people with diabetes. We found evidence that hyaluronic acid probably improves complete ulcer healing and may slightly decrease pain and increase change in ulcer size when compared with neutral vehicle. Future research into the effects of hyaluronic acid in the healing of chronic wounds should consider higher sample size and blinding to minimise bias and improve the quality of evidence.

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LOW

musculoskeletal system and dermatology

Does NIPPV reduce the need for additional ventilatory support in preterm infants after extubation compared to NCPAP?

Nasal continuous positive airway pressure (NCPAP) is a useful method for providing respiratory support after extubation. Nasal intermittent positive pressure ventilation (NIPPV) can augment NCPAP by delivering ventilator breaths via nasal prongs.

Primary objective To determine the effects of management with NIPPV versus NCPAP on the need for additional ventilatory support in preterm infants whose endotracheal tube was removed after a period of intermittent positive pressure ventilation. Secondary objectives To compare rates of abdominal distension, gastrointestinal perforation, necrotising enterocolitis, chronic lung disease, pulmonary air leak, mortality, duration of hospitalisation, rates of apnoea and neurodevelopmental status at 18 to 24 months for NIPPV and NCPAP. To compare the effect of NIPPV versus NCPAP delivered via ventilators versus bilevel devices, and assess the effects of the synchronisation of ventilation, and the strength of interventions in different economic settings.

NIPPV likely reduces the incidence of extubation failure and the need for reintubation within 48 hours to one-week postextubation more effectively than NCPAP in very preterm infants (GA 28 weeks and above). There is a paucity of data for infants less than 28 weeks' gestation. Pulmonary air leaks were also potentially reduced in the NIPPV group. However, it has no effect on other clinically relevant outcomes such as gastrointestinal perforation, NEC, chronic lung disease or mortality. Ventilator-generated NIPPV appears superior to bilevel devices in reducing the incidence of respiratory failure postextubation failure and need for reintubation. Synchronisation used to deliver NIPPV may be important; however, data are insufficient to support strong conclusions. Future trials should enrol a sufficient number of infants, particularly those less than 28 weeks' GA, to detect differences in death or chronic lung disease and should compare different categories of devices, establish the impact of synchronisation of NIPPV on safety and efficacy of the technique as well as the best combination of settings for NIPPV (rate, peak pressure and positive end-expiratory). Trials should strive to match the mean airway pressure between the intervention groups to allow a better comparison. Neurally adjusted ventilatory assist needs further assessment with properly powered randomised trials.

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MEDIUM

respiratory system

Did the review investigate the safety and efficacy of surgical interventions for apical vaginal prolapse?

Apical vaginal prolapse is the descent of the uterus or vaginal vault (post-hysterectomy). Various surgical treatments are available, but there are no guidelines to recommend which is the best.

To evaluate the safety and efficacy of any surgical intervention compared to another intervention for the management of apical vaginal prolapse.

Sacral colpopexy is associated with lower risk of awareness of prolapse, recurrent prolapse on examination, repeat surgery for prolapse, and postoperative SUI than a variety of vaginal interventions. The limited evidence does not support the use of transvaginal mesh compared to native tissue repair for apical vaginal prolapse. There were no differences in primary outcomes for different routes of sacral colpopexy. However, the laparoscopic approach is associated with a shorter operating time than robotic approach, and shorter admission than open approach. There were no significant differences between vaginal hysteropexy and vaginal hysterectomy for uterine prolapse nor between vaginal hysteropexy and abdominal hysteropexy/cervicopexy. There were no differences detected between absorbable and non absorbable sutures however, the certainty of evidence for mesh exposure and dyspareunia was low.

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MEDIUM

sexual and reproductive health

Does supplemental probiotics reduce the risk of NEC and associated mortality and morbidity in very preterm or very low birth weight infants?

Intestinal dysbiosis may contribute to the pathogenesis of necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Dietary supplementation with probiotics to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity in very preterm or VLBW infants.

To determine the effect of supplemental probiotics on the risk of NEC and associated mortality and morbidity in very preterm or very low birth weight infants.

Given the low to moderate certainty of evidence for the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or VLBW infants, and particularly for extremely preterm or ELBW infants, there is a need for further large, high-quality trials to provide evidence of sufficient validity and applicability to inform policy and practice.

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LOW

digestive system and metabolism

Is plasmapheresis an effective therapy to remove amyloid fibrin(ogen) particles in individuals with PCC?

The post-COVID-19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover. A new belief, arising from a few laboratory studies, is that 'microclots' cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term 'microclots' is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID-19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only. We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC.

Laboratory studies review To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC. Randomized controlled trials review To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials.

In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well-conducted randomized controlled trial.

REFUTED

LOW

cancer

Can cognitive behavioural therapy (CBT) reduce aggressive behaviors in patients with schizophrenia?

Schizophrenia and other psychoses are thought to be associated with a substantial increase in aggressive behaviour, violence and violent offending. However, acts of aggression or violence committed by people with severe mental illness are rare and circumscribed to a small minority of individuals. We know little about the frequency and variability of violent episodes for people with schizophrenia who present chronic or recurrent aggressive episodes, and of available interventions to reduce such problems. A psychological intervention, cognitive behavioural therapy (CBT), aims to challenge dysfunctional thoughts and has been used since the mid-1970s to improve mental health and emotional disorders. CBT includes different interventional procedures, such as cognitive therapy, elements of behavioural therapy, problem-solving interventions, and coping skills training, among others. Although CBT presents much diversity, interventions are characteristically problem-focused, goal-directed, future-oriented, time-limited (about 12 to 20 sessions over four to six months), and empirically based. CBT has shown clinically beneficial effects in persistent positive and negative symptoms of schizophrenia and its use as an add-on therapy to medication in the treatment of schizophrenia is supported by treatment guidelines. However, several Cochrane Reviews recently concluded that, due to the low quality of evidence available, no firm conclusions can currently be made regarding the effectiveness of adding CBT to standard care for people with schizophrenia, or about CBT compared to other psychosocial treatments for people with schizophrenia. Whereas CBT is not an emergency or crisis intervention that acts immediately on the known or unknown triggers underlying aggressive behaviour, might be a timely treatment used to manage persistent aggression or repeated aggressive episodes in people with schizophrenia.

To assess the efficacy and safety of

Whereas the evidence from only two studies with 184 participants suggests the use of CBT plus standard care may reduce some aggressive behaviours in patients with schizophrenia, the grading of the certainty of the evidence is very low. It implies that there is not yet reliable evidence to guide clinical decisions and therefore more evidence is needed to get a more precise estimate of the effect of the intervention. Currently, we have very little confidence in the effect estimate, and the true effect could be substantially different from its estimate.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Do non-surgical therapies have significant effects compared to placebo or no treatment in individuals with Peyronie's disease?

Peyronie's disease is a condition that results in the development of penile plaques that can lead to penile curvature, pain, and erectile dysfunction, making sexual activity difficult. A number of non-surgical interventions exist to improve this condition, which include topical and injection agents as well as mechanical methods; however, their effectiveness remains uncertain. We performed this review to determine the effects of these non-surgical treatments.

To assess the effects of non-surgical therapies compared to placebo or no treatment in individuals with Peyronie's disease.

There is little evidence supporting the effectiveness of most non-surgical treatments for Peyronie's disease. Existing trials are mostly of poor methodological quality and/or fail to address patient-centered outcomes. Injectional collagenase appears to have some effectiveness; however, many individuals may not experience the improvement as clinically relevant, and this comes with the risk of increased adverse events. There is a critical need for better non-surgical treatment options for men with Peyronie's disease.

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LOW

sexual and reproductive health

Do antiplatelets given with standard care influence the course of COVID-19 in general?

Severe coronavirus disease 2019 (COVID-19) can cause thrombotic events that lead to severe complications or death. Antiplatelet agents, such as acetylsalicylic acid, have been shown to effectively reduce thrombotic events in other diseases: they could influence the course of COVID-19 in general.

To assess the efficacy and safety of antiplatelets given with standard care compared to no treatment or standard care (with/without placebo) for adults with COVID-19.

In people with confirmed or suspected COVID-19 and moderate to severe disease, we found moderate-certainty evidence that antiplatelets probably result in little to no difference in 28-day mortality, clinical worsening or improvement, but probably result in a slight reduction in thrombotic events. They probably increase the occurrence of major bleeding events. Low-certainty evidence suggests that antiplatelets may result in a slight increase in serious adverse events. In people with confirmed COVID-19 and mild symptoms, we found low-certainty evidence that antiplatelets may result in little to no difference in 45-day mortality and serious adverse events, and may slightly reduce thrombotic events. The effects on the combined outcome admission to hospital or death up to day 45 and major bleeding events are very uncertain. Quality of life was not reported. Included studies were conducted in high- to lower middle-income settings using antiplatelets prior to vaccination roll-outs. We identified a lack of evidence concerning quality of life assessments, adverse events and people with asymptomatic infection. The 14 ongoing and three completed, unpublished RCTs that we identified in trial registries address similar settings and research questions as in the current body of evidence. We expect to incorporate the findings of these studies in future versions of this review.

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MEDIUM

respiratory system

Does CPAP have significant effects on apnoea of prematurity in preterm infants?

Apnoea of prematurity (AoP) is defined as a pause in breathing for 20 seconds or longer, or for less than 20 seconds when accompanied by bradycardia and hypoxaemia, in a preterm infant. An association between the severity of apnoea and neurodevelopmental delay has been reported. Continuous positive airway pressure (CPAP) is a form of non-invasive ventilatory assistance that has been shown to be relatively safe and effective in preventing and treating respiratory distress among preterm infants. It is less clear whether CPAP treatment is safe and effective in the prevention and treatment of AoP.

1. To assess the effects of CPAP on AoP in preterm infants (this may be compared to supportive care or mechanical ventilation). 2. To assess the effects of different CPAP delivery systems on AoP in preterm infants.

Due to the limited available evidence, we are very uncertain whether any CPAP device is more effective than other forms of supportive care, other CPAP devices, or mechanical ventilation for the prevention and treatment of AoP. The devices used in these studies included two types of variable flow CPAP device: bubble CPAP and ventilator CPAP. For each comparison, data were only available from a single study. There are theoretical reasons why these devices might have different effects on AoP, therefore further trials are indicated.

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LOW

respiratory system

Do medical interventions for people with eosinophilic esophagitis show efficacy and safety?

Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of EoE requires a constellation of clinical symptoms of esophageal dysfunction and histologic findings (at least 15 eosinophils/high-powered microscope field (eos/hpf)). Current guidelines no longer require the failure of response to proton pump inhibitor medications to establish a diagnosis of EoE, but continue to suggest the exclusion of other etiologies of esophageal eosinophilia. The treatment goals for EoE are improvement in clinical symptoms, resolution of esophageal eosinophilia and other histologic abnormalities, endoscopic improvement, improved quality of life, improved esophageal function, minimized adverse effects of treatment, and prevention of disease progression and subsequent complications. Currently, there is no cure for EoE, making long-term treatment necessary. Standard treatment modalities include dietary modifications, esophageal dilation, and pharmacologic therapy. Effective pharmacologic therapies include corticosteroids, rapidly emerging biological therapies, and proton pump inhibitor medications.

To evaluate the efficacy and safety of medical interventions for people with eosinophilic esophagitis.

Corticosteroids (as compared to placebo) may lead to clinical symptom improvement when reported both as dichotomous and continuous outcomes, from the primary study definitions. Corticosteroids lead to a large increase in histological improvement (dichotomous outcome) and may increase histological improvement (continuous outcome) when compared to placebo. Corticosteroids may or may not increase endoscopic improvement (depending on whether the outcome is measured dichotomously or continuously). Withdrawals due to adverse events (dichotomous outcome) may occur less frequently when corticosteroids are compared to placebo. Biologics (as compared to placebo) may not lead to clinical symptom improvement when reported as a dichotomous outcome and may lead to an increase in clinical symptom improvement (as a continuous outcome), from the primary study definitions. Biologics lead to a large increase in histological improvement when reported as a dichotomous outcome, but this is uncertain when reported as a continuous outcome, as compared to placebo. Biologics may not increase endoscopic improvement (dichotomous outcome), but this is uncertain when measured as a continuous outcome. Withdrawals due to adverse events as a dichotomous outcome may occur as frequently when biologics are compared to placebo.

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MEDIUM

digestive system and metabolism

Does DUS have a clear advantage over standard surveillance for lower limb revascularization in people with LEAD?

Lower extremity atherosclerotic disease (LEAD) - also known as peripheral arterial disease - refers to the obstruction or narrowing of the large arteries of the lower limbs, most commonly caused by atheromatous plaque. Although in many cases of less severe disease patients can be asymptomatic, the major clinical manifestations of LEAD are intermittent claudication (IC) and critical limb ischaemia, also known as chronic limb-threatening ischaemia (CLTI). Revascularisation procedures including angioplasty, stenting, and bypass grafting may be required for those in whom the disease is severe or does not improve with non-surgical interventions. Maintaining vessel patency after revascularisation remains a challenge for vascular surgeons, since approximately 30% of vein grafts may present with restenosis in the first year due to myointimal hyperplasia. Restenosis can also occur after angioplasty and stenting. Restenosis and occlusions that occur more than two years after the procedure are generally related to progression of the atherosclerosis. Surveillance programmes with duplex ultrasound (DUS) scanning as part of postoperative care may facilitate early diagnosis of restenosis and help avoid amputation in people who have undergone revascularisation.

To assess the effects of DUS versus pulse palpation, arterial pressure index, angiography, or any combination of these, for surveillance of lower limb revascularisation in people with LEAD.

Based on low certainty evidence, we found no clear difference between DUS and standard surveillance in preventing limb amputation, morbidity, and mortality after lower limb revascularisation. We found no studies on DUS surveillance after angioplasty or stenting (or both), only studies on bypass grafting. High-quality RCTs should be performed to better inform the best medical surveillance of lower limb revascularisation that may reduce the burden of peripheral arterial disease.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Does rifaximin have beneficial effects on hepatic encephalopathy in people with cirrhosis?

Hepatic encephalopathy describes the spectrum of neuropsychiatric changes that may complicate the course of cirrhosis and detrimentally affect outcomes. Ammonia plays a key role in its development. Rifaximin is a non-absorbable antibiotic that inhibits urease-producing bacteria and reduces absorption of dietary and bacterial ammonia.

To evaluate the beneficial and harmful effects of rifaximin versus placebo, no intervention, or non-absorbable disaccharides for: (i) the prevention of hepatic encephalopathy, and (ii) the treatment of minimal and overt hepatic encephalopathy, in people with cirrhosis, both when used alone and when combined with a non-absorbable disaccharide.

Compared to placebo/no intervention, rifaximin likely improves health-related quality of life in people with minimal hepatic encephalopathy, and may improve hepatic encephalopathy, particularly in populations with minimal hepatic encephalopathy and when it is used for prevention. Rifaximin likely has no overall effect on mortality, serious adverse events, health-related quality of life, or hepatic encephalopathy compared to non-absorbable disaccharides. However, when used in combination with a non-absorbable disaccharide, it likely reduces overall mortality risk, the risk of serious adverse events, improves hepatic encephalopathy, reduces the length of hospital stay, and prevents the occurrence/recurrence of hepatic encephalopathy. The certainty of evidence for these outcomes is very low to moderate; further high-quality trials are needed.

SUPPORTED

LOW

digestive system and metabolism

Do ACEi and ARB provide benefits in managing early stage CKD in patients without diabetes mellitus?

Chronic kidney disease (CKD) is a long-term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of the Kidney Disease Improving Global Outcomes (KDIGO) classifications. Early recognition and management of CKD affords the opportunity to prepare for progressive kidney impairment and impending kidney replacement therapy and for intervention to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosterone system. Beneficial effects of ACEi and ARB on kidney outcomes and survival in people with a wide range of severity of kidney impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain. This is an update of a review that was last published in 2011.

To evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD who do not have diabetes mellitus (DM).

There is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have DM. The available evidence is overall of very low certainty and high risk of bias. We have identified an area of large uncertainty for a group of patients who account for most of those diagnosed as having CKD.

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LOW

cardiovascular system

Does early NIPPV reduce the risk of respiratory failure and the need for intubation in preterm infants with respiratory distress syndrome?

Nasal continuous positive airway pressure (NCPAP) is a strategy to maintain positive airway pressure throughout the respiratory cycle through the application of a bias flow of respiratory gas to an apparatus attached to the nose. Early treatment with NCPAP is associated with decreased risk of mechanical ventilation exposure and might reduce chronic lung disease. Nasal intermittent positive pressure ventilation (NIPPV) is a form of noninvasive ventilation delivered through the same nasal interface during which patients are exposed to short inflations, along with background end-expiratory pressure.

To examine the risks and benefits of early (within the first six hours after birth) NIPPV versus early NCPAP for preterm infants at risk of or with respiratory distress syndrome (RDS). Primary endpoints are respiratory failure and the need for intubated ventilatory support during the first week of life. Secondary endpoints include the incidence of mortality, chronic lung disease (CLD) (oxygen therapy at 36 weeks' postmenstrual age), pneumothorax, duration of respiratory support, duration of oxygen therapy, and intraventricular hemorrhage (IVH).

When applied within six hours after birth, NIPPV likely reduces the risk of respiratory failure and the need for intubation and endotracheal tube ventilation in very preterm infants (GA 28 weeks and above) with respiratory distress syndrome or at risk for RDS. It may also decrease the rate of CLD slightly. However, most trials enrolled infants with a gestational age of approximately 28 to 32 weeks with an overall mean gestational age of around 30 weeks. As such, the results of this review may not apply to extremely preterm infants that are most at risk of needing mechanical ventilation or developing CLD. Additional studies are needed to confirm these results and to assess the safety of NIPPV compared with NCPAP alone in a larger patient population.

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MEDIUM

respiratory system

Do interventions to enhance adherence to airway clearance treatment and exercise therapy in people with CF affect health outcomes?

Cystic fibrosis (CF) is a life-limiting genetic disorder predominantly affecting the lungs and pancreas. Airway clearance techniques (ACTs) and exercise therapy are key components of physiotherapy, which is considered integral in managing CF; however, low adherence is well-documented. Poor physiotherapy adherence may lead to repeated respiratory infections, reduced exercise tolerance, breathlessness, reduced quality of life, malaise and reduced life expectancy, as well as increased use of pharmacology, healthcare access and hospital admission. Therefore, evidence-based strategies to inform clinical practice and improve adherence to physiotherapy may improve quality of life and reduce treatment burden.

To assess the effects of interventions to enhance adherence to airway clearance treatment and exercise therapy in people with CF and their effects on health outcomes, such as pulmonary exacerbations, exercise capacity and health-related quality of life.

We are uncertain whether a music-based motivational intervention may increase adherence to ACTs or affect the risk of hospitalisation for a respiratory infection. We are also uncertain whether an educational intervention increases adherence to exercise or reduces the frequency of respiratory infection-related hospital admission. However, these results are largely based on self-reported data and the impact of strategies to improve adherence to ACT and exercise in children and adolescents with stable CF remains inconclusive. Given that adherence to ACT and exercise therapy are fundamental to the clinical management of people with CF, there is an urgent need for well-designed, large-scale clinical trials in this area, which should conform to the CONSORT statement for standards of reporting and use appropriate, validated outcome measures. Studies should also ensure full disclosure of data for all important clinical outcomes.

NOT ENOUGH INFORMATION

LOW

respiratory system

Does statin therapy improve metabolic and endocrine effects in women with PCOS who are not actively trying to conceive?

Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary syndrome (PCOS), statins may also exert other beneficial metabolic and endocrine effects, such as reducing testosterone levels. This is an update of a Cochrane Review first published in 2011.

To assess the efficacy and safety of statin therapy in women with PCOS who are not actively trying to conceive.

The evidence for all main outcomes of this review was of very low certainty. Due to the limited evidence, we are uncertain if statins compared with placebo, or statins plus metformin compared with metformin alone, improve resumption of menstrual regularity. The trial evaluating statin plus OCP versus OCP alone reported neither of our primary outcomes. No other studies reported resumption of spontaneous ovulation. We are uncertain if statins improve hirsutism, acne severity, or testosterone. All trials that measured adverse events reported no significant differences between the groups.

NOT ENOUGH INFORMATION

LOW

endocrine system and hormones

Does vedolizumab provide benefits for the induction and maintenance of remission in Crohn's disease?

Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease.

To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease.

High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.

SUPPORTED

HIGH

digestive system and metabolism

Do mobile phone-based interventions improve contraception use?

Contraception provides significant benefits for women's and children's health, yet many women have an unmet need for contraception. Rapid expansion in the use of mobile phones in recent years has had a dramatic impact on interpersonal communication. Within the health domain text messages and smartphone applications offer means of communication between clients and healthcare providers. This review focuses on interventions delivered by mobile phone and their effect on use of contraception.

To evaluate the benefits and harms of mobile phone-based interventions for improving contraception use.

This review demonstrates there is evidence to support the use of mobile phone-based interventions in improving the use of contraception, with moderate-certainty evidence. Interactive mobile phone interventions appear more effective than unidirectional methods. The cost-effectiveness, cost benefits, safety and long-term effects of these interventions remain unknown, as does the evidence of this approach to support contraception use among specific populations. Future research should investigate the effectiveness and safety of mobile phone-based interventions with better quality trials to help establish the effects of interventions delivered by mobile phone on contraception use. This review is limited by the quality of the studies due to flaws in methodology, bias or imprecision of results.

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MEDIUM

sexual and reproductive health

Does early catheter removal (< 5 days post-transplant) result in lower incidence of UTIs and urological complications compared to late catheter removal (≥ 5 days post-transplant)?

The optimal treatment for end-stage kidney disease is kidney transplantation. During the operation, a catheter is introduced into the bladder and remains in place postoperatively to allow the bladder to drain. This decreases tension from the cysto-ureteric anastomosis and promotes healing. Unfortunately, urinary catheters can pose an infection risk to patients as they allow bacteria into the bladder, potentially resulting in a urinary tract infection (UTI). The longer the catheter remains in place, the greater the risk of developing a UTI. There is no consensus approach to the time a catheter should remain in place post-transplant. Furthermore, the different timings of catheter removal are thought to be associated with different incidences of UTI and postoperative complications, such as anastomotic breakdown.

This review aimed to compare patients who had their catheter removed < 5 days post-transplant surgery to those patients who had their catheter removed ≥ 5 days following their kidney transplant. Primary outcome measures between the two groups included: the incidence of symptomatic UTIs, the incidence of asymptomatic bacteriuria and the incidence of major urological complications requiring intervention and treatment.

A high-quality, well-designed RCT is required to compare the effectiveness of early catheter removal versus late catheter removal in patients following a kidney transplant. At the present time, there is insufficient evidence to suggest any difference between early and late catheter removal post-transplant, and the studies investigating this were generally of poor quality.

NOT ENOUGH INFORMATION

LOW

renal and urinary system

Did the interventions based on physical activity and education about physical activity prove to be more effective than usual care for children and adolescents with chronic musculoskeletal pain?

Chronic pain is a major health and socioeconomic burden, which is prevalent in children and adolescents. Among the most widely used interventions in children and adolescents are physical activity (including exercises) and education about physical activity.

To evaluate the effectiveness of physical activity, education about physical activity, or both, compared with usual care (including waiting-list, and minimal interventions, such as advice, relaxation classes, or social group meetings) or active medical care in children and adolescents with chronic musculoskeletal pain.

We are unable to confidently state whether interventions based on physical activity and education about physical activity are more effective than usual care for children and adolescents with chronic musculoskeletal pain. We found very low-certainty evidence that physical activity may reduce pain intensity and improve disability postintervention compared with usual care, for children and adolescents with juvenile idiopathic arthritis. We did not find any studies reporting educational interventions; it remains unknown how these interventions influence the outcomes in children and adolescents with chronic musculoskeletal pain. Treatment decisions should consider the current best evidence, the professional's experience, and the young person's preferences. Further randomised controlled trials in other common chronic musculoskeletal pain conditions, with high methodological quality, large sample size, and long-term follow-up are urgently needed.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Do first-line diuretic drugs have similar effectiveness to other individual first-line classes of antihypertensive drugs in reducing mortality and morbidity outcomes?

Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences.

To compare the effects of first-line diuretic drugs with other individual first-line classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. Secondary objectives included assessments of the need for added drugs, drug switching, and blood pressure-lowering.

When used as first-line agents for the treatment of hypertension, thiazides and thiazide-like drugs likely do not change total mortality and likely decrease some morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects, when compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers.

SUPPORTED

MEDIUM

cardiovascular system

Do acute assessment services affect patient flow following attendance at a hospital ED?

Emergency departments (EDs) are facing serious and significant issues in the delivery of effective and efficient care to patients. Acute assessment services have been implemented at many hospitals internationally to assist in maintaining patient flow for identified groups of patients attending the ED. Identifying the risks and benefits, and optimal configurations of these services may be beneficial to those wishing to utilise an acute assessment service to improve patient flow.

To assess the effects of acute assessment services on patient flow following attendance at a hospital ED.

At present there are no randomised controlled trials exploring the effects of acute assessment services on patient flow in hospital-based emergency departments compared to usual, ED-only care.

NOT ENOUGH INFORMATION

LOW

miscellaneous

Did the network meta-analysis compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis?

Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.

To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms.

Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Do interventions for people with type 2 diabetes fasting during Ramadan have clear benefits or harms?

Fasting during Ramadan is obligatory for adult Muslims, except those who have a medical illness. Many Muslims with type 2 diabetes (T2DM) choose to fast, which may increase their risks of hypoglycaemia and dehydration.

To assess the effects of interventions for people with type 2 diabetes fasting during Ramadan.

There is no clear evidence of the benefits or harms of interventions for individuals with T2DM who fast during Ramadan. All results should be interpreted with caution due to concerns about risk of bias, imprecision and inconsistency between studies, which give rise to low- to very low-certainty evidence. Major outcomes, such as mortality, health-related quality of life and severe hypoglycaemia, were rarely evaluated. Sufficiently powered studies that examine the effects of various interventions on these outcomes are needed.

NOT ENOUGH INFORMATION

LOW

endocrine system and hormones

Does the qualitative literature on healthcare workers' perceptions and experiences of PHC integration provide a characterisation of the evidence base?

Primary healthcare (PHC) integration has been promoted globally as a tool for health sector reform and universal health coverage (UHC), especially in low-resource settings. However, for a range of reasons, implementation and impact remain variable. PHC integration, at its simplest, can be considered a way of delivering PHC services together that sometimes have been delivered as a series of separate or 'vertical' health programmes. Healthcare workers are known to shape the success of implementing reform interventions. Understanding healthcare worker perceptions and experiences of PHC integration can therefore provide insights into the role healthcare workers play in shaping implementation efforts and the impact of PHC integration. However, the heterogeneity of the evidence base complicates our understanding of their role in shaping the implementation, delivery, and impact of PHC integration, and the role of contextual factors influencing their responses.

To map the qualitative literature on healthcare workers' perceptions and experiences of PHC integration to characterise the evidence base, with a view to better inform future syntheses on the topic.

This scoping review provides a systematic, descriptive overview of the heterogeneity in qualitative literature on healthcare workers' perceptions and experience of PHC integration, pointing to diversity with regard to country settings; study types; client populations; healthcare worker populations; and intervention focus, scope, and strategies. It would be important for researchers and decision-makers to understand how the diversity in PHC integration intervention design, implementation, and context may influence how healthcare workers shape PHC integration impact. The classification of studies on the various dimensions (e.g. integration focus, scope, strategy, and type of healthcare workers and client populations) can help researchers to navigate the way the literature varies and for specifying potential questions for future qualitative evidence syntheses.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health