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Does transjugular intrahepatic portosystemic shunts (TIPS) provide benefits in adults with hepatorenal syndrome compared to other treatments? | Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and portal hypertension. The prognosis is dismal, often with a survival of weeks to months. Hepatorenal syndrome is characterised by the development of intense splanchnic vasodilation favouring ascites and hypotension leading to renal vasoconstriction and acute renal failure. Therefore, treatment attempts focus on improving arterial pressure through the use of vasopressors, paracentesis, and increasing renal perfusion pressure. Several authors have reported that the placement of transjugular intrahepatic portosystemic shunts (TIPS) may be a therapeutic option because it decreases portal pressure and improves arterial and renal pressures. However, the evidence is not clearly documented and TIPS may cause adverse events. Accordingly, it is necessary to evaluate the evidence of the benefits and harms of TIPS to assess its value in people with hepatorenal syndrome. | To evaluate the benefits and harms of transjugular intrahepatic portosystemic shunts (TIPS) in adults with hepatorenal syndrome compared with sham, no intervention, conventional treatment, or other treatments. | TIPS placement was compared with conventional treatment, with a follow-up of 24 months, in adults with hepatorenal syndrome type 2. Based on two trials with insufficient sample size and trial limitations, we assessed the overall certainty of evidence as low or very low. We are unsure if TIPS may decrease all-cause mortality, serious adverse events, the number of people who did not receive a liver transplant, and the days of hospitalisation because of the very low-certainty evidence. We are unsure if TIPS, compared with conventional treatment, has better effects on overall morbidity (bacterial peritonitis, encephalopathy, or refractory ascites). TIPS may improve kidney function, but the certainty of evidence is low. The trials included no data on health-related quality of life, non-serious adverse events, and liver function associated with the TIPS placement. We identified one ongoing trial and one study awaiting classification which may contribute to the review when information becomes available. | NOT ENOUGH INFORMATION | LOW | 1 | digestive system and metabolism |
Do non-pharmacological interventions reduce pain during endotracheal suctioning in mechanically ventilated neonates? | Pain, when treated inadequately, puts preterm infants at a greater risk of developing clinical and behavioural sequelae because of their immature pain system. Preterm infants in need of intensive care are repeatedly and persistently exposed to noxious stimuli, and this happens during a critical window of their brain development with peak rates of brain growth, exuberant synaptogenesis and the developmental regulation of specific receptor populations. Nearly two-thirds of infants born at less than 29 weeks' gestation require mechanical ventilation for some duration during the newborn period. These neonates are endotracheally intubated and require repeated endotracheal suctioning. Endotracheal suctioning is identified as one of the most frequent and most painful procedures in premature infants, causing moderate to severe pain. Even with improved nursing performance and standard procedures based on neonatal needs, endotracheal suctioning remains associated with mild pain. | To evaluate the benefits and harms of non-pharmacological interventions for the prevention of pain during endotracheal suctioning in mechanically ventilated neonates. Non-pharmacological interventions were compared to no intervention, standard care or another non-pharmacological intervention. | Facilitated tucking / four-handed care / gentle human touch probably reduces PIPP score. The evidence of a single study suggests that facilitated tucking / four-handed care / gentle human touch slightly increases self-regulatory and approach behaviours during endotracheal suctioning. Based on a single study, familiar odour and white noise have little or no effect on any of the outcomes compared to no intervention. The use of expressed breast milk or oral sucrose suggests that there is no discernible advantage of one method over the other for reducing pain during endotracheal suctioning. None of the studies reported on any of the prespecified secondary outcomes of adverse events. | SUPPORTED | LOW | 0 | cognitive, mental, and mental health |
Are pharmacological interventions effective for preventing blood loss in hip or knee replacement surgery? | Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care. | To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology. | We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review. | SUPPORTED | MEDIUM | 0 | musculoskeletal system and dermatology |
Is there a benefit of off-midline flap procedures over midline closure for pilonidal sinus? | Pilonidal sinus disease is a common and debilitating condition. Surgical treatment remains the mainstay for managing chronic disease, with options including midline and off-midline wound closure methods. However, the optimal approach remains uncertain. Recent developments in tension-free midline techniques require further exploration. | To assess the effects of midline and off-midline wound closure methods for pilonidal sinus, and to determine the optimal off-midline flap procedures. | This Cochrane review examines the midline and off-midline wound closure options for pilonidal sinus, predominantly based on young adult studies. Off-midline flap procedures demonstrate there may be benefits over conventional midline closure for pilonidal sinus, with various off-midline flap techniques. When off-midline flap closures were compared to tension-free midline closure, low-certainty evidence indicated there may be improved wound healing and increased time to return to work for off-midline closure, whilst very low-certainty evidence indicated there may be no evidence of a difference in other outcomes. There may be no evidence of an advantage found amongst the off-midline techniques evaluated. The choice of either procedure is likely to be based on a clinician's preference, experience, patient characteristics, and the patients' preferences. To more accurately determine the benefits and potential harms of these closure techniques, further large-scale and meticulously-designed trials are essential. Specifically, there is a pressing need for more studies addressing the paediatric population, in addition to adult studies. | NOT ENOUGH INFORMATION | LOW | 0 | musculoskeletal system and dermatology |
Does testosterone replacement therapy have a significant effect on erectile function and sexual quality of life in men with sexual dysfunction? | Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. | To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. | In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care. | REFUTED | LOW | 2 | sexual and reproductive health |
Do psychological interventions have efficacy for modifying health and behavioral outcomes in children with asthma? | Rates of asthma are high in children and adolescents, and young people with asthma generally report poorer health outcomes than those without asthma. Young people with asthma experience a range of challenges that may contribute to psychological distress. This is compounded by the social, psychological, and developmental challenges experienced by all people during this life stage. Psychological interventions (such as behavioural therapies or cognitive therapies) have the potential to reduce psychological distress and thus improve behavioural outcomes such as self-efficacy and medication adherence. In turn, this may reduce medical contacts and asthma attacks. | To determine the efficacy of psychological interventions for modifying health and behavioural outcomes in children with asthma, compared with usual treatment, treatment with no psychological component, or no treatment. | Most studies that reported symptoms of anxiety, depression, asthma attacks, asthma symptoms, and medication use found a positive effect of psychological interventions versus control on at least one measure. However, some findings were mixed, it was difficult to judge clinical significance, and the evidence for all outcomes is very uncertain due to clinical heterogeneity, small sample sizes, incomplete reporting, and risk of bias. There is limited evidence to suggest that psychological interventions can reduce the need for medical contact or improve quality of life, and no studies reported adverse events. It was not possible to identify components of effective interventions and distinguish these from interventions showing no evidence of an effect due to substantial heterogeneity. Future investigations of evidence-based psychological techniques should consider standardising outcomes to support cross-comparison and better inform patient and policymaker decision-making. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Does alpha-lipoic acid have a disease-modifying effect on diabetic peripheral neuropathy? | Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN. Although alpha-lipoic acid (ALA, also known as thioctic acid) is widely used, there is no consensus about its benefits and harms. | To assess the effects of alpha-lipoic acid as a disease-modifying agent in people with diabetic peripheral neuropathy. | Our analysis suggests that ALA probably has little or no effect on neuropathy symptoms or adverse events at six months, and may have little or no effect on impairment at six months. All the studies were at high risk of attrition bias. Therefore, future RCTs should ensure complete follow-up and transparent reporting of any participants missing from the analyses. | REFUTED | MEDIUM | 2 | endocrine system and hormones |
Do oral killed cholera vaccines reduce cases of cholera among children and adults? | Cholera causes acute watery diarrhoea and death if not properly treated. Outbreaks occur in areas with poor sanitation, including refugee camps. Several vaccines have been developed and tested over the last 50 years. This is an update of a Cochrane review, originally published in 1998, which explored the effects of all vaccines for preventing cholera. This review examines oral vaccines made from killed bacteria. | To assess the effectiveness and safety of the available World Health Organization (WHO)-prequalified oral killed cholera vaccines among children and adults. | Two doses of Dukoral reduces cases of cholera at two-year follow-up. Two doses of Shanchol reduces cases of cholera at five-year follow-up, and a single dose of Shanchol reduces cases of cholera at two-year follow-up. Overall, the vaccines were safe and well-tolerated. We found no trials on other BivWC vaccines (Euvichol/Euvichol-Plus). However, BivWC products (Shanchol, Euvichol/Euvichol-Plus) are considered to produce comparable vibriocidal responses. Therefore, it is reasonable to apply the results from Shanchol trials to the other BivWC products (Euvichol/Euvichol-Plus). | SUPPORTED | MEDIUM | 0 | immune system and infections |
Do behavioural-change interventions promote the use of seat belts? | Over 1.3 million people die each year as a result of traffic collisions and hundreds of thousands of others are permanently and seriously injured. Most of these deaths occur in low- and middle-income countries, where mortality rates can be up to 10 times higher than those of some high-income countries. Seat belts are designed to accomplish two key functions - to prevent the occupant from being ejected from the vehicle by the force of impact, and to extend the time that the decelerating force is applied to a person. Seat belts also spread the area of impact both to larger and less vulnerable parts of the body. Since the 1950s, seat belts have been factory-fitted to most vehicles, and today around 90% of high-income countries have adopted seat belt legislation that makes it mandatory for some, if not all, vehicle occupants to wear seat belts. However, the simple passing of laws is not sufficient to ensure seat belt use, and, while the enforcement of seat belt laws does increase seat belt use, other interventions have been developed to encourage voluntary - and hence sustainable - behaviour change. | To evaluate the benefits of behavioural-change interventions (educational-based, incentive-based, engineering-based, or a combination, but not enforcement-based) that promote the use of seat belts, and to determine which types of interventions are most effective. | The evidence suggests that behavioural education-based interventions may promote seat belt use and HRA (including incentives) with or without additional interventions likely promote seat belt use. Likewise, for engineering-based interventions using in-vehicle data monitor systems with in-vehicle alerts, with or without notifications/feedback the evidence suggests the interventions may promote the use of seat belts. Well-designed RCTs are needed to further investigate the effectiveness of education and engineering-based interventions. High-quality trials that examine the potential benefits of incentives to promote seat belt use, either alone or in combination with other interventions, as well as trials to investigate other types of interventions (such as technology, media/publicity, enforcement, insurance schemes, employer programmes, etc.) to promote the use of seat belts, are needed. Evidence from low- and middle-income economies is required to improve the generalisability of the data. In addition, research focused on determining which interventions or types of interventions are most effective in different population groups is needed. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Did mindfulness-enhanced parent training programmes improve the psychosocial functioning of children and their parents? | Emotional and behavioural difficulties (EBD) in children are common, characterised by externalising or internalising behaviours that can be highly stable over time. EBD are an important cause of functional disability in childhood, and predictive of poorer psychosocial, academic, and occupational functioning into adolescence and adulthood. The prevalence, stability, and long-term consequences of EBD highlight the importance of intervening in childhood when behavioural patterns are more easily modified. Multiple factors contribute to the aetiology of EBD in children, and parenting plays an important role. The relationship between parenting and EBD has been described as bidirectional, with parents and children shaping one another's behaviour. One consequence of bidirectionality is that parents with insufficient parenting skills may become involved in increasingly negative behaviours when dealing with non-compliance in children. This can have a cyclical effect, exacerbating child behavioural difficulties and further increasing parental distress. Behavioural or skills-based parenting training can be highly effective in addressing EBD in children. However, emotional dysregulation may intercept some parents' ability to implement parenting skills, and there is recognition that skills-based interventions may benefit from adjunct components that better target parental emotional responses. Mindful parenting interventions have demonstrated some efficacy in improving child outcomes via improvements in parental emotion regulation, and there is potential for mindfulness training to enhance the effectiveness of standard parent training programmes. | To assess the effectiveness of mindfulness-enhanced parent training programmes on the psychosocial functioning of children (aged 0 to 18 years) and their parents. | Mindfulness-enhanced parenting training may improve some parent and child outcomes, with no studies reporting adverse effects. Evidence for the added value of mindfulness training to skills-based parenting training programmes is suggestive at present, with moderate reductions in parenting stress. Given the very low to low certainty evidence reviewed here, these estimates will likely change as more high-quality studies are produced. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Is retrograde distal access for below the knee angioplasty more beneficial than conventional femoral access? | The prevalence of peripheral artery disease (PAD) in the general population is about 12% to 14% and it increases with age. PAD increased from 164 million people in 2000 to 202 million people in 2010. More than two-thirds of people with PAD are based in low- or middle-income countries. Critical limb ischaemia (CLI) occurs in 1% to 2% of people with intermittent claudication over five years. One third of people with CLI have isolated below the knee (BTK) lesions. CLI and isolated BTK lesions are associated with a higher incidence of limb loss when compared with people with multilevel arterial disease. Endovascular procedures such as angioplasty (with or without stenting) are widely used to treat isolated BTK lesions, aiming to improve blood flow and limb salvage. The technical success of any angioplasty procedure depends on the ability to cross the target lesion. Failed attempts are underestimated in the literature and failures in the real world appear to be higher than reported. People with isolated BTK lesions undergoing angioplasty by conventional femoral access present a high failure rate to cross these lesions. Retrograde distal access may provide some advantages that can lead to successful crossing of the target lesion. | To evaluate the benefits and harms of retrograde distal access versus conventional femoral access for people undergoing below the knee angioplasty. | We identified no randomised or quasi-randomised controlled trials that compared retrograde distal access versus femoral access for BTK angioplasty. High-quality studies that compare retrograde distal access versus conventional femoral access for BTK angioplasty are needed. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Is one anticoagulation strategy for long-term hemodialysis more effective and safer than another? | Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding. | To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included. | Anticoagulant strategies, including UFH and LMWH, have uncertain comparative risks on extracorporeal circuit thrombosis, while major bleeding and minor bleeding were not adequately reported. Regional citrate may decrease minor bleeding, but the effects on major bleeding and extracorporeal circuit thrombosis were not reported. Evidence supporting clinical decision-making for different forms of anticoagulant strategies for HD is of low and very low certainty, as available studies have not been designed to measure treatment effects on important clinical outcomes. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Does pressure-garment therapy effectively prevent hypertrophic scarring after burn injury? | Burn damage to skin often results in scarring; however in some individuals the failure of normal wound-healing processes results in excessive scar tissue formation, termed 'hypertrophic scarring'. The most commonly used method for the prevention and treatment of hypertrophic scarring is pressure-garment therapy (PGT). PGT is considered standard care globally; however, there is continued uncertainty around its effectiveness. | To evaluate the benefits and harms of pressure-garment therapy for the prevention of hypertrophic scarring after burn injury. | There is insufficient evidence to recommend using either PGT or an alternative for preventing hypertrophic scarring after burn injury. PGT is already commonly used in practice and it is possible that continuing to do so may provide some benefit to some people. However, until more evidence becomes available, it may be appropriate to allow patient preference to guide therapy. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Does oral vitamin B have benefits and harms? | Vitamin B | To evaluate the benefits and harms of oral vitamin B | Oral vitamin B | NOT ENOUGH INFORMATION | LOW | 1 | nutrition and dietary supplements |
Does carpal tunnel release produce better outcomes than non-surgical treatment? | Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve at the wrist. Surgery is considered when symptoms persist despite the use of non-surgical treatments. It is unclear whether surgery produces a better outcome than non-surgical therapy. This is an update of a Cochrane review published in 2008. | To assess the evidence regarding the benefits and harms of carpal tunnel release compared with non-surgical treatment in the short (< 3 months) and long (> 3 months) term. | Currently, the efficacy of surgery in people with CTS is unclear. It is also unclear if the results can be applied to people who are not satisfied after trying various non-surgical options. Future studies should preferably blind participants from treatment allocation and randomise people who are dissatisfied after being treated non-surgically. The decision for a patient to opt for surgery should balance the small benefits and potential risks of surgery. Patients with severe symptoms, a high preference for clinical improvement and reluctance to adhere to non-surgical options, and who do not consider potential surgical risks and morbidity a burden, may choose surgery. On the other hand, those who have tolerable symptoms, who have not tried non-surgical options and who want to avoid surgery-related morbidity can start with non-surgical options and have surgery only if necessary. We are uncertain if the risk of adverse effects differs between surgery and non-surgical treatments. The severity of adverse effects may also be different. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Does disulfiram show efficacy and safety for the treatment of cocaine dependence? | Cocaine is a psychostimulant used by approximately 0.4% of the general population worldwide. Cocaine dependence is a chronic mental disorder characterised by the inability to control cocaine use and a host of severe medical and psychosocial complications. There is current no approved pharmacological treatment for cocaine dependence. Some researchers have proposed disulfiram, a medication approved to treat alcohol use disorder. This is an update of a Cochrane review first published in 2010. | To evaluate the efficacy and safety of disulfiram for the treatment of cocaine dependence. | Our results show that disulfiram compared to placebo may increase point abstinence. However, disulfiram compared to placebo or no pharmacological treatment may have little or no effect on frequency of cocaine use, amount of cocaine use, continued abstinence, and dropout for any reason. We are unsure if disulfiram has any adverse effects in this population. Caution is required when transferring our results to clinical practice. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Do population-based interventions effectively prevent falls and fall-related injuries in older people? | Around one-third of older adults aged 65 years or older who live in the community fall each year. Interventions to prevent falls can be designed to target the whole community, rather than selected individuals. These population-level interventions may be facilitated by different healthcare, social care, and community-level agencies. They aim to tackle the determinants that lead to risk of falling in older people, and include components such as community-wide polices for vitamin D supplementation for older adults, reducing fall hazards in the community or people's homes, or providing public health information or implementation of public health programmes that reduce fall risk (e.g. low-cost or free gym membership for older adults to encourage increased physical activity). | To review and synthesise the current evidence on the effects of population-based interventions for preventing falls and fall-related injuries in older people. We defined population-based interventions as community-wide initiatives to change the underlying societal, cultural, or environmental conditions increasing the risk of falling. | Given the very low-certainty evidence, we are unsure whether population-based multicomponent or nutrition and medication interventions are effective at reducing falls and fall-related injuries in older adults. Methodologically robust cluster RCTs with sufficiently large communities and numbers of clusters are needed. Establishing a rate of sampling for population-based studies would help in determining the size of communities to include. Interventions should be described in detail to allow investigation of effectiveness of individual components of multicomponent interventions; using the ProFaNE taxonomy for this would improve consistency between studies. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Does ibuprofen effectively manage acute postoperative pain in children compared to placebo or other active comparators? | Children often require pain management following surgery to avoid suffering. Effective pain management has consequences for healing time and quality of life. Ibuprofen, a frequently used non-steroidal anti-inflammatory drug (NSAID) administered to children, is used to treat pain and inflammation in the postoperative period. | 1) To assess the efficacy and safety of ibuprofen (any dose) for acute postoperative pain management in children compared with placebo or other active comparators. 2) To compare ibuprofen administered at different doses, routes (e.g. oral, intravenous, etc.), or strategies (e.g. as needed versus as scheduled). | Despite identifying 43 RCTs, we remain uncertain about the effect of ibuprofen compared to placebo or active comparators for some critical outcomes and in the comparisons between different doses, schedules and routes for ibuprofen administration. This is largely due to poor reporting on important outcomes such as serious adverse events, and poor study conduct or reporting that reduced our confidence in the results, along with small underpowered studies. Compared to placebo, ibuprofen likely results in pain reduction less than two hours postintervention, however, the efficacy might be lower at two hours to 24 hours. Compared to paracetamol, ibuprofen likely results in pain reduction up to 24 hours postintervention. We could not explore if there was a different effect in different kinds of surgeries or procedures. Ibuprofen likely results in a reduction in adverse events compared to morphine, and in little to no difference in bleeding when compared to paracetamol. We remain mostly uncertain about the safety of ibuprofen compared to other drugs. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does individualising gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI affect live birth/ongoing pregnancy rates? | During a stimulated cycle of in vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. A normal response to stimulation (e.g. retrieval of 5 to 15 oocytes) is considered desirable. Generally, the number of eggs retrieved is associated with the dose of FSH. Both hyper-response and poor response are associated with an increased chance of cycle cancellation. In hyper-response, this is due to increased risk of ovarian hyperstimulation syndrome (OHSS), while poor response cycles are cancelled because the quantity and quality of oocytes is expected to be low. Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response. Traditionally, this meant women's age, but increasingly, clinicians use various ovarian reserve tests (ORTs). These include basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose improves clinical outcomes. This review updates the 2018 version. | To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. | We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT) affected live birth/ongoing pregnancy rates, but we could not rule out differences, due to sample size limitations. Low-certainty evidence suggests that it is unclear if ORT-based individualisation leads to an increase in live birth/ongoing pregnancy rates compared to a policy of giving all women 150 IU. The confidence interval is consistent with an increase of up to around six percentage points with ORT-based dosing (e.g. from 25% to 31%) or a very small decrease (< 1%). A difference of this magnitude could be important to many women. It is unclear if this is driven by improved outcomes in a particular subgroup. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU. However, the size of the effect is also unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates. It is likely that different ORT algorithms differ in their effectiveness. Current evidence does not provide a clear justification for adjusting the dose of 150 IU in poor or normal responders, especially as increased dose is associated with greater total FSH dose and cost. It is unclear whether a decreased dose in predicted high responders reduces OHSS, although this would appear to be the most likely explanation for the results. | NOT ENOUGH INFORMATION | LOW | 1 | sexual and reproductive health |
Does maintenance therapy, including various agents, have significant effects on individuals with CLL? | Chronic lymphocytic leukaemia (CLL) is the most common lymphoproliferative disease in adults and currently remains incurable. As the progression-free period shortens after each successive treatment, strategies such as maintenance therapy are needed to improve the degree and duration of response to previous therapies. Monoclonal antibodies, immunomodulatory agents, and targeted therapies are among the available options for maintenance therapy. People with CLL who achieve remission after previous therapy may choose to undergo medical observation or maintenance therapy to deepen the response. Even though there is widespread use of therapeutic maintenance agents, the benefits and harms of these treatments are still uncertain. | To assess the effects and safety of maintenance therapy, including anti-CD20 monoclonal antibody, immunomodulatory drug therapy, anti-CD52 monoclonal antibody, Bruton tyrosine kinase inhibitor, and B-cell lymphoma-2 tyrosine kinase inhibitor, for individuals with CLL. | There is currently moderate- to very low-certainty evidence available regarding the benefits and harms of maintenance therapy in people with CLL. Anti-CD20 mAbs maintenance improved PFS, but also increased grade 3/4 AEs and all AEs. IMiD maintenance had a large effect on PFS, but also increased grade 3/4 AEs. However, none of the above-mentioned maintenance interventions show differences in OS between the maintenance and control groups. The effects of alemtuzumab maintenance are uncertain, coupled with a warning for drug-related infectious toxicity. We found no studies evaluating other novel maintenance interventions, such as B-cell receptor inhibitors, B-cell leukaemia-2/lymphoma-2 inhibitors, or obinutuzumab. | NOT ENOUGH INFORMATION | LOW | 0 | cancer |
Did the review investigate and compare the effect estimates from RCTs and observational studies? | Researchers and decision-makers often use evidence from randomised controlled trials (RCTs) to determine the efficacy or effectiveness of a treatment or intervention. Studies with observational designs are often used to measure the effectiveness of an intervention in 'real world' scenarios. Numerous study designs and their modifications (including both randomised and observational designs) are used for comparative effectiveness research in an attempt to give an unbiased estimate of whether one treatment is more effective or safer than another for a particular population. An up-to-date systematic analysis is needed to identify differences in effect estimates from RCTs and observational studies. This updated review summarises the results of methodological reviews that compared the effect estimates of observational studies with RCTs from evidence syntheses that addressed the same health research question. | To assess and compare synthesised effect estimates by study type, contrasting RCTs with observational studies. To explore factors that might explain differences in synthesised effect estimates from RCTs versus observational studies (e.g. heterogeneity, type of observational study design, type of intervention, and use of propensity score adjustment). To identify gaps in the existing research comparing effect estimates across different study types. | We found no difference or a very small difference between effect estimates from RCTs and observational studies. These findings are largely consistent with findings from recently published research. Factors other than study design need to be considered when exploring reasons for a lack of agreement between results of RCTs and observational studies, such as differences in the population, intervention, comparator, and outcomes investigated in the respective studies. Our results underscore that it is important for review authors to consider not only study design, but the level of heterogeneity in meta-analyses of RCTs or observational studies. A better understanding is needed of how these factors might yield estimates reflective of true effectiveness. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Do certain treatments for relapsing-remitting multiple sclerosis decrease relapses more than others? | Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear. This is an update of a Cochrane review published in 2015. | To compare the efficacy and safety, through network meta-analysis, of interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1-a and beta 1-b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS. | We are highly confident that, compared to placebo, two-year treatment with natalizumab, cladribine, or alemtuzumab decreases relapses more than with other DMTs. We are moderately confident that a two-year treatment with natalizumab may slow disability progression. Compared to those on placebo, people with RRMS treated with most of the assessed DMTs showed a higher frequency of treatment discontinuation due to AEs: we are moderately confident that this could happen with fingolimod, teriflunomide, interferon beta-1a, laquinimod, natalizumab and daclizumab, while our certainty with other DMTs is lower. We are also moderately certain that treatment with alemtuzumab is associated with fewer discontinuations due to adverse events than placebo, and moderately certain that interferon beta-1b probably results in a slight reduction in people who experience serious adverse events, but our certainty with regard to other DMTs is lower. Insufficient evidence is available to evaluate the efficacy and safety of DMTs in a longer term than two years, and this is a relevant issue for a chronic condition like MS that develops over decades. More than half of the included studies were sponsored by pharmaceutical companies and this may have influenced their results. Further studies should focus on direct comparison between active agents, with follow-up of at least three years, and assess other patient-relevant outcomes, such as quality of life and cognitive status, with particular focus on the impact of sex/gender on treatment effects. | SUPPORTED | HIGH | 0 | cognitive, mental, and mental health |
Does the position of the newborn during lumbar puncture affect the success rate and safety of the procedure? | Lumbar puncture is a common invasive procedure performed in newborns for diagnostic and therapeutic purposes. Approximately one in two lumbar punctures fail, resulting in both short- and long-term negative consequences for the clinical management of patients. The most common positions used to perform lumbar puncture are the lateral decubitus and sitting position, and each can impact the success rate and safety of the procedure. However, it is uncertain which position best improves patient outcomes. | To assess the benefits and harms of the lateral decubitus, sitting, and prone positions for lumbar puncture in newborn infants. | When compared to sitting position, lateral decubitus position probably results in little to no difference in successful lumbar puncture procedure at first attempt. None of the included studies reported the total number of lumbar puncture attempts as specified in this review. Furthermore, infants in a sitting position likely experience less episodes of bradycardia and oxygen desaturation than in the lateral decubitus, and there may be little to no difference in episodes of apnea. Lateral decubitus position results in little to no difference in time to perform the lumbar puncture compared to sitting position. Pain intensity during and after the procedure was reported using a pain scale that was not included in our prespecified tools for pain assessment due to its high risk of bias. Most study participants were term newborns, thereby limiting the applicability of these results to preterm babies. When compared to prone position, lateral decubitus position may reduce successful lumbar puncture procedure at first attempt. Only one study reported on this comparison and did not evaluate adverse effects. Further research exploring harms and benefits and the effect on patients' pain experience of different positions during lumbar puncture using validated pain scoring tool may increase the level of confidence in our conclusions. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Is cranberry effective for treating UTIs? | Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in treating such infections. | To assess the effectiveness of cranberries for the treatment of UTIs. | After a thorough search, no RCTs which assessed the effectiveness of cranberry juice for the treatment of UTIs were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of UTIs. Well-designed parallel-group, double-blind studies comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating UTIs are needed. Outcomes should include a reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. The dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these studies. | NOT ENOUGH INFORMATION | LOW | 2 | urinary system |
Did medically assisted hydration (MAH) improve quality of life and survival in adults receiving palliative care compared to placebo and standard care? | Many people receiving palliative care have reduced oral intake during their illness, and particularly at the end of their life. Management of this can include the provision of medically assisted hydration (MAH) with the aim of improving their quality of life (QoL), prolonging their life, or both. This is an updated version of the original Cochrane Review published in Issue 2, 2008, and updated in February 2011 and March 2014. | To determine the effectiveness of MAH compared with placebo and standard care, in adults receiving palliative care on their QoL and survival, and to assess for potential adverse events. | پیشینه: بسیاری از افرادی که مراقبت تسکینی دریافت میکنند، در طول بیماری خود، و به ویژه در پایان عمر، مصرف مواد خوراکی را کاهش دادهاند. مدیریت این امر میتواند شامل ارائه هیدراتاسیون کمکی پزشکی (medically assisted hydration; MAH) با هدف بهبود کیفیت زندگی (quality of life; QoL)، طولانی کردن عمر آنها، یا هر دو، باشد. این یک نسخه بهروز شده از مرور اصلی کاکرین است که در شماره 2، سال 2008 منتشر و در فوریه 2011 و مارچ 2014 بهروز شد. اهداف: تعیین اثربخشی MAH در مقایسه با دارونما (placebo) و مراقبت استاندارد، در بزرگسالان دریافتکننده مراقبت تسکینی بر QoL و بقای (survival) آنها، و ارزیابی عوارض جانبی بالقوه. روشهای جستوجو: برای یافتن مطالعات به جستوجو در پایگاه مرکزی ثبت کارآزماییهای کنترل شده کاکرین (CENTRAL)؛ MEDLINE؛ Embase؛ CINAHL؛ CANCERLIT؛ CareSearch؛ Dissertation Abstracts؛ Science Citation Index و فهرست منابع همه مطالعات واجد شرایط، کتابهای درسی کلیدی، و مرورهای سیستماتیک قبلی پرداختیم. تاریخ آخرین جستوجوی انجام شده در CENTRAL؛ MEDLINE و Embase؛ 17 نوامبر 2022 بود. معیارهای انتخاب: همه کارآزماییهای تصادفیسازی و کنترل شده (randomised controlled trials; RCTs) مرتبط را در مورد مطالعات مربوط به MAH در بزرگسالان دریافتکننده مراقبت تسکینی در سن 18 سال و بالاتر وارد کردیم. معیار ورود، مقایسه MAH با دارونما یا مراقبت استاندارد بود. گردآوری و تجزیهوتحلیل دادهها: سه نویسنده مرور بهطور مستقل از هم عناوین و چکیدههای مقالات را به لحاظ مرتبط بودن مرور کرده و دو نویسنده مرور دادهها را استخراج کردند و ارزیابی خطر سوگیری (bias) را انجام دادند. پیامد اولیه شامل QoL با استفاده از مقیاسهای معتبر؛ و پیامدهای ثانویه شامل بقا و عوارض جانبی بودند. برای پیامدهای پیوسته (continuous outcome)، میانگین حسابی و انحراف معیار (standard deviation; SD) را اندازهگیری کرده و تفاوت میانگین (MD) را با 95% فاصله اطمینان (CI) میان گروهها گزارش کردیم. برای پیامدهای دو حالتی (dichotomous outcome)، خطر نسبی (RR) را با 95% CIهای میان گروهها تخمین زده و مقایسه کردیم. برای دادههای زمان‐تا‐رویداد (time‐to‐event)، قصد داشتیم زمان بقا را از تاریخ تصادفیسازی محاسبه کرده و تاثیر مداخله را در قالب نسبت خطر (HR) تخمین زده و بیان کنیم. سطح قطعیت شواهد را با استفاده از رویکرد درجهبندی توصیه، ارزیابی، توسعه و ارزشیابی (Grading of Recommendations Assessment, Development and Evaluation; GRADE) ارزیابی کرده و دو جدول خلاصهای از یافتهها را تهیه کردیم. نتایج اصلی: یک مطالعه جدید (200 شرکتکننده) را یافتیم، که در مجموع چهار مطالعه در این نسخه بهروز شده (422 شرکتکننده) حضور دارند. همه شرکتکنندگان تشخیص سرطان پیشرفته داشتند. به استثنای 29 شرکتکننده که بدخیمی خونی داشتند، بقیه مبتلا به سرطانهای ارگانهای توپُر (solid organ cancer) بودند. دو مطالعه هر کدام MAH را با دارونما و مراقبت استاندارد مقایسه کردند. مطالعات وارد شده بسیار کمی برای ارزیابی زیر گروههای مختلف، مانند نوع شرکتکننده، مداخله، زمانبندی مداخله، و محل انجام مطالعه وجود داشت. یک مطالعه را در معرض خطر بالای سوگیری عملکرد (performance bias) و تشخیص (detection bias) ناشی از عدم کورسازی (blinding) در نظر گرفتیم؛ در غیر این صورت، خطر سوگیری در سطح پائین یا نامشخص ارزیابی شد. MAH در مقایسه با دارونما کیفیت زندگی یک مطالعه تغییر QoL را در یک هفته با استفاده از ارزیابی عملکردی درمان سرطان‐عمومی (Functional Assessment of Cancer Therapy ‐ General; FACT‐G) اندازهگیری کرد (مقیاس از 0 تا 108 امتیاز؛ امتیاز بالاتر = QoL بهتر). هیچ دادهای از مطالعه دیگر در دسترس نبود. ما مطمئن نیستیم که MAH باعث بهبود QoL میشود یا خیر (MD: 4.10؛ 95% CI؛ 1.63‐ تا 9.83؛ 1 مطالعه، 93 شرکتکننده، شواهد با قطعیت بسیار پائین). بقا یک مطالعه گزارشی را از بقای بیمار از زمان ورود به مطالعه تا آخرین تاریخ پیگیری یا مرگومیر ارائه داد. ما نتوانستیم HR را تخمین بزنیم. هیچ دادهای از مطالعه دیگر در دسترس نبود. ما مطمئن نیستیم که MAH باعث بهبود بقای بیمار میشود یا خیر (1 مطالعه، 93 شرکتکننده، شواهد با قطعیت بسیار پائین). عوارض جانبی یک مطالعه، شدت عوارض جانبی را در دو روز با استفاده از مقیاس رتبهبندی عددی گزارش کرد (مقیاس از 0 تا 10 امتیاز؛ امتیاز کمتر = سمیّت کمتر). هیچ دادهای از مطالعه دیگر در دسترس نبود. ما مطمئن نیستیم که MAH منجر به عوارض جانبی میشود یا خیر (درد در محل تزریق: MD: 0.35؛ 95% CI؛ 1.19‐ تا 1.89؛ تورم محل تزریق: (MD: ‐0.59؛ 95% CI؛ 1.40‐ تا 0.22؛ 1 مطالعه، 49 شرکتکننده، شواهد با قطعیت بسیار پائین). MAH در مقایسه با مراقبت استاندارد کیفیت زندگی هیچ دادهای برای QoL در دسترس نبود. بقا یک مطالعه بقا را از زمان تصادفیسازی تا آخرین تاریخ پیگیری در 14 روز یا زمان فوت بیمار اندازهگیری کرد. هیچ دادهای از مطالعه دیگر در دسترس نبود. ما مطمئن نیستیم که MAH باعث بهبود بقا میشود یا خیر (HR: 0.36؛ 95% CI؛ 0.22 تا 0.59؛ 1 مطالعه، 200 شرکتکننده، شواهد با قطعیت بسیار پائین). عوارض جانبی دو مطالعه عوارض جانبی را در دوره پیگیری (بین 2 و 14 روز) اندازهگیری کردند. ما مطمئن نیستیم که MAH منجر به بروز عوارض جانبی میشود یا خیر (RR: 11.62؛ 95% CI؛ 1.62 تا 83.41؛ 2 مطالعه، 242 شرکتکننده، شواهد با قطعیت بسیار پائین). نتیجهگیریهای نویسندگان: از زمان نسخه بهروز شده قبلی این مرور، یک مطالعه جدید را پیدا کردهایم. در بزرگسالانی که در مرحله پایانی بیماری خود مراقبت تسکینی دریافت میکنند، شواهد کافی برای تعیین اینکه MAH در مقایسه با دارونما یا مراقبت استاندارد باعث بهبود QoL یا افزایش بقا میشود یا خیر، وجود ندارد. با توجه به اینکه همه شرکتکنندگان، افراد بستری شده مبتلا به سرطان پیشرفته در پایان زندگی خود بودند، یافتههای ما قابل تعمیم به بزرگسالانی نیست که در دیگر مراکز، برای بیماریهای غیر سرطانی، دمانس یا بیماریهای نورودژنراتیو مراقبت تسکینی دریافت کرده، یا برای بیمارانی که دارای پیشآگهی طولانی هستند. متخصصان بالینی باید بر اساس مزایا و آسیبهای درک شده MAH برای شرایط هر فرد تصمیمگیری کنند، بدون آنکه مزیتی با شواهدی با کیفیت بالا داشته باشند که آنها را راهنمایی کند. | NOT ENOUGH INFORMATION | LOW | 0 | cancer |
Do topical and oral steroids have significant benefits for treating OME 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. Although most episodes of OME in children resolve spontaneously within a few months, when persistent it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and other treatments, such as autoinflation. Oral or topical steroids are sometimes used to reduce inflammation in the middle ear. | To assess the effects (benefits and harms) of topical and oral steroids for OME in children. | Overall, oral steroids may have little effect in the treatment of OME, with little improvement in the number of children with normal hearing and no effect on quality of life. There may be a reduction in the proportion of children with persistent disease after 12 months. However, this benefit may be small and must be weighed against the potential for adverse effects associated with oral steroid use. The evidence for nasal steroids was all low- or very low-certainty. It is therefore less clear if nasal steroids have any impact on hearing, quality of life or persistence of OME. Evidence on adverse effects was very limited. OME is likely to resolve spontaneously for most children. The potential benefit of treatment may therefore be small and should be balanced with the risk of adverse effects. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children. | REFUTED | LOW | 2 | cognitive, mental, and mental health |
Does motivational interviewing affect substance use, readiness to change, and retention in treatment? | Substance use is a global issue, with around 30 to 35 million individuals estimated to have a substance-use disorder. Motivational interviewing (MI) is a client-centred method that aims to strengthen a person's motivation and commitment to a specific goal by exploring their reasons for change and resolving ambivalence, in an atmosphere of acceptance and compassion. This review updates the 2011 version by Smedslund and colleagues. | To assess the effectiveness of motivational interviewing for substance use on the extent of substance use, readiness to change, and retention in treatment. | Motivational interviewing may reduce substance use compared with no intervention up to a short follow-up period. MI probably reduces substance use slightly compared with assessment and feedback over medium- and long-term periods. MI may make little to no difference to substance use compared to treatment as usual and another active intervention. It is unclear if MI has an effect on readiness to change and retention in treatment. The studies included in this review were heterogeneous in many respects, including the characteristics of participants, substance(s) used, and interventions. Given the widespread use of MI and the many studies examining MI, it is very important that counsellors adhere to and report quality conditions so that only studies in which the intervention implemented was actually MI are included in evidence syntheses and systematic reviews. Overall, we have moderate to no confidence in the evidence, which forces us to be careful about our conclusions. Consequently, future studies are likely to change the findings and conclusions of this review. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Do enzyme replacement therapies improve outcomes in people with late-onset Pompe disease? | Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme deficiency; people with late-onset Pompe disease (LOPD) retain some residual enzyme activity. GAA deficiency is treated with an intravenous infusion of recombinant human acid alglucosidase alfa, an enzyme replacement therapy (ERT). Alglucosidase alfa and avalglucosidase alfa are approved treatments, but cipaglucosidase alfa with miglustat is not yet approved. | To assess the effects of enzyme replacement therapies in people with late-onset Pompe disease. | One trial compared the effect of ERT to placebo in LOPD, showing that alglucosidase alfa probably improves 6MWT and respiratory function (both moderate-certainty evidence). Avalglucosidase alfa probably improves 6MWT compared with alglucosidase alfa (moderate-certainty evidence). Cipaglucosidase plus miglustat probably improves FVC compared to alglucosidase alfa plus placebo (moderate-certainty evidence). Other trials studied the adjunct effect of clenbuterol and albuterol along with alglucosidase alfa, with little to no evidence of benefit. No significant rise in adverse events was noted with all ERTs. The impact of ERT on some outcomes remains unclear, and longer RCTs are needed to generate relevant information due to the progressive nature of LOPD. Alternative resources, such as post-marketing registries, could capture some of this information. | SUPPORTED | MEDIUM | 0 | musculoskeletal system and dermatology |
Is diclofenac effective for managing acute postoperative pain in children? | Many children undergo various surgeries, which often lead to acute postoperative pain. This pain influences recovery and quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs), specifically cyclo-oxygenase (COX) inhibitors such as diclofenac, can be used to treat pain and reduce inflammation. There is uncertainty regarding diclofenac's benefits and harms compared to placebo or other drugs for postoperative pain. | To assess the efficacy and safety of diclofenac (any dose) for acute postoperative pain management in children compared with placebo, other active comparators, or diclofenac administered by different routes (e.g. oral, rectal, etc.) or strategies (e.g. 'as needed' versus 'as scheduled'). | We remain uncertain about the efficacy of diclofenac compared to placebo, active comparators, or by different routes of administration, for postoperative pain management in children. This is largely due to authors not reporting on clinically important outcomes; unclear reporting of the trials; or poor trial conduct reducing our confidence in the results. We remain uncertain about diclofenac's safety compared to placebo or active comparators, except for the comparison of diclofenac with opioids: diclofenac probably results in less nausea and vomiting compared with opioids, but more bleeding events. For healthcare providers managing postoperative pain, diclofenac is a COX inhibitor option, along with other pharmacological and non-pharmacological approaches. Healthcare providers should weigh the benefits and risks based on what is known of their respective pharmacological effects, rather than known efficacy. For surgical interventions in which bleeding or nausea and vomiting are a concern postoperatively, the risks of adverse events using opioids or diclofenac for managing pain should be considered. | NOT ENOUGH INFORMATION | LOW | 1 | miscellaneous |
Does add-on lamotrigine reduce seizures in people with drug-resistant focal epilepsy? | This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30% of cases, epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is a second-generation antiseizure medication. When used as an add-on (in combination with other antiseizure medications), lamotrigine can reduce seizures, but with some adverse effects. | To evaluate the benefits and harms of add-on lamotrigine, compared with add-on placebo or no add-on treatment in people with drug-resistant focal epilepsy. | Lamotrigine as an add-on treatment for drug-resistant focal seizures is probably effective for reducing seizure frequency. Certain adverse effects (ataxia, dizziness, diplopia, and nausea) are probably more likely to occur with lamotrigine compared with placebo. There is probably little or no difference in the number of people who withdraw from treatment with lamotrigine versus placebo. The trials were of relatively short duration and provided no long-term evidence. In addition, some trials had few participants. Further trials are needed to assess the long-term effects of lamotrigine and to compare lamotrigine with other add-on drugs. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Can reducing or stopping prescription of medications with anticholinergic properties improve cognitive outcomes in older people? | Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden. A high anticholinergic burden may cause cognitive impairment in people who are otherwise cognitively healthy, or cause further cognitive decline in people with pre-existing cognitive problems. Reducing anticholinergic burden through deprescribing interventions may help to prevent onset of cognitive impairment or slow the rate of cognitive decline. | Primary objective • To assess the efficacy and safety of anticholinergic medication reduction interventions for improving cognitive outcomes in cognitively healthy older adults and older adults with pre-existing cognitive issues. Secondary Objectives • To compare the effectiveness of different types of reduction interventions (e.g. pharmacist-led versus general practitioner-led, educational versus audit and feedback) for reducing overall anticholinergic burden. • To establish optimal duration of anticholinergic reduction interventions, sustainability, and lessons learnt for upscaling • To compare results according to differing anticholinergic scales used in medication reduction intervention trials • To assess the efficacy of anticholinergic medication reduction interventions for improving other clinical outcomes, including mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, and neurobehavioral outcomes. | There is insufficient evidence to reach any conclusions on the effects of anticholinergic burden reduction interventions on cognitive outcomes in older adults with or without prior cognitive impairment. The evidence from RCTs was of very low certainty so cannot support or refute the hypothesis that actively reducing or stopping prescription of medications with anticholinergic properties can improve cognitive outcomes in older people. There is no evidence from RCTs that anticholinergic burden reduction interventions improve other clinical outcomes such as mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, or neurobehavioral outcomes. Larger RCTs investigating long-term outcomes are needed. Future RCTs should also investigate potential benefits of anticholinergic reduction interventions in cognitively healthy populations and cognitively impaired populations separately. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does sinus surgery alone or in combination with medical treatment have a significant impact on nasal and pulmonary function in people with CF diagnosed with CRS with nasal polyposis? | Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in paranasal sinuses determines chronic rhinosinusitis (CRS) and nasal polyposis. Endoscopic sinus surgery is used to open the sinuses and allow medical treatment to work properly. | To determine the effects of sinus surgery alone or in combination with medical treatment (non-surgical) compared to medical treatment (non-surgical) alone on both nasal and pulmonary function in people with CF diagnosed with CRS with nasal polyposis. Further, to evaluate the impact of sinus surgery (with or without medical treatment) on hospitalization rates, use of antibiotics and pulmonary exacerbation rates. | Very low-certainty evidence means we are not certain if endoscopic sinus surgery to treat chronic rhinosinusitis with nasal polyposis in cystic fibrosis is effective. Future research should be multicentric to increase the number of participants and increase statistical power. Adequate randomization and allocation concealment are important to guarantee that the groups are similar. Blinding, however, may not be possible in an ethical trial; even without blinding, results can achieve high-level evidence if the outcomes used are objective parameters. Future research should follow participants of all ages for at least 12 months to evaluate the evolution of nasal polyposis, its recurrence and how symptoms may return. We also consider mortality an important outcome to be assessed. Future clinical research should consider the effects of cystic fibrosis transmembrane conductance regulators, a new group of drugs that may affect the development of nasal polyps. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Does minimally invasive aortic valve replacement via a limited sternotomy have different effects compared to conventional aortic valve replacement via median sternotomy in people with aortic valve disease requiring surgical replacement? | Aortic valve disease is a common condition easily treatable with cardiac surgery. This is conventionally performed by opening the sternum ('median sternotomy') and replacing the valve under cardiopulmonary bypass. Median sternotomy is well tolerated, but as less invasive options become available, the efficacy of limited incisions has been called into question. In particular, the effects of reducing the visibility and surgical access have raised safety concerns with regard to the placement of cannulae, venting of the heart, epicardial wire placement, and de-airing of the heart at the end of the procedure. These difficulties may increase operating times, affecting outcome. The benefits of smaller incisions are thought to include decreased pain; improved respiratory mechanics; reductions in wound infections, bleeding, and need for transfusion; shorter intensive care stay; better cosmesis; and a quicker return to normal activity. This is an update of a Cochrane review first published in 2017, with seven new studies. | To assess the effects of minimally invasive aortic valve replacement via a limited sternotomy versus conventional aortic valve replacement via median sternotomy in people with aortic valve disease requiring surgical replacement. | The evidence was of very low to moderate certainty. Sample sizes were small and underpowered to demonstrate differences in some outcomes. Clinical heterogeneity was also noted. Considering these limitations, there may be little to no effect on mortality. Differences in extracorporeal support times are uncertain, comparing upper hemi-sternotomy to full sternotomy for aortic valve replacement. Before widespread adoption of the minimally invasive approach can be recommended, there is a need for a well-designed and adequately powered prospective randomised controlled trial. Such a study would benefit from also performing a robust cost analysis. Growing patient preference for minimally invasive techniques merits thorough quality of life analyses to be included as end points, as well as quantitative measures of physiological reserve. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Does adding an ICS to combination LABA/LAMA inhalers have beneficial effects for the treatment of stable COPD? | Management of chronic obstructive pulmonary disease (COPD) commonly involves a combination of long-acting bronchodilators including beta2-agonists (LABA) and muscarinic antagonists (LAMA). LABA and LAMA bronchodilators are now available in single-combination inhalers. In individuals with persistent symptoms or frequent exacerbations, inhaled corticosteroids (ICS) are also used with combination LABA and LAMA inhalers. However, the benefits and risks of adding ICS to combination LABA/LAMA inhalers as a triple therapy remain unclear. | To assess the effects of adding an ICS to combination LABA/LAMA inhalers for the treatment of stable COPD. | The available evidence suggests that triple therapy may reduce rates of COPD exacerbations (low-certainty evidence) and results in an improvement in health-related quality of life (high-certainty evidence) compared to combination LABA/LAMA inhalers, but probably confers an increased pneumonia risk as a serious adverse event (moderate-certainty evidence). Triple therapy probably improves respiratory symptoms and may improve lung function (moderate- and low-certainty evidence, respectively); however, these benefits do not appear to be clinically significant. Triple therapy may reduce the risk of all-cause mortality compared to combination LABA/LAMA inhalers (low-certainty evidence). The certainty of the evidence was downgraded most frequently for inconsistency or indirectness. Across the four included studies, there were important differences in inclusion criteria, trial medications, and duration of follow-up. Investigation of heterogeneity was limited due to the small number of included studies. We found limited data on the effects of triple therapy compared to combination LABA/LAMA inhalers in patients with mild-moderate COPD and those without a recent exacerbation history. | SUPPORTED | LOW | 0 | respiratory system |
Do intervention strategies effectively boost childhood immunisation coverage in low- and middle-income countries? | Immunisation plays a major role in reducing childhood morbidity and mortality. Getting children immunised against potentially fatal and debilitating vaccine-preventable diseases remains a challenge despite the availability of efficacious vaccines, particularly in low- and middle-income countries. With the introduction of new vaccines, this becomes increasingly difficult. There is therefore a current need to synthesise the available evidence on the strategies used to bridge this gap. This is a second update of the Cochrane Review first published in 2011 and updated in 2016, and it focuses on interventions for improving childhood immunisation coverage in low- and middle-income countries. | To evaluate the effectiveness of intervention strategies to boost demand and supply of childhood vaccines, and sustain high childhood immunisation coverage in low- and middle-income countries. | Health education, home-based records, a combination of involvement of community leaders with health provider intervention, and integration of immunisation services may improve vaccine uptake. The certainty of the evidence for the included interventions ranged from moderate to very low. Low certainty of the evidence implies that the true effect of the interventions might be markedly different from the estimated effect. Further, more rigorous RCTs are, therefore, required to generate high-certainty evidence to inform policy and practice. | SUPPORTED | LOW | 0 | immune system and infections |
Can corticosteroids prevent postherpetic neuralgia? | Postherpetic neuralgia (PHN) is a common, serious, painful complication of herpes zoster. Corticosteroids have anti-inflammatory properties, and might be beneficial. This is an update of a review first published in 2008, and previously updated in 2013. | To assess the effects (benefits and harms) of corticosteroids in preventing postherpetic neuralgia. | Based on the current available evidence, we are uncertain about the effects of corticosteroids given orally during an acute herpes zoster infection on preventing postherpetic neuralgia. Corticosteroids given orally or intramuscularly may result in little to no difference in the risk of adverse events in people with acute herpes zoster. Some researchers have recommended using corticosteroids to relieve the zoster-associated pain in the acute phase of the disease. If further research is designed to evaluate the efficacy of corticosteroids for herpes zoster, long-term follow-up should be included to observe their effect on the transition from acute pain to postherpetic neuralgia. Future trials should include measurements of function and quality of life, as well as updated measures of pain. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Can automated oxygen delivery systems benefit preterm infants with respiratory dysfunction? | Many preterm infants require respiratory support to maintain an optimal level of oxygenation, as oxygen levels both below and above the optimal range are associated with adverse outcomes. Optimal titration of oxygen therapy for these infants presents a major challenge, especially in neonatal intensive care units (NICUs) with suboptimal staffing. Devices that offer automated oxygen delivery during respiratory support of neonates have been developed since the 1970s, and individual trials have evaluated their effectiveness. | To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy. | Automated oxygen delivery compared to routine manual oxygen delivery probably increases time in desired SpO | SUPPORTED | MEDIUM | 0 | respiratory system |
Do immunotherapies for people with MS or CIS increase adverse effects compared to placebo? | Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects mainly young adults (two to three times more frequently in women than in men) and causes significant disability after onset. Although it is accepted that immunotherapies for people with MS decrease disease activity, uncertainty regarding their relative safety remains. | To compare adverse effects of immunotherapies for people with MS or clinically isolated syndrome (CIS), and to rank these treatments according to their relative risks of adverse effects through network meta-analyses (NMAs). | We found mostly low and very low-certainty evidence that drugs used to treat MS may not increase SAEs, but may increase withdrawals compared with placebo. The results suggest that there is no important difference in the occurrence of SAEs between first- and second-line drugs and between oral, injectable, or infused drugs, compared with placebo. Our review, along with other work in the literature, confirms poor-quality reporting of adverse events from RCTs of interventions. At the least, future studies should follow the CONSORT recommendations about reporting harm-related issues. To address adverse effects, future systematic reviews should also include non-randomized studies. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Can progestogens effectively prevent premature ovulation in women undergoing controlled ovarian hyperstimulation? | Currently, gonadotrophin releasing hormone (GnRH) analogues are used to prevent premature ovulation in ART cycles. However, their costs remain high, the route of administration is invasive and has some adverse effects. Oral progestogens could be cheaper and effective to prevent a premature LH surge. | To evaluate the effectiveness and safety of using progestogens to avoid spontaneous ovulation in women undergoing controlled ovarian hyperstimulation (COH). | Little or no differences in LBR may exist when comparing MPA 4 mg with GnRH agonists in normo-responders. OPCR may be slightly increased in the MPA 4 mg group, but MPA 4 mg reduces the doses of gonadotropins in comparison to GnRH agonists. Little or no differences in OPCR may exist between progestogens and GnRH antagonists in normo-responders and donors. However, micronised progesterone could improve by 2 to 6 MII oocytes. When comparing one progestogen to another, dydrogesterone suggested slightly lower OPCR than MPA and micronised progesterone, and MPA suggested slightly lower OPCR than the micronised progesterone 100 mg. Finally, MPA 10 mg suggests a lower OPCR than MPA 4 mg. There is uncertainty regarding the rest of the outcomes due to imprecision and no solid conclusions can be drawn. | NOT ENOUGH INFORMATION | LOW | 0 | sexual and reproductive health |
Can strategies effectively increase response to postal and electronic questionnaires? | Self-administered questionnaires are widely used to collect data in epidemiological research, but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of epidemiological research. | To identify effective strategies to increase response to postal and electronic questionnaires. | Researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this Cochrane review. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Does nirmatrelvir/ritonavir plus standard of care reduce the risk of all-cause mortality and hospital admission or death in COVID-19 outpatients infected with the Delta variant? | Oral nirmatrelvir/ritonavir (Paxlovid) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. It remains to be evaluated for which indications and patient populations the drug is suitable. | To assess the efficacy and safety of nirmatrelvir/ritonavir plus standard of care (SoC) compared to SoC with or without placebo, or any other intervention for treating COVID-19 or preventing SARS-CoV-2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in-between publication of review updates. | Low-certainty evidence suggests nirmatrelvir/ritonavir reduces the risk of all-cause mortality and hospital admission or death in high-risk, unvaccinated COVID-19 outpatients infected with the Delta variant of SARS-CoV-2. There is low- to moderate-certainty evidence of the safety of nirmatrelvir/ritonavir. Very low-certainty evidence exists regarding the effects of nirmatrelvir/ritonavir on all-cause mortality and viral clearance in mildly to moderately affected, mostly unvaccinated COVID-19 inpatients infected with the Omicron variant of SARS-CoV-2. Insufficient and inconsistent information prevents the assessment of safety outcomes. No reliable differences in effect size and direction were found regarding equity aspects. There is no available evidence supporting the use of nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection. We are continually updating our search and making search results available on the OSF platform. | SUPPORTED | LOW | 0 | immune system and infections |
Do statins provide benefits in reducing death and major cardiovascular events in adults with CKD not requiring dialysis? | Cardiovascular disease is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), and the absolute risk of cardiovascular events is similar to people with coronary artery disease. This is an update of a review first published in 2009 and updated in 2014, which included 50 studies (45,285 participants). | To evaluate the benefits and harms of statins compared with placebo, no treatment, standard care or another statin in adults with CKD not requiring dialysis. | Statins reduce death and major cardiovascular events by about 20% and probably make no difference to stroke or kidney failure in people with CKD not requiring dialysis. However, due to limited reporting, the effect of statins on elevated creatinine kinase or rhabdomyolysis is unclear. Statins have an important role in the primary prevention of cardiovascular events and death in people who have CKD and do not require dialysis. Editorial note: This is a living systematic review. We will search for new evidence every three months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. | SUPPORTED | MEDIUM | 0 | cardiovascular system |
Can red flags obtained in a clinical history or physical examination accurately screen for vertebral fracture in patients with low-back pain? | Low-back pain (LBP) is a common condition seen in primary care. A principal aim during a clinical examination is to identify patients with a higher likelihood of underlying serious pathology, such as vertebral fracture, who may require additional investigation and specific treatment. All 'evidence-based' clinical practice guidelines recommend the use of red flags to screen for serious causes of back pain. However, it remains unclear if the diagnostic accuracy of red flags is sufficient to support this recommendation. | To assess the diagnostic accuracy of red flags obtained in a clinical history or physical examination to screen for vertebral fracture in patients presenting with LBP. | The available evidence does not support the use of many red flags to specifically screen for vertebral fracture in patients presenting for LBP. Based on evidence from single studies, few individual red flags appear informative as most have poor diagnostic accuracy as indicated by imprecise estimates of likelihood ratios. When combinations of red flags were used the performance appeared to improve. From the limited evidence, the findings give rise to a weak recommendation that a combination of a small subset of red flags may be useful to screen for vertebral fracture. It should also be noted that many red flags have high false positive rates; and if acted upon uncritically there would be consequences for the cost of management and outcomes of patients with LBP. Further research should focus on appropriate sets of red flags and adequate reporting of both index and reference tests. | REFUTED | LOW | 2 | musculoskeletal system and dermatology |
Does peer reviewer training have a significant effect on the quality of grant and journal peer review? | Funders and scientific journals use peer review to decide which projects to fund or articles to publish. Reviewer training is an intervention to improve the quality of peer review. However, studies on the effects of such training yield inconsistent results, and there are no up-to-date systematic reviews addressing this question. | To evaluate the effect of peer reviewer training on the quality of grant and journal peer review. | Evidence from 10 RCTs suggests that training peer reviewers may lead to little or no improvement in the quality of peer review. There is a need for studies with more participants and a broader spectrum of valid and reliable outcome measures. Studies evaluating stakeholders' assessments of the quality of peer review should ensure that these instruments have sufficient levels of validity and reliability. | REFUTED | MEDIUM | 2 | cognitive, mental, and mental health |
Does oral dextrose gel effectively prevent hypoglycemia in at-risk newborn infants and reduce long-term neurodevelopmental impairment? | Neonatal hypoglycaemia is a common condition that can be associated with brain injury. Current practice usually includes early identification of at-risk infants (e.g. infants of diabetic mothers; preterm, small- or large-for-gestational-age infants), and prophylactic measures are advised. However, these measures often involve use of formula milk or admission to the neonatal unit. Dextrose gel is non-invasive, inexpensive and effective for treatment of neonatal hypoglycaemia. Prophylactic dextrose gel can reduce the incidence of neonatal hypoglycaemia, thus potentially reducing separation of mother and baby and supporting breastfeeding, as well as preventing brain injury. This is an update of a previous Cochrane Review published in 2021. | To assess the effectiveness and safety of oral dextrose gel in preventing hypoglycaemia before first hospital discharge and reducing long-term neurodevelopmental impairment in newborn infants at risk of hypoglycaemia. | Prophylactic oral dextrose gel reduces the risk of neonatal hypoglycaemia in at-risk infants and probably reduces the risk of treatment for hypoglycaemia without adverse effects. It may make little to no difference to the risk of major neurological disability at two years, but the confidence intervals include the possibility of substantial benefit or harm. Evidence at six to seven years is limited to a single small study. In view of its limited short-term benefits, prophylactic oral dextrose gel should not be incorporated into routine practice until additional information is available about the balance of risks and harms for later neurological disability. Additional large follow-up studies at two years of age or older are required. Future research should also be undertaken in other high-income countries, low- and middle-income countries, preterm infants, using other dextrose gel preparations, and using comparators other than placebo gel. There are three studies awaiting classification and one ongoing study which may alter the conclusions of the review when published. | SUPPORTED | MEDIUM | 0 | miscellaneous |
Do different classes of drugs show varying effectiveness and acceptability in the acute treatment of panic disorder? | A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. | To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. | In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Does mesh hernia repair provide clear benefits compared to non-mesh hernia repair in emergency groin hernia surgery? | A groin hernia is a collective name for inguinal and femoral hernias, which can present acutely with incarceration or strangulation of the hernia sac content, requiring emergency treatment. Timely repair of emergency groin hernias is crucial due to the risk of reduced blood supply and thus damage to the bowel, but the optimal surgical approach is unclear. While mesh repair is the standard treatment for elective hernia surgery, using mesh for emergency groin hernia repair remains controversial due to the risk of surgical site infection. | To assess the benefits and harms of mesh compared with non-mesh in emergency groin hernia repair in adult patients with an inguinal or femoral hernia. | Our results show that in terms of 30-day surgical site infections, 30-day mortality, and hernia recurrence within one year, the evidence for the use of mesh hernia repair compared with non-mesh hernia repair in emergency groin hernia surgery is very uncertain. Unfortunately, firm conclusions cannot be drawn due to very low-certainty evidence and meta-analyses based on small-sized and low-quality studies. There is a need for future high-quality RCTs or high-quality registry-based studies if RCTs are unfeasible. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Can perceptions and experiences of various individuals influence the prevention, detection, and management of postpartum haemorrhage? | Postpartum haemorrhage (PPH), defined as blood loss of 500 mL or more after childbirth, is the leading cause of maternal mortality worldwide. It is possible to prevent complications of PPH with timely and appropriate detection and management. However, implementing the best methods of PPH prevention, detection and management can be challenging, particularly in low- and middle-income countries. | Our overall objective was to explore the perceptions and experiences of women, community members, lay health workers, and skilled healthcare providers who have experience with PPH or with preventing, detecting, and managing PPH, in community or health facility settings. | Our findings highlight how improving PPH prevention, detection, and management is underpinned by a complex system of interacting roles and behaviours (community, women, health workers of different types and with different experiences). Multiple individual, sociocultural, and environmental factors influence the decisions and behaviours of women, families, communities, health workers, and managers. It is crucial to consider the broader health and social systems when designing and implementing PPH interventions to change or influence these behaviours. We have developed a set of prompts that may help programme managers, policymakers, researchers, and other key stakeholders to identify and address factors that affect implementation and scale-up of interventions to improve PPH prevention, detection, and management. | SUPPORTED | MEDIUM | 0 | sexual and reproductive health |
Are stem cell-based interventions beneficial for treating stroke in newborn infants? | Perinatal stroke refers to a diverse but specific group of cerebrovascular diseases that occur between 20 weeks of fetal life and 28 days of postnatal life. Acute treatment options for perinatal stroke are limited supportive care, such as controlling hypoglycemia and seizures. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. Preclinical findings have culminated in ongoing human neonatal studies. | To evaluate the benefits and harms of stem cell-based interventions for the treatment of stroke in newborn infants compared to control (placebo or no treatment) or stem-cell based interventions of a different type or source. | No evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment of stroke in newborn infants. We identified no ongoing studies. Future clinical trials should focus on standardizing the timing and method of cell delivery and cell processing to optimize the therapeutic potential of stem cell-based interventions and safety profiles. Phase 1 and large animal studies might provide the groundwork for future randomized trials. Outcome measures should include all-cause mortality, major neurodevelopmental disability and immune rejection, and any other serious adverse events. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does antibiotic administration prior to or at the time of embryo transfer (ET) improve pregnancy rates during assisted reproductive technology (ART) cycles? | After an assisted reproductive technology (ART) cycle, embryo transfer (ET) involves the placement of one or more embryos into the uterine cavity, usually by passing a catheter through the cervical os. Despite the transfer of high-quality embryos, many ETs do not result in a pregnancy. There are many factors that may affect the success of ET. There is some evidence to suggest that increased endocervical microbial colonization at the time of ET results in lower pregnancy rates. The association between the cervico-vaginal microbiome and reduced pregnancy rates after ET may indicate either pre-existing dysbiosis in this patient population, or that the passage of the ET catheter itself may be introducing microbes that alter the microbiome of the endometrial cavity or lead to infection. Such an upper genital tract infection, contamination or alteration may have a negative impact on implantation and in vitro fertilization (IVF) success rates by both endometrial and embryonic mechanisms. The administration of antibiotics at the time of ET has been suggested as an intervention to reduce levels of microbial colonization and hence improve pregnancy rates. | To evaluate the benefits and harms of antibiotic administration prior to or at the time of embryo transfer (ET) during assisted reproductive technology (ART) cycles. | We are uncertain if administration of antibiotics prior to or at the time of ET improves LBR in women undergoing ART based on a single study of 27 women with low-certainty evidence. We are uncertain whether there was a difference in CPR. There was evidence for a reduction in genital tract colonization rates, but the evidence was very low certainty. Data were lacking on other secondary outcomes. The pooled results should be interpreted with caution, due to the small number of women included in the analysis. | NOT ENOUGH INFORMATION | LOW | 1 | sexual and reproductive health |
Can the CAM-ICU accurately diagnose delirium in adult patients in critical care units? | Delirium is an underdiagnosed clinical syndrome typified by an acute alteration of mental state. It is an important problem in critical care and intensive care units (ICU) due to its high prevalence and its association with adverse outcomes. Delirium is a very distressing condition for patients, with a huge impact on their well-being. Diagnosis of delirium in the critical care setting is challenging. This is especially true for patients who are mechanically ventilated and are therefore unable to engage in a verbal interview. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is a tool specifically designed to assess for delirium in the context of ICU patients, including those on mechanical ventilation. CAM-ICU can be administered by non-specialists to give a dichotomous delirium present/absent result. | To determine the diagnostic accuracy of the CAM-ICU for the diagnosis of delirium in adult patients in critical care units. | The CAM-ICU tool may have a role in the early identification of delirium, in adult patients hospitalized in intensive care units, including those on mechanical ventilation, when non-specialized, properly trained clinical personnel apply the CAM-ICU. The test is most useful for exclusion of delirium. The test may miss a proportion of patients with incident delirium, therefore in situations where detection of all delirium cases is desirable, it may be best to repeat the test or combine CAM-ICU with another assessment. Future studies should compare different screening tests proposed for bedside assessment of delirium, as this approach will reveal which tool yields superior accuracy. In addition, future studies should consider and report the flow and timing of the tests and clearly report key characteristics related to patient selection. Finally, future research should focus on the impact of CAM-ICU screening on patient outcomes. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Does postoperative face-down positioning have a significant effect on the outcome of surgery for macular hole? | Macular holes cause severe impairment of sight. With the aim of improving the outcome of surgery for macular holes, particularly larger macular holes (those measuring over 400 μm), a variable period of face-down positioning may be advised. This review is an update of a Cochrane Review published in 2011. | To evaluate the effect of postoperative face-down positioning on the outcome of surgery for macular hole. | We identified eight RCTs evaluating face-down positioning following surgery for macular hole. The included studies were not all directly comparable due to differences in the surgical techniques used and the durations of postoperative positioning advised. Low-certainty evidence suggests that face-down positioning may have little or no effect on macular hole closure after surgery. Face-down positioning is a low-risk intervention, with serious adverse events affecting fewer than 1 in 300 people. We suggest that any future trials focus on patients with larger macular holes, with interventions and outcome measures used in previous trials (i.e. with inner limiting membrane peeling, positioning durations of three to five days, and validated quality of life metrics) to allow future meta-analyses to determine any effect with greater precision and confidence. | NOT ENOUGH INFORMATION | LOW | 0 | sensory organs |
Can CFTR correctors (with or without potentiators) provide clinically important benefits for people with cystic fibrosis caused by class II CFTR mutations? | Cystic fibrosis (CF) is a common life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class II CFTR variant F508del is the commonest CF-causing variant (found in up to 90% of people with CF (pwCF)). The F508del variant lacks meaningful CFTR function - faulty protein is degraded before reaching the cell membrane, where it needs to be to effect transepithelial salt transport. Corrective therapy could benefit many pwCF. This review evaluates single correctors (monotherapy) and any combination of correctors (most commonly lumacaftor, tezacaftor, elexacaftor, VX-659, VX-440 or VX-152) and a potentiator (e.g. ivacaftor) (dual and triple therapies). | To evaluate the effects of CFTR correctors (with or without potentiators) on clinically important benefits and harms in pwCF of any age with class II CFTR mutations (most commonly F508del). | There is insufficient evidence of clinically important effects from corrector monotherapy in pwCF with F508del/F508del. Additional data in this review reduced the evidence for efficacy of dual therapy; these agents can no longer be considered as standard therapy. Their use may be appropriate in exceptional circumstances (e.g. if triple therapy is not tolerated or due to age). Both dual therapies (lumacaftor-ivacaftor, tezacaftor-ivacaftor) result in similar small improvements in QoL and respiratory function with lower pulmonary exacerbation rates. While the effect sizes for QoL and FEV | NOT ENOUGH INFORMATION | LOW | 2 | respiratory system |
Is infliximab more effective than purine analogues alone or placebo in inducing remission in Crohn's disease? | Infliximab is a monoclonal antibody that binds and neutralises tumour necrosis factor-alpha (TNF-α), which is present in high levels in the blood serum, mucosa and stool of people with Crohn's disease. | To evaluate the benefits and harms of infliximab alone or in combination with another agent for induction of remission in Crohn's disease compared to placebo or active medical therapies. | Infliximab in combination with purine analogues is probably more effective than purine analogues alone in inducing clinical remission and clinical response. Infliximab alone may be more effective in inducing clinical remission and response than purine analogues alone or placebo. Infliximab may be similar in efficacy to a CT-P13 biosimilar and there may be little or no difference in withdrawals due to adverse events. We were unable to draw meaningful conclusions as to whether infliximab alone is effective when used for exclusively fistulating populations. There was evidence that there may be little or no difference in withdrawal due to adverse events between infliximab plus purines compared with purines alone, as well as infliximab alone compared with purines alone. Meaningful conclusions cannot be drawn on all other outcomes related to adverse events due to very low certainty evidence. | SUPPORTED | MEDIUM | 0 | digestive system and metabolism |
Does early tracheostomy result in little to no difference in overall mortality in critically ill COVID-19 patients compared to late tracheostomy? | The role of early tracheostomy as an intervention for critically ill COVID-19 patients is unclear. Previous reports have described prolonged intensive care stays and difficulty weaning from mechanical ventilation in critically ill COVID-19 patients, particularly in those developing acute respiratory distress syndrome. Pre-pandemic evidence on the benefits of early tracheostomy is conflicting but suggests shorter hospital stays and lower mortality rates compared to late tracheostomy. | To assess the benefits and harms of early tracheostomy compared to late tracheostomy in critically ill COVID-19 patients. | We found low-certainty evidence that early tracheostomy may result in little to no difference in overall mortality in critically ill COVID-19 patients requiring prolonged mechanical ventilation compared with late tracheostomy. In terms of clinical improvement, early tracheostomy may result in little to no difference in duration to liberation from mechanical ventilation compared with late tracheostomy. We are not certain about the impact of early tracheostomy on clinical worsening in terms of the incidence of adverse events, need for renal replacement therapy, ventilator-associated pneumonia, or the length of stay in the ICU. Future RCTs should provide additional data on the benefits and harms of early tracheostomy for defined main outcomes of COVID-19 research, as well as of comparable diseases, especially for different population subgroups to reduce clinical heterogeneity, and report a longer observation period. Then it would be possible to draw conclusions regarding which patient groups might benefit from early intervention. Furthermore, validated scoring systems for more accurate predictions of the need for prolonged mechanical ventilation should be developed and used in new RCTs to ensure safer indication and patient safety. High-quality (prospectively registered) NRSIs should be conducted in the future to provide valuable answers to clinical questions. This could enable us to draw more reliable conclusions about the potential benefits and harms of early tracheostomy in critically ill COVID-19 patients. | NOT ENOUGH INFORMATION | LOW | 0 | respiratory system |
Can calcium channel blockers plus standard iron chelation therapy reduce cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia? | Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018. | To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. | The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis. | SUPPORTED | LOW | 0 | cardiovascular system |
Can artificial intelligence accurately detect keratoconus in people with refractive errors and those suspected of having keratoconus? | Keratoconus remains difficult to diagnose, especially in the early stages. It is a progressive disorder of the cornea that starts at a young age. Diagnosis is based on clinical examination and corneal imaging; though in the early stages, when there are no clinical signs, diagnosis depends on the interpretation of corneal imaging (e.g. topography and tomography) by trained cornea specialists. Using artificial intelligence (AI) to analyse the corneal images and detect cases of keratoconus could help prevent visual acuity loss and even corneal transplantation. However, a missed diagnosis in people seeking refractive surgery could lead to weakening of the cornea and keratoconus-like ectasia. There is a need for a reliable overview of the accuracy of AI for detecting keratoconus and the applicability of this automated method to the clinical setting. | To assess the diagnostic accuracy of artificial intelligence (AI) algorithms for detecting keratoconus in people presenting with refractive errors, especially those whose vision can no longer be fully corrected with glasses, those seeking corneal refractive surgery, and those suspected of having keratoconus. AI could help ophthalmologists, optometrists, and other eye care professionals to make decisions on referral to cornea specialists. Secondary objectives To assess the following potential causes of heterogeneity in diagnostic performance across studies. • Different AI algorithms (e.g. neural networks, decision trees, support vector machines) • Index test methodology (preprocessing techniques, core AI method, and postprocessing techniques) • Sources of input to train algorithms (topography and tomography images from Placido disc system, Scheimpflug system, slit-scanning system, or optical coherence tomography (OCT); number of training and testing cases/images; label/endpoint variable used for training) • Study setting • Study design • Ethnicity, or geographic area as its proxy • Different index test positivity criteria provided by the topography or tomography device • Reference standard, topography or tomography, one or two cornea specialists • Definition of keratoconus • Mean age of participants • Recruitment of participants • Severity of keratoconus (clinically manifest or subclinical) SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), Ovid MEDLINE, Ovid Embase, OpenGrey, the ISRCTN registry, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). There were no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 November 2022. | AI appears to be a promising triage tool in ophthalmologic practice for diagnosing keratoconus. Test accuracy was very high for manifest keratoconus and slightly lower for subclinical keratoconus, indicating a higher chance of missing a diagnosis in people without clinical signs. This could lead to progression of keratoconus or an erroneous indication for refractive surgery, which would worsen the disease. We are unable to draw clear and reliable conclusions due to the high risk of bias, the unexplained heterogeneity of the results, and high applicability concerns, all of which reduced our confidence in the evidence. Greater standardization in future research would increase the quality of studies and improve comparability between studies. | NOT ENOUGH INFORMATION | LOW | 0 | sensory organs |
Do interventions to prevent or cease e-cigarette use in children and adolescents show effectiveness compared to no intervention or alternative interventions? | The prevalence of e-cigarette use has increased globally amongst children and adolescents in recent years. In response to the increasing prevalence and emerging evidence about the potential harms of e-cigarettes in children and adolescents, leading public health organisations have called for approaches to address increasing e-cigarette use. Whilst evaluations of approaches to reduce uptake and use regularly appear in the literature, the collective long-term benefit of these is currently unclear. | The co-primary objectives of the review were to: (1) evaluate the effectiveness of interventions to prevent e-cigarette use in children and adolescents (aged 19 years and younger) with no prior use, relative to no intervention, waitlist control, usual practice, or an alternative intervention; and (2) evaluate the effectiveness of interventions to cease e-cigarette use in children and adolescents (aged 19 years and younger) reporting current use, relative to no intervention, waitlist control, usual practice, or an alternative intervention. Secondary objectives were to: (1) examine the effect of such interventions on child and adolescent use of other tobacco products (e.g. cigarettes, cigars types, and chewing tobacco); and (2) describe the unintended adverse effects of the intervention on individuals (e.g. physical or mental health of individuals), or on organisations (e.g. intervention displacement of key curricula or learning opportunities for school students) where such interventions are being implemented. | We identified no RCTs that met the inclusion criteria for the review, and as such, there is no evidence available from RCTs to assess the potential impact of interventions targeting children and adolescent e-cigarette use, tobacco use, or any unintended adverse effects. Evidence from studies employing other trial designs (e.g. non-randomised) may exist; however, such studies were not eligible for inclusion in the review. Evidence from studies using non-randomised designs should be examined to guide actions to prevent or cease e-cigarette use. This is a living systematic review. We search for new evidence every month and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Do ventilation tubes (grommets) have significant benefits for OME in children? | Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. It may cause hearing loss which, when persistent, may lead to developmental delay, social difficulty and poor quality of life. Management includes watchful waiting, autoinflation, medical and surgical treatment. Insertion of ventilation tubes has often been used as the preferred treatment. | To evaluate the effects (benefits and harms) of ventilation tubes (grommets) for OME in children. | There may be small short- and medium-term improvements in hearing and persistence of OME with VTs, but it is unclear whether these persist after longer follow-up. The RCTs included do not allow us to say when (or how much) VTs improve hearing in any specific child. However, interpretation of the evidence is difficult: many children in the control groups recover spontaneously or receive VTs during follow-up, VTs may block or extrude, and OME may recur. The limited evidence in this review also affects the generalisability/applicability of our findings to situations involving children with underlying conditions (e.g. craniofacial syndromes) or the use of long-acting tubes. Consequently, RCTs may not be the best way to determine whether an intervention is likely to be effective in any individual child. Instead, we must better understand the different OME phenotypes to target interventions to children who will benefit most, and avoid over-treating when spontaneous resolution is likely. | NOT ENOUGH INFORMATION | LOW | 1 | sensory organs |
Can CBT reduce fear of falling in older people living in the community? | Fear of falling (FoF) is a lasting concern about falling that leads to an individual avoiding activities that he/she remains capable of performing. It is a common condition amongst older adults and may occur independently of previous falls. Cognitive behavioural therapy (CBT), a talking therapy that helps change dysfunctional thoughts and behaviour, with and without exercise, may reduce FoF, for example, by reducing catastrophic thoughts related to falls, and modifying dysfunctional behaviour. | To assess the benefits and harms of CBT for reducing FoF in older people living in the community, and to assess the effects of interventions where CBT is used in combination with exercise. | CBT with and without exercise interventions probably reduces FoF in older people living in the community immediately after the intervention (moderate-certainty evidence). The improvements may be sustained during the period up to six months after intervention (low-certainty evidence), and probably are sustained beyond six months (moderate-certainty evidence). Further studies are needed to improve the certainty of evidence for sustainability of FoF effects up to six months. Of the secondary outcomes, we are uncertain whether CBT interventions for FoF reduce the occurrence of falls (very low-certainty evidence). However, CBT interventions for reducing FoF may reduce the level of activity avoidance, and may reduce depression (low-certainty evidence). No studies reported adverse effects. Future studies could investigate different populations (e.g. nursing home residents or people with comorbidities), intervention characteristics (e.g. duration), or comparisons (e.g. CBT versus exercise), investigate adverse effects of the interventions, and add outcomes (e.g. gait analysis). Future systematic reviews could search specifically for secondary outcomes. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Do different antibiotics show clinically relevant differences in treating GABHS tonsillopharyngitis? | Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2021. | To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. | We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and disadvantaged populations, where the risk of complications remains high. | NOT ENOUGH INFORMATION | LOW | 1 | immune system and infections |
Do antibiotics have a significant effect on children with acute otitis media? | Acute otitis media (AOM) is one of the most common diseases in childhood for which antibiotics are commonly prescribed; a systematic review reported a pooled prevalence of 85.6% in high-income countries. This is an update of a Cochrane Review first published in the Cochrane Library in 1997 and updated in 1999, 2005, 2009, 2013 and 2015. | To assess the effects of antibiotics for children with AOM. | This review reveals that antibiotics probably have no effect on pain at 24 hours, a slight effect on pain in the days following and only a modest effect on the number of children with tympanic perforations, contralateral otitis episodes and abnormal tympanometry findings at two to four weeks compared with placebo in children with AOM. In high-income countries, most cases of AOM spontaneously remit without complications. The benefits of antibiotics must be weighed against the possible harms: for every 14 children treated with antibiotics, one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics were withheld. For most children with mild disease in high-income countries, an expectant observational approach seems justified. Therefore, clinical management should emphasise advice about adequate analgesia and the limited role for antibiotics. | REFUTED | MEDIUM | 2 | sensory organs |
Do interventions effectively improve health literacy in migrants, and do female and male migrants respond differently to these interventions? | Health literacy (HL) is a determinant of health and important for autonomous decision-making. Migrants are at high risk for limited HL. Improving HL is important for equitable promotion of migrants' health. | To assess the effectiveness of interventions for improving HL in migrants. To assess whether female or male migrants respond differently to the identified interventions. | Adequately powered studies measuring long-term effects (more than six months) of HL interventions in female and male migrants are needed, using well-validated tools and representing various healthcare systems. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does percutaneous nephrolithotomy (PCNL) have better outcomes compared to retrograde intrarenal surgery (RIRS) for treating renal stones in adults? | Kidney stones (also called renal stones) can be a source of pain, obstruction, and infection. Depending on size, location, composition, and other patient factors, the treatment of kidney stones can involve observation, shock wave lithotripsy, retrograde intrarenal surgery (RIRS; i.e. ureteroscopic approaches), percutaneous nephrolithotomy (PCNL), or a combination of these approaches. | To assess the effects of percutaneous nephrolithotomy (PCNL) versus retrograde intrarenal surgery (RIRS) for the treatment of renal stones in adults. | Based on a large body of evidence from 42 trials, we found that PCNL compared with RIRS may improve stone-free rates and may reduce the need for secondary interventions, but probably has little or no effect on major complications. PCNL compared with RIRS may have little or no effect on ureteral stricture rates and may increase length of hospital stay. We found no evidence on unplanned medical visits or participant quality of life. Because of the considerable shortcomings of the included trials, the evidence for most outcomes was of low certainty. Access size for PCNL was less than 24 Fr in most studies that provided this information. We expect the findings of this review to be helpful for shared decision-making about management choices for individuals with renal stones. | SUPPORTED | LOW | 0 | urinary system |
Can different nebuliser systems, when used with different inhaled medications for people with CF, impact time efficiency, effectiveness, safety, cost, and quality of life? | Nebuliser systems are used to deliver medications to the lungs, to control the symptoms and the progression of lung disease in people with cystic fibrosis (CF). There are many different nebulised-medications prescribed for people with CF and there are many different types of nebuliser systems. Some of these nebulised medications are licenced for, and can be taken via only one type of nebuliser system; some are licensed for, and can be taken via more than one type of nebuliser system. This is an update to a previous systematic review. | To assess the time efficiency, effectiveness, safety, cost and impact of use (e.g. burden of care, adherence, quality of life (QoL)) of different nebuliser systems, when used with different inhaled medications for people with CF. | Newer technologies e.g. AAD and VMT have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, preference and adherence. Data are lacking for all varieties of medications which are used in CF care, including different inhaled antibiotics or hypertonic saline, with all delivery (nebuliser system) possibilities. Long-term RCTs are needed to evaluate different nebuliser systems to determine patient-focused outcomes (such as QoL and burden of care), safe and effective dosing levels of a wide variety of medications, clinical outcomes (such as hospitalisations and need for antibiotics), and an economic evaluation of their use. There are insufficient data to establish whether one nebuliser system is better than another overall. Clinicians should be aware of the variability in the performance of different nebuliser systems, compatibility with specific nebulised medication, and they must work with their patients to choose the best nebuliser system for each individual. This is likely to be an ongoing process as the needs and circumstances of each individual change over time. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Does surgical treatment lead to improved functional outcome compared to conservative treatment for displaced intra-articular calcaneal fractures? | Fractures of the calcaneus (heel bone) comprise up to 2% of all fractures. These fractures are mostly caused by a fall from a height, and are common in younger adults. Treatment can be surgical or non-surgical; however, there is clinical uncertainty over optimal management. This is an update of a Cochrane Review first published in 2013. | To assess the effects (benefits and harms) of surgical versus conservative treatment of displaced intra-articular calcaneal fractures. | Our confidence in the evidence is limited. Although pooled evidence indicated that surgical treatment may lead to improved functional outcome but with an increased risk of unplanned second operations, we judged the evidence to be of low certainty as it was often derived from few participants in studies that were not sufficiently robust in design. We found no evidence of a difference between treatment options in the number of people who needed late reconstruction surgery for subtalar arthritis, although the estimate included the possibility of important harms and benefits. Large, well-conducted studies that attempt to minimise detection bias and that measure functional outcomes using calcaneal-specific measurement tools would increase the confidence in these findings. Given that minimally invasive surgical procedures are already becoming more prevalent in practice, research is urgently needed to determine whether these newer surgical techniques offer better outcomes with regard to function, pain, quality of life, and postoperative complications for intra-articular displaced calcaneal fractures. | NOT ENOUGH INFORMATION | LOW | 0 | musculoskeletal system and dermatology |
Can human insulin be stored above or below the manufacturers' recommended temperature range without a clinically relevant loss of potency? | Health authorities stress the temperature sensitivity of human insulin, advising protection from heat and freezing, with manufacturers suggesting low-temperature storage for intact vials, and once opened, storage at room temperature for four to six weeks, though usage time and maximum temperature recommendations vary. For human insulin, the recommendations of current shelf life in use may range from 10 to 45 days, and the maximum temperature in use varies between 25 °C and 37 °C. Optimal cold-chain management of human insulin from manufacturing until the point of delivery to people with diabetes should always be maintained, and people with diabetes and access to reliable refrigeration should follow manufacturers' recommendations. However, a growing segment of the diabetes-affected global population resides in challenging environments, confronting prolonged exposure to extreme heat due to the climate crisis, all while grappling with limited access to refrigeration. | To analyse the effects of storing human insulin above or below the manufacturers' recommended insulin temperature storage range or advised usage time, or both, after dispensing human insulin to people with diabetes. | Under difficult living conditions, pharmaceutical companies' data indicate that it is possible to store unopened SAI and IAI vials and cartridges at up to 25 °C for a maximum of six months and at up to 37 °C for a maximum of two months without a clinically relevant loss of insulin potency. Also, oscillating temperatures between 25 °C and 37 °C for up to three months result in no loss of insulin activity for SAI, IAI and MI. In addition, ambient temperature can be lowered by use of simple cooling devices such as clay pots for insulin storage. Clinical studies on opened and unopened insulin containers should be performed to measure insulin potency and stability after varying storage conditions. Furthermore, more data are needed on MI, insulin pumps, sterility and cold climate conditions. | NOT ENOUGH INFORMATION | LOW | 0 | endocrine system and hormones |
Can PDE5 inhibitors benefit the treatment of Raynaud's phenomenon? | Raynaud's phenomenon is a vasodilatory phenomenon characterised by digital pallor, cyanosis, and pain of the extremities. Primary Raynaud's phenomenon has no underlying disease associated with it, while secondary Raynaud's phenomenon is associated with connective tissue disorders such as systemic sclerosis. Systemic sclerosis causes fibrosis and commonly affects the skin and internal organs such as the gastrointestinal tract, lungs, kidney, and heart. Phosphodiesterase 5 inhibitors (PDE5i) are a class of drugs that increases blood flow to the extremities and may be beneficial in the treatment of Raynaud's phenomenon. | To assess the benefits and harms of PDE5i compared to placebo for the treatment of Raynaud's phenomenon. | Based on low-certainty evidence, PDE5i may reduce the frequency of attacks of Raynaud's phenomenon by a small amount per week, result in a small reduction in the duration of attack, improve patients' global assessment of their disease, and result in little to no difference in pain. PDE5i probably result in little or no difference in serious adverse events but slightly increase the likelihood of withdrawing from treatment due to an adverse event. | SUPPORTED | LOW | 0 | cardiovascular system |
Does higher protein intake in healthy, formula-fed term infants have significant benefits or harms compared to lower protein intake? | Many infants are fed infant formulas to promote growth. Some formulas have a high protein content (≥ 2.5 g per 100 kcal) to accelerate weight gain during the first year of life. The risk-benefit balance of these formulas is unclear. | To evaluate the benefits and harms of higher protein intake versus lower protein intake in healthy, formula-fed term infants. | We are unsure if feeding healthy infants high-protein formula compared to standard-protein formula has an effect on undernutrition, overweight, or obesity. There may be little or no difference in the risk of adverse effects between infants fed with high-protein formula versus those fed with standard-protein formula. We are unsure if feeding healthy infants standard-protein formula compared to low-protein formula has any effect on undernutrition. There may be little or no difference in the risk of adverse effects between infants fed with standard-protein formula versus those fed with low-protein formula. The findings of six ongoing studies and two studies awaiting classification studies may change the conclusions of this review. | NOT ENOUGH INFORMATION | LOW | 1 | nutrition and dietary supplements |
Did antioxidant therapy show benefits on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients? | Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. | To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients. | We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents. | REFUTED | LOW | 2 | cardiovascular system |
Can the HINTS and HINTS Plus examinations accurately identify a central etiology for AVS? | Dizziness is a common reason for people to seek medical care. Acute vestibular syndrome (AVS) is a specific type of dizziness, which can include severe vertigo, nausea and vomiting, nystagmus, or unsteadiness. Acute vestibular syndrome can be due to peripheral or central causes. It is important to determine the cause, as the intervention and outcomes differ if it is from a peripheral or central cause. Clinicians can assess for the cause using risk factors, patient history, examination findings, or advanced imaging, such as a magnetic resonance imaging (MRI). The head impulse, nystagmus, test of skew (HINTS) examination is a three-part examination performed by clinicians to determine if AVS is due to a peripheral or central cause. This includes assessing how the eyes move in response to rapidly turning a person's head (head impulse), assessing the direction of involuntary eye movements (nystagmus), and assessing whether the eyes are aligned or misaligned (test of skew). The HINTS Plus examination includes an additional assessment of auditory function. | To assess the diagnostic accuracy of the HINTS and HINTS Plus examinations, with or without video assistance, for identifying a central etiology for AVS. | The HINTS and HINTS Plus examinations had good sensitivity and reasonable specificity for diagnosing a central cause for AVS in the emergency department when performed by trained clinicians. Overall, the evidence was of low certainty. There were limited data for the role of video-assistance or specific subgroups. Future research should include more high-quality studies of the HINTS and HINTS Plus examination; assessment of inter-rater reliability across users; accuracy across different providers, specialties, and experience; and direct comparison with no HINTS or MRI to assess the effect on clinical care. | SUPPORTED | LOW | 0 | cognitive, mental, and mental health |
Do methylxanthines have a positive impact on the outcomes of preterm infants? | Very preterm infants often require respiratory support and are therefore exposed to an increased risk of chronic lung disease and later neurodevelopmental disability. Although methylxanthines are widely used to prevent and treat apnea associated with prematurity and to facilitate extubation, there is uncertainty about the benefits and harms of different types of methylxanthines. | To assess the effects of methylxanthines on the incidence of apnea, death, neurodevelopmental disability, and other longer-term outcomes in preterm infants (1) at risk for or with apnea, or (2) undergoing extubation. | Caffeine probably reduces the risk of death, major neurodevelopmental disability at 18 to 24 months, and the composite outcome DMND at 18 to 24 months. Administration of any methylxanthine to preterm infants for any indication probably leads to a reduction in the risk of any apneic episodes, failed apnea reduction after two to seven days, cerebral palsy, developmental delay, and may reduce receipt of positive-pressure ventilation after institution of treatment. Methylxanthine used for any indication reduces chronic lung disease (defined as the use of supplemental oxygen at 36 weeks' postmenstrual age). | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Are single-incision sling operations effective for treating urinary incontinence in women? | Stress urinary incontinence imposes a significant health and economic burden on individuals and society. Single-incision slings are a minimally-invasive treatment option for stress urinary incontinence. They involve passing a short synthetic device through the anterior vaginal wall to support the mid-urethra. The use of polypropylene mesh in urogynaecology, including mid-urethral slings, is restricted in many countries. This is a review update (previous search date 2012). | To assess the effects of single-incision sling operations for treating urinary incontinence in women, and to summarise the principal findings of relevant economic evaluations. | Single-incision sling operations have been extensively researched in randomised controlled trials. They may be as effective as retropubic slings and are as effective as transobturator slings for subjective cure or improvement of stress urinary incontinence at 12 months. It is uncertain if single-incision slings lead to better or worse rates of subjective cure or improvement compared with autologous fascial slings. There are still uncertainties regarding adverse events and longer-term outcomes. Therefore, longer-term data are needed to clarify the safety and long-term effectiveness of single-incision slings compared to other mid-urethral slings. | NOT ENOUGH INFORMATION | MEDIUM | 0 | sexual and reproductive health |
Do home-based and supervised centre-based cardiac rehabilitation have similar effects on mortality and morbidity, exercise capacity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease? | Cardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based and technology-supported cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation, especially during the SARS-CoV-2 pandemic. This is an update of a review previously published in 2009, 2015, and 2017. | To compare the effect of home-based (which may include digital/telehealth interventions) and supervised centre-based cardiac rehabilitation on mortality and morbidity, exercise-capacity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease SEARCH METHODS: We updated searches from the previous Cochrane Review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) on 16 September 2022. We also searched two clinical trials registers as well as previous systematic reviews and reference lists of included studies. No language restrictions were applied. | This update supports previous conclusions that home- (± digital/telehealth platforms) and centre-based forms of cardiac rehabilitation formally supported by healthcare staff seem to be similarly effective in improving clinical and health-related quality of life outcomes in patients after myocardial infarction, or revascularisation, or with heart failure. This finding supports the continued expansion of healthcare professional supervised home-based cardiac rehabilitation programmes (± digital/telehealth platforms), especially important in the context of the ongoing global SARS-CoV-2 pandemic that has much limited patients in face-to-face access of hospital and community health services. Where settings are able to provide both supervised centre- and home-based programmes, consideration of the preference of the individual patient would seem appropriate. Although not included in the scope of this review, there is an increasing evidence base supporting the use of hybrid models that combine elements of both centre-based and home-based cardiac rehabilitation delivery. Further data are needed to determine: (1) whether the short-term effects of home/digital-telehealth and centre-based cardiac rehabilitation models of delivery can be confirmed in the longer term; (2) the relative clinical effectiveness and safety of home-based programmes for other heart patients, e.g. post-valve surgery and atrial fibrillation. | SUPPORTED | MEDIUM | 0 | cardiovascular system |
Does TXA reduce complications in individuals undergoing PCNL for kidney stones? | Percutaneous nephrolithotomy (PCNL) is the gold standard for the treatment of large kidney stones but comes with an increased risk of bleeding compared to other treatments, such as ureteroscopy and shock wave lithotripsy. Tranexamic acid (TXA) is an antifibrinolytic agent that has been used to reduce bleeding complications in other settings. | To assess the effects of TXA in individuals with kidney stones undergoing PCNL. | Based on 10 RCTs with substantial methodological limitations that lowered all CoE of effect, we found that systemic TXA in PCNL may reduce blood transfusions, major and minor surgical complications, and hospital LOS, as well as improve SFRs; however, it may increase AEs. We are uncertain about the effects of systemic TXA on other outcomes. Findings of this review should assist urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL. | SUPPORTED | LOW | 0 | cancer |
Can surfactant treatment guided by rapid tests for surfactant deficiency minimize the need for surfactant treatment and prevent bronchopulmonary dysplasia and mortality in preterm infants at risk for or having RDS? | Administration of various exogenous surfactant preparations has been shown to decrease lung injury and pneumothorax and improve survival in very preterm infants with respiratory distress syndrome (RDS). There is no consensus on the threshold for surfactant administration, to allow timely intervention and avoid over-treatment, also considering the invasiveness of the procedure and its cost. Rapid tests for lung maturity, which include the click test, lamellar body counts and stable microbubble test, might guide the identification of those infants needing surfactant administration. | To assess the effects of surfactant treatment guided by rapid tests for surfactant deficiency in preterm infants at risk for or having RDS. Comparison 1: In preterm infants at risk for RDS, does surfactant treatment guided by rapid tests for surfactant deficiency compared to prophylactic surfactant administration to all high-risk infants minimize the need for surfactant treatment and prevent bronchopulmonary dysplasia and mortality? Comparison 2: In preterm infants who require early respiratory support, does surfactant treatment guided by rapid tests for surfactant deficiency compared to surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria minimize the need for surfactant treatment and prevent bronchopulmonary dysplasia and mortality? | No studies compared surfactant treatment guided by rapid tests for surfactant deficiency to prophylactic surfactant administration to all high-risk infants. Low to very low-certainty evidence from three studies is available on surfactant therapy guided by rapid tests for surfactant deficiency versus surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria. No studies reported neonatal mortality, the composite outcome 'bronchopulmonary dysplasia or mortality', or neurodevelopmental outcomes. Compared with surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria, the evidence is very uncertain about the effect of surfactant treatment guided by rapid tests for surfactant deficiency on mortality prior to hospital discharge. Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in bronchopulmonary dysplasia, surfactant utilization and any pneumothorax. The findings of the two large ongoing trials identified in this review are likely to have an important impact on establishing the effects of surfactant treatment guided by rapid tests for surfactant deficiency in preterm infants. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Does doxapram administration have benefits on the incidence of apnea and other clinical outcomes in preterm infants? | Apnea of prematurity is a common problem in preterm infants that may have significant consequences on their development. Methylxanthines (aminophylline, theophylline, and caffeine) are effective in the treatment of apnea of prematurity. Doxapram is used as a respiratory stimulant in cases refractory to the methylxanthine treatment. | To evaluate the benefits and harms of doxapram administration on the incidence of apnea and other short-term and longer-term clinical outcomes in preterm infants. | In treating apnea of prematurity, doxapram may slightly reduce failure in apnea reduction when compared to no treatment and there may be little to no difference in side effects against both no treatment and alternative treatment. The evidence is very uncertain about the need for positive pressure ventilation when compared to no treatment or alternative treatment and about failed apnea reduction when used as alternative or adjunct therapy to methylxanthine. For use to prevent reintubation, doxapram may reduce apnea episodes when administered in adjunct to methylxanthine, but with little to no difference in failed extubation. The evidence is very uncertain about doxapram's effect on death when used as adjunct therapy to methylxanthine and about failed extubation when used as alternative or adjunct therapy to methylxanthine. There is a knowledge gap about the use of doxapram as a therapy to prevent apnea. More studies are needed to clarify the role of doxapram in the treatment of apnea of prematurity, addressing concerns about long-term outcomes. The ongoing studies may provide useful data. | NOT ENOUGH INFORMATION | LOW | 0 | respiratory system |
Is any anti-seizure medication more effective than an alternative medication in achieving seizure control and improving neurodevelopmental outcomes in neonates? | Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive. | 1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates. | Phenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes. In neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence). In neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence). All findings of this review apply only to term and late preterm neonates. We need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Did the interventions delivered by primary workers improve mental health outcomes? | There is a significant research gap in the field of universal, selective, and indicated prevention interventions for mental health promotion and the prevention of mental disorders. Barriers to closing the research gap include scarcity of skilled human resources, large inequities in resource distribution and utilization, and stigma. | To assess the effectiveness of delivery by primary workers of interventions for the promotion of mental health and universal prevention, and for the selective and indicated prevention of mental disorders or symptoms of mental illness in low- and middle-income countries (LMICs). To examine the impact of intervention delivery by primary workers on resource use and costs. | The evidence indicated that prevention interventions delivered through primary workers - a form of task-shifting - may improve mental health outcomes. Certainty in the evidence was influenced by the risk of bias and by substantial levels of heterogeneity. A supportive network of infrastructure and research would enhance and reinforce this delivery modality across LMICs. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Do organ protection interventions targeting the innate immune response have a treatment effect on inflammation, important clinical outcomes, or both? | Organ injury is a common and severe complication of cardiac surgery that contributes to the majority of deaths. There are no effective treatment or prevention strategies. It has been suggested that innate immune system activation may have a causal role in organ injury. A wide range of organ protection interventions targeting the innate immune response have been evaluated in randomised controlled trials (RCTs) in adult cardiac surgery patients, with inconsistent results in terms of effectiveness. | The aim of the review was to summarise the results of RCTs of organ protection interventions targeting the innate immune response in adult cardiac surgery. The review considered whether the interventions had a treatment effect on inflammation, important clinical outcomes, or both. | A systematic review of RCTs of organ protection interventions targeting innate immune system activation did not resolve uncertainty as to the effectiveness of these treatments, or the role of innate immunity in organ injury following cardiac surgery. | NOT ENOUGH INFORMATION | LOW | 1 | immune system and infections |
Do synbiotics, prebiotics, and probiotics provide benefits for people with chronic kidney disease? | Chronic kidney disease (CKD) is a major public health problem affecting 13% of the global population. Prior research has indicated that CKD is associated with gut dysbiosis. Gut dysbiosis may lead to the development and/or progression of CKD, which in turn may in turn lead to gut dysbiosis as a result of uraemic toxins, intestinal wall oedema, metabolic acidosis, prolonged intestinal transit times, polypharmacy (frequent antibiotic exposures) and dietary restrictions used to treat CKD. Interventions such as synbiotics, prebiotics, and probiotics may improve the balance of the gut flora by altering intestinal pH, improving gut microbiota balance and enhancing gut barrier function (i.e. reducing gut permeability). | This review aimed to evaluate the benefits and harms of synbiotics, prebiotics, and probiotics for people with CKD. | We found very few studies that adequately test biotic supplementation as alternative treatments for improving kidney function, GI symptoms, dialysis outcomes, allograft function, patient-reported outcomes, CVD, cancer, reducing uraemic toxins, and adverse effects. We are not certain whether synbiotics, prebiotics, or probiotics are more or less effective compared to one another, antibiotics, or standard care for improving patient outcomes in people with CKD. Adverse events were uncommon and mild. | NOT ENOUGH INFORMATION | LOW | 1 | digestive system and metabolism |
Does the lateral decubitus position improve the success rate and safety of lumbar puncture in newborn infants? | Lumbar puncture is a common invasive procedure performed in newborns for diagnostic and therapeutic purposes. Approximately one in two lumbar punctures fail, resulting in both short- and long-term negative consequences for the clinical management of patients. The most common positions used to perform lumbar puncture are the lateral decubitus and sitting position, and each can impact the success rate and safety of the procedure. However, it is uncertain which position best improves patient outcomes. | To assess the benefits and harms of the lateral decubitus, sitting, and prone positions for lumbar puncture in newborn infants. | When compared to sitting position, lateral decubitus position may result in little to no difference in successful lumbar puncture procedure at first attempt. None of the included studies reported the total number of lumbar puncture attempts. Furthermore, infants in a lateral decubitus position likely experience more episodes of bradycardia and oxygen desaturation, and there may be little to no difference in episodes of apnea. The evidence is very uncertain regarding time to perform lumbar puncture. Pain intensity during and after the procedure was reported using a pain scale that was not included in our prespecified tools for pain assessment due to its high risk of bias. Most study participants were term newborns, thereby limiting the applicability of these results to preterm babies. When compared to prone position, lateral decubitus position may reduce successful lumbar puncture procedure at first attempt. Only one study reported on this comparison and did not evaluate adverse effects. Further research exploring harms and benefits and the effect on patients' pain experience of different positions during lumbar puncture using validated pain scoring tool may increase the level of confidence in our conclusions. | NOT ENOUGH INFORMATION | LOW | 2 | miscellaneous |
Do oral antibiotics have clear benefits for 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 developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Antibiotics are sometimes used to treat any bacteria present in the effusion, or associated biofilms. | To assess the effects (benefits and harms) of oral antibiotics for otitis media with effusion (OME) in children. | The evidence for the use of antibiotics for OME is of low to very low certainty. Although the use of antibiotics compared to no treatment may have a slight beneficial effect on the resolution of OME at up to three months, the overall impact on hearing is very uncertain. The long-term effects of antibiotics are unclear and few of the studies included in this review reported on potential harms. These important endpoints should be considered when weighing up the potential short- and long-term benefits and harms of antibiotic treatment in a condition with a high spontaneous resolution rate. | NOT ENOUGH INFORMATION | LOW | 1 | ear, nose, and throat |
Do immunoglobulins have a significant effect on RSV-proven lower respiratory tract infections in children aged up to three years, admitted to hospital? | Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids) are ineffective or have limited effect. Respiratory syncytial virus immunoglobulin may be used prophylactically to prevent hospital admission from RSV-related illness. It may be considered for the treatment of established severe RSV infection or for treatment in an immunocompromised host, although it is not licensed for this purpose. It is unclear whether immunoglobulins improve outcomes when used as a treatment for established RSV infection in infants and young children admitted to hospital. This is an update of a review first published in 2019. | To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections (LRTIs) in children aged up to three years, admitted to hospital. | We are very uncertain about the effect of immunoglobulins on mortality. We are moderately certain that use of immunoglobulins in hospitalised infants and children may result in little to no difference in the length of hospitalisation. Immunoglobulins may result in little to no difference in adverse events, the need for or duration of mechanical ventilation, supplemental oxygen, or admission to the intensive care unit, though we are less certain about this evidence and the true effect of immunoglobulins on these outcomes may differ markedly from the estimated effect observed in this review. All trials were conducted in high-income countries, and data from populations in which the rate of death from RSV infection is higher are lacking. | NOT ENOUGH INFORMATION | LOW | 1 | immune system and infections |
Did haemostatic therapies have a significant effect on reducing death or dependence after acute spontaneous intracerebral haemorrhage? | Outcome after acute spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume. ICH expansion occurs in about 20% of people with acute ICH. Early haemostatic therapy might improve outcome by limiting ICH expansion. This is an update of a Cochrane Review first published in 2006, and last updated in 2018. | To examine 1. the effects of individual classes of haemostatic therapies, compared with placebo or open control, in adults with acute spontaneous ICH, and 2. the effects of each class of haemostatic therapy according to the use and type of antithrombotic drug before ICH onset. | In this updated Cochrane Review including 20 RCTs involving 4652 participants, rFVIIa likely results in little to no difference in reducing death or dependence after spontaneous ICH with or without surgery; antifibrinolytic drugs result in little to no difference in reducing death or dependence after spontaneous ICH, but result in a slight reduction in ICH expansion within 24 hours; platelet transfusion likely increases death or dependence after antiplatelet-associated ICH; and the evidence is very uncertain about the effect of PCC compared to FFP on death or dependence after anticoagulant-associated ICH. Thirteen RCTs are ongoing and are likely to increase the certainty of the estimates of treatment effect. | NOT ENOUGH INFORMATION | LOW | 2 | cognitive, mental, and mental health |
Do the treatments for alopecia areata result in increased hair regrowth? | Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth stimulants, and contact immunotherapy. | To assess the benefits and harms of the treatments for alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) in children and adults. | We found that treatment with baricitinib results in an increase in short- and long-term hair regrowth compared to placebo. Although we found inconclusive results for the risk of serious adverse effects with baricitinib, the reported small incidence of serious adverse events in the baricitinib arm should be balanced with the expected benefits. We also found that the impact of other treatments on hair regrowth is very uncertain. Evidence for health-related quality of life is still scant. | SUPPORTED | MEDIUM | 0 | musculoskeletal system and dermatology |
Does adenoidectomy, either alone or in combination with ventilation tubes (grommets), benefit children with OME? | 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 developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Adenoidectomy has often been used as a potential treatment for this condition. | To assess the benefits and harms of adenoidectomy, either alone or in combination with ventilation tubes (grommets), for OME in children. | When assessed with the GRADE approach, the evidence for adenoidectomy in children with OME is very uncertain. Adenoidectomy may reduce the persistence of OME, although evidence about the effect of this on hearing is unclear. For patients and carers, a return to normal hearing is likely to be important, but few studies measured this outcome. We did not identify any evidence on disease-specific quality of life. There were few data on adverse effects, in particular postoperative bleeding. The risk of haemorrhage appears to be small, but should be considered when choosing a treatment strategy for children with OME. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Did the immunomodulatory interventions effectively reduce seizure frequency in children and adults with focal epilepsy? | This is an updated version of an original Cochrane Review published in 2013 (Walker 2013). Epilepsy is a common neurological disorder affecting 0.5% to 1% of the population. Pharmacological treatment remains the first choice to control epilepsy. However, up to 30% of people do not respond to drug treatment, and therefore do not achieve seizure remission. Experimental and clinical evidence supports a role for inflammatory pathway activation in the pathogenesis of epilepsy which, if effectively targeted by immunomodulatory interventions, highlights a potentially novel therapeutic strategy. | To assess the efficacy and tolerability of immunomodulatory interventions on seizures, adverse effect profile, cognition, and quality of life, compared to placebo controls, when used as additional therapy for focal epilepsy in children and adults. | Immunomodulatory interventions as add-on treatment for children and adults with focal epilepsy appear to be effective in reducing seizure frequency. It is not possible to draw any conclusions about the tolerability of these agents in children and adults with epilepsy. Further randomised controlled trials are needed. | SUPPORTED | LOW | 0 | cognitive, mental, and mental health |
Does higher sodium supplementation in preterm infants have significant effects compared to lower supplementation? | Infants born preterm are at increased risk of early hypernatraemia (above-normal blood sodium levels) and late hyponatraemia (below-normal blood sodium levels). There are concerns that imbalances of sodium intake may impact neonatal morbidities, growth and developmental outcomes. | To determine the effects of higher versus lower sodium supplementation in preterm infants. | Early (< 7 days following birth) higher sodium supplementation may result in an increased incidence of hypernatraemia and may result in a similar incidence of hyponatraemia compared to lower supplementation. We are uncertain if there are any effects on mortality or neonatal morbidity. Growth and longer-term development outcomes were largely unreported in trials of early sodium supplementation. Late (≥ 7 days following birth) higher sodium supplementation may reduce the incidence of hyponatraemia. We are uncertain if late higher intake affects the incidence of hypernatraemia compared to lower supplementation. Late higher sodium intake may reduce postnatal growth failure. We are uncertain if late higher sodium intake affects mortality, other neonatal morbidities or longer-term development. We are uncertain if early and late higher versus lower sodium supplementation affects outcomes. | NOT ENOUGH INFORMATION | LOW | 0 | cognitive, mental, and mental health |
Does child growth monitoring and promotion effectively improve key child health indicators in low- and middle-income countries? | Undernutrition in the critical first 1000 days of life is the most common form of childhood malnutrition, and a significant problem in low- and middle-income countries (LMICs). The effects of undernutrition in children aged under five years are wide-ranging and include increased susceptibility to and severity of infections; impaired physical and cognitive development, which diminishes school and work performance later in life; and death. Growth monitoring and promotion (GMP) is a complex intervention that comprises regular measurement and charting of growth combined with promotion activities. Policymakers, particularly in international aid agencies, have differing and changeable interpretations and perceptions of the purpose of GMP. The effectiveness of GMP as an approach to preventing malnutrition remains a subject of debate, particularly regarding the added value of growth monitoring compared with promotion alone. | To evaluate the effectiveness of child growth monitoring and promotion for identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact with and use of health services in children under five years of age in low- and middle-income countries. | There is limited uncertain evidence on the effectiveness of GMP for identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact with and use of health services in children aged under five years in LMICs. Future studies should explore the reasons for the apparent limited impact of GMP on key child health indicators. Reporting of GMP interventions and important outcomes must be transparent and consistent. | NOT ENOUGH INFORMATION | LOW | 1 | nutrition and dietary supplements |
Did interventions to improve appropriate polypharmacy result in clinically significant improvement? | Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, so that many medicines may be used to achieve better clinical outcomes for patients. This is the third update of this Cochrane Review. | To assess the effects of interventions, alone or in combination, in improving the appropriate use of polypharmacy and reducing medication-related problems in older people. | It is unclear whether interventions to improve appropriate polypharmacy resulted in clinically significant improvement. Since the last update of this review in 2018, there appears to have been an increase in the number of studies seeking to address potential prescribing omissions and more interventions being delivered by multidisciplinary teams. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does Cerebrolysin or Cerebrolysin-like agents have a beneficial effect on treating acute ischaemic stroke? | Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain, which has potential neuroprotective properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. This is an update of a review first published in 2010 and last updated in 2020. | To assess the benefits and harms of Cerebrolysin or Cerebrolysin-like agents for treating acute ischaemic stroke. | Moderate-certainty evidence indicates that Cerebrolysin or Cerebrolysin-like peptide mixtures derived from cattle brain probably have no beneficial effect on preventing all-cause death in acute ischaemic stroke. Moderate-certainty evidence suggests that Cerebrolysin probably has no beneficial effect on the total number of people with serious adverse events. Moderate-certainty evidence also indicates a potential increase in non-fatal serious adverse events with Cerebrolysin use. | REFUTED | MEDIUM | 2 | cognitive, mental, and mental health |
Does different intensities of glycaemic control in pregnant women with GDM affect maternal and infant health outcomes? | Gestational diabetes mellitus (GDM) has major short- and long-term implications for both the mother and her baby. GDM is defined as a carbohydrate intolerance resulting in hyperglycaemia or any degree of glucose intolerance with onset or first recognition during pregnancy from 24 weeks' gestation onwards and which resolves following the birth of the baby. Rates for GDM can be as high as 25% depending on the population and diagnostic criteria used, and overall rates are increasing globally. There is wide variation internationally in glycaemic treatment target recommendations for women with GDM that are based on consensus rather than high-quality trials. | To assess the effect of different intensities of glycaemic control in pregnant women with GDM on maternal and infant health outcomes. | This review is based on four trials (1731 women) with an overall unclear risk of bias. The trials provided data on most primary outcomes and suggest that tighter glycaemic control may increase the risk of hypertensive disorders of pregnancy. The risk of birth of a large-for-gestational-age infant and perinatal mortality may be similar between groups, and tighter glycaemic targets may result in a possible reduction in composite of death or severe infant morbidity. However, the CIs for these outcomes are wide, suggesting both benefit and harm. There remains limited evidence regarding the benefit of different glycaemic targets for women with GDM to minimise adverse effects on maternal and infant health. Glycaemic target recommendations from international professional organisations vary widely and are currently reliant on consensus given the lack of high-certainty evidence. Further high-quality trials are needed, and these should assess both short- and long-term health outcomes for women and their babies; include women's experiences; and assess health services costs in order to confirm the current findings. Two trials are ongoing. | NOT ENOUGH INFORMATION | LOW | 1 | endocrine system and hormones |
Is one magnesium sulphate regimen better than another for the care of women with pre-eclampsia or eclampsia to reduce the risk of severe morbidity and mortality for the woman and her baby? | Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but there is no clarity on the comparative benefits or harm of alternative regimens. This is an update of a review first published in 2010. | To assess if one magnesium sulphate regimen is better than another when used for the care of women with pre-eclampsia or eclampsia, or both, to reduce the risk of severe morbidity and mortality for the woman and her baby. | Despite the number of trials evaluating various magnesium sulphate regimens for eclampsia prophylaxis and treatment, there is still no compelling evidence that one particular regimen is more effective than another. Well-designed randomised controlled trials are needed to answer this question. | NOT ENOUGH INFORMATION | LOW | 1 | sexual and reproductive health |
Do pharmacological interventions effectively manage the behaviors of irritability, aggression, and self-injury in ASD? | Pharmacological interventions are frequently used for people with autism spectrum disorder (ASD) to manage behaviours of concern, including irritability, aggression, and self-injury. Some pharmacological interventions might help treat some behaviours of concern, but can also have adverse effects (AEs). | To assess the effectiveness and AEs of pharmacological interventions for managing the behaviours of irritability, aggression, and self-injury in ASD. | Evidence suggests that atypical antipsychotics probably reduce irritability, ADHD-related medications may reduce irritability slightly, and neurohormones may have little to no effect on irritability in the short term in people with ASD. There was some evidence that atypical antipsychotics may reduce self-injury in the short term, although the evidence is uncertain. There was no clear evidence that antidepressants had an effect on irritability. There was also little to no difference in aggression between atypical antipsychotics and placebo, or self-injury between ADHD-related medications and placebo. However, there was some evidence that atypical antipsychotics may result in a large reduction in self-injury, although the evidence is uncertain. No data were reported (or could be used) for self-injury or aggression for neurohormones versus placebo. Studies reported a wide range of potential AEs. Atypical antipsychotics and ADHD-related medications in particular were associated with an increased risk of metabolic and neurological AEs, although the evidence is uncertain for atypical antipsychotics and very uncertain for ADHD-related medications. The other drug classes had minimal or no associated AEs. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Do immune checkpoint inhibitors have a significant effect on the treatment of advanced or metastatic urothelial carcinoma? | Immune checkpoint inhibitors are increasingly important in the treatment algorithm for locally advanced and metastatic bladder cancer. Numerous ongoing studies are investigating these agents as first- and second-line therapies, both alone and in combination with chemotherapy or in a maintenance therapy setting. | To assess the effects of immune checkpoint inhibitors compared to chemotherapy as first- and second-line treatment of advanced or metastatic urothelial carcinoma. | Compared to chemotherapy, immunotherapy for treating advanced or metastatic urothelial carcinoma probably has little to no effect on the risk of death from any cause when used as first-line therapy. Still, it may reduce the risk of death from any cause when used as second-line therapy. Health-related quality of life for participants receiving first- and second-line therapy does not appear to be affected by immunotherapy. Immunotherapy probably reduces or may reduce adverse events grade 3 to 5 when used as first- and second-line therapy, respectively. | REFUTED | MEDIUM | 2 | cancer |
Are there relevant, feasible, and effective communication approaches to promote acceptance, uptake, and adherence to physical distancing measures for COVID-19 prevention and control? | This review is an update of a rapid review undertaken in 2020 to identify relevant, feasible and effective communication approaches to promote acceptance, uptake and adherence to physical distancing measures for COVID-19 prevention and control. The rapid review was published when little was known about transmission, treatment or future vaccination, and when physical distancing measures (isolation, quarantine, contact tracing, crowd avoidance, work and school measures) were the cornerstone of public health responses globally. This updated review includes more recent evidence to extend what we know about effective pandemic public health communication. This includes considerations of changes needed over time to maintain responsiveness to pandemic transmission waves, the (in)equities and variable needs of groups within communities due to the pandemic, and highlights again the critical role of effective communication as integral to the public health response. | To update the evidence on the question 'What are relevant, feasible and effective communication approaches to promote acceptance, uptake and adherence to physical distancing measures for COVID-19 prevention and control?', our primary focus was communication approaches to promote and support acceptance, uptake and adherence to physical distancing. | Implications for practice Evidence highlights the critical role of communication throughout a public health emergency. Like any intervention, communication can be done well or poorly, but the consequences of poor communication during a pandemic may mean the difference between life and death. The approaches to effective communication identified in this review can be used by policymakers and decision-makers, working closely with communication teams, to plan, implement and adjust public communications over the course of a public health emergency like the COVID-19 pandemic. Implications for research Despite massive growth in research during the COVID-19 period, gaps in the evidence persist and require high-quality, meaningful research. This includes investigating the experiences of people at heightened COVID-19 risk, and identifying barriers to implementing public communication and protective health measures particular to lower- and middle-income countries, and how to overcome these. | SUPPORTED | MEDIUM | 0 | immune system and infections |
Does ESPB improve postoperative pain intensity compared to no block? | Acute and chronic postoperative pain are important healthcare problems, which can be treated with a combination of opioids and regional anaesthesia. The erector spinae plane block (ESPB) is a new regional anaesthesia technique, which might be able to reduce opioid consumption and related side effects. | To compare the analgesic effects and side effect profile of ESPB against no block, placebo block or other regional anaesthetic techniques. | ESPB in addition to standard care probably does not improve postoperative pain intensity 24 hours after surgery compared to no block. The number of block-related adverse events following ESPB was low. Further research is required to study the possibility of extending the duration of analgesia. We identified 37 new studies in the updated search and there are three ongoing studies, suggesting possible changes to the effect estimates and the certainty of the evidence in the future. | REFUTED | MEDIUM | 2 | musculoskeletal system and dermatology |
Does SOD have a significant effect on preventing and treating BPD and its complications in preterm infants? | Free oxygen radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. Superoxide dismutase (SOD) is a naturally occurring enzyme which provides a defense against such oxidant injury. Providing supplementary SOD has been tested in clinical trials to prevent BPD in preterm infants. | To determine the efficacy and safety of SOD in the prevention and treatment of BPD on mortality and other complications of prematurity in infants at risk for, or having BPD. | The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality and mortality prior to discharge compared to placebo. No studies reported BPD or death at 36 weeks' postmenstrual age and need for supplemental oxygen. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage and severe retinopathy of prematurity. No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. The effects of SOD in preterm infants has not been reported in any trial in the last few decades, considering that the most recent trial on SOD in preterm infants was conducted in 1997/1998, and no new studies are ongoing. In the light of the limited available evidence, new data from preclinical and observational studies are needed to justify the conduction of new RCTs. Observational studies might report how SOD is administered, including indication, dose and association with relevant outcomes such as mortality, BPD and long-term neurodevelopment. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Does bladder training provide benefits for treating adults with OAB compared to other treatments or no treatment? | Overactive bladder (OAB) is a common chronic and bothersome condition. Bladder training is widely prescribed as a first-line treatment for OAB, but the efficacy has been systematically evaluated for urinary incontinence rather than OAB alone. | To evaluate the benefits and harms of bladder training for treating adults with OAB compared to no treatment, anticholinergics, β3-adrenoceptor agonists, or pelvic floor muscle training (PFMT) alone or in combination. | This review focused on the effect of bladder training to treat OAB. However, most of the evidence was low or very-low certainty. Based on the low- or very low-certainty evidence, bladder training may cure or improve OAB compared to no treatment. Bladder training may be more effective to cure or improve OAB than anticholinergics, and there may be fewer adverse events. There may be no difference in efficacy or safety between bladder training and PFMT. More well-designed trials are needed to reach a firm conclusion. | NOT ENOUGH INFORMATION | LOW | 0 | urinary system |
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Dataset Card for "MedREQAL"
This dataset is the converted version of MedREQAL.
Reference
If you use MedREQAL, please cite the original paper:
@inproceedings{vladika-etal-2024-medreqal,
title = "{M}ed{REQAL}: Examining Medical Knowledge Recall of Large Language Models via Question Answering",
author = "Vladika, Juraj and
Schneider, Phillip and
Matthes, Florian",
editor = "Ku, Lun-Wei and
Martins, Andre and
Srikumar, Vivek",
booktitle = "Findings of the Association for Computational Linguistics ACL 2024",
month = aug,
year = "2024",
address = "Bangkok, Thailand and virtual meeting",
publisher = "Association for Computational Linguistics",
url = "https://aclanthology.org/2024.findings-acl.860",
pages = "14459--14469",
abstract = "In recent years, Large Language Models (LLMs) have demonstrated an impressive ability to encode knowledge during pre-training on large text corpora. They can leverage this knowledge for downstream tasks like question answering (QA), even in complex areas involving health topics. Considering their high potential for facilitating clinical work in the future, understanding the quality of encoded medical knowledge and its recall in LLMs is an important step forward. In this study, we examine the capability of LLMs to exhibit medical knowledge recall by constructing a novel dataset derived from systematic reviews {--} studies synthesizing evidence-based answers for specific medical questions. Through experiments on the new MedREQAL dataset, comprising question-answer pairs extracted from rigorous systematic reviews, we assess six LLMs, such as GPT and Mixtral, analyzing their classification and generation performance. Our experimental insights into LLM performance on the novel biomedical QA dataset reveal the still challenging nature of this task.",
}
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