question
stringlengths 35
322
| background
stringlengths 9
6.76k
| objective
stringlengths 13
1.83k
| conclusion
stringlengths 13
24.8k
| verdicts
stringclasses 3
values | strength
stringclasses 7
values | label
int64 0
2
| category
stringclasses 24
values |
|---|---|---|---|---|---|---|---|
Does altered salt intake affect blood pressure and markers of cardiovascular disease and chronic kidney disease in people with diabetes? | There is strong evidence that our current consumption of salt is a major factor in the development of increased blood pressure (BP) and that a reduction in our salt intake lowers BP, whether BP levels are normal or raised initially. Effective control of BP in people with diabetes lowers the risk of strokes, heart attacks and heart failure and slows the progression of chronic kidney disease (CKD) in people with diabetes. This is an update of a review first published in 2010. | To evaluate the effect of altered salt intake on BP and markers of cardiovascular disease and of CKD in people with diabetes. | This systematic review shows an important reduction in SBP and DBP in people with diabetes with normal GFR during short periods of salt restriction, similar to that obtained with single drug therapy for hypertension. These data support the international recommendations that people with diabetes with or without hypertension or evidence of kidney disease should reduce salt intake to less than 5 g/day (2 g sodium). | SUPPORTED | MEDIUM | 0 | cardiovascular system |
Can remote ischaemic preconditioning provide benefits in people undergoing elective major vascular and endovascular surgery? | Despite advances in perioperative care, elective major vascular surgical procedures still carry a significant risk of morbidity and mortality. Remote ischaemic preconditioning (RIPC) is the temporary blocking of blood flow to vascular beds remote from those targeted by surgery. It has the potential to provide local tissue protection from further prolonged periods of ischaemia. However, the efficacy and safety of RIPC in people undergoing major vascular surgery remain unknown. This is an update of a review published in 2011. OBJECTIVES: To assess the benefits and harms of RIPC versus no RIPC in people undergoing elective major vascular and endovascular surgery. | Search methods: | Trial registration: | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Was the effectiveness and optimal timing of surgical and non-surgical treatment options for infantile esotropia examined to improve ocular alignment and achieve or allow the development of binocular single vision? | Infantile esotropia (IE) is the inward deviation of the eye. Various aspects of the clinical management of IE are unclear; mainly, the most effective type of intervention and the age at intervention. | To examine the effectiveness and optimal timing of surgical and non-surgical treatment options for IE to improve ocular alignment and achieve or allow the development of binocular single vision. | Medial rectus recessions may increase the incidence of treatment success compared with botulinum toxin injections alone, but the evidence was very uncertain. No evidence of important difference was found between bilateral surgery and unilateral surgery. Due to insufficient evidence, it was not possible to resolve the controversies regarding type of surgery, non-surgical intervention, or age of intervention in this review. There is clearly a need to conduct good quality trials in these areas to improve the evidence base for the management of IE. | NOT ENOUGH INFORMATION | LOW | 1 | sensory organs |
Do different regimens of systemic opioid analgesics in neonates undergoing surgery have clear effects on mortality, pain, and significant neurodevelopmental disability? | Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature. | To determine the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability. Potentially assessed regimens might include: different doses of the same opioid, different routes of administration of the same opioid, continuous infusion versus bolus administration, or 'as needed' administration versus 'as scheduled' administration. | limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. we are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. only one small study reported on morphine infusion with parent- or nurse-controlled analgesia. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does baclofen benefit achieving and maintaining abstinence or reducing alcohol consumption in people with AUD compared to placebo or other pharmacological treatments? | Alcohol use disorder (AUD) is one of the most widespread psychiatric disorders leading to detrimental consequences to people with this disorder and others. Worldwide, the prevalence of heavy episodic drinking (30-day prevalence of at least one occasion of 60 g of pure alcohol intake among current drinkers) is estimated at 20% and the prevalence of AUD at 5% of the adult general population, with highest prevalence in Europe and North America. Therapeutic approaches, including pharmacotherapy, play an important role in treating people with AUD. This is an update of a Cochrane Review first published in 2018. | To evaluate the benefits and harms of baclofen on achieving and maintaining abstinence or reducing alcohol consumption in people with AUD compared to placebo, no treatment or any other pharmacological relapse prevention treatment. | Baclofen likely reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. It does not increase the number of participants with at least one adverse event, those who dropout for any reason or due to adverse events. It probably does not reduce number of heavy drinking days and the number of drinks per drinking days. Current evidence suggests that baclofen may help people with AUD in maintaining abstinence. The results of comparisons of baclofen with acamprosate and naltrexone were mainly based on only one study. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Did telerehabilitation show similar effects to face-to-face vision rehabilitation services for improving vision-related quality of life and near reading ability? | Low vision affects over 300 million people worldwide and can compromise both activities of daily living and quality of life. Rehabilitative training and vision assistive equipment (VAE) may help, but some visually impaired people have limited resources to attend in-person visits to rehabilitation clinics to be trained to learn to use VAE. These people may be able to overcome barriers to care through access to remote, internet-based consultation (telerehabilitation). | To compare the effects of telerehabilitation with face-to-face (e.g. in-office or inpatient) vision rehabilitation services for improving vision-related quality of life and near reading ability in people with visual function loss due to any ocular condition. Secondary objectives were to evaluate compliance with scheduled rehabilitation sessions, abandonment rates for VAE devices, and patient satisfaction ratings. | the included trial found similar efficacy between telerehabilitation with a therapist and an active control intervention of self-guided training in mostly younger to middle-aged adults with low vision who received a new wearable electronic aid. given the disease burden and the growing interest in telemedicine, the two ongoing studies, when completed, may provide further evidence of the potential for telerehabilitation as a platform for providing services to people with low vision. | SUPPORTED | MEDIUM | 0 | sensory organs |
Do HbF inducers have a beneficial effect on reducing blood transfusion for people with NTDβT? | Non-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDβT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use. | To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDβT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer. | We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDβT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing. | NOT ENOUGH INFORMATION | LOW | 1 | blood and lymphatic system |
Does vitamin D supplementation as an adjunct to antibiotics have important effects on outcomes of acute childhood pneumonia? | Children with acute pneumonia may be vitamin D deficient. Clinical trials have found that prophylactic vitamin D supplementation decreases children's risk of developing pneumonia. Data on the therapeutic effects of vitamin D in acute childhood pneumonia are limited. This is an update of a Cochrane Review first published in 2018. | To evaluate the efficacy and safety of vitamin D supplementation as an adjunct to antibiotics for the treatment of acute childhood pneumonia. | Based on the available evidence, we are uncertain whether vitamin D supplementation has important effects on outcomes of acute pneumonia when used as an adjunct to antibiotics. The trials reported no major adverse events. Uncertainty in the evidence is due to imprecision, risk of bias, inconsistency, and indirectness. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Does totally percutaneous access provide significant benefits compared to cut-down femoral artery access in elective bifurcated abdominal endovascular aneurysm repair (EVAR)? | Abdominal aortic aneurysms (AAAs) are a vascular condition with significant risk attached, particularly if they rupture. Therefore, it is critical to identify and repair these as an elective procedure before they rupture and require emergency surgery. Repair has traditionally been an open surgical technique that required a large incision across the abdomen. Endovascular abdominal aortic aneurysm repairs (EVARs) are now a common alternative. In this procedure, the common femoral artery is exposed via a cut-down approach and a graft is introduced to the aneurysm in this way. This Cochrane Review examines a totally percutaneous approach to EVAR. This technique gives a minimally invasive approach to femoral artery access that may reduce groin wound complication rates and improve recovery time. However, the technique may be less applicable in people with, for example, groin scarring or arterial calcification. This is an update of the previous Cochrane Review published in 2017. | To evaluate the benefits and harms of totally percutaneous access compared to cut-down femoral artery access in people undergoing elective bifurcated abdominal endovascular aneurysm repair (EVAR). | Skin puncture may make little to no difference to short-term mortality. There is probably little or no difference in failure of aneurysm exclusion (failure to seal the aneurysms), wound infection, major complications within 30 days or while in hospital, medium- to long-term (six months) complications and bleeding complications between the two groups. Compared with exposing the femoral artery, skin puncture may reduce the operating time slightly. We downgraded the certainty of the evidence to moderate and low as a result of imprecision due to the small number of participants, low event rates and wide CIs, and inconsistency due to clinical heterogeneity. As the number of included studies was limited, further research into this technique would be beneficial. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Did psychological interventions have a positive effect on psychological morbidities and quality of life among women with non-metastatic breast cancer? | Breast cancer is the most common cancer affecting women worldwide. It is a distressing diagnosis and, as a result, considerable research has examined the psychological sequelae of being diagnosed and treated for breast cancer. Breast cancer is associated with increased rates of depression and anxiety and reduced quality of life. As a consequence, multiple studies have explored the impact of psychological interventions on the psychological distress experienced after a diagnosis of breast cancer. This review is an update of a Cochrane Review first published in 2015. | To assess the effect of psychological interventions on psychological morbidities and quality of life among women with non-metastatic breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov up to 16 March 2021. We also scanned the reference lists of relevant articles. | Based on the available evidence, psychological intervention may have produced favourable effects on psychological outcomes, in particular depression, anxiety, mood disturbance and stress. There was also an improvement in quality of life in the psychological intervention group compared to control group. Overall, there was substantial variation across the studies in the range of psychological interventions used, control conditions, measures of the same outcome and timing of follow-up. | SUPPORTED | MEDIUM | 0 | cancer |
Do glucocorticoids have significant effects in treating croup in children? | Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018. | To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below. | The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low-dose dexamethasone at 0.15 mg/kg to treat croup. | SUPPORTED | MEDIUM | 0 | respiratory system |
Do bisphosphonates affect the frequency of fractures, bone mineral density, and quality of life in people with cystic fibrosis? | Osteoporosis is a disorder of bone mineralisation occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and decrease the risk of new fractures in post-menopausal women and people receiving long-term oral corticosteroids. This is an updated version of a previous review. | To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, trial withdrawals, and survival in people with cystic fibrosis. | Oral and intravenous bisphosphonates may increase bone mineral density in people with cystic fibrosis, but there are insufficient data to determine whether treatment reduces fractures. Severe bone pain and flu-like symptoms may occur with intravenous bisphosphonates. Before any firm conclusions can be drawn, trials in larger populations, including children, and of longer duration are needed to determine effects on fracture rate and survival. Additional trials are needed to determine if bone pain is more common or severe (or both) with the more potent zoledronate and if corticosteroids can ameliorate or prevent these adverse events. Future trials should also assess gastrointestinal adverse effects associated with oral bisphosphonates. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Is fetal scalp stimulation a reliable method to confirm fetal well-being during labor? | Continuous fetal heart rate monitoring by cardiotocography (CTG) is used in labour for women with complicated pregnancies. Fetal heart rate abnormalities are common and may result in the decision to expedite delivery by caesarean section. Fetal scalp stimulation (FSS) is a second-line test of fetal well-being that may provide reassurance that the labour can continue. | To evaluate methods of FSS as second-line tests of intrapartum fetal well-being in cases of non-reassuring CTG. FSS and CTG were compared to CTG alone, and to CTG with fetal blood sampling (FBS). | There is very low-certainty evidence available which makes it unclear whether stimulating the fetal scalp is a safe and effective way to confirm fetal well-being in labour. Evidence was downgraded based on limitations in study design and imprecision. Further high-quality studies of adequate sample size are required to evaluate this research question. In order to be generalisable, these trials should be conducted in different settings, including broad clinical criteria at both preterm and term gestational ages, and standardising the method of stimulation. There is an ongoing study (FIRSST) that will be incorporated into this review in a subsequent update. | NOT ENOUGH INFORMATION | LOW | 1 | sexual and reproductive health |
Do PPAR-γ agonists effectively prevent stroke and related vascular events in people with stroke or TIA? | Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in December 2017 and October 2019. | To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA). | Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA. | SUPPORTED | LOW | 0 | cardiovascular system |
Does hormonal contraception use increase the risk of thromboembolism in women with COVID-19? | The novel coronavirus disease (COVID-19) has led to significant mortality and morbidity, including a high incidence of related thrombotic events. There has been concern regarding hormonal contraception use during the COVID-19 pandemic, as this is an independent risk factor for thrombosis, particularly with estrogen-containing formulations. However, higher estrogen levels may be protective against severe COVID-19 disease. Evidence for risks of hormonal contraception use during the COVID-19 pandemic is sparse. We therefore conducted a living systematic review that will be updated as new data emerge on the risk of thromboembolism with hormonal contraception use in patients with COVID-19. | To determine if use of hormonal contraception increases risk of venous and arterial thromboembolism in women with COVID-19. To determine if use of hormonal contraception increases other markers of COVID-19 severity including hospitalization in the intensive care unit, acute respiratory distress syndrome, intubation, and mortality. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. | There are no comparative studies assessing risk of thromboembolism in COVID-19 patients who use hormonal contraception, which was the primary objective of this review. Very little evidence exists examining the risk of increased COVID-19 disease severity for combined hormonal contraception users compared to non-users of hormonal contraception, and the evidence that does exist is of very low certainty. The odds of hospitalization for COVID-19 positive users of combined hormonal contraceptives may be slightly decreased compared with those of hormonal contraceptive non-users, but the evidence is very uncertain as this is based on one study restricted to patients with BMI under 35 kg/m | NOT ENOUGH INFORMATION | LOW | 1 | endocrine system and hormones |
Does iridotomy have a significant effect on slowing progression of visual field loss in primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect? | Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. For example, contact between the iris and lens at the pupillary margin creates a pupillary block that increases resistance to aqueous outflow. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy ('iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber, which is achieved by creating a hole in the iris using laser. Iridotomy is used to treat patients with primary angle-closure glaucoma, patients with primary angle-closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). However, the effectiveness of iridotomy on slowing progression of visual field loss is uncertain. | To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect. | we did not find sufficient evidence to draw any meaningful conclusions on the use of iridotomy for the purpose of slowing progression of visual field loss. no study reported on progressive visual field loss, the primary outcome of this review. although there is moderate certainty evidence that iridotomy results in improved gonioscopic findings, in is unclear if these findings translate to clinically meaningful benefits. | NOT ENOUGH INFORMATION | MEDIUM | 1 | sensory organs |
Does inspiratory muscle training (IMT) improve outcomes in chronic obstructive pulmonary disease (COPD), either alone or when combined with pulmonary rehabilitation (PR)? | Inspiratory muscle training (IMT) aims to improve respiratory muscle strength and endurance. Clinical trials used various training protocols, devices and respiratory measurements to check the effectiveness of this intervention. The current guidelines reported a possible advantage of IMT, particularly in people with respiratory muscle weakness. However, it remains unclear to what extent IMT is clinically beneficial, especially when associated with pulmonary rehabilitation (PR). OBJECTIVES: To assess the effect of inspiratory muscle training (IMT) on chronic obstructive pulmonary disease (COPD), as a stand-alone intervention and when combined with pulmonary rehabilitation (PR). | Search methods: | IMT may not improve dyspnea, functional exercise capacity and life quality when associated with PR. However, IMT is likely to improve these outcomes when provided alone. For both interventions, a larger effect in participants with respiratory muscle weakness and with longer training durations is still to be confirmed. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Does physical exercise have an effect on the severity of motor signs and quality of life in adults with Parkinson's disease? | Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear. | To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs). | We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD. | SUPPORTED | MEDIUM | 0 | musculoskeletal system and dermatology |
Is silicone gel sheeting effective for treating keloid scars compared with standard care or other therapies? | Keloid scarring is one of the most common types of pathological scarring. Keloid scars that fail to heal can affect a person's physical and psychological function by causing pain, pruritus, contractures, and cosmetic disfigurement. Silicone gel sheeting (SGS) is made from medical-grade silicone reinforced with a silicone membrane backing and is one of the most commonly used treatments for keloid scars. However, there is no up-to-date systematic review assessing the effectiveness of SGS for keloid scars. A clear and rigorous review of current evidence is required to guide clinicians, healthcare managers and people with keloid scarring. | To assess the effectiveness of silicone gel sheeting for the treatment of keloid scars compared with standard care or other therapies. | There is currently a lack of RCT evidence about the clinical effectiveness of SGS in the treatment of keloid scars. From the two studies identified, there is insufficient evidence to demonstrate whether the use of SGS compared with no treatment, non-SGS, or intralesional injections of triamcinolone acetonide makes any difference in the treatment of keloid scars. Evidence from the included studies is of very low certainty, mainly driven by the risk of bias, indirectness, and imprecision due to small sample size. Further well-designed studies that have good reporting methodologies and address important clinical, quality of life and economic outcomes are required to reduce uncertainty around decision-making in the use of SGS to treat keloid scars. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Did non-pharmacological interventions consistently improve sleep disturbances in people with dementia? | Sleep disturbances occur frequently in people with dementia with a reported prevalence of up to 40%. Common problems are increased number and duration of awakenings and increased percentage of light sleep. Sleep disturbances are associated with a number of problems for people with dementia, their relatives, and carers. In people with dementia, they may lead to worsening of cognitive symptoms, challenging behaviours such as restlessness or wandering, and further harms, such as accidental falls. Sleep disturbances are also associated with significant carer distress and have been reported as a factor contributing to institutionalisation of people with dementia. As pharmacological approaches have shown unsatisfactory results, there is a need to synthesise the research evidence on non-pharmacological strategies to improve sleep in people with dementia. As interventions are often complex, consisting of more than one active component, and implemented in complex contexts, it may not be easy to identify effective intervention components. | To evaluate the benefits and harms of non-pharmacological interventions on sleep disturbances in people with dementia compared to usual care, no treatment, any other non-pharmacological intervention, or any drug treatment intended to improve sleep, and to describe the components and processes of any complex intervention included. | Despite the inclusion of 19 randomised controlled trials, there is a lack of conclusive evidence concerning non-pharmacological interventions for sleep problems in people with dementia. Although neither single nor multimodal interventions consistently improved sleep with sufficient certainty, we found some positive effects on physical and social activities as well as carer interventions. Future studies should use rigorous methods to develop and evaluate the effectiveness of multimodal interventions using current guidelines on the development and evaluation of complex interventions. At present, no single or multimodal intervention can be clearly identified as suitable for widespread implementation. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does low protein diet prevent the progression of chronic kidney disease towards kidney failure and reduce the incidence of kidney failure and death in adult patients with diabetic kidney disease? | Diabetic kidney disease (DKD) continues to be the leading cause of kidney failure across the world. For decades dietary protein restriction has been proposed for patients with DKD with the aim to retard the progression of chronic kidney disease (CKD) towards kidney failure. However, the relative benefits and harms of dietary protein restriction for slowing the progression of DKD have not been addressed. | To determine the efficacy and safety of low protein diets (LPD) (0.6 to 0.8 g/kg/day) in preventing the progression of CKD towards kidney failure and in reducing the incidence of kidney failure and death (any cause) in adult patients with DKD. Moreover, the effect of LPD on adverse events (e.g. malnutrition, hyperglycaemic events, or health-related quality of life (HRQoL)) and compliance were also evaluated. | Dietary protein restriction has uncertain effects on changes in kidney function over time. However, it may make little difference to the risk of death and kidney failure. Questions remain about protein intake levels and compliance with protein-restricted diets. There are limited data on HRQoL and adverse effects such as nutritional measures and hyperglycaemic events. Large-scale pragmatic RCTs with sufficient follow-up are required for different stages of CKD. | NOT ENOUGH INFORMATION | LOW | 1 | nutrition and dietary supplements |
Can inhaled corticosteroids reduce mortality or BPD in preterm infants at risk of developing bronchopulmonary dysplasia? | Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks' postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation may be an effective and safe alternative. | To assess the benefits and harms of inhaled corticosteroids versus placebo, initiated between seven days of postnatal life and 36 weeks' postmenstrual age, to preterm infants at risk of developing bronchopulmonary dysplasia. | Based on the available evidence, we do not know if inhaled corticosteroids initiated from seven days of life in preterm infants at risk of developing BPD reduces mortality or BPD at 36 weeks' PMA. There is a need for larger randomised placebo-controlled trials to establish the benefits and harms of inhaled corticosteroids. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Is paracetamol effective and safe for the closure of a PDA in preterm infants? | The different management strategies for patent ductus arteriosus (PDA) in preterm infants are expectant management, surgery, or medical treatment with non-selective cyclo-oxygenase inhibitors. Randomized controlled trials (RCTs) have suggested that paracetamol may be an effective and safe agent for the closure of a PDA. | To determine the efficacy and safety of paracetamol as monotherapy or as part of combination therapy via any route of administration, compared with placebo, no intervention, or another prostaglandin inhibitor, for prophylaxis or treatment of an echocardiographically-diagnosed PDA in preterm or low birth weight infants. | Trial registration: | SUPPORTED | MEDIUM | 0 | cardiovascular system |
Did the vaccines for preventing the common cold show clinical effectiveness and safety in healthy people? | The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8 ºC). Whilst the common cold is generally not harmful, it is a cause of economic burden due to school and work absenteeism. In the United States, economic loss due to the common cold is estimated at more than USD 40 billion per year, including an estimate of 70 million workdays missed by employees, 189 million school days missed by children, and 126 million workdays missed by parents caring for children with a cold. Additionally, data from Europe show that the total cost per episode may be up to EUR 1102. There is also a large expenditure due to inappropriate antimicrobial prescription. Vaccine development for the common cold has been difficult due to antigenic variability of the common cold viruses; even bacteria can act as infective agents. Uncertainty remains regarding the efficacy and safety of interventions for preventing the common cold in healthy people, thus we performed an update of this Cochrane Review, which was first published in 2011 and updated in 2013 and 2017. | To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. | this cochrane review was based on one study with very low-certainty evidence, which showed that there may be no difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold. we identified a need for well-designed, adequately powered rcts to investigate vaccines for the common cold in healthy people. future trials on interventions for preventing the common cold should assess a variety of virus vaccines for this condition, and should measure such outcomes as common cold incidence, vaccine safety, and mortality (all-cause and related to the vaccine). | NOT ENOUGH INFORMATION | LOW | 1 | immune system and infections |
Does completing root canal treatment in a single visit provide greater benefits compared to completing it over two or more visits, with or without medication, in people aged over 10 years? | Root canal treatment (RoCT), or endodontic treatment, is a common procedure in dentistry. The main indications for RoCT are irreversible pulpitis and necrosis of the dental pulp caused by carious processes, coronal crack or fracture, or dental trauma. Successful RoCT is characterised by an absence of symptoms (i.e. pain) and clinical signs (i.e. swelling and sinus tract) in teeth without radiographic evidence of periodontal involvement (i.e. normal periodontal ligament). The success of RoCT depends on a number of variables related to the preoperative condition of the tooth, as well as the endodontic procedures. RoCT can be carried out with a single-visit approach, which involves root canal system obturation (filling and sealing) directly after instrumentation and irrigation, or with a multiple-visits approach, in which the treatment is completed in two or more sessions and obturation is performed in the last session. This review updates the previous versions published in 2007 and 2016. | To evaluate the benefits and harms of completion of root canal treatment (RoCT) in a single visit compared to RoCT over two or more visits, with or without medication, in people aged over 10 years. | As in the previous two versions of the review, there is currently no evidence to suggest that one treatment regimen (single-visit or multiple-visit RoCT) is more effective than the other. Neither regimen can prevent pain and other complications in the 12-month postoperative period. There was moderate-certainty evidence of higher proportion of participants reporting pain within one week in single-visit groups compared to multiple-visit groups. In contrast to the results of the last version of the review, there was no difference in analgesic use. | NOT ENOUGH INFORMATION | MEDIUM | 1 | dental and oral health |
Did family-centered interventions delivered by primary healthcare services in Canada, Australia, New Zealand, and the USA improve the overall health and well-being of Indigenous children, parents, and families? | Primary healthcare, particularly Indigenous-led services, are well placed to deliver services that reflect the needs of Indigenous children and their families. Important characteristics identified by families for primary health care include services that support families, accommodate sociocultural needs, recognise extended family child-rearing practices, and Indigenous ways of knowing and doing business. Indigenous family-centred care interventions have been developed and implemented within primary healthcare services to plan, implement, and support the care of children, immediate and extended family and the home environment. The delivery of family-centred interventions can be through environmental, communication, educational, counselling, and family support approaches. | To evaluate the benefits and harms of family-centred interventions delivered by primary healthcare services in Canada, Australia, New Zealand, and the USA on a range of physical, psychosocial, and behavioural outcomes of Indigenous children (aged from conception to less than five years), parents, and families. | There is some evidence to suggest that family-centred care delivered by primary healthcare services improves the overall health and well-being of Indigenous children, parents, and families. However, due to lack of data, there was not enough evidence to determine whether specific outcomes such as child health and development improved as a result of family-centred interventions. Seven of the 11 studies delivered family-centred education interventions. Seven studies were from the USA and centred on two particular trials, the 'Healthy Children, Strong Families' and 'Family Spirit' trials. As the evidence is very low certainty for all outcomes, further high-quality trials are needed to provide robust evidence for the use of family-centred care interventions for Indigenous children aged less than five years. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Did oral homeopathic medicinal products show consistent benefit compared to placebo or conventional therapy in preventing and treating ARTIs in children? | Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although most infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most treatments have minimal benefit and may lead to adverse events. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for their effectiveness is established. This is an update of a review first published in 2018. | To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat ARTIs in children. | Pooling of five prevention and six treatment studies did not show any consistent benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We assessed the certainty of the evidence as low to very low for the majority of outcomes. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, and we could not draw conclusions regarding safety. | REFUTED | LOW | 2 | immune system and infections |
Is laser photocoagulation therapy effective in treating SCD-related proliferative retinopathy? | Sickle cell disease (SCD) includes a group of inherited haemoglobinopathies affecting multiple organs including the eyes. Some people with SCD develop ocular manifestations. Vision-threatening complications are mainly due to proliferative sickle retinopathy, which is characterised by proliferation of new blood vessels. Laser photocoagulation is widely applicable in proliferative retinopathies. It is important to evaluate the efficacy and safety of laser photocoagulation in the treatment of proliferative sickle retinopathy (PSR) to prevent sight-threatening complications. | To evaluate the effectiveness of various techniques of laser photocoagulation therapy in SCD-related proliferative retinopathy. | Our conclusions are based on the data from three trials (two of which were conducted over 30 years ago). Given the limited evidence available, which we assessed to be of low- or very low-certainty, we are uncertain whether laser therapy for sickle cell retinopathy improves the outcomes measured in this review. This treatment does not appear to have an effect on clinical outcomes such as regression of PSR and development of new incidences. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors (VEGFs) . Patient-important outcomes as well as cost-effectiveness should be addressed. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Is ultrasound guidance more effective than the landmark method for peripheral intravenous cannulation in adults? | Peripheral intravenous cannulation is one of the most fundamental and common procedures in medicine. Securing a peripheral line is occasionally difficult with the landmark method. Ultrasound guidance has become a standard procedure for central venous cannulation, but its efficacy in achieving peripheral venous cannulation is unclear. | To evaluate the effectiveness and safety of ultrasound guidance compared to the landmark method for peripheral intravenous cannulation in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 29 November 2021. | Trial registration: | NOT ENOUGH INFORMATION | LOW | 1 | miscellaneous |
Do BNP and NT-proBNP have diagnostic accuracy for haemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates? | Echocardiogram is the reference standard for the diagnosis of haemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. A simple blood assay for brain natriuretic peptide (BNP) or amino-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in the diagnosis and management of hsPDA, but a summary of the diagnostic accuracy has not been reviewed recently. | Primary objective: To determine the diagnostic accuracy of the cardiac biomarkers BNP and NT-proBNP for diagnosis of haemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates. Our secondary objectives were: to compare the accuracy of BNP and NT-proBNP; and to explore possible sources of heterogeneity among studies evaluating BNP and NT-proBNP, including type of commercial assay, chronological age of the infant at testing, gestational age at birth, whether used to initiate medical or surgical treatment, test threshold, and criteria of the reference standard (type of echocardiographic parameter used for diagnosis, clinical symptoms or physical signs if data were available). | Low-certainty evidence suggests that BNP and NT-proBNP have moderate accuracy in diagnosing hsPDA and may work best as a triage test to select infants for echocardiography. The studies evaluating the diagnostic accuracy of BNP and NT-proBNP for hsPDA varied considerably by assay characteristics (assay kit and threshold) and infant characteristics (gestational and chronological age); hence, generalisability between centres is not possible. We recommend that BNP or NT-proBNP assays be locally validated for specific populations and outcomes, to initiate therapy or follow response to therapy. | SUPPORTED | LOW | 0 | cardiovascular system |
Does the addition of a fundoplication affect postoperative reflux and dysphagia in people undergoing Laparoscopic Heller's cardiomyotomy (LHC)? | Laparoscopic Heller's cardiomyotomy (LHC) is the preferred treatment of achalasia. It improves dysphagia by dividing muscles of the lower oesophageal sphincter, but this intervention can result in debilitating gastro-oesophageal reflux symptoms in some patients. To prevent these reflux symptoms, most surgeons add a fundoplication to Heller's cardiomyotomy, but there is no consensus regarding this or the type of fundoplication which is best suited for the purpose. | To assess how the addition of a fundoplication affects postoperative reflux and dysphagia in people undergoing LHC and compare the different types of fundoplications used in combination with LHC to determine which is better at controlling reflux without worsening the dysphagia. | When LHC was performed with minimal hiatal dissection, we were very uncertain whether the addition of a Dor fundoplication made a difference in controlling postoperative reflux, and we were uncertain if it increased the risk of severe postoperative dysphagia. There may be little to no difference in the outcomes of postoperative pathological acid reflux or severe dysphagia between Dor and Toupet fundoplications when used in combination with LHC, but the certainty of the evidence is low. Nissen (total) fundoplication used in combination with LHC for achalasia increased the risk of severe postoperative dysphagia. The angle of His accentuation and Dor fundoplication had a similar effect on severe postoperative dysphagia when combined with LHC, but their effect on postoperative pathological acid reflux was not reported. | NOT ENOUGH INFORMATION | LOW | 1 | digestive system and metabolism |
Do bioengineered nerve wraps or conduits show better effects and lower complication rates compared to standard surgical repair for traumatic peripheral nerve injuries of the upper limb? | Traumatic peripheral nerve injury is common and incurs significant cost to individuals and society. Healing following direct nerve repair or repair with autograft is slow and can be incomplete. Several bioengineered nerve wraps or devices have become available as an alternative to direct repair or autologous nerve graft. Nerve wraps attempt to reduce axonal escape across a direct repair site and nerve devices negate the need for a donor site defect, required by an autologous nerve graft. Comparative evidence to guide clinicians in their potential use is lacking. We collated existing evidence to guide the clinical application of currently available nerve wraps and conduits. | To assess and compare the effects and complication rates of licensed bioengineered nerve conduits or wraps for surgical repair of traumatic peripheral nerve injuries of the upper limb. To compare effects and complications against the current gold surgical standard (direct repair or nerve autograft). | Based on the available evidence, this review does not support use of currently available nerve repair devices over standard repair. There is significant heterogeneity in participants, injury pattern, repair timing, and outcome measures and their timing across studies of nerve repair using bioengineered devices, which make comparisons unreliable. Studies were generally small and at high or unclear risk of bias. These factors render the overall certainty of evidence for any outcome low or very low. The data reviewed here provide some evidence that more people may experience adverse events with use of currently available bioengineered devices than with standard repair techniques, and the need for revision surgery may also be greater. The evidence for sensory recovery is very uncertain and there are no data for muscle strength at 24 months (our primary outcome measures). We need further trials, adhering to a minimum standard of outcome reporting (with at least 12 months' follow-up, including integrated sensorimotor evaluation and patient-reported outcomes) to provide high-certainty evidence and facilitate more detailed analysis of effectiveness of emerging, increasingly sophisticated, bioengineered repair devices. | REFUTED | LOW | 2 | musculoskeletal system and dermatology |
Do COVID-19 vaccines reduce the proportion of participants with confirmed symptomatic COVID-19 and severe or critical disease? | Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2. | Search methods: | Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital. | SUPPORTED | HIGH | 0 | immune system and infections |
Does carnitine supplementation effectively treat dialysis-related complications in CKD patients requiring dialysis? | Carnitine deficiency is common in patients with chronic kidney disease (CKD) who require dialysis. Several clinical studies have suggested that carnitine supplementation is beneficial for dialysis-related symptoms. However, the clinical effectiveness and potential adverse effects of carnitine supplementation in dialysis patients have not been determined. | This review aimed to evaluate the effectiveness and safety of carnitine supplementation for the treatment of dialysis-related complications in CKD patients requiring dialysis. | The available evidence does not currently support the use of carnitine supplementation in the treatment of dialysis-related carnitine deficiency. Although carnitine supplementation may slightly improve anaemia-related markers, carnitine supplementation makes little or no difference to adverse events. However, these conclusions are based on limited data and, therefore, should be interpreted with caution. | REFUTED | LOW | 2 | endocrine system and hormones |
Did the review investigate the benefits and harms of interventions for improving health literacy in people with chronic kidney disease? | Low health literacy affects 25% of people with chronic kidney disease (CKD) and is associated with increased morbidity and death. Improving health literacy is a recognised priority, but effective interventions are not clear. | This review looked the benefits and harms of interventions for improving health literacy in people with CKD. | Interventions to improve aspects of health literacy are a very broad category, including educational interventions, self-management interventions and educational with self-management interventions. Overall, this type of health literacy intervention is probably beneficial in this cohort however, due to methodological limitations and high heterogeneity in interventions and outcomes, the evidence is of low certainty. | SUPPORTED | LOW | 0 | cognitive, mental, and mental health |
Does triple therapy reduce steroid-requiring asthma exacerbations compared to dual therapy and varying doses of ICS in adolescents and adults with uncontrolled asthma? | Current guidelines recommend a higher-dose inhaled corticosteroids (ICS) or adding a long-acting muscarinic antagonist (LAMA) when asthma is not controlled with medium-dose (MD) ICS/long-acting beta2-agonist (LABA) combination therapy. | To assess the effectiveness and safety of dual (ICS/LABA) and triple therapies (ICS/LABA/LAMA) compared with each other and with varying doses of ICS in adolescents and adults with uncontrolled asthma. | Medium-dose and HD triple therapies reduce steroid-requiring asthma exacerbations, but not asthma-related hospitalisations, compared to MD-ICS/LABA especially in those with a history of asthma exacerbations in the previous year. High-dose triple therapy is likely superior to MD triple therapy in reducing steroid-requiring asthma exacerbations. Triple therapy is unlikely to result in clinically meaningful improvement in symptoms or quality of life compared to dual therapy considering the MCIDs. High-dose triple therapy, but not MD triple, results in a reduction in all-cause AEs and likely reduces dropouts due to AEs compared to MD-ICS/LABA. Triple therapy results in little to no difference in all-cause or asthma-related SAEs compared to dual therapy. HD-ICS/LABA is unlikely to result in any significant benefit or harm compared to MD-ICS/LABA, although long-term safety of higher rather than MD- ICS remains to be demonstrated given the median duration of included studies was six months. The above findings may assist deciding on a treatment option when asthma is not controlled with MD-ICS/LABA. | SUPPORTED | MEDIUM | 0 | respiratory system |
Does the use of inhaled, short-acting bronchodilators for acute chest syndrome reduce morbidity and mortality in people with sickle cell disease and cause adverse effects? | Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review. | The aim of the review is to determine whether the use of inhaled, short-acting bronchodilators for acute chest syndrome reduces morbidity and mortality in people with sickle cell disease and to assess whether this treatment causes adverse effects. | If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Can cervical pessary prevent preterm birth in women with singleton pregnancies and risk factors for cervical insufficiency? | Preterm birth (PTB), defined as birth prior to 37 weeks of gestation, occurs in ten percent of all pregnancies. PTB is responsible for more than half of neonatal and infant mortalities and morbidities. Because cervical insufficiency is a common cause of PTB, one possible preventive strategy involves insertion of a cervical pessary to support the cervix. Several published studies have compared the use of pessary with different management options and obtained questionable results. This highlights the need for an up-to-date systematic review of the evidence. | To evaluate the benefits and harms of cervical pessary for preventing preterm birth in women with singleton pregnancies and risk factors for cervical insufficiency compared to no treatment, vaginal progesterone, cervical cerclage or bedrest. | In women with a singleton pregnancy, cervical pessary compared with no treatment or vaginal progesterone may reduce the risk of delivery before 34 weeks or 37 weeks, although these results should be viewed with caution due to uncertainty around the effect estimates. There is insufficient evidence with regard to the effect of cervical pessary compared with cervical cerclage on PTB. Due to low certainty-evidence in many of the prespecified outcomes and non-reporting of several other outcomes of interest for this review, there is a need for further robust RCTs that use standardised terminology for maternal and offspring outcomes. Future trials should take place in a range of settings to improve generalisability of the evidence. Further research should concentrate on comparisons of cervical pessary versus cervical cerclage and bed rest. Investigation of different phenotypes of PTB may be relevant. | NOT ENOUGH INFORMATION | LOW | 0 | sexual and reproductive health |
Is surgery effective and safe for mild to moderate chronic arthropathy in people with haemophilia A or B? | Chronic arthropathy is a potentially debilitating complication for people with haemophilia - a genetic, X-linked, recessive bleeding disorder, characterised by the absence or deficiency of a clotting factor protein. Staging classifications, such as the Arnold-Hilgartner classification for haemophilic arthropathy of the knee, radiologically reflect the extent of knee joint destruction with underlying chronic synovitis. Management of this highly morbid disease process involves intensive prophylactic measures, and chemical or radioisotope synovectomy in its early stages. However, failure of non-surgical therapy in people with progression of chronic arthropathy often prompts surgical management, including synovectomy, joint debridement, arthrodesis, and arthroplasty, depending on the type of joint and extent of the damage. To date, management of people with mild to moderate chronic arthropathy from haemophilia remains controversial; there is no agreed standard treatment. Thus, the benefits and disadvantages of non-surgical and surgical management of mild to moderate chronic arthropathy in people with haemophilia needs to be systematically reviewed. OBJECTIVES: To assess the efficacy and safety of surgery for mild to moderate chronic arthropathy in people with haemophilia A or B. | Search methods: | The review authors did not identify any trials to include in this review. Due to a lack of research in this particular area, we plan to update the literature search every two years, and will update review if any new evidence is reported. There is a need for a well-designed RCT that assesses the safety and efficacy of surgical versus non-surgical interventions for chronic arthropathy in people with haemophilia. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Does maintaining a relatively high blood pressure improve desirable outcomes in people undergoing cardiac surgery with CPB? | Cardiac surgery is performed worldwide. Most types of cardiac surgery are performed using cardiopulmonary bypass (CPB). Cardiac surgery performed with CPB is associated with morbidities. CPB needs an extracorporeal circulation that replaces the heart and lungs, and performs circulation, ventilation, and oxygenation of the blood. The lower limit of mean blood pressure to maintain blood flow to vital organs increases in people with chronic hypertension. Because people undergoing cardiac surgery commonly have chronic hypertension, we hypothesised that maintaining a relatively high blood pressure improves desirable outcomes among the people undergoing cardiac surgery with CPB. | To evaluate the benefits and harms of higher versus lower blood pressure targets during cardiac surgery with CPB. | A high blood pressure target may result in little to no difference in patient outcomes including acute kidney injury and mortality. Given the wide CIs, further studies are needed to confirm the efficacy of a higher blood pressure target among those who undergo cardiac surgery with CPB. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Does adjunctive Coriolus versicolor (Trametes versicolor) and its extracts have a significant impact on adverse effects and survival during colorectal cancer treatment? | Radiotherapy and chemotherapy are used to improve survival in colorectal cancer but adverse effects can be a problem. Severe adverse effects may result in dose reduction or cessation of treatment, which have an impact on survival. Coriolus versicolor (Trametes versicolor or 'Turkey Tail') mushroom and its extracts have been used by cancer patients to help with adverse effects. | To assess the effects of adjunctive Coriolus versicolor (Trametes versicolor) and its extracts on adverse effects and on survival during colorectal cancer treatment (chemotherapy and radiotherapy) compared with no adjunctive treatment. | Due to the very low certainty of evidence, we were uncertain about the effect of adjunctive Coriolus (in the form of an extract PSK) on adverse events resulting from conventional chemotherapy for colorectal cancer. This includes effects on withdrawal of treatment due to adverse events and on specific adverse outcomes such as neutropenia and nausea. The uncertainty in the evidence also means that it was unclear whether any adverse events were due to the chemotherapy or to the extract itself. While there was low-certainty evidence of a small effect on overall survival at five years, the influence of reduced adverse effects on this could not be determined. In addition, chemotherapy regimens used in assessing this outcome do not reflect current preferred practice. | NOT ENOUGH INFORMATION | LOW | 1 | cancer |
Does pre-emptive antifungal therapy reduce the use of antifungal agents and associated adverse effects compared to empirical therapy in people with cancer who have febrile neutropenia? | Intensive cytotoxic chemotherapy for people with cancer can cause severe and prolonged cytopenia, especially neutropenia, a critical condition that is potentially life-threatening. When manifested by fever and neutropenia, it is called febrile neutropenia (FN). Invasive fungal disease (IFD) is one of the serious aetiologies of chemotherapy-induced FN. In pre-emptive therapy, physicians only initiate antifungal therapy when an invasive fungal infection is detected by a diagnostic test. Compared to empirical antifungal therapy, pre-emptive therapy may reduce the use of antifungal agents and associated adverse effects, but may increase mortality. The benefits and harms associated with the two treatment strategies have yet to be determined. OBJECTIVES: To assess the relative efficacy, safety, and impact on antifungal agent use of pre-emptive versus empirical antifungal therapy in people with cancer who have febrile neutropenia. | Search methods: | For people with cancer who are at high-risk of febrile neutropenia, pre-emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over-all and IFD-related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain. | SUPPORTED | MEDIUM | 0 | cancer |
Do interventions effectively prevent or ameliorate cognitive deficits in adults treated with cranial irradiation? | Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014. | To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation. | In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required. | SUPPORTED | LOW | 0 | cognitive, mental, and mental health |
Does day 5 embryo biopsy show clear benefits over day 3 biopsy in PGT-M for women undergoing IVF or ICSI cycles? | Assisted reproductive technology (ART) has allowed couples with a family history of a monogenic genetic disease, or a disease-carrying gene, to reduce the chance of them having a child with the genetic disorder. This is achieved by genetically testing the embryos using an advanced process called preimplantation genetic testing for monogenic or single gene disorders (PGT-M), such as Huntington's disease or cystic fibrosis. This current terminology (PGT-M) has replaced the formerly-known preimplantation genetic diagnosis (PGD). During PGT-M, one or more embryo cells are biopsied and analysed for genetic or chromosomal anomalies before transferring the embryos to the endometrial cavity. Biopsy for PGT-M can be performed at day 3 of cleavage-stage embryo development when the embryo is at the six- to the eight-cell stage, with either one or two blastomeres being removed for analysis. Biopsy for PGT-M can also be performed on day 5 of the blastocyst stage of embryo development when the embryo has 80 to 100 cells, with five to six cells being removed for analysis. Day 5 biopsy has taken over from day 3 biopsy as the most widely-used biopsy technique; however, there is a lack of summarised evidence from randomised controlled trials (RCTs) that assesses the effectiveness and safety of day 5 biopsy compared to day 3 biopsy. Since biopsy is an invasive process, whether it is carried out at day 3 or day 5 of embryo development may have different impacts on further development, implantation, pregnancy, live birth and perinatal outcomes. | To assess the benefits and harms of day 5 embryo biopsy, in comparison to day 3 biopsy, in PGT-M in women undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. | We are uncertain if there is a difference in live births and miscarriages, viable intrauterine pregnancies, ectopic pregnancies, stillbirths or termination of pregnancies between day 5 and day 3 embryo biopsy for PGT-M. There was insufficient evidence to draw any conclusions regarding other adverse outcomes. The results should be interpreted with caution, as the evidence was of very low certainty due to limited studies, high risk of bias in the included study, and an overall low level of precision. | NOT ENOUGH INFORMATION | LOW | 1 | sexual and reproductive health |
Are cephalosporins effective for treating enteric fever compared to other antimicrobials? | Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. | To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. | Based on very low- to low-certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones. We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial. | SUPPORTED | LOW | 0 | immune system and infections |
Can reducing antipsychotic doses for people with schizophrenia maintain efficacy and safety compared to continuing the current dose? | Antipsychotic drugs are the mainstay treatment for schizophrenia, yet they are associated with diverse and potentially dose-related side effects which can reduce quality of life. For this reason, the lowest possible doses of antipsychotics are generally recommended, but higher doses are often used in clinical practice. It is still unclear if and how antipsychotic doses could be reduced safely in order to minimise the adverse-effect burden without increasing the risk of relapse. | To assess the efficacy and safety of reducing antipsychotic dose compared to continuing the current dose for people with schizophrenia. | this review synthesised the latest evidence on the reduction of antipsychotic doses for stable individuals with schizophrenia. there was no difference between dose reduction and continuation groups in quality of life, functioning, and number of participants with at least one adverse effect. however, there was a higher risk for relapse and dropouts, and potentially for rehospitalisations, with dose reduction. of note, the majority of the trials focused on relapse prevention rather potential beneficial outcomes on quality of life, functioning, and adverse effects, and in some studies there was rapid and substantial reduction of doses. further well-designed rcts are therefore needed to provide more definitive answers. | REFUTED | MEDIUM | 2 | cognitive, mental, and mental health |
Does early initiation of kidney replacement therapy (KRT) improve clinical outcomes in critically ill patients with acute kidney injury (AKI)? | Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs) and is associated with high numbers of deaths. Kidney replacement therapy (KRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate KRT so as to improve clinical outcomes remains uncertain. This is an update of a review first published in 2018. This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury. | To assess the effects of different timing (early and standard) of KRT initiation on death and recovery of kidney function in critically ill patients with AKI. | Based on mainly low to moderate certainty of the evidence, early KRT has no beneficial effect on death and may increase the recovery of kidney function. Earlier KRT probably reduces the length of ICU and hospital stay but increases the risk of adverse events. Further adequate-powered RCTs using robust and validated tools that complement clinical judgement are needed to define the optimal time of KRT in critical patients with AKI in order to improve their outcomes. The surgical AKI population should be considered in future research. | NOT ENOUGH INFORMATION | LOW | 1 | renal and urinary system |
Did pharmacological interventions have a significant impact on venous thromboembolism and other health outcomes in people undergoing bariatric surgery? | Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is the leading cause of preventable death in hospitalised people and the third most common cause of mortality in surgical patients. People undergoing bariatric surgery have the additional risk factor of being overweight. Although VTE prophylaxis in surgical patients is well established, the best way to prevent VTE in those undergoing bariatric surgery is less clear. | To evaluate the benefits and harms of pharmacological interventions (alone or in combination) on venous thromboembolism and other health outcomes in people undergoing bariatric surgery compared to the same pharmacological intervention administered at a different dose or frequency, the same pharmacological intervention or started at a different time point, another pharmacological intervention, no intervention or placebo. | Higher-dose heparin may make little or no difference to venous thromboembolism or major bleeding in people undergoing bariatric surgery when compared to standard-dose heparin. Heparin may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to pentasaccharide. There are inadequate data to draw conclusions about the effects of heparin compared to pentasaccharide on major bleeding. Starting prophylaxis with heparin 12 hours before bariatric surgery may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to starting heparin after bariatric surgery. There are inadequate data to draw conclusions about the effects of heparin started before versus after surgery on major bleeding. Combining mechanical and pharmacological prophylaxis (started 12 hours before surgery) may reduce VTE events in people undergoing bariatric surgery when compared to mechanical prophylaxis alone. No data are available relating to major bleeding. The certainty of the evidence is limited by small sample sizes, few or no events, and risk of bias concerns. Future trials must be sufficiently large to enable analysis of relevant clinical outcomes, and should standardise the time of treatment and follow-up. They should also address the effect of direct oral anticoagulants and antiplatelets, preferably grouping them according to the type of intervention. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Does follicular flushing yield a larger number of oocytes and is hence associated with greater potential for pregnancy than aspiration only? | Follicular aspiration under transvaginal ultrasound guidance is routinely performed as part of assisted reproductive technology (ART) to retrieve oocytes for in vitro fertilisation (IVF). The process involves aspiration of the follicular fluid followed by the introduction of flush, typically culture media, back into the follicle followed by re-aspiration. However, there is a degree of controversy as to whether this intervention yields a larger number of oocytes and is hence associated with greater potential for pregnancy than aspiration only. | To assess the safety and efficacy of follicular flushing as compared with aspiration only performed in women undergoing ART. | The effect of follicular flushing on both live birth and miscarriage rates compared with aspiration alone is uncertain. Although the evidence does not permit any firm conclusions on the impact of follicular flushing on oocyte yield, total number of embryos, number of cryopreserved embryos, or clinical pregnancy rate, it may be that the procedure itself takes longer than aspiration alone. The evidence was insufficient to permit any firm conclusions with respect to adverse events or safety. | NOT ENOUGH INFORMATION | LOW | 1 | sexual and reproductive health |
Can PCCs benefit people undergoing cardiac surgery with coagulopathic non-surgical bleeding? | Coagulopathy following cardiac surgery is associated with considerable blood product transfusion and high morbidity and mortality. The treatment of coagulopathy following cardiac surgery is challenging, with the replacement of clotting factors being based on transfusion of fresh frozen plasma (FFP). Prothrombin complex concentrate (PCCs) is an alternative method to replace clotting factors and warrants evaluation. PCCs are also an alternative method to treat refractory ongoing bleeding post-cardiac surgery compared to recombinant factor VIIa (rFVIIa) and also warrants evaluation. OBJECTIVES: Assess the benefits and harms of PCCs in people undergoing cardiac surgery who have coagulopathic non-surgical bleeding. | Search methods: | Trial registration: | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Does lower blood pressure target (systolic/diastolic 135/85 mmHg or less) reduce mortality and morbidity compared with standard blood pressure targets (140 mmHg to 160mmHg/90 mmHg to 100 mmHg or less) in people with hypertension and a history of cardiovascular disease? | This is the third update of the review first published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure to below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. | To determine if lower blood pressure targets (systolic/diastolic 135/85 mmHg or less) are associated with reduction in mortality and morbidity compared with standard blood pressure targets (140 mmHg to 160mmHg/90 mmHg to 100 mmHg or less) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). | We found there is probably little to no difference in total mortality and cardiovascular mortality between people with hypertension and cardiovascular disease treated to a lower compared to a standard blood pressure target. There may also be little to no difference in serious adverse events or total cardiovascular events. This suggests that no net health benefit is derived from a lower systolic blood pressure target. We found very limited evidence on withdrawals due to adverse effects, which led to high uncertainty. At present, evidence is insufficient to justify lower blood pressure targets (135/85 mmHg or less) in people with hypertension and established cardiovascular disease. Several trials are still ongoing, which may provide an important input to this topic in the near future. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Does yoga provide significant benefits for treating chronic non-specific low back pain in adults compared to other treatments? | Non-specific low back pain is a common, potentially disabling condition usually treated with self-care and non-prescription medication. For chronic low back pain, current guidelines recommend exercise therapy. Yoga is a mind-body exercise sometimes used for non-specific low back pain. | To evaluate the benefits and harms of yoga for treating chronic non-specific low back pain in adults compared to sham yoga, no specific treatment, a minimal intervention (e.g. education), or another active treatment, focusing on pain, function, quality of life, and adverse events. | There is low- to moderate-certainty evidence that yoga compared to no exercise results in small and clinically unimportant improvements in back-related function and pain. There is probably little or no difference between yoga and other back-related exercise for back-related function at three months, although it remains uncertain whether there is any difference between yoga and other exercise for pain and quality of life. Yoga is associated with more adverse events than no exercise, but may have the same risk of adverse events as other exercise. In light of these results, decisions to use yoga instead of no exercise or another exercise may depend on availability, cost, and participant or provider preference. Since all studies were unblinded and at high risk of performance and detection bias, it is unlikely that blinded comparisons would find a clinically important benefit. | REFUTED | LOW | 2 | musculoskeletal system and dermatology |
Does combined pars plana vitrectomy and intravitreal antibiotics show potential in the acute management of exogenous endophthalmitis compared to the standard of care? | Endophthalmitis is a sight-threatening emergency that requires prompt diagnosis and treatment. The condition is characterised by purulent inflammation of the intraocular fluids caused by an infective agent. In exogenous endophthalmitis, the infective agent is foreign and typically introduced into the eye through intraocular surgery or open globe trauma. | To assess the potential role of combined pars plana vitrectomy and intravitreal antibiotics in the acute management of exogenous endophthalmitis, versus the standard of care, defined as vitreous tap and intravitreal antibiotics. | we identified a single rct (published 27 years ago) for the role of early vitrectomy in exogenous endophthalmitis, which suggests that there may be no difference between groups (vit vs tap) for visual acuity at three or nine months' follow-up. we are of the opinion that there is a clear need for more randomised studies comparing the role of primary vitrectomy in exogenous endophthalmitis. moreover, since the original rct study, there have been incremental changes in the surgical techniques with which vitrectomy is performed. such advances are likely to influence the outcome of early vitrectomy in exogenous endophthalmitis. | NOT ENOUGH INFORMATION | LOW | 1 | sensory organs |
Can antibody tests accurately determine current and past SARS-CoV-2 infection? | The diagnostic challenges associated with the COVID-19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS-CoV-2 infection. Serology tests to detect the presence of antibodies to SARS-CoV-2 enable detection of past infection and may detect cases of SARS-CoV-2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS-CoV-2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS-CoV-2 epidemiology. | To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARS-CoV-2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARS-CoV-2. Sources of heterogeneity investigated included: timing of test, test method, SARS-CoV-2 antigen used, test brand, and reference standard for non-SARS-CoV-2 cases. | Some antibody tests could be a useful diagnostic tool for those in whom molecular- or antigen-based tests have failed to detect the SARS-CoV-2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with post-acute sequelae of COVID-19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for sero-epidemiological purposes. The applicability of results for detection of vaccination-induced antibodies is uncertain. | SUPPORTED | MEDIUM | 0 | immune system and infections |
Can pharmaceutical treatment reduce the frequency and severity of crying or laughing episodes in people with emotionalism after stroke? | Antidepressants may be useful in the treatment of abnormal crying associated with stroke. This is an update of a Cochrane Review first published in 2004 and last updated in 2019. | To evaluate the benefits and harms of pharmaceutical treatment in people with emotionalism after stroke. | Antidepressants may reduce the frequency and severity of crying or laughing episodes when compared to placebo, based on very low-certainty evidence. Our conclusions must be qualified by several methodological deficiencies in the trials and interpreted with caution despite the effect being very large. The effect does not seem specific to one drug or class of drugs. More reliable data are required before appropriate conclusions can be made about the treatment of post-stroke emotionalism. Future trialists investigating the effect of antidepressants in people with emotionalism after stroke should consider developing and using a standardised method to diagnose emotionalism, determine severity, and assess change over time; provide treatment for a sufficient duration and follow-up to better assess rates of relapse or maintenance; and include careful assessment and complete reporting of adverse events. | SUPPORTED | LOW | 0 | cognitive, mental, and mental health |
Do systemic corticosteroids effectively and safely treat people with COVID-19? | Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. Nonetheless, size of effect, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated. | To assess whether and at which doses systemic corticosteroids are effective and safe in the treatment of people with COVID-19, to explore equity-related aspects in subgroup analyses, and to keep up to date with the evolving evidence base using a living systematic review approach. | Systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in people hospitalised because of symptomatic COVID-19, while the evidence is very uncertain about the effect on all-cause mortality up to 120 days. For younger people (under 70 years of age) there was a potential advantage, as well as for Black, Asian, or people of a minority ethnic group; further subgroup analyses showed no relevant effects. Evidence related to the most effective type, dose, or timing of systemic corticosteroids remains immature. Currently, there is no evidence on asymptomatic or mild disease (non-hospitalised participants). Due to the low to very low certainty of the current evidence, we cannot assess safety adequately to rule out harmful effects of the treatment, therefore there is an urgent need for good-quality safety data. Findings of equity-related subgroup analyses should be interpreted with caution because of their explorative nature, low precision, and missing data. We identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design, suggesting there may be possible changes of the effect estimates and certainty of the evidence in the future. | SUPPORTED | LOW | 0 | immune system and infections |
Does surgical decompression improve outcomes in people with malignant oedema after ischaemic stroke? | Large territory middle cerebral artery (MCA) ischaemic strokes account for around 10% of all ischaemic strokes and have a particularly devastating prognosis when associated with malignant oedema. Progressive cerebral oedema starts developing in the first 24 to 48 hours of stroke ictus with an associated rise in intracranial pressure. The rise in intracranial pressure may eventually overwhelm compensatory mechanisms leading to a cascading secondary damage to surrounding unaffected parenchyma. This downward spiral can rapidly progress to death or severe neurological disability. Early decompressive craniectomy to relieve intracranial pressure and associated tissue shift can help ameliorate this secondary damage and improve outcomes. Evidence has been accumulating of the benefit of early surgical decompression in stroke patients. Earlier studies have excluded people above the age of 60 due to associated poor outcomes; however, newer trials have included this patient subgroup. This review follows a Cochrane Review published in 2012. | To assess the effectiveness of surgical decompression in people with malignant oedema after ischaemic stroke with regard to reduction in mortality and improved functional outcome. We also aimed to examine the adverse effects of surgical decompression in this patient cohort. | Surgical decompression improves outcomes in the management of malignant oedema after acute ischaemic stroke, including a considerable reduction in death or severe disability (mRS > 4) and a reduction in death or moderate disability (mRS > 3). Whilst there is evidence that this positive treatment effect is present in patients > 60 years old, it is important to take into account that these patients have a poorer prospect of functional survival independent of this treatment effect. In interpreting these results it must also be considered that the data demonstrating benefit are drawn from a unique patient subset with profound neurological deficit, reduced level of consciousness, and no pre-morbid disability or severe comorbidity. | SUPPORTED | MEDIUM | 0 | cancer |
Can electronic cigarettes (ECs) help people who smoke achieve long-term smoking abstinence? | Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, although some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review. | To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence. | There is high-certainty evidence that ECs with nicotine increase quit rates compared to NRT and moderate-certainty evidence that they increase quit rates compared to ECs without nicotine. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the effect size. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, with no difference in AEs between nicotine and non-nicotine ECs nor between nicotine ECs and NRT. Overall incidence of SAEs was low across all study arms. We did not detect evidence of serious harm from nicotine EC, but longest follow-up was two years and the number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates, but further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this review is a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status. | SUPPORTED | HIGH | 0 | respiratory system |
Does Ginkgo biloba have significant effects on tinnitus in adults and children? | Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy (TRT), cognitive behavioural therapy (CBT), sound enrichment using ear-level sound generators or hearing aids, and drug therapies to manage co-morbid symptoms such as insomnia, anxiety or depression. OBJECTIVES: To assess the effects of Ginkgo biloba for tinnitus in adults and children. | Search methods: | There is uncertainty about the benefits and harms of Ginkgo biloba for the treatment of tinnitus when compared to placebo. We were unable to draw meaningful conclusions regarding the benefits and harms of Ginkgo biloba when used with concurrent intervention (hearing aids). The certainty of the evidence for the reported outcomes, assessed using GRADE, ranged from low to very low. Future research into the effectiveness of Ginkgo biloba in patients with tinnitus should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the use of validated, patient-centred outcome measures for research in the field of tinnitus. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Do oral care measures prevent nursing home-acquired pneumonia? | Pneumonia in residents of nursing homes can be termed nursing home-acquired pneumonia (NHAP). NHAP is one of the most common infections identified in nursing home residents and has the highest mortality of any infection in this population. NHAP is associated with poor oral hygiene and may be caused by aspiration of oropharyngeal flora into the lung. Oral care measures to remove or disrupt oral plaque might reduce the risk of NHAP. This is the first update of a review published in 2018. | To assess effects of oral care measures for preventing nursing home-acquired pneumonia in residents of nursing homes and other long-term care facilities. | Although low-certainty evidence suggests that professional oral care may reduce mortality compared to usual care when measured at 24 months, the effect of professional oral care on preventing NHAP remains largely unclear. Low-certainty evidence was inconclusive about the effects of this intervention on incidence and number of first episodes of NHAP. Due to differences in study design, effect measures, follow-up duration, and composition of the interventions, we cannot determine the optimal oral care protocol from current evidence. Future trials will require larger samples, robust methods that ensure low risk of bias, and more practicable interventions for nursing home residents. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Did pharmacological treatment have a significant effect on people with BPD? | Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods. | To assess the effects of pharmacological treatment for people with BPD. | This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples. | REFUTED | LOW | 2 | cognitive, mental, and mental health |
Does the use of nasal masks compared with nasal prongs reduce CPAP treatment failure, nasal trauma, or mortality and other morbidity in newborn preterm infants with or at risk of respiratory distress? | Nasal masks and nasal prongs are used as interfaces for providing continuous positive airway pressure (CPAP) for preterm infants with or at risk of respiratory distress, either as primary support after birth or as ongoing support after endotracheal extubation from mechanical ventilation. It is unclear which type of interface is associated with lower rates of CPAP treatment failure, nasal trauma, or mortality and other morbidity. | To assess the benefits and harms of nasal masks versus nasal prongs for reducing CPAP treatment failure, nasal trauma, or mortality and other morbidity in newborn preterm infants with or at risk of respiratory distress. | The available trial data provide low-certainty evidence that use of masks compared with prongs as the nasal CPAP interface may reduce treatment failure and nasal injury, and may have little or no effect on mortality or the risk of pneumothorax in newborn preterm infants with or at risk of respiratory distress. The effect on bronchopulmonary dysplasia is very uncertain. Large, high-quality trials would be needed to provide evidence of sufficient validity and applicability to inform policy and practice. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Can skin care interventions such as emollients prevent eczema and food allergy in infants? | Eczema and food allergy are common health conditions that usually begin in early childhood and often occur in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective for preventing eczema or food allergy. | Primary objective To assess the effects of skin care interventions such as emollients for primary prevention of eczema and food allergy in infants. Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated with the greatest treatment benefit or harm for both eczema and food allergy. | Based on low- to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection. Further study is needed to understand whether different approaches to infant skin care might prevent eczema or food allergy. | REFUTED | LOW | 2 | immune system and infections |
Do immunostimulants prevent respiratory exacerbations in adults with chronic obstructive pulmonary disease or chronic bronchitis? | Individuals with chronic obstructive pulmonary disease (COPD) or chronic bronchitis may experience recurrent exacerbations, which negatively impact prognosis and quality of life, and can impose a significant socioeconomic burden on the individual and wider society. Immunostimulants are a broad category of therapies that may theoretically enhance non-specific immunity against several respiratory insults, thereby reducing exacerbation risk and severity. However, evidence to date for their use in this population is limited. | To determine the efficacy of immunostimulants in preventing respiratory exacerbations in adults with chronic obstructive pulmonary disease, chronic bronchitis, or both. | In participants with chronic bronchitis or COPD, we are moderately confident that treatment with immunostimulants is associated with a small reduction in the likelihood of having an exacerbation and a moderate reduction in the requirement for antibiotics. Low numbers of events limit interpretation of the effect of immunostimulants on all-cause and respiratory-related mortality. We are uncertain whether immunostimulants improve quality of life, and whether they are associated with a reduction in exacerbation and respiratory-related hospitalisation durations, although immunostimulants were generally associated with a positive effect direction in the studies that examined these outcomes. Immunostimulants appear to be safe and well-tolerated, and are not associated with an increased risk of adverse events. | SUPPORTED | MEDIUM | 0 | respiratory system |
Does long-term inhaled antibiotic therapy in people with cystic fibrosis have a positive impact on clinical outcomes and quality of life? | Inhaled antibiotics are commonly used to treat persistent airway infection with Pseudomonas aeruginosa that contributes to lung damage in people with cystic fibrosis. Current guidelines recommend inhaled tobramycin for individuals with cystic fibrosis and persistent Pseudomonas aeruginosa infection who are aged six years or older. The aim is to reduce bacterial load in the lungs so as to reduce inflammation and deterioration of lung function. This is an update of a previously published review. | To evaluate the effects of long-term inhaled antibiotic therapy in people with cystic fibrosis on clinical outcomes (lung function, frequency of exacerbations and nutrition), quality of life and adverse events (including drug-sensitivity reactions and survival). | Long-term treatment with inhaled anti-pseudomonal antibiotics probably improves lung function and reduces exacerbation rates, but pooled estimates of the level of benefit were very limited. The best evidence available is for inhaled tobramycin. More evidence from trials measuring similar outcomes in the same way is needed to determine a better measure of benefit. Longer-term trials are needed to look at the effect of inhaled antibiotics on quality of life, survival and nutritional outcomes. | NOT ENOUGH INFORMATION | LOW | 2 | respiratory system |
Can mosquito aquatic habitat modification or manipulation have beneficial effects on malaria control? | Larval source management (LSM) may help reduce Plasmodium parasite transmission in malaria-endemic areas. LSM approaches include habitat modification (permanently or temporarily reducing mosquito breeding aquatic habitats); habitat manipulation (temporary or recurrent change to environment); or use of chemical (e.g. larviciding) or biological agents (e.g. natural predators) to breeding sites. We examined the effectiveness of habitat modification or manipulation (or both), with and without larviciding. This is an update of a review published in 2013. | 1. To describe and summarize the interventions on mosquito aquatic habitat modification or mosquito aquatic habitat manipulation, or both, on malaria control. 2. To evaluate the beneficial and harmful effects of mosquito aquatic habitat modification or mosquito aquatic habitat manipulation, or both, on malaria control. | Habitat modification and manipulation interventions for preventing malaria has some indication of benefit in both epidemiological and entomological outcomes. While the data are quite mixed and further studies could help improve the knowledge base, these varied approaches may be useful in some circumstances. | SUPPORTED | MEDIUM | 0 | immune system and infections |
Do SDM interventions improve a range of outcomes for people with mental health conditions? | One person in every four will suffer from a diagnosable mental health condition during their life. Such conditions can have a devastating impact on the lives of the individual and their family, as well as society. International healthcare policy makers have increasingly advocated and enshrined partnership models of mental health care. Shared decision-making (SDM) is one such partnership approach. Shared decision-making is a form of service user-provider communication where both parties are acknowledged to bring expertise to the process and work in partnership to make a decision. This review assesses whether SDM interventions improve a range of outcomes. This is the first update of this Cochrane Review, first published in 2010. | To assess the effects of SDM interventions for people of all ages with mental health conditions, directed at people with mental health conditions, carers, or healthcare professionals, on a range of outcomes including: clinical outcomes, participation/involvement in decision-making process (observations on the process of SDM; user-reported, SDM-specific outcomes of encounters), recovery, satisfaction, knowledge, treatment/medication continuation, health service outcomes, and adverse outcomes. | This review update suggests that people exposed to SDM interventions may perceive greater levels of involvement immediately after an encounter compared with those in control groups. Moreover, SDM interventions probably have little or no effect on the length of consultations. Overall we found that most evidence was of low or very low certainty, meaning there is a generally low level of certainty about the effects of SDM interventions based on the studies assembled thus far. There is a need for further research in this area. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Do exercise interventions for acutely hospitalised older medical inpatients have benefits on functional ability, quality of life, and participant global assessment of success compared to usual care or a sham-control intervention? | Approximately 30% of hospitalised older adults experience hospital-associated functional decline. Exercise interventions that promote in-hospital activity may prevent deconditioning and thereby maintain physical function during hospitalisation. This is an update of a Cochrane Review first published in 2007. | To evaluate the benefits and harms of exercise interventions for acutely hospitalised older medical inpatients on functional ability, quality of life (QoL), participant global assessment of success and adverse events compared to usual care or a sham-control intervention. | Exercise may make little difference to independence in activities of daily living or QoL, but probably does not result in more falls in older medical inpatients. We are uncertain about the effect of exercise on functional mobility, incidence of delirium and medical deterioration. Certainty of evidence was limited by risk of bias and inconsistency. Future primary research on the effect of exercise on acute hospitalisation could focus on more consistent and uniform reporting of participant's characteristics including their baseline level of functional ability, as well as exercise dose, intensity and adherence that may provide an insight into the reasons for the observed inconsistencies in findings. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Do pharmacological interventions for pain and sedation management affect analgesia and sedation in newborn infants undergoing therapeutic hypothermia? | Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and invasive care is needed, pharmacological interventions are often used. Moreover, painful procedures in the newborn period can affect pain responses later in life, impair brain development, and possibly have a long-term negative impact on neurodevelopment and quality of life. | To determine the effects of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge. | We found no studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does antifibrinolytic treatment improve outcomes in people with aneurysmal subarachnoid haemorrhage? | Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the blood clot at the site of the aneurysm rupture by natural fibrinolytic activity. This review is an update of previously published Cochrane Reviews. | To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. | The current evidence does not support the routine use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage. More specifically, early administration with concomitant treatment strategies to prevent delayed cerebral ischaemia does not improve clinical outcome. There is sufficient evidence from multiple randomised controlled trials to incorporate this conclusion in treatment guidelines. | REFUTED | HIGH | 2 | cognitive, mental, and mental health |
Do interventions for long-term prevention of HAE attacks benefit people with Type I, Type II, or Type III HAE? | Hereditary angioedema (HAE) is a serious and potentially life-threatening condition that causes acute attacks of swelling, pain and reduced quality of life. People with Type I HAE (approximately 80% of all HAE cases) have insufficient amounts of C1 esterase inhibitor (C1-INH) protein; people with Type II HAE (approximately 20% of all cases) may have normal C1-INH concentrations, but, due to genetic mutations, these do not function properly. A few people, predominantly females, experience HAE despite having normal C1-INH levels and C1-INH function (rare Type III HAE). Several new drugs have been developed to treat acute attacks and prevent recurrence of attacks. There is currently no systematic review and meta-analysis that included all preventive medications for HAE. | To assess the benefits and harms of interventions for the long-term prevention of HAE attacks in people with Type I, Type II or Type III HAE. | The available data suggest that berotralstat, C1-INH (subcutaneous, plasma-derived, nanofiltered and recombinant), danazol and lanadelumab are effective in lowering the risk or incidence (or both) of HAE attacks. In addition, C1-INH and lanadelumab decrease the severity of breakthrough attacks (data for other drugs were not available). Avoralstat, berotralstat, C1-INH (all forms) and lanadelumab increase quality of life and do not increase the risk of adverse events, including serious adverse events. It is possible that danazol, subcutaneous C1-INH and recombinant human C1-INH are more effective than berotralstat and lanadelumab in reducing the risk of breakthrough attacks, but the small number of studies and the small size of the studies means that the certainty of the evidence is low. This and the lack of head-to-head trials prevented us from drawing firm conclusions on the relative efficacy of the drugs. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Did interventions for perceptual disorders after stroke show effectiveness on measures of performance in activities of daily living? | Perception is the ability to understand information from our senses. It allows us to experience and meaningfully interact with our environment. A stroke may impair perception in up to 70% of stroke survivors, leading to distress, increased dependence on others, and poorer quality of life. Interventions to address perceptual disorders may include assessment and screening, rehabilitation, non-invasive brain stimulation, pharmacological and surgical approaches. | To assess the effectiveness of interventions aimed at perceptual disorders after stroke compared to no intervention or control (placebo, standard care, attention control), on measures of performance in activities of daily living. SEARCH METHODS: We searched the trials registers of the Cochrane Stroke Group, CENTRAL, MEDLINE, Embase, and three other databases to August 2021. We also searched trials and research registers, reference lists of studies, handsearched journals, and contacted authors. | following a detailed, systematic search, we identified limited rct evidence of the effectiveness of interventions for perceptual disorders following stroke. there is insufficient evidence to support or refute the suggestion that perceptual interventions are effective. more high-quality trials of interventions for perceptual disorders in stroke are needed. they should recruit sufficient participant numbers, include a 'usual care' comparison, and measure longer-term functional outcomes, at time points beyond the initial intervention period. people with impaired perception following a stroke should continue to receive neurorehabilitation according to clinical guidelines. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does folic acid supplementation, at various doses, affect malaria susceptibility and severity in people living in malaria-endemic areas? | Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria since it was first introduced in Malawi in 1993 (Filler 2006). Due to increasing resistance to SP, in 2000 the WHO recommended that one of several artemisinin-based combination therapies (ACTs) be used instead of SP for the treatment of uncomplicated malaria caused by Plasmodium falciparum (Global Partnership to Roll Back Malaria 2001). However, despite these recommendations, SP continues to be advised for intermittent preventive treatment in pregnancy (IPTp) and intermittent preventive treatment in infants (IPTi), whether the person has malaria or not (WHO 2013). Description of the intervention Folate (vitamin B9) includes both naturally occurring folates and folic acid, the fully oxidized monoglutamic form of the vitamin, used in dietary supplements and fortified food. Folate deficiency (e.g. red blood cell (RBC) folate concentrations of less than 305 nanomoles per litre (nmol/L); serum or plasma concentrations of less than 7 nmol/L) is common in many parts of the world and often presents as megaloblastic anaemia, resulting from inadequate intake, increased requirements, reduced absorption, or abnormal metabolism of folate (Bailey 2015; WHO 2015a). Pregnant women have greater folate requirements; inadequate folate intake (evidenced by RBC folate concentrations of less than 400 nanograms per millilitre (ng/mL), or 906 nmol/L) prior to and during the first month of pregnancy increases the risk of neural tube defects, preterm delivery, low birthweight, and fetal growth restriction (Bourassa 2019). The WHO recommends that all women who are trying to conceive consume 400 micrograms (µg) of folic acid daily from the time they begin trying to conceive through to 12 weeks of gestation (WHO 2017). In 2015, the WHO added the dosage of 0.4 mg of folic acid to the essential drug list (WHO 2015c). Alongside daily oral iron (30 mg to 60 mg elemental iron), folic acid supplementation is recommended for pregnant women to prevent neural tube defects, maternal anaemia, puerperal sepsis, low birthweight, and preterm birth in settings where anaemia in pregnant women is a severe public health problem (i.e. where at least 40% of pregnant women have a blood haemoglobin (Hb) concentration of less than 110 g/L). How the intervention might work Potential interactions between folate status and malaria infection The malaria parasite requires folate for survival and growth; this has led to the hypothesis that folate status may influence malaria risk and severity. In rhesus monkeys, folate deficiency has been found to be protective against Plasmodium cynomolgi malaria infection, compared to folate-replete animals (Metz 2007). Alternatively, malaria may induce or exacerbate folate deficiency due to increased folate utilization from haemolysis and fever. Further, folate status measured via RBC folate is not an appropriate biomarker of folate status in malaria-infected individuals since RBC folate values in these individuals are indicative of both the person's stores and the parasite's folate synthesis. A study in Nigeria found that children with malaria infection had significantly higher RBC folate concentrations compared to children without malaria infection, but plasma folate levels were similar (Bradley-Moore 1985). Why it is important to do this review The malaria parasite needs folate for survival and growth in humans. For individuals, adequate folate levels are critical for health and well-being, and for the prevention of anaemia and neural tube defects. Many countries rely on folic acid supplementation to ensure adequate folate status in at-risk populations. Different formulations for folic acid supplements are available in many international settings, with dosages ranging from 400 µg to 5 mg. Evaluating folic acid dosage levels used in supplementation efforts may increase public health understanding of its potential impacts on malaria risk and severity and on treatment failures. Examining folic acid interactions with antifolate antimalarial medications and with malaria disease progression may help countries in malaria-endemic areas determine what are the most appropriate lower dose folic acid formulations for at-risk populations. The WHO has highlighted the limited evidence available and has indicated the need for further research on biomarkers of folate status, particularly interactions between RBC folate concentrations and tuberculosis, human immunodeficiency virus (HIV), and antifolate antimalarial drugs (WHO 2015b). An earlier Cochrane Review assessed the effects and safety of iron supplementation, with or without folic acid, in children living in hyperendemic or holoendemic malaria areas; it demonstrated that iron supplementation did not increase the risk of malaria, as indicated by fever and the presence of parasites in the blood (Neuberger 2016). Further, this review stated that folic acid may interfere with the efficacy of SP; however, the efficacy and safety of folic acid supplementation on these outcomes has not been established. This review will provide evidence on the effectiveness of daily folic acid supplementation in healthy and malaria-infected individuals living in malaria-endemic areas. Additionally, it will contribute to achieving both the WHO Global Technical Strategy for Malaria 2016-2030 (WHO 2015d), and United Nations Sustainable Development Goal 3 (to ensure healthy lives and to promote well-being for all of all ages) (United Nations 2021), and evaluating whether the potential effects of folic acid supplementation, at different doses (e.g. 0.4 mg, 1 mg, 5 mg daily), interferes with the effect of drugs used for prevention or treatment of malaria. | To examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure? | Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (including but not limited to sulfadoxine/pyrimethamine (SP), pyrimethamine-dapsone, pyrimethamine, chloroquine and proguanil, cotrimoxazole) for the prevention or treatment of malaria (studies will be included if more than 70% of the participants live in malaria-endemic regions) Studies assessing participants with or without anaemia and with or without malaria parasitaemia at baseline will be included Exclusion criteria Individuals not taking antifolate antimalarial medications for prevention or treatment of malaria Individuals living in non-malaria endemic areas Types of interventions Inclusion criteria Folic acid supplementation Form: in tablet, capsule, dispersible tablet at any dose, during administration, or periodically Timing: during, before, or after (within a period of four to six weeks) administration of antifolate antimalarials Iron-folic acid supplementation Folic acid supplementation in combination with co-interventions that are identical between the intervention and control groups. Co-interventions include: anthelminthic treatment; multivitamin or multiple micronutrient supplementation; 5-methyltetrahydrofolate supplementation. Exclusion criteria Folate through folate-fortified water Folic acid administered through large-scale fortification of rice, wheat, or maize Comparators Placebo No treatment No folic acid/different doses of folic acid Iron Types of outcome measures Primary outcomes Uncomplicated malaria (defined as a history of fever with parasitological confirmation; acceptable parasitological confirmation will include rapid diagnostic tests (RDTs), malaria smears, or nucleic acid detection (i.e. polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), etc.)) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Severe malaria (defined as any case with cerebral malaria or acute P. falciparum malaria, with signs of severity or evidence of vital organ dysfunction, or both) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Parasite clearance (any Plasmodium species), defined as the time it takes for a patient who tests positive at enrolment and is treated to become smear-negative or PCR negative. This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Treatment failure (defined as the inability to clear malaria parasitaemia or prevent recrudescence after administration of antimalarial medicine, regardless of whether clinical symptoms are resolved) (WHO 2019). This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Secondary outcomes Duration of parasitaemia Parasite density Haemoglobin (Hb) concentrations (g/L) Anaemia: severe anaemia (defined as Hb less than 70 g/L in pregnant women and children aged six to 59 months; and Hb less than 80 g/L in other populations); moderate anaemia (defined as Hb less than 100 g/L in pregnant women and children aged six to 59 months; and less than 110 g/L in others) Death from any cause Among pregnant women: stillbirth (at less than 28 weeks gestation); low birthweight (less than 2500 g); active placental malaria (defined as Plasmodium detected in placental blood by smear or PCR, or by Plasmodium detected on impression smear or placental histology). Search methods for identification of studies A search will be conducted to identify completed and ongoing studies, without date or language restrictions. Electronic searches A search strategy will be designed to include the appropriate subject headings and text word terms related to each intervention of interest and study design of interest (see Appendix 1). Searches will be broken down by these two criteria (intervention of interest and study design of interest) to allow for ease of prioritization, if necessary. The study design filters recommended by the Scottish Intercollegiate Guidelines Network (SIGN), and those designed by Cochrane for identifying clinical trials for MEDLINE and Embase, will be used (SIGN 2020). There will be no date or language restrictions. Non-English articles identified for inclusion will be translated into English. If translations are not possible, advice will be requested from the Cochrane Infectious Diseases Group and the record will be stored in the "Awaiting assessment" section of the review until a translation is available. The following electronic databases will be searched for primary studies. Cochrane Central Register of Controlled Trials. Cumulative Index to Nursing and Allied Health Literature (CINAHL). Embase. MEDLINE. Scopus. Web of Science (both the Social Science Citation Index and the Science Citation Index). We will conduct manual searches of ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the United Nations Children's Fund (UNICEF) Evaluation and Research Database (ERD), in order to identify relevant ongoing or planned trials, abstracts, and full-text reports of evaluations, studies, and surveys related to programmes on folic acid supplementation in malaria-endemic areas. Additionally, manual searches of grey literature to identify RCTs that have not yet been published but are potentially eligible for inclusion will be conducted in the following sources. Global Index Medicus (GIM). African Index Medicus (AIM). Index Medicus for the Eastern Mediterranean Region (IMEMR). Latin American & Caribbean Health Sciences Literature (LILACS). Pan American Health Organization (PAHO). Western Pacific Region Index Medicus (WPRO). Index Medicus for the South-East Asian Region (IMSEAR). The Spanish Bibliographic Index in Health Sciences (IBECS) (ibecs.isciii.es/). Indian Journal of Medical Research (IJMR) (journals.lww.com/ijmr/pages/default.aspx). Native Health Database (nativehealthdatabase.net/). Scielo (www.scielo.br/). Searching other resources Handsearches of the five journals with the highest number of included studies in the last 12 months will be conducted to capture any relevant articles that may not have been indexed in the databases at the time of the search. We will contact the authors of included studies and will check reference lists of included papers for the identification of additional records. For assistance in identifying ongoing or unpublished studies, we will contact the Division of Nutrition, Physical Activity, and Obesity (DNPAO) and the Division of Parasitic Diseases and Malaria (DPDM) of the CDC, the United Nations World Food Programme (WFP), Nutrition International (NI), Global Alliance for Improved Nutrition (GAIN), and Hellen Keller International (HKI). Data collection and analysis Selection of studies Two review authors will independently screen the titles and abstracts of articles retrieved by each search to assess eligibility, as determined by the inclusion and exclusion criteria. Studies deemed eligible for inclusion by both review authors in the abstract screening phase will advance to the full-text screening phase, and full-text copies of all eligible papers will be retrieved. If full articles cannot be obtained, we will attempt to contact the authors to obtain further details of the studies. If such information is not obtained, we will classify the study as "awaiting assessment" until further information is published or made available to us. The same two review authors will independently assess the eligibility of full-text articles for inclusion in the systematic review. If any discrepancies occur between the studies selected by the two review authors, a third review author will provide arbitration. Each trial will be scrutinized to identify multiple publications from the same data set, and the justification for excluded trials will be documented. A PRISMA flow diagram of the study selection process will be presented to provide information on the number of records identified in the literature searches, the number of studies included and excluded, and the reasons for exclusion (Moher 2009). The list of excluded studies, along with their reasons for exclusion at the full-text screening phase, will also be created. Data extraction and management Two review authors will independently extract data for the final list of included studies using a standardized data specification form. Discrepancies observed between the data extracted by the two authors will be resolved by involving a third review author and reaching a consensus. Information will be extracted on study design components, baseline participant characteristics, intervention characteristics, and outcomes. For individually randomized trials, we will record the number of participants experiencing the event and the number analyzed in each treatment group or the effect estimate reported (e.g. risk ratio (RR)) for dichotomous outcome measures. For count data, we will record the number of events and the number of person-months of follow-up in each group. If the number of person-months is not reported, the product of the duration of follow-up and the number of children evaluated will be used to estimate this figure. We will calculate the rate ratio and standard error (SE) for each study. Zero events will be replaced by 0.5. We will extract both adjusted and unadjusted covariate incidence rate ratios if they are reported in the original studies. For continuous data, we will extract means (arithmetic or geometric) and a measure of variance (standard deviation (SD), SE, or confidence interval (CI)), percentage or mean change from baseline, and the numbers analyzed in each group. SDs will be computed from SEs or 95% CIs, assuming a normal distribution of the values. Haemoglobin values in g/dL will be calculated by multiplying haematocrit or packed cell volume values by 0.34, and studies reporting haemoglobin values in g/dL will be converted to g/L. In cluster-randomized trials, we will record the unit of randomization (e.g. household, compound, sector, or village), the number of clusters in the trial, and the average cluster size. The statistical methods used to analyze the trials will be documented, along with details describing whether these methods adjusted for clustering or other covariates. We plan to extract estimates of the intra-cluster correlation coefficient (ICC) for each outcome. Where results are adjusted for clustering, we will extract the treatment effect estimate and the SD or CI. If the results are not adjusted for clustering, we will extract the data reported. Assessment of risk of bias in included studies Two review authors (KSC, LFY) will independently assess the risk of bias for each included trial using the Cochrane 'Risk of bias 2' tool (RoB 2) for randomized studies (Sterne 2019). Judgements about the risk of bias of included studies will be made according to the recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). Disagreements will be resolved by discussion, or by involving a third review author. The interest of our review will be to assess the effect of assignment to the interventions at baseline. We will evaluate each primary outcome using the RoB2 tool. The five domains of the Cochrane RoB2 tool include the following. Bias arising from the randomization process. Bias due to deviations from intended interventions. Bias due to missing outcome data. Bias in measurement of the outcome. Bias in selection of the reported result. Each domain of the RoB2 tool comprises the following. A series of 'signalling' questions. A judgement about the risk of bias for the domain, facilitated by an algorithm that maps responses to the signalling questions to a proposed judgement. Free-text boxes to justify responses to the signalling questions and 'Risk of bias' judgements. An option to predict (and explain) the likely direction of bias. Responses to signalling questions elicit information relevant to an assessment of the risk of bias. These response options are as follows. Yes (may indicate either low or high risk of bias, depending on the most natural way to ask the question). Probably yes. Probably no. No. No information (may indicate no evidence of that problem or an absence of information leading to concerns about there being a problem). Based on the answer to the signalling question, a 'Risk of bias' judgement is assigned to each domain. These judgements include one of the following. High risk of bias Low risk of bias Some concerns To generate the risk of bias judgement for each domain in the randomized studies, we will use the Excel template, available at www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2. This file will be stored on a scientific data website, available to readers. Risk of bias in cluster randomized controlled trials For the cluster randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 1b (bias arising from the timing of identification or recruitment of participants) and its related signalling questions. To generate the risk of bias judgement for each domain in the cluster RCTs, we will use the Excel template available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-cluster-randomized-trials. This file will be stored on a scientific data website, available to readers. Risk of bias in cross-over randomized controlled trials For cross-over randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 2 (bias due to deviations from intended interventions), and Domain 3 (bias due to missing outcome data), and their respective signalling questions. To generate the risk of bias judgement for each domain in the cross-over RCTs, we will use the Excel template, available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-crossover-trials, for each risk of bias judgement of cross-over randomized studies. This file will be stored on a scientific data website, available to readers. Overall risk of bias The overall 'Risk of bias' judgement for each specific trial being assessed will be based on each domain-level judgement. The overall judgements include the following. Low risk of bias (the trial is judged to be at low risk of bias for all domains). Some concerns (the trial is judged to raise some concerns in at least one domain but is not judged to be at high risk of bias for any domain). High risk of bias (the trial is judged to be at high risk of bias in at least one domain, or is judged to have some concerns for multiple domains in a way that substantially lowers confidence in the result). The 'risk of bias' assessments will inform our GRADE evaluations of the certainty of evidence for our primary outcomes presented in the 'Summary of findings' tables and will also be used to inform the sensitivity analyses; (see Sensitivity analysis). If there is insufficient information in study reports to enable an assessment of the risk of bias, studies will be classified as "awaiting assessment" until further information is published or made available to us. Measures of treatment effect Dichotomous data For dichotomous data, we will present proportions and, for two-group comparisons, results as average RR or odds ratio (OR) with 95% CIs. Ordered categorical data Continuous data We will report results for continuous outcomes as the mean difference (MD) with 95% CIs, if outcomes are measured in the same way between trials. Where some studies have reported endpoint data and others have reported change-from-baseline data (with errors), we will combine these in the meta-analysis, if the outcomes were reported using the same scale. We will use the standardized mean difference (SMD), with 95% CIs, to combine trials that measured the same outcome but used different methods. If we do not find three or more studies for a pooled analysis, we will summarize the results in a narrative form. Unit of analysis issues Cluster-randomized trials We plan to combine results from both cluster-randomized and individually randomized studies, providing there is little heterogeneity between the studies. If the authors of cluster-randomized trials conducted their analyses at a different level from that of allocation, and they have not appropriately accounted for the cluster design in their analyses, we will calculate the trials' effective sample sizes to account for the effect of clustering in data. When one or more cluster-RCT reports RRs adjusted for clustering, we will compute cluster-adjusted SEs for the other trials. When none of the cluster-RCTs provide cluster-adjusted RRs, we will adjust the sample size for clustering. We will divide, by the estimated design effects (DE), the number of events and number evaluated for dichotomous outcomes and the number evaluated for continuous outcomes, where DE = 1 + ((average cluster size 1) * ICC). The derivation of the estimated ICCs and DEs will be reported. We will utilize the intra-cluster correlation coefficient (ICC), derived from the trial (if available), or from another source (e.g., using the ICCs derived from other, similar trials) and then calculate the design effect with the formula provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). If this approach is used, we will report it and undertake sensitivity analysis to investigate the effect of variations in ICC. Studies with more than two treatment groups If we identify studies with more than two intervention groups (multi-arm studies), where possible we will combine groups to create a single pair-wise comparison or use the methods set out in the Cochrane Handbook to avoid double counting study participants (Higgins 2021). For the subgroup analyses, when the control group was shared by two or more study arms, we will divide the control group (events and total population) over the number of relevant subgroups to avoid double counting the participants. Trials with several study arms can be included more than once for different comparisons. Cross-over trials From cross-over trials, we will consider the first period of measurement only and will analyze the results together with parallel-group studies. Multiple outcome events In several outcomes, a participant might experience more than one outcome event during the trial period. For all outcomes, we will extract the number of participants with at least one event. Dealing with missing data We will contact the trial authors if the available data are unclear, missing, or reported in a format that is different from the format needed. We aim to perform a 'per protocol' or 'as observed' analysis; otherwise, we will perform a complete case analysis. This means that for treatment failure, we will base the analyses on the participants who received treatment and the number of participants for which there was an inability to clear malarial parasitaemia or prevent recrudescence after administration of an antimalarial medicine reported in the studies. Assessment of heterogeneity Heterogeneity in the results of the trials will be assessed by visually examining the forest plot to detect non-overlapping CIs, using the Chi2 test of heterogeneity (where a P value of less than 0.1 indicates statistical significance) and the I2 statistic of inconsistency (with a value of greater than 50% denoting moderate levels of heterogeneity). When statistical heterogeneity is present, we will investigate the reasons for it, using subgroup analysis. Assessment of reporting biases We will construct a funnel plot to assess the effect of small studies for the main outcome (when including more than 10 trials). Data synthesis The primary analysis will include all eligible studies that provide data regardless of the overall risk of bias as assessed by the RoB2 tool. Analyses will be conducted using Review Manager 5.4 (Review Manager 2020). Cluster-RCTs will be included in the main analysis after adjustment for clustering (see the previous section on cluster-RCTs). The meta-analysis will be performed using the Mantel-Haenszel random-effects model or the generic inverse variance method (when adjustment for clustering is performed by adjusting SEs), as appropriate. Subgroup analysis and investigation of heterogeneity The overall risk of bias will not be used as the basis in conducting our subgroup analyses. However, where data are available, we plan to conduct the following subgroup analyses, independent of heterogeneity. Dose of folic acid supplementation: higher doses (4 mg or more, daily) versus lower doses (less than 4 mg, daily). Moderate-severe anaemia at baseline (mean haemoglobin of participants in a trial at baseline below 100 g/L for pregnant women and children aged six to 59 months, and below 110 g/L for other populations) versus normal at baseline (mean haemoglobin above 100 g/L for pregnant women and children aged six to 59 months, and above 110 g/L for other populations). Antimalarial drug resistance to parasite: known resistance versus no resistance versus unknown/mixed/unreported parasite resistance. Folate status at baseline: Deficient (e.g. RBC folate concentration of less than 305 nmol/L, or serum folate concentration of less than 7nmol/L) and Insufficient (e.g. RBC folate concentration from 305 to less than 906 nmol/L, or serum folate concentration from 7 to less than 25 nmol/L) versus Sufficient (e.g. RBC folate concentration above 906 nmol/L, or serum folate concentration above 25 nmol/L). Presence of anaemia at baseline: yes versus no. Mandatory fortification status: yes, versus no (voluntary or none). We will only use the primary outcomes in any subgroup analyses, and we will limit subgroup analyses to those outcomes for which three or more trials contributed data. Comparisons between subgroups will be performed using Review Manager 5.4 (Review Manager 2020). Sensitivity analysis We will perform a sensitivity analysis, using the risk of bias as a variable to explore the robustness of the findings in our primary outcomes. We will verify the behaviour of our estimators by adding and removing studies with a high risk of bias overall from the analysis. That is, studies with a low risk of bias versus studies with a high risk of bias. Summary of findings and assessment of the certainty of the evidence For the assessment across studies, we will use the GRADE approach, as outlined in (Schünemann 2021). We will use the five GRADE considerations (study limitations based on RoB2 judgements, consistency of effect, imprecision, indirectness, and publication bias) to assess the certainty of the body of evidence as it relates to the studies which contribute data to the meta-analyses for the primary outcomes. The GRADEpro Guideline Development Tool (GRADEpro) will be used to import data from Review Manager 5.4 (Review Manager 2020) to create 'Summary of Findings' tables. The primary outcomes for the main comparison will be listed with estimates of relative effects, along with the number of participants and studies contributing data for those outcomes. These tables will provide outcome-specific information concerning the overall certainty of evidence from studies included in the comparison, the magnitude of the effect of the interventions examined, and the sum of available data on the outcomes we considered. We will include only primary outcomes in the summary of findings tables. For each individual outcome, two review authors (KSC, LFY) will independently assess the certainty of the evidence using the GRADE approach (Balshem 2011). For assessments of the overall certainty of evidence for each outcome that includes pooled data from included trials, we will downgrade the evidence from 'high certainty' by one level for serious (or by two for very serious) study limitations (risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates, or potential publication bias). | NOT ENOUGH INFORMATION | LOW | 1 | nutrition and dietary supplements |
Is there enough evidence to determine the most effective and safe DMARD for treating NIIPPU in adults? | Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid-sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non-biologic, disease-modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU. | To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults. | There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid-sparing control (moderate-certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low-certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate. | NOT ENOUGH INFORMATION | LOW | 2 | musculoskeletal system and dermatology |
Does immediate postpartum insertion of implants and IUDs improve contraceptive initiation rates compared to delayed insertion? | Long-acting reversible contraception (LARC), including intrauterine devices (IUDs) and contraceptive implants, are highly effective, reversible methods of contraception. Providing LARC methods during the postpartum period is important to support contraceptive choice, and to prevent unintended pregnancy and short interpregnancy intervals. Delaying offering contraception to postpartum people until the first comprehensive postpartum visit, traditionally at around six weeks postpartum, may put some postpartum people at risk of unintended pregnancy, either due to loss to follow-up or because of initiation of sexual intercourse prior to receiving contraception. Therefore, immediate provision of highly effective contraception, prior to discharge from hospital, has the potential to improve contraceptive use and prevent unintended pregnancies and short interpregnancy intervals. | To compare the initiation rate, utilization rates (at six months and 12 months after delivery), effectiveness, and adverse effects of immediate versus delayed postpartum insertion of implants and IUDs for contraception. | Evidence from this updated review indicates that immediate postpartum insertion improves the initiation rate of both contraceptive implants and IUDs by the first postpartum visit compared to delayed insertion. However, it is not clear whether that there are differences in utilization rates at six and 12 months postpartum. We are uncertain whether there is any difference in the unintended pregnancy rate at 12 months. Provision of progestin-releasing implants and IUDs immediately postpartum may have little or no negative impact on breastfeeding. However, the expulsion rate of IUDs and prolonged vaginal bleeding associated with immediate implants appears to be higher. | SUPPORTED | MEDIUM | 0 | sexual and reproductive health |
Did the study investigate the effectiveness of different types of breastfeeding support interventions? | There is extensive evidence of important health risks for infants and mothers related to not breastfeeding. In 2003, the World Health Organization recommended that infants be breastfed exclusively until six months of age, with breastfeeding continuing as an important part of the infant's diet until at least two years of age. However, current breastfeeding rates in many countries do not reflect this recommendation. | 1. To describe types of breastfeeding support for healthy breastfeeding mothers with healthy term babies. 2. To examine the effectiveness of different types of breastfeeding support interventions in terms of whether they offered only breastfeeding support or breastfeeding support in combination with a wider maternal and child health intervention ('breastfeeding plus' support). 3. To examine the effectiveness of the following intervention characteristics on breastfeeding support: a. type of support (e.g. face-to-face, telephone, digital technologies, group or individual support, proactive or reactive); b. intensity of support (i.e. number of postnatal contacts); c. person delivering the intervention (e.g. healthcare professional, lay person); d. to examine whether the impact of support varied between high- and low-and middle-income countries. | Trial registration: | SUPPORTED | MEDIUM | 0 | nutrition and dietary supplements |
Does intentional endometrial injury improve the probability of pregnancy in infertile women or couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI)? | Intentional endometrial injury is being proposed as a technique to improve the probability of pregnancy in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF). Endometrial injury is often performed by pipelle biopsy and is a common gynaecological procedure with established safety. However, it causes a moderate degree of discomfort/pain and requires an additional pelvic examination. The effectiveness of this procedure outside of ART, in women or couples attempting to conceive via sexual intercourse or with intrauterine insemination (IUI), remains unclear. | To assess the effectiveness and safety of intentional endometrial injury performed in infertile women or couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI). | Evidence is insufficient to show whether there is a difference in live birth/ongoing pregnancy between endometrial injury and no intervention/a sham procedure in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution, as the evidence was of low to very low quality due to high risk of bias present in most included studies and an overall low level of precision. Furthermore, studies investigating the effect of timing of endometrial injury did not report the outcome live birth/ongoing pregnancy; therefore no conclusions could be drawn for this outcome. Further well-conducted RCTs that recruit large numbers of participants and minimise bias are required to confirm or refute these findings. Current evidence is insufficient to support routine use of endometrial injury in women undergoing IUI or attempting to conceive via sexual intercourse. | NOT ENOUGH INFORMATION | LOW | 1 | sexual and reproductive health |
Does non-invasive positive pressure ventilation (NIPV) effectively treat adults with central sleep apnoea (CSA)? | Central sleep apnoea (CSA) is characterised by abnormal patterns of ventilation during sleep due to a dysfunctional drive to breathe. Consequently, people with CSA may present poor sleep quality, sleep fragmentation, inattention, fatigue, daytime sleepiness, and reduced quality of life. | To assess the effectiveness and safety of non-invasive positive pressure ventilation (NIPV) for the treatment of adults with CSA. | CPAP plus best supportive care may reduce central AHI in people with CSA associated with chronic heart failure compared to best supportive care alone. Although ASV plus best supportive care may reduce AHI in people with CSA associated with chronic heart failure, it likely increases cardiovascular mortality in these individuals. In people with CPAP-induced CSA, ASV may slightly reduce central AHI compared to bilevel ventilation and to CPAP. In the absence of data showing a favourable impact on meaningful patient-centred outcomes and defining clinically important differences in outcomes in CSA patients, these findings need to be interpreted with caution. Considering the level of certainty of the available evidence and the heterogeneity of participants with CSA, we could draw no definitive conclusions, and further high-quality trials focusing on patient-centred outcomes, such as quality of life, quality of sleep, and longer-term survival, are needed to determine whether one mode of NIPV is better than another or than best supportive care for any particular CSA patient group. | NOT ENOUGH INFORMATION | LOW | 1 | respiratory system |
Do antidepressants provide significant benefits for the treatment of symptomatic knee and hip osteoarthritis in adults? | Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has resulted in the investigation of medications affecting pain processing with central effects. Antidepressants contribute to pain management in other conditions where pain sensitisation is present. | To assess the benefits and harms of antidepressants for the treatment of symptomatic knee and hip osteoarthritis in adults. | There is high-certainty evidence that use of antidepressants for knee osteoarthritis leads to a non-clinically important improvement in mean pain and function. However, a small number of people will have a 50% or greater important improvement in pain and function. This finding was consistent across all trials. Pain in osteoarthritis may be due to a variety of causes that differ between individuals. It may be that the cause of pain that responds to this therapy is only present in a small number of people. There is moderate-certainty evidence that antidepressants have a small positive effect on quality of life with heterogeneity between trials. High-certainty evidence indicates antidepressants result in more adverse events and moderate-certainty evidence indicates more withdrawal due to adverse events. There was little to no difference in serious adverse events (low-certainty evidence due to low numbers of events). This suggests that if antidepressants were being considered, there needs to be careful patient selection to optimise clinical benefit given the known propensity for adverse events with antidepressant use. Future trials should include alternative antidepressant agents or phenotyping of pain in people with osteoarthritis, or both. | REFUTED | MEDIUM | 2 | musculoskeletal system and dermatology |
Do topical corticosteroids provide effective relief for dry eye disease symptoms? | Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks). | To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED. | overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. for dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond csa. however, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. the available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on iop elevation or cataract formation or progression. future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile. | NOT ENOUGH INFORMATION | LOW | 1 | sensory organs |
Do systemic corticosteroids provide benefits for low back pain? | Corticosteroids are medications with anti-inflammatory and immunosuppressant properties. Systemic corticosteroids administered through the oral, intravenous, or intramuscular routes have been used to treat various types of low back pain, including radicular back pain (not due to spinal stenosis), non-radicular back pain, and spinal stenosis. However, there is uncertainty about the benefits and harms of systemic corticosteroids for low back pain. | To evaluate the benefits and harms of systemic corticosteroids versus placebo or no corticosteroid for radicular low back pain, non-radicular low back pain, and symptomatic spinal stenosis in adults. | Systemic corticosteroids appear to be slightly effective at improving short-term pain and function in people with radicular low back pain not due to spinal stenosis, and might slightly improve long-term function. The effects of systemic corticosteroids in people with non-radicular low back pain are unclear and systemic corticosteroids are probably ineffective for spinal stenosis. A single dose or short course of systemic corticosteroids for low back pain does not appear to cause serious harms, but evidence is limited. | SUPPORTED | MEDIUM | 0 | musculoskeletal system and dermatology |
Do antihistamines effectively prevent and treat motion sickness in adults and children? | Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving visual environments. The most common symptoms are nausea and vomiting. Antihistamines have been used in the management of motion sickness for decades, however studies have shown conflicting results regarding their efficacy. | To assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children. | There is probably a reduction in the risk of developing motion sickness symptoms under naturally occurring conditions of motion when using first-generation antihistamines, in motion sickness-susceptible adults, compared to placebo. Antihistamines may be more likely to cause sedation when compared to placebo. No studies evaluated the treatment of existing motion sickness, and there are few data on the effect of antihistamines in children. The evidence for all other outcomes and comparisons (versus scopolamine, antiemetics and acupuncture) was of low or very low certainty and we are therefore uncertain about these effects of antihistamines. | SUPPORTED | LOW | 0 | miscellaneous |
Can point-of-care biomarker tests of inflammation reduce antibiotic prescriptions for acute respiratory infections in primary care settings? | Acute respiratory infections (ARIs) are by far the most common reason for prescribing an antibiotic in primary care, even though the majority of ARIs are of viral or non-severe bacterial aetiology. It follows that in many cases antibiotic use will not be beneficial to a patient's recovery but may expose them to potential side effects. Furthermore, limiting unnecessary antibiotic use is a key factor in controlling antibiotic resistance. One strategy to reduce antibiotic use in primary care is point-of-care biomarkers. A point-of-care biomarker (test) of inflammation identifies part of the acute phase response to tissue injury regardless of the aetiology (infection, trauma, or inflammation) and may be used as a surrogate marker of infection, potentially assisting the physician in the clinical decision whether to use an antibiotic to treat ARIs. Biomarkers may guide antibiotic prescription by ruling out a serious bacterial infection and help identify patients in whom no benefit from antibiotic treatment can be anticipated. This is an update of a Cochrane Review first published in 2014. | To assess the benefits and harms of point-of-care biomarker tests of inflammation to guide antibiotic treatment in people presenting with symptoms of acute respiratory infections in primary care settings regardless of patient age. | The use of C-reactive protein point-of-care tests as an adjunct to standard care likely reduces the number of participants given an antibiotic prescription in primary care patients who present with symptoms of acute respiratory infection. The use of C-reactive protein point-of-care tests likely does not affect recovery rates. It is unlikely that further research will substantially change our conclusion regarding the reduction in number of participants given an antibiotic prescription, although the size of the estimated effect may change. The use of C-reactive protein point-of-care tests may not increase mortality within 28 days follow-up, but there were very few events. Studies that recorded deaths and hospital admissions were performed in children from low- and middle-income countries and older adults with comorbidities. Future studies should focus on children, immunocompromised individuals, and people aged 80 years and above with comorbidities. More studies evaluating procalcitonin and potential new biomarkers as point-of-care tests used in primary care to guide antibiotic prescription are needed. Furthermore, studies are needed to validate C-reactive protein decision algorithms, with a specific focus on potential age group differences. | SUPPORTED | MEDIUM | 0 | immune system and infections |
Does adjunctive therapy used in addition to land-based exercise therapy show significant benefits compared to placebo or exercise only for people with hip or knee osteoarthritis? | Land-based exercise therapy is recommended in clinical guidelines for hip or knee osteoarthritis. Adjunctive non-pharmacological therapies are commonly used alongside exercise in hip or knee osteoarthritis management, but cumulative evidence for adjuncts to land-based exercise therapy is lacking. | To evaluate the benefits and harms of adjunctive therapies used in addition to land-based exercise therapy compared with placebo adjunctive therapy added to land-based exercise therapy, or land-based exercise therapy only for people with hip or knee osteoarthritis. | Moderate- to low-certainty evidence showed no difference in pain, physical function or QOL between adjunctive therapies and placebo adjunctive therapies, or in pain, physical function, QOL or joint structural changes, compared to exercise only. Participant-reported global assessment was not reported for placebo comparisons, but there is probably a slight clinical benefit for adjunctive therapies plus exercise compared with exercise, based on a small number of studies. This may be explained by additional constructs captured in global measures compared with specific measures. Although results indicate no increased adverse events for adjunctive therapies used with exercise, these were poorly reported. Most studies evaluated short-term effects, with limited medium- or long-term evaluation. Due to a preponderance of knee osteoarthritis trials, we urge caution in extrapolating the findings to populations with hip osteoarthritis. | REFUTED | LOW | 2 | musculoskeletal system and dermatology |
Do TNF inhibitors effectively treat JIA-U? | Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by intraocular inflammation. Current treatment for JIA-associated uveitis (JIA-U) is largely based on physician experience, observational evidence and consensus guidelines, resulting in considerable variations in practice. OBJECTIVES: To evaluate the effectiveness and safety of tumor necrosis factor (TNF) inhibitors used for treatment of JIA-U. | Search methods: | Adalimumab appears to increase the likelihood of treatment success and decrease the likelihood of treatment failure when compared with placebo. The evidence was less conclusive about a positive treatment effect with etanercept. Adverse events from JIA-U trials are in keeping with the known side effect profile of TNF inhibitors. Standard validated JIA-U outcome measures are required to homogenize assessment and to allow for comparison and analysis of multiple datasets. | SUPPORTED | MEDIUM | 0 | musculoskeletal system and dermatology |
Does reconstructive surgery for treating pressure ulcers have clear benefits compared to no surgery or alternative surgical approaches? | There are several possible interventions for managing pressure ulcers (sometimes referred to as pressure injuries), ranging from pressure-relieving measures, such as repositioning, to reconstructive surgery. The surgical approach is usually reserved for recalcitrant wounds (where the healing process has stalled, or the wound is not responding to treatment) or wounds with full-thickness skin loss and exposure of deeper structures such as muscle fascia or bone. Reconstructive surgery commonly involves wound debridement followed by filling the wound with new tissue. Whilst this is an accepted means of ulcer management, the benefits and harms of different surgical approaches, compared with each other or with non-surgical treatments, are unclear. This is an update of a Cochrane Review published in 2016. | To assess the effects of different types of reconstructive surgery for treating pressure ulcers (category/stage II or above), compared with no surgery or alternative reconstructive surgical approaches, in any care setting. | Currently there is very little randomised evidence on the role of reconstructive surgery in pressure ulcer management, although it is considered a priority area. More rigorous and robust research is needed to explore this intervention. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Is splinting effective for the non-operative management of DDH in babies under six months of age? | Developmental dysplasia of the hip (DDH) describes the abnormal development of a hip in childhood, ranging from complete dislocation of the hip joint to subtle immaturity of a hip that is enlocated and stable within the socket. DDH occurs in around 10 per 1000 live births, though only one per 1000 are completely dislocated. There is variation in treatment pathways for DDH, which differs between hospitals and even between clinicians within the same hospital. The variation is related to the severity of dysplasia that is believed to require treatment, and the techniques used to treat dysplasia. | To determine the effectiveness of splinting and the optimal treatment strategy for the non-operative management of DDH in babies under six months of age. | There is a paucity of RCT evidence for splinting for the non-operative management of DDH: we included only six RCTs with 576 babies. Moreover, there was considerable heterogeneity between the studies, precluding meta-analysis. We judged the RCT evidence for all primary outcomes as being of very low certainty, meaning we are very uncertain about the true effects. Results from individual studies provide limited evidence of intervention effects on different severities of DDH. Amongst stable dysplastic hips, there was no evidence to suggest that treatment at any stage expedited the development of the acetabulum. For dislocatable hips, a delay in treatment onset to six weeks does not appear to result in any evidence of a difference in the development of the acetabulum at one year or increased risk of surgery. However, delayed splinting may reduce the number of babies requiring treatment with a harness. No RCTs compared static splinting with delayed or no splinting, staged weaning versus immediate removal or double nappies versus delayed or no splinting. There were few operative interventions or complications amongst the RCTs and the non-randomised studies. There's no apparent signal to indicate a higher frequency of either outcome in either intervention group. Given the frequency of this disease, and the fact that many countries undertake mandatory DDH screening, there is a clear need to develop an evidence-based pathway for treatment. Particular uncertainties requiring future research are the effectiveness of splinting amongst stable dysplastic hips, the optimal timing for the onset of splinting, the optimal type of splint to use and the need for 'weaning of splints'. Only once a robust pathway for treatment is established, can we properly assess the cost-effectiveness of screening interventions for DDH. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Does collective leadership for healthcare providers have effects on professional practice, healthcare outcomes, and staff well-being compared with usual centralised leadership approaches? | Collective leadership is strongly advocated by international stakeholders as a key approach for health service delivery, as a response to increasingly complex forms of organisation defined by rapid changes in health technology, professionalisation and growing specialisation. Inadequate leadership weakens health systems and can contribute to adverse events, including refusal to prioritise and implement safety recommendations consistently, and resistance to addressing staff burnout. Globally, increases in life expectancy and the number of people living with multiple long-term conditions contribute to greater complexity of healthcare systems. Such a complex environment requires the contribution and leadership of multiple professionals sharing viewpoints and knowledge. OBJECTIVES: To assess the effects of collective leadership for healthcare providers on professional practice, healthcare outcomes and staff well-being, when compared with usual centralised leadership approaches. | Search methods: | Trial registration: | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Is the effectiveness and safety of different hormonal regimens on uterine and endometrial development in women with POI clear? | Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic hypogonadism, characterised by amenorrhoea or oligomenorrhoea, with low ovarian sex hormones (oestrogen deficiency) and elevated pituitary gonadotrophins. POI with primary amenorrhoea may occur as a result of chromosomal and genetic abnormalities, such as Turner syndrome, Fragile X, or autosomal gene defects; secondary amenorrhoea may be iatrogenic after the surgical removal of the ovaries, radiotherapy, or chemotherapy. Other causes include autoimmune diseases, viral infections, and environmental factors; in most cases, POI is idiopathic. Appropriate replacement of sex hormones in women with POI may facilitate the achievement of near normal uterine development. However, the optimal effective hormone therapy (HT) regimen to maximise the reproductive potential for women with POI remains unclear. | To investigate the effectiveness and safety of different hormonal regimens on uterine and endometrial development in women with POI. | No clear conclusions can be drawn in this systematic review, due to the very low-certainty of the evidence. There is a need for pragmatic, well designed, randomised controlled trials, with adequate power to detect differences between various HT regimens on uterine growth, endometrial development, and pregnancy outcomes following the transfer of donated gametes or embryos in women diagnosed with POI. | NOT ENOUGH INFORMATION | LOW | 1 | endocrine system and hormones |
Do house modifications aiming to reduce exposure to mosquitoes reduce malaria disease and transmission? | Malaria remains an important public health problem. Research in 1900 suggested house modifications may reduce malaria transmission. A previous version of this review concluded that house screening may be effective in reducing malaria. This update includes data from five new studies. | To assess the effects of house modifications that aim to reduce exposure to mosquitoes on malaria disease and transmission. | House modifications - largely screening, sometimes combined with insecticide and lure and kill devices - were associated with a reduction in malaria parasite prevalence and a reduction in people with anaemia. Findings on malaria incidence were mixed. Modifications were also associated with lower indoor adult mosquito density, but this effect was not present in some studies. | SUPPORTED | MEDIUM | 0 | immune system and infections |
Is there enough evidence to determine the best treatment for fractures of the distal femur in adults? | Fractures of the distal femur (the far end of the thigh bone just above the knee) are a considerable cause of morbidity. Various different surgical and non-surgical treatments have been used in the management of these injuries but the best treatment remains unknown. | To evaluate the benefits and harms of interventions for treating fractures of the distal femur in adults. | This review highlights the major limitations of the available evidence concerning current treatment interventions for fractures of the distal femur. The currently available evidence is incomplete and insufficient to inform clinical practice. Priority should be given to randomised controlled trials comparing contemporary treatments for people with fractures of the distal femur. At a minimum, these should report validated patient-reported functional and quality-of-life outcomes at one and two years, with an agreed core outcome set. All trials should be reported in full using the CONSORT guidelines. | NOT ENOUGH INFORMATION | LOW | 1 | musculoskeletal system and dermatology |
Did the review findings support the benefits of psychosocial interventions for survivors of sexual abuse and violence? | It is well-established that experiencing sexual abuse and violence can have a range of detrimental impacts; a wide variety of interventions exist to support survivors in the aftermath. Understanding the experiences and perspectives of survivors receiving such interventions, along with those of their family members, and the professionals who deliver them is important for informing decision making as to what to offer survivors, for developing new interventions, and enhancing their acceptability. | This review sought to: 1. identify, appraise and synthesise qualitative studies exploring the experiences of child and adult survivors of sexual abuse and violence, and their caregivers, regarding psychosocial interventions aimed at supporting survivors and preventing negative health outcomes in terms of benefits, risks/harms and barriers; 2. identify, appraise and synthesise qualitative studies exploring the experiences of professionals who deliver psychosocial interventions for sexual abuse and violence in terms of perceived benefits, risks/harms and barriers for survivors and their families/caregivers; 3. develop a conceptual understanding of how different factors influence uptake, dropout or completion, and outcomes from psychosocial interventions for sexual abuse and violence; 4. develop a conceptual understanding of how features and types of interventions responded to the needs of different user/survivor groups (e.g. age groups; types of abuse exposure; migrant populations) and contexts (healthcare/therapeutic settings; low- and middle-income countries (LMICs)); 5. explore how the findings of this review can enhance our understanding of the findings from the linked and related reviews assessing the effectiveness of interventions aimed at supporting survivors and preventing negative health outcomes. | We had high or moderate confidence in all but one of our review findings. Further research in low- and middle-income settings, with male survivors of sexual abuse and violence and those from minority groups could strengthen the evidence for low and moderate confidence findings. We found that few interventions had published quantitative and qualitative evaluations. Since this QES has highlighted important aspects that could enable interventions to be more suitable for survivors, using a range of methodologies would provide valuable information that could enhance intervention uptake, completion and effectiveness. This study has shown that although survivors often found interventions difficult, they also appreciated that they needed to work through trauma, which they said resulted in a wide range of benefits. Therefore, listening to survivors and providing appropriate interventions, at the right time for them, can make a significant difference to their health and well-being. | SUPPORTED | MEDIUM | 0 | cognitive, mental, and mental health |
Can periodontal therapy prevent cardiovascular disease in people with chronic periodontitis? | There may be an association between periodontitis and cardiovascular disease (CVD); however, the evidence so far has been uncertain about whether periodontal therapy can help prevent CVD in people diagnosed with chronic periodontitis. This is the third update of a review originally published in 2014, and most recently updated in 2019. Although there is a new multidimensional staging and grading system for periodontitis, we have retained the label 'chronic periodontitis' in this version of the review since available studies are based on the previous classification system. | To investigate the effects of periodontal therapy for primary or secondary prevention of CVD in people with chronic periodontitis. | For primary prevention of cardiovascular disease (CVD) in people diagnosed with periodontitis and metabolic syndrome, very low-certainty evidence was inconclusive about the effects of scaling and root planning plus antibiotics compared to supragingival scaling. There is no reliable evidence available regarding secondary prevention of CVD in people diagnosed with chronic periodontitis and CVD. Further trials are needed to reach conclusions about whether treatment for periodontal disease can help prevent occurrence or recurrence of CVD. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Can pharmacological interventions effectively prevent antipsychotic-induced weight gain in people with schizophrenia? | Antipsychotic-induced weight gain is an extremely common problem in people with schizophrenia and is associated with increased morbidity and mortality. Adjunctive pharmacological interventions may be necessary to help manage antipsychotic-induced weight gain. This review splits and updates a previous Cochrane Review that focused on both pharmacological and behavioural approaches to this problem. | To determine the effectiveness of pharmacological interventions for preventing antipsychotic-induced weight gain in people with schizophrenia. | There is low-certainty evidence to suggest that metformin may be effective in preventing weight gain. Interpretation of this result and those for other agents, is limited by the small number of studies, small sample size, and short study duration. In future, we need studies that are adequately powered and with longer treatment durations to further evaluate the efficacy and safety of interventions for managing weight gain. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Does electromagnetic-guided placement of postpyloric nasoenteral feeding tubes show comparable efficacy and safety to endoscopic-guided placement? | For people who are malnourished and unable to consume food by mouth, nasoenteral feeding tubes are commonly used for the administration of liquid food and drugs. Postpyloric placement is when the tip of the feeding tube is placed beyond the pylorus, in the small intestine. Endoscopic-guided placement of postpyloric feeding tubes is the most common approach. Usually, an endoscopist and two or more medical professionals perform this procedure using a guidewire technique. The position of the tube is then confirmed with fluoroscopy or radiography, which requires moving people undergoing the procedure to the radiology department. Alternatively, electromagnetic-guided placement of postpyloric nasoenteral feeding tubes can be performed by a single trained nurse, at the bedside and with less equipment than endoscopic-guided placement. Hence, electromagnetic-guided placement may represent a promising alternative to endoscopic-guided placement, especially in settings where endoscopy and radiographic facilities are unavailable or difficult to access. | To assess the efficacy and safety of electromagnetic-guided placement of postpyloric nasoenteral feeding tubes compared to endoscopic-guided placement. | We found low-certainty evidence that electromagnetic-guided placement at the bedside results in little to no difference in technical success in insertion and aspiration pneumonitis, compared to endoscopic-guided placement. The heterogeneity of the healthcare professionals who performed the procedures and the small sample sizes limited our confidence in the evidence. Future research should be based on large studies with well-defined endpoints to potentially elucidate the differences between these two procedures. | NOT ENOUGH INFORMATION | LOW | 1 | digestive system and metabolism |
Does upper limb exercise benefit AVF maturation in patients with kidney failure? | The failure of arteriovenous fistulas (AVF) to mature is a major problem in patients with kidney failure who require haemodialysis (HD). Preoperative planning is an important factor in increasing functional AVF. Upper limb exercise has been recommended to gain AVF maturation. Studies of pre- and post-operative upper limb exercises in patients with kidney failure patients have been reported; however, the optimal program for this population is unknown due to inconsistent results among these programs. | We aimed to determine if upper limb exercise would be beneficial for AVF maturation (prior to and post AVF creation) in patients with kidney failure and to improve AVF outcomes. This review also aimed to identify adverse events related to upper limb exercise. | Our findings suggest that the current research evidence examining upper limb exercise programs is of low quality, attributable to variability in the type of interventions used and the overall low number of studies and participants. | NOT ENOUGH INFORMATION | LOW | 1 | cardiovascular system |
Does preoperative exercise training reduce the risk of postoperative pulmonary complications for people undergoing lung resection for NSCLC? | Surgical resection for early-stage non-small cell lung cancer (NSCLC) offers the best chance of cure, but it is associated with a risk of postoperative pulmonary complications. It is unclear if preoperative exercise training, and the potential resultant improvement in exercise capacity, may improve postoperative outcomes. This review updates our initial 2017 systematic review. | 1. To evaluate the benefits and harm of preoperative exercise training on postoperative outcomes, such as the risk of developing a postoperative pulmonary complication and the postoperative duration of intercostal catheter, in adults scheduled to undergo lung resection for NSCLC. 2. To determine the effect on length of hospital stay (and costs associated with postoperative hospital stay), fatigue, dyspnoea, exercise capacity, lung function and postoperative mortality. | preoperative exercise training results in a large reduction in the risk of developing a postoperative pulmonary complication compared to no preoperative exercise training for people with nsclc. it may also reduce postoperative length of hospital stay, and improve exercise capacity and lung function in people undergoing lung resection for nsclc. the findings of this review should be interpreted with caution due to risk of bias. research investigating the cost-effectiveness and long-term outcomes associated with preoperative exercise training in nsclc is warranted. | SUPPORTED | MEDIUM | 0 | respiratory system |
Does rPMS improve activities of daily living and functional ability in people after stroke? | Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive treatment method that can penetrate to deeper structures with painless stimulation to improve motor function in people with physical impairment due to brain or nerve disorders. rPMS for people after stroke has proved to be a feasible approach to improving activities of daily living and functional ability. However, the effectiveness and safety of this intervention for people after stroke remain uncertain. This is an update of the review published in 2019. | To assess the effects of rPMS for improving activities of daily living and functional ability in people after stroke. | There is insufficient evidence to permit the drawing of any conclusions about routine use of rPMS for people after stroke. Additional trials with large sample sizes are needed to provide robust evidence for rPMS after stroke. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Do most preschool children diagnosed with autism spectrum disorder before six years of age continue to meet diagnostic criteria at follow-up one or more years later? | Autism spectrum disorder is a neurodevelopmental disorder characterised by social communication difficulties, restricted interests and repetitive behaviours. The clinical pathway for children with a diagnosis of autism spectrum disorder is varied, and current research suggests some children may not continue to meet diagnostic criteria over time. | The primary objective of this review was to synthesise the available evidence on the proportion of preschool children who have a diagnosis of autism spectrum disorder at baseline (diagnosed before six years of age) who continue to meet diagnostic criteria at follow-up one or more years later (up to 19 years of age). | Overall, we found that nine out of 10 children who were diagnosed with autism spectrum disorder before six years of age continued to meet diagnostic criteria for autism spectrum disorder a year or more later, however the evidence was uncertain. Confidence in the evidence was rated low using GRADE, due to heterogeneity and risk of bias, and there were few studies that included children diagnosed using a current classification system, such as the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or the eleventh revision of the International Classification of Diseases (ICD-11). Future studies that are well-designed, prospective and specifically assess prognosis of autism spectrum disorder diagnoses are needed. These studies should also include contemporary diagnostic assessment methods across a broad range of participants and investigate a range of relevant prognostic factors. | NOT ENOUGH INFORMATION | LOW | 1 | cognitive, mental, and mental health |
Is ECP effective and safe for managing aGvHD in children and adolescents after HSCT? | Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of paediatric recipients. Currently, the therapeutic mainstay for aGvHD is treatment with corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and reinfusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and updated in 2015. | To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT. | The efficacy of ECP in the treatment of aGvHD in children and adolescents after HSCT is unknown, and its use should be restricted to within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2021 review update brought about no additions to these conclusions. | NOT ENOUGH INFORMATION | LOW | 1 | immune system and infections |