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Does supplementation of human milk with fat compared with unsupplemented human milk improve outcomes for preterm infants?
Specialist nursing roles to manage stable disease populations are being used to meet the needs of both patients and health services. With increasing cost pressures on health departments, alternative models such as nurse-led care are gaining momentum as a substitute for traditional doctor-led care. This review evaluates the safety, effectiveness, and health outcomes of nurses practising in autonomous roles while using advanced practice skills, within the context of bronchiectasis management in subacute, ambulatory, and/or community care.
To compare the effectiveness of nurse-led care versus doctor-led care in the management of stable bronchiectasis.
This update of the review shows that only one trial met review criteria. Review authors were unable to demonstrate effectiveness of nurse-led care compared with doctor-led care on the basis of findings of a single study. The included study reported no significant differences, but limited evidence means that differences in clinical outcomes between nurse-led care and usual care within the setting of a specialist clinic remain unclear. Further research is required to determine whether nurse-led care is cost-effective, if guidelines and protocols for bronchiectasis management are followed does this increases costs and how effective nurse-led management of bronchiectasis is in other clinical settings such as inpatient and outreach.
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nutrition and dietary supplements
Does direct fetal corticosteroid treatment provide better efficacy and safety?
As preterm infants do not experience the nutrient accretion and rapid growth phase of the third trimester of pregnancy, they are vulnerable to postnatal nutritional deficits, including of fat. Consequently, they require higher fat intakes compared to their full term counterparts to achieve adequate growth and development. Human milk fat provides the major energy needs of the preterm infant and also contributes to several metabolic and physiological functions. Although human milk has many benefits for this population, its fat content is highly variable and may be inadequate for their optimum growth and development. This is a 2018 update of a Cochrane Review last published in 2000.
To determine whether supplementation of human milk with fat compared with unsupplemented human milk fed to preterm infants improves growth, body composition, cardio-metabolic, and neurodevelopmental outcomes without significant adverse effects.
The one included trial suggests no evidence of an effect of fat supplementation of human milk on short-term growth and feeding intolerance in preterm infants. However, the very low-quality evidence, small sample size, few events, and low precision diminishes our confidence that these results reflect the true effect of fat supplementation of human milk in preterm infants, and no long-term outcomes were reported. Further high-quality research should evaluate the effect on short and long-term growth, neurodevelopmental and cardio-metabolic outcomes in the context of the development of multicomponent fortifiers. Optimal dosage, adverse effects, and delivery practices should also be evaluated.
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sexual and reproductive health
Did individual drugs or combinations of drugs have an effect in preventing rejection following lung transplantation in people with cystic fibrosis?
Alzheimer's disease is the most common cause of dementia in older people. One approach to symptomatic treatment of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by blocking the action of the enzyme responsible for the breakdown of the neurotransmitter acetylcholine. This can be done by a group of drugs known as cholinesterase inhibitors. Donepezil is a cholinesterase inhibitor.This review is an updated version of a review first published in 1998.
To assess the clinical efficacy and safety of donepezil in people with mild, moderate or severe dementia due to Alzheimer's disease; to compare the efficacy and safety of different doses of donepezil; and to assess the effect of donepezil on healthcare resource use and costs.
There is moderate-quality evidence that people with mild, moderate or severe dementia due to Alzheimer's disease treated for periods of 12 or 24 weeks with donepezil experience small benefits in cognitive function, activities of daily living and clinician-rated global clinical state. There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total healthcare resource costs. Benefits on 23 mg/day were no greater than on 10 mg/day, and benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose, but the rates of withdrawal and of adverse events before end of treatment were higher the higher the dose.
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respiratory system
Is the efficacy and safety of LMWHs, DOACs, and VKAs compared for the long-term treatment of VTE in people with cancer?
For people with cystic fibrosis and advanced pulmonary damage, lung transplantation is an available and viable option. However, graft rejection is an important potential consequence after lung transplantation. Immunosuppressive therapy is needed to prevent episodes of graft rejection and thus subsequently reduce morbidity and mortality in this population. There are a number of classes of immunosuppressive drugs which act on different components of the immune system. There is considerable variability in the use of immunosuppressive agents after lung transplantation in cystic fibrosis. While much of the research in immunosuppressive drug therapy has focused on the general population of lung transplant recipients, little is known about the comparative effectiveness and safety of these agents in people with cystic fibrosis. This is an update of a previously published review.
To assess the effects of individual drugs or combinations of drugs compared to placebo or other individual drugs or combinations of drugs in preventing rejection following lung transplantation in people with cystic fibrosis.
The lack of currently available evidence makes it impossible to draw conclusions about the comparative efficacy and safety of the various immunosuppressive drugs among people with cystic fibrosis after lung transplantation. A 2013 Cochrane Review comparing tacrolimus with cyclosporine in all lung transplant recipients (not restricted to those with cystic fibrosis) reported no significant difference in mortality and risk of acute rejection. However, tacrolimus use was associated with lower risk of broncholitis obliterans syndrome and arterial hypertension and higher risk of diabetes mellitus. It should be noted that this wider review contained only a small number of included studies (n = 3) with a high risk of bias. Additional randomised studies are required to provide evidence for the benefit and safety of the use of immunosuppressive therapy among people with cystic fibrosis after lung transplantation.
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cancer
Do antipsychotics have an effect on the duration of delirium in hospitalized adults?
Cancer increases the risk of thromboembolic events, especially in people receiving anticoagulation treatments.
To compare the efficacy and safety of low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) for the long-term treatment of venous thromboembolism (VTE) in people with cancer.
For the long-term treatment of VTE in people with cancer, evidence shows that LMWHs compared to VKAs probably produces an important reduction in VTE and DOACs compared to LMWH, may likely reduce VTE but may increase risk of major bleeding. Decisions for a person with cancer and VTE to start long-term LMWHs versus oral anticoagulation should balance benefits and harms and integrate the person's values and preferences for the important outcomes and alternative management strategies.Editorial note: this is a living systematic review (LSR). LSRs offer new approaches to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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cognitive, mental, and mental health
Can shock wave therapy aid in the healing of venous leg ulcers?
Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence.
Our primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects.
There were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics.
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musculoskeletal system and dermatology
Can dual antibiotic therapy effectively manage exacerbations and reduce symptoms in bronchiectasis?
Venous leg ulcers are open skin wounds on the lower leg which can be slow to heal, and are both painful and costly. The point prevalence of open venous leg ulcers in the UK is about 3 cases per 10,000 people, and many people experience recurrent episodes of prolonged ulceration. First-line treatment for venous leg ulcers is compression therapy, but a wide range of dressings and topical treatments are also used. This diversity of treatments makes evidence-based decision-making challenging, and a clear and current overview of all the evidence is required. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents.
To assess the effects of (1) dressings and (2) topical agents for healing venous leg ulcers in any care setting and to rank treatments in order of effectiveness, with assessment of uncertainty and evidence quality.
More research is needed to determine whether particular dressings or topical agents improve the probability of healing of venous leg ulcers. However, the NMA is uninformative regarding which interventions might best be included in a large trial, largely because of the low certainty of the whole network and of individual comparisons.The results of this NMA focus exclusively on complete healing; whilst this is of key importance to people living with venous leg ulcers, clinicians may wish to take into account other patient-important outcomes and factors such as patient preference and cost.
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respiratory system
Does the route of corticosteroid administration have effects on health outcomes for women and their babies?
Despite major advances in medical technology, the incidence of preterm birth remains high. The use of antenatal corticosteroid administered transplacentally, by intramuscular injection to women at risk of preterm birth, has reduced the incidence of respiratory distress syndrome and increased the survival rates of preterm infants. However, this intervention also comes with its own risks and side effects. Animal studies and early studies in pregnant women at risk of preterm birth have reported the use of an alternative route of administration, by direct intramuscular injection of corticosteroid into the fetus under ultrasound guidance, in an attempt to minimise the side-effect profile. Direct fetal corticosteroid administration may have benefits over maternal administration in terms of safety and efficacy.
To assess if different routes of corticosteroid administration (maternal versus direct fetal) have effects on health outcomes for women and their babies.
The available clinical studies carried out so far on animals and human have shown that direct intramuscular injection of corticosteroid into the fetus under ultrasound guidance is feasible, but data on health outcomes are lacking. Uncertainty therefore persists as to which method could provide better efficacy and safety. Randomised controlled trials are required focusing on the benefits and harms of transplacental versus direct fetal corticosteroid treatment. Until the uncertainties have been addressed, it is advisable to stay with the current standard of antenatal transplacental maternally-administered corticosteroid treatment.
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sexual and reproductive health
Does iridotomy have significant effects compared to no iridotomy for primary angle-closure glaucoma?
Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. 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 (often just called 'iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber through use of a laser to create a hole in the iris. It is commonly 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). The effectiveness of iridotomy on slowing progression of visual field loss, however, is uncertain.
To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle closure, and primary angle-closure suspects.
The available studies that directly compared iridotomy to no iridotomy have not yet published full trial reports. At present, we cannot draw reliable conclusions based on randomized controlled trials as to whether iridotomy slows progression of visual field loss at one year compared to no iridotomy. Full publication of the results from the studies may clarify the benefits of iridotomy.
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sensory organs
Does controlled (permissive) hypotension resuscitation have different effects compared to normotensive resuscitation strategies for people with ruptured AAA?
An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mmHg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 mmHg to 100 mmHg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. This is an update of a review first published in 2016.
To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA.
We found no RCTs that compared controlled hypotension and normotensive resuscitation strategies in the management of haemorrhagic shock in patients with ruptured abdominal aortic aneurysm that assessed mortality, presence of coagulopathy, intensive care unit length of stay, and the presence of myocardial infarct and renal failure. High quality studies that evaluate the best strategy for managing haemorrhagic shock in ruptured abdominal aortic aneurysms are required.
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cardiovascular system
Can laxative agents of differing types prevent DIOS in children and adults with CF?
Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However, gastrointestinal problems such as constipation and distal intestinal obstruction syndrome (DIOS) are also important and well-recognised complications in CF. They share similar symptoms e.g. bloating, abdominal pain, but are distinct conditions. Constipation occurs when there is gradual faecal impaction of the colon, but DIOS occurs when there is an accumulation of faeces and sticky mucus, forming a mass in the distal part of the small intestine. The mass may partially block the intestine (incomplete DIOS) or completely block the intestine (complete DIOS). Symptoms of DIOS can affect quality of life and other aspects of CF health, such as airway clearance, exercise, sleep and nutritional status. Treatment of constipation and prevention of complete bowel obstruction are required for gastrointestinal management in CF. However, many different strategies are used in clinical practice and there is a lack of consensus. The importance of this topic was highlighted in a recent research priority setting exercise by the James Lind Alliance.
To evaluate the effectiveness and safety of laxative agents of differing types for preventing DIOS (complete and incomplete) in children and adults with CF.
There is an absence of evidence for interventions for the prevention of DIOS. As there was only one included trial, we could not perform a meta-analysis of the data. Furthermore, the included trial compared a prokinetic agent (cisapride) that is no longer licensed for use in a number of countries due to the risk of serious cardiac events, a finding that came to light after the trial was conducted. Therefore, the limited findings from the trial are not applicable in current clinical practice.Overall, a great deal more research needs to be undertaken on gastrointestinal complications in CF, as this is a very poorly studied area compared to respiratory complications in CF.
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digestive system and metabolism
Does oral fluphenazine have an effect on the treatment of schizophrenia compared to placebo?
Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades.
To compare the effects of oral fluphenazine with placebo for the treatment of schizophrenia. To evaluate any available economic studies and value outcome data.
The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. Fluphenazine's global position as an effective treatment for psychoses is not threatened by the outcome of this review. However, fluphenazine is an imperfect treatment and if accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia.
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cognitive, mental, and mental health
Does extracorporeal shock wave therapy have effects on the healing and management of venous leg ulceration?
Leg ulcers are chronic wounds of the lower leg, caused by poor blood flow, that can take a long time to heal. The pooling of blood in the veins can damage the skin and surrounding tissues, causing an ulcer to form. Venous leg ulcers are associated with impaired quality of life, reduced mobility, pain, stress and loss of dignity. The standard treatment for venous leg ulcers is compression bandages or stockings. Shock wave therapy may aid the healing of these wounds through the promotion of angiogenesis (the formation and development of blood vessels) and reduction of inflammation, though this process is poorly understood at present.
To assess the effects of extracorporeal shock wave therapy on the healing and management of venous leg ulceration.
We found no RCTs assessing the effectiveness of extracorporeal shock wave therapy in the healing and management of venous leg ulceration. The lack of high-quality evidence in this area highlights a gap in research and may serve to justify the need for further research and evidence to provide guidance concerning the use of this treatment option for this condition. Future trials should be of clear design and include concomitant use of the current best practice treatment, multilayer compression therapy. Recruitment should aspire to best represent patients seen in clinical practice and patient-related outcome measures should be included in study design.
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musculoskeletal system and dermatology
Does dual antibiotics have an effect in treating bronchiectasis?
Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation of the smaller airways and associated with a mortality rate greater than twice that of the general population. Antibiotics serve as front-line therapy for managing bacterial load, but their use is weighed against the development of antibiotic resistance. Dual antibiotic therapy has the potential to suppress infection from multiple strains of bacteria, leading to more successful treatment of exacerbations, reduced symptoms, and improved quality of life. Further evidence is required on the efficacy of dual antibiotics in terms of management of exacerbations and extent of antibiotic resistance.
To evaluate the effects of dual antibiotics in the treatment of adults and children with bronchiectasis.
A small number of studies in adults have generated high-quality evidence that is insufficient to inform robust conclusions, and studies in children have provided no evidence. We identified only one dual-therapy combination of oral and inhaled antibiotics. Results from this single trial of 53 adults that we were able to include in the quantitative synthesis showed no evidence of treatment benefit with oral plus inhaled dual therapy in terms of successful treatment of exacerbations, serious adverse events, sputum volume, lung function, and antibiotic resistance. Further high-quality research is required to determine the efficacy and safety of other combinations of dual antibiotics for both adults and children with bronchiectasis, particularly in terms of antibiotic resistance.
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respiratory system
Does enteral nutrition have a significant impact on mortality and adverse events in critically ill adults?
Critically ill people are at increased risk of malnutrition. Acute and chronic illness, trauma and inflammation induce stress-related catabolism, and drug-induced adverse effects may reduce appetite or increase nausea and vomiting. In addition, patient management in the intensive care unit (ICU) may also interrupt feeding routines. Methods to deliver nutritional requirements include provision of enteral nutrition (EN), or parenteral nutrition (PN), or a combination of both (EN and PN). However, each method is problematic. This review aimed to determine the route of delivery that optimizes uptake of nutrition.
To compare the effects of enteral versus parenteral methods of nutrition, and the effects of enteral versus a combination of enteral and parenteral methods of nutrition, among critically ill adults, in terms of mortality, number of ICU-free days up to day 28, and adverse events.
We found insufficient evidence to determine whether EN is better or worse than PN, or than combined EN and PN for mortality in hospital, at 90 days and at 180 days, and on the number of ventilator-free days and adverse events. We found fewer deaths at 30 days when studies gave combined EN and PN, and reduced sepsis for EN rather than PN. We found no studies that reported number of ICU-free days up to day 28. Certainty of the evidence for all outcomes is either low or very low. The 11 studies awaiting classification may alter the conclusions of the review once assessed.
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nutrition and dietary supplements
Does IV perioperative lidocaine have a beneficial impact on pain scores and gastrointestinal recovery in the early postoperative phase?
Couple therapy for depression has the twofold aim of modifying negative interaction patterns and increasing mutually supportive aspects of intimate relationships, changing the interpersonal context of depression. Couple therapy is included in several guidelines among the suggested treatments for depression.
1. The main objective was to examine the effects of couple therapy compared to individual psychotherapy for depression.2. Secondary objectives were to examine the effects of couple therapy compared to drug therapy and no/minimal treatment for depression.
Although there is suggestion that couple therapy is as effective as individual psychotherapy in improving depressive symptoms and more effective in improving relations in distressed couples, the low or very low quality of the evidence seriously limits the possibility of drawing firm conclusions. Very few data were available for comparisons with no/minimal treatment and drug therapy. Future trials of high quality should test in large samples with a long follow-up of the effects of couple therapy in comparison to other interventions in discordant couples with a depressed partner, considering the role of relationship quality as a potential effect mediator in the improvement of depression.
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miscellaneous
Does the prophylactic use of ergot alkaloids in the third stage of labor prevent postpartum hemorrhage?
Previous research has shown that the prophylactic use of uterotonic agents in the third stage of labour reduces postpartum blood loss and moderate to severe postpartum haemorrhage (PPH). PPH is defined as a blood loss of 500 mL or more within 24 hours after birth. This is one of a series of systematic reviews assessing the effects of prophylactic use of uterotonic drugs; in this review prophylactic ergot alkaloids as a whole, and different regimens of administration of ergot alkaloids, are compared with no uterotonic agents. This is an update of a Cochrane Review which was first published in 2007 and last updated in 2011.
To determine the effectiveness and safety of prophylactic use of ergot alkaloids in the third stage of labour by any route (intravenous (IV), intramuscular (IM), or oral) compared with no uterotonic agents, for the prevention of PPH.
prophylactic im or iv injections of ergot alkaloids may be effective in reducing blood loss, reducing pph (estimated blood loss of at least 500 ml), and increasing maternal haemoglobin. ergot alkaloids may also decrease the use of therapeutic uterotonics, but adverse effects may include elevated blood pressure and pain after birth requiring analgesia. there were no differences between groups in terms of other adverse effects (vomiting, nausea, headache or eclamptic fit). there is a lack of evidence on the effects of ergot alkaloids on severe pph, and retained or manual removal of placenta. there is also a lack of evidence on the oral route of administration of ergot alkaloids.
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sexual and reproductive health
Does intermittent administration of antibiotic treatment in bronchiectasis reduce antibiotic selection pressure and prevent the development of resistance?
Parenteral opioids (intramuscular and intravenous drugs including patient-controlled analgesia) are used for pain relief in labour in many countries throughout the world. This review is an update of a review first published in 2010.
To assess the effectiveness, safety and acceptability to women of different types, doses and modes of administration of parenteral opioid analgesia in labour. A second objective is to assess the effects of opioids in labour on the baby in terms of safety, condition at birth and early feeding.
Though most evidence is of low- or very-low quality, for healthy women with an uncomplicated pregnancy who are giving birth at 37 to 42 weeks, parenteral opioids appear to provide some relief from pain in labour but are associated with drowsiness, nausea, and vomiting in the woman. Effects on the newborn are unclear. Maternal satisfaction with opioid analgesia was largely unreported. The review needs to be examined alongside related Cochrane reviews. More research is needed to determine which analgesic intervention is most effective, and provides greatest satisfaction to women with acceptable adverse effects for mothers and their newborn.
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respiratory system
Is ribavirin effective for treating people with Crimean Congo haemorrhagic fever?
Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of treatment for pain in cancer and in palliative care, resulting in increased morbidity and reduced quality of life.This is an update of two Cochrane reviews. One was published in 2011, Issue 1 on laxatives and methylnaltrexone for the management of constipation in people receiving palliative care; this was updated in 2015 and excluded methylnaltrexone. The other was published in 2008, Issue 4 on mu-opioid antagonists (MOA) for OIBD. In this updated review, we only included trials on MOA (including methylnaltrexone) for OIBD in people with cancer and people receiving palliative care.
To assess the effectiveness and safety of MOA for OIBD in people with cancer and people receiving palliative care.
In this update, the conclusions for naldemedine are new. There is moderate-quality evidence to suggest that, taken orally, naldemedine improves bowel function over two weeks in people with cancer and OIBD but increases the risk of adverse events. The conclusions on naloxone and methylnaltrexone have not changed. The trials on naloxone did not assess laxation at 24 hours or over two weeks. There is moderate-quality evidence that methylnaltrexone improves bowel function in people receiving palliative care in the short term and over two weeks, and low-quality evidence that it does not increase adverse events. There is a need for more trials including more evaluation of adverse events. None of the current trials evaluated effects in children.
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immune system and infections
Does prescribed hypocaloric nutrition support have different effects compared to standard nutrition support for critically-ill adults?
Crimean Congo haemorrhagic fever (CCHF) is a tick-borne disease that occurs in parts of Asia, Europe and Africa. Since 2000 the infection has caused epidemics in Turkey, Iran, Russia, Uganda and Pakistan. Good-quality general supportive medical care helps reduce mortality. There is uncertainty and controversy about treating CCHF with the antiviral drug ribavirin.
To assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever.
We do not know if ribavirin is effective for treating Crimean Congo haemorrhagic fever. Non-randomized studies are often cited as evidence of an effect, but the risk of bias in these studies is high.
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nutrition and dietary supplements
Does perioperative IV lidocaine infusion have an effect on postoperative pain and recovery in adults undergoing various surgical procedures?
There are controversies about the amount of calories and the type of nutritional support that should be given to critically-ill people. Several authors advocate the potential benefits of hypocaloric nutrition support, but the evidence is inconclusive.
To assess the effects of prescribed hypocaloric nutrition support in comparison with standard nutrition support for critically-ill adults SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, Embase and LILACS (from inception to 20 June 2017) with a specific strategy for each database. We also assessed three websites, conference proceedings and reference lists, and contacted leaders in the field and the pharmaceutical industry for undetected/unpublished studies. There was no restriction by date, language or publication status.
The included studies had substantial clinical heterogeneity. We found very low-quality evidence about the effects of prescribed hypocaloric nutrition support on mortality in hospital, in the ICU and at 30 days, as well as in length of hospital and ICU stay, infectious complications and the length of mechanical ventilation. For these outcomes there is uncertainty about the effects of prescribed hypocaloric nutrition, since the range of estimates includes both appreciable benefits and harms.Given these limitations, results must be interpreted with caution in the clinical field, considering the unclear balance of the risks and harms of this intervention. Future research addressing the clinical heterogeneity of participants and interventions, study limitations and sample size could clarify the effects of this intervention.
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1
cancer
Can interventions for preventing upper GI bleeding in people admitted to ICUs have a clear effect and risk-benefit profile?
The management of postoperative pain and recovery is still unsatisfactory in a number of cases in clinical practice. Opioids used for postoperative analgesia are frequently associated with adverse effects, including nausea and constipation, preventing smooth postoperative recovery. Not all patients are suitable for, and benefit from, epidural analgesia that is used to improve postoperative recovery. The non-opioid, lidocaine, was investigated in several studies for its use in multimodal management strategies to reduce postoperative pain and enhance recovery. This review was published in 2015 and updated in January 2017.
To assess the effects (benefits and risks) of perioperative intravenous (IV) lidocaine infusion compared to placebo/no treatment or compared to epidural analgesia on postoperative pain and recovery in adults undergoing various surgical procedures.
We are uncertain whether IV perioperative lidocaine, when compared to placebo or no treatment, has a beneficial impact on pain scores in the early postoperative phase, and on gastrointestinal recovery, postoperative nausea, and opioid consumption. The quality of evidence was limited due to inconsistency, imprecision, and study quality. Lidocaine probably has no clinically relevant effect on pain scores later than 24 hours. Few studies have systematically assessed the incidence of adverse effects. There is a lack of evidence about the effects of IV lidocaine compared with epidural anaesthesia in terms of the optimal dose and timing (including the duration) of the administration. We identified three ongoing studies, and 18 studies are awaiting classification; the results of the review may change when these studies are published and included in the review.
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MEDIUM
1
digestive system and metabolism
Does videolaryngoscopy decrease the time and attempts required for endotracheal intubation and increase the success rate at first intubation in neonates?
Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress ulceration refers to GI mucosal injury related to the stress of being critically ill. ICU patients with major bleeding as a result of stress ulceration might have mortality rates approaching 48.5% to 65%. However, the incidence of stress-induced GI bleeding in ICUs has decreased, and not all critically ill patients need prophylaxis. Stress ulcer prophylaxis can result in adverse events such as ventilator-associated pneumonia; therefore, it is necessary to evaluate strategies that safely decrease the incidence of GI bleeding.
To assess the effect and risk-benefit profile of interventions for preventing upper GI bleeding in people admitted to ICUs.
This review shows that antacids, sucralfate, and H2 receptor antagonists might be more effective in preventing upper GI bleeding in ICU patients compared with placebo or no prophylaxis. The effect estimates of any treatment versus no prophylaxis on nosocomial pneumonia were consistent with benefits and harms. Evidence of low certainty suggests that proton pump inhibitors might be more effective than H2 receptor antagonists. Therefore, patient-relevant benefits and especially harms of H2 receptor antagonists compared with proton pump inhibitors need to be assessed by larger, high-quality RCTs to confirm the results of previously conducted, smaller, and older studies.
SUPPORTED
MEDIUM
0
respiratory system
Can NRT help people increase their chances of successfully stopping smoking?
Establishment of a secure airway is a critical part of neonatal resuscitation in the delivery room and the neonatal unit. Videolaryngoscopy has the potential to facilitate successful endotracheal intubation and decrease adverse consequences of delay in airway stabilization. Videolaryngoscopy may enhance visualization of the glottis and intubation success in neonates.
To determine the efficacy and safety of videolaryngoscopy compared to direct laryngoscopy in decreasing the time and attempts required for endotracheal intubation and increasing the success rate at first intubation in neonates.
Moderate to very low quality evidence suggests that videolaryngoscopy increases the success of intubation in the first attempt but does not decrease the time to intubation or the number of attempts for intubation. However, these studies were conducted with trainees performing the intubations and these results highlight the potential usefulness of the videolaryngoscopy as a teaching tool. Well-designed, adequately powered RCTs are necessary to confirm efficacy and address safety and cost-effectiveness of videolaryngoscopy for endotracheal intubation in neonates by trainees and those proficient in direct laryngoscopy.
SUPPORTED
HIGH
0
respiratory system
Is continuous antibiotics more effective than intermittent antibiotics in treating bronchiectasis?
Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection, inflammation and tissue damage. Antibiotics are a main treatment for bronchiectasis. The aim of continuous therapy with prophylactic antibiotics is to suppress bacterial load, but bacteria may become resistant to the antibiotic, leading to a loss of effectiveness. On the other hand, intermittent prophylactic antibiotics, given over a predefined duration and interval, may reduce antibiotic selection pressure and reduce or prevent the development of resistance. This systematic review aimed to evaluate the current evidence for studies comparing continuous versus intermittent administration of antibiotic treatment in bronchiectasis in terms of clinical efficacy, the emergence of resistance and serious adverse events.
To evaluate the effectiveness of continuous versus intermittent antibiotics in the treatment of adults and children with bronchiectasis, using the primary outcomes of exacerbations, antibiotic resistance and serious adverse events.
No randomised controlled trials have compared the effectiveness and risks of continuous antibiotic therapy versus intermittent antibiotic therapy for bronchiectasis. High-quality clinical trials are needed to establish which of these interventions is more effective for reducing the frequency and duration of exacerbations, antibiotic resistance and the occurrence of serious adverse events.
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respiratory system
Can a single dose of intramuscular corticosteroids be as effective and safe as a short course of oral corticosteroids in treating acute asthma patients discharged from an ED or equivalent acute care setting?
Acute asthma is a common cause of presentations to acute care centres, such as the emergency department (ED), and while the majority of patients can be discharged, relapse requiring additional medical care is common. Systemic corticosteroids are a major part in the treatment of moderate to severe acute asthma; however, there is no clear evidence regarding the most effective route of administration for improving outcomes in patients discharged from acute care.
To examine the effectiveness and safety of a single dose of intramuscular (IM) corticosteroids provided prior to discharge compared to a short course of oral corticosteroids in the treatment of acute asthma patients discharged from an ED or equivalent acute care setting.
There is insufficient evidence to identify whether IM corticosteroids are more effective in reducing relapse compared to oral corticosteroids among children or adults discharged from an ED or equivalent acute care setting for acute asthma. While we found no statistical differences, patients receiving IM corticosteroids reported fewer adverse events. Additional studies comparing the effectiveness of IM versus oral corticosteroids could provide further evidence clarity. Furthermore, there is a need for studies comparing different IM corticosteroids (e.g. IM dexamethasone versus IM methylprednisone) and different oral corticosteroids (e.g. oral dexamethasone versus oral prednisone), with consideration for dosing and pharmacokinetic properties, to better identify the optimal IM or oral corticosteroid regimens to improve patient outcomes. Other factors, such as patient preference and potential issues with adherence, may dictate practitioner prescribing.
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respiratory system
Did different medical and surgical interventions have effects in the treatment of urinary tract stones of the kidney or ureter in children?
Urolithiasis is a condition where crystalline mineral deposits (stones) form within the urinary tract. Urinary stones can be located in any part of the urinary tract. Affected children may present with abdominal pain, blood in the urine or signs of infection. Radiological evaluation is used to confirm the diagnosis, to assess the size of the stone, its location, and the degree of possible urinary obstruction.
To assess the effects of different medical and surgical interventions in the treatment of urinary tract stones of the kidney or ureter in children.
Based on mostly very low-quality evidence for most comparisons and outcomes, we are uncertain about the effect of nearly all medical and surgical interventions to treat stone disease in children.Common reasons why we downgraded our assessments of the quality of evidence were: study limitations (risk of bias), indirectness, and imprecision. These issues make it difficult to draw clinical inferences. It is important that affected individuals, clinicians, and policy-makers are aware of these limitations of the evidence. There is a critical need for better quality trials assessing patient-important outcomes in children with stone disease to inform future guidelines on the management of this condition.
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miscellaneous
Can anticoagulation be effective and safe for thromboprophylaxis in people with cancer with a CVC?
Central venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis-related morbidity and mortality. This is an update of the Cochrane Review published in 2014.
To evaluate the efficacy and safety of anticoagulation for thromboprophylaxis in people with cancer with a CVC.
The evidence was not conclusive for the effect of LMWH on mortality, the effect of VKA on mortality and catheter-related VTE, and the effect of LMWH compared to VKA on mortality and catheter-related VTE. We found moderate-certainty evidence that LMWH reduces catheter-related VTE compared to no LMWH. People with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.
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cancer
Do different pulp treatment techniques and associated medicaments have effects on the treatment of extensive decay in primary teeth?
In children, dental caries (tooth decay) is among the most prevalent chronic diseases worldwide. Pulp interventions are indicated for extensive tooth decay. Depending on the severity of the disease, three pulp treatment techniques are available: direct pulp capping, pulpotomy and pulpectomy. After treatment, the cavity is filled with a medicament. Materials commonly used include mineral trioxide aggregate (MTA), calcium hydroxide, formocresol or ferric sulphate.This is an update of a Cochrane Review published in 2014 when insufficient evidence was found to clearly identify one superior pulpotomy medicament and technique.
To assess the effects of different pulp treatment techniques and associated medicaments for the treatment of extensive decay in primary teeth.
Pulp treatment for extensive decay in primary teeth is generally successful. Many included trials had no clinical or radiological failures in either trial arm, and the overall proportion of failures was low. Any future trials in this area would require a very large sample size and follow up of a minimum of one year.The evidence suggests MTA may be the most efficacious medicament to heal the root pulp after pulpotomy of a deciduous tooth. As MTA is relatively expensive, future research could be undertaken to confirm if Biodentine, enamel matrix derivative, laser treatment or Ankaferd Blood Stopper are acceptable second choices, and whether, where none of these treatments can be used, application of sodium hypochlorite is the safest option. Formocresol, though effective, has known concerns about toxicity.Regarding pulpectomy, there is no conclusive evidence that one medicament or technique is superior to another, and so the choice of medicament remains at the clinician's discretion. Research could be undertaken to confirm if ZOE paste is more effective than Vitapex and to evaluate other alternatives.Regarding direct pulp capping, the small number of studies and low quality of the evidence limited interpretation. Formocresol may be more successful than calcium hydroxide; however, given its toxicity, any future research should focus on alternatives.
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dental and oral health
Can nicotine replacement therapy effectively achieve long-term smoking cessation compared to placebo or 'no NRT' interventions?
Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence.
To determine the effectiveness and safety of nicotine replacement therapy (NRT), including gum, transdermal patch, intranasal spray and inhaled and oral preparations, for achieving long-term smoking cessation, compared to placebo or 'no NRT' interventions.
There is high-quality evidence that all of the licensed forms of NRT (gum, transdermal patch, nasal spray, inhalator and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50% to 60%, regardless of setting, and further research is very unlikely to change our confidence in the estimate of the effect. The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. NRT often causes minor irritation of the site through which it is administered, and in rare cases can cause non-ischaemic chest pain and palpitations.
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respiratory system
Is cryotherapy effective in treating prostate cancer compared to other treatments?
Necrotizing soft tissue infections (NSTIs) are severe and rapidly spreading soft tissue infections of the subcutaneous tissue, fascia, or muscle, which are mostly caused by bacteria. Associated rates of mortality and morbidity are high, with the former estimated at around 23%, and disability, sequelae, and limb loss occurring in 15% of patients. Standard management includes intravenous empiric antimicrobial therapy, early surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies such as intravenous immunoglobulin (IVIG).
To assess the effects of medical and surgical treatments for necrotizing soft tissue infections (NSTIs) in adults in hospital settings.
We found very little evidence on the effects of medical and surgical treatments for NSTI. We cannot draw conclusions regarding the relative effects of any of the interventions on 30-day mortality or serious adverse events due to the very low quality of the evidence.The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real-life population.Management of NSTI participants (critically-ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo-controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long-term functional outcomes, e.g. quality of life (in the chronic phase).
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cancer
Can vaccines prevent typhoid fever?
Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages.
To assess the effects of vaccines for preventing typhoid fever.
The licensed Ty21a and Vi polysaccharide vaccines are efficacious in adults and children older than two years in endemic countries. The Vi-rEPA vaccine is just as efficacious, although data is only available for children. The new Vi-TT vaccine (PedaTyph) requires further evaluation to determine if it provides protection against typhoid fever. At the time of writing, there were only efficacy data from a human challenge setting in adults on the Vi-TT vaccine (Tybar), which clearly justify the ongoing field trials to evaluate vaccine efficacy.
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immune system and infections
Did the IMT effectively improve visual acuity and quality of life in people with late or advanced AMD?
Age-related macular degeneration (AMD) causes progressive and irreversible damage to the retina, resulting in loss of central vision. AMD is the third leading cause of irreversible visual impairment worldwide and the leading cause of blindness in industrialized countries. Since AMD is more common in older individuals, the number of affected individuals will increase significantly as the population ages. The implantable miniature telescope (IMT) is an ophthalmic device developed to improve vision in individuals who have lost vision due to AMD. Once implanted, the IMT is used to enlarge objects in the central visual field and focus them onto healthy areas of the retina not affected by AMD, allowing individuals to recognize objects that they otherwise could not see. It is unclear whether and how much the IMT can improve vision in individuals with end-stage AMD.
To assess the effectiveness and safety of the IMT in improving visual acuity and quality of life in people with late or advanced AMD.
We found no RCT or quasi-RCT and can draw no conclusion about the effectiveness and safety of the IMT in improving visual acuity in individuals with late or advanced AMD. Since the IMT is typically implanted monocularly based upon which eye has better best-corrected distance visual acuity, randomization between eyes within an individual may not be acceptable. Studies are needed that compare outcomes between individuals randomized to the device versus individuals not implanted, at least during study follow-up, who serve as controls.
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sensory organs
Does endoscopic stent placement have benefits over surgical palliation for people with symptomatic malignant gastric outlet obstruction?
Malignant gastric outlet obstruction is the clinical and pathological consequence of cancerous disease causing a mechanical obstruction to gastric emptying. It usually occurs when malignancy is at an advanced stage; therefore, people have a limited life expectancy. It is of paramount importance to restore oral intake to improve quality of life for the person in a manner that has a minimal risk of complications and a short recovery period.
To assess the benefits and harms of endoscopic stent placement versus surgical palliation for people with symptomatic malignant gastric outlet obstruction.
The use of duodenal stent placement in malignant gastric outlet obstruction has the benefits of a quicker resumption of oral intake and a reduced inpatient hospital stay; however, this is balanced by an increase in the recurrence of symptoms and the need for further intervention.It is impossible to draw further conclusions on these and the other measured outcomes, primarily due to the low number of eligible studies and small number of participants which resulted in low-quality evidence. It was not possible to analyse the impact on quality of life each intervention had for these participants.
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digestive system and metabolism
Can interventions targeting speech and language in children and adolescents with CAS be effective?
Childhood apraxia of speech (CAS) affects a child's ability to produce sounds and syllables precisely and consistently, and to produce words and sentences with accuracy and correct speech rhythm. It is a rare condition, affecting only 0.1% of the general population. Consensus has been reached that three core features have diagnostic validity: (1) inconsistent error production on both consonants and vowels across repeated productions of syllables or words; (2) lengthened and impaired coarticulatory transitions between sounds and syllables; and (3) inappropriate prosody (ASHA 2007). A deficit in motor programming or planning is thought to underlie the condition. This means that children know what they would like to say but there is a breakdown in the ability to programme or plan the fine and rapid movements required to accurately produce speech. Children with CAS may also have impairments in one or more of the following areas: non-speech oral motor function, dysarthria, language, phonological production impairment, phonemic awareness or metalinguistic skills and literacy, or combinations of these. High-quality evidence from randomised controlled trials (RCTs) is lacking on interventions for CAS.
To assess the efficacy of interventions targeting speech and language in children and adolescents with CAS as delivered by speech and language pathologists/therapists.
There is limited evidence that, when delivered intensively, both the NDP-3 and ReST may effect improvement in word accuracy in 4- to 12-year-old children with CAS, measured by the accuracy of production on treated and non-treated words, speech production consistency and the accuracy of connected speech. The study did not measure functional communication. No formal analyses were conducted to compare NDP-3 and ReST by the original study authors, hence one treatment cannot be reliably advocated over the other. We are also unable to say whether either treatment is better than no treatment or treatment as usual. No evidence currently exists to support the effectiveness of other treatments for children aged 4 to 12 years with idiopathic CAS without other comorbid neurodevelopmental disorders. Further RCTs replicating this study would strengthen the evidence base. Similarly, further RCTs are needed of other interventions, in other age ranges and populations with CAS and with co-occurring disorders.
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cognitive, mental, and mental health
Does respiratory muscle training improve clinical outcomes in cystic fibrosis?
The effectiveness of interventions to increase influenza vaccination uptake in people aged 60 years and older varies by country and participant characteristics. This review updates versions published in 2010 and 2014.
To assess access, provider, system, and societal interventions to increase the uptake of influenza vaccination in people aged 60 years and older in the community.
We identified interventions that demonstrated significant positive effects of low (postcards), medium (personalised phone calls), and high (home visits, facilitators) intensity that increase community demand for vaccination, enhance access, and improve provider/system response. The overall GRADE assessment of the evidence was moderate quality. Conclusions are unchanged from the 2014 review.
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respiratory system
Does NMES have a beneficial effect on people with COPD?
In people with chronic obstructive pulmonary disease (COPD), the use of neuromuscular electrostimulation (NMES) either alone, or together with conventional exercise training, might improve the condition of the peripheral muscles, increase exercise capacity and functional performance, reduce symptoms and improve health-related quality of life (HRQoL).
To determine the effects of NMES, applied in isolation or concurrently with conventional exercise training to one or more peripheral muscles, on peripheral muscle force and endurance, muscle size, exercise capacity, functional performance, symptoms, HRQoL and adverse events in people with COPD.
NMES, when applied in isolation, increased quadriceps force and endurance, 6MWD and time to symptom limitation exercising at a submaximal intensity, and reduced the severity of leg fatigue on completion of exercise testing. It may increase VO
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respiratory system
Is cryotherapy effective for the primary treatment of prostate cancer?
Traditionally, radical prostatectomy and radiotherapy with or without androgen deprivation therapy have been the main treatment options to attempt to cure men with localised or locally advanced prostate cancer. Cryotherapy is an alternative option for treatment of prostate cancer that involves freezing of the whole prostate (whole gland therapy) or only the cancer (focal therapy), but it is unclear how effective this is in comparison to other treatments.
To assess the effects of cryotherapy (whole gland or focal) compared with other interventions for primary treatment of clinically localised (cT1-T2) or locally-advanced (cT3) non-metastatic prostate cancer.
Based on very low quality evidence, primary whole gland cryotherapy has uncertain effects on oncologic outcomes, QoL, and major adverse events compared to external beam radiotherapy. Reasons for downgrading the QoE included serious study limitations, indirectness due to the use of lower doses of radiation in the comparison group than currently recommended, and serious or very serious imprecision.
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cancer
Can mirtazapine be effective as adjunct treatment for people with schizophrenia?
Many individuals who have a diagnosis of schizophrenia experience a range of distressing and debilitating symptoms. These can include positive symptoms (such as delusions, hallucinations, disorganised speech), cognitive symptoms (such as trouble focusing or paying attention or using information to make decisions), and negative symptoms (such as diminished emotional expression, avolition, alogia, and anhedonia). Antipsychotic drugs are often only partially effective, particularly in treating negative symptoms, indicating the need for additional treatment. Mirtazapine is an antidepressant drug that when taken in addition to an antipsychotic may offer some benefit for negative symptoms.
To systematically assess the effects of mirtazapine as adjunct treatment for people with schizophrenia.
The available evidence is primarily of very low quality and indicates that mirtazapine adjunct is not clearly associated with an effect for negative symptoms, but there is some indication of a positive effect on overall mental state and akathisia. No effect was found for global state or leaving the study early and data were not available for quality of life or service use. Due to limitations of the quality and applicability of the evidence it is not possible to make any firm conclusions, the role of mirtazapine adjunct in routine clinical practice remains unclear. This underscores the need for new high-quality evidence to further evaluate mirtazapine adjunct for schizophrenia.
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cognitive, mental, and mental health
Do educational interventions for healthcare professionals affect pressure ulcer prevention?
Pressure ulcers, also known as bed sores or pressure sores, are localised areas of tissue damage arising due to excess pressure and shearing forces. Education of healthcare staff has been recognised as an integral component of pressure ulcer prevention. These educational programmes are directed towards influencing behaviour change on the part of the healthcare professional, to encourage preventative practices with the aim of reducing the incidence of pressure ulcer development.
To assess the effects of educational interventions for healthcare professionals on pressure ulcer prevention.
We are uncertain whether educating healthcare professionals about pressure ulcer prevention makes any difference to pressure ulcer incidence, or to nurses' knowledge of pressure ulcer prevention. This is because the included studies provided very low-certainty evidence. Therefore, further information is required to clarify the impact of education of healthcare professionals on the prevention of pressure ulcers.
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musculoskeletal system and dermatology
Do blue-light filtering IOLs prevent the development and progression of age-related macular degeneration (AMD)?
Embryo incubation and assessment is a vital step in assisted reproductive technology (ART). Traditionally, embryo assessment has been achieved by removing embryos from a conventional incubator daily for quality assessment by an embryologist, under a light microscope. Over recent years time-lapse systems have been developed which can take digital images of embryos at frequent time intervals. This allows embryologists, with or without the assistance of embryo selection software, to assess the quality of the embryos without physically removing them from the incubator.The potential advantages of a time-lapse system (TLS) include the ability to maintain a stable culture environment, therefore limiting the exposure of embryos to changes in gas composition, temperature and movement. A TLS has the potential advantage of improving embryo selection for ART treatment by utilising additional information gained through continuously monitoring embryo development. Use of a TLS often adds significant extra cost onto an in vitro fertilisation (IVF) cycle.
To determine the effect of a TLS compared to conventional embryo incubation and assessment on clinical outcomes in couples undergoing ART.
There is insufficient evidence of differences in live birth, miscarriage, stillbirth or clinical pregnancy to choose between TLS, with or without embryo selection software, and conventional incubation. The studies were at high risk of bias for randomisation and allocation concealment, the result should be interpreted with extreme caution.
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sensory organs
Are aromatase inhibitors effective and safe for subfertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination (IUI)?
Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of women worldwide and often leads to anovulatory subfertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI letrozole is at least as effective as the first-line treatment clomiphene citrate (CC).
To evaluate the effectiveness and safety of aromatase inhibitors for subfertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination (IUI).
Letrozole appears to improve live birth and pregnancy rates in subfertile women with anovulatory polycystic ovary syndrome, compared to clomiphene citrate. There is high-quality evidence that OHSS rates are similar with letrozole or clomiphene citrate. There is high-quality evidence of no difference in miscarriage rates or multiple pregnancy rates. There is low-quality evidence of no difference in live birth and pregnancy rates between letrozole and laparoscopic ovarian drilling, although there were few relevant studies. For the 2018 update, we added good-quality trials, upgrading the quality of the evidence.
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sexual and reproductive health
Does respiratory muscle training affect clinical outcomes in people with cystic fibrosis?
Cystic fibrosis is the most common autosomal recessive disease in white populations, and causes respiratory dysfunction in the majority of individuals. Numerous types of respiratory muscle training to improve respiratory function and health-related quality of life in people with cystic fibrosis have been reported in the literature. Hence a systematic review of the literature is needed to establish the effectiveness of respiratory muscle training (either inspiratory or expiratory muscle training) on clinical outcomes in cystic fibrosis. This is an update of a previously published review.
To determine the effectiveness of respiratory muscle training on clinical outcomes in people with cystic fibrosis.
There is insufficient evidence to suggest whether this intervention is beneficial or not. Healthcare practitioners should consider the use of respiratory muscle training on a case-by-case basis. Further research of reputable methodological quality is needed to determine the effectiveness of respiratory muscle training in people with cystic fibrosis. Researchers should consider the following clinical outcomes in future studies; respiratory muscle function, pulmonary function, exercise capacity, hospital admissions, and health-related quality of life. Sensory-perceptual changes, such as respiratory effort sensation (e.g. rating of perceived breathlessness) and peripheral effort sensation (e.g. rating of perceived exertion) may also help to elucidate mechanisms underpinning the effectiveness of respiratory muscle training.
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respiratory system
Are bioresorbable fixation systems as effective as titanium systems for managing facial fractures?
Rigid internal fixation of the jaw bones is a routine procedure for the management of facial fractures. Titanium plates and screws are routinely used for this purpose. The limitations of this system has led to the development of plates manufactured from bioresorbable materials which, in some cases, omits the necessity for the second surgery. However, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions.
To compare the effectiveness of bioresorbable fixation systems with titanium systems for the management of facial fractures.
This review illustrates that there are no published randomised controlled clinical trials relevant to this review question. There is currently insufficient evidence for the effectiveness of resorbable fixation systems compared with conventional titanium systems for facial fractures. The findings of this review, based on the results of the aborted trials, do not suggest that resorbable plates are as effective as titanium plates. In future, the results of ongoing clinical trials may provide high level reliable evidence for assisting clinicians and patients for decision making. Trialists should design their studies accurately and comprehensively to meet the aims and objectives defined for the study.
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musculoskeletal system and dermatology
Can education improve complementary feeding practices?
This is an updated version of the Cochrane Review previously published in Issue 3, 2015.The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs).
To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective.
There is limited, low-quality evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.
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nutrition and dietary supplements
Can different treatments of Angle Class III malocclusion in adults be evaluated?
Prominent lower front teeth may be associated with a large or prognathic lower jaw (mandible) or a small or retrusive upper jaw (maxilla). Edward Angle, who may be considered the father of modern orthodontics, classified the malocclusion in this situation as Class III. The individual is described as having a negative or reverse overjet as the lower front teeth are more prominent than the upper front teeth.
The purpose of this systematic review was to evaluate different treatments of Angle Class III malocclusion in adults.
There is insufficient evidence from the two included trials, to conclude that one procedure is better or worse than another. The included trials compared different interventions and were at high risk of bias and therefore no implications for practice can be given. Further high quality randomized controlled trials with long term follow-up are required.
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dental and oral health
Is a 1-stage implant placement procedure as effective as a 2-stage procedure?
Implants may be placed penetrating the oral mucosa (1-stage procedure) or can be completely buried under the oral mucosa (2-stage procedure) during the healing phase of the bone at the implant surface. With a 2-stage procedure the risk of having unwanted loading onto the implants is minimized, but a second minor surgical intervention is needed to connect the healing abutments and more time is needed prior to start the prosthetic phase because of the wound-healing period required in relation to the second surgical intervention.
To evaluate whether a 1-stage implant placement procedure is as effective as a 2-stage procedure.
The number of patients included in the trials was too small to draw definitive conclusions. The 1-stage approach might be preferable in partially edentulous patients since it avoids one surgical intervention and shortens treatment times, while a 2-stage submerged approach could be indicated when an implant has not obtained an optimal primary stability or when barriers are used for guided tissue regeneration, or when it is expected that removable temporary prostheses could transmit excessive forces on the penetrating abutments especially in fully edentulous patients.
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dental and oral health
Does blue-light filtering IOLs provide protection to macular health and function?
An intraocular lens (IOL) is a synthetic lens that is surgically implanted within the eye following removal of the crystalline lens, during cataract surgery. While all modern IOLs attenuate the transmission of ultra-violet (UV) light, some IOLs, called blue-blocking or blue-light filtering IOLs, also reduce short-wavelength visible light transmission. The rationale for blue-light filtering IOLs derives primarily from cell culture and animal studies, which suggest that short-wavelength visible light can induce retinal photoxicity. Blue-light filtering IOLs have been suggested to impart retinal protection and potentially prevent the development and progression of age-related macular degeneration (AMD). We sought to investigate the evidence relating to these suggested benefits of blue-light filtering IOLs, and to consider any potential adverse effects.
To assess the effects of blue-light filtering IOLs compared with non-blue-light filtering IOLs, with respect to providing protection to macular health and function.
This systematic review shows with moderate certainty that there is no clinically meaningful difference in short-term BCVA with the two types of IOLs. Further, based upon available data, these findings suggest that there is no clinically meaningful difference in short-term contrast sensitivity with the two interventions, although there was a low level of certainty for this outcome due to a small number of included studies and their inherent risk of bias. Based upon current, best-available research evidence, it is unclear whether blue-light filtering IOLs preserve macular health or alter risks associated with the development and progression of AMD, or both. Further research is required to fully understand the effects of blue-light filtering IOLs for providing protection to macular health and function.
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sensory organs
Are oral contraceptive preparations effective, safe, and cost-effective in treating painful symptoms of laparoscopically proven endometriosis?
Endometriosis is a common gynaecological condition which affects many women of reproductive age worldwide and is a major cause of pain and infertility. The combined oral contraceptive pill (COCP) is widely used to treat pain occurring as a result of endometriosis, although the evidence for its efficacy is limited.
To determine the effectiveness, safety and cost-effectiveness of oral contraceptive preparations in the treatment of painful symptoms ascribed to the diagnosis of laparoscopically proven endometriosis.
Based on the limited evidence from two trials at high risk of bias and limited data for the prespecified outcomes for this review, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with placebo and the findings cannot be generalised.Based on the limited evidence from one small trial that was at high risk of bias, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with other medical treatments. Only one comparison was possible, with the medical intervention being goserelin, and the findings cannot be generalised.Further research is needed to fully evaluate the role of COCPs in managing pain-related symptoms associated with endometriosis. There are other formulations of the combined hormonal contraception such as the transdermal patch, vaginal ring or combined injectable contraceptives which this review did not cover but should be considered in future updates.
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sexual and reproductive health
Does epidural analgesia, including combined-spinal-epidural (CSE), effectively and safely relieve pain during labor?
Epidural analgesia is a central nerve block technique achieved by injection of a local anaesthetic close to the nerves that transmit pain, and is widely used as a form of pain relief in labour. However, there are concerns about unintended adverse effects on the mother and infant. This is an update of an existing Cochrane Review (Epidural versus non-epidural or no analgesia in labour), last published in 2011.
To assess the effectiveness and safety of all types of epidural analgesia, including combined-spinal-epidural (CSE) on the mother and the baby, when compared with non-epidural or no pain relief during labour.
Low-quality evidence shows that epidural analgesia may be more effective in reducing pain during labour and increasing maternal satisfaction with pain relief than non-epidural methods. Although overall there appears to be an increase in assisted vaginal birth when women have epidural analgesia, a post hoc subgroup analysis showed this effect is not seen in recent studies (after 2005), suggesting that modern approaches to epidural analgesia in labour do not affect this outcome. Epidural analgesia had no impact on the risk of caesarean section or long-term backache, and did not appear to have an immediate effect on neonatal status as determined by Apgar scores or in admissions to neonatal intensive care. Further research may be helpful to evaluate rare but potentially severe adverse effects of epidural analgesia and non-epidural analgesia on women in labour and long-term neonatal outcomes.
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cognitive, mental, and mental health
Can educational interventions effectively improve complementary feeding practices and related health outcomes in infants?
Although complementary feeding is a universal practice, the methods and manner in which it is practiced vary between cultures, individuals and socioeconomic classes. The period of complementary feeding is a critical time of transition in the life of an infant, and inappropriate complementary feeding practices, with their associated adverse health consequences, remain a significant global public health problem. Educational interventions are widely acknowledged as effective in promoting public health strategy, and those aimed at improving complementary feeding practices provide information about proper complementary feeding practices to caregivers of infants/children. It is therefore important to summarise evidence on the effectiveness of educational interventions to improve the complementary feeding practices of caregivers of infants.
To assess the effectiveness of educational interventions for improving the complementary feeding (weaning) practices of primary caregivers of children of complementary feeding age, and related health and growth outcomes in infants.
Overall, we found evidence that education improves complementary feeding practices.
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nutrition and dietary supplements
Can interventions designed to increase the consumption of fruit, vegetables or both benefit children aged five years and under?
Insufficient consumption of fruits and vegetables in childhood increases the risk of future non-communicable diseases, including cardiovascular disease. Interventions to increase consumption of fruit and vegetables, such as those focused on specific child-feeding strategies and parent nutrition education interventions in early childhood may therefore be an effective strategy in reducing this disease burden.
To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under.
Despite identifying 63 eligible trials of various intervention approaches, the evidence for how to increase children's fruit and vegetable consumption remains limited. There was very low- and low-quality evidence respectively that child-feeding practice and multicomponent interventions may lead to very small increases in fruit and vegetable consumption in children aged five years and younger. It is uncertain whether parent nutrition education interventions are effective in increasing fruit and vegetable consumption in children aged five years and younger. Given that the quality of the evidence is very low or low, future research will likely change estimates and conclusions. Long-term follow-up is required and future research should adopt more rigorous methods to advance the field.This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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LOW
1
nutrition and dietary supplements
Can automated mandatory bolus prevent or minimize postoperative delirium and cognitive dysfunction?
Childbirth may cause the most severe pain some women experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour and is considered to be the reference standard. Traditionally epidural analgesia has been delivered as a continuous infusion via a catheter in the epidural space, with or without the ability for the patient to supplement the analgesia received by activating a programmable pump to deliver additional top-up doses, known as patient-controlled epidural analgesia (PCEA). There has been interest in delivering maintenance analgesic medication via bolus dosing (automated mandatory bolus - AMB) instead of the traditional continuous basal infusion (BI); recent randomized controlled trials (RCTs) have shown that the AMB technique leads to improved analgesia and maternal satisfaction.
To assess the effects of automated mandatory bolus versus basal infusion for maintaining epidural analgesia in labour.
There is predominantly moderate-certainty evidence that AMB is similar to BI for maintaining epidural analgesia for labour for all measured outcomes and may have the benefit of decreasing the risk of breakthrough pain and improving maternal satisfaction while decreasing the amount of local anaesthetic needed.
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LOW
1
cognitive, mental, and mental health
Does optimized anaesthesia guided by processed EEG indices reduce the risk of postoperative delirium in patients aged 60 years or over undergoing non-cardiac surgical and non-neurosurgical procedures?
Water immersion during labour and birth is increasingly popular and is becoming widely accepted across many countries, and particularly in midwifery-led care settings. However, there are concerns around neonatal water inhalation, increased requirement for admission to neonatal intensive care unit (NICU), maternal and/or neonatal infection, and obstetric anal sphincter injuries (OASIS). This is an update of a review last published in 2011.
To assess the effects of water immersion during labour and/or birth (first, second and third stage of labour) on women and their infants.
In healthy women at low risk of complications there is moderate to low-quality evidence that water immersion during the first stage of labour probably has little effect on mode of birth or perineal trauma, but may reduce the use of regional analgesia. The evidence for immersion during the second stage of labour is limited and does not show clear differences on maternal or neonatal outcomes intensive care. There is no evidence of increased adverse effects to the fetus/neonate or woman from labouring or giving birth in water. Available evidence is limited by clinical variability and heterogeneity across trials, and no trial has been conducted in a midwifery-led setting.
SUPPORTED
MEDIUM
0
cognitive, mental, and mental health
Can inhaled corticosteroids reduce the severity and frequency of acute respiratory exacerbations and affect long-term pulmonary function decline in bronchiectasis patients?
Bronchiectasis is being increasingly diagnosed and recognised as an important contributor to chronic lung disease in both adults and children in high- and low-income countries. It is characterised by irreversible dilatation of airways and is generally associated with airway inflammation and chronic bacterial infection. Medical management largely aims to reduce morbidity by controlling the symptoms, reduce exacerbation frequency, improve quality of life and prevent the progression of bronchiectasis. This is an update of a review first published in 2000.
To evaluate the efficacy and safety of inhaled corticosteroids (ICS) in children and adults with stable state bronchiectasis, specifically to assess whether the use of ICS: (1) reduces the severity and frequency of acute respiratory exacerbations; or (2) affects long-term pulmonary function decline.
This updated review indicates that there is insufficient evidence to support the routine use of ICS in adults with stable state bronchiectasis. Further, we cannot draw any conclusion for the use of ICS in adults during an acute exacerbation or in children (for any state), as there were no studies.
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LOW
1
respiratory system
Can psychotherapy added to usual care be beneficial for patients with treatment-resistant depression?
Endometrial cancer is the sixth most common cancer in women worldwide and most commonly occurs after the menopause (75%) (globocan.iarc.fr). About 319,000 new cases were diagnosed worldwide in 2012. Endometrial cancer is commonly considered as a potentially 'curable cancer,' as approximately 75% of cases are diagnosed before disease has spread outside the uterus (FIGO (International Federation of Gynecology and Obstetrics) stage I). The overall five-year survival for all stages is about 86%, and, if the cancer is confined to the uterus, the five-year survival rate may increase to 97%. The majority of women diagnosed with endometrial cancer have early-stage disease, leading to a good prognosis after hysterectomy and removal of the ovaries (oophorectomy), with or without radiotherapy. However, women may have early physiological and psychological postmenopausal changes, either pre-existing or as a result of oophorectomy, depending on age and menopausal status at the time of diagnosis. Lack of oestrogen can cause hot flushes, night sweats, genital tract atrophy and longer-term adverse effects, such as osteoporosis and cardiovascular disease. These changes may be temporarily managed by using oestrogens, in the form of hormone replacement therapy (HRT). However, there is a theoretical risk of promoting residual tumour cell growth and increasing cancer recurrence. Therefore, this is a potential survival disadvantage in a woman who has a potentially curable cancer. In premenopausal women with endometrial cancer, treatment induces early menopause and this may adversely affect overall survival. Additionally, most women with early-stage disease will be cured of their cancer, making longer-term quality of life (QoL) issues more pertinent. Following bilateral oophorectomy, premenopausal women may develop significant and debilitating menopausal symptoms, so there is a need for information about the risk and benefits of taking HRT, enabling women to make an informed decision, weighing the advantages and disadvantages of using HRT for their individual circumstances.
To assess the risks and benefits of HRT (oestrogen alone or oestrogen with progestogen) for women previously treated for endometrial cancer.
Currently, there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer. The available evidence (both the single RCT and non-randomised evidence) does not suggest significant harm, if HRT is used after surgical treatment for early-stage endometrial cancer. There is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above). The use of HRT after endometrial cancer treatment should be individualised, taking account of the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use.
SUPPORTED
MEDIUM
0
cognitive, mental, and mental health
Does trihexyphenidyl have effects on people with dystonic cerebral palsy?
Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder amongst those with cerebral palsy is dystonia: sustained or intermittent involuntary muscle spasms and contractions that cause twisting, repetitive movements and abnormal postures. The involuntary contractions are often very painful and distressing and cause significant limitations to activity and participation.Oral medications are often the first line of medical treatment for dystonia. Trihexyphenidyl is one such medication that clinicians often use to treat dystonia in people with cerebral palsy.
To assess the effects of trihexyphenidyl in people with dystonic cerebral palsy, according to the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) domains of impairment, activity and participation. We also assessed the type and incidence of adverse effects in people taking the drug.
At present, there is insufficient evidence regarding the effectiveness of trihexyphenidyl for people with cerebral palsy for the outcomes of: change in dystonia, adverse effects, increased upper limb function and improved participation in activities of daily living. The study did not measure pain or quality of life. There is a need for larger randomised, controlled, multicentre trials that also examine the effect on pain and quality of life in order to determine the effectiveness of trihexyphenidyl for people with cerebral palsy.
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LOW
1
cognitive, mental, and mental health
Do nursing record systems affect nursing practice and patient outcomes?
A nursing record system is the record of care that was planned or given to individual patients and clients by qualified nurses or other caregivers under the direction of a qualified nurse. Nursing record systems may be an effective way of influencing nurse practice.
To assess the effects of nursing record systems on nursing practice and patient outcomes.
We found some limited evidence of effects on practice attributable to changes in record systems. It is clear from the literature that it is possible to set up the randomised trials or other quasi-experimental designs needed to produce evidence for practice. Qualitative nursing research to explore the relationship between practice and information use could be used as a precursor to the design and testing of nursing information systems.
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LOW
1
cognitive, mental, and mental health
Does L-ornithine L-aspartate have beneficial effects in people with cirrhosis and hepatic encephalopathy?
Hepatic encephalopathy is a common complication of cirrhosis and has high associated morbidity and mortality. The condition is classified as overt if it is clinically apparent or minimal if only evident though psychometric testing. The exact pathogenesis of this syndrome is unknown although ammonia is thought to play a key role. L-ornithine L-aspartate has ammonia-lowering properties and may, therefore, benefit people with cirrhosis and hepatic encephalopathy.
To evaluate the beneficial and harmful effects of L-ornithine L-aspartate versus placebo, no intervention, or other active interventions in people with cirrhosis and hepatic encephalopathy.
The results of this review suggest a possible beneficial effect of L-ornithine L-aspartate on mortality, hepatic encephalopathy, and serious adverse events in comparisons with placebo or no-intervention, but, because the quality of the evidence is very low, we are very uncertain about these findings. There was very low quality evidence of a possible beneficial effect of L-ornithine L-aspartate on hepatic encephalopathy, when compared with probiotics, but no other benefits were demonstrated in comparison with other active agents. Additional access to data from completed, but unpublished trials, and new randomised placebo-controlled, double-blind clinical trials are needed.
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LOW
1
digestive system and metabolism
Can the use of processed EEG or auditory evoked potential indices reduce the risk of POD and POCD in non-cardiac surgical or non-neurosurgical adult patients undergoing general anesthesia?
Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) may complicate a patient's postoperative recovery in several ways. Monitoring of processed electroencephalogram (EEG) or evoked potential (EP) indices may prevent or minimize POD and POCD, probably through optimization of anaesthetic doses.
To assess whether the use of processed EEG or auditory evoked potential (AEP) indices (bispectral index (BIS), narcotrend index, cerebral state index, state entropy and response entropy, patient state index, index of consciousness, A-line autoregressive index, and auditory evoked potentials (AEP index)) as guides to anaesthetic delivery can reduce the risk of POD and POCD in non-cardiac surgical or non-neurosurgical adult patients undergoing general anaesthesia compared with standard practice where only clinical signs are used.
There is moderate-quality evidence that optimized anaesthesia guided by processed EEG indices could reduce the risk of postoperative delirium in patients aged 60 years or over undergoing non-cardiac surgical and non-neurosurgical procedures. We found moderate-quality evidence that postoperative cognitive dysfunction at three months could be reduced in these patients. The effect on POCD at one week and over one year after surgery is uncertain. There are no data available for patients under 60 years. Further blinded randomized controlled trials are needed to elucidate strategies for the amelioration of postoperative delirium and postoperative cognitive dysfunction, and their consequences such as dementia (including Alzheimer's disease (AD)) in both non-elderly (below 60 years) and elderly (60 years or over) adult patients. The one study awaiting classification and five ongoing studies may alter the conclusions of the review once assessed.
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LOW
1
cognitive, mental, and mental health
Can the Mallampati classification and other airway examination tests accurately assess the physical status of the airway in adult patients with no apparent anatomical airway abnormalities?
The unanticipated difficult airway is a potentially life-threatening event during anaesthesia or acute conditions. An unsuccessfully managed upper airway is associated with serious morbidity and mortality. Several bedside screening tests are used in clinical practice to identify those at high risk of difficult airway. Their accuracy and benefit however, remains unclear.
The objective of this review was to characterize and compare the diagnostic accuracy of the Mallampati classification and other commonly used airway examination tests for assessing the physical status of the airway in adult patients with no apparent anatomical airway abnormalities. We performed this individually for each of the four descriptors of the difficult airway: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation.
Bedside airway examination tests, for assessing the physical status of the airway in adults with no apparent anatomical airway abnormalities, are designed as screening tests. Screening tests are expected to have high sensitivities. We found that all investigated index tests had relatively low sensitivities with high variability. In contrast, specificities were consistently and markedly higher than sensitivities across all tests. The standard bedside airway examination tests should be interpreted with caution, as they do not appear to be good screening tests. Among the tests we examined, the upper lip bite test showed the most favourable diagnostic test accuracy properties. Given the paucity of available data, future research is needed to develop tests with high sensitivities to make them useful, and to consider their use for screening difficult face mask ventilation and failed intubation. The 27 studies in 'Studies awaiting classification' may alter the conclusions of the review, once we have assessed them.
NOT ENOUGH INFORMATION
MODERATE
1
respiratory system
Can withdrawal of immunosuppressant therapy impact the development of Crohn's disease-related complications?
Antidepressants are a first-line treatment for adults with moderate to severe major depression. However, many people prescribed antidepressants for depression don't respond fully to such medication, and little evidence is available to inform the most appropriate 'next step' treatment for such patients, who may be referred to as having treatment-resistant depression (TRD). National Institute for Health and Care Excellence (NICE) guidance suggests that the 'next step' for those who do not respond to antidepressants may include a change in the dose or type of antidepressant medication, the addition of another medication, or the start of psychotherapy. Different types of psychotherapies may be used for TRD; evidence on these treatments is available but has not been collated to date.Along with the sister review of pharmacological therapies for TRD, this review summarises available evidence for the effectiveness of psychotherapies for adults (18 to 74 years) with TRD with the goal of establishing the best 'next step' for this group.
To assess the effectiveness of psychotherapies for adults with TRD.
Moderate-quality evidence shows that psychotherapy added to usual care (with antidepressants) is beneficial for depressive symptoms and for response and remission rates over the short term for patients with TRD. Medium- and long-term effects seem similarly beneficial, although most evidence was derived from a single large trial. Psychotherapy added to usual care seems as acceptable as usual care alone.Further evidence is needed on the effectiveness of different types of psychotherapies for patients with TRD. No evidence currently shows whether switching to a psychotherapy is more beneficial for this patient group than continuing an antidepressant medication regimen. Addressing this evidence gap is an important goal for researchers.
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LOW
1
digestive system and metabolism
Can antidepressants effectively treat insomnia in adults?
Insomnia disorder is a subjective condition of unsatisfactory sleep (e.g. sleep onset, maintenance, early waking, impairment of daytime functioning). Insomnia disorder impairs quality of life and is associated with an increased risk of physical and mental health problems including anxiety, depression, drug and alcohol abuse, and increased health service use. hypnotic medications (e.g. benzodiazepines and 'Z' drugs) are licensed for sleep promotion, but can induce tolerance and dependence, although many people remain on long-term treatment. Antidepressant use for insomnia is widespread, but none is licensed for insomnia and the evidence for their efficacy is unclear. This use of unlicensed medications may be driven by concern over longer-term use of hypnotics and the limited availability of psychological treatments.
To assess the effectiveness, safety and tolerability of antidepressants for insomnia in adults.
We identified relatively few, mostly small studies with short-term follow-up and design limitations. The effects of SSRIs compared with placebo are uncertain with too few studies to draw clear conclusions. There may be a small improvement in sleep quality with short-term use of low-dose doxepin and trazodone compared with placebo. The tolerability and safety of antidepressants for insomnia is uncertain due to limited reporting of adverse events. There was no evidence for amitriptyline (despite common use in clinical practice) or for long-term antidepressant use for insomnia. High-quality trials of antidepressants for insomnia are needed.
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LOW
1
cognitive, mental, and mental health
Does increasing or maintaining the antipsychotic dose show clear differences in people with schizophrenia who do not respond to their initial treatment?
Various methods of conscious sedation and analgesia (CSA) have been used during oocyte retrieval for assisted reproduction. The choice of agent has been influenced by the quality of sedation and analgesia and by concerns about possible detrimental effects on reproductive outcomes.
To assess the effectiveness and safety of different methods of conscious sedation and analgesia for pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval.
The evidence does not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte retrieval. Simultaneous use of sedation combined with analgesia such as the opiates, further enhanced by paracervical block or acupuncture techniques, resulted in better pain relief than occurred with one modality alone. Evidence was insufficient to show conclusively whether any of the interventions influenced pregnancy rates. All techniques reviewed were associated with a high degree of patient satisfaction. Women's preferences and resource availability for choice of pain relief merit consideration in practice.
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LOW
1
cognitive, mental, and mental health
Does glucocorticosteroid administration following Kasai portoenterostomy have beneficial effects?
Biliary atresia is a life-threatening disease characterised by progressive destruction of both intra- and extra-hepatic biliary ducts. The mainstay of treatment is Kasai portoenterostomy, as soon as the disease has been confirmed. Glucocorticosteroids are steroid hormones which act on the glucocorticoid receptor and have a range of metabolic and immunomodulatory effects. Glucocorticosteroids are used to improve the postoperative outcomes in infants who have undergone Kasai portoenterostomy.
To assess the beneficial and harmful effects of glucocorticosteroid administration versus placebo or no intervention following Kasai portoenterostomy in infants with biliary atresia.
The two meta-analysed randomised clinical trials present insufficient evidence to determine the effects of using glucocorticosteroids versus placebo after Kasai portoenterostomy in infants with biliary atresia on any of the primary or secondary review outcomes. There is insufficient evidence to support glucocorticosteroid use in the postoperative management of infants with biliary atresia for long-term outcomes of all-cause mortality or liver transplantation. It is also unclear if glucocorticosteroids are able to reduce the numbers of infants who did not clear their jaundice by six months. Further randomised, placebo-controlled trials are required to be able to determine if glucocorticosteroids may be of benefit in the postoperative management of infants with biliary atresia treated with Kasai portoenterostomy. Such trials need to be conducted as multicentre trials.
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LOW
1
digestive system and metabolism
Is a therapeutic-only platelet transfusion policy as effective and safe as a prophylactic platelet transfusion policy in people with bone marrow failure disorders?
Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries.
To determine whether a therapeutic-only platelet transfusion policy (transfusion given when patient is bleeding) is as effective and safe as a prophylactic platelet transfusion policy (transfusion given to prevent bleeding according to a prespecified platelet threshold) in people with congenital or acquired bone marrow failure disorders.
We found no evidence to determine the safety and efficacy of therapeutic platelet transfusion compared with prophylactic platelet transfusion for people with long-term bone marrow failure disorders. This review underscores the urgency of prioritising research in this area. People with bone marrow failure depend on long-term platelet transfusion support, but the only trial that assessed a therapeutic strategy was halted. There is a need for good-quality studies comparing a therapeutic platelet transfusion strategy with a prophylactic platelet transfusion strategy; such trials should include outcomes that are important to patients, such as quality of life, length of hospital admission, and risk of bleeding.
NOT ENOUGH INFORMATION
LOW
1
hematologic system
Did non-pharmacological therapies improve chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)?
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms.
To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
Based on the findings of moderate quality evidence, this review found that some non-pharmacological interventions such as acupuncture and extracorporeal shockwave therapy are likely to result in a decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse event. The QoE for most other comparisons was predominantly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.
NOT ENOUGH INFORMATION
LOW
1
sexual and reproductive health
Is it feasible and safe to discontinue immunosuppressant or biologic drugs in patients with quiescent CD?
Crohn's disease (CD) is a chronic, relapsing and remitting disease of the gastrointestinal tract that can cause significant morbidity and disability. Current treatment guidelines recommend early intervention with immunosuppressant or biological therapy in high-risk patients with a severe disease phenotype at presentation. The feasibility of therapeutic de-escalation once remission is achieved is a commonly encountered question in clinical practice, driven by patient and clinician concerns regarding safety, adverse events, cost and national regulations. Withdrawal of immunosuppressant and biologic drugs in patients with quiescent CD may limit adverse events and reduce healthcare costs. Alternatively, stopping these drug therapies may result in negative outcomes such as disease relapse, drug desensitization, bowel damage and need for surgery.
To assess the feasibility and safety of discontinuing immunosuppressant or biologic drugs, administered alone or in combination, in patients with quiescent CD.
The effects of withdrawal of immunosuppressant therapy in people with quiescent Crohn's disease are uncertain. Low quality evidence suggests that continuing azathioprine monotherapy may be superior to withdrawal for avoiding clinical relapse, while very low quality evidence suggests that there may be no difference in clinical relapse rates between discontinuing azathioprine from a combination therapy regimen, compared to continuing combination therapy. It is unclear whether withdrawal of azathioprine, initially administered alone or in combination, impacts on the development of CD-related complications, adverse events, serious adverse events or withdrawal due to adverse events. Further high-quality research is needed in this area, particularly double-blind RCTs in which biologic therapy or an immunosuppressant other than azathioprine is withdrawn.
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LOW
1
digestive system and metabolism
Does topical intranasal Cyclamen europaeum extract effectively improve clinical response in adults and children with acute sinusitis?
Acute sinusitis is a common reason for primary care encounters. It causes significant symptoms including facial pain, congested nose, headache, thick nasal mucus, fever, and cough and often results in time off work or school. Sinusitis treatment focuses on eliminating causative factors and controlling the inflammatory and infectious components. The frozen, dried, natural fluid extract of the Cyclamen europaeum plant delivered intranasally is thought to have beneficial effects in relieving congestion by facilitating nasal drainage, and has an anti-inflammatory effect.
To assess the effectiveness of topical intranasal Cyclamen europaeum extract on clinical response in adults and children with acute sinusitis.
The effectiveness of Cyclamen europaeum for people with acute sinusitis is unknown. Although no serious side effects were observed, 50% of participants who received Cyclamen europaeum reported adverse events compared with 24% of those who received placebo.
NOT ENOUGH INFORMATION
LOW
1
respiratory system
Does increasing antipsychotic dose compared to keeping the same dose improve the treatment of people with schizophrenia who have not responded to an initial antipsychotic drug trial?
Many people with schizophrenia do not reach a satisfactory clinical response with a standard dose of an initially prescribed antipsychotic drug. In such cases, clinicians face the dilemma of increasing the antipsychotic dose in order to enhance antipsychotic efficacy.
To examine the efficacy of increasing antipsychotic dose compared to keeping the same dose in the treatment of people with schizophrenia who have not responded (as defined in the individual studies) to an initial antipsychotic drug trial. We also examine the adverse effects associated with such a procedure.
Current data do not show any clear differences between increasing or maintaining the antipsychotic dose for people with schizophrenia who do not respond to their initial antipsychotic treatment. Adverse effect reporting was limited and poor. There is an urgent need for further trials in order to determine the optional treatment strategy in such cases.
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LOW
1
cognitive, mental, and mental health
Can a policy of labor induction at or beyond term reduce the risks of stillbirth or neonatal death?
Many people with schizophrenia do not respond to an initially prescribed antipsychotic drug. In such cases, one treatment strategy could be to increase the antipsychotic dose; and another strategy could be to switch to a different antipsychotic drug.
To examine the efficacy of increasing the antipsychotic dose versus switching the antipsychotic drug in the treatment of non-responsive people with schizophrenia.
There is extremely limited evidence and no clear conclusions can be drawn. There is an urgent need for further trials in order to determine the optimal treatment strategy for people with schizophrenia who do not respond to their initial antipsychotic treatment.
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LOW
1
sexual and reproductive health
Does stiripentol as add-on treatment improve efficacy and tolerability for people with focal refractory epilepsy who are taking AEDs?
This is an updated version of the Cochrane review last published in 2015 (Issue 10). For nearly 30% of people with epilepsy, seizures are not controlled by current treatments. Stiripentol is a new antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 for the treatment of Dravet syndrome as an adjunctive therapy with valproate and clobazam, with promising effects.
To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with focal refractory epilepsy who are taking AEDs.
Since the last version of this review was published, we have found no new studies. Hence, we have made no changes to the conclusions of this update as presented in the initial review. We can draw no conclusions to support the use of stiripentol as add-on treatment for focal refractory epilepsy. Additional large, randomised, well-conducted trials are needed.
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LOW
1
cognitive, mental, and mental health
Can melatonin administration improve the quantity and quality of sleep in adults in the intensive care unit?
Patients in the intensive care unit (ICU) experience sleep deprivation caused by environmental disruption, such as high noise levels and 24-hour lighting, as well as increased patient care activities and invasive monitoring as part of their care. Sleep deprivation affects physical and psychological health, and patients perceive the quality of their sleep to be poor whilst in the ICU. Artificial lighting during night-time hours in the ICU may contribute to reduced production of melatonin in critically ill patients. Melatonin is known to have a direct effect on the circadian rhythm, and it appears to reset a natural rhythm, thus promoting sleep.
To assess whether the quantity and quality of sleep may be improved by administration of melatonin to adults in the intensive care unit. To assess whether melatonin given for sleep promotion improves both physical and psychological patient outcomes.
We found insufficient evidence to determine whether administration of melatonin would improve the quality and quantity of sleep in ICU patients. We identified sparse data, and noted differences in study methodology, in ICU sedation protocols, and in methods used to measure and report sleep. We identified five ongoing studies from database and clinical trial register searches. Inclusion of data from these studies in future review updates would provide more certainty for the review outcomes.
SUPPORTED
HIGH
0
cognitive, mental, and mental health
Does methylphenidate treatment for children and adolescents with ADHD in non-randomised studies have associated adverse events?
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood. The psychostimulant methylphenidate is the most frequently used medication to treat it. Several studies have investigated the benefits of methylphenidate, showing possible favourable effects on ADHD symptoms, but the true magnitude of the effect is unknown. Concerning adverse events associated with the treatment, our systematic review of randomised clinical trials (RCTs) demonstrated no increase in serious adverse events, but a high proportion of participants suffered a range of non-serious adverse events.
To assess the adverse events associated with methylphenidate treatment for children and adolescents with ADHD in non-randomised studies.
Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children and adolescents, which often lead to withdrawal of methylphenidate. Our certainty in the evidence is very low, and accordingly, it is not possible to accurately estimate the actual risk of adverse events. It might be higher than reported here.Given the possible association between methylphenidate and the adverse events identified, it may be important to identify people who are most susceptible to adverse events. To do this we must undertake large-scale, high-quality RCTs, along with studies aimed at identifying responders and non-responders.
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LOW
1
cognitive, mental, and mental health
Can EIBI effectively improve functional behaviors and skills, decrease autism severity, and improve intelligence and communication skills for young children with ASD?
The rising prevalence of autism spectrum disorders (ASD) increases the need for evidence-based behavioral treatments to lessen the impact of symptoms on children's functioning. At present, there are no curative or psychopharmacological therapies to effectively treat all symptoms of the disorders. Early intensive behavioral intervention (EIBI) is a treatment based on the principles of applied behavior analysis. Delivered for multiple years at an intensity of 20 to 40 hours per week, it is one of the more well-established treatments for ASD. This is an update of a Cochrane review last published in 2012.
To systematically review the evidence for the effectiveness of EIBI in increasing functional behaviors and skills, decreasing autism severity, and improving intelligence and communication skills for young children with ASD.
There is weak evidence that EIBI may be an effective behavioral treatment for some children with ASD; the strength of the evidence in this review is limited because it mostly comes from small studies that are not of the optimum design. Due to the inclusion of non-randomized studies, there is a high risk of bias and we rated the overall quality of evidence as 'low' or 'very low' using the GRADE system, meaning further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.It is important that providers of EIBI are aware of the current evidence and use clinical decision-making guidelines, such as seeking the family's input and drawing upon prior clinical experience, when making recommendations to clients on the use EIBI. Additional studies using rigorous research designs are needed to make stronger conclusions about the effects of EIBI for children with ASD.
NOT ENOUGH INFORMATION
LOW
1
cognitive, mental, and mental health
Does abdominal drainage prevent intra-peritoneal abscess after open appendectomy for complicated appendicitis?
Appendectomy, the surgical removal of the appendix, is performed primarily for acute appendicitis. Patients who undergo appendectomy for complicated appendicitis, defined as gangrenous or perforated appendicitis, are more likely to suffer from postoperative complications. The routine use of abdominal drainage to reduce postoperative complications after appendectomy for complicated appendicitis is controversial.This is an update of the review first published in 2015.
To assess the safety and efficacy of abdominal drainage to prevent intra-peritoneal abscess after open appendectomy for complicated appendicitis.
The quality of the current evidence is very low. The effect of abdominal drainage on the prevention of intra-peritoneal abscess or wound infection after open appendectomy is uncertain for patients with complicated appendicitis. The increased rates for overall complication rate and hospital stay for the drainage group compared to no drainage group is also subject to great uncertainty. Thus, there is no evidence for any clinical improvement by using abdominal drainage in patients undergoing open appendectomy for complicated appendicitis. The increased risk of mortality with drainage comes from eight deaths observed in just under 400 people recruited to the studies. Larger studies are needed to determine the effects of drainage on morbidity and mortality outcomes more reliably.
NOT ENOUGH INFORMATION
LOW
1
digestive system and metabolism
Does bilateral grommet insertion with or without concurrent adenoidectomy benefit children with rAOM?
Acute otitis media (AOM) is one of the most common childhood illnesses. While many children experience sporadic AOM episodes, an important group suffer from recurrent AOM (rAOM), defined as three or more episodes in six months, or four or more in one year. In this subset of children AOM poses a true burden through frequent episodes of ear pain, general illness, sleepless nights and time lost from nursery or school. Grommets, also called ventilation or tympanostomy tubes, can be offered for rAOM.
To assess the benefits and harms of bilateral grommet insertion with or without concurrent adenoidectomy in children with rAOM.
Current evidence on the effectiveness of grommets in children with rAOM is limited to five RCTs with unclear or high risk of bias, which were conducted prior to the introduction of pneumococcal vaccination. Low to very low-quality evidence suggests that children receiving grommets are less likely to have AOM recurrences compared to those managed by active monitoring and placebo medication, but the magnitude of the effect is modest with around one fewer episode at six months and a less noticeable effect by 12 months. The low to very low quality of the evidence means that these numbers need to be interpreted with caution since the true effects may be substantially different. It is uncertain whether or not grommets are more effective than antibiotic prophylaxis. The risk of persistent tympanic membrane perforation after grommet insertion was low.Widespread use of pneumococcal vaccination has changed the bacteriology and epidemiology of AOM, and how this might impact the results of prior trials is unknown. New and high-quality RCTs of grommet insertion in children with rAOM are therefore needed. These trials should not only focus on the frequency of AOM recurrences, but also collect data on the severity of AOM episodes, antibiotic consumption and adverse effects of both surgery and antibiotics. This is particularly important since grommets may reduce the severity of AOM recurrences and allow for topical rather than oral antibiotic treatment.
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ear, nose, and throat
Can acupuncture reduce pain or improve function in people with hip osteoarthritis?
Beyond term, the risks of stillbirth or neonatal death increase. It is unclear whether a policy of labour induction can reduce these risks. This Cochrane review is an update of a review that was originally published in 2006 and subsequently updated in 2012 OBJECTIVES: To assess the effects of a policy of labour induction at or beyond term compared with a policy of awaiting spontaneous labour or until an indication for birth induction of labour is identified) on pregnancy outcomes for infant and mother.
Search methods:
A policy of labour induction at or beyond term compared with expectant management is associated with fewer perinatal deaths and fewer caesarean sections; but more operative vaginal births. NICU admissions were lower and fewer babies had low Apgar scores with induction. No important differences were seen for most of the other maternal and infant outcomes.Most of the important outcomes assessed using GRADE had a rating of moderate or low-quality evidence - with downgrading decisions generally due to study limitations such as lack of blinding (a condition inherent in comparisons between a policy of acting and of waiting), or imprecise effect estimates. One outcome (length of maternal stay) was downgraded further to very low-quality evidence due to inconsistency.Although the absolute risk of perinatal death is small, it may be helpful to offer women appropriate counselling to help choose between scheduled induction for a post-term pregnancy or monitoring without (or later) induction).The optimal timing of offering induction of labour to women at or beyond term warrants further investigation, as does further exploration of risk profiles of women and their values and preferences. Individual participant meta-analysis is likely to help elucidate the role of factors, such as parity, in influencing outcomes of induction compared with expectant management.
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musculoskeletal system and dermatology
Can prophylactic HPV vaccines protect against cervical precancer and HPV16/18 infection?
Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide.
To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women.
There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.
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sexual and reproductive health
Can interventions improve adherence to iron chelation therapy in people with SCD or thalassaemia?
Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia (who are transfusion-dependent or non-transfusion-dependent) are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands; which can be prevented and treated with iron chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and well-being, which may affect adherence.
To identify and assess the effectiveness of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) to improve adherence to iron chelation therapy in people with SCD or thalassaemia.
The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects.Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation.Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy.Due to lack of evidence this review cannot comment on intervention strategies for different age groups.
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blood and lymphatic system
Does face-to-face intervention impact early childhood vaccination status and parental knowledge, attitudes, and intention to vaccinate?
Early childhood vaccination is an essential global public health practice that saves two to three million lives each year, but many children do not receive all the recommended vaccines. To achieve and maintain appropriate coverage rates, vaccination programmes rely on people having sufficient awareness and acceptance of vaccines.Face-to-face information or educational interventions are widely used to help parents understand why vaccines are important; explain where, how and when to access services; and address hesitancy and concerns about vaccine safety or efficacy. Such interventions are interactive, and can be adapted to target particular populations or identified barriers.This is an update of a review originally published in 2013.
To assess the effects of face-to-face interventions for informing or educating parents about early childhood vaccination on vaccination status and parental knowledge, attitudes and intention to vaccinate.
There is low- to moderate-certainty evidence suggesting that face-to-face information or education may improve or slightly improve children's vaccination status, parents' knowledge, and parents' intention to vaccinate.Face-to-face interventions may be more effective in populations where lack of awareness or understanding of vaccination is identified as a barrier (e.g. where people are unaware of new or optional vaccines). The effect of the intervention in a population where concerns about vaccines or vaccine hesitancy is the primary barrier is less clear. Reliable and validated scales for measuring more complex outcomes, such as attitudes or beliefs, are necessary in order to improve comparisons of the effects across studies.
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immune system and infections
Are the currently available treatment options beneficial for treating HCV-associated mixed cryoglobulinaemia with active manifestations of vasculitis?
Hepatitis C virus (HCV)-associated mixed cryoglobulinaemia is the manifestation of an inflammation of small and medium-sized vessels produced by a pathogenic IgM with rheumatoid factor activity generated by an expansion of B-cells. The immune complexes formed precipitate mainly in the skin, joints, kidneys or peripheral nerve fibres. Current therapeutic approaches are aimed at elimination of HCV infection, removal of cryoglobulins and also of the B-cell clonal expansions. The optimal treatment for it has not been established.
This review aims to look at the benefits and harms of the currently available treatment options to treat the HCV-associated mixed cryoglobulinaemia with active manifestations of vasculitis (cutaneous or glomerulonephritis).
To treat HCV-associated mixed cryoglobulinaemia, it may be beneficial to eliminate HCV infection by using antiviral treatment and to stop the immune response by using rituximab. For skin vasculitis and for some laboratory findings, it may be appropriate to combine antiviral treatment with deletion of B-cell clonal expansions by using of rituximab. The applicability of evidence reviewed here is limited by the absence of any studies with direct-acting antivirals, which are urgently needed to guide therapy.
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immune system and infections
Do stroke service interventions for implementing secondary stroke prevention strategies affect modifiable risk factor control and occurrence of secondary cardiovascular events?
People with stroke or transient ischaemic attack (TIA) are at increased risk of future stroke and other cardiovascular events. Stroke services need to be configured to maximise the adoption of evidence-based strategies for secondary stroke prevention. Smoking-related interventions were examined in a separate review so were not considered in this review. This is an update of our 2014 review.
To assess the effects of stroke service interventions for implementing secondary stroke prevention strategies on modifiable risk factor control, including patient adherence to prescribed medications, and the occurrence of secondary cardiovascular events.
We found that organisational interventions may be associated with an improvement in achieving blood pressure target but we did not find any clear evidence that these interventions improve other modifiable risk factors (lipid profile, HbA1c, medication adherence) or reduce the incidence of recurrent cardiovascular events. Interventions, including patient education alone, did not lead to improvements in modifiable risk factor control or the prevention of recurrent cardiovascular events.
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cardiovascular system
Does acupuncture provide benefits for patients with hip OA?
Hip osteoarthritis (OA) is a major cause of pain and functional limitation. Few hip OA treatments have been evaluated for safety and effectiveness. Acupuncture is a traditional Chinese medical therapy which aims to treat disease by inserting very thin needles at specific points on the body.
To assess the benefits and harms of acupuncture in patients with hip OA.
Acupuncture probably has little or no effect in reducing pain or improving function relative to sham acupuncture in people with hip osteoarthritis. Due to the small sample size in the studies, the confidence intervals include both the possibility of moderate benefits and the possibility of no effect of acupuncture. One unblinded trial found that acupuncture as an addition to routine primary physician care was associated with benefits on pain and function. However, these reported benefits are likely due at least partially to RCT participants' greater expectations of benefit from acupuncture. Possible side effects associated with acupuncture treatment were minor.
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musculoskeletal system and dermatology
Can pharmacotherapies effectively treat apathy in Alzheimer's disease?
Despite the high prevalence of apathy in Alzheimer's disease (AD), and its harmful effects, there are currently no therapies proven to treat this symptom. Recently, a number of pharmacological therapies have been investigated as potential treatments for apathy in AD.
Objective 1: To assess the safety and efficacy of pharmacotherapies for the treatment of apathy in Alzheimer's disease (AD).Objective 2: To assess the effect on apathy of pharmacotherapies investigated for other primary outcomes in the treatment of AD.
Methylphenidate may demonstrate a benefit for apathy and may have slight benefits for cognition and functional performance in people with AD, but this finding is associated with low-quality evidence. Our meta-analysis is limited by the small number of studies within each drug class, risk of bias, publication bias, imprecision and inconsistency between studies. Additional studies should be encouraged targeting people with AD with clinically significant apathy which investigate apathy as a primary outcome measure, and which have a longer duration and a larger sample size. This could increase the quality of evidence for methylphenidate, and may confirm whether or not it is an effective pharmacotherapy for apathy in AD.
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cognitive, mental, and mental health
Does the initial oxygen concentration during the resuscitation of preterm infants at birth affect short- and long-term mortality and morbidity?
Initial resuscitation with air is well tolerated by most infants born at term. However, the optimal fractional inspired oxygen concentration (FiO
To determine whether lower or higher initial oxygen concentrations, when titrated according to oxygen saturation targets during the resuscitation of preterm infants at birth, lead to improved short- and long-term mortality and morbidity.
There is uncertainty as to whether initiating post birth resuscitation in preterm infants using lower (FiO
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respiratory system
Is clonazepam effective and tolerable as an add-on therapy for refractory epileptic seizures?
Epilepsy affects about 50 million people worldwide, nearly a quarter of whom have drug-refractory epilepsy. People with drug-refractory epilepsy have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life.
To assess the efficacy and tolerability of clonazepam when used as an add-on therapy for adults and children with refractory focal onset or generalised onset epileptic seizures, when compared with placebo or another antiepileptic agent.
There is no evidence from double-blind randomised controlled trials for or against the use of clonazepam as an add-on therapy for adults and children with refractory focal or generalised onset epileptic seizures.
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cognitive, mental, and mental health
Does different platelet transfusion thresholds prior to a lumbar puncture or epidural anaesthesia affect people with thrombocytopenia?
People with a low platelet count (thrombocytopenia) often require lumbar punctures or an epidural anaesthetic. Lumbar punctures can be diagnostic (haematological malignancies, subarachnoid haematoma, meningitis) or therapeutic (spinal anaesthetic, administration of chemotherapy). Epidural catheters are placed for administration of epidural anaesthetic. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to lumbar punctures and epidural anaesthesia, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to these procedures varies significantly from country to country. This indicates significant uncertainty among clinicians regarding the correct management of these patients. The risk of bleeding appears to be low, but if bleeding occurs it can be very serious (spinal haematoma). Consequently, people may be exposed to the risks of a platelet transfusion without any obvious clinical benefit.This is an update of a Cochrane Review first published in 2016.
To assess the effects of different platelet transfusion thresholds prior to a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count).
We found no evidence from RCTs or non-randomised studies on which to base an assessment of the correct platelet transfusion threshold prior to insertion of a lumbar puncture needle or epidural catheter. There are no ongoing registered RCTs assessing the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia. Any future study would need to be very large to detect a difference in the risk of bleeding. A study would need to be designed with at least 47,030 participants to be able to detect an increase in the number of people who had major procedure-related bleeding from 1 in 1000 to 2 in 1000. The use of a central data collection register or routinely collected electronic records (big data) is likely to be the only method to systematically gather data relevant to this population.
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miscellaneous
Can rufinamide be effective as an add-on treatment for refractory epilepsy?
Identification of the causes of stillbirth is critical to the primary prevention of stillbirth and to the provision of optimal care in subsequent pregnancies. A wide variety of investigations are available, but there is currently no consensus on the optimal approach. Given their cost and potential to add further emotional burden to parents, there is a need to systematically assess the effect of these interventions on outcomes for parents, including psychosocial outcomes, economic costs, and on rates of diagnosis of the causes of stillbirth.
To assess the effect of different tests, protocols or guidelines for investigating and identifying the causes of stillbirth on outcomes for parents, including psychosocial outcomes, economic costs, and rates of diagnosis of the causes of stillbirth.
There is currently a lack of RCT evidence regarding the effectiveness of interventions for investigating and identifying the causes of stillbirth. Seeking to determine the causes of stillbirth is an essential component of quality maternity care, but it remains unclear what impact these interventions have on the psychosocial outcomes of parents and families, the rates of diagnosis of the causes of stillbirth, and the care and management of subsequent pregnancies following stillbirth. Due to the absence of trials, this review is unable to inform clinical practice regarding the investigation of stillbirths, and the specific investigations that would determine the causes.Future RCTs addressing this research question would be beneficial, but the settings in which the trials take place, and their design, need to be given careful consideration. Trials need to be conducted with the utmost care and consideration for the needs, concerns, and values of parents and families. Assessment of longer-term psychosocial variables, economic costs to health services, and effects on subsequent pregnancy care and outcomes should also be considered in any future trials.
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cognitive, mental, and mental health
Can primary preventive interventions and strategies prevent OIHD in healthy people at risk of skin damage?
Occupational irritant hand dermatitis (OIHD) causes significant functional impairment, disruption of work, and discomfort in the working population. Different preventive measures such as protective gloves, barrier creams and moisturisers can be used, but it is not clear how effective these are. This is an update of a Cochrane review which was previously published in 2010.
To assess the effects of primary preventive interventions and strategies (physical and behavioural) for preventing OIHD in healthy people (who have no hand dermatitis) who work in occupations where the skin is at risk of damage due to contact with water, detergents, chemicals or other irritants, or from wearing gloves.
Moisturisers used alone or in combination with barrier creams may result in a clinically important protective effect, either in the long- or short-term, for the primary prevention of OIHD. Barrier creams alone may have slight protective effect, but this does not appear to be clinically important. The results for all of these comparisons were imprecise, and the low quality of the evidence means that our confidence in the effect estimates is limited. For skin protection education, the results varied substantially across the trials, the effect was imprecise, and the pooled risk reduction was not large enough to be clinically important. The very low quality of the evidence means that we are unsure as to whether skin protection education reduces the risk of developing OIHD. The interventions probably cause few or no serious adverse effects.We conclude that at present there is insufficient evidence to confidently assess the effectiveness of interventions used in the primary prevention of OIHD. This does not necessarily mean that current measures are ineffective. Even though the update of this review included larger studies of reasonable quality, there is still a need for trials which apply standardised measures for the detection of OIHD in order to determine the effectiveness of the different prevention strategies.
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cardiovascular system
Is follicular flushing more effective than aspiration only in women undergoing ART?
Follicular aspiration under transvaginal ultrasound guidance is routinely performed as part of assisted reproductive technology (ART) to retrieve oocytes for in vitro fertilisation (IVF). However, controversy as to whether follicular flushing following aspiration yields a larger number of oocytes and hence is associated with greater potential for pregnancy than aspiration only is ongoing.
To assess the safety and efficacy of follicular flushing as compared with aspiration only performed in women undergoing ART.
This review suggests that follicular flushing probably has little or no effect on live birth rates compared with aspiration alone. None of the included trials reported on effects of follicular aspiration and flushing on the miscarriage rate. Data suggest little or no difference between follicular flushing and aspiration alone with respect to oocyte yield, total embryo number, or number of cryopreserved embryos. In addition, follicular flushing probably makes little or no difference in the clinical pregnancy rate. Evidence was insufficient to allow any firm conclusions with respect to adverse events or safety.
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sexual and reproductive health
Can cyclodestructive procedures effectively and safely manage non-refractory glaucoma?
Glaucoma is a leading cause of blindness worldwide. It results in a progressive loss of peripheral vision and, in late stages, loss of central vision leading to blindness. Early treatment of glaucoma aims to prevent or delay vision loss. Elevated intraocular pressure (IOP) is the main causal modifiable risk factor for glaucoma. Aqueous outflow obstruction is the main cause of IOP elevation, which can be mitigated either by increasing outflow or reducing aqueous humor production. Cyclodestructive procedures use various methods to target and destroy the ciliary body epithelium, the site of aqueous humor production, thereby lowering IOP. The most common approach is laser cyclophotocoagulation.
To assess the effectiveness and safety of cyclodestructive procedures for the management of non-refractory glaucoma (i.e. glaucoma in an eye that has not undergone incisional glaucoma surgery). We also aimed to compare the effect of different routes of administration, laser delivery instruments, and parameters of cyclophotocoagulation with respect to IOP control, visual acuity, pain control, and adverse events.
There is insufficient evidence to evaluate the relative effectiveness and safety of cyclodestructive procedures for the primary procedural management of non-refractory glaucoma. Results from the one included trial did not compare cyclophotocoagulation to other procedural interventions and yielded uncertainty about any difference in outcomes when comparing low-energy versus high-energy diode TSCPC. Overall, the effect of laser treatment on IOP control was modest and the number of eyes experiencing vision loss was limited. More research is needed specific to the management of non-refractory glaucoma.
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MEDIUM
0
sensory organs
Does local anaesthetics and regional anaesthesia prevent PPP beyond three months compared to conventional analgesia in adults and children undergoing elective surgery?
Regional anaesthesia may reduce the rate of persistent postoperative pain (PPP), a frequent and debilitating condition. This review was originally published in 2012 and updated in 2017.
To compare local anaesthetics and regional anaesthesia versus conventional analgesia for the prevention of PPP beyond three months in adults and children undergoing elective surgery.
We conclude that there is moderate-quality evidence that regional anaesthesia may reduce the risk of developing PPP after three to 18 months after thoracotomy and three to 12 months after caesarean section. There is low-quality evidence that regional anaesthesia may reduce the risk of developing PPP three to 12 months after breast cancer surgery. There is moderate evidence that intravenous infusion of local anaesthetics may reduce the risk of developing PPP three to six months after breast cancer surgery.Our conclusions are considerably weakened by the small size and number of studies, by performance bias, null bias, attrition and missing data. Larger, high-quality studies, including children, are needed. We caution that except for breast surgery, our evidence synthesis is based on only a few small studies. On a cautionary note, we cannot extend our conclusions to other surgical interventions or regional anaesthesia techniques, for example we cannot conclude that paravertebral block reduces the risk of PPP after thoracotomy. There are seven ongoing studies and 12 studies awaiting classification that may change the conclusions of the current review once they are published and incorporated.
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cancer
Is there an effective uterotonic drug to prevent PPH?
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can prevent PPH, and are routinely recommended. There are several uterotonic drugs for preventing PPH but it is still debatable which drug is best.
To identify the most effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile.
Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination were more effective for preventing PPH ≥ 500 mL than the current standard oxytocin. Ergometrine plus oxytocin combination was more effective for preventing PPH ≥ 1000 mL than oxytocin. Misoprostol plus oxytocin combination evidence is less consistent and may relate to different routes and doses of misoprostol used in the studies. Carbetocin had the most favourable side-effect profile amongst the top three options; however, most carbetocin trials were small and at high risk of bias.Amongst the 11 ongoing studies listed in this review there are two key studies that will inform a future update of this review. The first is a WHO-led multi-centre study comparing the effectiveness of a room temperature stable carbetocin versus oxytocin (administered intramuscularly) for preventing PPH in women having a vaginal birth. The trial includes around 30,000 women from 10 countries. The other is a UK-based trial recruiting more than 6000 women to a three-arm trial comparing carbetocin, oxytocin and ergometrine plus oxytocin combination. Both trials are expected to report in 2018.Consultation with our consumer group demonstrated the need for more research into PPH outcomes identified as priorities for women and their families, such as women's views regarding the drugs used, clinical signs of excessive blood loss, neonatal unit admissions and breastfeeding at discharge. To date, trials have rarely investigated these outcomes. Consumers also considered the side-effects of uterotonic drugs to be important but these were often not reported. A forthcoming set of core outcomes relating to PPH will identify outcomes to prioritise in trial reporting and will inform futures updates of this review. We urge all trialists to consider measuring these outcomes for each drug in all future randomised trials. Lastly, future evidence synthesis research could compare the effects of different dosages and routes of administration for the most effective drugs.
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sexual and reproductive health
Can smectite be effective for treating acute infectious diarrhea in children?
As mortality secondary to acute infectious diarrhoea has decreased worldwide, the focus shifts to adjuvant therapies to lessen the burden of disease. Smectite, a medicinal clay, could offer a complementary intervention to reduce the duration of diarrhoea.
To assess the effects of smectite for treating acute infectious diarrhoea in children.
Based on low-certainty evidence, smectite used as an adjuvant to rehydration therapy may reduce the duration of diarrhoea in children with acute infectious diarrhoea by a day; may increase cure rate by day 3; and may reduce stool output, but has no effect on hospitalization rates or need for intravenous therapy.
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digestive system and metabolism
Is rufinamide as an add-on treatment effective in people with refractory epilepsy?
Epilepsy is a central nervous system disorder (neurological disorder). Epileptic seizures are the result of excessive and abnormal cortical nerve cell electrical activity in the brain. Despite the development of more than 10 new antiepileptic drugs (AEDs) since the early 2000s, approximately a third of people with epilepsy remain resistant to pharmacotherapy, often requiring treatment with a combination of AEDs. In this review, we summarised the current evidence regarding rufinamide, a novel anticonvulsant medication, which, as a triazole derivative, is structurally unrelated to any other currently used anticonvulsant medication, when used as an add-on treatment for refractory epilepsy. In January 2009, rufinamide was approved by the US Food and Drug Administration for treatment of children four years of age and older with Lennox-Gastaut syndrome. It is also approved as an add-on treatment for adults and adolescents with focal seizures.
To evaluate the efficacy and tolerability of rufinamide when used as an add-on treatment in people with refractory epilepsy.
In people with drug-resistant focal epilepsy, rufinamide when used as an add-on treatment was effective in reducing seizure frequency. However, the trials reviewed were of relatively short duration and provided no evidence for the long-term use of rufinamide. In the short term, rufinamide as an add-on was associated with several adverse events. This review focused on the use of rufinamide in drug-resistant focal epilepsy and the results cannot be generalised to add-on treatment for generalised epilepsies. Likewise, no inference can be made about the effects of rufinamide when used as monotherapy.
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LOW
0
cognitive, mental, and mental health
Do antidepressants offer benefits for the treatment of people with co-occurring depression and alcohol dependence?
Alcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co-occurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes.
To assess the benefits and risks of antidepressants for the treatment of people with co-occurring depression and alcohol dependence.
We found low-quality evidence supporting the clinical use of antidepressants in the treatment of people with co-occurring depression and alcohol dependence. Antidepressants had positive effects on certain relevant outcomes related to depression and alcohol use but not on other relevant outcomes. Moreover, most of these positive effects were no longer significant when studies with high risk of bias were excluded. Results were limited by the large number of studies showing high or unclear risk of bias and the low number of studies comparing one antidepressant to another or antidepressants to other medication. In people with co-occurring depression and alcohol dependence, the risk of developing adverse effects appeared to be minimal, especially for the newer classes of antidepressants (such as selective serotonin reuptake inhibitors). According to these results, in people with co-occurring depression and alcohol dependence, antidepressants may be useful for the treatment of depression, alcohol dependence, or both, although the clinical relevance may be modest.
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cognitive, mental, and mental health
Did system-wide interventions decrease the incidence of VTE in hospitalized adult medical and surgical patients at risk for VTE?
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. While numerous randomized controlled trials (RCTs) have shown that the appropriate use of thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective, and cost-effective, thromboprophylaxis remains underused or inappropriately used. Our previous review suggested that system-wide interventions, such as education, alerts, and multifaceted interventions were more effective at improving the prescribing of thromboprophylaxis than relying on individual providers' behaviors. However, 47 of the 55 included studies in our previous review were observational in design. Thus, an update to our systematic review, focused on the higher level of evidence of RCTs only, was warranted.
To assess the effects of system-wide interventions designed to increase the implementation of thromboprophylaxis and decrease the incidence of VTE in hospitalized adult medical and surgical patients at risk for VTE, focusing on RCTs only.
We reviewed RCTs that implemented a variety of system-wide strategies aimed at improving thromboprophylaxis in hospitalized patients. We found increased prescription of prophylaxis associated with alerts and multifaceted interventions, and increased prescription of appropriate prophylaxis associated with alerts. While multifaceted interventions were found to be less effective than alerts, a multifaceted intervention with an alert was more effective than one without an alert. Alerts, particularly computer alerts, were associated with a reduction in symptomatic VTE at three months, although there were not enough studies to pool computer alerts and human alerts results separately.Our analysis was underpowered to assess the effect on mortality and safety outcomes, such as bleeding.The incomplete reporting of relevant study design features did not allow complete assessment of the certainty of the evidence. However, the certainty of the evidence for improvement in outcomes was judged to be better than for our previous review (low- to moderate-certainty evidence, compared to very low-certainty evidence for most outcomes). The results of our updated review will help physicians, hospital administrators, and policy makers make practical decisions about adopting specific system-wide measures to improve prescription of thromboprophylaxis, and ultimately prevent VTE in hospitalized patients.
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cardiovascular system
Can pharmacological interventions prevent insufficiency fractures and avascular necrosis in adults undergoing pelvic radiotherapy?
Postural drainage is used primarily in infants with cystic fibrosis from diagnosis up to the moment when they are mature enough to actively participate in self-administered treatments. However, there is a risk of gastroesophageal reflux associated with this technique.This is an update of a review published in 2015.
To compare the effects of standard postural drainage (15º to 45º head-down tilt) with modified postural drainage (15º to 30º head-up tilt) with regard to gastroesophageal reflux in infants and young children up to six years old with cystic fibrosis in terms of safety and efficacy.
The limited evidence regarding the comparison between the two regimens of postural drainage is still weak due to the small number of included studies, the small number of participants assessed, the inability to perform any meta-analyses and some methodological issues with the studies. However, it may be inferred that the use of a postural regimen with a 30° head-up tilt is associated with a lower number of gastroesophageal reflux episodes and fewer respiratory complications in the long term. The 20° head-down postural drainage position was not found to be significantly different from the 20° head-up tilt modified position. Nevertheless, the fact that the majority of reflux episodes reached the upper oesophagus should make physiotherapists carefully consider their treatment strategy. We do not envisage that there will be any new trials undertaken that will affect the conclusions of this review; therefore, we do not plan to update this review.
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MEDIUM
0
musculoskeletal system and dermatology
Can antidepressants effectively treat depressive symptoms in adults with cancer?
Pelvic radiotherapy is a treatment delivered to an estimated 150,000 to 300,000 people annually across high-income countries. Fractures due to normal stresses on weakened bone due to radiotherapy are termed insufficiency fractures. Pelvic radiotherapy-related interruption of the blood supply to the hip is termed avascular necrosis and is another recognised complication. The reported incidences of insufficiency fractures are 2.7% to 89% and risk of developing avascular necrosis is 0.5%. These complications lead to significant morbidity in terms of pain, immobility and consequently risk of infections, pressure sores and mortality.
To assess the effects of pharmacological interventions for preventing insufficiency fractures and avascular necrosis in adults over 18 years of age undergoing pelvic radiotherapy.
The evidence relating to interventions to prevent insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults is of very low certainty. This review highlights the need for prospective clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis. Future trials could involve prospective assessment of bone health including BMD and bone turnover markers prior to pelvic radiotherapy. The interventions for investigation could begin as radiotherapy commences and remain ongoing for 12 to 24 months. Bone turnover markers and BMD could be used as surrogate markers for bone health in addition to radiographic imaging to report on presence of insufficiency fractures and development of avascular necrosis. Clinical assessments and patient reported outcomes would help to identify any associated adverse effects of treatment and quality of life outcomes.
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cancer