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Lavita AI 17

Do low-carbohydrate weight-reducing diets have different effects on weight and cardiovascular risk compared to weight-reducing diets with balanced ranges of carbohydrates?

Debates on effective and safe diets for managing obesity in adults are ongoing. Low-carbohydrate weight-reducing diets (also known as 'low-carb diets') continue to be widely promoted, marketed and commercialised as being more effective for weight loss, and healthier, than 'balanced'-carbohydrate weight-reducing diets.

To compare the effects of low-carbohydrate weight-reducing diets to weight-reducing diets with balanced ranges of carbohydrates, in relation to changes in weight and cardiovascular risk, in overweight and obese adults without and with type 2 diabetes mellitus (T2DM).

there is probably little to no difference in weight reduction and changes in cardiovascular risk factors up to two years' follow-up, when overweight and obese participants without and with t2dm are randomised to either low-carbohydrate or balanced-carbohydrate weight-reducing diets.

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nutrition and dietary supplements

Did IL-1 blocking agents show beneficial effects compared to standard care or placebo in people with COVID-19?

Interleukin-1 (IL-1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19), on the premise that their immunomodulatory effect might be beneficial in people with COVID-19.

To assess the effects of IL-1 blocking agents compared with standard care alone or with placebo on effectiveness and safety outcomes in people with COVID-19. We will update this assessment regularly.

Overall, we did not find evidence for an important beneficial effect of IL-1 blocking agents. The evidence is uncertain or very uncertain for several outcomes. Sixteen trials of anakinra and canakinumab with no results are currently registered, of which four are completed, and four terminated. The findings of this review are updated on the COVID-NMA platform (covid-nma.com).

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immune system and infections

Does cephalomedullary nails show better effects than extramedullary fixation implants for treating extracapsular hip fractures in older adults?

Hip fractures are a major healthcare problem, presenting a substantial challenge and burden to patients, healthcare systems and society. The increased proportion of older adults in the world population means that the absolute number of hip fractures is rising rapidly across the globe. Most hip fractures are treated surgically. This Cochrane Review evaluates evidence for implants used to treat extracapsular hip fractures.

To assess the relative effects of cephalomedullary nails versus extramedullary fixation implants for treating extracapsular hip fractures in older adults.

Extramedullary devices, most commonly the sliding hip screw, yield very similar functional outcomes to cephalomedullary devices in the management of extracapsular fragility hip fractures. There is a reduced risk of infection and non-union with cephalomedullary nails, however there is an increased risk of implant-related fracture that is not attenuated with newer designs. Few studies considered patient-relevant outcomes such as performance of activities of daily living, health-related quality of life, mobility, or delirium. This emphasises the need to include the core outcome set for hip fracture in future RCTs.

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musculoskeletal system and dermatology

Do foot orthoses benefit the treatment of paediatric flat feet?

Paediatric flat feet are a common presentation in primary care; reported prevalence approximates 15%. A minority of flat feet can hurt and limit gait. There is no optimal strategy, nor consensus, for using foot orthoses (FOs) to treat paediatric flat feet.

To assess the benefits and harms of foot orthoses for treating paediatric flat feet.

Low to very low-certainty evidence shows that the effect of CFOs (high cost) or PFOs (low cost) versus shoes, and CFOs versus PFOs on pain, function and HRQoL is uncertain. This is pertinent for clinical practice, given the economic disparity between CFOs and PFOs. FOs may improve pain and function, versus shoes in children with JIA, with minimal delineation between costly CFOs and generic PFOs. This review updates that from 2010, confirming that in the absence of pain, the use of high-cost CFOs for healthy children with flexible flat feet has no supporting evidence, and draws very limited conclusions about FOs for treating paediatric flat feet. The availability of normative and prospective foot development data, dismisses most flat foot concerns, and negates continued attention to this topic. Attention should be re-directed to relevant paediatric foot conditions, which cause pain, limit function, or reduce quality of life. The agenda for researching asymptomatic flat feet in healthy children must be relegated to history, and replaced by a targeted research rationale, addressing children with indisputable foot pathology from discrete diagnoses, namely JIA, cerebral palsy, congenital talipes equino varus, trisomy 21 and Charcot Marie Tooth. Whether research resources should continue to be wasted on studying flat feet in healthy children that do not hurt, is questionable. Future updates of this review will address only relevant paediatric foot conditions.

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musculoskeletal system and dermatology

Does ultrafiltration have better clinical outcomes compared to diuretic therapy for acute heart failure?

Pharmacotherapies such as loop diuretics are the cornerstone treatment for acute heart failure (AHF), but resistance and poor response can occur. Ultrafiltration (UF) is an alternative therapy to reduce congestion, however its benefits, efficacy and safety are unclear.

To assess the effects of UF compared to diuretic therapy on clinical outcomes such as mortality and rehospitalisation rates.

Trial registration:

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cardiovascular system

Did the combination of antihistamine-decongestant-analgesic reduce the duration of symptoms and alleviate symptoms in children and adults with the common cold?

Although combination formulas containing antihistamines, decongestants, and/or analgesics are sold over-the-counter in large quantities for the common cold, the evidence for their effectiveness is limited. This is an update of a review first published in 2012.

To assess the effectiveness of antihistamine-decongestant-analgesic combinations compared with placebo or other active controls (excluding antibiotics) in reducing the duration of symptoms and alleviating symptoms (general feeling of illness, nasal congestion, rhinorrhoea, sneezing, and cough) in children and adults with the common cold.

We found a lack of data on the effectiveness of antihistamine-analgesic-decongestant combinations for the common cold. Based on these scarce data, the effect on individual symptoms is probably too small to be clinically relevant. The current evidence suggests that antihistamine-analgesic-decongestant combinations have some general benefit in adults and older children. These benefits must be weighed against the risk of adverse effects. There is no evidence of effectiveness in young children. In 2005, the US Food and Drug Administration issued a warning about adverse effects associated with the use of over-the-counter nasal preparations containing phenylpropanolamine.

SUPPORTED

MEDIUM

respiratory system

Does delayed introduction of progressive enteral feeds affect the risk of necrotising enterocolitis, mortality, and other morbidities in very preterm or VLBW infants?

Enteral feeding for very preterm or very low birth weight (VLBW) infants is often delayed for several days after birth due to concern that early introduction of feeding may not be tolerated and may increase the risk of necrotising enterocolitis. Concerns exist, however, that delaying enteral feeding may diminish the functional adaptation of the gastrointestinal tract and prolong the need for parenteral nutrition with its attendant infectious and metabolic risks.

To determine the effects of delayed introduction of progressive enteral feeds on the risk of necrotising enterocolitis, mortality and other morbidities in very preterm or VLBW infants.

delaying the introduction of progressive enteral feeds beyond four days after birth (compared with earlier introduction) may not reduce the risk of necrotising enterocolitis or death in very preterm or vlbw infants. delayed introduction may slightly reduce feed intolerance, and probably increases the risk of invasive infection.

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digestive system and metabolism

Can additionally implementing IRS, using non-pyrethroid-like or pyrethroid-like insecticides, improve malaria control in communities currently using ITNs?

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are used to prevent malaria transmission. Both interventions use insecticides to kill mosquitoes that bite and rest indoors. Adding IRS to ITNs may improve malaria control simply because two interventions can be better than one. Furthermore, IRS may improve malaria control where ITNs are failing due to insecticide resistance. Pyrethroid insecticides are the predominant class of insecticide used for ITNs, as they are more safe than other insecticide classes when in prolonged contact with human skin. While many mosquito populations have developed some resistance to pyrethroid insecticides, a wider range of insecticides can be used for IRS. This review is an update of the previous Cochrane 2019 edition.

To summarize the effect on malaria of additionally implementing IRS, using non-pyrethroid-like or pyrethroid-like insecticides, in communities currently using ITNs.

in communities using ITNs, the addition of IRS with 'non-pyrethroid-like' insecticides was associated with reduced malaria prevalence. Malaria incidence may also be reduced on average, but there was unexplained qualitative heterogeneity, and the effect may therefore not be observed in all settings. When using 'pyrethroid-like' insecticides, there was no detectable additional benefit of IRS in communities using ITNs.

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immune system and infections

Did the measures implemented in school settings effectively control the spread of COVID-19?

In response to the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the impact of coronavirus disease 2019 (COVID-19), governments have implemented a variety of measures to control the spread of the virus and the associated disease. Among these, have been measures to control the pandemic in primary and secondary school settings.

To assess the effectiveness of measures implemented in the school setting to safely reopen schools, or keep schools open, or both, during the COVID-19 pandemic, with particular focus on the different types of measures implemented in school settings and the outcomes used to measure their impacts on transmission-related outcomes, healthcare utilisation outcomes, other health outcomes as well as societal, economic, and ecological outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Educational Resources Information Center, as well as COVID-19-specific databases, including the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease (indexing preprints) on 9 December 2020. We conducted backward-citation searches with existing reviews.

Our review suggests that a broad range of measures implemented in the school setting can have positive impacts on the transmission of SARS-CoV-2, and on healthcare utilisation outcomes related to COVID-19. The certainty of the evidence for most intervention-outcome combinations is very low, and the true effects of these measures are likely to be substantially different from those reported here. Measures implemented in the school setting may limit the number or proportion of cases and deaths, and may delay the progression of the pandemic. However, they may also lead to negative unintended consequences, such as fewer days spent in school (beyond those intended by the intervention). Further, most studies assessed the effects of a combination of interventions, which could not be disentangled to estimate their specific effects. Studies assessing measures to reduce contacts and to make contacts safer consistently predicted positive effects on transmission and healthcare utilisation, but may reduce the number of days students spent at school. Studies assessing surveillance and response measures predicted reductions in hospitalisations and school days missed due to infection or quarantine, however, there was mixed evidence on resources needed for surveillance. Evidence on multicomponent measures was mixed, mostly due to comparators. The magnitude of effects depends on multiple factors. New studies published since the original search date might heavily influence the overall conclusions and interpretation of findings for this review.

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MEDIUM

immune system and infections

Do foot orthoses provide benefits for treating paediatric flat feet?

Paediatric flat feet are a common presentation in primary care; reported prevalence approximates 15%. A minority of flat feet can hurt and limit gait. There is no optimal strategy, nor consensus, for using foot orthoses (FOs) to treat paediatric flat feet.

To assess the benefits and harms of foot orthoses for treating paediatric flat feet.

Low to very low-certainty evidence shows that the effect of CFOs (high cost) or PFOs (low cost) versus shoes, and CFOs versus PFOs on pain, function and HRQoL is uncertain. This is pertinent for clinical practice, given the economic disparity between CFOs and PFOs. FOs may improve pain and function, versus shoes in children with JIA, with minimal delineation between costly CFOs and generic PFOs. This review updates that from 2010, confirming that in the absence of pain, the use of high-cost CFOs for healthy children with flexible flat feet has no supporting evidence, and draws very limited conclusions about FOs for treating paediatric flat feet. The availability of normative and prospective foot development data, dismisses most flat foot concerns, and negates continued attention to this topic. Attention should be re-directed to relevant paediatric foot conditions, which cause pain, limit function, or reduce quality of life. The agenda for researching asymptomatic flat feet in healthy children must be relegated to history, and replaced by a targeted research rationale, addressing children with indisputable foot pathology from discrete diagnoses, namely JIA, cerebral palsy, congenital talipes equino varus, trisomy 21 and Charcot Marie Tooth. Whether research resources should continue to be wasted on studying flat feet in healthy children that do not hurt, is questionable. Future updates of this review will address only relevant paediatric foot conditions.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Does immediate oral antiplatelet therapy reduce the volume of brain damage and the risk of early recurrent ischaemic stroke in people with acute presumed ischaemic stroke?

In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the brain. Such damage gives rise to the symptoms of stroke. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and also reduce the risk of early recurrent ischaemic stroke, thereby reducing the risk of early death and improving long-term outcomes in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage.

To assess the efficacy and safety of immediate oral antiplatelet therapy (i.e. started as soon as possible and no later than two weeks after stroke onset) in people with acute presumed ischaemic stroke.

Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who cannot swallow) and started within 48 hours of onset of presumed ischaemic stroke, significantly decreased death and dependency, and reduced the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications; long-term outcomes were improved.

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cardiovascular system

Does regular structured exercise training in adults undergoing dialysis improve patient-important outcomes?

Dialysis treatments weigh heavily on patients' physical and psychosocial health. Multiple studies have assessed the potential for exercise training to improve outcomes in adults undergoing dialysis. However, uncertainties exist in its relevance and sustainable benefits for patient-important outcomes. This is an update of a review first published in 2011.

To assess the benefits and safety of regular structured exercise training in adults undergoing dialysis on patient-important outcomes including death, cardiovascular events, fatigue, functional capacity, pain, and depression. We also aimed to define the optimal prescription of exercise in adults undergoing dialysis.

It is uncertain whether exercise training improves death, cardiovascular events, or the mental component of HRQoL in adults undergoing maintenance dialysis. Exercise training probably improves depressive symptoms, particularly when the intervention is maintained beyond four months. Exercise training is also likely to improve functional capacity. Low certainty evidence suggested that exercise training may improve fatigue, the physical component of quality of life, and pain. The safety of exercise training for adults undergoing dialysis remains uncertain.

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cancer

Does intravenous and subcutaneous immunoglobulin show efficacy and safety in people with MMN?

Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. Treatment options for MMN are few. People with MMN do not usually respond to steroids or plasma exchange. Uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin (IVIg). This is an update of a Cochrane Review first published in 2005, with an amendment in 2007. We updated the review to incorporate new evidence.

To assess the efficacy and safety of intravenous and subcutaneous immunoglobulin in people with MMN.

Low-certainty evidence from three small RCTs shows that IVIg may improve muscle strength in people with MMN, and low-certainty evidence indicates that it may improve disability; the estimate of the magnitude of improvement of disability has wide CIs and needs further studies to secure its significance. Based on moderate-certainty evidence, it is probable that most IVIg responders deteriorate in disability and muscle strength after IVIg withdrawal. SCIg might be an alternative treatment to IVIg, but the evidence is very uncertain. More research is needed to identify people in whom IVIg withdrawal is possible and to confirm efficacy of SCIg as an alternative maintenance treatment.

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immune system and infections

Is antecolic gastro- or duodenojejunostomy more effective and safer than retrocolic gastro- or duodenojejunostomy after partial pancreaticoduodenectomy?

Pancreatic cancer remains one of the five leading causes of cancer deaths in industrialised nations. For adenocarcinomas in the head of the gland and premalignant lesions, partial pancreaticoduodenectomy represents the standard treatment for resectable tumours. The gastro- or duodenojejunostomy after partial pancreaticoduodenectomy can be reestablished via either an antecolic or retrocolic route. The debate about the more favourable technique for bowel reconstruction is ongoing.

To compare the effectiveness and safety of antecolic and retrocolic gastro- or duodenojejunostomy after partial pancreaticoduodenectomy.

There was low- to moderate-certainty evidence suggesting that antecolic reconstruction after partial pancreaticoduodenectomy results in little to no difference in morbidity, mortality, length of hospital stay, or quality of life. Due to heterogeneity in definitions of the endpoints between trials, and differences in postoperative management, future research should be based on clearly defined endpoints and standardised perioperative management, to potentially elucidate differences between these two procedures. Novel strategies should be evaluated for prophylaxis and treatment of common complications, such as delayed gastric emptying.

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digestive system and metabolism

Does calcium supplementation reduce blood pressure in normotensive individuals and prevent primary hypertension?

Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of the review to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure.

To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the prevention of primary hypertension.

An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

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cardiovascular system

Does the rate of withdrawal of antiepileptic drugs (rapid or slow tapering) affect the risk of seizure recurrence in people with epilepsy in remission?

The ideal objective of treating a person with epilepsy is to induce remission (free of seizures for some time) using antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term adverse effects. Hence, when a person with epilepsy is in remission, it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review examines the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on seizure recurrence. This is an updated version of the Cochrane Review previously published in 2020.

To quantify risk of seizure recurrence after rapid (tapering period of three months or less) or slow (tapering period of more than three months) discontinuation of antiepileptic drugs in adults and children with epilepsy who are in remission, and to assess which variables modify the risk of seizure recurrence.

In view of methodological deficiencies, and small sample size of the two included studies, we cannot draw any reliable conclusions regarding the optimal rate of tapering of AEDs. Using GRADE, we assessed the certainty of the evidence as very low for outcomes for which data were available. We judged both studies to be at an overall high risk of bias. Further studies are needed in adults and children to investigate the optimal rate of withdrawal of AEDs and to study the effects of variables such as seizure types, aetiology, intellectual disability, electroencephalography abnormalities, presence of neurological deficits, and other comorbidities on the rate of tapering.

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cognitive, mental, and mental health

Did the systemic therapies have clear effects on the prevention or management of AIMSS in women with stage I to III hormone receptor-positive breast cancer?

Adjuvant aromatase inhibitors (AI) improve survival compared to tamoxifen in postmenopausal women with hormone receptor-positive stage I to III breast cancer. In approximately half of these women, AI are associated with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS), often described as symmetrical pain and soreness in the joints, musculoskeletal pain and joint stiffness. AIMSS may have significant and prolonged impact on women's quality of life. AIMSS reduces adherence to AI therapy in up to a half of women, potentially compromising breast cancer outcomes. Differing systemic therapies have been investigated for the prevention and treatment of AIMSS, but the effectiveness of these therapies remains unclear.

To assess the effects of systemic therapies on the prevention or management of AIMSS in women with stage I to III hormone receptor-positive breast cancer.

AIMSS are chronic and complex symptoms with a significant impact on women with early breast cancer taking AI. To date, evidence for safe and effective systemic therapies for prevention or treatment of AIMSS has been minimal. Although this review identified 17 studies with 2034 randomised participants, the review was challenging due to the heterogeneous systemic therapy interventions and study methodologies, and the unavailability of certain trial data. Meta-analysis was thus limited and findings of the review were inconclusive. Further research is recommended into systemic therapy for AIMSS, including high-quality adequately powered RCT, comprehensive descriptions of the intervention/placebo, and robust definitions of the condition and the outcomes being studied.

NOT ENOUGH INFORMATION

LOW

cancer

Did the COPD self-management interventions show effectiveness in improving health-related quality of life and reducing respiratory-related hospital admissions?

Self-management interventions help people with chronic obstructive pulmonary disease (COPD) to acquire and practise the skills they need to carry out disease-specific medical regimens, guide changes in health behaviour and provide emotional support to enable them to control their disease. Since the 2014 update of this review, several studies have been published.

Primary objectives To evaluate the effectiveness of COPD self-management interventions compared to usual care in terms of health-related quality of life (HRQoL) and respiratory-related hospital admissions. To evaluate the safety of COPD self-management interventions compared to usual care in terms of respiratory-related mortality and all-cause mortality. Secondary objectives To evaluate the effectiveness of COPD self-management interventions compared to usual care in terms of other health outcomes and healthcare utilisation. To evaluate effective characteristics of COPD self-management interventions.

Self-management interventions for people with COPD are associated with improvements in HRQoL, as measured with the SGRQ, and a lower probability of respiratory-related hospital admissions. No excess respiratory-related and all-cause mortality risks were observed, which strengthens the view that COPD self-management interventions are unlikely to cause harm. By using stricter inclusion criteria, we decreased heterogeneity in studies, but also reduced the number of included studies and therefore our capacity to conduct subgroup analyses. Data were therefore still insufficient to reach clear conclusions about effective (intervention) characteristics of COPD self-management interventions. As tailoring of COPD self-management interventions to individuals is desirable, heterogeneity is and will likely remain present in self-management interventions. For future studies, we would urge using only COPD self-management interventions that include iterative interactions between participants and healthcare professionals who are competent using behavioural change techniques (BCTs) to elicit participants' motivation, confidence and competence to positively adapt their health behaviour(s) and develop skills to better manage their disease. In addition, to inform further subgroup and meta-regression analyses and to provide stronger conclusions regarding effective COPD self-management interventions, there is a need for more homogeneity in outcome measures. More attention should be paid to behavioural outcome measures and to providing more detailed, uniform and transparently reported data on self-management intervention components and BCTs. Assessment of outcomes over the long term is also recommended to capture changes in people's behaviour. Finally, information regarding non-protocol interventions as well as analyses to estimate the effect of adhering to interventions should be included to increase the quality of evidence.

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MEDIUM

respiratory system

Are CCBs used as first-line therapy for hypertension different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events?

This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated.

To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events.

For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.

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cardiovascular system

Does PPI treatment initiated prior to endoscopy affect acute upper GI bleeding?

Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.

To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.

There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.

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digestive system and metabolism

Do ALK inhibitors given as monotherapy effectively treat advanced ALK-rearranged NSCLC?

Targeted therapies directed at specific driver oncogenes have improved outcomes for individuals with advanced non-small cell lung cancer (NSCLC). Approximately 5% of lung adenocarcinomas, the most common histologic subtype of NSCLC, harbour rearrangements in the anaplastic lymphoma kinase (ALK) gene leading to constitutive activity of the ALK kinase. Crizotinib was the first tyrosine kinase inhibitor (TKI) demonstrated to be effective in advanced NSCLC. Next-generation ALK TKIs have since been developed including ceritinib, alectinib, brigatinib, ensartinib, and lorlatinib, and have been compared with crizotinib or chemotherapy in randomised controlled trials (RCTs). These ALK-targeted therapies are currently used in clinical practice and are endorsed in multiple clinical oncology guidelines.

To evaluate the safety and efficacy of ALK inhibitors given as monotherapy to treat advanced ALK-rearranged NSCLC.

Next-generation ALK inhibitors including alectinib, brigatinib, and lorlatinib are the preferred first systemic treatment for individuals with advanced ALK-rearranged NSCLC. Further trials are ongoing including investigation of first-line ensartinib. Next-generation inhibitors have not been compared to each other, and it is unknown which should be used first and what subsequent treatment sequence is optimal.

NOT ENOUGH INFORMATION

MEDIUM

cancer

Did the review investigate the evidence base for early palliative care interventions for improving outcomes in adults diagnosed with a primary brain tumor and their carers?

Primary malignant brain tumours can have an unpredictable course, but high-grade gliomas typically have a relentlessly progressive disease trajectory. They can cause profound symptom burden, affecting physical, neurocognitive, and social functioning from an early stage in the illness. This can significantly impact on role function and on the experiences and needs of informal caregivers. Access to specialist palliative and supportive care early in the disease trajectory, for those with high-grade tumours in particular, has the potential to improve patients' and caregivers' quality of life. However, provision of palliative and supportive care for people with primary brain tumours - and their informal caregivers - is historically ill-defined and ad hoc, and the benefits of early palliative interventions have not been confirmed. It is therefore important to define the role and effectiveness of early referral to specialist palliative care services and/or the effectiveness of other interventions focused on palliating disease impact on people and their informal caregivers. This would help guide improvement to service provision, by defining those interventions which are effective across a range of domains, and developing an evidence-based model of integrated supportive and palliative care for this population.

To assess the evidence base for early palliative care interventions, including referral to specialist palliative care services compared to usual care, for improving outcomes in adults diagnosed with a primary brain tumour and their carers.

Currently there is a lack of research focusing on the introduction of early palliative interventions specifically for people with primary brain tumours, either as co-ordinated specialist palliative care approaches or interventions focusing on a specific aspect of palliation. Future research should address the methodological shortcomings described in early palliative intervention studies in other cancers and chronic conditions. In particular, the specific population under investigation, the timing and the setting of the intervention should be clearly described and the standardised palliative care-specific components of the intervention should be defined in detail.

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MEDIUM

cancer

Do heated tobacco products (HTPs) effectively aid in smoking cessation and reduce smoking prevalence?

Heated tobacco products (HTPs) are designed to heat tobacco to a high enough temperature to release aerosol, without burning it or producing smoke. They differ from e-cigarettes because they heat tobacco leaf/sheet rather than a liquid. Companies who make HTPs claim they produce fewer harmful chemicals than conventional cigarettes. Some people report stopping smoking cigarettes entirely by switching to using HTPs, so clinicians need to know whether they are effective for this purpose and relatively safe. Also, to regulate HTPs appropriately, policymakers should understand their impact on health and on cigarette smoking prevalence.

To evaluate the effectiveness and safety of HTPs for smoking cessation and the impact of HTPs on smoking prevalence. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register, CENTRAL, MEDLINE, and six other databases for relevant records to January 2021, together with reference-checking and contact with study authors and relevant groups.

No studies reported on cigarette smoking cessation, so the effectiveness of heated tobacco for this purpose remains uncertain. There was insufficient evidence for differences in risk of adverse or serious adverse events between people randomised to switch to heated tobacco, smoke cigarettes, or attempt tobacco abstinence in the short-term. There was moderate-certainty evidence that heated tobacco users have lower exposure to toxicants/carcinogens than cigarette smokers and very low- to moderate-certainty evidence of higher exposure than those attempting abstinence from all tobacco. Independently funded research on the effectiveness and safety of HTPs is needed. The rate of decline in cigarette sales accelerated after the introduction of heated tobacco to market in Japan but, as data were observational, it is possible other factors caused these changes. Moreover, falls in cigarette sales may not translate to declining smoking prevalence, and changes in Japan may not generalise elsewhere. To clarify the impact of rising heated tobacco use on smoking prevalence, there is a need for time-series studies that examine this association.

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miscellaneous

Does high-added sugar consumption impact the risk for cardiovascular disease in the general population?

High intake of added sugar have been suggested to impact the risk for cardiovascular disease (CVD). Knowledge on the subject can contribute to preventing CVD.

To assess the effects of a high versus low-added sugar consumption for primary prevention of CVD in the general population.

No trials investigating the effect of added sugar on cardiovascular events or all-cause mortality were identified in our searches. Evidence is uncertain whether low intake of added sugar has an effect on risk factors for CVD; the effect was small and the clinical relevance is, therefore, uncertain. Practical ways to achieve reductions in dietary added sugar includes following current dietary recommendations. Future trials should have longer follow-up time and report on all-cause mortality and cardiovascular events in order to clarify the effect of added sugar on these outcomes. Future trials should also aim for more direct interventions and preferably be more independent of industry funding.

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nutrition and dietary supplements

Is percutaneous thrombectomy or ultrasound-accelerated thrombolysis safer and more effective than standard treatment for acute limb ischaemia in adults?

Acute limb ischaemia (ALI), the sudden and significant reduction of blood flow to the limb, is considered a vascular emergency. In the general population, the incidence is estimated as 14 per 100,000. Prognosis depends on the time it takes to diagnose the condition and begin appropriate treatment. Standard initial interventional treatments include conventional open surgery and endovascular interventions such as catheter-directed thrombolysis (CDT). Percutaneous interventions, such as percutaneous thrombectomy (PT, including mechanical thrombectomy or pharmomechanical thrombectomy) and ultrasound-accelerated thrombolysis (USAT), are also performed as alternative endovascular techniques. The proposed advantages of PT and USAT include reduced time to revascularisation and when combined with catheter-directed thrombolysis, a reduction in dose of thrombolytic agents and infusion time. The benefits of PT or USAT versus open surgery or thrombolysis alone are still uncertain. In this review, we compared PT or USAT against standard treatment for ALI, in an attempt to determine if any technique is comparatively safer and more effective.

To assess the safety and effectiveness of percutaneous thrombectomy or ultrasound-accelerated thrombolysis for the initial management of acute limb ischaemia in adults.

There is insufficient evidence to assess the safety and effectiveness of USAT versus CDT alone for ALI for our evaluated outcomes: amputation rate, major bleeding, clinical success, and adverse effects. Primary and secondary patency were not reported separately. There was no RCT evidence for PT. Limitations of this systematic review derive from the single included study, small sample size, short clinical follow-up period, and high risk of bias in critical domains. For this reason, the applicability of the results is limited. There is a need for high-quality studies to compare PT or USAT against open surgery, thrombolysis alone, no treatment, or other PT modalities for ALI. Future trials should assess outcomes, such as primary patency, amputation rate, major bleeding, clinical success, secondary patency, and adverse effects.

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cardiovascular system

Does the combination of thermal ablation with TACE confer a more favorable prognosis than TACE alone in people with hepatocellular carcinoma?

Hepatocellular carcinoma is the sixth most common cancer worldwide. Hepatic resection is regarded as the curative therapy for hepatocellular carcinoma. However, only about 20% of people with hepatocellular carcinoma are candidates for resection, which highlights the importance of effective nonsurgical therapies. Until now, transcatheter arterial chemoembolisation (TACE) is the most common palliative therapy for hepatocellular carcinoma, but its clinical benefits remain unsatisfactory. During recent years, some studies have reported that the combination of TACE plus thermal ablation can confer a more favourable prognosis than TACE alone. However, clear and compelling evidence to prove the beneficial or harmful effects of the combination of TACE and thermal ablation therapy is lacking.

To assess the beneficial and harmful effects of the combination of thermal ablation with TACE versus TACE alone in people with hepatocellular carcinoma.

We could not find for inclusion any confirmed randomised clinical trials assessing the beneficial or harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma. Therefore, our results did not show or reject the efficiency of the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma. We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems.

NOT ENOUGH INFORMATION

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cancer

Can orthodontic intervention prevent or correct crowded teeth in children?

Crowded teeth develop when there is not enough space in the jaws into which the teeth can erupt. Crowding can affect baby teeth (deciduous dentititon), adult teeth (permanent dentition), or both, and is a common reason for referral to an orthodontist. Crowded teeth can affect a child's self-esteem and quality of life. Early loss of baby teeth as a result of tooth decay or trauma, can lead to crowded permanent teeth. Crowding tends to increase with age, especially in the lower jaw.

To assess the effects of orthodontic intervention for preventing or correcting crowded teeth in children. To test the null hypothesis that there are no differences in outcomes between different orthodontic interventions for preventing or correcting crowded teeth in children.

Most interventions were assessed by single, small studies. We found very low-certainty evidence that lip bumper, used in the mixed dentition, may be effective for preventing crowding in the early permanent dentition, and a Schwarz appliance may reduce crowding in the lower arch. We also found very low-certainty evidence that coaxial NiTi may be better at reducing crowding than single-stranded NiTi, and that NiTi may be better than copper NiTi. As the current evidence is of very low certainty, our findings may change with future research.

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dental and oral health

Can interceptive procedures effectively promote the eruption of a palatally displaced canine in young people aged 9 to 14 years old?

A permanent upper (maxillary) canine tooth that grows into the roof of the mouth and frequently does not appear (erupt) is called a palatally displaced canine (PDC). The reported prevalence of PDC in the population varies between 1% and 3%. Management of the unerupted PDC can be lengthy, involving surgery to uncover the tooth and prolonged orthodontic (brace) treatment to straighten it; therefore, various procedures have been suggested to encourage a PDC to erupt without the need for surgical intervention.

To assess the efficacy, safety and cost-effectiveness of any interceptive procedure to promote the eruption of a PDC compared to no treatment or other interceptive procedures in young people aged 9 to 14 years old.

The evidence that extraction of the primary canine in a young person aged between 9 and 14 years diagnosed with a PDC may increase the proportion of erupted PDCs, without surgical intervention, is very uncertain. There is no evidence that double extraction of primary teeth increases the proportion of erupted PDC compared with a single primary tooth extraction at 18 months or the proportion referred for surgery by 48 months. Because we have only low to very low certainty in these findings, future research is necessary to help us know for sure the best way to deal with upper permanent teeth that are not erupting as expected.

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dental and oral health

Does recombinant human thyrotropin-aided radioiodine treatment have beneficial effects for non-toxic multinodular goitre?

Multinodular goitre is common in women. Treatments for non-toxic multinodular goitre include surgery, levothyroxine suppressive therapy, and radioiodine. Radioiodine therapy is the only non-surgical alternative for non-toxic multinodular goitre. However, a high amount of radioiodine is needed to enable the thyroid nodules to adequately take up the radioiodine, because the multinodular goitre takes up a low amount of iodine. Recombinant human thyrotropin (rhTSH) has been used to increase radioiodine uptake and reduce thyroid volume of the multinodular goitre. Whether the improved reduction of the goitre resulting from rhTSH-stimulated radioiodine therapy is beneficial to the person remains controversial.

To assess the effects of recombinant human thyrotropin-aided radioiodine treatment for non-toxic multinodular goitre.

RhTSH-aided radioiodine treatment for non-toxic multinodular goitre, compared to radioiodine alone, probably increased the risk of hypothyroidism but probably led to a greater reduction in thyroid volume. Data on QoL and costs were sparse or missing.

NOT ENOUGH INFORMATION

LOW

endocrine system and hormones

Does propionyl-L-carnitine improve walking distance for people with stable intermittent claudication?

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in the lower limbs caused by chronic occlusive arterial disease. This pain develops in a limb during exercise and is relieved with rest. Propionyl-L-carnitine (PLC) is a drug that may alleviate the symptoms of PAD through a metabolic pathway, thereby improving exercise performance.

The objective of this review is to determine whether propionyl-L-carnitine is efficacious compared with placebo, other drugs, or other interventions used for treatment of intermittent claudication (e.g. exercise, endovascular intervention, surgery) in increasing pain-free and maximum walking distance for people with stable intermittent claudication, Fontaine stage II.

When PLC was compared with placebo, improvement in walking distance was mild to moderate and safety profiles were similar, with moderate overall certainty of evidence. Although In clinical practice, PLC might be considered as an alternative or an adjuvant to standard treatment when such therapies are found to be contraindicated or ineffective, we found no RCT evidence comparing PLC with standard treatment to directly support such use.

SUPPORTED

MEDIUM

cardiovascular system

Is the effectiveness and safety of laxative agents for preventing DIOS in people with cystic fibrosis well-established?

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

Did prophylactic corticosteroid administration before elective caesarean section at term improve fetal, neonatal, and maternal morbidity as compared to usual care?

Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in singleton preterm pregnancies accelerate lung maturation and reduce the incidence of respiratory complications. It is unclear whether administration at term gestations, prior to caesarean section, improves the respiratory outcomes for these babies without causing any unnecessary morbidity to the mother or the infant.

The objective of this review was to assess the effect of prophylactic corticosteroid administration before elective caesarean section at term, as compared to usual care (which could be placebo or no treatment), on fetal, neonatal and maternal morbidity. We also assessed the impact of the treatment on the child in later life.

Evidence from one randomised controlled trial suggests that prophylactic corticosteroids before elective caesarean section at term probably reduces admission to the neonatal intensive care unit for respiratory morbidity. It is uncertain if administration of antenatal corticosteroids reduces the rates of respiratory distress syndrome (RDS) or transient tachypnoea of the neonate (TTN). The overall certainty of the evidence for the primary outcomes was found to be low or very low, apart from the outcome of admission to neonatal special care (all levels) for respiratory morbidity, for which the evidence was of moderate certainty. Therefore, there is currently insufficient data to draw any firm conclusions. More evidence is needed to investigate the effect of prophylactic antenatal corticosteroids on the incidence of recognised respiratory morbidity such as RDS. Any future trials should assess the balance between respiratory benefit and potential immediate adverse effects (e.g. hypoglycaemia) and long-term adverse effects (e.g. academic performance) for the infant. There is very limited information on maternal health outcomes to provide any assurances that corticosteroids do not pose any increased risk of harm to the mother. Further research should consider investigating the effectiveness of antenatal steroids at different gestational ages prior to caesarean section. There are nine potentially eligible studies that are currently ongoing and could be included in future updates of this review.

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sexual and reproductive health

Does a restrictive red blood cell transfusion threshold lead to lower 30-day mortality and better clinical outcomes compared to a liberal threshold?

The optimal haemoglobin threshold for use of red blood cell (RBC) transfusions in anaemic patients remains an active field of research. Blood is a scarce resource, and in some countries, transfusions are less safe than in others because of inadequate testing for viral pathogens. If a liberal transfusion policy does not improve clinical outcomes, or if it is equivalent, then adopting a more restrictive approach could be recognised as the standard of care. OBJECTIVES: The aim of this review update was to compare 30-day mortality and other clinical outcomes for participants randomised to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all clinical conditions. The restrictive transfusion threshold uses a lower haemoglobin concentration as a threshold for transfusion (most commonly, 7.0 g/dL to 8.0 g/dL), and the liberal transfusion threshold uses a higher haemoglobin concentration as a threshold for transfusion (most commonly, 9.0 g/dL to 10.0 g/dL).

Search methods:

Transfusion at a restrictive haemoglobin concentration decreased the proportion of people exposed to RBC transfusion by 41% across a broad range of clinical contexts. Across all trials, no evidence suggests that a restrictive transfusion strategy impacted 30-day mortality, mortality at other time points, or morbidity (i.e. cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. Despite including 17 more randomised trials (and 8846 participants), data remain insufficient to inform the safety of transfusion policies in important and selected clinical contexts, such as myocardial infarction, chronic cardiovascular disease, neurological injury or traumatic brain injury, stroke, thrombocytopenia, and cancer or haematological malignancies, including chronic bone marrow failure. Further work is needed to improve our understanding of outcomes other than mortality. Most trials compared only two separate thresholds for haemoglobin concentration, which may not identify the actual optimal threshold for transfusion in a particular patient. Haemoglobin concentration may not be the most informative marker of the need for transfusion in individual patients with different degrees of physiological adaptation to anaemia. Notwithstanding these issues, overall findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds between the range of 7.0 g/dL and 8.0 g/dL. Some patient subgroups might benefit from RBCs to maintain higher haemoglobin concentrations; research efforts should focus on these clinical contexts.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Did the ACE inhibitor administration effectively decrease intraglomerular pressure, microalbuminuria, and proteinuria in people with sickle cell disease and was its safety assessed for adverse effects?

Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013 and 2015.

To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.

Overall, we judged the certainty of the evidence to be very low. The included study selectively reported its results, was not powered to detect a group difference, should it exist, and otherwise did not offer enough information to allow us to judge the bias inherent in the study. Indirectness (in relation to the limited age and type of population included) and imprecision (wide confidence intervals around the effect estimate) were observed. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study. Overall, we judged the certainty of this evidence to be very low.

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LOW

cardiovascular system

Did VR training for cataract surgery significantly impact the operating performance of postgraduate ophthalmology trainees?

Cataract surgery is the most common incisional surgical procedure in ophthalmology and is important in ophthalmic graduate medical education. Although most ophthalmology training programs in the United States (US) include virtual reality (VR) training for cataract surgery, comprehensive reviews that detail the impact of VR training on ophthalmology trainee performance are lacking.

To assess the impact of VR training for cataract surgery on the operating performance of postgraduate ophthalmology trainees, measured by operating time, intraoperative complications, postoperative complications, supervising physician ratings, and VR simulator task ratings.

current research suggests that vr training may be more effective than no supplementary training in improving trainee performance in the operating room and simulated settings for postgraduate ophthalmology trainees, but the evidence is uncertain. the evidence comparing vr with conventional or wet laboratory training was less consistent.

NOT ENOUGH INFORMATION

LOW

sensory organs

Can continuous glucose monitoring (CGM) reduce the need for blood sampling and keep glucose levels in the normal range for preterm infants at risk of hypoglycemia or hyperglycemia?

Preterm infants are susceptible to hyperglycaemia and hypoglycaemia, which may lead to adverse neurodevelopment. The use of continuous glucose monitoring (CGM) devices might help in keeping glucose levels in the normal range, and reduce the need for blood sampling. However, the use of CGM might be associated with harms in the preterm infant.

To assess the benefits and harms of CGM versus intermittent modalities to measure glycaemia in preterm infants 1. at risk of hypoglycaemia or hyperglycaemia; 2. with proven hypoglycaemia; or 3. with proven hyperglycaemia.

There is insufficient evidence to determine if CGM affects preterm infant mortality or morbidities. We are very uncertain of the safety of CGM and the available management algorithms, and many morbidities remain unreported. Preterm infants at risk of hypoglycaemia or hyperglycaemia were enrolled in all four included studies. No studies have been conducted in preterm infants with proven hypoglycaemia or hyperglycaemia. Long-term outcomes were not reported. Events of necrotizing enterocolitis, reported in the study published in 2021, were lower in the CGM group. However, the effect of CGM on this outcome remains very uncertain. Clinical trials are required to determine the most effective CGM and glycaemic management regimens in preterm infants before larger studies can be performed to assess the efficacy of CGM for reducing mortality, morbidity, and long-term neurodevelopmental impairments.

NOT ENOUGH INFORMATION

LOW

endocrine system and hormones

Does dietary advice with/without oral nutritional supplements improve survival, weight, anthropometry, and quality of life in adults with disease-related malnutrition?

Disease-related malnutrition has been reported in 10% to 55% of people in hospital and the community and is associated with significant health and social-care costs. Dietary advice (DA) encouraging consumption of energy- and nutrient-rich foods rather than oral nutritional supplements (ONS) may be an initial treatment.

To examine evidence that DA with/without ONS in adults with disease-related malnutrition improves survival, weight, anthropometry and quality of life (QoL).

We found no evidence of an effect of any intervention on mortality. There may be weight gain with DA and with DA plus ONS in the short term, but the benefits of DA when compared with ONS are uncertain. The size and direction of effect and the length of intervention and follow-up required for benefits to emerge were inconsistent for all other outcomes. There were too few data for many outcomes to allow meaningful conclusions. Studies focusing on both patient-centred and healthcare outcomes are needed to address the questions in this review.

NOT ENOUGH INFORMATION

LOW

nutrition and dietary supplements

Did biomarkers add predictive value to the RCRI for preoperatively predicting in-hospital MACE and other adverse outcomes in noncardiac surgery patients?

The Revised Cardiac Risk Index (RCRI) is a widely acknowledged prognostic model to estimate preoperatively the probability of developing in-hospital major adverse cardiac events (MACE) in patients undergoing noncardiac surgery. However, the RCRI does not always make accurate predictions, so various studies have investigated whether biomarkers added to or compared with the RCRI could improve this.

Primary: To investigate the added predictive value of biomarkers to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Secondary: To investigate the prognostic value of biomarkers compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Tertiary: To investigate the prognostic value of other prediction models compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery.

Studies included in this review suggest that the predictive performance of the RCRI in predicting MACE is improved when NT-proBNP, troponin or their combination are added. Other studies indicate that BNP and NT-proBNP, when used in isolation, may even have a higher discriminative performance than the RCRI. There was insufficient evidence of a difference between the predictive accuracy of the RCRI and other prediction models in predicting MACE. However, ACS-NSQIP-MICA and ACS-NSQIP-SRS outperformed the RCRI in predicting myocardial infarction and cardiac arrest combined, and all-cause mortality, respectively. Nevertheless, the results cannot be interpreted as conclusive due to high risks of bias in a majority of papers, and pooling was impossible due to heterogeneity in outcomes, prediction horizons, biomarkers and studied populations. Future research on the added prognostic value of biomarkers to existing prediction models should focus on biomarkers with good predictive accuracy in other settings (e.g. diagnosis of myocardial infarction) and identification of biomarkers from omics data. They should be compared to novel biomarkers with so far insufficient evidence compared to established ones, including NT-proBNP or troponins. Adherence to recent guidance for prediction model studies (e.g. TRIPOD; PROBAST) and use of standardised outcome definitions in primary studies is highly recommended to facilitate systematic review and meta-analyses in the future.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Does chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma, result in improved overall survival, improved disease-free survival, and/or improved locoregional control?

Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.

To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.

the results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. the evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or crt. adjuvant crt reduces the risk of death by 16%, as compared to radiotherapy alone. concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.

NOT ENOUGH INFORMATION

LOW

cancer

Does post-operative LNG-IUD effectively reduce recurrence of symptoms in women with symptomatic endometriosis?

Endometriosis is a condition characterised by the presence of ectopic deposits of endometrial-like tissue outside the uterus, usually in the pelvis. The impact of laparoscopic treatment on overall pain is uncertain and a significant proportion of women will require further surgery. Therefore, adjuvant medical therapies following surgery, such as the levonorgestrel-releasing intrauterine device (LNG-IUD), have been considered to reduce recurrence of symptoms. OBJECTIVES: To determine the effectiveness and safety of post-operative LNG-IUD in women with symptomatic endometriosis.

Search methods:

post-operative lng-iud is widely used to reduce endometriosis-related pain and to improve operative outcomes. this review demonstrates that there is no high-quality evidence to support this practice. this review highlights the need for further studies with large sample sizes to assess the effectiveness of post-operative adjuvant hormonal iud on the core endometriosis outcomes (overall pain, most troublesome symptom, and quality of life).

NOT ENOUGH INFORMATION

LOW

sexual and reproductive health

Did peer support interventions have a significant impact on the psychological and psychosocial outcomes of parents and family carers of children with complex needs?

Parents and family carers of children with complex needs experience a high level of pressure to meet children's needs while maintaining family functioning and, as a consequence, often experience reduced well-being and elevated psychological distress. Peer support interventions are intended to improve parent and carer well-being by enhancing the social support available to them. Support may be delivered via peer mentoring or through support groups (peer or facilitator led). Peer support interventions are widely available, but the potential benefits and risks of such interventions are not well established.

To assess the effects of peer support interventions (compared to usual care or alternate interventions) on psychological and psychosocial outcomes, including adverse outcomes, for parents and other family carers of children with complex needs in any setting.

Parents and carers of children with complex needs perceive peer support interventions as valuable, but this review found no evidence of either benefit or harm. Currently, there is uncertainty about the effects of peer support interventions for parents and carers of children with complex needs. However, given the overall low to very low certainty of available evidence, our estimates showing no effects of interventions may very well change with further research of higher quality.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does nifedipine effectively relieve uterine contractions during menstruation?

Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent, cramping pelvic pain that occurs with periods, in the presence of a normal uterus, ovaries and fallopian tubes. It is thought to be caused by uterine contractions (cramps) associated with a high level of production of local chemicals such as prostaglandins. The muscle of the uterus (the myometrium) responds to these high levels of prostaglandins by contracting forcefully, causing low oxygen levels and consequently pain. Nifedipine is a calcium channel blocker in widespread clinical use for preterm labour due to its ability to inhibit uterine contractions in that setting. This review addresses whether this effect of nifedipine also helps with relief of the uterine contractions during menstruation OBJECTIVES: To assess the effectiveness and safety of nifedipine for primary dysmenorrhoea.

Search methods:

The evidence is insufficient to confirm whether nifedipine is a possible medical treatment for primary dysmenorrhoea. The trials included in this review had very low numbers and were of low quality. Notably, there was a large imbalance in numbers randomised between placebo and treatment groups in one of the two trials with data available for analysis. While there was no evidence of a difference noted in adverse effects between groups, more data from larger participant numbers are needed for this outcome. Larger, more well-conducted trials are required to elucidate the potential role of nifedipine in the treatment of this common condition, as it could be a useful addition to the therapeutic options available if shown to be well tolerated and effective. The safety of nifedipine in women of reproductive age is well established from trials of its use in preterm labour, and clinicians are accustomed to off-label use for this indication. The drug is inexpensive and readily available. Other options for relief of primary dysmenorrhoea are not suitable for all women; NSAIDs and the oral contraceptive pill (OCP) are contraindicated for some women, and the OCP is not suitable for women who are trying to conceive. In addition, the trials examined suggest there may be a participant preference for nifedipine.

NOT ENOUGH INFORMATION

LOW

sexual and reproductive health

Is routine abdominal drainage after pancreatic surgery beneficial?

The use of surgical drains is a very common practice after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. This is the third update of a previously published Cochrane Review to address the uncertain benifits of prophylactic abdominal drainage in pancreatic surgery.

To assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal.

Compared with no drain use, it is unclear whether routine drain use has any effect on mortality at 30 days or postoperative complications after pancreatic surgery. Compared with no drain use, low-certainty evidence suggests that routine drain use may reduce mortality at 90 days. Compared with a passive drain, the evidence is very uncertain about the effect of an active drain on mortality at 30 days or postoperative complications. Compared with late drain removal, early drain removal may reduce intra-abdominal infection rate, morbidity, and length of hospital stay for people with low risk of postoperative pancreatic fistula, but the evidence is very uncertain.

NOT ENOUGH INFORMATION

LOW

digestive system and metabolism

Do antipsychotics show efficacy and safety for treating agitation and psychosis in people with Alzheimer's disease and vascular dementia?

Typical and atypical antipsychotics are widely used to treat agitation and psychosis in dementia. However, whether or not they are beneficial is uncertain. Some trials have yielded negative results and effectiveness may be outweighed by harms.

To assess the efficacy and safety of antipsychotics for the treatment of agitation and psychosis in people with Alzheimer's disease and vascular dementia.

There is some evidence that typical antipsychotics might decrease agitation and psychosis slightly in patients with dementia. Atypical antipsychotics reduce agitation in dementia slightly, but their effect on psychosis in dementia is negligible. The apparent effectiveness of the drugs seen in daily practice may be explained by a favourable natural course of the symptoms, as observed in the placebo groups. Both drug classes increase the risk of somnolence and other adverse events. If antipsychotics are considered for sedation in patients with severe and dangerous symptoms, this should be discussed openly with the patient and legal representative.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Do psychological and pharmacological interventions have significant effects on depression in CAD patients with comorbid depression?

Depression occurs frequently in individuals with coronary artery disease (CAD) and is associated with a poor prognosis.

To determine the effects of psychological and pharmacological interventions for depression in CAD patients with comorbid depression.

In individuals with CAD and depression, there is low certainty evidence that psychological intervention may result in a reduction in depression symptoms at the end of treatment. There was also low certainty evidence that pharmacological interventions may result in a large reduction of depression symptoms at the end of treatment. Moderate certainty evidence suggests that pharmacological intervention probably results in a moderate to large increase in depression remission at the end of treatment. Evidence on maintenance effects and the durability of these short-term findings is still missing. The evidence for our primary and secondary outcomes, apart from depression symptoms at end of treatment, is still sparse due to the low number of trials per outcome and the heterogeneity of examined populations and interventions. As psychological and pharmacological interventions can seemingly have a large to only a small or no effect on depression, there is a need for research focusing on extracting those approaches able to substantially improve depression in individuals with CAD and depression.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Is autogenic drainage clinically effective in people with cystic fibrosis compared to other physiotherapy airway clearance techniques?

Autogenic drainage is an airway clearance technique that was developed by Jean Chevaillier in 1967. The technique is characterised by breathing control using expiratory airflow to mobilise secretions from smaller to larger airways. Secretions are cleared independently by adjusting the depth and speed of respiration in a sequence of controlled breathing techniques during exhalation. The technique requires training, concentration and effort from the individual but it has previously been shown to be an effective treatment option for those who are seeking techniques to support and promote independence. However, at a time where the trajectory and demographics of the disease are changing, it is important to systematically review the evidence demonstrating that autogenic drainage is an effective intervention for people with cystic fibrosis.

To compare the clinical effectiveness of autogenic drainage in people with cystic fibrosis with other physiotherapy airway clearance techniques.

Autogenic drainage is a challenging technique that requires commitment from the individual. As such, this intervention merits systematic review to ensure its effectiveness for people with cystic fibrosis, particularly in an era where treatment options are changing rapidly. From the studies assessed, autogenic drainage was not found to be superior to any other form of airway clearance technique. Larger studies are required to better evaluate autogenic drainage in comparison to other airway clearance techniques in view of the relatively small number of participants in this review and the complex study designs. The studies recruited a range of participants and were not powered to assess non-inferiority. The varied length and design of the studies made the analysis of pooled data challenging.

NOT ENOUGH INFORMATION

LOW

respiratory system

Is endovascular repair a viable alternative to open surgery for treating complications of type B aortic dissection?

Appendicitis remains a difficult disease to diagnose, and imaging adjuncts are commonly employed. Magnetic resonance imaging (MRI) is an imaging test that can be used to diagnose appendicitis. It is not commonly regarded as a first-line imaging test for appendicitis, but the reported diagnostic accuracy in some studies is equivalent to computed tomography (CT) scans. As it does not expose patients to radiation, it is an attractive imaging modality, particularly in women and children.

The primary objective was to determine the diagnostic accuracy of MRI for detecting appendicitis in all patients. Secondary objectives: To investigate the accuracy of MRI in subgroups of pregnant women, children, and adults. To investigate the potential influence of MRI scanning variables such as sequences, slice thickness, or field of view.

MRI appears to be highly accurate in confirming and excluding acute appendicitis in adults, children, and pregnant women regardless of protocol. The methodological quality of the included studies was generally low due to incomplete and low standards of follow-up, so summary estimates of sensitivity and specificity may be biased. We could not assess the impact and direction of potential bias given the very low number of high-quality studies. Studies comparing MRI protocols were few, and although we found no influence of MRI protocol variables on the summary estimates of accuracy, our results do not rule out that some MRI protocols are more accurate than others.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Was the effectiveness and safety of thoracic aortic endovascular repair versus open surgical repair for treatment of complicated chronic Type B aortic dissection assessed?

Type B aortic dissection can lead to serious and life-threatening complications such as aortic rupture, stroke, renal failure, and paraplegia, all of which require intervention. Traditionally, these complications have been treated with open surgery. Recently however, endovascular repair has been proposed as an alternative.

To assess the effectiveness and safety of thoracic aortic endovascular repair versus open surgical repair for treatment of complicated chronic Type B aortic dissection (CBAD).

Due to lack of RCTs or CCTs investigating the effectiveness and safety of TEVAR compared to OSR for patients with complicated CBAD, we are unable to provide any evidence to inform decision-making on the optimal intervention for these patients. High-quality RCTs or CCTs addressing this objective are necessary. However, conducting such studies will be challenging for this life-threatening disease.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Did different periodontal treatment modalities have a significant impact on blood pressure in people with chronic periodontitis?

An association has been hypothesized between periodontitis and hypertension. Periodontal therapy is believed to reduce systemic inflammatory mediators and increase endothelial function, thus having the potential to prevent and treat hypertension.

To assess the effect and safety of different periodontal treatment modalities on blood pressure (BP) in people with chronic periodontitis.

We found no evidence of a difference of an impact of periodontal treatments on BP in most comparisons assessed in this review, and given the low certainty of evidence and the lack of relevant studies we could not draw conclusions about the effect of periodontal treatment on BP in people with chronic periodontitis. We found only one study suggesting that periodontal treatment may reduce SBP and DBP over a short period in people with hypertension and chronic periodontitis, but the certainty of evidence was moderate.

REFUTED

LOW

cardiovascular system

Can interventions increasing indoor air humidity effectively reduce or prevent dryness symptoms of the eyes, skin, and upper respiratory tract at work and in educational settings?

Indoor exposure to dry air during heating periods has been associated with dryness and irritation symptoms of the upper respiratory airways and the skin. The irritated or damaged mucous membrane poses an important entry port for pathogens causing respiratory infections.

To determine the effectiveness of interventions that increase indoor air humidity in order to reduce or prevent dryness symptoms of the eyes, the skin and the upper respiratory tract (URT) or URT infections, at work and in educational settings.

Indoor air humidification at the workplace may have little to no effect on dryness symptoms of the eyes, the skin and the URT. Studies investigating illness-related absenteeism from work or school could only be summarised narratively, due to different outcome measures assessed. The evidence suggests that increasing humidification may reduce the absenteeism, but the evidence is very uncertain. Future RCTs involving larger sample sizes, assessing dryness symptoms more technically or rigorously defining absenteeism and controlling for potential confounders are therefore needed to determine whether increasing indoor air humidity can reduce or prevent dryness symptoms of the eyes, the skin, the URT or URT infections at work and in educational settings over time.

NOT ENOUGH INFORMATION

LOW

respiratory system

Do psychological interventions focusing on mindfulness improve mental well-being and academic performance in medical students and junior doctors?

The early detection of oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD), followed by appropriate treatment, may improve survival and reduce the risk for malignant transformation respectively. This is an update of a Cochrane Review first published in 2013.

To estimate the diagnostic test accuracy of conventional oral examination, vital rinsing, light-based detection, mouth self-examination, remote screening, and biomarkers, used singly or in combination, for the early detection of OPMD or OSCC in apparently healthy adults.

There is a lack of high-certainty evidence to support the use of screening programmes for oral cavity cancer and OPMD in the general population. Frontline screeners such as general dentists, dental hygienists, other allied professionals, and community healthcare workers should remain vigilant for signs of OPMD and OSCC.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does long-term antibiotic therapy effectively treat chronic Burkholderia cepacia complex infection in people with cystic fibrosis?

Mindfulness interventions are increasingly popular as an approach to improve mental well-being. To date, no Cochrane Review examines the effectiveness of mindfulness in medical students and junior doctors. Thus, questions remain regarding the efficacy of mindfulness interventions as a preventative mechanism in this population, which is at high risk for poor mental health. OBJECTIVES: To assess the effects of psychological interventions with a primary focus on mindfulness on the mental well-being and academic performance of medical students and junior doctors.

Search methods:

the effectiveness of mindfulness in our target population remains unconfirmed. there have been relatively few studies of mindfulness interventions for junior doctors and medical students. the available studies are small, and we have some concerns about their risk of bias. thus, there is not much evidence on which to draw conclusions on effects of mindfulness interventions in this population. there was no evidence to determine the effects of mindfulness in the long term.

NOT ENOUGH INFORMATION

LOW

respiratory system

Does long-term oral and inhaled antibiotic therapy effectively improve lung function and reduce exacerbation rate in people with chronic BCC lung infections?

Cystic fibrosis (CF) a life-limiting inherited disease affecting a number of organs, but classically associated with chronic lung infection and progressive loss of lung function. Chronic infection by Burkholderia cepacia complex (BCC) is associated with increased morbidity and mortality and therefore represents a significant challenge to clinicians treating people with CF. This review examines the current evidence for long-term antibiotic therapy in people with CF and chronic BCC infection.

The objective of this review is to assess the effects of long-term oral and inhaled antibiotic therapy targeted against chronic BCC lung infections in people with CF. The primary objective is to assess the efficacy of treatments in terms of improvements in lung function and reductions in exacerbation rate. Secondary objectives include quantifying adverse events, mortality and changes in quality of life associated with treatment.

We found insufficient evidence from the literature to determine an effective strategy for antibiotic therapy for treating chronic BCC infection.

NOT ENOUGH INFORMATION

LOW

respiratory system

Is injection sclerotherapy effective for the treatment of varicose veins?

Varicose veins are enlarged and tortuous veins, affecting up to one-third of the world's population. They can be a cause of chronic venous insufficiency, which is characterised by oedema, pigmentation, eczema, lipodermatosclerosis, atrophie blanche, and healed or active venous ulcers. Injection sclerotherapy (liquid or foam) is widely used for treatment of varicose veins aiming to transform the varicose veins into a fibrous cord. However, there is limited evidence regarding its effectiveness and safety, especially in patients with more severe disease. This is the second update of the review first published in 2002.

To assess the effectiveness and safety of injection sclerotherapy for the treatment of varicose veins.

There is a very low to low-certainty evidence that, compared to placebo, sclerotherapy is an effective and safe treatment for varicose veins concerning cosmetic appearance, residual varicose veins, QoL, and persistence of symptoms. Rates of DVT may be slightly increased and there were no data concerning recurrent varicose veins. There was limited or no evidence for one concentration of foam compared to another; foam compared to liquid sclerotherapy; foam compared to any other substance; or one technique compared to another. There is a need for high-quality trials using standardised sclerosant doses, with clearly defined core outcome sets, and measurement time points to increase the certainty of the evidence.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Do non-steroidal anti-inflammatory drugs (NSAIDs) improve pain and have little to no effect on function, inflammation, or adverse events for treating acute gout?

Gout is an inflammatory arthritis resulting from the deposition of monosodium urate crystals in and around joints. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat acute gout. This is an update of a Cochrane Review first published in 2014.

To assess the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) (including cyclo-oxygenase-2 (COX-2) inhibitors (COXIBs)) for acute gout.

Low-certainty evidence from 1 placebo-controlled trial suggests that NSAIDs may improve pain at 24 hours and may have little to no effect on function, inflammation, or adverse events for treatment of acute gout. Moderate-certainty evidence shows that COXIBs and non-selective NSAIDs are probably equally beneficial with regards to improvement in pain, function, inflammation, and treatment success, although non-selective NSAIDs probably increase withdrawals due to adverse events and total adverse events. Moderate-certainty evidence shows that systemic glucocorticoids and NSAIDs probably are equally beneficial in terms of pain relief, improvement in function, and treatment success. Withdrawals due to adverse events were also similar between groups, but NSAIDs probably result in more total adverse events. Low-certainty evidence suggests no difference in inflammation between groups. Only low-certainty evidence was available for the comparisons NSAID versus rilonacept and NSAID versus acupuncture from single trials, or one NSAID versus another NSAID, which also included many NSAIDs that are no longer in clinical use. Although these data were insufficient to support firm conclusions, they do not conflict with clinical guideline recommendations based upon evidence from observational studies, findings for other inflammatory arthritis, and expert consensus, all of which support the use of NSAIDs for acute gout.

SUPPORTED

LOW

musculoskeletal system and dermatology

Did the study investigate the effects of antibiotics for reducing symptoms of sore throat for child and adult patients?

Human African trypanosomiasis, or sleeping sickness, is a severe disease affecting people in the poorest parts of Africa. It is usually fatal without treatment. Conventional treatments require days of intravenous infusion, but a recently developed drug, fexinidazole, can be given orally. Another oral drug candidate, acoziborole, is undergoing clinical development and will be considered in subsequent editions. OBJECTIVES: To evaluate the effectiveness and safety of currently used drugs for treating second-stage Trypanosoma brucei gambiense trypanosomiasis (gambiense human African trypanosomiasis, g-HAT).

Search methods:

oral treatment with fexinidazole is much easier to administer than conventional treatment, but deaths and relapse appear to be more common. however, the advantages or an oral option are considerable, in terms of convenience, avoiding hospitalisation and multiple intravenous infusions, thus increasing adherence.

SUPPORTED

MEDIUM

immune system and infections

Do antibiotics reduce the severity and duration of sore throat symptoms?

Sore throat is a common reason for people to present for medical care and to be prescribed antibiotics. Overuse of antibiotics in primary medicine is a concern, hence it is important to establish their efficacy in treating sore throat and preventing secondary complications. OBJECTIVES: To assess the effects of antibiotics for reducing symptoms of sore throat for child and adult patients.

Search methods:

Antibiotics probably reduce the number of people experiencing sore throat, and reduce the likelihood of headache, and some sore throat complications. As the effect on symptoms can be small, clinicians must judge on an individual basis whether it is clinically justifiable to use antibiotics to produce this effect, and whether the underlying cause of the sore throat is likely to be of bacterial origin. Furthermore, the balance between modest symptom reduction and the potential hazards of antimicrobial resistance must be recognised. Few trials have attempted to measure symptom severity. If antibiotics reduce the severity as well as the duration of symptoms, their benefit will have been underestimated in this meta-analysis. Additionally, more trials are needed in low-income countries, in socio-economically deprived sections of high-income countries, as well as in children.

NOT ENOUGH INFORMATION

LOW

immune system and infections

Was the optimal mode of delivery in women with, or carriers of, bleeding disorders investigated?

Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre-pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.

To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.

The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus. Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.

NOT ENOUGH INFORMATION

LOW

cancer

Is one type of parenteral anticoagulant probably superior to another for the initial treatment of VTE in people with cancer?

Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE.

To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer.

Low molecular weight heparin (LMWH) is probably superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.

SUPPORTED

MEDIUM

cancer

Is there enough evidence to draw reliable conclusions about the advantages and disadvantages of different monitoring strategies for clinical intervention studies?

Trial monitoring is an important component of good clinical practice to ensure the safety and rights of study participants, confidentiality of personal information, and quality of data. However, the effectiveness of various existing monitoring approaches is unclear. Information to guide the choice of monitoring methods in clinical intervention studies may help trialists, support units, and monitors to effectively adjust their approaches to current knowledge and evidence.

To evaluate the advantages and disadvantages of different monitoring strategies (including risk-based strategies and others) for clinical intervention studies examined in prospective comparative studies of monitoring interventions.

The evidence base is limited in terms of quantity and quality. Ideally, for each of the five identified comparisons, more prospective, comparative monitoring studies nested in clinical trials and measuring effects on all outcomes specified in this review are necessary to draw more reliable conclusions. However, the results suggesting risk-based, targeted, and mainly central monitoring as an efficient strategy are promising. The development of reliable triggers for on-site visits is ongoing; different triggers might be used in different settings. More evidence on risk indicators that identify sites with problems or the prognostic value of triggers is needed to further optimize central monitoring strategies. In particular, approaches with an initial assessment of trial-specific risks that need to be closely monitored centrally during trial conduct with triggered on-site visits should be evaluated in future research.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Did the review investigate the clinical efficacy of different pharmacological treatments for acute psychotic depression?

Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015.

1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment.

Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking.

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Do resilience-building programmes effectively prevent negative mental health outcomes in military and frontline emergency service personnel?

Military personnel and frontline emergency workers may be exposed to events that have the potential to precipitate negative mental health outcomes such as depression, symptoms of post-traumatic stress and even post-traumatic stress disorder (PTSD). Programmes have been designed to build psychological resilience before staff are deployed into the field. This review presents a synthesis of the literature on these "pre-deployment resilience-building programmes".

The objective of this review was to assess the effectiveness of programmes that seek to build resilience to potentially traumatic events among military and frontline emergency service personnel prior to their deployment. These resilience programmes were compared to other interventions, treatment as usual or no intervention.

While a number of evaluations of relevant programmes have been published, the quality of these evaluations limits our ability to determine if resilience-building programmes 'work' in terms of preventing negative outcomes such as depression, symptoms of post-traumatic stress and diagnoses of PTSD. Based on our findings we recommend that future research should: a) report pre-/post-means and standard deviation scores for scales used within respective studies, b) take the form of large, RCTs with protocols published in advance, and c) seek to measure defined psychological facets such as resilience, PTSD and stress, and measure these concepts using established psychometric tools. This will provide more certainty in future assessments of the evidence base. From a clinical implications point of view, overall there is mixed evidence that the interventions included in this review are effective at safe guarding military personnel or frontline emergency workers from experiencing negative mental health outcomes, including PTSD, following exposure to potentially traumatic events. Based on this, practitioners seeking to build resilience in their personnel need to be aware of the limitations of the evidence base. Practitioners should have modest expectations in relation to the efficacy of resilience-building programmes as a prophylactic approach to employment-related critical incident traumas.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Can carisbamate be useful for drug-resistant focal epilepsy?

Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 80% to 85% of all cases. For people with localised NSCLC (stages I to III), it has been speculated that immunotherapy may be helpful for reducing postoperative recurrence rates, or improving the clinical outcomes of current treatment for unresectable tumours. This is an update of a Cochrane Review first published in 2017 and it includes two new randomised controlled trials (RCTs).

To assess the effectiveness and safety of immunotherapy (excluding checkpoint inhibitors) among people with localised NSCLC of stages I to III who received curative intent of radiotherapy or surgery.

Trial registration:

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does carisbamate demonstrate efficacy and tolerability as an add-on therapy for drug-resistant focal epilepsy?

Epilepsy is one of the most common neurological disorders. Many people with epilepsy are drug-resistant and require add-on therapy, meaning that they concomitantly take multiple antiepileptic drugs. Carisbamate is a drug which is taken orally and inhibits voltage-gated sodium channels. Carisbamate may be useful for drug-resistant focal epilepsy.

To evaluate the efficacy and tolerability of carisbamate when used as an add-on therapy for drug-resistant focal epilepsy.

The results suggest that carisbamate may demonstrate efficacy and tolerability as an add-on therapy for drug-resistant focal epilepsy. Importantly, the evidence for all outcomes except responder rate was of low to very low certainty, therefore we are uncertain of the accuracy of the reported effects. The certainty of the evidence is limited by the significant risk of bias associated with the included studies, as well as the statistical heterogeneity detected for some outcomes. Consequently, it is difficult for these findings to inform clinical practice. The studies were all of short duration and only included adult study populations. There is a need for further RCTs with more clear methodology, long-term follow-up, more clinical outcomes, more seizure types, and a broader range of participants.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Is implanted spinal neuromodulation effective for chronic pain?

Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity.

To evaluate the efficacy, effectiveness, adverse events, and cost-effectiveness of implanted spinal neuromodulation interventions for people with chronic pain.

We found very low-certainty evidence that SCS may not provide clinically important benefits on pain intensity compared to placebo stimulation. We found low- to very low-certainty evidence that SNMD interventions may provide clinically important benefits for pain intensity when added to conventional medical management or physical therapy. SCS is associated with complications including infection, electrode lead failure/migration and a need for reoperation/re-implantation. The level of certainty regarding the size of those risks is very low. SNMD may lead to serious adverse events, including death. We found no evidence to support or refute the use of DRGS for chronic pain.

REFUTED

LOW

musculoskeletal system and dermatology

Can antioxidant agents prevent respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition?

The main focus of treatment for children hospitalised with bronchiolitis is supportive, including oxygen supplementation, respiratory support, and fluid therapy. Up to half of infants hospitalised with bronchiolitis require non-oral fluid therapy due to dehydration or concerns related to the safety of oral feeding. The two main modalities used for non-oral fluid therapy are parenteral (intravenous (IV)) and enteral tube (nasogastric (NG) or orogastric (OG)). However, it is not known which mode is optimal in young children.

To systematically review randomised clinical trials (RCTs) of the effectiveness and safety of parenteral and enteral tube fluid therapy for children under two years of age hospitalised with bronchiolitis.

Based on two RCTs, enteral tube feeding likely results in little to no difference in length of hospital stay compared with the IV fluid group. However, enteral tube fluid therapy likely results in a large increase in the success of insertion of fluid modality at first attempt, and a large reduction in change in modality of fluid therapy. It also probably reduces local complications compared to the IV fluid group. Despite bronchiolitis being one of the most prevalent childhood conditions, we identified only two studies with under 1000 participants in total, which highlights the need for multicentre trials. Future studies should explore type of fluid administered, parent-reported outcomes and preferences, and the role of shared decision-making.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Can blue light-enhanced transurethral resection of bladder cancer (TURBT) improve staging and achieve a complete resection of non-muscle invasive bladder cancer (NMIBC)?

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.

Selection criteria:

Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

NOT ENOUGH INFORMATION

LOW

cancer

Does blue light-enhanced TURBT reduce the risk of disease recurrence and progression compared to white light-based TURBT?

Disease recurrence and progression remain major challenges in the treatment of non-muscle invasive bladder cancer (NMIBC). Blue light-enhanced transurethral resection of bladder cancer (TURBT) is an approach to improve staging and achieve a complete resection of NMIBC.

To assess the effects of blue light-enhanced TURBT compared to white light-based TURBT in the treatment of NMIBC.

Blue light-enhanced TURBT for the treatment of non-muscle invasive bladder cancer compared to white light-based TURBT may reduce the risk of disease recurrence and disease progression over time depending on baseline risk. There may be little or no effect on serious surgical complications. The certainty of evidence for our findings was low, meaning that future studies are likely change to the reported estimates of effect. Frequent issues that led to downgrading of the certainty of the evidence were study limitations, inconsistency, and imprecision.

SUPPORTED

LOW

cancer

Is the appropriate pressure levels to apply during nasal CPAP use uncertain?

About one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have previously been considered to be ineligible for thrombolytic treatment because the time of stroke onset is unknown. However, recent studies suggest benefit from recanalisation therapies in selected patients.

To assess the effects of intravenous thrombolysis and endovascular thrombectomy versus control in people with acute ischaemic stroke presenting on awakening from sleep.

In selected patients with acute ischaemic wake-up stroke, both intravenous thrombolytic treatment and endovascular thrombectomy of large vessel occlusion improved functional outcome without increasing the risk of death. However, a possible increased risk of symptomatic intracranial haemorrhage associated with thrombolytic treatment cannot be ruled out. The criteria used for selecting patients to treatment differed between the trials. All studies were relatively small, and six of the seven studies were terminated early. More studies are warranted in order to determine the optimal criteria for selecting patients for treatment.

NOT ENOUGH INFORMATION

NOT APPLICABLE

respiratory system

Can abdominal pain in Crohn's disease be multifaceted and not solely related to disease relapse?

Preterm infants are at risk of lung atelectasis due to various anatomical and physiological immaturities, placing them at high risk of respiratory failure and associated harms. Nasal continuous positive airway pressure (CPAP) is a positive pressure applied to the airways via the nares. It helps prevent atelectasis and supports adequate gas exchange in spontaneously breathing infants. Nasal CPAP is used in the care of preterm infants around the world. Despite its common use, the appropriate pressure levels to apply during nasal CPAP use remain uncertain.

To assess the effects of 'low' (≤ 5 cm H

there are insufficient data from randomized trials to guide nasal cpap level selection in preterm infants, whether provided as initial respiratory support or following extubation from invasive mechanical ventilation. we are uncertain as to whether low or moderate-high nasal cpap levels improve morbidity and mortality in preterm infants. well-designed trials evaluating this important aspect of a commonly used neonatal therapy are needed.

NOT ENOUGH INFORMATION

LOW

digestive system and metabolism

Did the interventions for managing abdominal pain in people with Crohn's disease and IBD show clear efficacy and safety?

Crohn's disease is a remitting and relapsing disorder that can affect the whole gastrointestinal tract. Active disease symptoms include abdominal pain, fatigue, weight loss, and diarrhoea. There is no known cure; however, the disease can be managed, and therefore places a huge financial burden on healthcare systems. Abdominal pain is a common and debilitating symptom of Crohn's and other inflammatory bowel diseases (IBDs), and is multifaceted. Abdominal pain in Crohn's disease could be a symptom of disease relapse or related to medication adverse effects, surgical complications and strictures or adhesions secondary to IBD. In the absence of these factors, around 20 to 50% of people with Crohn's in remission still experience pain.

To assess the efficacy and safety of interventions for managing abdominal pain in people with Crohn's disease and IBD (where data on ulcerative colitis and Crohn's disease could not be separated).

We found low certainty evidence that transcranial direct current stimulation may improve pain intensity compared to sham stimulation. We could not reach any conclusions on the efficacy of any other interventions on pain intensity, pain frequency, and treatment success. The certainty of the evidence was very low due to the low numbers of studies and participants in each comparison and clinical heterogeneity amongst the studies. While no serious or total adverse events were elicited explicitly with any of the treatments studied, the reported events were very low. The certainty of the evidence for all comparisons was very low, so no conclusions can be drawn.

NOT ENOUGH INFORMATION

LOW

digestive system and metabolism

Does insulin therapy guided by continuous glucose monitoring have a significant impact on the lives of people with CFRD compared to other forms of glucose data collection?

Cystic fibrosis (CF) is one of the most common life-shortening autosomal-recessive genetic conditions with around 100,000 people affected globally. CF mainly affects the respiratory system, but cystic fibrosis-related diabetes (CFRD) is a common extrapulmonary co-morbidity and causes excess morbidity and mortality in this population. Continuous glucose monitoring systems (CGMS) are a relatively new technology and, as yet, the impact of these on the monitoring and subsequent management of CFRD remains undetermined.

To establish the impact of insulin therapy guided by continuous glucose monitoring compared to insulin therapy guided by other forms of glucose data collection on the lives of people with CFRD.

No studies were included in the review, indicating that there is currently insufficient evidence to determine the impact of insulin therapy guided by CGMS compared to insulin therapy guided by other forms of glucose data collection on the lives of people with CFRD, nor on potential adverse effects of continuous glucose monitoring in this context. Randomised controlled studies are needed to generate evidence on the efficacy and safety of continuous glucose monitoring in people with CFRD. There is one relevant ongoing study that may be eligible for inclusion in a future update of this Cochrane Review, and whose results may help answer the review question.

NOT ENOUGH INFORMATION

LOW

endocrine system and hormones

Did Roselle show a clear effect on blood pressure in people with primary hypertension?

Hypertension is considered to be a serious health problem worldwide. Controlling and lowering blood pressure are of significant benefit to people with hypertension because hypertension is a risk factor for stroke, heart disease, and cardiovascular disease. Roselle, the tropical plant Hibiscus sabdariffa, also commonly called sour tea or red tea, has been used as both a thirst-quenching drink and for medicinal purposes.

To assess the effect of Roselle on blood pressure in people with primary hypertension.

The evidence is currently insufficient to determine the effectiveness of Roselle compared to placebo for controlling or lowering blood pressure in people with hypertension. The certainty of evidence was very low due to methodological limitations, imprecision, and indirectness. There is a need for rigorous RCTs that address the review question.

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Is hysteroscopy done in an outpatient setting using different media for distending the uterine cavity effective?

Delirium is an acute neuropsychological disorder that is common in hospitalised patients. It can be distressing to patients and carers and it is associated with serious adverse outcomes. Treatment options for established delirium are limited and so prevention of delirium is desirable. Non-pharmacological interventions are thought to be important in delirium prevention. OBJECTIVES: To assess the effectiveness of non-pharmacological interventions designed to prevent delirium in hospitalised patients outside intensive care units (ICU).

Search methods:

there is moderate-certainty evidence regarding the benefit of multicomponent non-pharmacological interventions for the prevention of delirium in hospitalised adults, estimated to reduce incidence by 43% compared to usual care. we found no evidence of an effect on mortality. there is emerging evidence that these interventions may reduce hospital length of stay, with a trend towards reduced delirium duration, although the effect on delirium severity remains uncertain. further research should focus on implementation and detailed analysis of the components of the interventions to support more effective, tailored practice recommendations.

NOT ENOUGH INFORMATION

LOW

sexual and reproductive health

Did the study evaluate the safety and efficacy of therapies for NETs and provide estimates of relative efficiency of the different treatment options?

Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into improved care faces several challenges, as a direct comparison of the most pertinent therapies is incomplete.

To evaluate the safety and efficacy of therapies for NETs, to guide clinical decision-making, and to provide estimates of relative efficiency of the different treatment options (including placebo) and rank the treatments according to their efficiency based on a network meta-analysis.

The findings from this study suggest that a range of efficient therapies with different safety profiles is available for people with NETs.

SUPPORTED

MEDIUM

cancer

Did the interventions effectively reduce medication errors in adults in hospital settings?

Medication errors are preventable events that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional or patient. Medication errors in hospitalised adults may cause harm, additional costs, and even death.

To determine the effectiveness of interventions to reduce medication errors in adults in hospital settings.

Low- to moderate-certainty evidence suggests that, compared to usual care, medication reconciliation, CPOE/CDSS, barcoding, feedback and dispensing systems in surgical wards may reduce medication errors and ADEs. However, the results are imprecise for some outcomes related to medication reconciliation and CPOE/CDSS. The evidence for other interventions is very uncertain. Powered and methodologically sound studies are needed to address the identified evidence gaps. Innovative, synergistic strategies -including those that involve patients- should also be evaluated.

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Did the review find sufficient evidence to support the efficacy and tolerability of topiramate in the treatment of JME?

Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2019.

To evaluate the efficacy and tolerability of topiramate in the treatment of JME.

We have found no new studies since the last version of this review was published in 2019. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.

REFUTED

LOW

cognitive, mental, and mental health

Did n-3 polyunsaturated fatty acids show clear effects as a treatment for major depressive disorder in adults?

Major depressive disorder (MDD) is highly debilitating, difficult to treat, has a high rate of recurrence, and negatively impacts the individual and society as a whole. One potential treatment for MDD is n-3 polyunsaturated fatty acids (n-3PUFAs), also known as omega-3 oils, naturally found in fatty fish, some other seafood, and some nuts and seeds. Various lines of evidence suggest a role for n-3PUFAs in MDD, but the evidence is far from conclusive. Reviews and meta-analyses clearly demonstrate heterogeneity between studies. Investigations of heterogeneity suggest different effects of n-3PUFAs, depending on the severity of depressive symptoms, where no effects of n-3PUFAs are found in studies of individuals with mild depressive symptomology, but possible benefit may be suggested in studies of individuals with more severe depressive symptomology. Hence it is important to establish their effectiveness in treating MDD. This review updates and incorporates an earlier review with the same research objective (Appleton 2015).

To assess the effects of n-3 polyunsaturated fatty acids (also known as omega-3 fatty acids) versus a comparator (e.g. placebo, antidepressant treatment, standard care, no treatment, wait-list control) for major depressive disorder (MDD) in adults.

At present, we do not have sufficient high-certainty evidence to determine the effects of n-3PUFAs as a treatment for MDD. Our primary analyses may suggest a small-to-modest, non-clinically beneficial effect of n-3PUFAs on depressive symptomology compared to placebo; however the estimate is imprecise, and we judged the certainty of the evidence on which this result is based to be low to very low. Our data may also suggest similar rates of adverse events and trial non-completion in n-3PUFA and placebo groups, but again our estimates are very imprecise. Effects of n-3PUFAs compared to antidepressants are very imprecise and uncertain. More complete evidence is required for both the potential positive and negative effects of n-3PUFAs for MDD.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Does active information provision improve stroke-survivor knowledge and quality of life, and reduce anxiety and depression?

A stroke is a sudden loss of brain function caused by lack of blood supply. Stroke can lead to death or physical and cognitive impairment and can have long lasting psychological and social implications. Research shows that stroke survivors and their families are dissatisfied with the information provided and have a poor understanding of stroke and associated issues.

The primary objective is to assess the effects of active or passive information provision for stroke survivors (people with a clinical diagnosis of stroke or transient ischaemic attack (TIA)) or their identified carers. The primary outcomes are knowledge about stroke and stroke services, and anxiety.

Active information provision may improve stroke-survivor knowledge and quality of life, and may reduce anxiety and depression. However, the reductions in anxiety and depression scores were small and may not be important. In contrast, providing information passively may slightly worsen stroke-survivor anxiety and depression scores, although again the importance of this is unclear. Evidence relating to carers and to other outcomes of passive information provision is generally very uncertain. Although the best way to provide information is still unclear, the evidence is better for strategies that actively involve stroke survivors and carers and include planned follow-up for clarification and reinforcement.

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Did the adjuvant pharmacological therapies have a clear effect on mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis?

Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial meningitis is antibiotics and corticosteroids. Although these therapies significantly improve outcomes, bacterial meningitis still has a high risk of death and a high risk of neurological sequelae in survivors. New adjuvant therapies are needed to further reduce the risk of death and neurological sequelae in bacterial meningitis.

To assess the effects of non-corticosteroid adjuvant pharmacological therapies for mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis.

Few adjuvant therapies for bacterial meningitis have been tested in RCTs. Paracetamol may make little or no difference to mortality, with a high level of uncertainty in the absolute effects (low certainty evidence). Paracetamol may make little or no difference to hearing loss, neurological sequelae other than hearing loss, and severe hearing loss (all low certainty evidence). Paracetamol may lead to slightly more short-term and long-term neurological sequelae other than hearing loss (both outcomes low certainty evidence). There is insufficient evidence to determine whether any of the adjuvant therapies included in this review (paracetamol, immunoglobulins, heparin, pentoxifylline, or a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide) are beneficial or detrimental in acute bacterial meningitis.

NOT ENOUGH INFORMATION

LOW

immune system and infections

Does the implementation of EWS and RRS lead to improved outcomes for adults who deteriorate on acute hospital wards?

Early warning systems (EWS) and rapid response systems (RRS) have been implemented internationally in acute hospitals to facilitate early recognition, referral and response to patient deterioration as a solution to address suboptimal ward-based care. EWS and RRS facilitate healthcare decision-making using checklists and provide structure to organisational practices through governance and clinical audit. However, it is unclear whether these systems improve patient outcomes. This is the first update of a previously published (2007) Cochrane Review.

To determine the effect of EWS and RRS implementation on adults who deteriorate on acute hospital wards compared to people receiving hospital care without EWS and RRS in place.

Given the low-to-very low certainty evidence for all outcomes from non-randomised studies, we have drawn our conclusions from the randomised evidence. This evidence provides low-certainty evidence that EWS and RRS may lead to little or no difference in hospital mortality, unplanned ICU admissions, length of hospital stay or adverse events; and moderate-certainty evidence of little to no difference on composite outcome. The evidence from this review update highlights the diversity in outcome selection and poor methodological quality of most studies investigating EWS and RRS. As a result, no strong recommendations can be made regarding the effectiveness of EWS and RRS based on the evidence currently available. There is a need for development of a patient-informed core outcome set comprising clear and consistent definitions and recommendations for measurement as well as EWS and RRS interventions conforming to a standard to facilitate meaningful comparison and future meta-analyses.

NOT ENOUGH INFORMATION

LOW

cancer

Did the use of growth hormone as an adjunct to IVF treatment show clear effectiveness in improving live birth rates and mean number of oocytes retrieved?

In an effort to improve outcomes of in vitro fertilisation (IVF) cycles, the use of growth hormone (GH) has been considered as adjuvant treatment in ovarian stimulation. Improving the outcomes of IVF is especially important for women with infertility who are considered 'poor responders'. We have compared the outcomes of IVF with adjuvant GH versus no adjuvant treatment in routine use, and specifically in poor responders.

To assess the effectiveness and safety of growth hormone as an adjunct to IVF compared to standard IVF for women with infertility SEARCH METHODS: We searched the following databases (to November 2020): Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL, MEDLINE, Embase, CINAHL, Epistemonikos database and trial registers together with reference checking and contact with study authors and experts in the field to identify additional trials.

The use of adjuvant GH in IVF treatment protocols has uncertain effect on live birth rates and mean number of oocytes retrieved in normal responders. However, it slightly increases the number of oocytes retrieved and pregnancy rates in poor responders, while there is an uncertain effect on live birth rates in this group. The results however, need to be interpreted with caution, as the included trials were small and few in number, with significant bias and imprecision. Also, the dose and regimen of GH used in trials was variable. Therefore, further research is necessary to fully define the role of GH as adjuvant therapy in IVF.

NOT ENOUGH INFORMATION

LOW

endocrine system and hormones

Does macrolides have an effect on managing chronic asthma compared with placebo?

Asthma is a chronic disease in which inflammation of the airways causes symptomatic wheezing, coughing and difficult breathing. Macrolides are antibiotics with antimicrobial and anti-inflammatory activities that have been explored for the long-term control of asthma symptoms.

To assess the effects of macrolides compared with placebo for managing chronic asthma.

Existing evidence suggests an effect of macrolides compared with placebo on the rate of exacerbations requiring hospitalisation. Macrolides probably reduce severe exacerbations (requiring ED visit and/or treatment with systemic steroids) and may reduce symptoms. However, we cannot rule out the possibility of other benefits or harms because the evidence is of very low quality due to heterogeneity among patients and interventions, imprecision and reporting biases. The results were mostly driven by a well-designed, well powered RCT, indicating that azithromycin may reduce exacerbation rate and improve symptom scores in severe asthma. The review highlights the need for researchers to report outcomes accurately and according to standard definitions. Macrolides can reduce exacerbation rate in people with severe asthma. Future trials could evaluate if this effect is sustained across all the severe asthma phenotypes, the comparison with newer biological drugs, whether effects persist or wane after treatment cessation and whether effects are associated with infection biomarkers.

SUPPORTED

LOW

respiratory system

Did the study assess the effectiveness, safety, and adverse effects of certain vaccines given to children?

Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.

To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.

existing evidence on the safety and effectiveness of mmr/mmrv vaccines support their use for mass immunisation. campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. more evidence is needed to assess whether the protective effect of mmr/mmrv could wane with time since immunisation.

SUPPORTED

MEDIUM

immune system and infections

Does vitamin C supplementation have an impact on preventing and treating pneumonia?

Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different approaches, including a more intensified antihypertensive therapy, lifestyle modifications or both, have largely failed to improve patients' outcomes and to reduce cardiovascular and renal risk. As renal sympathetic hyperactivity is a major driver of resistant hypertension, in the last decade renal sympathetic ablation (renal denervation) has been proposed as a possible therapeutic alternative to treat this condition.

We sought to evaluate the short- and long-term effects of renal denervation in individuals with resistant hypertension on clinical end points, including fatal and non-fatal cardiovascular events, all-cause mortality, hospital admissions, quality of life, blood pressure control, left ventricular hypertrophy, cardiovascular and metabolic profile and kidney function, as well as the potential adverse events related to the procedure.

Trial registration:

NOT ENOUGH INFORMATION

LOW

nutrition and dietary supplements

Can altering blood pressure reduce the risk of complications in people with acute subarachnoid haemorrhage?

Rotavirus is a common cause of diarrhoea, diarrhoea-related hospital admissions, and diarrhoea-related deaths worldwide. Rotavirus vaccines prequalified by the World Health Organization (WHO) include Rotarix (GlaxoSmithKline), RotaTeq (Merck), and, more recently, Rotasiil (Serum Institute of India Ltd.), and Rotavac (Bharat Biotech Ltd.).

To evaluate rotavirus vaccines prequalified by the WHO for their efficacy and safety in children.

Trial registration:

NOT ENOUGH INFORMATION

LOW

cardiovascular system

Do antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids provide superior prevention of chemotherapy-induced nausea and vomiting compared to treatment combinations including 5-HT₃ receptor antagonists and corticosteroids solely?

Acute limb ischaemia usually is caused by a blood clot blocking an artery or a bypass graft. Severe acute ischaemia will lead to irreversible damage to muscles and nerves if blood flow is not restored in a few hours. Once irreversible damage occurs, amputation will be necessary and the condition can be life-threatening. Infusion of clot-busting drugs (thrombolysis) is a useful tool in the management of acute limb ischaemia. Fibrinolytic drugs are used to disperse blood clots (thrombi) to clear arterial occlusion and restore blood flow. Thrombolysis is less invasive than surgery. A variety of techniques are used to deliver fibrinolytic agents. This is an update of a review first published in 2004.

To compare the effects of infusion techniques during peripheral arterial thrombolysis for treatment of patients with acute limb ischaemia.

There is insufficient evidence to show that any thrombolytic regimen provides a benefit over any other in terms of amputation-free survival, amputation, or 30-day mortality. The rate of CVA or major bleeding requiring surgery or blood transfusion did not clearly differ between regimens but may occur more frequently in high dose and IV regimens. This evidence was limited and of very low certainty. Minor bleeding may be more common with high-dose and IV regimens. In this context, thrombolysis may be an acceptable therapy for patients with marginally threatened limbs (Rutherford grade IIa) compared with surgery. Caution is advised for patients who do not have limb-threatening ischaemia (Rutherford grade I) because of risks of major haemorrhage, cerebrovascular accident, and death from thrombolysis.

NOT ENOUGH INFORMATION

LOW

cancer

Does palivizumab continue to effectively prevent severe RSV disease in children?

About 70% to 80% of adults with cancer experience chemotherapy-induced nausea and vomiting (CINV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5-hydroxytryptamine-3 (5-HT₃) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK₁) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head-to-head comparisons do not allow comparison of all treatments versus another. OBJECTIVES: • In adults with solid cancer or haematological malignancy receiving HEC - To compare the effects of antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting in network meta-analysis (NMA) - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy • In adults with solid cancer or haematological malignancy receiving MEC - To compare whether antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting to treatment combinations including 5-HT₃ receptor antagonists and corticosteroids solely, in network meta-analysis - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs).

Selection criteria:

This field of supportive cancer care is very well researched. However, new drugs or drug combinations are continuously emerging and need to be systematically researched and assessed. For people receiving HEC, synthesised evidence does not suggest one superior treatment for prevention and control of chemotherapy-induced nausea and vomiting. For people receiving MEC, synthesised evidence does not suggest superiority for treatments including both NK₁ and 5-HT₃ inhibitors when compared to treatments including 5-HT₃ inhibitors only. Rather, the results of our NMA suggest that the choice of 5-HT₃ inhibitor may have an impact on treatment efficacy in preventing CINV. When interpreting the results of this systematic review, it is important for the reader to understand that NMAs are no substitute for direct head-to-head comparisons, and that results of our NMA do not necessarily rule out differences that could be clinically relevant for some individuals.

NOT ENOUGH INFORMATION

LOW

respiratory system

Does palivizumab reduce severe RSV infection in children?

Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population. Palivizumab is administered intramuscularly every month during five months in the first RSV season to prevent serious RSV LRTI in children. Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children.

To assess the effects of palivizumab for preventing severe RSV infection in children.

The available evidence suggests that prophylaxis with palivizumab reduces hospitalisation due to RSV infection and results in little to no difference in mortality or adverse events. Moreover, palivizumab results in a slight reduction in hospitalisation due to respiratory-related illness and may result in a large reduction in RSV infections. Palivizumab also reduces the number of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumab on children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, children lacking breastfeeding, living in poverty, or members of families in overcrowded situations.

SUPPORTED

MEDIUM

respiratory system

Did siponimod interventions show clear benefits for people diagnosed with MS?

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, with an unpredictable course. Current MS therapies such as disease-modifying therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. Siponimod (BAF312) is an oral treatment, a selective sphingosine-1-phosphate (S1P) receptor modulator, for the treatment of adults with relapsing forms of MS including active, secondary progressive MS with relapses.

To assess the benefits and adverse effects of siponimod as monotherapy or combination therapy versus placebo or any active comparator for people diagnosed with MS.

Based on the findings of the RCTs included in this review, we are uncertain whether siponimod interventions are beneficial for people with MS. There was low-certainty evidence to support that siponimod at a dose of 2 mg orally once daily as monotherapy compared with placebo may reduce the annualised relapse rate and the number of participants who experienced disability worsening, at 6 months. However, the certainty of the evidence to support the benefit in reducing the number of people with a relapse is very low. The risk of withdrawals due to adverse events requires careful monitoring of participants over time. The duration of all studies was less than 24 months, so the efficacy and safety of siponimod over 24 months are still uncertain, and further exploration is needed in the future. There is no high-certainty data available to evaluate the benefit on MRI outcomes. We assessed the certainty of the body of evidence for all outcomes was low to very low, downgraded due to serious study limitations, imprecision and indirectness. We are uncertain whether siponimod is beneficial for people with MS. More new studies with robust methodology and longer follow-up are needed to evaluate the benefit of siponimod for the management of MS and to observe long-term adverse effects. Also, in addition to comparing with placebo, more new studies are needed to evaluate siponimod versus other therapeutic options.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Did SSRIs make a difference in improving outcomes for people less than 12 months post-stroke compared to placebo or usual care?

Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post-stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019.

To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects.

There is high-quality evidence that SSRIs do not make a difference to disability or independence after stroke compared to placebo or usual care, reduced the risk of future depression, increased bone fractures and probably increased seizure risk.

REFUTED

HIGH

cognitive, mental, and mental health

Did the review evaluate the safety and efficacy of different immunosuppressive treatments for adult patients with PMN and nephrotic syndrome?

Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Without treatment, approximately 30% of patients will experience spontaneous remission and one third will have persistent proteinuria. Approximately one-third of patients progress toward end-stage kidney disease (ESKD) within 10 years. Immunosuppressive treatment aims to protect kidney function and is recommended for patients who do not show improvement of proteinuria by supportive therapy, and for patients with severe nephrotic syndrome at presentation due to the high risk of developing ESKD. The efficacy and safety of different immunosuppressive regimens are unclear. This is an update of a Cochrane review, first published in 2004 and updated in 2013.

The aim was to evaluate the safety and efficacy of different immunosuppressive treatments for adult patients with PMN and nephrotic syndrome.

This updated review strengthened the evidence that immunosuppressive therapy is probably superior to non-immunosuppressive therapy in inducing remission and reducing the number of patients that progress to ESKD. However, these benefits need to be balanced against the side effects of immunosuppressive drugs. The number of included studies with high-quality design was relatively small and most studies did not have adequate follow-up. Clinicians should inform their patients of the lack of high-quality evidence. An alkylating agent (cyclophosphamide or chlorambucil) combined with a corticosteroid regimen had short- and long-term benefits, but this was associated with a higher rate of adverse events. CNI (tacrolimus and cyclosporin) showed equivalency with alkylating agents however, the certainty of this evidence remains low. Novel immunosuppressive treatments with the biologic rituximab or use of adrenocorticotropic hormone require further investigation and validation in large and high-quality RCTs.

SUPPORTED

MEDIUM

renal and urinary system

Does multidisciplinary rehabilitation for older people with hip fracture result in improved outcomes?

Hip fracture is a major cause of morbidity and mortality in older people, and its impact on society is substantial. After surgery, people require rehabilitation to help them recover. Multidisciplinary rehabilitation is where rehabilitation is delivered by a multidisciplinary team, supervised by a geriatrician, rehabilitation physician or other appropriate physician. This is an update of a Cochrane Review first published in 2009.

To assess the effects of multidisciplinary rehabilitation, in either inpatient or ambulatory care settings, for older people with hip fracture.

In a hospital inpatient setting, there is moderate-certainty evidence that rehabilitation after hip fracture surgery, when delivered by a multidisciplinary team and supervised by an appropriate medical specialist, results in fewer cases of 'poor outcome' (death or deterioration in residential status). There is low-certainty evidence that multidisciplinary rehabilitation may result in fewer deaths in hospital and at 4 to 12 months; however, it may also result in slightly more. There is low-certainty evidence that multidisciplinary rehabilitation may reduce the numbers of people with poorer mobility at 12 months. No conclusions can be drawn on other outcomes, for which the evidence is of very low certainty. The generally very low-certainty evidence available for supported discharge and multidisciplinary home rehabilitation means that we are very uncertain whether the findings of little or no difference for all outcomes between the intervention and usual care is true. Given the prevalent clinical emphasis on early discharge, we suggest that research is best orientated towards early supported discharge and identifying the components of multidisciplinary inpatient rehabilitation to optimise patient recovery within hospital and the components of multidisciplinary rehabilitation, including social care, subsequent to hospital discharge.

SUPPORTED

MEDIUM

musculoskeletal system and dermatology

Does late systemic postnatal corticosteroid treatment reduce the risks of mortality and BPD for preterm infants with evolving or established BPD?

Many infants born preterm develop bronchopulmonary dysplasia (BPD), with lung inflammation playing a role. Corticosteroids have powerful anti-inflammatory effects and have been used to treat individuals with established BPD. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs.

To examine the relative benefits and adverse effects of late (starting at seven or more days after birth) systemic postnatal corticosteroid treatment for preterm infants with evolving or established BPD.

Late systemic postnatal corticosteroid treatment (started at seven days or more after birth) reduces the risks of mortality and BPD, and the combined outcome of mortality or BPD, without evidence of increased cerebral palsy. However, the methodological quality of studies determining long-term outcomes is limited, and no studies were powered to detect increased rates of important adverse long-term neurodevelopmental outcomes. This review supports the use of late systemic corticosteroids for infants who cannot be weaned from mechanical ventilation. The role of late systemic corticosteroids for infants who are not intubated is unclear and needs further investigation. Longer-term follow-up into late childhood is vital for assessment of important outcomes that cannot be assessed in early childhood, such as effects of late systemic corticosteroid treatment on higher-order neurological functions, including cognitive function, executive function, academic performance, behaviour, mental health, motor function, and lung function. Further RCTs of late systemic corticosteroids should include longer-term survival free of neurodevelopmental disability as the primary outcome.

SUPPORTED

MEDIUM

cognitive, mental, and mental health

Did perioperative NSAID use have a significant impact on postoperative outcomes in women undergoing breast surgery?

Breast surgery encompasses oncologic, reconstructive, and cosmetic procedures. With the recent focus on the over-prescribing of opioids in the literature, it is important to assess the effectiveness and safety of non-opioid pain medication regimens including nonsteroidal anti-inflammatory drugs (NSAIDs) or NSAID pain medications. Clinicians have differing opinions on the safety of perioperative (relating to, occurring in, or being the period around the time of a surgical operation) NSAIDs for breast surgery given the unclear risk/benefit ratio. NSAIDs have been shown to decrease inflammation, pain, and fever, while potentially increasing the risks of bleeding complications.

To assess the effects of perioperative NSAID use versus non-NSAID analgesics (other pain medications) in women undergoing any form of breast surgery.

Low-certainty evidence suggests that NSAIDs may reduce postoperative pain, nausea and vomiting, and postoperative opioid use. However, there was very little evidence to indicate whether NSAIDs affect the rate of breast hematoma or bleeding from any location within 90 days of breast surgery, the need for blood transfusion and incidence of other side effects compared to placebo or other analgesics. High-quality large-scale RCTs are required before definitive conclusions can be made.

NOT ENOUGH INFORMATION

LOW

cancer

Does decision coaching have a measurable impact on diagnostic accuracy?

Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma and can emerge throughout the whole body. For patients with newly diagnosed RMS, prognosis for survival depends on multiple factors such as histology, tumour site, and extent of the disease. Patients with metastatic disease at diagnosis have impaired prognosis compared to those with localised disease. Appropriate staging at diagnosis therefore plays an important role in choosing the right treatment regimen for an individual patient. Fluorine-18-fluorodeoxyglucose (

To determine the diagnostic accuracy of

The diagnostic accuracy of

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Did the antioxidant agents prevent respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition?

Decision coaching is non-directive support delivered by a healthcare provider to help patients prepare to actively participate in making a health decision. 'Healthcare providers' are considered to be all people who are engaged in actions whose primary intent is to protect and improve health (e.g. nurses, doctors, pharmacists, social workers, health support workers such as peer health workers). Little is known about the effectiveness of decision coaching.

To determine the effects of decision coaching (I) for people facing healthcare decisions for themselves or a family member (P) compared to (C) usual care or evidence-based intervention only, on outcomes (O) related to preparation for decision making, decisional needs and potential adverse effects.

Decision coaching may improve participants' knowledge when used with evidence-based information. Our findings do not indicate any significant adverse effects (e.g. decision regret, anxiety) with the use of decision coaching. It is not possible to establish strong conclusions for other outcomes. It is unclear if decision coaching always needs to be paired with evidence-informed information. Further research is needed to establish the effectiveness of decision coaching for a broader range of outcomes.

NOT ENOUGH INFORMATION

LOW

musculoskeletal system and dermatology

Does rituximab show beneficial effects for adults with MS?

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.

Selection criteria:

Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

NOT ENOUGH INFORMATION

LOW

cognitive, mental, and mental health

Is there evidence to recommend surgery for individuals with lamellar macular holes (LMHs) to stabilize the LMH and prevent further visual deterioration?

Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available. OBJECTIVES: To assess beneficial and adverse effects of rituximab as 'first choice' and as 'switching' for adults with MS.

Search methods:

For preventing relapses in relapsing MS, rituximab as 'first choice' and as 'switching' may compare favourably with a wide range of approved DMTs. A protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab for progressive MS. The evidence is uncertain about the effect of rituximab on SAEs. They are relatively rare in people with MS, thus difficult to study, and they were not well reported in studies. There is an increased risk of common infections with rituximab, but absolute risk is small. Rituximab is widely used as off-label treatment in people with MS; however, randomised evidence is weak. In the absence of randomised evidence, remaining uncertainties on beneficial and adverse effects of rituximab for MS might be clarified by making real-world data available.

NOT ENOUGH INFORMATION

LOW

sensory organs

Did surgical interventions demonstrate improvements in post-operative visual and anatomical outcomes in people with a confirmed LMH?

Lamellar macular holes (LMHs) are small, partial-thickness defects of the macula defined by characteristic features on optical coherence tomography (OCT), including a newly recognised type of epiretinal membrane termed 'epiretinal proliferation'. There may be a rationale to recommend surgery for individuals with LMHs, particularly those with functional or anatomical deterioration, or poor baseline vision causing significant disability, to stabilise the LMH and prevent further visual deterioration; however, there is currently no evidence-based consensus.

To assess the effect of surgical interventions on post-operative visual and anatomical outcomes in people with a confirmed LMH.

The included single trial demonstrated improvements in visual and anatomical outcome measures for participants with a LMH who underwent surgery compared with observation only. Therefore, we can conclude that participants who undergo surgery may achieve superior post-operative best corrected visual acuity and anatomical outcomes compared with observation only. However, the results of a single and small RCT provides limited evidence to support or refute surgery as an effective management option for LMHs. Future RCTs with a larger number of participants and with fewer methodological limitations and biases are necessary to inform future clinical practice.

SUPPORTED

LOW

sensory organs