Background
Dementia is a progressive global cognitive impairment syndrome. In 2010, more than 35 million people worldwide were estimated to be living with dementia. Some people with mild cognitive ...impairment (MCI) will progress to dementia but others remain stable or recover full function. There is great interest in finding good predictors of dementia in people with MCI. The Mini‐Mental State Examination (MMSE) is the best‐known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings.
Objectives
To determine the diagnostic accuracy of the MMSE at various thresholds for detecting individuals with baseline MCI who would clinically convert to dementia in general, Alzheimer’s disease dementia or other forms of dementia at follow‐up.
Search methods
We searched ALOIS (Cochrane Dementia and Cognitive Improvement Specialized Register of diagnostic and intervention studies (inception to May 2014); MEDLINE (OvidSP) (1946 to May 2014); EMBASE (OvidSP) (1980 to May 2014); BIOSIS (Web of Science) (inception to May 2014); Web of Science Core Collection, including the Conference Proceedings Citation Index (ISI Web of Science) (inception to May 2014); PsycINFO (OvidSP) (inception to May 2014), and LILACS (BIREME) (1982 to May 2014). We also searched specialized sources of diagnostic test accuracy studies and reviews, most recently in May 2014: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of s of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). No language or date restrictions were applied to the electronic searches and methodological filters were not used as a method to restrict the search overall so as to maximize sensitivity. We also checked reference lists of relevant studies and reviews, tracked citations in Scopus and Science Citation Index, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on MMSE for dementia diagnosis to try to locate possibly relevant but unpublished data.
Selection criteria
We considered longitudinal studies in which results of the MMSE administered to MCI participants at baseline were obtained and the reference standard was obtained by follow‐up over time. We included participants recruited and clinically classified as individuals with MCI under Petersen and revised Petersen criteria, Matthews criteria, or a Clinical Dementia Rating = 0.5. We used acceptable and commonly used reference standards for dementia in general, Alzheimer’s dementia, Lewy body dementia, vascular dementia and frontotemporal dementia.
Data collection and analysis
We screened all titles generated by the electronic database searches. Two review authors independently assessed the s of all potentially relevant studies. We assessed the identified full papers for eligibility and extracted data to create two by two tables for dementia in general and other dementias. Two authors independently performed quality assessment using the QUADAS‐2 tool. Due to high heterogeneity and scarcity of data, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic curve.
Main results
In this review, we included 11 heterogeneous studies with a total number of 1569 MCI patients followed for conversion to dementia. Four studies assessed the role of baseline scores of the MMSE in conversion from MCI to all‐cause dementia and eight studies assessed this test in conversion from MCI to Alzheimer´s disease dementia. Only one study provided information about the MMSE and conversion from MCI to vascular dementia. For conversion from MCI to dementia in general, the accuracy of baseline MMSE scores ranged from sensitivities of 23% to 76% and specificities from 40% to 94%. In relationship to conversion from MCI to Alzheimer’s disease dementia, the accuracy of baseline MMSE scores ranged from sensitivities of 27% to 89% and specificities from 32% to 90%. Only one study provided information about conversion from MCI to vascular dementia, presenting a sensitivity of 36% and a specificity of 80% with an incidence of vascular dementia of 6.2%. Although we had planned to explore possible sources of heterogeneity, this was not undertaken due to the scarcity of studies included in our analysis.
Authors' conclusions
Our review did not find evidence supporting a substantial role of MMSE as a stand‐alone single‐administration test in the identification of MCI patients who could develop dementia. Clinicians could prefer to request additional and extensive tests to be sure about the management of these patients. An important aspect to assess in future updates is if conversion to dementia from MCI stages could be predicted better by MMSE changes over time instead of single measurements. It is also important to assess if a set of tests, rather than an isolated one, may be more successful in predicting conversion from MCI to dementia.
This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can assess the results and the certainty of evidence ...(also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA).
We present an overview of the GRADE approach and guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests. Part 1 of the two parts in this 21st guidance article about how to apply GRADE focuses on understanding study design issues in test accuracy, provide an overview of the domains, and describe risk of bias and indirectness specifically.
Supplemented by practical examples, we describe how raters of the evidence using GRADE can evaluate study designs focusing on tests and how they apply the GRADE domains risk of bias and indirectness to a body of evidence of TA studies.
Rating the certainty of a body of evidence using GRADE in Cochrane and other reviews and World Health Organization and other guidelines dealing with in TA studies helped refining our approach. The resulting guidance will help applying GRADE successfully for questions and recommendations focusing on tests.
This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can rate the certainty of evidence (also known as ...quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA) on the domains imprecision, inconsistency, publication bias, and other domains. It also provides guidance for how to present synthesized information in evidence profiles and summary of findings tables.
We present guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests.
Supplemented by practical examples, we describe how raters of the evidence can apply the GRADE domains inconsistency, imprecision, and publication bias to a body of evidence of TA studies.
Using GRADE in Cochrane and other reviews as well as World Health Organization and other guidelines helped refining the GRADE approach for rating the certainty of a body of evidence from TA studies. Although several of the GRADE domains (e.g., imprecision and magnitude of the association) require further methodological research to help operationalize them, judgments need to be made on the basis of what is known so far.
Background
Post‐dural puncture headache (PDPH) is one of the most common complications of diagnostic and therapeutic lumbar punctures. PDPH is defined as any headache occurring after a lumbar ...puncture that worsens within 15 minutes of sitting or standing and is relieved within 15 minutes of the patient lying down. Researchers have suggested many types of interventions to help prevent PDPH. It has been suggested that aspects such as needle tip and gauge can be modified to decrease the incidence of PDPH.
Objectives
To assess the effects of needle tip design (traumatic versus atraumatic) and diameter (gauge) on the prevention of PDPH in participants who have undergone dural puncture for diagnostic or therapeutic causes.
Search methods
We searched CENTRAL, MEDLINE, Embase, CINAHL and LILACS, as well as trial registries via the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal in September 2016. We adopted the MEDLINE strategy for searching the other databases. The search terms we used were a combination of thesaurus‐based and free‐text terms for both interventions (lumbar puncture in neurological, anaesthesia or myelography settings) and headache.
Selection criteria
We included randomized controlled trials (RCTs) conducted in any clinical/research setting where dural puncture had been used in participants of all ages and both genders, which compared different tip designs or diameters for prevention of PDPH
Data collection and analysis
We used the standard methodological procedures expected by Cochrane.
Main results
We included 70 studies in the review; 66 studies with 17,067 participants were included in the quantitative analysis. An additional 18 studies are awaiting classification and 12 are ongoing. Fifteen of the 18 studies awaiting classification mainly correspond to congress summaries published before 2010, in which the available information does not allow the complete evaluation of all their risks of bias and characteristics. Our main outcome was prevention of PDPH, but we also assessed the onset of severe PDPH, headache in general and adverse events. The quality of evidence was moderate for most of the outcomes mainly due to risk of bias issues. For the analysis, we undertook three main comparisons: 1) traumatic needles versus atraumatic needles; 2) larger gauge traumatic needles versus smaller gauge traumatic needles; and 3) larger gauge atraumatic needles versus smaller gauge atraumatic needles. For each main comparison, if data were available, we performed a subgroup analysis evaluating lumbar puncture indication, age and posture.
For the first comparison, the use of traumatic needles showed a higher risk of onset of PDPH compared to atraumatic needles (36 studies, 9378 participants, risk ratio (RR) 2.14, 95% confidence interval (CI) 1.72 to 2.67, I2 = 9%).
In the second comparison of traumatic needles, studies comparing various sizes of large and small gauges showed no significant difference in effects in terms of risk of PDPH, with the exception of one study comparing 26 and 27 gauge needles (one study, 658 participants, RR 6.47, 95% CI 2.55 to 16.43).
In the third comparison of atraumatic needles, studies comparing various sizes of large and small gauges showed no significant difference in effects in terms of risk of PDPH.
We observed no significant difference in the risk of paraesthesia, backache, severe PDPH and any headache between traumatic and atraumatic needles. Sensitivity analyses of PDPH results between traumatic and atraumatic needles omitting high risk of bias studies showed similar results regarding the benefit of atraumatic needles in the prevention of PDPH (three studies, RR 2.78, 95% CI 1.26 to 6.15; I2 = 51%).
Authors' conclusions
There is moderate‐quality evidence that atraumatic needles reduce the risk of post‐dural puncture headache (PDPH) without increasing adverse events such as paraesthesia or backache. The studies did not report very clearly on aspects related to randomization, such as random sequence generation and allocation concealment, making it difficult to interpret the risk of bias in the included studies. The moderate quality of the evidence for traumatic versus atraumatic needles suggests that further research is likely to have an important impact on our confidence in the estimate of effect.
Background
Infantile haemangiomas (previously known as strawberry birthmarks) are soft, raised swellings of the skin that occur in 3% to 10% of infants. These benign vascular tumours are usually ...uncomplicated and tend to regress spontaneously. However, when haemangiomas occur in high‐risk areas, such as near the eyes, throat, or nose, impairing their function, or when complications develop, intervention may be necessary. This is an update of a Cochrane Review first published in 2011.
Objectives
To assess the effects of interventions for the management of infantile haemangiomas in children.
Search methods
We updated our searches of the following databases to February 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, LILACS, and CINAHL. We also searched five trials registries and checked the reference lists of included studies for further references to relevant trials.
Selection criteria
Randomised controlled trials (RCTs) of all types of interventions, versus placebo, active monitoring, or other interventions, in any child with single or multiple infantile haemangiomas (IHs) located on the skin.
Data collection and analysis
We used standard methodological procedures expected by Cochrane. The primary outcome measures were clearance, a subjective measure of improvement, and adverse events. Secondary outcomes were other measures of resolution; proportion of parents or children who consider there is still a problem; aesthetic appearance; and requirement for surgical correction. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
Main results
We included 28 RCTs, with a total of 1728 participants, assessing 12 different interventions, including lasers, beta blockers (e.g. propranolol, timolol maleate), radiation therapy, and steroids. Comparators included placebo, an active monitoring approach, sham radiation, and interventions given alone or in combination.
Studies were conducted in a number of countries, including China, Egypt, France, and Australia. Participant age ranged from 12 weeks to 13.4 years. Most studies (23/28) included a majority of females and different types of IHs. Duration of follow‐up ranged from 7 days to 72 months.
We considered most of the trials as at low risk of random sequence generation, attrition bias, and selective reporting bias. Domains such as allocation concealment and blinding were not clearly reported in general. We downgraded evidence for issues related to risk of bias and imprecision.
We report results for the three most important comparisons, which we chose on the basis of current use. Outcome measurement of these comparisons was at 24 weeks' follow‐up.
Oral propranolol versus placebo
Compared with placebo, oral propranolol 3 mg/kg/day probably improves clinician‐assessed clearance (risk ratio (RR) 16.61, 95% confidence interval (CI) 4.22 to 65.34; 1 study; 156 children; moderate‐quality evidence) and probably leads to a clinician‐assessed reduction in mean haemangioma volume of 45.9% (95% CI 11.60 to 80.20; 1 study; 40 children; moderate‐quality evidence). We found no evidence of a difference in terms of short‐ or long‐term serious adverse events (RR 1.05, 95% CI 0.33 to 3.39; 3 studies; 509 children; low‐quality evidence), nor in terms of bronchospasm, hypoglycaemia, or serious cardiovascular adverse events. The results relating to clearance and resolution for this comparison were based on one industry‐sponsored study.
Topical timolol maleate versus placebo
The chance of reduction of redness, as a measure of clinician‐assessed resolution, may be improved with topical timolol maleate 0.5% gel applied twice daily when compared with placebo (RR 8.11, 95% CI 1.09 to 60.09; 1 study; 41 children;low‐quality evidence). Regarding short‐ or long‐term serious cardiovascular events, we found no instances of bradycardia (slower than normal heart rate) or hypotension in either group (1 study; 41 children; low‐quality evidence). No other safety data were assessed, and clearance was not measured.
Oral propranolol versus topical timolol maleate
When topical timolol maleate (0.5% eye drops applied twice daily) was compared with oral propranolol (via a tablet taken once per day, at a 1.0 mg/kg dose), there was no evidence of a difference in haemangioma size (as a measure of resolution) when measured by the proportion of patients with a clinician‐assessed reduction of 50% or greater (RR 1.13, 95% CI 0.64 to 1.97; 1 study; 26 participants; low‐quality evidence). Although there were more short‐ or long‐term general adverse effects (such as severe diarrhoea, lethargy, and loss of appetite) in the oral propranolol group, there was no evidence of a difference between groups (RR 7.00, 95% CI 0.40 to 123.35; 1 study; 26 participants; very low‐quality evidence). This comparison did not measure clearance.
None of our key comparisons evaluated, at any follow‐up, a subjective measure of improvement assessed by the parent or child; proportion of parents or children who consider there is still a problem; or physician‐, child‐, or parent‐assessed aesthetic appearance.
Authors' conclusions
We found there to be a limited evidence base for the treatment of infantile haemangiomas: a large number of interventions and outcomes have not been assessed in RCTs.
Our key results indicate that in the management of IH in children, oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harms. We found no evidence of a difference between oral propranolol and topical timolol maleate with regard to reducing haemangioma size, but we are uncertain if there is a difference in safety. Oral propranolol is currently the standard treatment for this condition, and our review has not found evidence to challenge this. However, these results are based on moderate‐ to very low‐quality evidence.
The included studies were limited by small sample sizes and risk of bias in some domains. Future trials should blind personnel and participants; describe trials thoroughly in publications; and recruit a sufficient number of children to deduce meaningful results. Future trials should assess patient‐reported outcomes, as well as objective outcomes of benefit, and should report adverse events comprehensively. Propranolol and timolol maleate require further assessment in RCTs of all types of IH, including those considered problematic, as do other lesser‐used interventions and new interventions. All treatments should be compared against propranolol and timolol maleate, as beta blockers are approved as standard care.
Background
The definition of sepsis has evolved over time, along with the clinical and scientific knowledge behind it. For years, sepsis was defined as a systemic inflammatory response syndrome ...(SIRS) in the presence of a documented or suspected infection. At present, sepsis is defined as a life‐threatening organ dysfunction resulting from a dysregulated host response to infection. Even though sepsis is one of the leading causes of mortality in critically ill patients, and the World Health Organization (WHO) recognizes it as a healthcare priority, it still lacks an accurate diagnostic test. Determining the accuracy of interleukin‐6 (IL‐6) concentrations in plasma, which is proposed as a new biomarker for the diagnosis of sepsis, might be helpful to provide adequate and timely management of critically ill patients, and thus reduce the morbidity and mortality associated with this condition.
Objectives
To determine the diagnostic accuracy of plasma interleukin‐6 (IL‐6) concentration for the diagnosis of bacterial sepsis in critically ill adults.
Search methods
We searched CENTRAL, MEDLINE, Embase, LILACS, and Web of Science on 25 January 2019. We screened references in the included studies to identify additional studies. We did not apply any language restriction to the electronic searches.
Selection criteria
We included diagnostic accuracy studies enrolling critically ill adults aged 18 years or older under suspicion of sepsis during their hospitalization, where IL‐6 concentrations were evaluated by serological measurement.
Data collection and analysis
Two review authors independently screened the references to identify relevant studies and extracted data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non‐linear mixed model. We explored sources of heterogeneity using the HSROC model parameters. We conducted all analyses in the SAS statistical software package and R software.
Main results
We included 23 studies (n = 4192) assessing the accuracy of IL‐6 for the diagnosis of sepsis in critically ill adults. Twenty studies that were available as conference proceedings only are awaiting classification. The included participants were heterogeneous in terms of their distribution of age, gender, main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and origin of infection, among other factors. Prevalence of sepsis greatly varied across studies, ranging from 12% to 78%. We considered all studies to be at high risk of bias due to issues related to the index test domain in QUADAS‐2. The SROC curve showed a great dispersion in individual studies accuracy estimates (21 studies, 3650 adult patients), therefore the considerable heterogeneity in the collected data prevented us from calculating formal accuracy estimates. Using a fixed prevalence of sepsis of 50% and a fixed specificity of 74%, we found a sensitivity of 66% (95% confidence interval 60 to 72). If we test a cohort 1000 adult patients under suspicion of sepsis with IL‐6, we will find that 330 patients would receive appropriate and timely antibiotic therapy, while 130 patients would be wrongly considered to have sepsis. In addition, 370 out of 1000 patients would avoid unnecessary antibiotic therapy, and 170 patients would have been undiagnosed of sepsis. This numerical approach should be interpreted with caution due to the limitations described above.
Authors' conclusions
Our evidence assessment of plasma interleukin‐6 concentrations for the diagnosis of sepsis in critically ill adults reveals several limitations. High heterogeneity of collected evidence regarding the main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and the origin of infection, among other factors, along with the potential number of misclassifications, remain significant constraints for its implementation. The 20 conference proceedings assessed as studies awaiting classification may alter the conclusions of the review once they are fully published and evaluated. Further studies about the accuracy of interleukin‐6 for the diagnosis of sepsis in adults that apply rigorous methodology for conducting diagnostic test accuracy studies are needed. The conclusions of the review will likely change once the 20 studies pending publication are fully published and included.
A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse ...transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19.
We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020.
We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues.
There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence).
Protocol available on the OSF website: https://tinyurl.com/vvbgqya.
Background
Hepatic encephalopathy is a common and devastating neuropsychiatric complication of acute liver failure or chronic liver disease. Ammonia content in the blood seems to play a role in the ...development of hepatic encephalopathy. Treatment for hepatic encephalopathy is complex. Acetyl‐L‐carnitine is a substance that may reduce ammonia toxicity. This review assessed the benefits and harms of acetyl‐L‐carnitine for patients with hepatic encephalopathy.
Objectives
To assess the benefits and harms of acetyl‐L‐carnitine for patients with hepatic encephalopathy.
Search methods
We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and Science Citation Index Expanded for randomised clinical trials. We sought additional randomised clinical trials from the World Health Organization Clinical Trials Search Portal and ClinicalTrials.gov. We performed all electronic searches until 10 September 2018. We looked through the reference lists of retrieved publications and review articles, and we searched the FDA and EMA websites.
Selection criteria
We searched for randomised clinical trials in any setting, recruiting people with hepatic encephalopathy. Trials were eligible for inclusion if they compared acetyl‐L‐carnitine plus standard care (e.g. antibiotics, lactulose) versus placebo or no acetyl‐L‐carnitine plus standard care. We are well aware that by selecting randomised clinical trials, we placed greater focus on potential benefits than on potential harms.
Data collection and analysis
We selected randomised clinical trials, assessed risk of bias in eight domains, and extracted data in a duplicate and independent fashion. We estimated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. We measured statistical heterogeneity using I² and D² statistics. We subjected our analyses to fixed‐effect and random‐effects model meta‐analyses. We assessed bias risk domains to control systematic errors. We assessed overall quality of the data for each individual outcome by using the GRADE approach.
Main results
We identified five randomised clinical trials involving 398 participants. All trials included only participants with cirrhosis as the underlying cause of hepatic encephalopathy. Trials included participants with covert or overt hepatic encephalopathy. All trials were conducted in Italy by a single team and assessed acetyl‐L‐carnitine compared with placebo. Oral intervention was the most frequent route of administration. All trials were at high risk of bias and were underpowered. None of the trials were sponsored by the pharmaceutical industry.
None of the identified trials reported information on all‐cause mortality, serious adverse events, or days of hospitalisation. Only one trial assessed quality of life using the Short Form (SF)‐36 scale (67 participants; very low‐quality evidence). The effects of acetyl‐L‐carnitine compared with placebo on general health at 90 days are uncertain (MD ‐6.20 points, 95% confidence interval (CI) ‐9.51 to ‐2.89). Results for additional domains of the SF‐36 are also uncertain. One trial assessed fatigue using the Wessely and Powell test (121 participants; very low‐quality evidence). The effects are uncertain in people with moderate‐grade hepatic encephalopathy (mental fatigue: MD 0.40 points, 95% CI ‐0.21 to 1.01; physical fatigue: MD ‐0.20 points, 95% CI ‐0.92 to 0.52) and mild‐grade hepatic encephalopathy (mental fatigue: ‐0.80 points, 95% CI ‐1.48 to ‐0.12; physical fatigue: 0.20 points, 95% CI ‐0.72 to 1.12). Meta‐analysis showed a reduction in blood ammonium levels favouring acetyl‐L‐carnitine versus placebo (MD ‐13.06 mg/dL, 95% CI ‐17.24 to ‐8.99; 387 participants; 5 trials; very low‐quality evidence). It is unclear whether acetyl‐L‐carnitine versus placebo increases the risk of non‐serious adverse events (8/126 (6.34%) vs 3/120 (2.50%); RR 2.51, 95% CI 0.68 to 9.22; 2 trials; very low‐quality evidence). Overall, adverse events data were poorly reported and harms may have been underestimated.
Authors' conclusions
This Cochrane systematic review analysed a heterogeneous group of five trials at high risk of bias and with high risk of random errors conducted by only one research team. We assessed acetyl‐L‐carnitine versus placebo in participants with cirrhosis with covert or overt hepatic encephalopathy. Hence, we have no data on the drug for hepatic encephalopathy in acute liver failure. We found no information about all‐cause mortality, serious adverse events, or days of hospitalisation. We found no clear differences in effect between acetyl‐L‐carnitine and placebo regarding quality of life, fatigue, and non‐serious adverse events. Acetyl‐L‐carnitine reduces blood ammonium levels compared with placebo. We rated all evidence as of very low quality due to pitfalls in design and execution, inconsistency, small sample sizes, and very few events. The harms profile for acetyl‐L‐carnitine is presently unclear. Accordingly, we need further randomised clinical trials to assess acetyl‐L‐carnitine versus placebo conducted according to the SPIRIT statements and reported according to the CONSORT statements.
Interventions for treating acute high altitude illness Simancas‐Racines, Daniel; Arevalo‐Rodriguez, Ingrid; Osorio, Dimelza ...
Cochrane database of systematic reviews,
06/2018, Letnik:
2018, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Background
Acute high altitude illness is defined as a group of cerebral and pulmonary syndromes that can occur during travel to high altitudes. It is more common above 2500 metres, but can be seen ...at lower elevations, especially in susceptible people. Acute high altitude illness includes a wide spectrum of syndromes defined under the terms 'acute mountain sickness' (AMS), 'high altitude cerebral oedema' and 'high altitude pulmonary oedema'. There are several interventions available to treat this condition, both pharmacological and non‐pharmacological; however, there is a great uncertainty regarding their benefits and harms.
Objectives
To assess the clinical effectiveness, and safety of interventions (non‐pharmacological and pharmacological), as monotherapy or in any combination, for treating acute high altitude illness.
Search methods
We searched CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science, CINAHL, Wanfang database and the World Health Organization International Clinical Trials Registry Platform for ongoing studies on 10 August 2017. We did not apply any language restriction.
Selection criteria
We included randomized controlled trials evaluating the effects of pharmacological and non‐pharmacological interventions for individuals suffering from acute high altitude illness: acute mountain sickness, high altitude pulmonary oedema or high altitude cerebral oedema.
Data collection and analysis
Two review authors independently assessed the eligibility of study reports, the risk of bias for each and performed the data extraction. We resolved disagreements through discussion with a third author. We assessed the quality of evidence with GRADE.
Main results
We included 13 studies enrolling a total of 468 participants. We identified two ongoing studies. All studies included adults, and two studies included both teenagers and adults. The 13 studies took place in high altitude areas, mostly in the European Alps. Twelve studies included participants with acute mountain sickness, and one study included participants with high altitude pulmonary oedema. Follow‐up was usually less than one day. We downgraded the quality of the evidence in most cases due to risk of bias and imprecision. We report results for the main comparisons as follows.
Non‐pharmacological interventions (3 studies, 124 participants)
All‐cause mortality and complete relief of AMS symptoms were not reported in the three included trials. One study in 64 participants found that a simulated descent of 193 millibars versus 20 millibars may reduce the average of symptoms to 2.5 vs 3.1 units after 12 hours of treatment (clinical score ranged from 0 to 11 ‒ worse; reduction of 0.6 points on average with the intervention; low quality of evidence). In addition, no complications were found with use of hyperbaric chambers versus supplementary oxygen (one study; 29 participants; low‐quality evidence).
Pharmacological interventions (11 trials, 375 participants)
All‐cause mortality was not reported in the 11 included trials. One trial found a greater proportion of participants with complete relief of AMS symptoms after 12 and 16 hours when dexamethasone was administered in comparison with placebo (47.1% versus 0%, respectively; one study; 35 participants; low quality of evidence). Likewise, when acetazolamide was compared with placebo, the effects on symptom severity was uncertain (standardized mean difference (SMD) −1.15, 95% CI −2.56 to 0.27; 2 studies, 25 participants; low‐quality evidence). One trial of dexamethasone in comparison with placebo in 35 participants found a reduction in symptom severity (difference on change in the AMS score: 3.7 units reported by authors; moderate quality of evidence). The effects from two additional trials comparing gabapentin with placebo and magnesium with placebo on symptom severity at the end of treatment were uncertain. For gabapentin versus placebo: mean visual analogue scale (VAS) score of 2.92 versus 4.75, respectively; 24 participants; low quality of evidence. For magnesium versus placebo: mean scores of 9 and 10.3 units, respectively; 25 participants; low quality of evidence). The trials did not find adverse events from either treatment (low quality of evidence). One trial comparing magnesium sulphate versus placebo found that flushing was a frequent event in the magnesium sulphate arm (percentage of flushing: 75% versus 7.7%, respectively; one study; 25 participants; low quality of evidence).
Authors' conclusions
There is limited available evidence to determine the effects of non‐pharmacological and pharmacological interventions in treating acute high altitude illness. Low‐quality evidence suggests that dexamethasone and acetazolamide might reduce AMS score compared to placebo. However, the clinical benefits and harms related to these potential interventions remain unclear. Overall, the evidence is of limited practical significance in the clinical field. High‐quality research in this field is needed, since most trials were poorly conducted and reported.
This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows:
To determine the diagnostic accuracy of the Confusion Assessment Method for the Intensive Care Unit ...(CAM‐ICU) for the diagnosis of delirium in adult patients in critical care settings.
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