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and contacted research groups conducting work on MMSE for dementia diagnosis to try to locate possibly relevant but unpublished data.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.
Background
The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether diet, physical activity or both can prevent or ...delay T2DM and its associated complications in at‐risk people is unknown.
Objectives
To assess the effects of diet, physical activity or both on the prevention or delay of T2DM and its associated complications in people at increased risk of developing T2DM.
Search methods
This is an update of the Cochrane Review published in 2008. We searched the CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, ICTRP Search Portal and reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was January 2017. We continuously used a MEDLINE email alert service to identify newly published studies using the same search strategy as described for MEDLINE up to September 2017.
Selection criteria
We included randomised controlled trials (RCTs) with a duration of two years or more.
Data collection and analysis
We used standard Cochrane methodology for data collection and analysis. We assessed the overall quality of the evidence using GRADE.
Main results
We included 12 RCTs randomising 5238 people. One trial contributed 41% of all participants. The duration of the interventions varied from two to six years. We judged none of the included trials at low risk of bias for all 'Risk of bias' domains.
Eleven trials compared diet plus physical activity with standard or no treatment. Nine RCTs included participants with impaired glucose tolerance (IGT), one RCT included participants with IGT, impaired fasting blood glucose (IFG) or both, and one RCT included people with fasting glucose levels between 5.3 to 6.9 mmol/L. A total of 12 deaths occurred in 2049 participants in the diet plus physical activity groups compared with 10 in 2050 participants in the comparator groups (RR 1.12, 95% CI 0.50 to 2.50; 95% prediction interval 0.44 to 2.88; 4099 participants, 10 trials; very low‐quality evidence). The definition of T2DM incidence varied among the included trials. Altogether 315 of 2122 diet plus physical activity participants (14.8%) developed T2DM compared with 614 of 2389 comparator participants (25.7%) (RR 0.57, 95% CI 0.50 to 0.64; 95% prediction interval 0.50 to 0.65; 4511 participants, 11 trials; moderate‐quality evidence). Two trials reported serious adverse events. In one trial no adverse events occurred. In the other trial one of 51 diet plus physical activity participants compared with none of 51 comparator participants experienced a serious adverse event (low‐quality evidence). Cardiovascular mortality was rarely reported (four of 1626 diet plus physical activity participants and four of 1637 comparator participants (the RR ranged between 0.94 and 3.16; 3263 participants, 7 trials; very low‐quality evidence). Only one trial reported that no non‐fatal myocardial infarction or non‐fatal stroke had occurred (low‐quality evidence). Two trials reported that none of the participants had experienced hypoglycaemia. One trial investigated health‐related quality of life in 2144 participants and noted that a minimal important difference between intervention groups was not reached (very low‐quality evidence). Three trials evaluated costs of the interventions in 2755 participants. The largest trial of these reported an analysis of costs from the health system perspective and society perspective reflecting USD 31,500 and USD 51,600 per quality‐adjusted life year (QALY) with diet plus physical activity, respectively (low‐quality evidence). There were no data on blindness or end‐stage renal disease.
One trial compared a diet‐only intervention with a physical‐activity intervention or standard treatment. The participants had IGT. Three of 130 participants in the diet group compared with none of the 141 participants in the physical activity group died (very low‐quality evidence). None of the participants died because of cardiovascular disease (very low‐quality evidence). Altogether 57 of 130 diet participants (43.8%) compared with 58 of 141 physical activity participants (41.1%) group developed T2DM (very low‐quality evidence). No adverse events were recorded (very low‐quality evidence). There were no data on non‐fatal myocardial infarction, non‐fatal stroke, blindness, end‐stage renal disease, health‐related quality of life or socioeconomic effects.
Two trials compared physical activity with standard treatment in 397 participants. One trial included participants with IGT, the other trial included participants with IGT, IFG or both. One trial reported that none of the 141 physical activity participants compared with three of 133 control participants died. The other trial reported that three of 84 physical activity participants and one of 39 control participants died (very low‐quality evidence). In one trial T2DM developed in 58 of 141 physical activity participants (41.1%) compared with 90 of 133 control participants (67.7%). In the other trial 10 of 84 physical activity participants (11.9%) compared with seven of 39 control participants (18%) developed T2DM (very low‐quality evidence). Serious adverse events were rarely reported (one trial noted no events, one trial described events in three of 66 physical activity participants compared with one of 39 control participants ‐ very low‐quality evidence). Only one trial reported on cardiovascular mortality (none of 274 participants died ‐ very low‐quality evidence). Non‐fatal myocardial infarction or stroke were rarely observed in the one trial randomising 123 participants (very low‐quality evidence). One trial reported that none of the participants in the trial experienced hypoglycaemia. One trial investigating health‐related quality of life in 123 participants showed no substantial differences between intervention groups (very low‐quality evidence). There were no data on blindness or socioeconomic effects.
Authors' conclusions
There is no firm evidence that diet alone or physical activity alone compared to standard treatment influences the risk of T2DM and especially its associated complications in people at increased risk of developing T2DM. However, diet plus physical activity reduces or delays the incidence of T2DM in people with IGT. Data are lacking for the effect of diet plus physical activity for people with intermediate hyperglycaemia defined by other glycaemic variables. Most RCTs did not investigate patient‐important outcomes.
Background
A major determinant of treatment offered to patients with non‐small cell lung cancer (NSCLC) is their intrathoracic (mediastinal) nodal status. If the disease has not spread to the ...ipsilateral mediastinal nodes, subcarinal (N2) nodes, or both, and the patient is otherwise considered fit for surgery, resection is often the treatment of choice. Planning the optimal treatment is therefore critically dependent on accurate staging of the disease. PET‐CT (positron emission tomography–computed tomography) is a non‐invasive staging method of the mediastinum, which is increasingly available and used by lung cancer multidisciplinary teams. Although the non‐invasive nature of PET‐CT constitutes one of its major advantages, PET‐CT may be suboptimal in detecting malignancy in normal‐sized lymph nodes and in ruling out malignancy in patients with coexisting inflammatory or infectious diseases.
Objectives
To determine the diagnostic accuracy of integrated PET‐CT for mediastinal staging of patients with suspected or confirmed NSCLC that is potentially suitable for treatment with curative intent.
Search methods
We searched the following databases up to 30 April 2013: The Cochrane Library, MEDLINE via OvidSP (from 1946), Embase via OvidSP (from 1974), PreMEDLINE via OvidSP, OpenGrey, ProQuest Dissertations & Theses, and the trials register www.clinicaltrials.gov. There were no language or publication status restrictions on the search. We also contacted researchers in the field, checked reference lists, and conducted citation searches (with an end‐date of 9 July 2013) of relevant studies.
Selection criteria
Prospective or retrospective cross‐sectional studies that assessed the diagnostic accuracy of integrated PET‐CT for diagnosing N2 disease in patients with suspected resectable NSCLC. The studies must have used pathology as the reference standard and reported participants as the unit of analysis.
Data collection and analysis
Two authors independently extracted data pertaining to the study characteristics and the number of true and false positives and true and false negatives for the index test, and they independently assessed the quality of the included studies using QUADAS‐2. We calculated sensitivity and specificity with 95% confidence intervals (CI) for each study and performed two main analyses based on the criteria for test positivity employed: Activity > background or SUVmax ≥ 2.5 (SUVmax = maximum standardised uptake value), where we fitted a summary receiver operating characteristic (ROC) curve using a hierarchical summary ROC (HSROC) model for each subset of studies. We identified the average operating point on the SROC curve and computed the average sensitivities and specificities. We checked for heterogeneity and examined the robustness of the meta‐analyses through sensitivity analyses.
Main results
We included 45 studies, and based on the criteria for PET‐CT positivity, we categorised the included studies into three groups: Activity > background (18 studies, N = 2823, prevalence of N2 and N3 nodes = 679/2328), SUVmax ≥ 2.5 (12 studies, N = 1656, prevalence of N2 and N3 nodes = 465/1656), and Other/mixed (15 studies, N = 1616, prevalence of N2 to N3 nodes = 400/1616). None of the studies reported (any) adverse events. Under‐reporting generally hampered the quality assessment of the studies, and in 30/45 studies, the applicability of the study populations was of high or unclear concern.
The summary sensitivity and specificity estimates for the 'Activity > background PET‐CT positivity criterion were 77.4% (95% CI 65.3 to 86.1) and 90.1% (95% CI 85.3 to 93.5), respectively, but the accuracy estimates of these studies in ROC space showed a wide prediction region. This indicated high between‐study heterogeneity and a relatively large 95% confidence region around the summary value of sensitivity and specificity, denoting a lack of precision. Sensitivity analyses suggested that the overall estimate of sensitivity was especially susceptible to selection bias; reference standard bias; clear definition of test positivity; and to a lesser extent, index test bias and commercial funding bias, with lower combined estimates of sensitivity observed for all the low 'Risk of bias' studies compared with the full analysis.
The summary sensitivity and specificity estimates for the SUVmax ≥ 2.5 PET‐CT positivity criterion were 81.3% (95% CI 70.2 to 88.9) and 79.4% (95% CI 70 to 86.5), respectively.In this group, the accuracy estimates of these studies in ROC space also showed a very wide prediction region. This indicated very high between‐study heterogeneity, and there was a relatively large 95% confidence region around the summary value of sensitivity and specificity, denoting a clear lack of precision. Sensitivity analyses suggested that both overall accuracy estimates were marginally sensitive to flow and timing bias and commercial funding bias, which both lead to slightly lower estimates of sensitivity and specificity.
Heterogeneity analyses showed that the accuracy estimates were significantly influenced by country of study origin, percentage of participants with adenocarcinoma, (¹⁸F)‐2‐fluoro‐deoxy‐D‐glucose (FDG) dose, type of PET‐CT scanner, and study size, but not by study design, consecutive recruitment, attenuation correction, year of publication, or tuberculosis incidence rate per 100,000 population.
Authors' conclusions
This review has shown that accuracy of PET‐CT is insufficient to allow management based on PET‐CT alone. The findings therefore support National Institute for Health and Care (formally 'clinical') Excellence (NICE) guidance on this topic, where PET‐CT is used to guide clinicians in the next step: either a biopsy or where negative and nodes are small, directly to surgery. The apparent difference between the two main makes of PET‐CT scanner is important and may influence the treatment decision in some circumstances. The differences in PET‐CT accuracy estimates between scanner makes, NSCLC subtypes, FDG dose, and country of study origin, along with the general variability of results, suggest that all large centres should actively monitor their accuracy. This is so that they can make reliable decisions based on their own results and identify the populations in which PET‐CT is of most use or potentially little value.
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 accuracy of the Mini Mental State Examination for the early detection of dementia in people with mild cognitive impairment
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.
Background
Evidence from systematic reviews of observational studies suggests that hormone therapy may have beneficial effects in reducing the incidence of cardiovascular disease events in ...post‐menopausal women, however the results of randomised controlled trials (RCTs) have had mixed results. This is an updated version of a Cochrane review published in 2013.
Objectives
To assess the effects of hormone therapy for the prevention of cardiovascular disease in post‐menopausal women, and whether there are differential effects between use in primary or secondary prevention.
Secondary aims were to undertake exploratory analyses to (i) assess the impact of time since menopause that treatment was commenced (≥ 10 years versus < 10 years), and where these data were not available, use age of trial participants at baseline as a proxy (≥ 60 years of age versus < 60 years of age); and (ii) assess the effects of length of time on treatment.
Search methods
We searched the following databases on 25 February 2014: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE and LILACS. We also searched research and trials registers, and conducted reference checking of relevant studies and related systematic reviews to identify additional studies.
Selection criteria
RCTs of women comparing orally administered hormone therapy with placebo or a no treatment control, with a minimum of six months follow‐up.
Data collection and analysis
Two authors independently assessed study quality and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome. We combined results using random effects meta‐analyses, and undertook further analyses to assess the effects of treatment as primary or secondary prevention, and whether treatment was commenced more than or less than 10 years after menopause.
Main results
We identified six new trials through this update. Therefore the review includes 19 trials with a total of 40,410 post‐menopausal women. On the whole, study quality was good and generally at low risk of bias; the findings are dominated by the three largest trials. We found high quality evidence that hormone therapy in both primary and secondary prevention conferred no protective effects for all‐cause mortality, cardiovascular death, non‐fatal myocardial infarction, angina, or revascularisation. However, there was an increased risk of stroke in those in the hormone therapy arm for combined primary and secondary prevention (RR 1.24, 95% CI 1.10 to 1.41). Venous thromboembolic events were increased (RR 1.92, 95% CI 1.36 to 2.69), as were pulmonary emboli (RR 1.81, 95% CI 1.32 to 2.48) on hormone therapy relative to placebo.
The absolute risk increase for stroke was 6 per 1000 women (number needed to treat for an additional harmful outcome (NNTH) = 165; mean length of follow‐up: 4.21 years (range: 2.0 to 7.1)); for venous thromboembolism 8 per 1000 women (NNTH = 118; mean length of follow‐up: 5.95 years (range: 1.0 to 7.1)); and for pulmonary embolism 4 per 1000 (NNTH = 242; mean length of follow‐up: 3.13 years (range: 1.0 to 7.1)).
We performed subgroup analyses according to when treatment was started in relation to the menopause. Those who started hormone therapy less than 10 years after the menopause had lower mortality (RR 0.70, 95% CI 0.52 to 0.95, moderate quality evidence) and coronary heart disease (composite of death from cardiovascular causes and non‐fatal myocardial infarction) (RR 0.52, 95% CI 0.29 to 0.96; moderate quality evidence), though they were still at increased risk of venous thromboembolism (RR 1.74, 95% CI 1.11 to 2.73, high quality evidence) compared to placebo or no treatment. There was no strong evidence of effect on risk of stroke in this group. In those who started treatment more than 10 years after the menopause there was high quality evidence that it had little effect on death or coronary heart disease between groups but there was an increased risk of stroke (RR 1.21, 95% CI 1.06 to 1.38, high quality evidence) and venous thromboembolism (RR 1.96, 95% CI 1.37 to 2.80, high quality evidence).
Authors' conclusions
Our review findings provide strong evidence that treatment with hormone therapy in post‐menopausal women overall, for either primary or secondary prevention of cardiovascular disease events has little if any benefit and causes an increase in the risk of stroke and venous thromboembolic events.
Evidence from systematic reviews of observational studies suggest that hormone replacement therapy (HT) may have beneficial effects in reducing the incidence of cardiovascular disease (CVD) events in ...post-menopausal women. This is an updated version of a Cochrane review first published in 2005 (Gabriel-Sanchez 2005).
To assess the effects of HT for the prevention of CVD in post-menopausal women, and whether there are differential effects between use of single therapy alone compared to combination HT and use in primary or secondary prevention.
We searched the following databases to April 2010: Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE and LILACS.
Randomised controlled trials (RCTs) of women comparing orally administered HT with placebo with a minimum of six-months follow-up.
Two authors independently assessed study quality and extracted data. Risk Ratios (RR) with 95% confidence intervals were calculated for each outcome. Results were combined using fixed-effect meta-analyses, and where possible, further stratified analyses conducted to assess the effect of time on treatment. Additionally, univariate meta-regression analyses were undertaken to assess whether length of trial follow-up, single or combination treatment, or whether treatment for primary or secondary prevention were potential predictors for a number of CVD outcomes in the trials.
Four new trials were identified through the update; one trial included in the previous review was excluded. Therefore the review included 13 trials with a total of 38,171 post-menopausal women. Overall, single and combination HT in both primary and secondary prevention conferred no protective effects for all cause mortality, CVD death, non-fatal MI, or angina. There were no significant differences in the number of coronary artery by-pass procedures or angioplasties performed between the trial arms. However there was an increased risk of stroke for both primary and secondary prevention when combination and single HT was combined, RR 1.26 (95% CI 1.11 to 1.43), in venous thromboembolic events, RR 1.89 (95% CI 1.58 to 2.26) and in pulmonary embolism RR 1.84 (95% CI 1.42 to 2.37) relative to placebo. The associated numbers needed-to-harm (NNH) were 164, 109 and 243 for stroke, venous thromboembolism and pulmonary embolism respectively.
Treatment with HT in post-menopausal women for either primary or secondary prevention of CVD events is not effective, and causes an increase in the risk of stroke, and venous thromboembolic events. HT should therefore only be considered for women seeking relief from menopausal symptoms. Short-term HT treatment should be at the lowest effective dose, and used with caution in women with predisposing risk factors for CVD events.
Background
Post‐dural puncture headache (PDPH) is a common complication of lumbar punctures. Several theories have identified the leakage of cerebrospinal fluid (CSF) through the hole in the dura as ...a cause of this side effect. It is therefore necessary to take preventive measures to avoid this complication. Prolonged bed rest has been used to treat PDPH once it has started, but it is unknown whether prolonged bed rest can also be used to prevent it. Similarly, the value of administering fluids additional to those of normal dietary intake to restore the loss of CSF produced by the puncture is unknown. This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 7, 2013) on "Posture and fluids for preventing post‐dural puncture headache".
Objectives
To assess whether prolonged bed rest combined with different body and head positions, as well as administration of supplementary fluids after lumbar puncture, prevent the onset of PDPH in people undergoing lumbar puncture for diagnostic or therapeutic purposes.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS, as well as trial registries up to February 2015.
Selection criteria
We identified randomized controlled trials that compared the effects of bed rest versus immediate mobilization, head‐down tilt versus horizontal position, prone versus supine positions during bed rest, and administration of supplementary fluids versus no/less supplementation, as prevention measures for PDPH in people who have undergone lumbar puncture.
Data collection and analysis
Two review authors independently assessed the studies for eligibility through the web‐based software EROS (Early Review Organizing Software). Two different review authors independently assessed risk of bias using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We resolved any disagreements by consensus. We extracted data on cases of PDPH, severe PDPH, and any headache after lumbar puncture and performed intention‐to‐treat analyses and sensitivity analyses by risk of bias. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.
Main results
We included 24 trials with 2996 participants in this updated review. The number of participants in each trial varied from 39 to 382. Most of the included studies compared bed rest versus immediate mobilization, and only two assessed the effects of supplementary fluids versus no supplementation. We judged the overall risk of bias of the included studies as low to unclear. The overall quality of evidence was low to moderate, downgraded because of the risk of bias assessment in most cases. The primary outcome in our review was the presence of PDPH.
There was low quality evidence for an absence of benefits associated with bed rest compared with immediate mobilization on the incidence of severe PDPH (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.68 to 1.41; participants = 1568; studies = 9) and moderate quality evidence on the incidence of any headache after lumbar puncture (RR 1.16; 95% CI 1.02 to 1.32; participants = 2477; studies = 18). Furthermore, bed rest probably increased PDPH (RR 1.24; 95% CI 1.04 to 1.48; participants = 1519; studies = 12) compared with immediate mobilization. An analysis restricted to the most methodologically rigorous trials (i.e. those with low risk of bias in allocation method, missing data and blinding of outcome assessment) gave similar results. There was low quality evidence for an absence of benefits associated with fluid supplementation on the incidence of severe PDPH (RR 0.67; 95% CI 0.26 to 1.73; participants = 100; studies = 1) and PDPH (RR 1; 95% CI 0.59 to 1.69; participants = 100; studies = 1), and moderate quality evidence on the incidence of any headache after lumbar puncture (RR 0.94; 95% CI 0.66 to 1.34; participants = 200; studies = 2). We did not expect other adverse events and did not assess them in this review.
Authors' conclusions
Since the previous version of this review, we found one new study for inclusion, but the conclusion remains unchanged. We considered the quality of the evidence for most of the outcomes assessed in this review to be low to moderate. As identified studies had shortcomings on aspects related to randomization and blinding of outcome assessment, we therefore downgraded the quality of the evidence. In general, there was no evidence suggesting that routine bed rest after dural puncture is beneficial for the prevention of PDPH onset. The role of fluid supplementation in the prevention of PDPH remains unclear.
Background
Early enteral nutrition support (within 48 hours of admission or injury) is frequently recommended for the management of patients in intensive care units (ICU). Early enteral nutrition is ...recommended in many clinical practice guidelines, although there appears to be a lack of evidence for its use and benefit.
Objectives
To evaluate the efficacy and safety of early enteral nutrition (initiated within 48 hours of initial injury or ICU admission) versus delayed enteral nutrition (initiated later than 48 hours after initial injury or ICU admission), with or without supplemental parenteral nutrition, in critically ill adults.
Search methods
We searched CENTRAL (2019, Issue 4), MEDLINE Ovid (1946 to April 2019), Embase Ovid SP (1974 to April 2019), CINAHL EBSCO (1982 to April 2019), and ISI Web of Science (1945 to April 2019). We also searched Turning Research Into Practice (TRIP), trial registers (ClinicalTrials.gov, ISRCTN registry), and scientific conference reports, including the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. We applied no restrictions by language or publication status.
Selection criteria
We included all randomized controlled trials (RCTs) that compared early versus delayed enteral nutrition, with or without supplemental parenteral nutrition, in adults who were in the ICU for longer than 72 hours. This included individuals admitted for medical, surgical, and trauma diagnoses, and who required any type of enteral nutrition.
Data collection and analysis
Two review authors extracted study data and assessed the risk of bias in the included studies. We expressed results as risk ratios (RR) for dichotomous data, and as mean differences (MD) for continuous data, both with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE.
Main results
We included seven RCTs with a total of 345 participants. Outcome data were limited, and we judged many trials to have an unclear risk of bias in several domains.
Early versus delayed enteral nutrition
Six trials (318 participants) assessed early versus delayed enteral nutrition in general, medical, and trauma ICUs in the USA, Australia, Greece, India, and Russia.
Primary outcomes
Five studies (259 participants) measured mortality. It is uncertain whether early enteral nutrition affects the risk of mortality within 30 days (RR 1.00, 95% CI 0.16 to 6.38; 1 study, 38 participants; very low‐quality evidence). Four studies (221 participants) reported mortality without describing the timeframe; we did not pool these results. None of the studies reported a clear difference in mortality between groups.
Three studies (156 participants) reported infectious complications. We were unable to pool the results due to unreported data and substantial clinical heterogeneity. The results were inconsistent across studies.
One trial measured feed intolerance or gastrointestinal complications; it is uncertain whether early enteral nutrition affects this outcome (RR 0.84, 95% CI 0.35 to 2.01; 59 participants; very low‐quality evidence).
Secondary outcomes
One trial assessed hospital length of stay and reported a longer stay in the early enteral group (median 15 days (interquartile range (IQR) 9.5 to 20) versus 12 days (IQR 7.5 to15); P = 0.05; 59 participants; very low‐quality evidence).
Three studies (125 participants) reported the duration of mechanical ventilation. We did not pool the results due to clinical and statistical heterogeneity. The results were inconsistent across studies.
It is uncertain whether early enteral nutrition affects the risk of pneumonia (RR 0.77, 95% CI 0.55 to 1.06; 4 studies, 192 participants; very low‐quality evidence).
Early enteral nutrition with supplemental parenteral nutrition versus delayed enteral nutrition with supplemental parenteral nutrition
We identified one trial in a burn ICU in the USA (27 participants).
Primary outcomes
It is uncertain whether early enteral nutrition with supplemental parenteral nutrition affects the risk of mortality (RR 0.74, 95% CI 0.25 to 2.18; very low‐quality evidence), or infectious complications (MD 0.00, 95% CI ‐1.94 to 1.94; very low‐quality evidence). There were no data available for feed intolerance or gastrointestinal complications.
Secondary outcomes
It is uncertain whether early enteral nutrition with supplemental parenteral nutrition reduces the duration of mechanical ventilation (MD 9.00, 95% CI ‐10.99 to 28.99; very low‐quality evidence). There were no data available for hospital length of stay or pneumonia.
Authors' conclusions
Due to very low‐quality evidence, we are uncertain whether early enteral nutrition, compared with delayed enteral nutrition, affects the risk of mortality within 30 days, feed intolerance or gastrointestinal complications, or pneumonia.
Due to very low‐quality evidence, we are uncertain if early enteral nutrition with supplemental parenteral nutrition compared with delayed enteral nutrition with supplemental parenteral nutrition reduces mortality, infectious complications, or duration of mechanical ventilation.
There is currently insufficient evidence; there is a need for large, multicentred studies with rigorous methodology, which measure important clinical outcomes.
Background
Infection of burn wounds is a serious problem because it can delay healing, increase scarring and invasive infection may result in the death of the patient. Antibiotic prophylaxis is one ...of several interventions that may prevent burn wound infection and protect the burned patient from invasive infections.
Objectives
To assess the effects of antibiotic prophylaxis on rates of burn wound infection.
Search methods
In January 2013 we searched the Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE ‐ In‐Process & Other Non‐Indexed Citations (2013); Ovid EMBASE; EBSCO CINAHL and reference lists of relevant articles. There were no restrictions with respect to language, date of publication or study setting.
Selection criteria
All randomised controlled trials (RCTs) that evaluated the efficacy and safety of antibiotic prophylaxis for the prevention of BWI. Quasi‐randomised studies were excluded.
Data collection and analysis
Two review authors independently selected studies, assessed the risk of bias, and extracted relevant data. Risk ratio (RR) and mean difference (MD) were estimated for dichotomous data and continuous data, respectively. When sufficient numbers of comparable RCTs were available, trials were pooled in a meta‐analysis to estimate the combined effect.
Main results
This review includes 36 RCTs (2117 participants); twenty six (72%) evaluated topical antibiotics, seven evaluated systemic antibiotics (four of these administered the antibiotic perioperatively and three administered upon hospital admission or during routine treatment), two evaluated prophylaxis with non absorbable antibiotics, and one evaluated local antibiotics administered via the airway.
The 11 trials (645 participants) that evaluated topical prophylaxis with silver sulfadiazine were pooled in a meta analysis. There was a statistically significant increase in burn wound infection associated with silver sulfadiazine compared with dressings/skin substitute (OR = 1.87; 95% CI: 1.09 to 3.19, I2 = 0%). These trials were at high, or unclear, risk of bias. Silver sulfadiazine was also associated with significantly longer length of hospital stay compared with dressings/skin substitute (MD = 2.11 days; 95% CI: 1.93 to 2.28).
Systemic antibiotic prophylaxis in non‐surgical patients was evaluated in three trials (119 participants) and there was no evidence of an effect on rates of burn wound infection. Systemic antibiotics (trimethoprim‐sulfamethoxazole) were associated with a significant reduction in pneumonia (only one trial, 40 participants) (RR = 0.18; 95% CI: 0.05 to 0.72) but not sepsis (two trials 59 participants) (RR = 0.43; 95% CI: 0.12 to 1.61).
Perioperative systemic antibiotic prophylaxis had no effect on any of the outcomes of this review.
Selective decontamination of the digestive tract with non‐absorbable antibiotics had no significant effect on rates of all types of infection (2 trials, 140 participants). Moreover, there was a statistically significant increase in rates of MRSA associated with use of non‐absorbable antibiotics plus cefotaxime compared with placebo (RR = 2.22; 95% CI: 1.21 to 4.07).
There was no evidence of a difference in mortality or rates of sepsis with local airway antibiotic prophylaxis compared with placebo (only one trial, 30 participants).
Authors' conclusions
The conclusions we are able to draw regarding the effects of prophylactic antibiotics in people with burns are limited by the volume and quality of the existing research (largely small numbers of small studies at unclear or high risk of bias for each comparison). The largest volume of evidence suggests that topical silver sulfadiazine is associated with a significant increase in rates of burn wound infection and increased length of hospital stay compared with dressings or skin substitutes; this evidence is at unclear or high risk of bias. Currently the effects of other forms of antibiotic prophylaxis on burn wound infection are unclear. One small study reported a reduction in incidence of pneumonia associated with a specific systematic antibiotic regimen.
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.
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