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International Journal of Molecular... Jan 2020Alzheimer's disease (AD) is the leading cause of dementia worldwide. It involves progressive impairment of cognitive function. A growing number of neuroprotective...
Alzheimer's disease (AD) is the leading cause of dementia worldwide. It involves progressive impairment of cognitive function. A growing number of neuroprotective compounds have been identified with potential anti-AD properties through in vitro and in vivo models of AD. Quercetin, a natural flavonoid contained in a wide range of plant species, is repeatedly reported to exert neuroprotective effects in experimental animal AD models. However, a systematic analysis of methodological rigor and the comparison between different studies is still lacking. A systematic review uses a methodical approach to minimize the bias in each independent study, providing a less biased, comprehensive understanding of research findings and an objective judgement of the strength of evidence and the reliability of conclusions. In this review, we identified 14 studies describing the therapeutic efficacy of quercetin on animal AD models by electronic and manual retrieval. Some of the results of the studies included were meta-analyzed by forest plot, and the methodological quality of each preclinical trial was assessed with SYRCLE's risk of bias tool. Our results demonstrated the consistent neuroprotective effects of quercetin on different AD models, and the pharmacological mechanisms of quercetin on AD models are summarized. This information eliminated the bias of each individual study, providing guidance for future tests and supporting evidence for further implementation of quercetin into clinical trials. However, the limitations of some studies, such as the absence of sample size calculations and low method quality, should also be noted.
Topics: Alzheimer Disease; Animals; Disease Models, Animal; Humans; Neuroprotective Agents; Quercetin
PubMed: 31941000
DOI: 10.3390/ijms21020493 -
Autism Research : Official Journal of... Oct 2019Problems with timing and time perception have been suggested as key characteristics of autism spectrum condition (ASC). Studies and personal accounts from clinicians,...
Problems with timing and time perception have been suggested as key characteristics of autism spectrum condition (ASC). Studies and personal accounts from clinicians, parents, caregivers, and self-reports from autistic people themselves often refer to problems with time. Although a number of empirical studies have examined aspects relating to time in autistic individuals, there remains no clear consensus on whether or how timing mechanisms may be affected in autism. A key reason for this lack of clarity is the wide range of timing processes that exist and subsequently the wide range of methodologies, research paradigms, and samples that time-based studies have used with autism populations. In order to summarize and organize the available literature on this issue, a systematic review was conducted. Five electronic databases were consulted. From an initial 597 records (after duplicates were removed), 45 papers were selected and reviewed. The studies are reviewed within different sections based on the different types of timing ability that have been explored in the neurotypical (NT) population: time sensitivity, interval timing, and higher-order time perception. Within each section cognitive models, methodologies, possible clinical implications, and research results are discussed. The results show different consistency across studies between the three types of timing ability. The highest consistency of results showing atypical time perception abilities is found in high-level time perception studies. It remains unclear if autism is characterized by a fundamental time perception impairment. Suggestions for future research are discussed. Autism Res 2019, 12: 1440-1462. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This systematic review examines the different types of timing and time perception behavior that have been investigated in autism. Overall, there are a number of studies that show differences between autistic and non-autistic individuals, but some studies do not find such differences. Group differences are more consistent across studies using complex tasks rather than simpler more fundamental timing tasks. We suggest that experiments across a range of timing tasks would be fruitful to address gaps in our knowledge.
Topics: Adolescent; Autism Spectrum Disorder; Female; Humans; Male; Time Perception
PubMed: 31336032
DOI: 10.1002/aur.2170 -
The Cochrane Database of Systematic... Jun 2019Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of people with diabetes. A complete and comprehensive management strategy for the prevention and treatment of DPN, whether painful or not, has not yet been defined.Research into treatment for DPN has been characterised by a series of failed clinical trials, with few noteworthy advances. Strategies that support peripheral nerve regeneration and restore neurological function in people with painful or painless DPN are needed. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation. ALC supplementation also induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation targets several mechanisms relevant to potential nerve repair and regeneration, and could have clinical therapeutic potential. There is a need for a systematic review of the evidence from clinical trials.
OBJECTIVES
To assess the effects of ALC for the treatment of DPN.
SEARCH METHODS
On 2 July 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We checked references, searched citations, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs of ALC compared with placebo, other therapy, or no intervention in the treatment of DPN. Participants could be of any sex and age, and have type 1 or type 2 diabetes mellitus, of any severity, with painful or painless DPN. We accepted any definition of minimum criteria for DPN, in accordance with the Toronto Consensus. We imposed no language restriction.Pain was the primary outcome, measured as the proportion of participants with at least 30% (moderate) or 50% (substantial) decrease in pain over baseline, or as the score on a visual analogue scale (VAS) or Likert scale for pain.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods.
MAIN RESULTS
We included four studies with 907 participants, which were reported in three publications. Three trials studied ALC versus placebo (675 participants); in one trial the dose of ALC was 2000 mg/day, and in the other two trials, it was 1500 mg/day or 3000 mg/day. The fourth trial studied ALC 1500 mg/day versus methylcobalamin 1.5 mg/day (232 participants). The risk of bias was high in both trials of different ALC doses and low in the other two trials.No included trial measured the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain). At doses of 1500 mg/day or less, the VAS score after ALC treatment was little different from placebo (MD -0.05, 95% CI -10.00 to 9.89; two studies; 159 participants; P = 0.99; I² = 0%), but at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD -14.93, 95% CI -19.16 to -10.70; three studies; 381 participants; P < 0.00001; I² = 0%). This subgroup analysis should be viewed with caution as the evidence was even less certain than the overall analysis, which was already of very low certainty.Two placebo-controlled studies reported that vibration perception improved after 12 months. We graded this evidence as very low certainty, due to inconsistency and a high risk of bias, as the trial authors did not provide any numerical data. The placebo-controlled studies did not measure functional impairment and disability scores. No study used validated symptom scales. One study performed sensory testing, but the evidence was very uncertain.The fourth included study compared ALC with methylcobalamin, but did not report effects on pain. There was a reduction from baseline to 24 weeks in functional impairment and disability, based on the change in mean Neuropathy Disability Score (NDS; scale from zero to 10), but there was no important difference between the ALC group (mean score 1.66 ± 1.90) and the methylcobalamin group (mean score 1.35 ± 1.65) groups (P = 0.23; low-certainty evidence).One placebo-controlled study reported that six of 147 participants in the ALC > 1500 mg/day group (4.1%) and two of 147 participants in the placebo group (1.4%) discontinued treatment because of adverse events (headache, facial paraesthesia, and gastrointestinal disorders) (P = 0.17). The other two placebo-controlled studies reported no dropouts due to adverse events, and more pain, paraesthesia, and hyperaesthesias in the placebo group than the 3000 mg/day ALC group, but provided no numerical data. The overall certainty of adverse event evidence for the comparison of ALC versus placebo was low.The study comparing ALC with methylcobalamin reported that 34/117 participants (29.1%) experienced adverse events in the ALC group versus 33/115 (28.7%) in the methylcobalamin group (P = 0.95). Nine participants discontinued treatment due to adverse events (ALC: 4 participants, methylcobalamin: 5 participants), which were most commonly gastrointestinal symptoms. The certainty of the adverse event evidence for ALC versus methylcobalamin was low.Two studies were funded by the manufacturer of ALC and the other two studies had at least one co-author who was a consultant for an ALC manufacturer.
AUTHORS' CONCLUSIONS
We are very uncertain whether ALC causes a reduction in pain after 6 to 12 months' treatment in people with DPN, when compared with placebo, as the evidence is sparse and of low certainty. Data on functional and sensory impairment and symptoms are lacking, or of very low certainty. The evidence on adverse events is too uncertain to make any judgements on safety.
Topics: Acetylcarnitine; Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Placebos; Randomized Controlled Trials as Topic; Sensation; Vibration; Vitamin B 12
PubMed: 31201734
DOI: 10.1002/14651858.CD011265.pub2 -
JAMA Psychiatry Feb 2019Many studies have investigated impairments in cognitive domains in adults with autism spectrum disorder (ASD). Yet, to date, a comprehensive overview on the patterns of... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Many studies have investigated impairments in cognitive domains in adults with autism spectrum disorder (ASD). Yet, to date, a comprehensive overview on the patterns of cognitive functioning is lacking.
OBJECTIVE
To provide an overview of nonsocial and social cognitive functioning in various domains in adults with ASD, allowing for comparison of the severity of deficits between different domains.
DATA SOURCES
A literature search performed in an academic medical setting was conducted using PubMed, PsycINFO, Embase, and Medline databases with the combination of the following free-text and Medical Subject Headings where applicable: [cogniti* OR neurocogniti* OR neuropsycholog* OR executive function* OR IQ OR intelligence quotient OR social cognition OR emotion perception OR affect perception OR emotion recognition OR attribution OR ToM OR mentalising OR mentalizing OR prosody OR social knowledge OR mind reading OR social cue OR social judgment] AND [autis* OR ASD OR Asperger OR Asperger's OR PDD OR pervasive developmental disorder]. The search was further limited to studies published between 1980 (first inclusion of autism diagnosis in the DSM-III) and July 2018.
STUDY SELECTION
Studies included were published as a primary peer-reviewed research article in English, included individuals with ASD 16 years or older, and assessed at least 1 domain of neurocognitive functioning or social cognition using standard measures.
DATA EXTRACTION AND SYNTHESIS
Of 9892 articles identified and screened, 75 met the inclusion criteria for the systematic review and meta-analysis.
MAIN OUTCOMES AND MEASURES
Hedges g effect sizes were computed, and random-effects models were used for all analyses. Moderators of between-study variability in effect sizes were assessed using meta-regressions.
RESULTS
The systematic review and meta-analysis included 75 studies, with a combined sample of 3361 individuals with ASD (mean [SD] age, 32.0 [9.3] years; 75.9% male) and 5344 neurotypical adults (mean [SD] age, 32.3 [9.1] years; 70.1% male). Adults with ASD showed large impairments in theory of mind (g = -1.09; 95% CI, -1.25 to -0.92; number of studies = 39) and emotion perception and processing (g = -0.80; 95% CI, -1.04 to -0.55; n = 18), followed by medium impairments in processing speed (g = -0.61; 95% CI, -0.83 to -0.38; n = 21) and verbal learning and memory (g = -0.55; 95% CI, -0.86 to -0.25; n = 12). The least altered cognitive domains were attention and vigilance (g = -0.30; 95% CI, -0.81 to 0.21; n = 5) and working memory (g = -0.23; 95% CI, -0.47 to 0.01; n = 19). Meta-regressions confirmed robustness of the results.
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that adults with ASD show impairments in social cognitive domains and in specific nonsocial cognitive domains. These findings contribute to the understanding of the patterns of cognitive functioning in adults with ASD and may assist in the identification of targets for cognitive interventions.
Topics: Adult; Autism Spectrum Disorder; Cognition; Female; Humans; Male; Social Perception
PubMed: 30601878
DOI: 10.1001/jamapsychiatry.2018.3645 -
Dementia & Neuropsychologia 2018Metamemory is the awareness of one's own knowledge and control of memory, and refers to the online ability to gather information about the current state of the memory...
UNLABELLED
Metamemory is the awareness of one's own knowledge and control of memory, and refers to the online ability to gather information about the current state of the memory system.
OBJECTIVE
Metamemory is one's own knowledge and control of memory. A systematic review was performed to identify the types of tasks used for evaluating metamemory monitoring, the stimuli used in these tasks, their limitations and the outcomes in people with Alzheimer's disease (PwAD).
METHODS
This systematic review followed PRISMA methodology. A search of Pubmed, Scopus and Web of Science electronic databases was carried out in September, 2018, identifying experimental investigations of metamemory and dementia.
RESULTS
We included 21 studies. The most common tasks used were judgement of learning, feeling of knowing, judgement of confidence and global prediction. The rates of discrepancy between PwAD and caregivers still need further research. The Rey Auditory Verbal Learning Test was the most used list of words. PwAD are able to accurately rate their memory functioning and performance, when the evaluation is done soon afterwards. PwAD tend to overestimate their functioning and performance when the judgement involves forward-looking vision.
CONCLUSION
In the context of metamemory impairment, clinicians and caregivers should seek interventions aiming to identify compensatory styles of functioning. This systematic review provides initial evidence for the use of metamemory measures as part of broader assessments evaluating Alzheimer's disease.
PubMed: 30546843
DOI: 10.1590/1980-57642018dn12-040002 -
The Journal of Pain Feb 2019The left/right judgment task (LRJT) is the most commonly used method of assessing motor imagery performance. Abnormally long response times are thought to reflect... (Meta-Analysis)
Meta-Analysis
The left/right judgment task (LRJT) is the most commonly used method of assessing motor imagery performance. Abnormally long response times are thought to reflect delayed processing of body/spatial representations, and poor accuracy is thought to reflect disrupted cortical proprioceptive representations or body schema. Slower and less accurate responses on the LRJT have been reported in a variety of chronic musculoskeletal pain conditions. To date, no systematic review of the literature has been conducted to assess if altered motor imagery performance as measured by the LRJT is characteristic of all chronic musculoskeletal pain conditions. Therefore, the aim of this study was to conduct a comprehensive systematic review and meta-analysis of the literature to answer the following question: Do people with chronic musculoskeletal pain have impaired left/right body part judgment? Twenty-five studies (2,266 participants) including a range of chronic pain populations who undertook an LRJT were identified from searches of 8 electronic databases from inception to March 2017. Results indicate that chronic musculoskeletal pain conditions affecting the limbs and face (P ≤ .01) are associated with altered motor imagery performance as measured by the LRJT. PERSPECTIVES: This review synthesizes evidence of altered motor imagery performance using the LRJT across chronic musculoskeletal pain conditions. Consistent evidence was found for altered motor imagery performance in peripheral pain conditions, but evidence was less consistent for axial conditions. Treatment to restore a normal body schema may be beneficial in chronic limb and facial pain.
Topics: Chronic Pain; Humans; Imagination; Motor Activity; Musculoskeletal Pain; Proprioception; Space Perception
PubMed: 30098404
DOI: 10.1016/j.jpain.2018.07.004 -
The Cochrane Database of Systematic... Jul 2018Autism spectrum disorder (ASD) is a behaviourally diagnosed condition. It is defined by impairments in social communication or the presence of restricted or repetitive... (Review)
Review
BACKGROUND
Autism spectrum disorder (ASD) is a behaviourally diagnosed condition. It is defined by impairments in social communication or the presence of restricted or repetitive behaviours, or both. Diagnosis is made according to existing classification systems. In recent years, especially following publication of the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5; APA 2013), children are given the diagnosis of ASD, rather than subclassifications of the spectrum such as autistic disorder, Asperger syndrome, or pervasive developmental disorder - not otherwise specified. Tests to diagnose ASD have been developed using parent or carer interview, child observation, or a combination of both.
OBJECTIVES
Primary objectives1. To identify which diagnostic tools, including updated versions, most accurately diagnose ASD in preschool children when compared with multi-disciplinary team clinical judgement.2. To identify how the best of the interview tools compare with CARS, then how CARS compares with ADOS.a. Which ASD diagnostic tool - among ADOS, ADI-R, CARS, DISCO, GARS, and 3di - has the best diagnostic test accuracy?b. Is the diagnostic test accuracy of any one test sufficient for that test to be suitable as a sole assessment tool for preschool children?c. Is there any combination of tests that, if offered in sequence, would provide suitable diagnostic test accuracy and enhance test efficiency?d. If data are available, does the combination of an interview tool with a structured observation test have better diagnostic test accuracy (i.e. fewer false-positives and fewer false-negatives) than either test alone?As only one interview tool was identified, we modified the first three aims to a single aim (Differences between protocol and review): This Review evaluated diagnostic tests in terms of sensitivity and specificity. Specificity is the most important factor for diagnosis; however, both sensitivity and specificity are of interest in this Review because there is an inherent trade-off between these two factors.Secondary objectives1. To determine whether any diagnostic test has greater diagnostic test accuracy for age-specific subgroups within the preschool age range.
SEARCH METHODS
In July 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and the reference lists of all included publications.
SELECTION CRITERIA
Publications had to: 1. report diagnostic test accuracy for any of the following six included diagnostic tools: Autism Diagnostic Interview - Revised (ADI-R), Gilliam Autism Rating Scale (GARS), Diagnostic Interview for Social and Communication Disorder (DISCO), Developmental, Dimensional, and Diagnostic Interview (3di), Autism Diagnostic Observation Schedule - Generic (ADOS), and Childhood Autism Rating Scale (CARS); 2. include children of preschool age (under six years of age) suspected of having an ASD; and 3. have a multi-disciplinary assessment, or similar, as the reference standard.Eligible studies included cohort, cross-sectional, randomised test accuracy, and case-control studies. The target condition was ASD.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed all studies for inclusion and extracted data using standardised forms. A third review author settled disagreements. We assessed methodological quality using the QUADAS-2 instrument (Quality Assessment of Studies of Diagnostic Accuracy - Revised). We conducted separate univariate random-effects logistical regressions for sensitivity and specificity for CARS and ADI-R. We conducted meta-analyses of pairs of sensitivity and specificity using bivariate random-effects methods for ADOS.
MAIN RESULTS
In this Review, we included 21 sets of analyses reporting different tools or cohorts of children from 13 publications, many with high risk of bias or potential conflicts of interest or a combination of both. Overall, the prevalence of ASD for children in the included analyses was 74%.For versions and modules of ADOS, there were 12 analyses with 1625 children. Sensitivity of ADOS ranged from 0.76 to 0.98, and specificity ranged from 0.20 to 1.00. The summary sensitivity was 0.94 (95% confidence interval (CI) 0.89 to 0.97), and the summary specificity was 0.80 (95% CI 0.68 to 0.88).For CARS, there were four analyses with 641 children. Sensitivity of CARS ranged from 0.66 to 0.89, and specificity ranged from 0.21 to 1.00. The summary sensitivity for CARS was 0.80 (95% CI 0.61 to 0.91), and the summary specificity was 0.88 (95% CI 0.64 to 0.96).For ADI-R, there were five analyses with 634 children. Sensitivity for ADI-R ranged from 0.19 to 0.75, and specificity ranged from 0.63 to 1.00. The summary sensitivity for the ADI-R was 0.52 (95% CI 0.32 to 0.71), and the summary specificity was 0.84 (95% CI 0.61 to 0.95).Studies that compared tests were few and too small to allow clear conclusions.In two studies that included analyses for both ADI-R and ADOS, tests scored similarly for sensitivity, but ADOS scored higher for specificity. In two studies that included analyses for ADI-R, ADOS, and CARS, ADOS had the highest sensitivity and CARS the highest specificity.In one study that explored individual and additive sensitivity and specificity of ADOS and ADI-R, combining the two tests did not increase the sensitivity nor the specificity of ADOS used alone.Performance for all tests was lower when we excluded studies at high risk of bias.
AUTHORS' CONCLUSIONS
We observed substantial variation in sensitivity and specificity of all tests, which was likely attributable to methodological differences and variations in the clinical characteristics of populations recruited.When we compared summary statistics for ADOS, CARS, and ADI-R, we found that ADOS was most sensitive. All tools performed similarly for specificity. In lower prevalence populations, the risk of falsely identifying children who do not have ASD would be higher.Now available are new versions of tools that require diagnostic test accuracy assessment, ideally in clinically relevant situations, with methods at low risk of bias and in children of varying abilities.
PubMed: 30075057
DOI: 10.1002/14651858.CD009044.pub2 -
The Cochrane Database of Systematic... Feb 2017Cataract and age-related macular degeneration (AMD) are common causes of decreased vision that often occur simultaneously in people over age 50. Although cataract... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cataract and age-related macular degeneration (AMD) are common causes of decreased vision that often occur simultaneously in people over age 50. Although cataract surgery is an effective treatment for cataract-induced visual loss, some clinicians suspect that such an intervention may increase the risk of worsening of underlying AMD and thus have deleterious effects on vision.
OBJECTIVES
The objective of this review was to evaluate the effectiveness and safety of cataract surgery compared with no surgery in eyes with AMD.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 December 2016.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-randomized trials that enrolled participants whose eyes were affected by both cataract and AMD in which cataract surgery was compared with no surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated the search results against the inclusion and exclusion criteria. Two review authors independently extracted data, assessed risk of bias for included studies, and graded the certainty of evidence. We followed methods as recommended by Cochrane.
MAIN RESULTS
We included two RCTs with a total of 114 participants (114 study eyes) with visually significant cataract and AMD. We identified no ongoing trials. Participants in each RCT were randomized to immediate cataract surgery (within two weeks of enrollment) or delayed cataract surgery (six months after enrollment). The risk of bias was unclear for most domains in each study; one study was registered prospectively.In one study conducted in Australia outcomes were reported only at six months (before participants in the delayed-surgery group had cataract surgery). At six months, the immediate-surgery group showed mean improvement in best-corrected visual acuity (BCVA) compared with the delayed-surgery group (mean difference (MD) -0.15 LogMAR, 95% confidence interval (CI) -0.28 to -0.02; 56 participants; moderate-certainty evidence). In the other study, conducted in Austria, outcomes were reported only at 12 months (12 months after participants in the immediate-surgery group and six months after participants in the delayed-surgery group had cataract surgery). There was uncertainty as to which treatment group had better improvement in distance visual acuity at 12 months (unit of measure not reported; very low-certainty evidence).At 12 months, the mean change from baseline between groups in cumulated drusen or geographic atrophy area size was small and there was uncertainty which, if either, of the groups was favored (MD 0.76, 95% CI -8.49 to 10.00; 49 participants; low-certainty evidence). No participant in one study had exudative AMD develop in the study eye during 12 months of follow-up; in the other study, choroidal neovascularization developed in the study eye of 1 of 27 participants in the immediate-surgery group versus 0 of 29 participants in the delayed-surgery group at six months (risk ratio 3.21, 95% CI 0.14 to 75.68; 56 participants; very low-certainty evidence). Quality of life was measured using two different questionnaires. Scores on the Impact of Vision Impairment (IVI) questionnaire suggested that the immediate-surgery group fared better regarding vision-related quality of life than the delayed-surgery group at six months (MD in IVI logit scores 1.60, 95% CI 0.61 to 2.59; low-certainty evidence). However, we could not analyze scores from the Visual Function-14 (VF-14) questionnaire from the other study due to insufficient data. No postoperative complication was reported from either study.
AUTHORS' CONCLUSIONS
At this time, it is not possible to draw reliable conclusions from the available data as to whether cataract surgery is beneficial or harmful in people with AMD after 12 months. Although cataract surgery provides short-term (six months) improvement in BCVA in eyes with AMD compared with no surgery, it is unclear whether the timing of surgery has an effect on long-term outcomes. Physicians must make recommendations to their AMD patients regarding cataract surgery based on experience and clinical judgment until large controlled trials are conducted and their findings published.There is a need for prospective RCTs in which cataract surgery is compared with no surgery in people with AMD to better evaluate whether cataract surgery is beneficial or harmful in all or a subset of AMD patients. However, ethical considerations preclude withholding surgery, or delaying it for several years, if it may be a potentially beneficial treatment. Designers of future trials are encouraged to utilize existing standardized systems for grading cataract and AMD and for measuring key outcomes: visual acuity, change in visual acuity, worsening of AMD, quality of life measures, and adverse events.
Topics: Cataract; Cataract Extraction; Disease Progression; Humans; Macular Degeneration; Middle Aged; Randomized Controlled Trials as Topic; Time Factors; Visual Acuity
PubMed: 28206671
DOI: 10.1002/14651858.CD006757.pub4 -
The Cochrane Database of Systematic... Aug 2016Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric... (Review)
Review
BACKGROUND
Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review.
OBJECTIVES
To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 12 May 2016.
SELECTION CRITERIA
All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment.
DATA COLLECTION AND ANALYSIS
Both authors independently selected trials, assessed trial quality and extracted data.
MAIN RESULTS
The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival.
AUTHORS' CONCLUSIONS
Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
Topics: Abdominal Pain; Adult; Child; Cystic Fibrosis; Dietary Fats; Gastric Acid; Gastrointestinal Agents; Histamine H2 Antagonists; Humans; Intestinal Absorption; Pancreas; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 27546383
DOI: 10.1002/14651858.CD003424.pub4 -
The Cochrane Database of Systematic... Sep 2015Foot infection is the most common cause of non-traumatic amputation in people with diabetes. Most diabetic foot infections (DFIs) require systemic antibiotic therapy and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Foot infection is the most common cause of non-traumatic amputation in people with diabetes. Most diabetic foot infections (DFIs) require systemic antibiotic therapy and the initial choice is usually empirical. Although there are many antibiotics available, uncertainty exists about which is the best for treating DFIs.
OBJECTIVES
To determine the effects and safety of systemic antibiotics in the treatment of DFIs compared with other systemic antibiotics, topical foot care or placebo.
SEARCH METHODS
In April 2015 we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library); Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE, and EBSCO CINAHL. We also searched in the Database of Abstracts of Reviews of Effects (DARE; The Cochrane Library), the Health Technology Assessment database (HTA; The Cochrane Library), the National Health Service Economic Evaluation Database (NHS-EED; The Cochrane Library), unpublished literature in OpenSIGLE and ProQuest Dissertations and on-going trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating the effects of systemic antibiotics (oral or parenteral) in people with a DFI. Primary outcomes were clinical resolution of the infection, time to its resolution, complications and adverse effects.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed the risk of bias, and extracted data. Risk ratios (RR) were estimated for dichotomous data and, when sufficient numbers of comparable trials were available, trials were pooled in a meta-analysis.
MAIN RESULTS
We included 20 trials with 3791 participants. Studies were heterogenous in study design, population, antibiotic regimens, and outcomes. We grouped the sixteen different antibiotic agents studied into six categories: 1) anti-pseudomonal penicillins (three trials); 2) broad-spectrum penicillins (one trial); 3) cephalosporins (two trials); 4) carbapenems (four trials); 5) fluoroquinolones (six trials); 6) other antibiotics (four trials).Only 9 of the 20 trials protected against detection bias with blinded outcome assessment. Only one-third of the trials provided enough information to enable a judgement about whether the randomisation sequence was adequately concealed. Eighteen out of 20 trials received funding from pharmaceutical industry-sponsors.The included studies reported the following findings for clinical resolution of infection: there is evidence from one large trial at low risk of bias that patients receiving ertapenem with or without vancomycin are more likely to have resolution of their foot infection than those receiving tigecycline (RR 0.92, 95% confidence interval (CI) 0.85 to 0.99; 955 participants). It is unclear if there is a difference in rates of clinical resolution of infection between: 1) two alternative anti-pseudomonal penicillins (one trial); 2) an anti-pseudomonal penicillin and a broad-spectrum penicillin (one trial) or a carbapenem (one trial); 3) a broad-spectrum penicillin and a second-generation cephalosporin (one trial); 4) cephalosporins and other beta-lactam antibiotics (two trials); 5) carbapenems and anti-pseudomonal penicillins or broad-spectrum penicillins (four trials); 6) fluoroquinolones and anti-pseudomonal penicillins (four trials) or broad-spectrum penicillins (two trials); 7) daptomycin and vancomycin (one trial); 8) linezolid and a combination of aminopenicillins and beta-lactamase inhibitors (one trial); and 9) clindamycin and cephalexin (one trial).Carbapenems combined with anti-pseudomonal agents produced fewer adverse effects than anti-pseudomonal penicillins (RR 0.27, 95% CI 0.09 to 0.84; 1 trial). An additional trial did not find significant differences in the rate of adverse events between a carbapenem alone and an anti-pseudomonal penicillin, but the rate of diarrhoea was lower for participants treated with a carbapenem (RR 0.58, 95% CI 0.36 to 0.93; 1 trial). Daptomycin produced fewer adverse effects than vancomycin or other semi-synthetic penicillins (RR 0.61, 95%CI 0.39 to 0.94; 1 trial). Linezolid produced more adverse effects than ampicillin-sulbactam (RR 2.66; 95% CI 1.49 to 4.73; 1 trial), as did tigecycline compared to ertapenem with or without vancomycin (RR 1.47, 95% CI 1.34 to 1.60; 1 trial). There was no evidence of a difference in safety for the other comparisons.
AUTHORS' CONCLUSIONS
The evidence for the relative effects of different systemic antibiotics for the treatment of foot infections in diabetes is very heterogeneous and generally at unclear or high risk of bias. Consequently it is not clear if any one systemic antibiotic treatment is better than others in resolving infection or in terms of safety. One non-inferiority trial suggested that ertapenem with or without vancomycin is more effective in achieving clinical resolution of infection than tigecycline. Otherwise the relative effects of different antibiotics are unclear. The quality of the evidence is low due to limitations in the design of the included trials and important differences between them in terms of the diversity of antibiotics assessed, duration of treatments, and time points at which outcomes were assessed. Any further studies in this area should have a blinded assessment of outcomes, use standardised criteria to classify severity of infection, define clear outcome measures, and establish the duration of treatment.
Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cephalosporins; Diabetic Foot; Fluoroquinolones; Humans; Penicillins; Randomized Controlled Trials as Topic
PubMed: 26337865
DOI: 10.1002/14651858.CD009061.pub2