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PloS One 2014The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children.
SUBJECTS AND METHODS
Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0-24 hours after leaving the operation room were included in the analysis.
RESULTS
The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics.
CONCLUSION
Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study.
Topics: Adolescent; Analgesics, Opioid; Child; Child, Preschool; Female; Humans; Infant; Ketamine; Male; Pain, Postoperative; Preoperative Care; Tonsillectomy; Treatment Outcome
PubMed: 24979227
DOI: 10.1371/journal.pone.0101259 -
Health Technology Assessment... May 2014Tobacco smoking is one of the leading causes of deaths worldwide. Nearly one-fifth of adults in the UK regularly smoke cigarettes. The ill-health associated with smoking... (Review)
Review
BACKGROUND
Tobacco smoking is one of the leading causes of deaths worldwide. Nearly one-fifth of adults in the UK regularly smoke cigarettes. The ill-health associated with smoking costs the NHS over £3B every year. A number of pharmacological interventions are available that can help people to quit smoking. These include nicotinic receptor partial agonists such as varenicline or cytisine. Varenicline is a synthetic product licensed for use in the UK, while cytisine is derived naturally from the seeds of the plant Cytisus laborinum L. (golden rain acacia).
OBJECTIVES
To review the evidence on the clinical effectiveness and safety of cytisine from smoking cessation compared with varenicline; to develop an economic model to estimate the cost-effectiveness of cytisine and varenicline; and to provide recommendations based on value of information analyses as to whether or not a head-to-head trial of cytisine and varenicline would represent effective use of resources.
DATA SOURCES
Efficacy and adverse events data were sourced from a recent Cochrane review. These data were supplemented with an updated search of twelve electronic databases, including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature and The Cochrane Library, for the period from December 2011 to January 2013. The review included randomised controlled trials (RCTs) of adult smokers attempting to quit using varenicline or cytisine. Further interventions were considered (placebo, nicotine replacement therapy, bupropion) to allow an indirect comparison between varenicline and cytisine. The primary outcome was abstinence at a minimum of 6 months' follow-up. Secondary outcomes were common adverse events such as abnormal dreams, headache, nausea, insomnia and serious adverse events.
REVIEW METHODS
A systematic review and network meta-analysis of the clinical evidence was undertaken. A random-effects model was used to allow for heterogeneity between studies. The economic model structure was based on a published model. Probabilistic sensitivity analyses were undertaken to estimate the treatment expected to be most cost-effective given current information. Formal expected value of perfect information, perfect partial information and of sample information were performed.
RESULTS
Twenty-three (RCTs) were included in the systematic review, comprising a total of 10,610 participants. Twenty-one trials of varenicline of differing dosing schedules and two trials of cytisine at standard dose met the inclusion criteria. No head-to-head trials comparing varenicline with cytisine were identified. The methodological quality of the studies was judged to be moderate to good. Cytisine was more efficacious than placebo [hazard ratio (HR) 4.27, 95% credible interval (CrI) 2.05 to 10.05], as was standard-dose varenicline (HR 2.58, 95% Crl 2.16 to 3.15). Standard-dose varenicline treatment was associated with significantly higher rates of headache, insomnia and nausea than placebo; there was no significant difference in the rates of abnormal dreams. There were no significant differences in the rates of headache or nausea between cytisine and placebo; data were identified for neither abnormal dreams nor insomnia. Using expected values, cytisine is anticipated to dominate varenicline, in that it produces more quality-adjusted life-years at a lower associated cost. This occurred in approximately 90% of the scenarios performed. However, owing to the large number of people who wish to quit smoking (estimated to be 3 million over a 10-year period), the implications of making an incorrect decision is large. The expected value of sample information indicated that conducting a head-to-head trial of cytisine and varenicline was worthwhile, and that 1000 smokers per arm was an appropriate number to recruit.
CONCLUSIONS
On the basis of the evidence included in this review, varenicline and cytisine are both effective interventions to aid smoking cessation when compared with placebo. Cytisine is estimated to be both more clinically effective and cost-effective than varenicline. However, there is uncertainty in the decision, and a head-to-head trial of cytisine and varenicline would appear to be an effective use of resources.
STUDY REGISTRATION
The study was registered as PROSPERO CRD42012003455.
FUNDING DETAILS
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Aged; Alkaloids; Azocines; Benzazepines; Cost-Benefit Analysis; Humans; Middle Aged; Nicotinic Agonists; Quality-Adjusted Life Years; Quinolizines; Quinoxalines; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; State Medicine; United Kingdom; Varenicline
PubMed: 24831822
DOI: 10.3310/hta18330 -
The Cochrane Database of Systematic... Sep 2012Mild cognitive impairment is hypothesised to represent a pre-clinical stage of dementia but forms a heterogeneous group with variable prognosis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mild cognitive impairment is hypothesised to represent a pre-clinical stage of dementia but forms a heterogeneous group with variable prognosis.
OBJECTIVES
To assess the safety and efficacy of cholinesterase inhibitors in people with mild cognitive impairment.
SEARCH METHODS
Trials were identified from the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, which is frequently updated from the major healthcare databases (MEDLINE, EMBASE, CINAHL, PsycINFO and Lilacs) as well as trial registers and grey literature.
SELECTION CRITERIA
Double-blind, placebo-controlled randomised trials of any cholinesterase inhibitor in people with mild cognitive impairment.
DATA COLLECTION AND ANALYSIS
Data were extracted from the published reports of the included studies, combined by meta-analysis where appropriate, and treatment efficacy and risk of adverse events were estimated.
MAIN RESULTS
Nine studies (from eight published reports) of 5149 individuals with mild cognitive impairment (however defined) were included in the review. Limited pooling of results was possible owing to different lengths of trials. Meta-analysis of the three studies reporting conversion to dementia gives no strong evidence of a beneficial effect of cholinesterase inhibitors on the progression to dementia at one, two or three years. The risk ratio (RR) for conversion at two years was significantly different from unity (0.67; 95% confidence interval (CI) 0.55 to 0.83), but this is based on only two studies reported in the same article. There was essentially no effect of cholinesterase inhibitors on cognitive test scores.Based on the results from 4207 individuals, there were significantly more adverse events in the cholinesterase inhibitor groups (RR 1.09; 95% CI 1.02 to 1.16), but no more serious adverse events or deaths. Gastrointestinal side effects were much more common (diarrhoea: RR 2.10; 95% CI 1.30 to 3.39; nausea: RR 2.97; 95% CI 2.57 to 3.42; vomiting: RR 4.42; 95% CI 3.23 to 6.05). Cardiac problems were no more likely in either group (RR 0.71; 95% CI 0.25 to 2.02). Other side effects reported significantly more often in the cholinesterase inhibitor group were muscle spasms/leg cramps (RR 7.52; 95% CI 4.34 to 13.02), headache (RR 1.34; 95% CI 1.05 to 1.71), syncope or dizziness (RR 1.62; 95% CI 1.36 to 1.93), insomnia (RR 1.66; 95% CI 1.36 to 2.02) and abnormal dreams (RR 4.25; 95% CI 2.57 to 7.04).
AUTHORS' CONCLUSIONS
There is very little evidence that cholinesterase inhibitors affect progression to dementia or cognitive test scores in mild cognitive impairment. This weak evidence is overwhelmed by the increased risk of adverse events, particularly gastrointestinal. Cholinesterase inhibitors should not be recommended for mild cognitive impairment.
Topics: Cholinesterase Inhibitors; Cognitive Dysfunction; Dementia; Diarrhea; Disease Progression; Humans; Nausea; Randomized Controlled Trials as Topic; Vomiting
PubMed: 22972133
DOI: 10.1002/14651858.CD009132.pub2 -
Evidence-based Complementary and... 2012A systematic review was conducted to examine traditional Chinese medicine (TCM) patterns commonly diagnosed in subjects with insomnia and clinical features associated...
A systematic review was conducted to examine traditional Chinese medicine (TCM) patterns commonly diagnosed in subjects with insomnia and clinical features associated with the TCM patterns, and an insomnia symptom checklist for TCM diagnostic purpose was developed based on the review. Two independent researchers searched the China Academic Journals Full-Text Database and 10 English databases. A total of 103 studies and 9499 subjects were analyzed. There was a wide variation in terminology relating to symptomatology and TCM pattern. We identified 69 patterns, with the top 3 patterns (i.e., deficiency of both the heart and spleen, hyperactivity of fire due to yin deficiency, and liver-qi stagnation transforming into fire) and the top 10 patterns covering 51.8% and 77.4% of the 9499 subjects, respectively. There were 19 sleep-related, 92 non-sleep-related, 14 tongue, and 7 pulse features included as diagnostic criteria of the top 10 TCM patterns for insomnia. Excessive dreaming, dizziness, red tongue, and fine pulse were the most common sleep-related, non-sleep-related, tongue, and pulse features. Overlapping symptomatology between the TCM patterns was present. A standardized symptom checklist consisted of 92 items, including 13 sleep-related, 61 non-sleep-related, 11 tongue, and 7 pulse items, holds promise as a diagnostic tool and merits further validation.
PubMed: 22899958
DOI: 10.1155/2012/735078 -
Mayo Clinic Proceedings Sep 2012Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic... (Review)
Review
Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic options. We performed a systematic review to evaluate the evidence for the use of prazosin in the treatment of nightmares. A comprehensive search was performed using the databases EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, from their inception to March 9, 2012, using keywords prazosin and nightmares/PTSD or associated terms (see text). Two authors independently reviewed titles and abstracts and selected relevant studies. Descriptive data and outcomes of interest from eligible studies were extracted by 1 author, and checked by 2 others. The risk of bias of randomized controlled trials (RCTs) was assessed independently by 2 reviewers. Articles met criteria for inclusion if prazosin was used to treat nightmares, and outcome measures included nightmares or related symptoms of sleep disorders. Our search yielded 21 studies, consisting of 4 RCTs, 4 open-label studies, 4 retrospective chart reviews, and 9 single case reports. The prazosin dose ranged from 1 to 16 mg/d. Results were mixed for the 4 RCTs: 3 reported significant improvement in the number of nightmares, and 1 found no reduction in the number of nightmares. Reduced nightmare severity with use of prazosin was consistently reported in the open-label trials, retrospective chart reviews, and single case reports.
Topics: Adrenergic alpha-1 Receptor Antagonists; Dreams; Humans; Prazosin; Sleep Wake Disorders; Stress Disorders, Post-Traumatic
PubMed: 22883741
DOI: 10.1016/j.mayocp.2012.05.015 -
Journal of Clinical Sleep Medicine :... Oct 2008The aim of this review is to evaluate the effectiveness of cognitive behavioral therapy (CBT) on nightmare frequency and to determine which kind of CBT is the most... (Comparative Study)
Comparative Study Review
The aim of this review is to evaluate the effectiveness of cognitive behavioral therapy (CBT) on nightmare frequency and to determine which kind of CBT is the most effective treatment. A systematic literature search was carried out in PsychInfo and PubMed articles published on or before May 1, 2008. The inclusion criteria were: nightmare treatment study, use of nonpharmacological treatment, not a qualitative case study, randomized-controlled trial (RCT). After selection, 12 peer-reviewed studies about 9 RCTs remained (2 follow-up studies and one displaying preliminary results). Several interventions have been reviewed including, recording one's nightmares, relaxation, exposure, and techniques of cognitive restructuring. The 12 evaluated articles varied in quality, and none fulfilled CONSORT guidelines. All articles used nightmare frequency as the primary dependent variable, and all found significant in-group differences (pre vs. post) for intervention or placebo (range d = 0.7-2.9). Five studies were able to find a significant group effect for the intervention compared to a waiting list control group. Only one study found significant differences between 2 intervention groups. Nightmare-focused CBT (exposure and imagery rehearsal therapy [IRT]) revealed better treatment outcomes than indirect CBT (relaxation, recording). IRT and exposure showed no meaningful differences, but only one RCT directly compared both techniques. Three different research groups demonstrated the effects of exposure, but only one group showed the effect of IRT. Thus, RCTs that compare IRT with exposure by independent research groups are much needed.
Topics: Cognitive Behavioral Therapy; Desensitization, Psychologic; Dreams; Humans; Imagination; Practice, Psychological; Randomized Controlled Trials as Topic; Relaxation Therapy
PubMed: 18853707
DOI: No ID Found -
Annals of the Rheumatic Diseases Nov 2007Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour necrosis factor alpha (TNFalpha) showed high response percentages in the groups... (Comparative Study)
Comparative Study Review
BACKGROUND
Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour necrosis factor alpha (TNFalpha) showed high response percentages in the groups treated with active drugs.
OBJECTIVE
To compare the efficacy of anti-TNF treatments for rheumatoid arthritis (RA) patients in RCTs and in daily clinical practice, with an emphasis on the efficacy for patients eligible and not eligible for RCTs of anti-TNF treatments.
METHODS
First, randomised placebo-controlled trials written in English for etanercept, infliximab and adalimumab for patients with RA were selected by a systematic review. Second, the DREAM (Dutch Rheumatoid Arthritis Monitoring) register with patients starting for the first time on one of the TNF-blocking agents was used. Patient characteristics, doses of medication and co-medication as well as the ACR20 response percentages were compared between RCTs and DREAM data, stratified for trial eligibility.
RESULTS
In 10 of 11 comparisons, the ACR20 response percentages were lower in daily clinical practice than in the RCT active drug group, which was significant in five of 11 comparisons. Only 34-79% of DREAM patients fulfilled the selection criteria for disease activity in the several RCTs examined. DREAM patients eligible for RCTs had higher response percentages than ineligible DREAM patients. ACR20 response percentages of eligible DREAM patients were comparable with the ACR20 response percentages of the RCT active drug group in 10 of 11 comparisons.
CONCLUSION
The efficacy of TNF-blocking agents in RCTs exceeded the efficacy of these drugs in clinical practice. However, in clinical practice more patients with lower disease activity were treated with TNF-blocking agents compared with those treated in RCTs. For daily practice patients who were eligible for RCTs, responses were more similar to responses reached in RCTs.
Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Etanercept; Female; Humans; Immunoglobulin G; Immunologic Factors; Infliximab; Male; Middle Aged; Netherlands; Patient Selection; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Receptors, Tumor Necrosis Factor; Registries; Research Design; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 17426065
DOI: 10.1136/ard.2007.072447 -
The Cochrane Database of Systematic... 2001The main pharmacological approach for the treatment of Alzheimer's disease (AD) has been based on the use of agents potentiating cholinergic transmission, particularly... (Review)
Review
BACKGROUND
The main pharmacological approach for the treatment of Alzheimer's disease (AD) has been based on the use of agents potentiating cholinergic transmission, particularly by inhibiting acetylcholinesterase (AChE), the enzyme that destroys acetylcholine after it has been secreted into the synaptic clefts. Physostigmine is an AChE inhibitor originally extracted from calabar beans. It is licensed in many countries as an agent for reversing the effect of drugs and poisons causing the anticholinergic syndrome. Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Investigation of this property has been limited by the very short half-life of physostigmine. Various forms of administering the drug have been tried to overcome this problem, most recently a controlled-release (CR) oral formulation, and a skin patch. It has been proposed as a potential drug for the symptomatic treatment of AD.
OBJECTIVES
To determine whether there is evidence of beneficial effects for the use of physostigmine in Alzheimer's disease. To assess the incidence and severity of adverse effects.
SEARCH STRATEGY
The Cochrane Controlled Trials Register was searched using the following terms: 'physostigmine', 'physostigmine salicylate', 'Synapton' and 'Antilirium' in accordance with the Cochrane Dementia and Cognitive Improvement Group's search strategy. The pharmaceutical company was contacted.
SELECTION CRITERIA
All relevant unconfounded, double-blind, randomized, placebo-controlled trials in which physostigmine was administered for more than one day to patients with dementia of Alzheimer type. Trials in which the allocation to the treatment was not randomized, or in which the allocation to the treatment was not concealed were excluded.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two reviewers (JMC & JB), pooled where appropriate and possible, and the weighted or standardized mean differences or Peto odds ratios (95% CI) were estimated. Where possible, intention-to-treat analysis was used.
MAIN RESULTS
Fifteen studies were included using four different methods of administration of physostigmine. Four studies, involving 29 people in total, used intravenous infusion; seven, involving 131 people, used a conventional oral form; four, involving 1456 participants, used a controlled-release oral form, and one study of 181 people used a verum skin patch. There are no usable results from the intravenous infusion trials, and the few results from the conventional oral form showed no benefit of physostigmine compared with placebo. The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period. The best dose physostigmine (mean 25mg/day) was associated with a 1.75 point improvement on ADAS-Cog score (mean difference -1.75, 95% confidence interval -2.90, -0.60 on an intention-to-treat basis) and a 0.26 point improvement on the CGIC score (treated as a continuous scale) (mean difference -0.26, 95% confidence interval 0.06, 0.46 on an intention-to-treat basis) compared with placebo at 6 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial (22/183 vs 2/183)(OR 5.92, 95% confidence limits 2.59, 13.54) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, flatulence or sweating compared with placebo at 6 weeks. The best dose physostigmine (mean 27mg/day) was associated with a 2.0 point improvement on ADAS-Cog score (mean difference -2.02, 95% confidence interval -3.59, -0.45 on an intention to treat basis) compared with placebo at 12 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial due to adverse events (13/83 vs 5/93)(OR 3.05, 95% confidence limits 1.15, 8.07) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, tremor, asthenia or sweating compared with placebo at 12 weeks. When no attempt was made to identify responders and all relevant patients with Alzheimer's disease were randomized, fixed dose physostigmine (mean 33 mg/day) was associated with a statistically significantly higher number withdrawing (234/358 vs 31/117)(OR 4.82, 95% confidence limits 3.17, 7.33), withdrawing due to adverse events (196/358 vs 10/117) (OR 6.54, 95%confidence limits 4.29, 9.95) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, dyspepsia, sweating, asthenia, dyspnoea or abnormal dreaming compared with placebo at 24 weeks. The results from the study of the verum patch physostigmine show that the double dose (delivering mean dose 12mg/day) was associated with statistically significantly higher numbers suffering at least one adverse event of vomiting, nausea or abdominal cramps compared with placebo at 24 weeks, but placebo was associated with statistically significantly greater numbers of gastrointestinal complaints at 24 weeks compared with single-dose physostigmine.
REVIEWERS' CONCLUSIONS
The evidence of effectiveness of physostigmine for the symptomatic treatment of Alzheimer's disease is limited. Even in a controlled release formulation designed to overcome the short half-life, physostigmine showed no convincing benefit and adverse effects remained common leading to a high rate of withdrawal.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Humans; Physostigmine; Randomized Controlled Trials as Topic
PubMed: 11405996
DOI: 10.1002/14651858.CD001499