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The Cochrane Database of Systematic... Jul 2015Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (1 to 14 headaches per month), and chronic TTH (15 headaches a month or more). Ibuprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH.
OBJECTIVES
To assess the efficacy and safety of oral ibuprofen for treatment of acute episodic TTH in adults.
SEARCH METHODS
We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and our own in-house database to January 2015. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers' websites.
SELECTION CRITERIA
We included randomised, placebo-controlled studies (parallel-group or cross-over) using oral ibuprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective and include at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, and extracted data. Numbers of participants achieving each outcome were used to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or number needed to treat for an additional harmful outcome (NNH) of oral ibuprofen compared to placebo for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).
MAIN RESULTS
We included 12 studies, all of which enrolled adult participants with frequent episodic TTH. Nine used the IHS diagnostic criteria, but two used the older classification of the Ad Hoc Committee, and one did not describe diagnostic criteria but excluded participants with migraines. While 3094 people with TTH participated in these studies, the numbers available for any form of analysis were lower than this; placebo was taken by 733, standard ibuprofen 200 mg by 127, standard ibuprofen 400 mg by 892, and fast-acting ibuprofen 400 mg by 230. Participants had moderate or severe pain at the start of treatment. Other participants were either in studies not reporting outcomes we could analyse, or were given one of several active comparators in single studies.For the IHS-preferred outcome of being pain free at 2 hours the NNT for ibuprofen 400 mg (all formulations) compared with placebo was 14 (95% confidence interval (CI), 8.4 to 47) in four studies, with no significant difference from placebo at 1 hour (moderate quality evidence). The NNT was 5.9 (4.2 to 9.5) for the global evaluation of 'very good' or 'excellent' in three studies (moderate quality evidence). No study reported the number of participants experiencing no worse than mild pain at 1 or 2 hours. The use of rescue medication was lower with ibuprofen 400 mg than with placebo, with the number needed to treat to prevent one event (NNTp) of 8.9 (5.6 to 21) in two studies (low quality evidence).Adverse events were not different between ibuprofen 400 mg and placebo; RR 1.1 (0.64 to 1.7) (high-quality evidence). No serious adverse events were reported.
AUTHORS' CONCLUSIONS
Ibuprofen 400 mg provides an important benefit in terms of being pain free at 2 hours for a small number of people with frequent episodic tension-type headache who have an acute headache with moderate or severe initial pain. There is no information about the lesser benefit of no worse than mild pain at 2 hours.
Topics: Acetaminophen; Administration, Oral; Adult; Analgesics, Non-Narcotic; Cyclooxygenase Inhibitors; Diclofenac; Humans; Ibuprofen; Ketoprofen; Naproxen; Numbers Needed To Treat; Pain Measurement; Piroxicam; Randomized Controlled Trials as Topic; Tension-Type Headache; Time Factors
PubMed: 26230487
DOI: 10.1002/14651858.CD011474.pub2 -
The Cochrane Database of Systematic... May 2015This review updates the original review, 'Pharmacological treatments for fatigue associated with palliative care' and also incorporates the review 'Drug therapy for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review updates the original review, 'Pharmacological treatments for fatigue associated with palliative care' and also incorporates the review 'Drug therapy for the management of cancer-related fatigue'.In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients' fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Fatigue frequently occurs in patients with advanced disease (e.g. cancer-related fatigue) and modalities used to treat cancer can often contribute. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The pathophysiology is not fully understood and evidence-based treatment approaches are needed.
OBJECTIVES
To evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. We searched the references of identified articles and contacted authors to obtain unreported data. To validate the search strategy we selected sentinel references.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) concerning adult palliative care with a focus on pharmacological treatment of fatigue compared to placebo, application of two drugs, usual care or a non-pharmacological intervention. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). We did not include studies on fatigue related to antineoplastic treatment (e.g. chemotherapy, radiotherapy, surgical intervention). We also included secondary outcomes that were assessed in fatigue-related studies (e.g. exhaustion, tiredness).
DATA COLLECTION AND ANALYSIS
Two review authors (MM and MC) independently assessed trial quality and extracted data. We screened the search results and included studies if they met the selection criteria. If we identified two or more studies that investigated a specific drug with the same dose in a population with the same disease and using the same assessment instrument or scale, we conducted meta-analysis. In addition, we compared the type of drug investigated in specific populations, as well as the frequent adverse effects of fatigue treatment, by creating overview tables.
MAIN RESULTS
For this update, we screened 1645 publications of which 45 met the inclusion criteria (20 additional studies to the previous reviews). In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials and we discuss the reasons for this in the review. There were some sources of potential bias in the included studies, including a lack of description of the methods of blinding and allocation concealment, and the small size of the study populations. We included studies investigating pemoline and modafinil in participants with multiple sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue in meta-analysis. Treatment results pointed to weak and inconclusive evidence for the efficacy of amantadine, pemoline and modafinil in multiple sclerosis and for carnitine and donepezil in cancer-related fatigue. Methylphenidate and pemoline seem to be effective in patients with HIV, but this is based only on one study per intervention, with only a moderate number of participants in each study. Meta-analysis shows an estimated superior effect for methylphenidate in cancer-related fatigue (standardised mean difference (SMD) 0.49, 95% confidence interval (CI) 0.15 to 0.83). Therapeutic effects could not be described for dexamphetamine, paroxetine or testosterone. There were a variety of results for the secondary outcomes in some studies. Most studies had low participant numbers and were heterogeneous. In general, adverse reactions were mild and had little or no impact.
AUTHORS' CONCLUSIONS
Based on limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Fatigue research in palliative care seems to focus on modafinil and methylphenidate, which may be beneficial for the treatment of fatigue associated with palliative care although further research about their efficacy is needed. Dexamethasone, methylprednisolone, acetylsalicylic acid, armodafinil, amantadine and L-carnitine should be further examined. Consensus is needed regarding fatigue outcome parameters for clinical trials.
Topics: Adult; Amantadine; Benzhydryl Compounds; Carnitine; Central Nervous System Stimulants; Chronic Disease; Fatigue; Humans; Kidney Failure, Chronic; Methylphenidate; Modafinil; Multiple Sclerosis; Neoplasms; Palliative Care; Pemoline; Randomized Controlled Trials as Topic
PubMed: 26026155
DOI: 10.1002/14651858.CD006788.pub3 -
Medicine Oct 2017Dexmedetomidine showed some potential in pain control in patients undergoing knee arthroscopy. We conducted a systematic review and meta-analysis to explore the efficacy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dexmedetomidine showed some potential in pain control in patients undergoing knee arthroscopy. We conducted a systematic review and meta-analysis to explore the efficacy of dexmedetomidine in patients undergoing knee arthroscopy.
METHODS
We searched the randomized controlled trials (RCTs) assessing the effect of dexmedetomidine on knee arthroscopy in PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases. The primary outcome was pain scores. Meta-analysis was performed using the random-effect model.
RESULTS
Five RCTs were included. Overall, compared with control intervention in patients with knee arthroscopy, dexmedetomidine intervention could significantly reduce the pain scores [Std. mean difference = -0.84; 95% confidence interval (95% CI) = -1.24 to -0.44; P < .0001] and postoperative diclofenac sodium consumption (Std. mean difference = -1.76; 95% CI = -3.32 to -0.21; P = .03), improve duration of analgesic effect (Std. mean difference = 1.78; 95% CI = 0.56-3.00; P = .004), but showed no influence on hypotension [risk ratio (RR) = 0.93; 95% CI = 0.14-5.92; P = .94], bradycardia (RR = 4.93; 95% CI = 0.91-26.58; P = .06), nausea, and vomiting (RR = 1.96; 95% CI = 0.31-12.58; P = .48).
CONCLUSION
Dexmedetomidine intervention was able to significantly reduce the pain scores and postoperative diclofenac sodium consumption, and improve duration of analgesic effect in patients undergoing knee arthroscopy, but had no influence on hypotension, bradycardia, nausea, and vomiting.
Topics: Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Knee; Dexmedetomidine; Diclofenac; Humans; Pain, Postoperative
PubMed: 29068980
DOI: 10.1097/MD.0000000000007938 -
PLoS Medicine Sep 2011Randomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Here, we... (Review)
Review
BACKGROUND
Randomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings.
METHODS AND FINDINGS
We performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR) estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study) analyses, generating ratios of RRs (RRRs). Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies), the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59), and diclofenac, 1.40 (1.27, 1.55), and the lowest with ibuprofen, 1.18 (1.11, 1.25), and naproxen, 1.09 (1.02, 1.16). In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57), celecoxib, 1.26 (1.09, 1.47), and diclofenac, 1.22 (1.12, 1.33), and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88), etodolac, 1.55 (1.28, 1.87), and indomethacin, 1.30 (1.19, 1.41), had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR = 1.68 (99% CI 1.14, 2.49), and naproxen, RRR = 1.75 (1.16, 2.64); etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR = 0.92 (0.87, 0.99). RR estimates were constant with different background risks for cardiovascular disease and rose early in the course of treatment.
CONCLUSIONS
This review suggests that among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Diclofenac in doses available without prescription elevates risk. The data for etoricoxib were sparse, but in pair-wise comparisons this drug had a significantly higher RR than naproxen or ibuprofen. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk casts doubt on its continued clinical use. Please see later in the article for the Editors' Summary.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Diclofenac; Humans; Ibuprofen; Naproxen
PubMed: 21980265
DOI: 10.1371/journal.pmed.1001098 -
The Cochrane Database of Systematic... Sep 2012Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly taken orally, but they are also available in topical preparations to be applied to or rubbed onto the skin of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly taken orally, but they are also available in topical preparations to be applied to or rubbed onto the skin of a painful joint, typically one affected by arthritis, with the aim of relieving pain locally. Topical NSAIDs are widely used in some parts of the world for acute and chronic painful conditions, but have not been universally accepted until recently. One of the problems has been that older clinical studies were generally short, lasting four weeks or less, and short duration studies are not regarded as adequate in ongoing painful conditions.
OBJECTIVES
To examine the use of topical NSAIDs in chronic musculoskeletal pain, focusing on studies of high methodological quality, and examining the measured effect of the preparations according to study duration. The principal aim was to estimate treatment efficacy in longer duration studies of at least 8 weeks.
SEARCH METHODS
A series of electronic searches, together with bibliographic searches, and searches of in-house databases were combined with electronic searches of clinical trial registers and manufacturers of topical NSAIDs, or companies known to be actively researching topical NSAIDs. There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily.
SELECTION CRITERIA
Randomised, double blind studies with placebo or active comparators, where at least one treatment was a topical NSAID product, in any topical formulation (cream, gel, patch, solution), in studies lasting at least two weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk (RR) and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment.
MAIN RESULTS
Information was available from 7688 participants in 34 studies from 32 publications; 23 studies compared a topical NSAID with placebo. Topical NSAIDs were significantly more effective than placebo for reducing pain due to chronic musculoskeletal conditions. The best data were for topical diclofenac in osteoarthritis, where the NNT for at least 50% pain relief over 8 to 12 weeks compared with placebo was 6.4 for the solution, and 11 for the gel formulation. There were too few data of good quality to calculate NNTs for other individual topical NSAIDs compared with placebo. Direct comparison of topical NSAID with an oral NSAID did not show any difference in efficacy. There was an increase in local adverse events (mostly mild skin reactions) with topical NSAIDs compared with placebo or oral NSAIDs, but no increase in serious adverse events. Gastrointestinal adverse events with topical NSAID did not differ from placebo, but were less frequent than with oral NSAIDs.A substantial amount of data from unpublished studies was unavailable. Much of this probably relates to formulations that have never been marketed.
AUTHORS' CONCLUSIONS
Topical NSAIDs can provide good levels of pain relief; topical diclofenac solution is equivalent to that of oral NSAIDs in knee and hand osteoarthritis, but there is no evidence for other chronic painful conditions. Formulation can influence efficacy. The incidence of local adverse events is increased with topical NSAIDs, but gastrointestinal adverse events are reduced compared with oral NSAIDs.
Topics: Administration, Topical; Adult; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Diclofenac; Humans; Musculoskeletal Pain; Randomized Controlled Trials as Topic
PubMed: 22972108
DOI: 10.1002/14651858.CD007400.pub2 -
The Cochrane Database of Systematic... Jul 2009Aceclofenac is the prodrug of the non-steroidal anti-inflammatory drug (NSAID) diclofenac, widely used to treat acute and chronic pain. There are no known systematic... (Review)
Review
BACKGROUND
Aceclofenac is the prodrug of the non-steroidal anti-inflammatory drug (NSAID) diclofenac, widely used to treat acute and chronic pain. There are no known systematic reviews of its analgesic efficacy in acute postoperative pain. This review sought to evaluate the efficacy and safety of oral aceclofenac in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
OBJECTIVES
To assess the efficacy of single dose oral aceclofenac in acute postoperative pain, and any associated adverse events.
SEARCH STRATEGY
We searched The Cochrane Library (Issue 1, 2009), MEDLINE via Ovid (1966 to March 2009); EMBASE via Ovid (1980 to March 2009); the Oxford Pain Relief Database (1950 to 1994); and reference lists of articles.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled clinical trials of oral aceclofenac for relief of acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive the proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
MAIN RESULTS
Searches identified only one study (217 participants total), which used oral aceclofenac 150 mg in patients with established postoperative pain. Aceclofenac 150 mg could not be distinguished from placebo, though ibuprofen 400 mg was distinguished from placebo.
AUTHORS' CONCLUSIONS
In the absence of evidence of efficacy for oral aceclofenac in acute postoperative pain (at least at 150 mg single dose), its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies are lacking, use in other indications should be evaluated carefully. Given the large number of effective drugs available in this and similar classes of analgesics, there is no urgent research agenda required to demonstrate the effective dose of aceclofenac in acute postoperative pain.
Topics: Acute Disease; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Pain, Postoperative
PubMed: 19588436
DOI: 10.1002/14651858.CD007588.pub2 -
British Journal of Clinical Pharmacology Jan 2014The aims of this review were to summarize the scientific evidence about the risks of using methylphenidate for ADHD in pregnancy and lactation, to present a case in... (Review)
Review
AIMS
The aims of this review were to summarize the scientific evidence about the risks of using methylphenidate for ADHD in pregnancy and lactation, to present a case in which interruption of treatment after delivery and during breastfeeding was harmful and to discuss the implications of treating or not treating ADHD in pregnancy and lactation.
METHODS
For the systematic review, databases searched included Pubmed, Psychinfo, Web of Science, Embase, Biosis and Medline.
RESULTS
Three articles were found with a total sample of 41 children exposed to methylphenidate in pregnancy. Malformations reported included congenital heart defects (n = 2), finger abnormalities (syndactyly, adactyly and polydactyly n = 2) and limb malformations (n = 1). Other problems included premature birth, asphyxia and growth retardation. One case report (n = 1) and one case series (n = 3) were identified regarding exposure to methylphenidate through breast feeding. In all cases, children developed normally and no adverse effects were reported. In our case report we describe an infant exposed to methylphenidate during pregnancy and breast feeding, who developed normally having no detectable congenital abnormalities.
CONCLUSIONS
The number and size of the studies found were small. Identified cases were not representative of the general adult ADHD population having methylphenidate as monotherapy during pregnancy as all the articles reported combinations of methylphenidate with either known teratogenic drugs or drugs of abuse. There is a paucity of data regarding the use of methylphenidate in pregnancy and further studies are required. Although the default medical position is to interrupt any non-essential pharmacological treatment during pregnancy and lactation, in ADHD this may present a significant risk. Doctors need to evaluate each case carefully before interrupting treatment.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Breast Feeding; Child Development; Female; Humans; Infant; Lactation; Methylphenidate; Pregnancy; Prenatal Exposure Delayed Effects; Young Adult
PubMed: 23593966
DOI: 10.1111/bcp.12138 -
The Cochrane Database of Systematic... Apr 2009Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an earlier review published in The Cochrane Database of Systematic Reviews (Issue 2, 2004) on 'Single dose oral diclofenac for postoperative pain'.
OBJECTIVES
To assess single dose oral diclofenac for the treatment of acute postoperative pain.
SEARCH STRATEGY
Cochrane CENTRAL, MEDLINE, EMBASE, Biological Abstracts, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants with at least 50% pain relief over 4 to 6 hours, using validated equations. Relative benefit (risk) and number needed to treat to benefit (NNT) were calculated. Information on adverse events, time to remedication, and participants needing additional analgesia was also collected.
MAIN RESULTS
Fifteen studies (eight additional studies) with 1512 participants more than doubled the information available at each dose. Overall 50% to 60% of participants experienced at least 50% pain relief over 4 to 6 hours at any dose with diclofenac, compared to 10 to 20% with placebo, giving NNTs of about 2.5 for doses of 25 mg to 100 mg (similar to earlier review); no dose response was demonstrated. At 50 mg and 100 mg, NNTs for diclofenac potassium (2.1 (1.8 to 2.4) and 1.9 (1.7 to 2.2)) were significantly lower (better) than for diclofenac sodium (6.7 (4.2 to 17) and 4.5 (3.2 to 7.7)). The median time to use of rescue medication was 2 hours for placebo, 4.3 hours for diclofenac 50 mg and 4.9 hours for diclofenac 100 mg. Adverse events were reported at a similar rate to placebo, with no serious events.
AUTHORS' CONCLUSIONS
Oral diclofenac is an effective single-dose treatment for moderate to severe postoperative pain. Significantly more participants experienced at least 50% pain relief over 4 to 6 hours with diclofenac potassium than with diclofenac sodium. There was no significant difference between diclofenac and placebo in the incidence of adverse events.
Topics: Acute Disease; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Cyclooxygenase Inhibitors; Diclofenac; Humans; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 19370609
DOI: 10.1002/14651858.CD004768.pub2 -
The Cochrane Database of Systematic... Apr 2018Ureteral colic is a common reason for patients to seek medical care. Alpha-blockers are commonly used to improve stone passage through so-called medical expulsive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ureteral colic is a common reason for patients to seek medical care. Alpha-blockers are commonly used to improve stone passage through so-called medical expulsive therapy (MET), but their effectiveness remains controversial. This is an update of a 2014 Cochrane review; since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant.
OBJECTIVES
To assess effects of alpha-blockers compared with standard therapy for ureteral stones 1 cm or smaller confirmed by imaging in adult patients presenting with symptoms of ureteral stone disease.
SEARCH METHODS
On 18 November 2017, we searched CENTRAL, MEDLINE Ovid, and Embase. We also searched ClinicalTrials.gov and the WHO Portal/ICTRP to identify all published/unpublished and ongoing trials. We checked all references of included and review articles and conference proceedings for articles relevant to this review. We sent letters to investigators to request information about unpublished or incomplete studies.
SELECTION CRITERIA
We included RCTs of ureteral stone passage in adult patients that compared alpha-blockers versus standard therapy.
DATA COLLECTION AND ANALYSIS
Two review authors screened studies for inclusion and extracted data using standard methodological procedures. We performed meta-analysis using a random-effects model. Primary outcomes were stone clearance and major adverse events; secondary outcomes were stone expulsion time, number of pain episodes, use of diclofenac, hospitalisation, and surgical intervention. We assessed the quality of evidence on a per-outcome basis using the GRADE approach.
MAIN RESULTS
We included 67 studies with 10,509 participants overall. Of these, 15 studies with 5787 participants used a placebo.Stone clearance: Based on the overall analysis, treatment with an alpha-blocker may result in a large increase in stone clearance (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.36 to 1.55; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that the likely effect is probably smaller (RR 1.16, 95% CI 1.07 to 1.25; moderate-quality evidence), corresponding to 116 more (95% CI 51 more to 182 more) stone clearances per 1000 participants.Major adverse events: Based on the overall analysis, treatment with an alpha-blocker may have little effect on major adverse events (RR 1.25, 95% CI 0.80 to 1.96; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that alpha-blockers likely increase the risk of major adverse events slightly (RR 2.09, 95% CI 1.13 to 3.86), corresponding to 29 more (95% CI 3 more to 75 more) major adverse events per 1000 participants.Patients treated with alpha-blockers may experience shorter stone expulsion times (mean difference (MD) -3.40 days, 95% CI -4.17 to -2.63; low-quality evidence), may use less diclofenac (MD -82.41, 95% CI -122.51 to -42.31; low-quality evidence), and likely require fewer hospitalisations (RR 0.51, 95% CI 0.34 to 0.77; moderate-quality evidence), corresponding to 69 fewer hospitalisations (95% CI 93 fewer to 32 fewer) per 1000 participants. Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI 0.53 to 1.02; low-quality evidence), corresponding to 28 fewer surgical interventions (95% CI 51 fewer to 2 more) per 1000 participants.A predefined subgroup analysis (test for subgroup differences; P = 0.002) suggests that effects of alpha-blockers may vary with stone size, with RR of 1.06 (95% CI 0.98 to 1.15; P = 0.16; I² = 62%) for stones 5 mm or smaller versus 1.45 (95% CI 1.22 to 1.72; P < 0.0001; I² = 59%) for stones larger than 5 mm. We found no evidence suggesting possible subgroup effects based on stone location or alpha-blocker type.
AUTHORS' CONCLUSIONS
For patients with ureteral stones, alpha-blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that alpha-blockers may be less effective for smaller (5 mm or smaller) than for larger stones (greater than 5 mm).
Topics: Adrenergic alpha-Antagonists; Adult; Analgesics; Diclofenac; Hospitalization; Humans; Randomized Controlled Trials as Topic; Time Factors; Ureteral Calculi
PubMed: 29620795
DOI: 10.1002/14651858.CD008509.pub3 -
Journal of Autism and Developmental... Oct 2013Many children with pervasive developmental disorders (PDD) exhibit behaviors and symptoms of attention-deficit/hyperactivity disorder (ADHD). We sought to determine the... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of pharmacological treatment of the symptoms of attention-deficit/hyperactivity disorder in children with pervasive developmental disorders.
Many children with pervasive developmental disorders (PDD) exhibit behaviors and symptoms of attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of medications for treating ADHD symptoms in children with PDD by identifying all double-blind, randomized, placebo-controlled trials examining the efficacy of medications for treating ADHD symptoms in children with PDD. We located seven trials involving 225 children. A random effects meta-analysis of four methylphenidate trials showed methylphenidate to be effective for treating ADHD symptoms in children with PDD (ES = .67). Several adverse events were greater for children were taking methylphenidate compared to placebo. An individual trial of clonidine and two trials of atomoxetine suggest these agents may also be effective in treating ADHD symptoms in children with PDD.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child Development Disorders, Pervasive; Child, Preschool; Double-Blind Method; Female; Humans; Methylphenidate; Propylamines; Randomized Controlled Trials as Topic
PubMed: 23468071
DOI: 10.1007/s10803-013-1793-z