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Osteoarthritis of the knee and hip. Part II: therapy with ibuprofen and a review of clinical trials.The Journal of Pharmacy and Pharmacology May 2012We review the pharmacological properties and clinical evidence pertaining to the efficacy of ibuprofen as a first-line treatment in hip and knee osteoarthritis (OA). In... (Review)
Review
OBJECTIVES
We review the pharmacological properties and clinical evidence pertaining to the efficacy of ibuprofen as a first-line treatment in hip and knee osteoarthritis (OA). In the context of our previous paper's exploration of the aetiology and pathogenesis of OA as a basis for pharmacotherapy, we discuss the pharmacokinetics (PK) and clinical pharmacodynamics (PD) of ibuprofen relevant to OA.
KEY FINDINGS
Although widely used, the benefits and risks of ibuprofen, especially compared with other non-steroidal anti-inflammatory drugs (NSAIDs) and placebo, have only recently been evaluated in OA of the hip and knee in randomized-controlled clinical trials (RCT). The efficacy and occurrence of adverse reactions from ibuprofen was compared with placebo in a structural review of the literature and systematic review of RCTs in large-scale clinical trials. Ibuprofen has been found to result in approximately 50-60% improvement over placebo in WOMAC scores, including those reflecting inflammatory joint pain in knee and hip OA or other indices of pain, disability and impaired function. Mega-trials performed in comparison with the newer NSAIDs, the coxibs, have shown that ibuprofen has comparable therapeutic benefits and although serious gastrointestinal conditions are sometimes more frequent after short-term treatment, longer-term (several months) therapy in OA reduces the advantages of the coxibs over other NSAIDs including ibuprofen. Cardiovascular risk, though present with coxibs and some NSAIDs in OA, is lower or slightly so with ibuprofen compared with coxibs.
SUMMARY
Ibuprofen is effective and relatively safe (especially at low over-the-counter doses and in the short term) for mild-to-moderate OA of the knee and hip. The PK properties of ibuprofen in OA (short plasma t½) confer advantages of this drug for OA, while evidence for clinically relevant PD benefits in joints of patients with OA, though limited, is suggestive of local anti-inflammatory activity.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Hip; Hip Joint; Humans; Ibuprofen; Knee; Knee Joint; Osteoarthritis, Hip; Osteoarthritis, Knee; Treatment Outcome
PubMed: 22471358
DOI: 10.1111/j.2042-7158.2012.01456.x -
International Journal of Pediatric... Oct 2011This study is aimed at updating the relationships between physical activity (PA) and the metabolic syndrome (MetS) and/or insulin resistance (IR) in youth.... (Review)
Review
This study is aimed at updating the relationships between physical activity (PA) and the metabolic syndrome (MetS) and/or insulin resistance (IR) in youth. Cross-sectional, prospective cohort and intervention studies, which examined the effect of PA on MetS, its components and IR in children and adolescents (<18 yrs), were searched by applying a combination of criteria in the PubMed database. The electronic search of studies published from 2000-2010 yielded >150 references. Of these, 37 studies were included. Twenty-six studies (70%) were cross-sectional observation studies, and two studies (8%) were prospective cohort studies. The remaining eight studies (22%) were interventions, of which three (<10% of all included studies) were randomized controlled trials. Commonly, higher PA levels were consistently associated with an improved metabolic profile and a reduced risk for MetS and/or IR in these populations. The impact of PA on MetS and/or IR appeared to be either independent of other factors, or alternatively or simultaneously mediated by the physical fitness and adiposity of youth. However, more-robustly designed interventions (i.e., some mega-randomized controlled trials based on lifestyle interventions) and additional cohort studies are required to make definitive inference about the magnitude and role of PA as a single genuine preventive and treatment strategy for the metabolic and cardiovascular risk of youth in the current obesogenic context.
Topics: Adiposity; Adolescent; Child; Cohort Studies; Cross-Sectional Studies; Exercise; Humans; Insulin Resistance; Metabolic Syndrome; Physical Fitness
PubMed: 21851163
DOI: 10.3109/17477166.2011.605896 -
The Cochrane Database of Systematic... Jul 2007The role of vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for 60 years, but is widely sold and used as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for 60 years, but is widely sold and used as both a preventive and therapeutic agent.
OBJECTIVES
To discover whether oral doses of 0.2 g or more daily of vitamin C reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of symptoms.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2006); MEDLINE (1966 to December 2006); and EMBASE (1990 to December 2006).
SELECTION CRITERIA
Papers were excluded if a dose less than 0.2 g per day of vitamin C was used, or if there was no placebo comparison.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes.
MAIN RESULTS
Thirty trial comparisons involving 11,350 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold whilst taking prophylactic vitamin C. The pooled RR was 0.96 (95% confidence intervals (CI) 0.92 to 1.00). A subgroup of six trials involving a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95% CI 0.38 to 0.66). Thirty comparisons involving 9676 respiratory episodes contributed to a meta-analysis on common cold duration during prophylaxis. A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adults and 13.6% (95% CI 5% to 22%) for children. Seven trial comparisons involving 3294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C initiated after the onset of symptoms. No significant differences from placebo were seen. Four trial comparisons involving 2753 respiratory episodes contributed to the meta-analysis of cold severity during therapy and no significant differences from placebo were seen.
AUTHORS' CONCLUSIONS
The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence suggests that it could be justified in people exposed to brief periods of severe physical exercise or cold environments.
Topics: Administration, Oral; Ascorbic Acid; Common Cold; Humans; Randomized Controlled Trials as Topic; Respiratory Tract Infections
PubMed: 17636648
DOI: 10.1002/14651858.CD000980.pub3 -
The Cochrane Database of Systematic... Oct 2005The use of mega-vitamin intervention began in the 1950s with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with... (Review)
Review
BACKGROUND
The use of mega-vitamin intervention began in the 1950s with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with "autism syndrome" when speech and language improvement was observed in some children as a result of large doses of B6. A number of studies attempted to assess the effects of vitamin B6-Magnesium (Mg) was found to reduce undesirable side effects from B6) on characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism.
OBJECTIVES
To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication, and behavioural responses of children and adults with autism.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966 to January 2002), EMBASE (1980 to January 2002), PsycINFO (1887 to January 2002), Dissertation Abstracts International (1861 to January 2002). The search engine FirstSearch was also used (January 2002). All searches were updated in April 2005. Reference lists for all the obtained studies and other review articles were examined for additional studies.
SELECTION CRITERIA
All studies in which the participants had been diagnosed with autistic spectrum disorder were randomly allocated prior to intervention and in which outcomes were compared to either a placebo or non-treated group were included.
DATA COLLECTION AND ANALYSIS
Two reviewers independently evaluated and extracted data from all potential studies identified for inclusion.
MAIN RESULTS
This update includes a new trial (Kuriyama 2002) to bring the total of included studies to three (total n=33). One study, which used a cross-over design (Tolbert 1993) provided insufficient data to conduct an analysis. Another crossover study (Findling 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. The latest study (Kuriyama 2002) was motivated by evidence from epilepsy research and was focussed on a subgroup of children with pervasive developmental disorders (PDDs) who exhibited clinical features similar to those with pyroxidine-dependent epilepsy. This small study (n=8) only measured IQ and 'Social Quotient' and found a statistically significant benefit for IQ (5.2, 95% CI = [0.2 to 10.3]) when in the treated group, by using change scores.
AUTHORS' CONCLUSIONS
Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.
Topics: Adult; Autistic Disorder; Child; Drug Therapy, Combination; Humans; Magnesium; Randomized Controlled Trials as Topic; Vitamin B 6; Vitamin B Complex
PubMed: 16235322
DOI: 10.1002/14651858.CD003497.pub2 -
The Cochrane Database of Systematic... Oct 2004The role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment.
OBJECTIVES
To discover whether oral vitamin C in doses of 200 mg or more daily, reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of cold symptoms.
SEARCH STRATEGY
This updated review added to earlier searches, a full search of the following electronic databases: the Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June 2004); and EMBASE (1990 to June 2004).
SELECTION CRITERIA
Papers were excluded if a dose less than 200 mg daily of vitamin C was used; if there was no placebo comparison; if methods of outcome assessment were inadequately described; and if the report did not record any of the three study outcomes (incidence, duration or severity) in sufficient detail to enter into the meta-analysis. Three criteria of study quality were assessed: Jadad scores, placebo distinguish-ability, and allocation concealment.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes and 'severity' of these episodes was assessed by days confined indoors, off work or school. or by symptom severity scores.
MAIN RESULTS
Twenty-nine trial comparisons involving 11,077 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold while taking prophylaxis. The pooled RR was 0.96 (95% CI 0.92 to 1.00). A subgroup of six trials that involved a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95%CI 0.38 to 0.66). Thirty comparisons that involved 9,676 respiratory episodes contributed to the meta-analysis on common cold duration during prophylaxis . A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adult participants and 13.5% (95% CI 5% to 21%) for child participants. Fifteen trial comparisons that involved 7,045 respiratory episodes contributed to the meta-analysis of severity of episodes experienced while on prophylaxis. The pooled results revealed a difference favouring those on vitamin C when days confined to home and off work or school were taken as a measure of severity (p = 0.02), and when restricting to studies which used symptom severity scores (p = 0.16), and for the both measures of severity combined (p = 0.004). Seven trial comparisons that involved 3,294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C that was initiated after the onset of cold symptoms, and no significant difference from placebo was seen. Four trial comparisons that involved 2,753 respiratory episodes, contributed to the meta-analysis of cold severity during therapy and no significant difference from placebo was seen.In laboratory studies, differing methods of artificial transmission of virus to vitamin C or placebo treated volunteers in residential experiments gave different results. Volunteers infected by nasal installation showed small or no benefit from vitamin C, whereas a group who were infected more naturally, reported less severe symptom severity scores (p = 0.04).
REVIEWERS' CONCLUSIONS
The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence shows that it could be justified in persons exposed to brief periods of severe physical exercise and/or cold environments. Also, the consistent and statistically significant small benefits on duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defence mechanisms. The trials in which vitamin C was introduced at the onset of colds as therapy did not show any benefit in doses up to 4 grams daily, but one large trial reported equivocal benefit from an 8 gram therapeutic dose at onset of symptoms.
Topics: Administration, Oral; Ascorbic Acid; Common Cold; Humans; Respiratory Tract Infections
PubMed: 15495002
DOI: 10.1002/14651858.CD000980.pub2 -
Cerebrovascular Diseases (Basel,... 2004Endovascular treatment for carotid artery stenosis avoids some of the complications of carotid endarterectomy, but has not been widely accepted. Concerns about the risks... (Comparative Study)
Comparative Study Meta-Analysis
Endovascular treatment for carotid artery stenosis avoids some of the complications of carotid endarterectomy, but has not been widely accepted. Concerns about the risks and benefits of endovascular treatment led to the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). There was no difference in major outcome events between endovascular treatment and carotid endarterectomy, but the rate of procedural stroke or death was higher than desirable. There was no difference either in the rate of stroke during follow-up, but the confidence intervals were very wide and severe ipsilateral carotid stenosis was more frequent 1 year after endovascular treatment than after carotid surgery. Two other randomised trials of carotid stenting were stopped early after poor outcomes in stented patients. These early trials used techniques which have now been superseded, but the results emphasise the need to improve the safety of endovascular treatment. Recent advances designed to improve safety include new designs of stents and delivery systems, and devices designed to protect the brain from embolisation during stenting. However, there is little convincing evidence that these new devices reduce the rate of stroke. Moreover, a systematic review of the existing randomised trial data concluded that there the current evidence does not support a shift away from recommending carotid endarterectomy as the standard treatment for carotid stenosis. There is therefore a clear need for further randomised trials of carotid stenting. Three of the ongoing trials, EVA-3S, SPACE and ICSS (CAVATAS-2), have prospectively agreed to combine individual patient data after completion of follow-up. This meta-analysis will provide results similar to a mega-trial and should also allow informative subgroup analyses. The co-operation between the trials in agreeing to perform this meta-analysis is a major advance in trial design. The result should determine whether carotid stenting truly rivals carotid endarterectomy as the treatment of choice for carotid stenosis.
Topics: Carotid Stenosis; Endarterectomy, Carotid; Humans; Randomized Controlled Trials as Topic; Risk Factors; Stents; Stroke
PubMed: 15178988
DOI: 10.1159/000078750 -
The Cochrane Database of Systematic... 2003Basal cell carcinoma (BCC) is the most common skin malignancy in humans. BCCs are defined as slow-growing, locally invasive, malignant (but not life threatening),... (Review)
Review
BACKGROUND
Basal cell carcinoma (BCC) is the most common skin malignancy in humans. BCCs are defined as slow-growing, locally invasive, malignant (but not life threatening), epidermal skin tumours which mainly affect white skinned people. The first line treatment is usually surgical excision, but numerous alternatives are available.
OBJECTIVES
To assess the effects of treatments for basal cell carcinoma.
SEARCH STRATEGY
We searched the Cochrane Database of Systematic Reviews (2002 issue 1) and Cochrane Controlled Trials Register (2002 issue 1), the Cochrane Skin Group Specialised Register (January 2002), MEDLINE (from 1966-2002), EMBASE (from 1980-2002), the Mega Register of Controlled trials and the National Research Register (2002 issue 1). In addition the cited references of all trials identified and key review articles were searched. Pharmaceutical companies were contacted where appropriate for reviews or unpublished trials.
SELECTION CRITERIA
Inclusion criteria were adults with one or more histologically proven, primary basal cell carcinoma. The primary outcome measure was recurrence at 3- 5 years, measured clinically. The secondary outcome included early treatment failure within 6 months, measured histologically. Adverse effect of treatment was evaluated by reviewing aesthetic appearance (to patient and blinded observer) and pain during and after treatment.
DATA COLLECTION AND ANALYSIS
Study selection and assessment of methodological quality were carried out by two independent reviewers.
MAIN RESULTS
19 studies (13 published and 6 abstracts) were identified which include 7 broad therapeutic categories. Only one RCT of surgery versus radiotherapy had primary outcome data at four years, which showed that there were significantly more persistent tumours and recurrences, measured histologically, in the radiotherapy group as compared to the surgery group, which translates to an odds ratio of 0.09 (95%CI, 0.01 to 0.67) in favour of surgery. Cryotherapy, although convenient and less expensive than surgery, showed no significant difference in recurrences at one year, measured clinically, when compared to surgery, OR 0.23 (0.01 to 6.78). However when radiotherapy was compared to cryotherapy there were significantly more recurrences at one year, measured histologically, in the cryotherapy group, this translates to an odds ratio of 14.80 (95%CI, 3.17 to 69) in favour of radiotherapy. Preliminary studies suggest a high success rate (87-88%) for imiquimod in the treatment of superficial BCC using a once-daily regimen for 6 weeks and a useful (76%) treatment response when treating nodular BCC for 12 weeks, when measured histologically. However this cream has not been compared to surgery.
REVIEWER'S CONCLUSIONS
There has been very little good quality research on efficacy of the treatment modalities used. Most of the trials have looked only at BCCs in low risk areas. Surgery and radiotherapy appear to be the most effective treatments with surgery showing the lowest failure rates. Other treatments might have some use but few have been compared to surgery. Imiquimod emerged as a possible new treatment although it has not been compared to surgery or any other modality.
Topics: Adult; Carcinoma, Basal Cell; Humans; Randomized Controlled Trials as Topic; Skin Neoplasms; Treatment Outcome
PubMed: 12804465
DOI: 10.1002/14651858.CD003412 -
The Cochrane Database of Systematic... 2002The use of mega-vitamin intervention began in the early 1950's with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of mega-vitamin intervention began in the early 1950's with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with "autism syndrome" when speech and language improvement was observed in some children as a result of large doses of B6. A number of published studies attempted to assess the effects of vitamin B6-Mg (Mg was found to reduce undesirable side effects from B6) on a variety of characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism.
OBJECTIVES
To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication and behavioural responses of children and adults with autism.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966- January 2002), EMBASE (1980-January 2002), PsychINFO (1887 - January 2002), Dissertation Abstracts International (1861 - January 2002). The search engine FirstSearch was also used (January 2002). Reference lists for all the obtained studies and other review articles were examined for additional studies.
SELECTION CRITERIA
All studies in which the participants were randomly allocated prior to intervention and in which outcomes were compared to either a placebo or non-treated group were included.
DATA COLLECTION AND ANALYSIS
Two reviewers independently evaluated all potential studies identified as indicated above for inclusion.
MAIN RESULTS
Two trials were included in the review. Both studies used a double-blind crossover design. One study (Tolbert 1993) provided insufficient data to conduct an analysis. The senior author was contacted for supporting data but was unable to provide the needed information. The remaining study (Findling, 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity.
REVIEWER'S CONCLUSIONS
Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.
Topics: Adult; Autistic Disorder; Child; Drug Therapy, Combination; Humans; Magnesium; Vitamin B 6
PubMed: 12519599
DOI: 10.1002/14651858.CD003497