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Acta Cirurgica Brasileira 2014This study is a systematic literature review and meta-analysis concerning the use of a testosterone synthetic analog, oxandrolone, and its use in severe adult burns. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This study is a systematic literature review and meta-analysis concerning the use of a testosterone synthetic analog, oxandrolone, and its use in severe adult burns.
METHODS
Randomized prospective clinical studies, in English, Portuguese or Spanish, were sought on the following databases: MEDLINE, COCHRANE, EMBASE and LILACS. There was no restriction in relation to the publication date.
RESULTS
This search produced 24 studies on MEDLINE and twelve articles were presented on the COCHRANE database .Sixteen were excluded due to the title not being related to this search or by including children. Of the eigth residual studies, after adaptation to the inclusion criteria, only four were selected. After analyzing the results, two were discarded since they did not present adequate patient characterization and the facts on these articles were analyzed differently from the others, hindering the meta-analysis.
CONCLUSION
The analysis of the available data demonstrated significant benefits (p<0.05) considering lesser loss of corporal mass, lesser nitrogen loss, and shorter donor area healing time, when Oxandrolone was used, comparatively with the control group (placebo or not).
Topics: Adult; Body Mass Index; Burns; Humans; Length of Stay; Nitrogen; Oxandrolone; Randomized Controlled Trials as Topic; Time Factors; Wound Healing
PubMed: 25351160
DOI: 10.1590/s0102-86502014001700013 -
Cureus Aug 2022Wounds with delayed or impaired healing represent a considerable challenge in medical practice. These patients develop a sustained hypermetabolic and catabolic state,... (Review)
Review
Wounds with delayed or impaired healing represent a considerable challenge in medical practice. These patients develop a sustained hypermetabolic and catabolic state, directly impacting the wound healing process. The use of oxandrolone has been studied to control this metabolic imbalance and protect lean body mass as a beneficial resource in wound healing. This systematic review aims to analyze previously conducted randomized controlled trials to evaluate the evidence of the applicability of oxandrolone therapy. We compared its use in adult patients with burns and adult patients with pressure ulcers in terms of wound healing and healing time of the skin graft donor site in days. The digital searches were done from March 23-28, 2022, within the databases: Google Scholar, PubMed/MEDLINE, and EBSCO (Elton B. Stephens Company). Data from six studies were analyzed and included in this review. Analysis of the available data demonstrated a significant advantage in skin healing using oxandrolone in adult burn patients as an adjunct. For adult patients with pressure ulcers, the drug showed no benefit on wound healing and skin graft site healing. Importantly, we found only one study evaluating the use of oxandrolone in patients with decubitus ulcers that met our eligibility criteria, and the certainty of the evidence was low. Thus, further prospective randomized studies with larger samples and standard wound care protocols are needed to produce more solid results, allowing more definitive conclusions to be made on this theme.
PubMed: 36127967
DOI: 10.7759/cureus.28079 -
The Cochrane Database of Systematic... Jun 2017Pressure ulcers, also known as bed sores, pressure sores or decubitus ulcers develop as a result of a localised injury to the skin or underlying tissue, or both. The... (Review)
Review
BACKGROUND
Pressure ulcers, also known as bed sores, pressure sores or decubitus ulcers develop as a result of a localised injury to the skin or underlying tissue, or both. The ulcers usually arise over a bony prominence, and are recognised as a common medical problem affecting people confined to a bed or wheelchair for long periods of time. Anabolic steroids are used as off-label drugs (drugs which are used without regulatory approval) and have been used as adjuvants to usual treatment with dressings, debridement, nutritional supplements, systemic antibiotics and antiseptics, which are considered to be supportive in healing of pressure ulcers. Anabolic steroids are considered because of their ability to stimulate protein synthesis and build muscle mass. Comprehensive evidence is required to facilitate decision making, regarding the benefits and harms of using anabolic steroids.
OBJECTIVES
To assess the effects of anabolic steroids for treating pressure ulcers.
SEARCH METHODS
In March 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
Published or unpublished randomised controlled trials (RCTs) comparing the effects of anabolic steroids with alternative treatments or different types of anabolic steroids in the treatment of pressure ulcers.
DATA COLLECTION AND ANALYSIS
Two review authors independently carried out study selection, data extraction and risk of bias assessment.
MAIN RESULTS
The review contains only one trial with a total of 212 participants, all with spinal cord injury and open pressure ulcers classed as stage III and IV. The participants were mainly male (98.2%, 106/108) with a mean age of 58.4 (standard deviation 10.4) years in the oxandrolone group and were all male (100%, 104/104) with a mean age of 57.3 (standard deviation 11.6) years in the placebo group. This trial compared oxandrolone (20 mg/day, administered orally) with a dose of placebo (an inactive substance consisting of 98% starch and 2% magnesium stearate) and reported data on complete healing of ulcers and adverse events. There was very low-certainty evidence on the relative effect of oxandrolone on complete ulcer healing at the end of a 24-week treatment period (risk ratio RR) 0.81, 95% confidence interval (CI) 0.52 to 1.26) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, we are uncertain whether oxandrolone improves or reduces the complete healing of pressure ulcers, as we assessed the certainty of the evidence as very low.There was low-certainty evidence on the risk of non-serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 3.85, 95% CI 1.12 to 13.26) (downgraded once for imprecision and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, the treatment with oxandrolone may increase the risk of non-serious adverse events reported in participants.There was very low-certainty evidence on the risk of serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 0.54, 95% CI 0.25 to 1.17) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Of the five serious adverse events reported in the oxandrolone-treated group, none were classed by the trial teams as being related to treatment. We are uncertain whether oxandrolone increases or decreases the risk of serious adverse events as we assessed the certainty of the evidence as very low.Secondary outcomes such as pain, length of hospital stay, change in wound size or wound surface area, incidence of different type of infection, cost of treatment and quality of life were not reported in the included trial.Overall the evidence in this study was of very low quality (downgraded for imprecision and indirectness). This trial stopped early when the futility analysis (interim analysis) in the opinion of the study authors showed that oxandrolone had no benefit over placebo for improving ulcer healing.
AUTHORS' CONCLUSIONS
There is no high quality evidence to support the use of anabolic steroids in treating pressure ulcers.Further well-designed, multicenter trials, at low risk of bias, are necessary to assess the effect of anabolic steroids on treating pressure ulcers, but careful consideration of the current trial and its early termination are required when planning future research.
Topics: Female; Humans; Male; Middle Aged; Off-Label Use; Oxandrolone; Pressure Ulcer; Starch; Stearic Acids; Testosterone Congeners; Wound Healing
PubMed: 28631809
DOI: 10.1002/14651858.CD011375.pub2 -
The Cochrane Database of Systematic... Jul 2015Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness.... (Review)
Review
BACKGROUND
Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment.
OBJECTIVES
To assess the effects of treatment for IBM.
SEARCH METHODS
On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials.
SELECTION CRITERIA
We considered randomised or quasi-randomised trials, including cross-over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta-1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) -0.06, 95% CI -0.15 to 0.03) between IFN beta-1a and placebo (moderate-quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate-quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low-quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re-analysis. Other comparisons were also reported in single trials. An open trial of anti-T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events.
AUTHORS' CONCLUSIONS
Trials of interferon beta-1a and MTX provided moderate-quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures.
PubMed: 35658164
DOI: 10.1002/14651858.CD001555.pub5 -
The Cochrane Database of Systematic... Sep 2014Recombinant human growth hormone (rhGH) increases protein synthesis, therefore it is used in burns with a total body surface area (TBSA) greater than 40%, where there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recombinant human growth hormone (rhGH) increases protein synthesis, therefore it is used in burns with a total body surface area (TBSA) greater than 40%, where there is frequently an increase in protein breakdown and a decrease in protein synthesis. This change in protein metabolism correlates with poor wound healing of the burn and donor sites.
OBJECTIVES
To determine the effects of rhGH on the healing rate of burn wounds and donor sites in people with burns.
SEARCH METHODS
For this first update we searched the Cochrane Wounds Group Specialised Register (searched 04 September 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2014, Issue 3); Ovid MEDLINE (1950 to September Week 4 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations September 8, 2014); Ovid EMBASE (1980 to 2014 Week 35); and EBSCO CINAHL (1982 to 8 September 2014).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing rhGH with any comparator intervention, e.g. oxandrolone or placebo, in adults or children with burns.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed trial quality and extracted data. The primary outcomes were the healing of the burn wound and donor sites and the occurrence of wound infections. The secondary outcomes were mortality rate, length of hospital stay, scar assessment, and adverse events: hyperglycaemia and septicaemia.
MAIN RESULTS
We included 13 RCTs (701 people). Six of the RCTs included only children aged 1 to 18 years and seven involved only adults (from 18 to 65 years of age). The mean TBSA of the included participants was greater than 49%. Twelve studies compared rhGH with placebo and one study compared rhGH with oxandrolone. Two trials found that compared with placebo, burn wounds in adults treated with rhGH healed more quickly (by 9.07 days; 95% confidence interval (CI) 4.39 to 13.76, I² = 0%). The donor site healing time was significantly shorter in rhGH-treated adults compared with placebo-treated participants (by 3.15 days; 95% CI 1.54 to 4.75, I² = 0%). Two studies in children with the outcome of donor site healing time could be pooled and the donor site healing time was shorter in the rhGH-treated children (by 1.70 days; 95% CI 0.87 to 2.53, I² = 0%). No studies reporting the outcome of wound infection were found. The incidence of hyperglycaemia was higher in adults during rhGH treatment compared with placebo (risk ratio (RR) 2.43; 95% CI 1.54 to 3.85), but not in children. Pooling the studies of adults and children yielded a significantly higher incidence of hyperglycaemia in the rhGH-treated participants (RR 2.65; 95% CI 1.68 to 4.16).
AUTHORS' CONCLUSIONS
There is some evidence that using rhGH in people with large burns (more than 40% of the total body surface area) could result in more rapid healing of the burn wound and donor sites in adults and children, and in reduced length of hospital stay, without increased mortality or scarring, but with an increased risk of hyperglycaemia. This evidence is based on studies with small sample sizes and risk of bias and requires confirmation in higher quality, adequately powered trials.
Topics: Adolescent; Adult; Aged; Anabolic Agents; Body Surface Area; Burns; Child; Child, Preschool; Human Growth Hormone; Humans; Infant; Middle Aged; Oxandrolone; Randomized Controlled Trials as Topic; Recombinant Proteins; Transplant Donor Site; Wound Healing; Young Adult
PubMed: 25222766
DOI: 10.1002/14651858.CD008990.pub3 -
Critical Care Medicine Jun 2016ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary... (Review)
Review
OBJECTIVES
ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary work to inform the design of a randomized trial of a complex intervention to improve recovery from critical illness, we sought to identify pharmacological interventions that may play a role in this area.
DATA SOURCES
We systematically reviewed the published literature relating to pharmacological intervention for the treatment and prevention of ICU-acquired weakness.
STUDY SELECTION
We searched MEDLINE, EMBASE, CINAHL+, Web of Science, and both U.S. and European trial registries up to July 2014 alongside reviews and reference lists from populations with no age or language restrictions. We included studies that reported a measure of muscle structure or physical function as an outcome measure.
DATA EXTRACTION
We estimated pooled odds ratios and 95% CI using data extracted from published articles or where available, original data provided by the authors. Assessment of bias was performed using the Cochrane Collaboration's risk of bias tool.
DATA SYNTHESIS
Ten studies met the inclusion criteria. The current body of evidence does not support the use of any pharmacological agent in this setting, although maintaining euglycemia may reduce the prevalence of critical illness polyneuropathy.
CONCLUSIONS
At present, no pharmacological intervention can be recommended to prevent or treat ICU-acquired weakness. Further research is required into this field to include more novel agents such as myostatin inhibitors. Challenges in the conduct of research in this area are highlighted.
Topics: Adrenergic beta-Antagonists; Anabolic Agents; Critical Illness; Glutamine; Growth Hormone; Humans; Hyperglycemia; Hypoglycemic Agents; Immunoglobulins, Intravenous; Immunologic Factors; Insulin; Muscle Weakness; Oxandrolone; Polyneuropathies; Propranolol
PubMed: 26958749
DOI: 10.1097/CCM.0000000000001652 -
The Cochrane Database of Systematic... Oct 2019The final adult height of untreated girls aged up to 18 years with Turner syndrome (TS) is approximately 20 cm shorter compared with healthy females. Treatment with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The final adult height of untreated girls aged up to 18 years with Turner syndrome (TS) is approximately 20 cm shorter compared with healthy females. Treatment with growth hormone (GH) increases the adult height of people with TS. The effects of adding the androgen, oxandrolone, in addition to GH are unclear. Therefore, we conducted this systematic review to investigate the benefits and harms of oxandrolone as an adjuvant therapy for people with TS treated with GH.
OBJECTIVES
To assess the effects of oxandrolone on growth hormone-treated girls aged up to 18 years with Turner syndrome.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, the ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was October 2018. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled clinical trials (RCTs) that enrolled girls aged up to 18 years with TS who were treated with GH and oxandrolone compared with GH only treatment.
DATA COLLECTION AND ANALYSIS
Three review authors independently screened titles and abstracts for relevance, selected trials, extracted data and assessed risk of bias. We resolved disagreements by consensus, or by consultation with a fourth review author. We assessed trials for overall certainty of the evidence using the GRADE instrument.
MAIN RESULTS
We included six trials with 498 participants with TS, 267 participants were randomised to oxandrolone plus GH treatment and 231 participants were randomised to GH only treatment. The individual trial sample size ranged between 22 and 133 participants. The included trials were conducted in 65 different paediatric endocrinology healthcare facilities including clinics, centres, hospitals and academia in the USA and Europe. The duration of interventions ranged between 3 and 7.6 years. The mean age of participants at start of therapy ranged from 9 to 12 years. Overall, we judged only one trial at low risk of bias in all domains and another trial at high risk of bias in most domains. We downgraded the level of evidence mainly because of imprecision (low number of trials, low number of participants or both). Comparing oxandrolone plus GH with GH only for final adult height showed a mean difference (MD) of 2.7 cm in favour of oxandrolone plus GH treatment (95% confidence interval (CI) 1.3 to 4.1; P < 0.001; 5 trials, 270 participants; moderate-quality evidence). The 95% prediction interval ranged between 0.3 cm and 5.1 cm. For adverse events, we based our main analysis on reliable date from two trials with overall low risk of bias. There was no evidence of a difference between oxandrolone plus GH and GH for adverse events (RR 1.81, 95% CI 0.83 to 3.96; P = 0.14; 2 trials, 170 participants; low-quality evidence). Six out of 86 (18.6%) participants receiving oxandrolone plus GH compared with 8/84 (9.5%) participants receiving GH only reported adverse events, mainly signs of virilisation (e.g. deepening of the voice). One trial each investigated the effects of treatments on speech (voice frequency; 88 participants), cognition (51 participants) and psychological status (106 participants). The overall results for these comparisons were inconclusive (very low-quality evidence). No trial reported on health-related quality of life or all-cause mortality.
AUTHORS' CONCLUSIONS
Addition of oxandrolone to the GH therapy led to a modest increase in the final adult height of girls aged up to 18 years with TS. Adverse effects identified included virilising effects such as deepening of the voice, but reporting was inadequate in some trials.
Topics: Adolescent; Androgens; Body Height; Female; Human Growth Hormone; Humans; Oxandrolone; Randomized Controlled Trials as Topic; Turner Syndrome
PubMed: 31684688
DOI: 10.1002/14651858.CD010736.pub2 -
The Cochrane Database of Systematic... 2004Facioscapulohumeral muscular dystrophy is a progressive muscle disease which has no agreed treatment. Early suggestions that corticosteroids might be helpful were not... (Review)
Review
BACKGROUND
Facioscapulohumeral muscular dystrophy is a progressive muscle disease which has no agreed treatment. Early suggestions that corticosteroids might be helpful were not supported by a subsequent open label study. The beta 2 adrenergic agonist albuterol, also known as salbutamol, is known to have anabolic effects which might be beneficial for facioscapulohumeral muscular dystrophy. Creatine has been used as a muscle performance enhancer by athletes and it might be helpful in muscular dystrophies including facioscapulohumeral muscular dystrophy.
OBJECTIVES
The objective of the review was to determine whether there is any drug treatment which alters the progression of facioscapulohumeral muscular dystrophy.
SEARCH STRATEGY
We searched the Cochrane Neuromuscular Disease Group specialised register (searched August 2003), MEDLINE (January 1966 to August 2003) and EMBASE (January 1980 to August 2003) for any references to facioscapulohumeral muscular dystrophy. Abstracts from the major neurological meetings and trial bibliographies were also searched for further references to trials. Experts were contacted for information regarding unpublished trials or trials in progress.
SELECTION CRITERIA
We included all randomised or quasi-randomised trials of any drug treatment for facioscapulohumeral muscular dystrophy, in adults with a recognised diagnosis of facioscapulohumeral muscular dystrophy. Trials had to include an assessment of muscle strength at one year.
DATA COLLECTION AND ANALYSIS
All identified trials were independently assessed by both reviewers to ensure that they fulfilled the selection criteria and were then rated for their quality. Trial data were extracted and entered by one reviewer and checked by the other. If appropriate data existed a weighted treatment effect was to be calculated across trials using the Cochrane statistical package, Review Manager. The results were to have been expressed as relative risks and 95% confidence intervals and risk differences and 95% confidence intervals for dichotomous outcomes, and weighted mean differences and 95% confidence intervals for continuous outcomes.
MAIN RESULTS
Two published high quality randomised controlled trials fulfilled the selection criteria. One compared creatine supplementation with placebo and the other compared high and low-dose albuterol with placebo. A further unpublished randomised controlled trial of albuterol in facioscapulohumeral muscular dystrophy was identified. The creatine trial showed a non-significant difference in favour of creatine. The albuterol trial showed no significant difference in muscle strength at one year but some secondary measures such as lean body mass and handgrip strength did improve.
REVIEWERS' CONCLUSIONS
There is no evidence from randomised controlled trials to support any drug treatment for facioscapulohumeral muscular dystrophy but only two randomised controlled trials have been published.
Topics: Adrenergic beta-Agonists; Albuterol; Creatine; Humans; Muscular Dystrophy, Facioscapulohumeral; Randomized Controlled Trials as Topic
PubMed: 15106171
DOI: 10.1002/14651858.CD002276.pub2