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The Cochrane Database of Systematic... May 2016Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood. Untreated, this incurable disease, which has an X-linked recessive inheritance, is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood. Untreated, this incurable disease, which has an X-linked recessive inheritance, is characterised by muscle wasting and loss of walking ability, leading to complete wheelchair dependence by 13 years of age. Prolongation of walking is a major aim of treatment. Evidence from randomised controlled trials (RCTs) indicates that corticosteroids significantly improve muscle strength and function in boys with DMD in the short term (six months), and strength at two years (two-year data on function are very limited). Corticosteroids, now part of care recommendations for DMD, are largely in routine use, although questions remain over their ability to prolong walking, when to start treatment, longer-term balance of benefits versus harms, and choice of corticosteroid or regimen.We have extended the scope of this updated review to include comparisons of different corticosteroids and dosing regimens.
OBJECTIVES
To assess the effects of corticosteroids on prolongation of walking ability, muscle strength, functional ability, and quality of life in DMD; to address the question of whether benefit is maintained over the longer term (more than two years); to assess adverse events; and to compare efficacy and adverse effects of different corticosteroid preparations and regimens.
SEARCH METHODS
On 16 February 2016 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, and LILACS. We wrote to authors of published studies and other experts. We checked references in identified trials, handsearched journal abstracts, and searched trials registries.
SELECTION CRITERIA
We considered RCTs or quasi-RCTs of corticosteroids (e.g. prednisone, prednisolone, and deflazacort) given for a minimum of three months to patients with a definite DMD diagnosis. We considered comparisons of different corticosteroids, regimens, and corticosteroids versus placebo.
DATA COLLECTION AND ANALYSIS
The review authors followed standard Cochrane methodology.
MAIN RESULTS
We identified 12 studies (667 participants) and two new ongoing studies for inclusion. Six RCTs were newly included at this update and important non-randomised cohort studies have also been published. Some important studies remain unpublished and not all published studies provide complete outcome data.
PRIMARY OUTCOME MEASURE
one two-year deflazacort RCT (n = 28) used prolongation of ambulation as an outcome measure but data were not adequate for drawing conclusions.
SECONDARY OUTCOME MEASURES
meta-analyses showed that corticosteroids (0.75 mg/kg/day prednisone or prednisolone) improved muscle strength and function versus placebo over six months (moderate quality evidence from up to four RCTs). Evidence from single trials showed 0.75 mg/kg/day superior to 0.3 mg/kg/day on most strength and function measures, with little evidence of further benefit at 1.5 mg/kg/day. Improvements were seen in time taken to rise from the floor (Gowers' time), timed walk, four-stair climbing time, ability to lift weights, leg function grade, and forced vital capacity. One new RCT (n = 66), reported better strength, function and quality of life with daily 0.75 mg/kg/day prednisone at 12 months. One RCT (n = 28) showed that deflazacort stabilised muscle strength versus placebo at two years, but timed function test results were too imprecise for conclusions to be drawn.One double-blind RCT (n = 64), largely at low risk of bias, compared daily prednisone (0.75 mg/kg/day) with weekend-only prednisone (5 mg/kg/weekend day), finding no overall difference in muscle strength and function over 12 months (moderate to low quality evidence). Two small RCTs (n = 52) compared daily prednisone 0.75 mg/kg/day with daily deflazacort 0.9 mg/kg/day, but study methods limited our ability to compare muscle strength or function.
ADVERSE EFFECTS
excessive weight gain, behavioural abnormalities, cushingoid appearance, and excessive hair growth were all previously shown to be more common with corticosteroids than placebo; we assessed the quality of evidence (for behavioural changes and weight gain) as moderate. Hair growth and cushingoid features were more frequent at 0.75 mg/kg/day than 0.3 mg/kg/day prednisone. Comparing daily versus weekend-only prednisone, both groups gained weight with no clear difference in body mass index (BMI) or in behavioural changes (low quality evidence for both outcomes, one study); the weekend-only group had a greater linear increase in height. Very low quality evidence suggested less weight gain with deflazacort than with prednisone at 12 months, and no difference in behavioural abnormalities. Data are insufficient to assess the risk of fractures or cataracts for any comparison.Non-randomised studies support RCT evidence in showing improved functional benefit from corticosteroids. These studies suggest sustained benefit for up to 66 months. Adverse effects were common, although generally manageable. According to a large comparative longitudinal study of daily or intermittent (10 days on, 10 days off) corticosteroid for a mean period of four years, a daily regimen prolongs ambulation and improves functional scores over the age of seven, but with a greater frequency of side effects than an intermittent regimen.
AUTHORS' CONCLUSIONS
Moderate quality evidence from RCTs indicates that corticosteroid therapy in DMD improves muscle strength and function in the short term (twelve months), and strength up to two years. On the basis of the evidence available for strength and function outcomes, our confidence in the effect estimate for the efficacy of a 0.75 mg/kg/day dose of prednisone or above is fairly secure. There is no evidence other than from non-randomised trials to establish the effect of corticosteroids on prolongation of walking. In the short term, adverse effects were significantly more common with corticosteroids than placebo, but not clinically severe. A weekend-only prednisone regimen is as effective as daily prednisone in the short term (12 months), according to low to moderate quality evidence from a single trial, with no clear difference in BMI (low quality evidence). Very low quality evidence indicates that deflazacort causes less weight gain than prednisone after a year's treatment. We cannot evaluate long-term benefits and hazards of corticosteroid treatment or intermittent regimens from published RCTs. Non-randomised studies support the conclusions of functional benefits, but also identify clinically significant adverse effects of long-term treatment, and a possible divergence of efficacy in daily and weekend-only regimens in the longer term. These benefits and adverse effects have implications for future research and clinical practice.
Topics: Adrenal Cortex Hormones; Glucocorticoids; Humans; Male; Muscle Strength; Muscular Dystrophy, Duchenne; Prednisolone; Prednisone; Pregnenediones; Quality of Life; Randomized Controlled Trials as Topic; Walking
PubMed: 27149418
DOI: 10.1002/14651858.CD003725.pub4 -
Chest Mar 2023Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality. Corticosteroids may be a beneficial adjunct in the treatment of bacterial pneumonia. (Meta-Analysis)
Meta-Analysis
Effect of Corticosteroids on Mortality and Clinical Cure in Community-Acquired Pneumonia: A Systematic Review, Meta-analysis, and Meta-regression of Randomized Control Trials.
BACKGROUND
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality. Corticosteroids may be a beneficial adjunct in the treatment of bacterial pneumonia.
RESEARCH QUESTION
Is there any benefit of corticosteroid therapy in the management of bacterial CAP among patients requiring hospitalization?
STUDY DESIGN AND METHODS
PubMed, Cochrane Library, and Embase were searched to identify randomized controlled trials assessing the use of systemic corticosteroids compared with standard care in the management of CAP. A systematic review, meta-analysis, and Trial Sequential Analysis (TSA) were performed. The primary outcome was all-cause mortality. Secondary outcomes included ICU admission, mechanical ventilation, treatment failure, readmission, and adverse events. Data are presented as risk ratio (RR) with 95% CI, P value, heterogeneity (I), and TSA-adjusted CIs.
RESULTS
Sixteen trials met the eligibility criteria. All-cause mortality (16 studies [3,842 patients]; RR, 0.85 [95% CI, 0.67-1.07]; P = .17; I = 14%; TSA-adjusted CI, 0.61-1.09), ICU admission (six studies [2,619 patients]; RR, 0.66 [95% CI, 0.45-0.97]; P = .04; I = 0%; TSA-adjusted CI, 0.37-1.12), treatment failure (six studies [2,093 patients]; RR, 0.78 [95% CI, 0.37-1.67]; P = .52; I = 68%; TSA-adjusted CI, 0.02-25.5), and the incidence of adverse events (six studies [2,487 patients]; RR, 1.10 [95% CI, 0.97-1.25]; P = .14; I = 53%; TSA-adjusted CI, 0.82-2.41) were similar between patients receiving corticosteroids and patients assigned to the control group. The need for mechanical ventilation (eight studies [1,457 patients]; RR, 0.51 [95% CI, 0.33-0.77]; P = .001; I = 0%; TSA-adjusted CI, 0.20-0.85) was lower among patients receiving corticosteroids compared with those receiving standard care. However, corticosteroid use may be associated with higher rates of hospital readmission (five studies [2,853 patients]; RR, 1.20 [95% CI, 1.05-1.38]; P = .008; I = 0%; TSA-adjusted CI, 0.89-1.98).
INTERPRETATION
Corticosteroid therapy is associated with a lower incidence of progression to requiring mechanical ventilation among patients hospitalized with CAP. No association was found between corticosteroid therapy and mortality, treatment failure, or adverse events.
TRIAL REGISTRY
PROSPERO; No.: CRD42021279359; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Adrenal Cortex Hormones; Pneumonia; Hospitalization
PubMed: 36087797
DOI: 10.1016/j.chest.2022.08.2229 -
International Journal of Molecular... Jul 2021Temporomandibular joint osteoarthritis (TMJ OA) is a low-inflammatory disorder with multifactorial etiology. The aim of this review was to present the current state of...
Mechanisms of Action and Efficacy of Hyaluronic Acid, Corticosteroids and Platelet-Rich Plasma in the Treatment of Temporomandibular Joint Osteoarthritis-A Systematic Review.
Temporomandibular joint osteoarthritis (TMJ OA) is a low-inflammatory disorder with multifactorial etiology. The aim of this review was to present the current state of knowledge regarding the mechanisms of action and the efficacy of hyaluronic acid (HA), corticosteroids (CS) and platelet-rich plasma (PRP) in the treatment of TMJ OA.: The PubMed database was analyzed with the keywords: "(temporomandibular joint) AND ((osteoarthritis) OR (dysfunction) OR (disorders) OR (pain)) AND ((treatment) OR (arthrocentesis) OR (arthroscopy) OR (injection)) AND ((hyaluronic acid) OR (corticosteroid) OR (platelet rich plasma))". After screening of 363 results, 16 studies were included in this review. Arthrocentesis alone effectively reduces pain and improves jaw function in patients diagnosed with TMJ OA. Additional injections of HA, either low-molecular-weight (LMW) HA or high-molecular-weight (HMW) HA, or CS at the end of the arthrocentesis do not improve the final clinical outcomes. CS present several negative effects on the articular cartilage. Results related to additional PRP injections are not consistent and are rather questionable. Further studies should be multicenter, based on a larger group of patients and should answer the question of whether other methods of TMJ OA treatment are more beneficial for the patients than simple arthrocentesis.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis; Platelet-Rich Plasma; Signal Transduction; Temporomandibular Joint Disorders
PubMed: 34299024
DOI: 10.3390/ijms22147405 -
Actas Dermo-sifiliograficas Jun 2020Pemphigus vulgaris (PV) is an uncommon, serious disease that is treated with systemic corticosteroids and corticosteroid-sparing agents.
BACKGROUND
Pemphigus vulgaris (PV) is an uncommon, serious disease that is treated with systemic corticosteroids and corticosteroid-sparing agents.
OBJECTIVES
To describe and analyze the demographic and clinical characteristics of patients with PV.
MATERIAL AND METHODS
Retrospective cohort study of adults diagnosed with PV over a period of 12years.
RESULTS
PV presented with mucosal lesions in 20 of the 32 patients studied (63%); the most common site was the oral mucosa followed by the vulva. Mucosal involvement was more common in women (P=.03). Lesions were found at more than 1 mucosal site in patients whose disease began in the mucosa, independently of age or sex (P=.003). Disease onset before the age of 40years was associated with generalized skin lesions (P=.003), a need for corticosteroid-sparing therapy (P=.05), and refractory PV (P=.02). Azathioprine was the most widely prescribed corticosteroid-sparing agent (in 22 patients). Eight patients (25%) were dependent on corticosteroids and disease recurred in 26 (81%). Complete remission, with or without treatment, was achieved in 15 patients (47%). Patients remained disease-free for a median of 14months, and 2 patients died (6%).
CONCLUSION
Onset before the age of 40 years could be a sign of poor prognosis in patients with PV, as it was significantly associated with a higher risk of generalized skin involvement, a need for corticosteroid-sparing therapy, and refractory disease.
Topics: Adrenal Cortex Hormones; Adult; Azathioprine; Female; Humans; Pemphigus; Retrospective Studies; Skin Diseases
PubMed: 32466985
DOI: 10.1016/j.ad.2019.10.004 -
European Annals of Allergy and Clinical... Sep 2017As anaphylaxis is a medical emergency, there are no randomized controlled clinical trials on its emergency management. Therefore, current guidelines are mostly based on...
As anaphylaxis is a medical emergency, there are no randomized controlled clinical trials on its emergency management. Therefore, current guidelines are mostly based on data from observational studies, animal and laboratory studies. Although epinephrine is the mainstay of recommended treatment, corticosteroids are also frequently used. This review evaluates the evidence on the use of corticosteroids in emergency management of anaphylaxis from published human and animal or laboratories studies. Thirty original research papers were found with 22 human studies and eight animal or laboratory studies. The average rate of corticosteroid use in emergency treatment was 67.99% (range 48% to 100%). Corticosteroids appear to reduce the length of hospital stay, but did not reduce revisits to the emergency department. There was no consensus on whether corticosteroids reduce biphasic anaphylactic reactions. None of the human studies had sufficient data to compare the response to treatment in different treatment groups (i.e. corticosteroids, epinephrine, antihistamines). Animal studies demonstrated that corticosteroids act through multiple mechanisms. These modulate gene expression, with effects becoming evident 4 to 24 hours after administration. A much quicker response has been detected within 5 to 30 minutes, through blockade of signal activation of glucocorticoid receptors independent of their genomic effects. Therefore, we conclude that there is no compelling evidence to support or oppose the use of corticosteroid in emergency treatment of anaphylaxis. However, based on the available data, it appears to be beneficial and there was no evidence of adverse outcomes related to the use of corticosteroids in emergency treatment of anaphylaxis.
Topics: Adrenal Cortex Hormones; Anaphylaxis; Animals; Emergency Service, Hospital; Evidence-Based Medicine; Humans; Length of Stay; Patient Safety; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 28884986
DOI: 10.23822/EurAnnACI.1764-1489.15 -
Respiratory Medicine Sep 2020A sarcoidosis patient may be refractory to corticosteroid therapy. This may be because corticosteroids are ineffective in relieving the sarcoidosis patient's... (Review)
Review
A sarcoidosis patient may be refractory to corticosteroid therapy. This may be because corticosteroids are ineffective in relieving the sarcoidosis patient's symptoms/dysfunction or because the clinician has determined that the risks of corticosteroids outweigh their benefits. Interestingly, when corticosteroids truly fail to improve a sarcoidosis patient's condition, it is very rarely because of failure of the drug as an anti-granulomatous agent; rather, it is usually because the patient's symptoms were unrelated to active sarcoid granulomas. In this manuscript, we review the causes of corticosteroid refractory sarcoidosis. The clinician should consider these causes when confronted with a sarcoidosis patient who is either not responding to corticosteroids, developing corticosteroid side-effects, or is at significant risk of developing such side-effects. We believe that determining the cause of corticosteroid refractory sarcoidosis may aid the clinicians in optimizing the care of sarcoidosis patients and clinical researchers in appropriately stratifying patients for clinical trials.
Topics: Adrenal Cortex Hormones; Humans; Patient Compliance; Sarcoidosis, Pulmonary; Treatment Failure
PubMed: 32658838
DOI: 10.1016/j.rmed.2020.106081 -
Nature Communications May 2021Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have...
Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.
Topics: Adrenal Cortex Hormones; Animals; Cells, Cultured; Delayed-Action Preparations; Dexamethasone; Dimerization; Disease Models, Animal; Drug Delivery Systems; Drug Implants; Drug Liberation; Polymers; Rabbits; Rats; Uveitis
PubMed: 34001908
DOI: 10.1038/s41467-021-23232-7 -
Actas Dermo-sifiliograficas Mar 2016Corticosteroids are widely used drugs in the clinical practice, especially by topic application in dermatology. These substances may act as allergens and produce... (Review)
Review
Corticosteroids are widely used drugs in the clinical practice, especially by topic application in dermatology. These substances may act as allergens and produce immediate and delayed hypersensitivity reactions. Allergic contact dermatitis is the most frequent presentation of corticosteroid allergy and it should be studied by patch testing in specific units. The corticosteroids included in the Spanish standard battery are good markers but not ideal. Therefore, if those makers are positive, it is useful to apply a specific battery of corticosteroids and the drugs provided by patients. Immediate reactions are relatively rare but potentially severe, and it is important to confirm the sensitization profile and to guide the use of alternative corticosteroids, because they are often necessary in several diseases. In this article we review the main concepts regarding these two types of hypersensitivity reactions in corticosteroid allergy, as well as their approach in the clinical practice.
Topics: Adrenal Cortex Hormones; Allergens; Dermatitis, Allergic Contact; Humans; Hypersensitivity, Delayed; Patch Tests
PubMed: 26621334
DOI: 10.1016/j.ad.2015.09.012 -
Journal of Otolaryngology - Head & Neck... Mar 2021In the specialty of Otolaryngology - Head and Neck Surgery, intranasal corticosteroids are the mainstay treatment for inflammatory processes within the nasal cavity. All...
BACKGROUND
In the specialty of Otolaryngology - Head and Neck Surgery, intranasal corticosteroids are the mainstay treatment for inflammatory processes within the nasal cavity. All too often, physician prescribing patterns are based on previous training, personal experience, and interactions with industry. The purpose of this commentary is to review the nuances of each intranasal corticosteroid.
COMMENTARY
There are nine intranasal corticosteroids approved for use in Canada. Each are discussed in detail, including their indication, bioavailability, effects on intranasal environment, and factors around patient adherence. Off-label use of budesonide irrigations is also discussed and cost information is presented in reference format for all available intranasal corticosteroids.
CONCLUSION
Although the efficacy of each intranasal corticosteroid has been shown to be similar, prescribing should be tailored based on bioavailability, intranasal environment, and factors that impact patient adherence such as dosing, cost and tolerability.
Topics: Administration, Intranasal; Adrenal Cortex Hormones; Canada; Humans; Nose Diseases; Off-Label Use; Practice Patterns, Physicians'; Therapeutic Irrigation
PubMed: 33731223
DOI: 10.1186/s40463-020-00480-z -
Clinics in Chest Medicine Mar 2019Corticosteroids are the most effective treatment for asthma; inhaled corticosteroids (ICSs) are the first-line treatment for children and adults with persistent... (Review)
Review
Corticosteroids are the most effective treatment for asthma; inhaled corticosteroids (ICSs) are the first-line treatment for children and adults with persistent symptoms. ICSs are associated with significant improvements in lung function. The anti-inflammatory effects of corticosteroids are mediated by both genomic and nongenomic factors. Variation in the response to corticosteroids has been observed. Patient characteristics, biomarkers, and genetic features may be used to predict response to ICSs. The existence of multiple mechanisms underlying glucocorticoid insensitivity raises the possibility that this might indeed reflect different diseases with a common phenotype.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Child; Humans; Treatment Outcome
PubMed: 30691710
DOI: 10.1016/j.ccm.2018.10.010