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The Cochrane Database of Systematic... Jan 2017BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment. SEARCH METHODS: We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews. SELECTION CRITERIA: We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods. MAIN RESULTS: We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use: from 2 per 1000 to between 3 and 7 per 1000), venous thromboembolism (after 1 year's use: from 2 per 1000 to between 4 and 11 per 1000), stroke (after 3 years' use: from 6 per 1000 to between 6 and 12 per 1000), breast cancer (after 5.6 years' use: from 19 per 1000 to between 20 and 30 per 1000), gallbladder disease (after 5.6 years' use: from 27 per 1000 to between 38 and 60 per 1000) and death from lung cancer (after 5.6 years' use plus 2.4 years' additional follow-up: from 5 per 1000 to between 6 and 13 per 1000).Oestrogen-only HT increased the risk of venous thromboembolism (after 1 to 2 years' use: from 2 per 1000 to 2 to 10 per 1000; after 7 years' use: from 16 per 1000 to 16 to 28 per 1000), stroke (after 7 years' use: from 24 per 1000 to between 25 and 40 per 1000) and gallbladder disease (after 7 years' use: from 27 per 1000 to between 38 and 60 per 1000) but reduced the risk of breast cancer (after 7 years' use: from 25 per 1000 to between 15 and 25 per 1000) and clinical fracture (after 7 years' use: from 141 per 1000 to between 92 and 113 per 1000) and did not increase the risk of coronary events at any follow-up time.Women over 65 years of age who were relatively healthy and taking continuous combined HT showed an increase in the incidence of dementia (after 4 years' use: from 9 per 1000 to 11 to 30 per 1000). Among women with cardiovascular disease, use of combined continuous HT significantly increased the risk of venous thromboembolism (at 1 year's use: from 3 per 1000 to between 3 and 29 per 1000). Women taking HT had a significantly decreased incidence of fracture with long-term use.Risk of fracture was the only outcome for which strong evidence showed clinical benefit derived from HT (after 5.6 years' use of combined HT: from 111 per 1000 to between 79 and 96 per 1000; after 7.1 years' use of oestrogen-only HT: from 141 per 1000 to between 92 and 113 per 1000). Researchers found no strong evidence that HT has a clinically meaningful impact on the incidence of colorectal cancer.One trial analysed subgroups of 2839 relatively healthy women 50 to 59 years of age who were taking combined continuous HT and 1637 who were taking oestrogen-only HT versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT: Their absolute risk remained low, at less than 1/500. However, other differences in risk cannot be excluded, as this study was not designed to have the power to detect differences between groups of women within 10 years of menopause.For most studies, risk of bias was low in most domains. The overall quality of evidence for the main comparisons was moderate. The main limitation in the quality of evidence was that only about 30% of women were 50 to 59 years old at baseline, which is the age at which women are most likely to consider HT for vasomotor symptoms. AUTHORS' CONCLUSIONS: Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT, provided they do not have specific contraindications. HT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer (such as breast cancer, in women with a uterus). The risk of endometrial cancer among women with a uterus taking oestrogen-only HT is well documented.HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia, nor for prevention of deterioration of cognitive function in postmenopausal women. Although HT is considered effective for the prevention of postmenopausal osteoporosis, it is generally recommended as an option only for women at significant risk for whom non-oestrogen therapies are unsuitable. Data are insufficient for assessment of the risk of long-term HT use in perimenopausal women and in postmenopausal women younger than 50 years of age.
Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Estrogen Replacement Therapy; Estrogens; Female; Hot Flashes; Humans; Middle Aged; Neoplasms; Perimenopause; Postmenopause; Progesterone; Randomized Controlled Trials as Topic; Venous Thromboembolism
PubMed: 28093732
DOI: 10.1002/14651858.CD004143.pub5 -
The Cochrane Database of Systematic... Mar 2013This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation.
OBJECTIVES
To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.
SEARCH METHODS
We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012.
SELECTION CRITERIA
Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology.
DATA COLLECTION AND ANALYSIS
Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables.
MAIN RESULTS
We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied.
AUTHORS' CONCLUSIONS
This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.
Topics: Acquired Immunodeficiency Syndrome; Anorexia; Appetite Stimulants; Cachexia; Humans; Megestrol Acetate; Neoplasms; Randomized Controlled Trials as Topic; Syndrome
PubMed: 23543530
DOI: 10.1002/14651858.CD004310.pub3 -
Molecular Psychiatry Feb 2020Leading biological hypotheses propose that biological changes may underlie major depressive disorder onset and relapse/recurrence. Here, we investigate if there is... (Meta-Analysis)
Meta-Analysis
Leading biological hypotheses propose that biological changes may underlie major depressive disorder onset and relapse/recurrence. Here, we investigate if there is prospective evidence for biomarkers derived from leading theories. We focus on neuroimaging, gastrointestinal factors, immunology, neurotrophic factors, neurotransmitters, hormones, and oxidative stress. Searches were performed in Pubmed, Embase and PsychInfo for articles published up to 06/2019. References and citations of included articles were screened to identify additional articles. Inclusion criteria were having an MDD diagnosis as outcome, a biomarker as predictor, and prospective design search terms were formulated accordingly. PRISMA guidelines were applied. Meta-analyses were performed using a random effect model when three or more comparable studies were identified, using a random effect model. Our search resulted in 67,464 articles, of which 75 prospective articles were identified on: Neuroimaging (N = 24), Gastrointestinal factors (N = 1), Immunology (N = 8), Neurotrophic (N = 2), Neurotransmitters (N = 1), Hormones (N = 39), Oxidative stress (N = 1). Meta-analyses on brain volumes and immunology markers were not significant. Only cortisol (N = 19, OR = 1.294, p = 0.024) showed a predictive effect on onset/relapse/recurrence of MDD, but not on time until MDD onset/relapse/recurrence. However, this effect disappeared when studies including participants with a baseline clinical diagnosis were removed from the analyses. Other studies were too heterogeneous to compare. Thus, there is a lack of evidence for leading biological theories for onset and maintenance of depression. Only cortisol was identified as potential predictor for MDD, but results are influenced by the disease state. High-quality (prospective) studies on MDD are needed to disentangle the etiology and maintenance of MDD.
Topics: Biomarkers; Depressive Disorder, Major; Humans; Hydrocortisone; Prospective Studies
PubMed: 31745238
DOI: 10.1038/s41380-019-0585-z -
The Cochrane Database of Systematic... Jan 2012Acute spinal cord injury is a devastating condition typically affecting young people, mostly males. Steroid treatment in the early hours after the injury is aimed at... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute spinal cord injury is a devastating condition typically affecting young people, mostly males. Steroid treatment in the early hours after the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life.
OBJECTIVES
To review randomized trials of steroids for human acute spinal cord injury.
SEARCH METHODS
We searched the Cochrane Injuries Group Specialised Register (searched 02 Aug 2011), The Cochrane Central Register of Controlled Trials 2011, issue 3 (The Cochrane Library), MEDLINE (Ovid) 1948 to July Week 3 2011, EMBASE (Ovid) 1974 to 2011 week 17, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to Aug 2011, ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) 1990 to Aug 2011 and PubMed [www.ncbi.nlm.nih.gov/sites/entrez/] (searched 04 Aug 2011) for records added to PubMed in the last 90 days). Files of the National Acute Spinal Cord Injury Study (NASCIS) were reviewed (NASCIS was founded in 1977 and has tracked trials in this area since that date). We also searched the reference lists of relevant studies and previously published reviews.
SELECTION CRITERIA
All randomized controlled trials of steroid treatment for acute spinal cord injury in any language.
DATA COLLECTION AND ANALYSIS
One review author extracted data from trial reports. Japanese and French studies were found through NASCIS and additional data (e.g. SDs) were obtained from the original study authors.
MAIN RESULTS
Eight trials are included in this review, seven used methylprednisolone. Methylprednisolone sodium succinate has been shown to improve neurologic outcome up to one year post-injury if administered within eight hours of injury and in a dose regimen of: bolus 30mg/kg over 15 minutes, with maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial results were replicated in a Japanese trial but not in the one from France. Data was obtained from the latter studies to permit appropriate meta-analysis of all three trials. This indicated significant recovery in motor function after methylprednisolone therapy, when administration commenced within eight hours of injury. A more recent trial indicates that, if methylprednisolone therapy is given for an additional 24 hours (a total of 48 hours), additional improvement in motor neurologic function and functional status are observed. This is particularly observed if treatment cannot be started until between three to eight hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries. A modified regimen was found to improve recovery after surgery for lumbar disc disease. The risk of bias was low in the largest methyprednisolne trials. Overall, there was no evidence of significantly increased complications or mortality from the 23 or 48 hour therapy.
AUTHORS' CONCLUSIONS
High-dose methylprednisolone steroid therapy is the only pharmacologic therapy shown to have efficacy in a phase three randomized trial when administered within eight hours of injury. One trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours, if start of treatment must be delayed to between three and eight hours after injury. There is an urgent need for more randomized trials of pharmacologic therapy for acute spinal cord injury.
Topics: Anti-Inflammatory Agents; Drug Administration Schedule; Glucocorticoids; Humans; Methylprednisolone; Neuroprotective Agents; Nimodipine; Randomized Controlled Trials as Topic; Spinal Cord Injuries
PubMed: 22258943
DOI: 10.1002/14651858.CD001046.pub2 -
Respiratory Research Nov 2022Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of corticosteroids remains controversial. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the safety and efficacy of corticosteroids.
METHODS
The RCTs investigating the safety and efficacy of corticosteroids in ARDS were searched from electronic databases (Embase, Medline, and the Cochrane Central Register of Controlled Trials). The primary outcome was 28-day mortality. Heterogeneity was assessed using the Chi square test and I with the inspection level of 0.1 and 50%, respectively.
RESULTS
Fourteen RCTs (n = 1607) were included for analysis. Corticosteroids were found to reduce the risk of death in patients with ARDS (relative risk (RR) = 0.78, 95% confidence interval (CI): 0.70-0.87; P < 0.01). Moreover, no significant adverse events were observed, compared to placebo or standard support therapy. Further subgroup analysis showed that variables, such as adults (RR = 0.78; 95% CI: 0.70-0.88; P < 0.01), non-COVID-19 (RR = 0.71; 95% CI: 0.62-0.83; P < 0.01), methylprednisolone (RR = 0.70; 95% CI: 0.56-0.88; P < 0.01), and hydrocortisone (RR = 0.79; 95% CI: 0.63-0.98; P = 0.03) were associated with 28-day mortality among patients who used corticosteroids. However, no association was found, regarding children (RR = 0.21; 95% CI: 0.01-4.10; P = 0.30).
CONCLUSION
The use of corticosteroids is an effective approach to reduce the risk of death in ARDS patients. However, this effect is associated with age, non-COVID-19 diseases, and methylprednisolone and hydrocortisone use. Therefore, evidence suggests patients with age ≥ 18 years and non-COVID-19 should be encouraged during the corticosteroid treatment. However, due to substantial differences in the use of corticosteroids among these studies, questions still remain regarding the dosage, optimal corticosteroid agent, and treatment duration in patients with ARDS.
Topics: Child; Adult; Humans; Adolescent; Hydrocortisone; Respiratory Distress Syndrome; Adrenal Cortex Hormones; Methylprednisolone; Randomized Controlled Trials as Topic
PubMed: 36333729
DOI: 10.1186/s12931-022-02186-4 -
BMJ (Clinical Research Ed.) Sep 2017To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat. Systematic review and meta-analysis of randomised control... (Meta-Analysis)
Meta-Analysis Review
To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat. Systematic review and meta-analysis of randomised control trials. Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews. Randomised controlled trials of the addition of corticosteroids to standard clinical care for patients aged 5 or older in emergency department and primary care settings with clinical signs of acute tonsillitis, pharyngitis, or the clinical syndrome of sore throat. Trials were included irrespective of language or publication status. Reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee ( Rapid Recommendation) provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. Random effects model was used for meta-analyses. Quality of evidence was assessed with the GRADE approach. 10 eligible trials enrolled 1426 individuals. Patients who received single low dose corticosteroids (the most common intervention was oral dexamethasone with a maximum dose of 10 mg) were twice as likely to experience pain relief after 24 hours (relative risk 2.2, 95% confidence interval 1.2 to 4.3; risk difference 12.4%; moderate quality evidence) and 1.5 times more likely to have no pain at 48 hours (1.5, 1.3 to 1.8; risk difference 18.3%; high quality). The mean time to onset of pain relief in patients treated with corticosteroids was 4.8 hours earlier (95% confidence interval -1.9 to -7.8; moderate quality) and the mean time to complete resolution of pain was 11.1 hours earlier (-0.4 to -21.8; low quality) than in those treated with placebo. The absolute pain reduction at 24 hours (visual analogue scale 0-10) was greater in patients treated with corticosteroids (mean difference 1.3, 95% confidence interval 0.7 to 1.9; moderate quality). Nine of the 10 trials sought information regarding adverse events. Six studies reported no adverse effects, and three studies reported few adverse events, which were mostly complications related to disease, with a similar incidence in both groups. Single low dose corticosteroids can provide pain relief in patients with sore throat, with no increase in serious adverse effects. Included trials did not assess the potential risks of larger cumulative doses in patients with recurrent episodes of acute sore throat. PROSPERO CRD42017067808.
Topics: Adrenal Cortex Hormones; Dexamethasone; Drug Administration Schedule; Humans; Pharyngitis; Tonsillitis
PubMed: 28931508
DOI: 10.1136/bmj.j3887 -
The Cochrane Database of Systematic... Jan 2023Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018.
OBJECTIVES
To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below.
SEARCH METHODS
We searched the Cochrane Library, which includes the Cochrane Central Register of Controlled Trials (CENTRAL; 2022 Issue 9), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 4 March 2022), Embase (Ovid) (1974 to 4 March 2022). We also searched the WHO ICTRP and ClinicalTrials.gov on 4 March 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in children (aged 18 years and below) with croup. We assessed the effect of glucocorticoids compared to the following: placebo, any other pharmacologic agents, any other glucocorticoids, any combination of other glucocorticoids, given by different modes of administration, or given in different doses. The included studies must have assessed at least one of our primary outcomes (defined as the change in croup score or return visits, (re)admissions to the hospital or both) or secondary outcomes (defined as the length of stay in hospital or emergency departments, patient improvement, use of additional treatments, or adverse events).
DATA COLLECTION AND ANALYSIS
Review authors independently extracted data, with another review author verified. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed studies for risk of bias using the Cochrane risk of bias tool. Two review authors assessed the certainty of the evidence for the primary outcomes using the GRADE approach.
MAIN RESULTS
This updated review includes 45 RCTs with a total of 5888 children, an increase of two RCTs with 1323 children since the last update. We also identified one ongoing study and one study awaiting classification. We assessed most studies (98%) as at high or unclear risk of bias. Any glucocorticoid compared to placebo Compared to placebo, glucocorticoids may result in greater reductions in croup score after two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs, 426 children; low-certainty evidence); six hours (SMD -0.76, 95% CI -1.12 to -0.40; 11 RCTs, 959 children; low-certainty evidence); and 12 hours (SMD -1.03, 95% CI -1.53 to -0.53; 8 RCTs, 571 children; low-certainty evidence). The evidence for change in croup score after 24 hours is very uncertain (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs, 351 children; very low-certainty evidence). One glucocorticoid compared to another glucocorticoid There was little to no difference between prednisolone and dexamethasone for reduction in croup score at two-hour post-baseline score (SMD 0.06, 95% CI -0.06 to 0.18; 1 RCT, 1231 children; high-certainty evidence). There was likely little to no difference between prednisolone and dexamethasone for reduction in croup score at six-hour post-baseline score (SMD 0.21, 95% CI -0.21 to 0.62; 1 RCT, 99 children; moderate-certainty evidence). However, dexamethasone probably reduced the return visits or (re)admissions for croup by almost half (risk ratio (RR) 0.55, 95% CI 0.28 to 1.11; 4 RCTs, 1537 children; moderate-certainty evidence), and showed a 28% reduction in the use of supplemental glucocorticoids as an additional treatment (RR 0.72, 95% CI 0.53 to 0.97; 2 RCTs, 926 children). Dexamethasone given in different doses Compared to 0.15 mg/kg, 0.60 mg/kg dexamethasone probably reduced the severity of croup as assessed by the croup scoring scale at 24-hour postbaseline score (SMD 0.63, 95% CI 0.16 to 1.10; 1 RCT, 72 children; moderate-certainty evidence); however, this was not the case at two hours (SMD -0.27, 95% CI -0.76 to 0.22; 2 RCTs, 861 children; high-certainty evidence). There was probably no reduction at six hours (SMD -0.45, 95% CI -1.26 to 0.35; 3 RCTs, 178 children; moderate-certainty evidence), and the evidence at 12 hours is very uncertain (SMD -0.60, 95% CI -4.39 to 3.19; 2 RCTs, 113 children; very low-certainty evidence). There was little to no difference between doses of dexamethasone in return visits or (re)admissions of children or both (RR 0.91, 95% CI 0.71 to 1.17; 3 RCTs, 949 children; high-certainty evidence) or length of stay in the hospital or emergency department (mean difference 0.12, 95% CI -0.32 to 0.56; 2 RCTs, 892 children). The need for additional treatments, such as epinephrine (RR 0.78, 95% CI 0.34 to 1.75; 2 RCTs, 885 children); intubation (risk difference 0.00, 95% CI -0.00 to 0.00; 2 RCTs, 861 children); or use of supplemental glucocorticoids (RR 0.77, 95% CI 0.51 to 1.15; 2 RCTs, 617 children), also did not differ between doses of dexamethasone. There were moderate to high levels of heterogeneity in the analyses for most comparisons. Adverse events were observed for some of the comparisons reported in the review.
AUTHORS' CONCLUSIONS
The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low-dose dexamethasone at 0.15 mg/kg to treat croup.
Topics: Child; Humans; Croup; Dexamethasone; Epinephrine; Glucocorticoids; Prednisolone; Respiratory Tract Infections; Randomized Controlled Trials as Topic; Adolescent
PubMed: 36626194
DOI: 10.1002/14651858.CD001955.pub5 -
The Cochrane Database of Systematic... Apr 2021Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime, and 15% to 20% of pregnancies ending in a miscarriage. Progesterone has an important role in maintaining a pregnancy, and supplementation with different progestogens in early pregnancy has been attempted to rescue a pregnancy in women with early pregnancy bleeding (threatened miscarriage), and to prevent miscarriages in asymptomatic women who have a history of three or more previous miscarriages (recurrent miscarriage).
OBJECTIVES
To estimate the relative effectiveness and safety profiles for the different progestogen treatments for threatened and recurrent miscarriage, and provide rankings of the available treatments according to their effectiveness, safety, and side-effect profile.
SEARCH METHODS
We searched the following databases up to 15 December 2020: Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies.
SELECTION CRITERIA
We included all randomised controlled trials assessing the effectiveness or safety of progestogen treatment for the prevention of miscarriage. Cluster-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded quasi- and non-randomised trials.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We performed pairwise meta-analyses and indirect comparisons, where possible, to determine the relative effects of all available treatments, but due to the limited number of included studies only direct or indirect comparisons were possible. We estimated the relative effects for the primary outcome of live birth and the secondary outcomes including miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy, congenital abnormalities, and adverse drug events. Relative effects for all outcomes are reported separately by the type of miscarriage (threatened and recurrent miscarriage). We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Our meta-analysis included seven randomised trials involving 5,682 women, and all provided data for meta-analysis. All trials were conducted in hospital settings. Across seven trials (14 treatment arms), the following treatments were used: three arms (21%) used vaginal micronized progesterone; three arms (21%) used dydrogesterone; one arm (7%) used oral micronized progesterone; one arm (7%) used 17-α-hydroxyprogesterone, and six arms (43%) used placebo. Women with threatened miscarriage Based on the relative effects from the pairwise meta-analysis, vaginal micronized progesterone (two trials, 4090 women, risk ratio (RR) 1.03, 95% confidence interval (CI) 1.00 to 1.07, high-certainty evidence), and dydrogesterone (one trial, 406 women, RR 0.98, 95% CI 0.89 to 1.07, moderate-certainty evidence) probably make little or no difference to the live birth rate when compared with placebo for women with threatened miscarriage. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with threatened miscarriage. The pre-specified subgroup analysis by number of previous miscarriages is only possible for vaginal micronized progesterone in women with threatened miscarriage. In women with no previous miscarriages and early pregnancy bleeding, there is probably little or no improvement in the live birth rate (RR 0.99, 95% CI 0.95 to 1.04, high-certainty evidence) when treated with vaginal micronized progesterone compared to placebo. However, for women with one or more previous miscarriages and early pregnancy bleeding, vaginal micronized progesterone increases the live birth rate compared to placebo (RR 1.08, 95% CI 1.02 to 1.15, high-certainty evidence). Women with recurrent miscarriage Based on the results from one trial (826 women) vaginal micronized progesterone (RR 1.04, 95% CI 0.95 to 1.15, high-certainty evidence) probably makes little or no difference to the live birth rate when compared with placebo for women with recurrent miscarriage. The evidence for dydrogesterone compared with placebo for women with recurrent miscarriage is of very low-certainty evidence, therefore the effects remain unclear. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with recurrent miscarriage. Additional outcomes All progestogen treatments have a wide range of effects on the other pre-specified outcomes (miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy) in comparison to placebo for both threatened and recurrent miscarriage. Moderate- and low-certainty evidence with a wide range of effects suggests that there is probably no difference in congenital abnormalities and adverse drug events with vaginal micronized progesterone for threatened (congenital abnormalities RR 1.00, 95% CI 0.68 to 1.46, moderate-certainty evidence; adverse drug events RR 1.07 95% CI 0.81 to 1.39, moderate-certainty evidence) or recurrent miscarriage (congenital abnormalities 0.75, 95% CI 0.31 to 1.85, low-certainty evidence; adverse drug events RR 1.46, 95% CI 0.93 to 2.29, moderate-certainty evidence) compared with placebo. There are limited data and very low-certainty evidence on congenital abnormalities and adverse drug events for the other progestogens.
AUTHORS' CONCLUSIONS
The overall available evidence suggests that progestogens probably make little or no difference to live birth rate for women with threatened or recurrent miscarriage. However, vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events. There is still uncertainty over the effectiveness and safety of alternative progestogen treatments for threatened and recurrent miscarriage.
Topics: Abortion, Habitual; Abortion, Spontaneous; Bias; Birth Rate; Dydrogesterone; Female; Humans; Hydroxyprogesterones; Live Birth; Network Meta-Analysis; Placebos; Pregnancy; Progesterone; Progestins; Randomized Controlled Trials as Topic; Stillbirth
PubMed: 33872382
DOI: 10.1002/14651858.CD013792.pub2 -
European Journal of Endocrinology Oct 2023To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; >... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test).
DESIGN
Systematic review and meta-analysis.
METHODS
Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs).
RESULTS
In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy.
CONCLUSIONS
The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities.
Topics: Humans; Adrenal Gland Neoplasms; Hydrocortisone; Cross-Sectional Studies; Hypertension; Dyslipidemias
PubMed: 37801655
DOI: 10.1093/ejendo/lvad134 -
BMC Oral Health May 2022To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP).
OBJECTIVE
To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP).
MATERIALS AND METHODS
A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered.
RESULTS
Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone.
CONCLUSION
Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.
Topics: Administration, Topical; Calcineurin Inhibitors; Clobetasol; Cyclosporins; Dexamethasone; Fluocinonide; Health Care Costs; Humans; Lichen Planus, Oral; Steroids; Tacrolimus; Treatment Outcome; Triamcinolone
PubMed: 35524296
DOI: 10.1186/s12903-022-02168-4