SHORT-COURSE ORAL CORTICOSTEROID TOXICITY IN CHILDREN

2015 ◽  
Vol 101 (1) ◽  
pp. e1.30-e1
Author(s):  
Fahad Ajebab ◽  
Imti Choonara ◽  
Sharon Conroy
Keyword(s):  
Blood Pressure ◽  
Relative Risk ◽  
Adverse Events ◽  
Hpa Axis ◽  
Oral Prednisolone ◽  
Incidence Rates ◽  
Cochrane Library ◽  
Behavioural Changes ◽  
Short Course ◽  
Oral Corticosteroids

BackgroundMultiple studies have evaluated and reported adverse drug reactions (ADRs) of corticosteroids. Short course oral corticosteroids are commonly used in children in the management of conditions such as asthma exacerbations. This systematic review aimed to identify the most common and serious ADRs associated with short courses of oral corticosteroids and to determine their relative risk levels in children.MethodsA literature search of the databases: Embase, Medline, International Pharmaceutical Abstracts, CINAHL, the Cochrane Library and PubMed was performed to identify all studies where corticosteroids had been administered to paediatric patients ranging from 28 days to 18 years of age for up to and including 14 days of treatment. Each database was searched from their earliest dates to December 2013. All types of studies that provided clear information on adverse events were included with no language restrictions. Quality assessments were performed on all studies by two independent reviewers.ResultsThirty eight studies met the inclusion criteria. These studies represented 3202 children and contained reports of 847 adverse events. The three most frequent ADRs were vomiting, increased blood pressure and behavioural changes. The incidence rates of these three ADRs were 6.3%, 8.5% and 4.8% of patients respectively. The risk of vomiting was greater with oral prednisolone than oral dexamethasone with a relative risk of 3.62 (95% CI 1.89, 6.95; P=0.0001). Prednisolone sodium phosphate was reported to cause vomiting less frequently than other prednisolone dosage forms (P=0.047). HPA axis suppression was detected in 43 of 53 patients who were tested. The relative risk of oral prednisolone to cause HPA axis suppression compared with inhaled steroids was 9.95 (95% CI 1.73, 53.03; P=0.010). Infection was one of the most serious ADRs, one child died after contracting a varicella zoster infection.ConclusionsVomiting, increased blood pressure and behavioural changes were the most frequent ADRs seen when short-course oral corticosteroids were given to children. In addition, infection was the most serious ADR. The majority of children who receive short course oral corticosteroids will experience HPA axis suppression.

scholarly journals Systematic review of the toxicity of short-course oral corticosteroids in children

2016 ◽  
Vol 101 (4) ◽  
pp. 365-370 ◽  
Author(s):  
Fahad Aljebab ◽  
Imti Choonara ◽  
Sharon Conroy
Keyword(s):  
Sleep Disturbance ◽  
Incidence Rates ◽  
Cochrane Library ◽  
Varicella Zoster ◽  
Risk Levels ◽  
Behavioural Changes ◽  
Susceptibility To Infection ◽  
Short Course ◽  
Oral Corticosteroids ◽  
Randomised Controlled

BackgroundShort-course oral corticosteroids are commonly used in children but are known to be associated with adverse drug reactions (ADRs). This review aimed to identify the most common and serious ADRs and to determine their relative risk levels.MethodsA literature search of EMBASE, MEDLINE, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions to identify studies in which oral corticosteroids were administered to patients aged 28 days to 18 years of age for up to and including 14 days of treatment. Each database was searched from their earliest dates to December 2013. All studies providing clear information on ADRs were included.ResultsThirty-eight studies including 22 randomised controlled trials (RCTs) met the inclusion criteria. The studies involved a total of 3200 children in whom 850 ADRs were reported. The three most frequent ADRs were vomiting, behavioural changes and sleep disturbance, with respective incidence rates of 5.4%, 4.7% and 4.3% of patients assessed for these ADRs. Infection was one of the most serious ADRs; one child died after contracting varicella zoster. When measured, 144 of 369 patients showed increased blood pressure; 21 of 75 patients showed weight gain; and biochemical hypothalamic–pituitary–adrenal axis suppression was detected in 43 of 53 patients.ConclusionsVomiting, behavioural changes and sleep disturbance were the most frequent ADRs seen when short-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.Trial registration numberCRD42014008774. By PROSPERO International prospective register of systematic reviews.

LONG-COURSE ORAL CORTICOSTEROID TOXICITY IN CHILDREN

2016 ◽  
Vol 101 (9) ◽  
pp. e2.53-e2 ◽  
Author(s):  
Fahad Aljebab ◽  
Imti Choonara ◽  
Sharon Conroy
Keyword(s):  
Weight Gain ◽  
Growth Retardation ◽  
Oral Prednisolone ◽  
Incidence Rates ◽  
Cochrane Library ◽  
Varicella Zoster ◽  
Susceptibility To Infection ◽  
Oral Corticosteroids ◽  
Long Course ◽  
Increased Susceptibility

BackgroundLong courses of oral corticosteroids are commonly used in children in the management of conditions such as nephrotic syndrome, leukaemia, asthma and others. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels.MethodsA literature search of several databases; Embase, Medline, International Pharmaceutical Abstracts, CINAHL, the Cochrane Library and PubMed was performed to identify all studies where corticosteroids had been administered to paediatric patients ranging from 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to March 2014. All types of studies that provided clear information on ADRs were included.Results91 relevant studies were found from 27 countries. These studies represented a total of 6653 children and contained reports of 4124 ADRs, the majority in patients with leukaemia, haemangioma and asthma. Oral prednisolone was the most commonly prescribed corticosteroid (74% of patients). The three most frequent ADRs were weight gain, Cushingoid features and growth retardation. The incidence rates of patients with these three ADRs were 22.4%, 20.6% and 18.9%, respectively. Increased susceptibility to infection was the most serious ADR. 24 children died from infections, ten from varicella zoster and the others from different microorganisms.ConclusionsWeight gain, Cushingoid features and growth retardation were the most frequent ADRs seen when long-course oral corticosteroids were given to children. In addition, increased susceptibility to infection was the most common cause of mortality.

Cognitive function and risk for depression in old age: a meta-analysis of published literature

2010 ◽  
Vol 23 (4) ◽  
pp. 516-525 ◽  
Author(s):  
Chang-Quan Huang ◽  
Zheng-Rong Wang ◽  
Yong-Hong Li ◽  
Yi-Zhou Xie ◽  
Qing-Xiu Liu
Keyword(s):  
Cognitive Impairment ◽  
Relative Risk ◽  
Cognitive Function ◽  
Longitudinal Studies ◽  
Old Age ◽  
Meta Analysis ◽  
Incidence Rates ◽  
Cochrane Library ◽  
Cross Sectional ◽  
Risk For Depression

ABSTRACTBackground: We assessed the relationship between cognitive impairment (including mild cognitive impairment with no signs of dementia, and dementia) and risk for depression in old age (60 years and older).Methods: MEDLINE, EMBASE and the Cochrane Library database were used to identify potential studies. All of the clinical studies that produced data on the association between cognitive function and risk of depression among individuals aged 55 years or older were identified and included in this review. The studies were classified into cross-sectional and longitudinal subsets. The quantitative meta-analysis of cross-sectional and longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively.Results: Since all but two studies found in the search were for individuals aged 60 years or over, we assessed and reported on results for this larger group only. In this review we included 13 cross-sectional and four prospective longitudinal studies. The quantitative meta-analysis showed that, in old age, individuals with non-dementia cognitive impairment had neither significant higher prevalence nor incidence rates of depression than those without (odds risk (OR): 1.48, 95% confidence intervals (95% CI): 0.87–2.52; relative risk (RR): 1.12, 95% CI: 0.62–2.01). In old age, individuals with dementia had both significant higher prevalence and incidence rates of depression than those without (OR: 1.82, 95% CI: 1.15–2.89; RR: 3.92, 95% CI: 1.93–7.99).Conclusions: Despite the methodological limitations of this meta-analysis, we found that in old age, there was no association between depression and cognitive impairment with no dementia; however, there was a definite association between depression and dementia and thus dementia might be a risk for depression.

A Systematic Review and Meta-Analysis of Thalidomide in Patients with Previously Untreated Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3570-3570 ◽  
Author(s):  
Lisa Hicks ◽  
Adam Haynes ◽  
Donna E. Reece ◽  
Irwin Walker ◽  
Jordan A. Herst ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Relative Risk ◽  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Response Rate ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Number Needed To Treat ◽  
Vte Prophylaxis ◽  
American Society

Abstract Background: Multiple myeloma disproportionately affects the elderly and is currently an incurable malignancy. New therapies for myeloma, particularly oral therapies, are urgently needed. Objectives: To determine if thalidomide with or without other agents, improves response rate (≥ 50% reduction in monoclonal protein), survival, and/or progression in patients with previously untreated myeloma. To determine the frequency and significance of major adverse events associated with thalidomide in this setting. Methods: A literature search of Medline (1966–June 2006), Embase (1980–June 2006), the Cochrane Library, abstracts from the annual meetings of the American Society of Hematology (1999–2005) and the American Society of Oncology (1999–2006) was completed with a pre-specified search strategy. No language restrictions were applied. Randomized controlled trials of induction thalidomide (any dose, any duration) for adults with previously untreated multiple myeloma were included. Trials of exclusively maintenance therapy were excluded. Two reviewers independently extracted data. The methodological quality of selected trials was assessed and summarized. Weighted data was expressed as relative risk, risk difference, number needed to treat (NNT), and number needed to harm (NNH). A random-effects model was used. Results: Six eligible studies involving almost two thousand patients (N=1875) were identified and meta-analyzed. Two studies were published and four were reported in abstract form only. Five studies reported overall response rate (ORR); the four largest trials reported statistically significant improvements in ORR with the addition of thalidomide to standard therapy. The weighted relative risk of responding to a thalidomide-containing regimen versus control was 1.50 (95% CI 1.21 to 1.86). The NNT to achieve one additional response with thalidomide was 4 (95% CI 2.9 to 8.3). Two trials reported improvements in EFS/PFS. One trial reported an improvement in OS. The risk of VTE, peripheral neuropathy, and constipation was consistently elevated with thalidomide such that for every 50 patients treated with a thalidomide-containing-regimen, one could expect 12 to 13 additional patients to respond, 4 additional patients to develop VTE (NNH 12.5; 95% CI 8.3 to 20), 2 additional patients to develop peripheral neuropathy (NNH 25; 95% CI 16.7 to 50), and 4 additional patients to develop constipation (NNH14; 95% CI 10 to 25). In our analyses, prophylactic anticoagulation appeared to decrease, but not abolish, the risk of VTE with thalidomide. Conclusions: Thalidomide improves response rate and possibly progression free and overall survival in patients with previously untreated myeloma. It also increases the incidence of VTE, neuropathy, constipation and other adverse events. Further studies are required to confirm the survival advantage seen in one study, and to determine the optimum strategy for VTE prophylaxis.

scholarly journals Do toe blood pressures predict healing after minor lower limb amputation in people with diabetes? A systematic review and meta-analysis

2020 ◽  
Vol 17 (3) ◽  
pp. 147916412092886
Author(s):  
Clare Linton ◽  
Angela Searle ◽  
Fiona Hawke ◽  
Peta Ellen Tehan ◽  
Mathew Sebastian ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Relative Risk ◽  
Systolic Blood Pressure ◽  
Meta Analysis ◽  
Limb Amputation ◽  
Cochrane Library ◽  
Amputation Level ◽  
Pressure Index ◽  
Blood Pressures ◽  
The Cochrane Library

Purpose of study: To investigate toe systolic blood pressure and/or toe-brachial pressure index in predicting healing post minor diabetic foot amputations. Key methods: A systematic search of EMBASE and PubMed (including Medline and The Cochrane Library) was conducted from database inception to 9 March 2020. Two authors independently reviewed and selected relevant studies. Quality was assessed with a modified Critical Appraisal Skill Programme checklist. Main results: Ten studies met the inclusion criteria. Nine studies investigating toe systolic blood pressure reported healing occurred at mean toe systolic blood pressure values ⩾30 mmHg, ranging between 30 and 83.6 mmHg. The meta-analysis (four studies) found toe systolic blood pressure <30 mmHg had 2.09 times the relative risk of non-healing post amputation, compared to toe systolic blood pressure ⩾30 mmHg (relative risk = 2.09, 95% confidence interval: 1.37–3.20, p = 0.001). Two studies investigating toe-brachial pressure index report successful healing where toe-brachial pressure index >0.2, with one study reporting a higher value of 0.8. Main conclusions: Successful post-amputation healing outcomes were reported at mean toe systolic blood pressure ⩾30 mmHg, and the results varied considerably between the studies. Further research should identify whether variables, including amputation level, method of wound closure and length of post-operative follow-up periods, affect the values of toe systolic blood pressure and toe-brachial pressure index observed in this review.

scholarly journals Observational study on the palatability and tolerability of oral prednisolone and oral dexamethasone in children in Saudi Arabia and the UK

2017 ◽  
Vol 103 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Fahad Aljebab ◽  
Mofadhi Alanazi ◽  
Imti Choonara ◽  
Sharon Conroy
Keyword(s):  
Sodium Phosphate ◽  
Oral Prednisolone ◽  
Oral Solution ◽  
Phosphate Solution ◽  
Dexamethasone Sodium Phosphate ◽  
Short Course ◽  
Daily Dose ◽  
Oral Corticosteroids ◽  
Sodium Phosphate Solution ◽  
The Uk

BackgroundShort-course oral corticosteroids are routinely used to treat acute asthma and croup. We evaluated their tolerability and palatability in Saudi Arabian (SA) and UK children.MethodsProspective observational/interview study (3 months in each country). Palatability was evaluated using a 5-point facial Hedonicscale and tolerability by direct questioning of patient/parents.ResultsIn SA, of 122 patients (2–10 years) recruited, 52 received prednisolone base tablets, 37 prednisolone sodium phosphate syrup and 33 received dexamethasone elixir. In the UK, of 133 patients (2–16 years), 38 received prednisolone base tablets (mainly crushed and dispersed), 42 prednisolone sodium phosphate soluble tablets and 53 received dexamethasone sodium phosphate oral solution.In both countries, dexamethasone had the highest palatability scores (SA mean: 1.97; UK mean: 3) and prednisolone base tablets had the lowest (SA mean: 1.12; UK mean: 1.39). Palatability scores improved for all formulations of prednisolone with each subsequent daily dose.In SA, prednisolone base tablets were associated with more nausea (24vs7 patients) and vomiting (5vs0 patients) than sodium phosphate syrup (p=0.008 and p=0.073, respectively). In the UK, vomiting occurred more frequently with prednisolone base (8 patients) than sodium phosphate soluble tablets (2 patients) (p=0.041).In both centres, dexamethasone was associated with less side effects. Vomiting (1vs0 patients), nausea (7vs3 patients) and abdominal pain (10vs8 patients) occurred more with dexamethasone sodium phosphate solution than dexamethasone elixir.ConclusionsDexamethasone sodium phosphate solution was the most palatable preparation. Prednisolone base tablets were rated least palatable and were least well tolerated. Palatability scores improved with each dose taken.

scholarly journals Patients With IBD Receiving Methotrexate Are at Higher Risk of Liver Injury Compared With Patients With Non-IBD Diseases: A Meta-Analysis and Systematic Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Wang ◽  
Yimin Li ◽  
Yun Liu ◽  
Yifan Zhang ◽  
Ziliang Ke ◽  
...  
Keyword(s):  
Relative Risk ◽  
Liver Injury ◽  
Adverse Events ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Future Research ◽  
The Difference ◽  
Trim And Fill ◽  
The Cochrane Library ◽  
Rr Relative Risk

Background: Methotrexate is well-known in treating inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis (Ps), and psoriatic arthritis (PsA). Several reports have indicated a higher incidence of methotrexate (MTX)-related liver adverse events in patients with IBD. We aim to investigate the risk of liver injury in patients with IBD and those with non-IBD diseases treated with MTX.Methods: We searched PubMed, Embase, and the Cochrane Library for articles that reported liver adverse events in patients with IBD, RA, and Ps/PsA, receiving MTX therapy. Additional articles were obtained by screening the references of recent meta-analysis and reviews. Raw data from included articles were pooled to calculate the cumulative incidence of total liver injury (TLI), MTX discontinuation (MTX-D), and liver fibrosis (LF). RR (relative risk) was calculated to compare the difference between patients with IBD and those with non-IBD diseases.Results: A total of 326 articles with 128,876 patients were included. The patients with IBD had higher incidence of TLI [11.2 vs. 9.2%; relative risk (RR) = 1.22; P = 0.224] and MTX-D (2.6 vs. 1.8%; RR, 1.48; P = 0.089) than patients with non-IBD diseases. Due to the publication bias, trim-and-fill was performed. Afterwards, the patients with IBD showed significantly higher risk of TLI (11.2 vs. 3%; RR = 3.76; p &lt; 0.001), MTX-D (3.3 vs. 0.7%; RR = 5; p &lt; 0.001) and LF (3.1 vs. 0.1%; RR = 38.62; P = 0.001) compared with patients with non-IBD diseases.Conclusion: IBD is associated with a higher risk of MTX-related liver injury. The mechanism of MTX-induced hepatotoxicity might be different in IBD and non-IBD diseases, and needs to be verified in future research.

Efficacy and Safety of Non-Steroidal Anti-Androgens in Patients with Metastatic Prostate Cancer: Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 15 (1) ◽  
pp. 34-47 ◽  
Author(s):  
Muhammed Rashid ◽  
Madhan Ramesh ◽  
K. Shamshavali ◽  
Amit Dang ◽  
Himanshu Patel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Quality Assessment ◽  
Cochrane Library ◽  
Control Group ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Significant Difference

Background: Prostate cancer (PCa) is the sixth primary cause of cancer death. However, conflicts are present about the efficacy and safety of Non-steroidal anti-androgens (NSAA) for its treatment. The aim of this study was to assess the efficacy and safety of NSAAs versus any comparator for the treatment of advanced or metastatic PCa (mPCa). Methodology: MEDLINE and the Cochrane Library were searched. References of included studies and clinicaltrials.gov were also searched for relevant studies. Only English language studies after 1990 were considered for review. Randomized controlled trials (RCTs) examining the efficacy and safety of NSAAs as compared with any other comparator including surgery or chemotherapy in mPCa patients were included. The outcomes include efficacy, safety and the tolerability of the treatment. The Cochrane Risk of Bias Assessment Tool was used for quality assessment. Two authors were independently involved in the selection, extraction and quality assessment of included studies and disagreements were resolved by discussion or by consulting a third reviewer. Results: Fifty-eight out of 1307 non-duplicate RCTs with 29154 patients were considered for the review. NSAA showed significantly better progression-free survival [PFS] (Hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.78; P=0.0001), time to distant metastasis or death [TTD] (HR, 0.80; 95% CI 0.73-0.91; p<0.0001), objective response (Odds ratio [OR], 1.64; 95% CI 1.06-2.54; P=0.03) and clinical benefits (OR, 1.33; 95% CI 1.08-1.63; P=0.006) as compared to the control group. There was no significant difference observed between the groups in terms of overall survival (HR, 0.95; 95%CI, 0.87-1.03; P=0.18) and time to progression (HR, 0.93; 95% CI 0.77-1.11; P=0.43). Treatment-related adverse events were more with the NSAA group, but the discontinuation due to lack of efficacy reason was 43% significantly lesser than the control group in patients with mPCa. Rest of the outcomes were appeared to be non-significant. Conclusion: Treatment with NSAA was appeared to be better efficacious with respect to PFS, TTD, and response rate with considerable adverse events when compared to the control group in patients with metastatic PCa.

scholarly journals Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK Biobank

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jessica Gong ◽  
Katie Harris ◽  
Sanne A. E. Peters ◽  
Mark Woodward
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Sex Differences ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Sex Difference ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
The Uk

Abstract Background Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.

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