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Burns : Journal of the International... Aug 2024To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength.
METHODS
A systematic literature search was conducted in PubMed, Embase, and Web of Science up to March 2021. Eligible interventional studies reported metrics on the height, weight, body composition, or muscle strength of pediatric burn patients in a peer-reviewed journal. Meta-analyses were performed if ≥ 2 trials of clinical homogeneity reported on an outcome measure at the same time point post-burn.
RESULTS
Twenty-six interventional studies were identified, including twenty-two randomised controlled trials and four non-randomised trials. Most studies were conducted by a single institution. On average, the burn covered 45.3% ( ± 9.9) of the total body surface area. Three categories of interventions could be distinguished: rehabilitative exercise programs, pharmacologic agents, and nutrition support.
CONCLUSIONS
Each of the interventions had a positive effect on height, weight, body composition, or muscle strength. The decision to initiate an intervention should be made on a case-by-case basis following careful consideration of the benefits and risks. In future research, it is important to evaluate the heterogeneity of intervention effects and whether participation in an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers.
Topics: Humans; Burns; Body Composition; Child; Muscle Strength; Body Weight; Body Height; Exercise Therapy; Nutritional Support; Treatment Outcome
PubMed: 38580580
DOI: 10.1016/j.burns.2024.03.012 -
Supportive Care in Cancer : Official... May 2021Antiresorptive drugs (ARD) are associated with a known serious adverse event, known as medication-related osteonecrosis of the jaws (MRONJ). Transition from one ARD to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antiresorptive drugs (ARD) are associated with a known serious adverse event, known as medication-related osteonecrosis of the jaws (MRONJ). Transition from one ARD to another has become common clinical practice with the advent of more potent or safer agents; however, the influence of sequential antiresorptive therapy as a risk factor for MRONJ has not been established.
OBJECTIVES
To investigate the prevalence of MRONJ in oncology or osteoporosis patients treated with two or more sequential ARDs as opposed to a single antiresorptive drug.
MATERIAL AND METHODS
Systematic electronic literature searches were conducted using Ovid MEDLINE, Ovid EMBASE, and Cochrane Central Register of Controlled Trials. Two review authors retrieved studies using pre-determined eligibility criteria and conducted quality assessment and data extraction. Fixed or random-effects meta-analysis models were used to summarize relative estimates for prevalence of MRONJ.
RESULTS
A total of 483 titles and abstracts were screened, and 18 full texts were retrieved for review. Twelve studies were included in the final qualitative and quantitative synthesis. Random effects meta-analysis models revealed a weighted pooled MRONJ prevalence of 19% (95% CI 10-27%) for sequential pamidronate-zoledronate therapy, 10% (95% CI 3-22%) for sequential ibandronate-zoledronate therapy. Pooled weighted prevalence of MRONJ was 13% (95% CI 3-22%) for sequential bisphosphonate-denosumab therapy while bisphosphonates only was 5% (95% CI 0-9%) and denosumab only was 4% (95% CI 3-5%).
CONCLUSIONS
The present systematic review suggests an increased prevalence of MRONJ associated with sequential ARD therapy for pamidronate-zoledronate and bisphosphonate-denosumab administration when compared to single ARD therapy.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Humans; Prevalence
PubMed: 33190182
DOI: 10.1007/s00520-020-05882-3 -
The Cochrane Database of Systematic... Dec 2020Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men with prostate cancer and bone metastases to prevent skeletal-related events (SREs). SREs such as pathologic fractures, spinal cord compression, surgery and radiotherapy to the bone, and hypercalcemia lead to morbidity, a poor performance status, and impaired quality of life. Efficacy and acceptability of the bone-targeted therapy is therefore of high relevance. Until now recommendations in guidelines on which bone-modifying agents should be used are rare and inconsistent.
OBJECTIVES
To assess the effects of bisphosphonates and RANKL-inhibitors as supportive treatment for prostate cancer patients with bone metastases and to generate a clinically meaningful treatment ranking according to their safety and efficacy using network meta-analysis.
SEARCH METHODS
We identified studies by electronically searching the bibliographic databases Cochrane Controlled Register of Trials (CENTRAL), MEDLINE, and Embase until 23 March 2020. We searched the Cochrane Library and various trial registries and screened abstracts of conference proceedings and reference lists of identified trials.
SELECTION CRITERIA
We included randomized controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for men with prostate cancer and bone metastases. We included men with castration-restrictive and castration-sensitive prostate cancer and conducted subgroup analyses according to this criteria.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the quality of trials. We defined proportion of participants with pain response and the adverse events renal impairment and osteonecrosis of the jaw (ONJ) as the primary outcomes. Secondary outcomes were SREs in total and each separately (see above), mortality, quality of life, and further adverse events such as grade 3 to 4 adverse events, hypocalcemia, fatigue, diarrhea, and nausea. We conducted network meta-analysis and generated treatment rankings for all outcomes, except quality of life due to insufficient reporting on this outcome. We compiled ranking plots to compare single outcomes of efficacy against outcomes of acceptability of the bone-modifying agents. We assessed the certainty of the evidence for the main outcomes using the GRADE approach.
MAIN RESULTS
Twenty-five trials fulfilled our inclusion criteria. Twenty-one trials could be considered in the quantitative analysis, of which six bisphosphonates (zoledronic acid, risedronate, pamidronate, alendronate, etidronate, or clodronate) were compared with each other, the RANKL-inhibitor denosumab, or no treatment/placebo. By conducting network meta-analysis we were able to compare all of these reported agents directly and/or indirectly within the network for each outcome. In the abstract only the comparisons of zoledronic acid and denosumab against the main comparator (no treatment/placebo) are described for outcomes that were predefined as most relevant and that also appear in the 'Summary of findings' table. Other results, as well as results of subgroup analyses regarding castration status of participants, are displayed in the Results section of the full text. Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants). For this outcome none of the trials reported results for the comparison with denosumab. The adverse event renal impairment probably occurs more often when treated with zoledronic acid compared to treatment/placebo (RR 1.63, 95% CI 1.08 to 2.45; per 1000 participants 78 more (10 more to 180 more); moderate-certainty evidence; network based on 6 trials including 1769 participants). Results for denosumab could not be included for this outcome, since zero events cannot be considered in the network meta-analysis, therefore it does not appear in the ranking. Treatment with denosumab results in increased occurrence of the adverse event ONJ (RR 3.45, 95% CI 1.06 to 11.24; per 1000 participants 30 more (1 more to 125 more); high-certainty evidence; 4 trials, 3006 participants) compared to no treatment/placebo. When comparing zoledronic acid to no treatment/placebo, the confidence intervals include the possibility of benefit or harm, therefore treatment with zoledronic acid probably neither reduces nor increases ONJ (RR 1.88, 95% CI 0.73 to 4.87; per 1000 participants 11 more (3 less to 47 more); moderate-certainty evidence; network based on 4 trials including 3006 participants). Compared to no treatment/placebo, treatment with zoledronic acid (RR 0.84, 95% CI 0.72 to 0.97) and denosumab (RR 0.72, 95% CI 0.54 to 0.96) may result in a reduction of the total number of SREs (per 1000 participants 75 fewer (131 fewer to 14 fewer) and 131 fewer (215 fewer to 19 fewer); both low-certainty evidence; 12 trials, 5240 participants). Treatment with zoledronic acid and denosumab likely neither reduces nor increases mortality when compared to no treatment/placebo (zoledronic acid RR 0.90, 95% CI 0.80 to 1.01; per 1000 participants 48 fewer (97 fewer to 5 more); denosumab RR 0.93, 95% CI 0.77 to 1.11; per 1000 participants 34 fewer (111 fewer to 54 more); both moderate-certainty evidence; 13 trials, 5494 participants). Due to insufficient reporting, no network meta-analysis was possible for the outcome quality of life. One study with 1904 participants comparing zoledronic acid and denosumab showed that more zoledronic acid-treated participants than denosumab-treated participants experienced a greater than or equal to five-point decrease in Functional Assessment of Cancer Therapy-General total scores over a range of 18 months (average relative difference = 6.8%, range -9.4% to 14.6%) or worsening of cancer-related quality of life.
AUTHORS' CONCLUSIONS
When considering bone-modifying agents as supportive treatment, one has to balance between efficacy and acceptability. Results suggest that Zoledronic acid likely increases both the proportion of participants with pain response, and the proportion of participants experiencing adverse events However, more trials with head-to-head comparisons including all potential agents are needed to draw the whole picture and proof the results of this analysis.
Topics: Adult; Alendronate; Antineoplastic Agents, Hormonal; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Clodronic Acid; Denosumab; Diphosphonates; Etidronic Acid; Humans; Male; Network Meta-Analysis; Pamidronate; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Quality of Life; RANK Ligand; Randomized Controlled Trials as Topic; Risedronic Acid; Zoledronic Acid
PubMed: 33270906
DOI: 10.1002/14651858.CD013020.pub2 -
Breast Cancer Research and Treatment Aug 2019Bone-modifying agents (BMAs) such as bisphosphonates and denosumab are usually administered every 4 weeks (standard) in patients with bone metastases from breast cancer... (Meta-Analysis)
Meta-Analysis
PURPOSE
Bone-modifying agents (BMAs) such as bisphosphonates and denosumab are usually administered every 4 weeks (standard) in patients with bone metastases from breast cancer to prevent skeletal-related events (SREs). Recent randomized controlled trials suggest every 12-week (de-escalated) dosing interval may be non-inferior. The objective of this systematic review and meta-analysis was to compare the efficacy and harms of standard with de-escalated administration of BMA's in patients with bone metastases from breast cancer.
METHODS
We searched Medline, PubMed, and the Cochrane Register of Controlled Trials from 1947 to March 14, 2018 and conference abstracts from (2014-March 14, 2018) for randomized clinical trials comparing every 4-week and every 12-week dosing interval of bone-modifying agents. Using PRISMA guidelines, meta-analyses were performed using random-effects models, with findings reported as risk ratios with 95% confidence intervals (CI).
RESULTS
From a total of 1311 citations, we identified 8 full-text articles and 1 abstract comprising data from 5 completed randomized clinical trials (n = 1807). Zoledronate administration every 12 weeks compared to every 4 weeks produced a summary risk ratio of 1.05 (95% CI 0.88-1.25) for patients with ≥ 1 on-study SRE indicating similar efficacy. These results did not differ whether patients had received prior intravenous bisphosphonate. De-escalation was associated with a non-statistically significant lower risk of increased creatinine (summary risk ratio 0.41 [95% CI 0.15-1.16]). Currently, there are insufficient data for pamidronate and denosumab de-escalation.
CONCLUSIONS
These data are supportive of de-escalation of zoledronate from onset for patients with bone metastases from breast cancer.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Female; Humans; Morbidity; Odds Ratio; Publication Bias; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31079283
DOI: 10.1007/s10549-019-05265-1 -
Osteoporosis International : a Journal... Jan 2020Skeletal fragility is a common complication of childhood acute lymphoblastic leukaemia (ALL) but the impact of bisphosphonate therapy on bone mass and fracture is...
UNLABELLED
Skeletal fragility is a common complication of childhood acute lymphoblastic leukaemia (ALL) but the impact of bisphosphonate therapy on bone mass and fracture is unclear. We aim to conduct a systematic review to evaluate the effects of bisphosphonates on bone mineral density (BMD) and fracture incidence in children with ALL.
METHODS
EMBASE, Medline and the Cochrane Library were thoroughly searched by two researchers. Inclusion criteria was any child under the age of 18 years with a diagnosis of ALL, who had received any bisphosphonate treatment and had serial measurements of bone density performed thereafter. All primary research studies of any study design, excluding case reports, were included.
RESULTS
Ten full text papers were identified with two exclusively meeting the inclusion criteria. Both studies administered bisphosphonates to children receiving maintenance chemotherapy for varying durations. Bone density was assessed at regular intervals by dual x-ray absorptiometry (DXA). The majority of participants had an improvement in bone density at the end of each study. However, no size adjustment of DXA data was performed. Limited information on fracture occurrence was provided by one study but did not include routine screening for vertebral fractures.
CONCLUSIONS
This systematic review identified that there is insufficient evidence to support routine use of prophylactic bisphosphonate therapy in childhood ALL for prevention of fracture and improvement of bone mass. Future well-designed clinical trials in those at highest risk of fractures in ALL are now needed.
Topics: Adolescent; Bone Density; Child; Diphosphonates; Female; Fractures, Bone; Humans; Incidence; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Retrospective Studies
PubMed: 31377915
DOI: 10.1007/s00198-019-05082-8