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The Cochrane Database of Systematic... Mar 2015Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer.... (Review)
Review
BACKGROUND
Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer. The current literature indicates that pain is not well managed, however the evidence base to guide clinicians is limited. There is a clear need for evidence from a systematic review to inform prescribing.
OBJECTIVES
To evaluate the evidence on the effectiveness of different pharmacological interventions used for pain in CYP with LLCs.
SEARCH METHODS
The following electronic databases were searched up to December 2014: CENTRAL (in the Cochrane Library), MEDLINE, EMBASE, PsycINFO and CINAHL. In addition, we searched conference proceedings and reference lists of included studies. For completeness, we also contacted experts in the field. No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs), quasi-randomised studies and other studies that included a clearly defined comparator group were included. The studies investigated pharmacological treatments for pain associated with LLCs in CYP. The treatment included those specifically developed to treat pain and those that acted as an adjuvant, where the treatment was not primarily developed to treat pain but has pain relieving properties. The LLC was identified by its inclusion in the Richard Hain Directory of LLCs.
DATA COLLECTION AND ANALYSIS
Citations were screened by five review authors. Data were extracted by one review author and checked by a second. Two review authors assessed the risk of bias of included studies. A sufficient number of studies using homogeneous outcomes was not identified so a meta-analysis was not possible.
MAIN RESULTS
We identified 24,704 citations from our database search. Nine trials with 379 participants fulfilled our inclusion criteria. Participants had cerebral palsy (CP) in five of the studies and osteogenesis imperfecta (OI) in the other four. Participants across the trials ranged in age from 2 to 19 years. All studies, apart from one cross-over trial, were parallel designed RCTs. Three of the trials on CP evaluated intrathecal baclofen (ITB) and two botulinum toxin A (BoNT-A). All of the OI trials evaluated the use of bisphosphonates (two alendronate and one pamidronate). No trials were identified that evaluated a commonly used analgesic in this patient group. Pain was a secondary outcome in five of the eight identified studies. Overall the quality of the trials was mixed. Only one study involved over 100 participants.For the two ITB studies for pain in CP, in the same study population but assessed at different time points in their disease, both found an effect on pain favouring the intervention compared to the control group (standard care or placebo) (mean difference (MD) 4.20, 95% confidence interval (CI) 2.15 to 6.25; MD 26.60, 95% CI 2.61 to 50.59, respectively). In these studies most of the adverse events related to the procedure or device for administration rather than the drug, such as swelling at the pump site. In one trial there were also eight serious adverse effects; these included difficulty swallowing and an epileptic seizure. The trial did not state if these occurred in the intervention group. At follow-up in both BoNT-A trials there was no evidence of a difference in pain between the trial arms among CP participants. The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures. Gastrointestinal problems were the most frequent adverse event in those who received alendronate. The trial investigating pamidronate found no evidence of a difference in pain compared to the control group. No adverse events were reported in this trial.
AUTHORS' CONCLUSIONS
Published, controlled evidence on the pharmacological interventions for pain in CYP with LLCs is limited. The evidence that is currently available evaluated pain largely as a secondary outcome and the drugs used were all adjuvants and not always commonly used in general paediatric palliative care for pain. Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs. Future trials with larger populations should examine the effects of the drugs commonly used as analgesics; with the rising prevalence of many LLCs this becomes more necessary.
Topics: Adolescent; Alendronate; Baclofen; Botulinum Toxins, Type A; Cerebral Palsy; Child; Child, Preschool; Diphosphonates; Gastrointestinal Diseases; Humans; Injections, Spinal; Neuromuscular Agents; Osteogenesis Imperfecta; Pain; Pamidronate; Seizures; Young Adult
PubMed: 25768935
DOI: 10.1002/14651858.CD010750.pub2 -
Journal of Bone and Mineral Research :... Mar 2020High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging modality for assessing volumetric bone mineral density (vBMD) and... (Meta-Analysis)
Meta-Analysis
High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (1) assess fracture-associated differences in HR-pQCT bone parameters; and (2) to determine if HR-pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR-pQCT (39/40 used XtremeCT scanners) to assess 1291 to 3253 and 3389 to 10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta-analysis. An additional meta-analysis of short-term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture-associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR-pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from -2.6% (95% confidence interval [CI] -3.4 to -1.9) in radial cortical vBMD to -12.6% (95% CI -15.0 to -10.3) in radial trabecular vBMD. Fracture-associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR-pQCT can predict incident fracture. Assessment of study quality, heterogeneity, and publication biases verified the validity of these findings. Finally, we demonstrated that fracture-associated deficits in total and trabecular vBMD and certain tibial cortical parameters can be reliably discerned from HR-pQCT-related precision error and can be used to detect fracture-associated differences in individual patients. Although differences in other HR-pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross-sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR-pQCT in clinical fracture prediction. © 2019 American Society for Bone and Mineral Research.
Topics: Bone Density; Cross-Sectional Studies; Fractures, Bone; Humans; Prospective Studies; Radius; Reproducibility of Results; Retrospective Studies
PubMed: 31643098
DOI: 10.1002/jbmr.3901 -
Frontiers in Immunology 2022Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet... (Meta-Analysis)
Meta-Analysis
Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet medical need. Common sources of MSCs include among others, bone marrow (BM), fat, umbilical cord, and placenta-derived decidua stromal cells (DSCs). We here summarize our more than 20-years of scientific experience in the clinical use of MSCs and DSCs in different clinical settings. BM-MSCs were first explored to enhance the engraftment of autografts in hematopoietic cell transplantation (HCT) and osteogenesis imperfecta around 30 years ago. In 2004, our group reported the first anti-inflammatory use of BM-MSCs in a child with grade IV acute graft-versus-host disease (GvHD). Subsequent studies have shown that MSCs appear to be more effective in acute than chronic GvHD. Today BM-MSC-therapy is registered for acute GvHD in Japan and for GvHD in children in Canada and New Zeeland. MSCs first home to the lung following intravenous injection and exert strong local and systemic immunomodulatory effects on the host immune system. Thus, they were studied for ameliorating the cytokine storm in acute respiratory distress syndrome (ARDS). Both, MSCs and DSCs were used to treat SARS-CoV-2 coronavirus-induced disease 2019 (COVID-19)-induced ARDS. In addition, they were also used for other novel indications, such as pneumomediastinum, colon perforation, and radiculomyelopathy. MSC and DSCs trigger coagulation and were thus explored to stop hemorrhages. DSCs appear to be more effective for acute GvHD, ARDS, and hemorrhages, but randomized studies are needed to prove superiority. Stromal cell infusion is safe, well tolerated, and only gives rise to a slight fever in a limited number of patients, but no major side effects have been reported in multiple safety studies and metaanalysis. In this review we summarize current evidence from studies, animal models, and importantly our clinical experience, to support stromal cell therapy in multiple clinical indications. This encloses MSC's effects on the immune system, coagulation, and their safety and efficacy, which are discussed in relation to prominent clinical trials within the field.
Topics: Animals; COVID-19; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pregnancy; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 35371003
DOI: 10.3389/fimmu.2022.839844 -
Frontiers in Endocrinology 2020Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive...
Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive radiographic imaging techniques and genetic analyses, bone biopsies are still valuable in the diagnosis of bone diseases. Advanced techniques for the assessment of bone quality in bone biopsies, which have emerged during the last decades, allows in-depth tissue analyses beyond structural changes visible in bone histology. In this review, we give an overview of the application and advantages of the advanced techniques for the analysis of bone biopsies in the clinical setting of various rare metabolic bone diseases. A systematic literature search on rare metabolic bone diseases and analyzing techniques of bone biopsies was performed in PubMed up to 2019 week 34. Advanced techniques for the analysis of bone biopsies were described for rare metabolic bone disorders including Paget's disease of bone, osteogenesis imperfecta, fibrous dysplasia, Fibrodysplasia ossificans progressiva, X-linked osteoporosis, Loeys-Diets syndrome, osteopetrosis, Erdheim-Chester disease, and Cherubism. A variety of advanced available analytical techniques were identified that may help to provide additional detail on cellular, structural, and compositional characteristics in rare bone diseases complementing classical histopathology. To date, these techniques have only been used in research and not in daily clinical practice. Clinical application of bone quality assessment techniques depends upon several aspects such as availability of the technique in hospitals, the existence of reference data, and a cooperative network of researchers and clinicians. The evaluation of rare metabolic bone disorders requires a repertoire of different methods, owing to their distinct bone tissue characteristics. The broader use of bone material obtained from biopsies could provide much more information about pathophysiology or treatment options and establish bone biopsies as a valuable tool in rare metabolic bone diseases.
Topics: Biopsy; Bone Diseases; Fibrous Dysplasia of Bone; Humans; Loeys-Dietz Syndrome; Myositis Ossificans; Osteitis Deformans; Osteogenesis Imperfecta; Osteopetrosis; Osteoporosis; Rare Diseases
PubMed: 32714279
DOI: 10.3389/fendo.2020.00399