-
PloS One 2018Research investigating Whiplash Associated Disorder (WAD) has largely focused on the cervical spine yet symptoms can be widespread. Thoracic spine pain prevalence is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Research investigating Whiplash Associated Disorder (WAD) has largely focused on the cervical spine yet symptoms can be widespread. Thoracic spine pain prevalence is reported ~66%; perhaps unsurprising given the forceful stretch/eccentric loading of posterior structures of the spine, and the thoracic spine's contribution to neck mobility/function. Approximately 50% WAD patients develop chronic pain and disability resulting in high levels of societal and healthcare costs. It is time to look beyond the cervical spine to fully understand anatomical dysfunction in WAD and provide new directions for clinical practice and research.
PURPOSE
To evaluate the scope and nature of dysfunction in the thoracic region in patients with WAD.
METHODS
A systematic review and data synthesis was conducted according to a pre-defined, registered (PROSPERO, CRD42015026983) and published protocol. All forms of observational study were included. A sensitive topic-based search strategy was designed from inception to 1/06/16. Databases, grey literature and registers were searched using a study population terms and key words derived from scoping search. Two reviewers independently searched information sources, assessed studies for inclusion, extracted data and assessed risk of bias. A third reviewer checked for consistency and clarity. Extracted data included summary data: sample size and characteristics, outcomes, and timescales to reflect disorder state. Risk of bias was assessed using the Newcastle-Ottawa Scale. Data were tabulated to allow enabling a semi-qualitative comparison and grouped by outcome across studies. Strength of the overall body of evidence was assessed using a modified GRADE.
RESULTS
Thirty eight studies (n>50,000) which were conducted across a range of countries were included. Few authors responded to requests for further data (5 of 9 contacted). Results were reported in the context of overall quality and were presented for measures of pain or dysfunction and presented, where possible, according to WAD severity and time point post injury. Key findings include: 1) high prevalence of thoracic pain (>60%); higher for those with more severe presentations and in the acute stage, 2) low prevalence of chest pain (<22%), 3) evidence of thoracic outlet syndrome, with some association to and involvement of the brachial plexus, 4) muscle dysfunction in the form of heightened activity of the sternocleidomastoid or delayed onset of action of the serratus anterior, 5) high prevalence of myofascial pain and trigger points in the scalene muscles, sternocleidomastoid and mid/lower fibres of trapezius muscle (48-65%), and 6) inconclusive evidence of altered thoracic posture or mobility.
CONCLUSIONS
Considerable evidence supports thoracic pain and dysfunction in patients with WAD, involving primarily nerves and muscles. Notwithstanding the low/very low level of evidence from this review, our findings do support a more extensive clinical evaluation of patients presenting with WAD. Additional high quality research is required to further characterise dysfunction across other structures in the thoracic region, including but not limited to the thoracic spine (mobility and posture) and thoracic muscles (stiffness, activation patterns). In turn this may inform the design of clinical trials targeting such dysfunction.
Topics: Brachial Plexus; Humans; Muscle, Skeletal; Pain; Publication Bias; Thorax; Whiplash Injuries
PubMed: 29570722
DOI: 10.1371/journal.pone.0194235 -
Metabolites Nov 2022In recent years, the importance of the gut microbiome in human health and disease has increased. Growing evidence suggests that gut dysbiosis might be a crucial risk... (Review)
Review
In recent years, the importance of the gut microbiome in human health and disease has increased. Growing evidence suggests that gut dysbiosis might be a crucial risk factor for coronary artery disease (CAD). Therefore, we conducted a systematic review and meta-analysis to determine whether or not CAD is associated with specific changes in the gut microbiome. The V3-V4 regions of the 16S rDNA from fecal samples were analyzed to compare the gut microbiome composition between CAD patients and controls. Our search yielded 1181 articles, of which 21 met inclusion criteria for systematic review and 7 for meta-analysis. The alpha-diversity, including observed OTUs, Shannon and Simpson indices, was significantly decreased in CAD, indicating the reduced richness of the gut microbiome. The most consistent results in a systematic review and meta-analysis pointed out the reduced abundance of and in CAD patients. Moreover, , , and taxa demonstrated an increased trend in CAD patients. The alterations in the gut microbiota composition are associated with qualitative and quantitative changes in bacterial metabolites, many of which have pro-atherogenic effects on endothelial cells, increasing the risk of developing and progressing CAD.
PubMed: 36557203
DOI: 10.3390/metabo12121165 -
Translational Psychiatry Feb 2021Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis... (Review)
Review
Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis that maltreatment is associated with epigenetic changes that may subsequently serve as mechanisms of disease. The current review uses a systematic approach to identify and summarize the literature related to childhood maltreatment and alterations in DNA methylation in humans. A total of 100 empirical articles were identified in our systematic review of research published prior to or during March 2020, including studies that focused on candidate genes and studies that leveraged epigenome-wide data in both children and adults. Themes arising from the literature, including consistent and inconsistent patterns of results, are presented. Several directions for future research, including important methodological considerations for future study design, are discussed. Taken together, the literature on childhood maltreatment and DNA methylation underscores the complexity of transactions between the environment and biology across development.
Topics: Adult; Child; Child Abuse; DNA Methylation; Epigenesis, Genetic; Epigenome; Humans; Risk Factors
PubMed: 33608499
DOI: 10.1038/s41398-021-01207-y -
Osteoporosis International : a Journal... Feb 2021Methotrexate (MTX)-related osteopathy is rare, defined by the triad of pain, osteoporosis, and "atypical fractures" when it was first described in the 1970s in children... (Review)
Review
INTRODUCTION
Methotrexate (MTX)-related osteopathy is rare, defined by the triad of pain, osteoporosis, and "atypical fractures" when it was first described in the 1970s in children treated with high doses MTX for acute leukemia. Since then, several cases have been reported in patients treated with low-dose MTX for inflammatory diseases.
METHODS
A systematic research of cases of MTX-related osteopathy was performed in records of Rheumatology Department of Rennes University Hospital. Data collection focused on demographic data, corticosteroid doses, MTX doses and intake method, cumulative doses, year of diagnosis, fracture location, bone densitometry value, and osteoporosis treatment if necessary. A literature review was also conducted to identify other cases in literature and try to understand the pathophysiological mechanisms of this rare entity.
RESULTS
We report 5 cases identified between 2011 and 2019, which represents the largest cohort described excluding oncology cases. Fracture locations were atypical for osteoporotic fractures. All patients improved in the following months with MTX withdrawal. All patients except one were treated with antiresorptives (bisphosphonates, denosumab). Two patients, treated with bisphosphonates, had a recurrence of fracture, once again of atypical location. Twenty-five cases were collected in literature with similar clinical presentation. The cellular studies that investigated the bone toxicity of MTX mainly showed a decrease in the number of osteoblasts, osteocytes, and chondrocytes in the growth plate and an increase in the number and activity of osteoclasts. In vitro, consequences of mechanical stimulation on human trabecular bone cells in the presence of MTX showed an alteration in mechano-transduction, with membrane hyperpolarization, acting on the integrin pathway. In contrast with our report, the cases described in the literature were not consistently associated with a decrease in bone mineral density (BMD).
CONCLUSION
MTX osteopathy while rare must be known by the rheumatologist, especially when using this treatment for inflammatory conditions. The mechanisms are still poorly understood, raising the question of a possible remnant effect of MTX on osteo-forming bone cells, potentially dose-dependent. Methotrexate (MTX) osteopathy, described as a clinical triad, pain, osteoporosis, and atypical stress fractures, while rare, must be known by the rheumatologist. Our cohort of 5 cases represent the largest series of the literature. Pathophysiological studies raised the question of a dose-dependent remnant effect of MTX on osteo-forming bone cells.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Bone Density; Bone Diseases; Child; Humans; Methotrexate; Osteoporosis
PubMed: 33128074
DOI: 10.1007/s00198-020-05664-x -
Advances in Radiation Oncology 2023Although the frequency of noninferiority trials is increasing, the consistency of the reporting of these trials can vary. The aim of this systematic review was to assess... (Review)
Review
PURPOSE
Although the frequency of noninferiority trials is increasing, the consistency of the reporting of these trials can vary. The aim of this systematic review was to assess the reporting quality of radiation therapy noninferiority trials.
METHODS AND MATERIALS
The PubMed, Embase, and Cochrane databases were queried for randomized controlled radiation therapy trials with noninferiority hypotheses published in English between January 2000 and July 2022, and this was performed by an information scientist. Descriptive statistics were used to summarize data.
RESULTS
Of 423 records screened, 59 (14%) were included after full-text review. All were published after 2003 and open label. The most common primary cancer type was breast (n = 15, 25%). Altered radiation fractionation (n = 26, 45%) and radiation de-escalation (n = 11, 19%) were the most common types of interventions. The most common primary endpoints were locoregional control (n = 17, 29%) and progression-free survival (n = 14, 24%). Fifty-three (90%) reported the noninferiority margin, and only 9 (17%) provided statistical justification for the margin. The median absolute noninferiority margin was 9% (interquartile range, 5%-10%), and the median relative margin was 1.51 (interquartile range, 1.33-2.04). Sample size calculations and confidence intervals were reported in 54 studies (92%). Both intention-to-treat and per-protocol analyses were reported in 27 studies (46%). In 31 trials (53%), noninferiority of the primary endpoint was reached.
CONCLUSIONS
There was variability in the reporting of key components of noninferiority trials. We encourage consideration of additional statistical reasoning such as guidelines or previous trials in the selection of the noninferiority margin, reporting both absolute and relative margins, and the avoidance of statistically vague or misleading language in the reporting of future noninferiority trials.
PubMed: 36852015
DOI: 10.1016/j.adro.2023.101178 -
Brain, Behavior, and Immunity Mar 2024While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and adolescents.
METHODS
We conducted a systematic review to identify immune and redox biomarker studies in children and adolescents (mean age ≤ 18 years old) across the psychosis spectrum: from psychotic like experiences, which are common in children, to threshold psychotic disorders like schizophrenia. We conducted meta-analyses when at least three studies measured the same biomarker.
RESULTS
The systematic review includes 38 pediatric psychosis studies. The meta-analyses found that youth with threshold psychotic disorders had higher neutrophil/lymphocyte ratio (Hedge's g = 0.40, 95 % CI 0.17 - 0.64), tumor necrosis factor (Hedge's g = 0.38, 95 % CI 0.06 - 0.69), C-reactive protein (Hedge's g = 0.38, 95 % CI 0.05 - 0.70), interleukin-6 (Hedge's g = 0.35; 95 % CI 0.11 - 0.64), and total white blood cell count (Hedge's g = 0.29, 95 % CI 0.12 - 0.46) compared to youth without psychosis. Other immune and oxidative stress meta-analytic findings were very heterogeneous.
CONCLUSION
Results from several studies are consistent with the hypothesis that signals often classified as "proinflammatory" are elevated in threshold pediatric psychotic disorders. Data are less clear for immune markers in subthreshold psychosis and redox markers across the subthreshold and threshold psychosis spectrum. Immune and redox biomarker intervention studies are lacking, and research investigating interventions targeting the immune system in threshold pediatric psychosis is especially warranted.
Topics: Adolescent; Humans; Child; Psychotic Disorders; Biomarkers; C-Reactive Protein; Interleukin-6; Oxidative Stress
PubMed: 38141839
DOI: 10.1016/j.bbi.2023.12.019 -
Developmental Cognitive Neuroscience Dec 2022Structural and functional brain alterations are found in adults with depression. It is not known whether these changes are a result of illness or exist prior to disorder... (Review)
Review
Structural and functional brain alterations are found in adults with depression. It is not known whether these changes are a result of illness or exist prior to disorder onset. Asymptomatic offspring of parents with depression offer a unique opportunity to research neural markers of familial risk to depression and clarify the temporal sequence between brain changes and disorder onset. We conducted a systematic review to investigate whether asymptomatic offspring at high familial risk have structural and functional brain changes like those reported in adults with depression. Our literature search resulted in 44 studies on 18,645 offspring ranging from 4 weeks to 25 years old. Reduced cortical thickness and white matter integrity, and altered striatal reward processing were the most consistent findings in high-risk offspring across ages. These alterations are also present in adults with depression, suggesting the existence of neural markers of familial risk for depression. Additional studies reproducing current results, streamlining fMRI data analyses, and investigating underexplored topics (i.e intracortical myelin, gyrification, subcortical shape) may be among the next steps required to improve our understanding of neural markers indexing the vulnerability to depression.
Topics: Adult; Humans; Depression; Genetic Predisposition to Disease; Reward; Magnetic Resonance Imaging; Brain
PubMed: 36242901
DOI: 10.1016/j.dcn.2022.101161 -
Biomedicines Mar 2022Unbalanced diets and altered micronutrient intake are prevalent in the aging adult population. We conducted a systematic review to appraise the evidence regarding the... (Review)
Review
Unbalanced diets and altered micronutrient intake are prevalent in the aging adult population. We conducted a systematic review to appraise the evidence regarding the association between single (α-carotene, β-carotene, lutein, lycopene, β-cryptoxanthin) or total carotenoids and frailty syndrome in the adult population. The literature was screened from study inception to December 2021, using six different electronic databases. After establishing inclusion criteria, two independent researchers assessed the eligibility of 180 retrieved articles. Only 11 fit the eligibility requirements, reporting five carotenoid entries. No exclusion criteria were applied to outcomes, assessment tools, i.e., frailty constructs or surrogates, recruitment setting, general health status, country, and study type (cohort or cross-sectional). Carotenoid exposure was taken as either dietary intake or serum concentrations. Cross-sectional design was more common than longitudinal design ( = 8). Higher dietary and plasma levels of carotenoids, taken individually or cumulatively, were found to reduce the odds of physical frailty markedly, and the evidence showed consistency in the direction of association across all selected studies. Overall, the methodological quality was rated from moderate (27%) to high (73%). Prevention of micronutrient deficiencies has some potential to counteract physical decline. Considering carotenoids as biological markers, when monitoring micronutrient status, stressing increased fruit and vegetable intake may be part of potential multilevel interventions to prevent or better manage disability.
PubMed: 35327434
DOI: 10.3390/biomedicines10030632 -
Pharmaceuticals (Basel, Switzerland) Apr 2022Platinum-based chemotherapy regimens have been proven to be effective in various cancers; however, considerable toxicities may develop and can even lead to treatment... (Review)
Review
Platinum-based chemotherapy regimens have been proven to be effective in various cancers; however, considerable toxicities may develop and can even lead to treatment discontinuation. Diverse factors may influence adverse treatment events, with pharmacogenetic variations being one prime example. Polymorphisms within the glutathione S-transferase pi 1 (GSTP1) gene may especially alter enzyme activity and, consequently, various toxicities in patients receiving platinum-based chemotherapy. Due to a lack of consistency in the degree of elevated complication risk, we performed a systematic literature review and meta-analysis to determine the level of platinum-associated toxicity in patients with the GSTP1 rs1695 polymorphism. We conducted a systematic search for eligible studies published before January 2022 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between the rs1695 polymorphism and various toxicities. Ten eligible studies met the inclusion criteria. The pooled ORs for hematological toxicity and neutropenia in the patients with the variant (G) allele were 1.7- and 2.6-times higher than those with the AA genotype (95% CI 1.06-2.73 and 1.07-6.35), respectively. In contrast, the rs1695 polymorphism resulted in a 44% reduced gastrointestinal toxicity compared to wild-type homozygotes. Our study found that the GSTP1 rs1695 polymorphism was significantly correlated with platinum-induced toxicities. The study also revealed that rs1695 expression exhibited tissue-specific patterns and thus yielded opposite effects in different tissues. A personalized chemotherapy treatment based on these polymorphisms may be considered for cancer patients in the future.
PubMed: 35455437
DOI: 10.3390/ph15040439 -
The Journal of Pain Aug 2017Prominent clinical models of chronic pain propose a fundamental role of classical conditioning in the development of pain-related disability. If classical conditioning... (Review)
Review
UNLABELLED
Prominent clinical models of chronic pain propose a fundamental role of classical conditioning in the development of pain-related disability. If classical conditioning is key to this process, then people with chronic pain may show a different response to pain-related conditioned stimuli than healthy control subjects. We set out to determine whether this is the case by undertaking a comprehensive and systematic review of the literature. To identify studies comparing classical conditioning between people with chronic pain and healthy control subjects, the databases MEDLINE, PsychINFO, PsychARTICLES, Scopus, and CINAHL were searched using key words and medical subject headings consistent with 'classical conditioning' and 'pain.' Articles were included when: 1) pain-free control and chronic pain groups were included, and 2) a differential classical conditioning design was used. The systematic search revealed 7 studies investigating differences in classical conditioning between people with chronic pain and healthy control participants. The included studies involved a total of 129 people with chronic pain (fibromyalgia syndrome, spinal pain, hand pain, irritable bowel syndrome), and 104 healthy control participants. Outcomes included indices of pain-related conditioning such as unconditioned stimulus (US) expectancy and contingency awareness, self-report and physiological measures of pain-related fear, evaluative judgements of conditioned stimulus pleasantness, and muscular and cortical responses. Because of variability in outcomes, meta-analyses included a maximum of 4 studies. People with chronic pain tended to show reduced differential learning and flatter generalization gradients with respect to US expectancy and fear-potentiated eyeblink startle responses. Some studies showed a propensity for greater muscular responses and perceptions of unpleasantness in response to pain-associated cues, relative to control cues.
PERSPECTIVE
The review revealed preliminary evidence that people with chronic pain may exhibit less differential US expectancy and fear learning. This characteristic may contribute to widespread fear-avoidance behavior. The assumption that altered classical conditioning may be a predisposing or maintaining factor for chronic pain remains to be verified.
Topics: Animals; Chronic Pain; Conditioning, Classical; Disabled Persons; Humans; Learning Disabilities
PubMed: 28385510
DOI: 10.1016/j.jpain.2017.02.430