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MedRxiv : the Preprint Server For... Apr 2023Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Efforts to prevent T1D have focused on modulating immune responses and...
BACKGROUND
Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Efforts to prevent T1D have focused on modulating immune responses and supporting beta cell health; however, heterogeneity in disease progression and responses to therapies have made these efforts difficult to translate to clinical practice, highlighting the need for precision medicine approaches to T1D prevention.
METHODS
To understand the current state of knowledge regarding precision approaches to T1D prevention, we performed a systematic review of randomized-controlled trials from the past 25 years testing disease-modifying therapies in T1D and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument.
RESULTS
We identified 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss in individuals at disease onset. Seventeen agents tested, mostly immunotherapies, showed benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employed precision analyses to assess features linked to treatment response. Age, measures of beta cell function and immune phenotypes were most frequently tested. However, analyses were typically not prespecified, with inconsistent methods reporting, and tended to report positive findings.
CONCLUSIONS
While the quality of prevention and intervention trials was overall high, low quality of precision analyses made it difficult to draw meaningful conclusions that inform clinical practice. Thus, prespecified precision analyses should be incorporated into the design of future studies and reported in full to facilitate precision medicine approaches to T1D prevention.
PLAIN LANGUAGE SUMMARY
Type 1 diabetes (T1D) results from the destruction of insulin-producing cells in the pancreas, necessitating lifelong insulin dependence. T1D prevention remains an elusive goal, largely due to immense variability in disease progression. Agents tested to date in clinical trials work in a subset of individuals, highlighting the need for precision medicine approaches to prevention. We systematically reviewed clinical trials of disease-modifying therapy in T1D. While age, measures of beta cell function, and immune phenotypes were most commonly identified as factors that influenced treatment response, the overall quality of these studies was low. This review reveals an important need to proactively design clinical trials with well-defined analyses to ensure that results can be interpreted and applied to clinical practice.
PubMed: 37131690
DOI: 10.1101/2023.04.12.23288421 -
Thorax Jul 2015The overlap between asthma and COPD is increasingly recognised. This review examines the new insights, treatment and remaining knowledge gaps for asthma-COPD overlap. (Review)
Review
BACKGROUND
The overlap between asthma and COPD is increasingly recognised. This review examines the new insights, treatment and remaining knowledge gaps for asthma-COPD overlap.
METHOD
A systematic literature review of cluster analyses of asthma and COPD was performed. Articles from 2009 to the present dealing with prevalence, morbidity and treatment of asthma-COPD overlap were identified and reviewed.
RESULTS
Asthma-COPD overlap was consistently recognised in studies using a variety of different study designs and sampling. The prevalence was approximately 20% in patients with obstructive airways diseases. Asthma-COPD overlap was associated with increased morbidity and possibly an increased mortality and comorbidity. There was evidence of a heterogeneous pattern of airway inflammation that included eosinophilic (in adult asthma), neutrophilic or mixed patterns (in severe asthma and COPD). Systemic inflammation was present in asthma-COPD overlap and resembled that of COPD. Within asthma-COPD overlap, there is evidence of different subgroups, and recognition using bronchodilator responsiveness has not been successful. Guidelines generally recommend a serial approach to assessment, with treatment recommendations dominated by an asthma paradigm. Research is needed into key clinical features that impact outcome, mechanisms and treatment approaches in asthma-COPD overlap. Identifying and treating disease components by multidimensional assessment shows promise.
CONCLUSIONS
Asthma-COPD overlap has drawn attention to the significant heterogeneity that exists within obstructive airway diseases. It should be replaced by novel approaches that identify and manage the components of this heterogeneity, such as multidimensional assessment and treatment. Future research is needed to test these novel and personalised approaches.
Topics: Asthma; Biomarkers; Cluster Analysis; Comorbidity; Humans; Inflammation Mediators; Practice Guidelines as Topic; Prevalence; Pulmonary Disease, Chronic Obstructive; Syndrome
PubMed: 25948695
DOI: 10.1136/thoraxjnl-2014-206740 -
Tidsskrift For Den Norske Laegeforening... Nov 2017Population groups of different ancestry appear to have varying prevalence of diabetes, different risks of developing cardiovascular disease and different responses to... (Review)
Review
BACKGROUND
Population groups of different ancestry appear to have varying prevalence of diabetes, different risks of developing cardiovascular disease and different responses to certain drugs that are used for these conditions. We wished to review the literature in this field.
MATERIAL AND METHOD
We have performed searches in several databases for systematic review articles published from the year 2000 onwards, and supplemented these with articles from reference lists, our own literature archives and a pyramid search in the Norwegian Electronic Health Library database. Altogether 37 articles were included.
RESULTS
With regard to diagnosed diabetes, the prevalence of coronary heart disease and stroke varies among groups of South Asian, East Asian, African and European ancestry. In patients of South Asian ancestry, the risk of coronary heart disease appears to be twice that of Europeans, and the disease occurs 5–10 years earlier. The prevalence of stroke is especially high in persons of African ancestry. Risk factors such as dyslipidemia and hypertension are distributed differently among these groups. The therapeutic response to drugs such as beta blockers, ACE inhibitors and various statins differs; for example, statin doses in Asians may often be halved in relation to those used for Caucasians, and ACE inhibitors are not recommended as monotherapy for hypertension in persons of African ancestry. These differences are partly attributable to variations in genetic disposition.
INTERPRETATION
The findings are clinically significant – better insight in this field enables optimal tailoring of treatment for each patient, with more rapid achievement of goals and reduced risk of adverse effects. The recommendations given in this article are consistent with and complement the Directorate of Health’s revised guidelines for the treatment of diabetes.
Topics: Antihypertensive Agents; Asian People; Black People; Cardiovascular Diseases; Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics; Stroke; White People
PubMed: 29181932
DOI: 10.4045/tidsskr.16.0680 -
Frontiers in Bioscience (Landmark... Dec 2021Both stress and hypertension (HTN) are considered major health problems that negatively impact the cerebral vasculature. In this article we summarize the possible... (Review)
Review
OBJECTIVES
Both stress and hypertension (HTN) are considered major health problems that negatively impact the cerebral vasculature. In this article we summarize the possible relationship between stress and HTN.
METHODS
We conducted a systematic review of the literature using a database search of MEDLINE, PubMed, Scopus, and Web of Science.
RESULTS
Psychological stress is known to be an important risk factor for essential hypertension. Acute stress can induce transient elevations of blood pressure in the context of the fight-or-flight response. With increased intensity and duration of a perceived harmful event, the normal physiological response is altered, resulting in a failure to return to the resting levels. These changes are responsible for the development of HTN. Genetic and behavioral factors are also very important for the pathogenesis of hypertension under chronic stress situation. In addition, HTN and chronic stress may lead to impaired auto-regulation, regional vascular remodeling, and breakdown of the blood brain barrier (BBB). The effects of both HTN and chronic stress on the cerebral blood vessels shows that both have common structural and functional effects including endothelial damage with subsequent increased wall thickness, vessel resistance, stiffness, arterial atherosclerosis, and altered hemodynamics.
CONCLUSION
Most of the above mentioned vascular effects of stress were primarily reported in animal models. Further in-vivo standardization of pathological vascular indices and imaging modalities is warranted. Radiological quantification of these cerebrovascular changes is therefore essential for in depth understanding of the healthy and diseased cerebral arteries functions, identification and stratification of patients at risk of cardiovascular and neurological adverse events, enactment of preventive measures prior to the onset of systemic HTN, and the initiation of personalized medical management.
Topics: Animals; Blood Pressure; Humans; Hypertension; Vascular Remodeling
PubMed: 34994178
DOI: 10.52586/5057 -
Gut Microbes Dec 2023Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been... (Review)
Review
Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been published investigating the associations between gut microbiota and disease activity or IBD therapy. We performed a systematic review to investigate the microbiome predictors of response to advanced therapy in IBD. Unlike previous studies, our review focused on predictors of response to therapy; so the included studies assessed microbiome predictors before the proposed time of response or remission. We also provide an update of the available data on mycobiomes and viromes. We highlight key themes in the literature that may serve as future biomarkers of treatment response: the abundance of fecal SCFA-producing bacteria and opportunistic bacteria, metabolic pathways related to butyrate synthesis, and non-butyrate metabolomic predictors, including bile acids (BAs), amino acids, and lipids, as well as mycobiome predictors of response.
Topics: Humans; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Feces; Fecal Microbiota Transplantation; Biomarkers
PubMed: 38044504
DOI: 10.1080/19490976.2023.2287073 -
Quality of Life Research : An... Dec 2021Diabetic foot disease is one of the most serious and expensive complications of diabetes. Patient-reported outcome measures (PROMs) analyse patients' perception of their... (Review)
Review
PURPOSE
Diabetic foot disease is one of the most serious and expensive complications of diabetes. Patient-reported outcome measures (PROMs) analyse patients' perception of their disability, functionality and health. The goal of this work was to conduct a systematic review regarding the specific PROMs related to the evaluation of diabetic foot disease and to extract and analyse the values of their measurement properties.
METHODS
Electronic databases included were PubMed, CINAHL, Scopus, PEDro, Cochrane, SciELO and EMBASE. The search terms used were foot, diabet*, diabetic foot, questionnaire, patient-reported outcome, self-care, valid*, reliabil*. Studies whose did not satisfy the Critical Appraisals Skills Programme (CASP) Diagnostic Study Checklist were excluded. The measurement properties extracted were: Internal Consistency, Test-retest, Inter-rater and Intra-rater, Standard Error of Measurement, Minimum Detectable Measurement Difference, Content Validity, Construct Validity, Criterion Validity and Responsiveness.
RESULTS
The PROMs selected for this review were 12 questionnaires. The Diabetic foot self-care questionnaire (DFSQ-UMA) and the Questionnaire for Diabetes Related Foot Disease (Q-DFD) were the PROMs that showed the highest number of completed measurement properties.
CONCLUSION
According to the results, it is relevant to create specific questionnaires for the evaluation of diabetic foot disease. It seems appropriate to use both DFSQ-UMA and Q-DFD when assessing patients with diabetic foot disease.
Topics: Diabetes Mellitus; Diabetic Foot; Foot Diseases; Humans; Patient Reported Outcome Measures; Quality of Life; Surveys and Questionnaires
PubMed: 34109501
DOI: 10.1007/s11136-021-02892-4 -
Neurotoxicity Research Jan 2016The formation of neutralizing antibodies (NAbs) directed specifically against the active neurotoxin part of the botulinum neurotoxin (BoNT) complex is often cited as a... (Meta-Analysis)
Meta-Analysis Review
The formation of neutralizing antibodies (NAbs) directed specifically against the active neurotoxin part of the botulinum neurotoxin (BoNT) complex is often cited as a major cause of secondary non-responsiveness (SnR) to treatment. This systematic and meta-analytic review evaluates the frequency of NAbs among patients treated with BoNT therapy for any clinical indication. A comprehensive database search strategy was designed to retrieve relevant clinical data from the published literature up to April 2013. All English-language publications that analyzed NAbs prevalence in more than ten patients were included, regardless of BoNT formulation, assay method, and study design. For the meta-analysis, patients were divided into three categories: secondary nonresponse (SnR) patients, clinically responding patients and all patients, independently of BoNT responsiveness. The meta-analysis included 61 studies reporting data for 8525 patients; 4972 dystonic patients, 1170 patients with spasticity, 294 patients with urologic indications, 396 patient with hyperhidrosis, 1659 patients with glabellar line, and 34 patients with hypersalivation. Among the ‘‘all patients’’ group NAbs frequency was 20%for dystonia, 5.9%for spasticity, and 2.7% for urologic patients and 1.1% for other conditions. The prevalence of NAbs was lower (3.5%) among clinically responding patients and higher in 53.5%SnR patients. About a half of patients with SnR do not have NAbs. NAbs was high among patients treated with RIMA but it was not associated with clinical non-responsiveness. Meta-analysis of the frequency of NAbs and SnR are limited by the heterogeneity of study design and reported outcomes. Indeed the analysis of several factors that can influence the development of NAbs, i.e.,MHCof patients, frequency and site of injection, injection technique, cumulative dose, and toxin denaturation, was not specifically evaluated due to the paucity and heterogeneity of data. The identification of all these missing data should be taken into account in order to improve the methodology of future studies.
Topics: Animals; Antibodies, Neutralizing; Botulinum Toxins, Type A; Databases, Bibliographic; Humans; Nervous System Diseases; Neuromuscular Agents
PubMed: 26467676
DOI: 10.1007/s12640-015-9565-5 -
Vaccine Apr 2022Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics.... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.
OBJECTIVE
A systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.
METHODS
The protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.
RESULTS
We retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found.
EFFICACY
limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration.
SAFETY
vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).
CONCLUSIONS
More evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.
Topics: Biological Products; Child; Humans; Immunogenicity, Vaccine; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Measles-Mumps-Rubella Vaccine; Pneumococcal Vaccines; Tumor Necrosis Factor Inhibitors
PubMed: 35370019
DOI: 10.1016/j.vaccine.2022.03.041 -
Neurological Sciences : Official... Jun 2023To provide new and comprehensive evidence for diagnosis and management of FOSMN syndrome. (Review)
Review
OBJECTIVE
To provide new and comprehensive evidence for diagnosis and management of FOSMN syndrome.
METHODS
We reviewed our database to identify patients with FOSMN syndrome. Online database including PubMed, EMBASE, and OVID were also searched for relevant cases.
RESULTS
We identified a total of 71 cases, including 4 cases from our database and 67 ones from online searching. A predominance of male was observed [44 (62.0%)] with median onset age of 53 (range: 7-75) years old. The median (range) disease duration was 60 (3-552) months at the time of the visit. The initial symptoms could be sensory deficits in face (80.3%) or oral cavity (4.2%), bulbar paralysis (7.0%), dysosmia (1.4%), dysgeusia (4.2%), weakness or numbness of upper limbs (5.6%), or lower limbs (1.4%). Abnormal blink reflex was presented in 64 (90.1%) patients. CSF tests showed elevated protein level in 5 (7.0%) patients. Six (8.5%) patients had MND-related gene mutation. Five (7.0%) patients showed transient responsiveness to immunosuppressive therapy, then deteriorated relentlessly. Fourteen (19.7%) patients died, with an average survival time of around 4 years. Among them, five patients died of respiratory insufficiency.
CONCLUSION
The age of onset, progress of disease course, and prognosis of FOSMN syndrome could be varied significantly. The prerequisites of diagnosis were progressive and asymmetric lower motor neuron dysfunction, with sensory dysfunction which usually showed in face at the onset. Immunosuppressive therapy could be tried in some patients with suspected inflammatory clues. In general, FOSMN syndrome tended to be motor neuron disease with sensory involvement.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Young Adult; Blinking; Bulbar Palsy, Progressive; Motor Neuron Disease; Mutation; Neurodegenerative Diseases
PubMed: 36864244
DOI: 10.1007/s10072-023-06703-1 -
Arthritis Research & Therapy Nov 2016Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth... (Review)
Review
BACKGROUND
Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth factor (CTGF) are key mediators in the pathogenesis of fibrotic disorders. The aim of this systematic review was to investigate the evidence for the expression of TGF-β, BMPs and CTGF along tendon disease progression and the response of tendon cells to these growth factors accordingly.
METHOD
We conducted a systematic screen of the scientific literature using the Medline database. The search terms used were "tendon AND TGF-β," "tendon AND BMP" or "tendon AND CTGF." Studies of human samples, animal tendon injury and overuse models were included.
RESULTS
Thirty-three studies were included. In eight studies the expression of TGF-β, BMPs or CTGF was dysregulated in chronic tendinopathy and tendon tear patient tissues in comparison with healthy control tissues. The expression of TGF-β, BMPs and CTGF was increased and showed temporal changes in expression in tendon tissues from animal injury or overuse models compared with the healthy control (23 studies), but the pattern of upregulation was inconsistent between growth factors and also the type of animal model. No study investigated the differences in the effect of TGF-β, BMPs or CTGF treatment between patient-derived cells from healthy and diseased tendon tissues. Tendon cells derived from animal models of tendon injury showed increased expression of extracellular matrix protein genes and increased cell signaling response to TGF-β and BMP treatments compared with the control cells (two studies).
CONCLUSION
The expression of TGF-β, BMPs and CTGF in tendon tissues is altered temporally during healing in animal models of tendon injury or overuse, but the transition during the development of human tendon disease is currently unknown. Findings from this systematic review suggest a potential and compelling role for TGF-β, BMPs and CTGF in tendon disease; however, there is a paucity of studies analyzing their expression and stimulated cellular response in well-phenotyped human samples. Future work should investigate the dynamic expression of these fibrotic growth factors and their interaction with tendon cells using patient samples at different stages of human tendon disease.
Topics: Animals; Bone Morphogenetic Proteins; Connective Tissue Growth Factor; Fibrosis; Humans; Tendinopathy; Transforming Growth Factor beta
PubMed: 27863509
DOI: 10.1186/s13075-016-1165-0