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BMC Pulmonary Medicine May 2022Antibiotics are frequently prescribed for acute exacerbations of COPD (AECOPD) even though most do not have a bacterial aetiology. Biomarkers may help clinicians target... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antibiotics are frequently prescribed for acute exacerbations of COPD (AECOPD) even though most do not have a bacterial aetiology. Biomarkers may help clinicians target antibiotic use by identifying AECOPD caused by bacterial pathogens. We aimed to summarise current evidence on the diagnostic accuracy of biomarkers for detecting bacterial versus non-bacterial AECOPD.
METHODS
We searched Embase and Medline using a search strategy including terms for COPD, biomarkers and bacterial infection. Data regarding diagnostic accuracy for each biomarker in predicting bacterial cause of exacerbation were extracted and summarised. We used to QUADAS-2 tool to assess risk of bias.
RESULTS
Of 509 papers identified, 39 papers evaluating 61 biomarkers were eligible for inclusion. Moderate quality evidence was found for associations between serum C-reactive protein (CRP), serum procalcitonin (PCT), sputum interleukin (IL)-8 and sputum tumour necrosis factor alpha (TNF-α), and the presence of bacterial pathogens in the sputum of patients with AECOPD. Having bacterial pathogens was associated with a mean difference (higher) CRP and PCT of 29.44 mg/L and 0.76 ng/mL respectively. There was inconsistent or weak evidence for associations between bacterial AECOPD and higher levels of sputum IL-1β, IL-6, myeloperoxidase (MPO) and neutrophil elastase (NE). We did not find any consistent evidence of diagnostic value for other biomarkers.
CONCLUSIONS
There is moderate evidence from heterogeneous studies that serum CRP and PCT are of value in differentiating bacterial from non-bacterial AECOPD, and little evidence for other biomarkers. Further high-quality research on the role of biomarkers in identifying bacterial exacerbations is needed.
Topics: Anti-Bacterial Agents; Bacteria; Biomarkers; C-Reactive Protein; Disease Progression; Humans; Procalcitonin; Pulmonary Disease, Chronic Obstructive
PubMed: 35549921
DOI: 10.1186/s12890-022-01958-4 -
Respiratory Medicine Oct 2022There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim of the current systematic review and meta-analysis was to evaluate the efficacy of baricitinib in COVID-19 patients.
METHODS
Databases like ScienceDirect, PubMed/Medline, Publons, Google Scholar and other sources like ClinicalTrials.gov, Cochrane, medRxiv, Research Square and reference lists were thoroughly searched.
RESULTS
Fifteen (15) articles which met the inclusion criteria were qualitatively and quantitatively analysed. Based on Cochrane and Newcastle-Ottawa Scale (NOS) risk of bias (RoB) analyses, 14/15 articles are grouped as high-quality. Meta-analyses revealed that randomised control trials (RCTs) and non-randomised control trials (nRCTs) statistically significantly reduced the mortality rate in COVID-19 patients, with a risk ratio (RR) in the fixed-effect model was RR = 0.64 [95% CI: 0.51 to 0.79; p < 0.0001] and RR = 0.58 [95% CI: 0.45 to 0.73; p < 0.00001], respectively, with insignificant heterogeneity and no publication bias found. For block/reduce disease progression (BDP), baricitinib did not statistically significantly reduce disease progression for RCTs. The RR in the random effect model was RR = 0.80 [95% CI: 0.58 to 1.10: p = 0.17], with significant heterogeneity, where I was 60%. On the other hand, baricitinib statistically significantly reduced disease progression in nRCTs, as the RR of the fixed effect model was RR = 0.54 [95% CI: 0.37 to 0.78; p = 0.001] with insignificant heterogeneity.
CONCLUSION
The current meta-analyses revealed that baricitinib statistically significantly reduced mortality rate and disease progression in COVID-19 patients.
PROSPERO REGISTRATION NUMBER
CRD42021281556.
Topics: Azetidines; Disease Progression; Humans; Purines; Pyrazoles; SARS-CoV-2; Sulfonamides; COVID-19 Drug Treatment
PubMed: 36150282
DOI: 10.1016/j.rmed.2022.106986 -
Clinical Gastroenterology and... Feb 2023Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease... (Review)
Review
BACKGROUND & AIMS
Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease progression, long-term impact of pharmacologic treatments can be assessed only by complementing emerging clinical trial evidence with data from other sources in disease progression modeling. Although this modeling is crucial for economic evaluation studies assessing the clinical and economic consequences of new treatments, the approach to modeling the natural history of NAFLD differs in contemporary research. This systematic literature review investigated modeling of the natural history of NAFLD.
METHODS
A systematic literature review was conducted searching PubMed, Scopus, Cochrane, and the National Health Service Economic Evaluation Database to identify articles focusing on modeling of the natural history of NAFLD. Model structure and transition probabilities were extracted from included studies.
RESULTS
Of the 28 articles identified, differences were seen in model structure and data input. Clear definitions of nonalcoholic steatohepatitis and NAFLD often were lacking; differences in the granularity of modeling fibrosis progression, the approach to disease regression, and modeling of advanced liver disease varied across studies. Observed transition probabilities for F0 to F1, F1 to F2, F2 to F3, and F3 to compensated cirrhosis varied between 0.059 to 0.095, 0.023 to 0.140, 0.018 to 0.070, and 0.040 to 0.118, respectively.
CONCLUSIONS
The difference in disease progression modeling for seemingly similar models warrants further inquiry regarding how to model the natural course of NAFLD. Such differences may have a large impact when assessing the value of emerging pharmacologic treatments.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Cost-Benefit Analysis; State Medicine; Liver Cirrhosis; Disease Progression
PubMed: 34757199
DOI: 10.1016/j.cgh.2021.10.040 -
Journal of Neurology Dec 2022Amyotrophic lateral sclerosis (ALS) is the most common subtype of motor neuron disease (MND). The current gold-standard measure of progression is the ALS Functional... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is the most common subtype of motor neuron disease (MND). The current gold-standard measure of progression is the ALS Functional Rating Scale-Revised (ALS-FRS(R)), a clinician-administered questionnaire providing a composite score on physical functioning. Technology offers a potential alternative for assessing motor progression in both a clinical and research capacity that is more sensitive to detecting smaller changes in function. We reviewed studies evaluating the utility and suitability of these devices to evaluate motor function and disease progression in people with MND (pwMND). We systematically searched Google Scholar, PubMed and EMBASE applying no language or date restrictions. We extracted information on devices used and additional assessments undertaken. Twenty studies, involving 1275 (median 28 and ranging 6-584) pwMND, were included. Sensor type included accelerometers (n = 9), activity monitors (n = 4), smartphone apps (n = 4), gait (n = 3), kinetic sensors (n = 3), electrical impedance myography (n = 1) and dynamometers (n = 2). Seventeen (85%) of studies used the ALS-FRS(R) to evaluate concurrent validity. Participant feedback on device utility was generally positive, where evaluated in 25% of studies. All studies showed initial feasibility, warranting larger longitudinal studies to compare device sensitivity and validity beyond ALS-FRS(R). Risk of bias in the included studies was high, with a large amount of information to determine study quality unclear. Measurement of motor pathology and progression using technology is an emerging, and promising, area of MND research. Further well-powered longitudinal validation studies are needed.
Topics: Humans; Amyotrophic Lateral Sclerosis; Digital Technology; Motor Neuron Disease; Disease Progression
PubMed: 35945397
DOI: 10.1007/s00415-022-11312-7 -
PloS One 2014Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential... (Review)
Review
BACKGROUND
Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true slowing of the neurodegenerative process. A systematic review was undertaken to determine what biomarkers for disease progression in Alzheimer's disease exist and how well they perform.
METHODS
MEDLINE and Embase (1950-2011) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with probable Alzheimer's disease diagnosed by formal criteria were included. We made no restriction on age, disease duration, or drug treatment. We only included studies with a longitudinal design, in which the putative biomarker and clinical measure were both measured at least twice, as this is the only appropriate study design to use when developing a disease progression biomarker. We included studies which attempted to draw associations between the changes over time in the biomarker used to investigate disease progression and a clinical measure of disease progression.
RESULTS
Fifty-nine studies were finally included. The commonest biomarker modality examined was brain MRI (17/59, 29% of included studies). Median follow-up in included studies was only 1.0 (IQR 0.8-1.7) year and most studies only measured the putative biomarker and clinical measure twice. Included studies were generally of poor quality with small numbers of participants (median 31 (IQR 17 to 64)), applied excessively restrictive study entry criteria, had flawed methodologies and conducted overly simplistic statistical analyses without adjusting for confounding factors.
CONCLUSIONS
We found insufficient evidence to recommend the use of any biomarker as an outcome measure for disease progression in Alzheimer's disease trials. However, further investigation into the efficacy of using MRI measurements of ventricular volume and whole brain volume appeared to be merited. A provisional 'roadmap' to improve the quality of future disease progression biomarker studies is presented.
Topics: Alzheimer Disease; Biomarkers; Disease Progression; Humans
PubMed: 24558437
DOI: 10.1371/journal.pone.0088854 -
Pulmonology 2021The COVID-19 pandemic originated in China and within about 4 months affected individuals all over the world. One of the limitations to the management of the COVID-19 is... (Review)
Review
INTRODUCTION
The COVID-19 pandemic originated in China and within about 4 months affected individuals all over the world. One of the limitations to the management of the COVID-19 is the diagnostic imaging to evaluate lung impairment and the patients' clinical evolution, mainly, in more severe cases that require admission into the intensive care unit. Among image examinations, lung ultrasound (LU) might be a useful tool to employ in the treatment of such patients.
METHODS
A survey was carried out on PubMed to locate studies using the descriptors: ((Lung ultrasound OR ultrasound OR lung ultrasonography OR lung US) AND (coronavirus disease-19 OR coronavirus disease OR corona virus OR COVID-19 OR COVID19 OR SARS-CoV-2)). The period covered by the search was November 2019 to October 2020 and the papers selected reported LU in COVID-19.
RESULTS
Forty-three studies were selected to produce this systematic review. The main LU findings referred to the presence of focal, multifocal and/or confluent B lines and the presence of pleural irregularities.
CONCLUSIONS
The use of LU in the evaluation of patients with COVID-19 should be encouraged due to its intrinsic characteristics; a low cost, radiation free, practical method, with easy to sanitize equipment, which facilitates structural evaluation of lung damage caused by SARS-CoV-2. With the increase in the number of studies and the use of ultrasound scans, LU has been shown as a useful tool to evaluate progression, therapeutic response and follow-up of pulmonary disease in the patients with COVID-19.
Topics: COVID-19; COVID-19 Testing; Disease Progression; Humans; Lung; Pandemics; Ultrasonography
PubMed: 33931378
DOI: 10.1016/j.pulmoe.2021.02.004 -
BMC Neurology Apr 2013Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential... (Review)
Review
BACKGROUND
Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist.
METHODS
MEDLINE and EMBASE (1950-2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came.
RESULTS
183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality--cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses.
CONCLUSION
We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.
Topics: Biomarkers; Disease Progression; Humans; Parkinson Disease
PubMed: 23587062
DOI: 10.1186/1471-2377-13-35 -
Respirology (Carlton, Vic.) Feb 2014Dietary intake attracts increasing interest in the risk for and progression of chronic obstructive pulmonary disease (COPD). In particular, dietary fibre and fatty acids... (Review)
Review
Dietary intake attracts increasing interest in the risk for and progression of chronic obstructive pulmonary disease (COPD). In particular, dietary fibre and fatty acids have drawn specific attention for their immunomodulating potential. The study aimed to review the current evidence on the potential roles of dietary fibre or fatty acid intake in the risk and progression of COPD. Pubmed, EMBASE, Cochrane Collaboration Database and conference databases for original studies in adults addressing the association between fibre or fatty acid intake and COPD in terms of risk, lung function and respiratory symptoms were searched. Nine articles were included of which four reported on dietary fibre and five on fatty acids. Data of studies could not be pooled because of methodological diversity. Greater intake of dietary fibre has been consistently associated with reduced COPD risk, better lung function and reduced respiratory symptoms. Results on the associations between fatty acids and COPD are inconsistent. Dietary quality deserves further attention in developing COPD prevention and management programs.
Topics: Dietary Fats; Dietary Fiber; Disease Progression; Humans; Pulmonary Disease, Chronic Obstructive; Risk; Vital Capacity
PubMed: 24372903
DOI: 10.1111/resp.12229 -
BMJ Open Jun 2023Studies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Studies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study was to determine whether PD increased the risk of COPD and COPD-related clinical events.
DESIGN
A systematic review and meta-analysis.
DATA SOURCES
PubMed, Ovid EMBASE and Ovid CENTRAL were searched from inception to 22 February 2023.
ELIGIBILITY CRITERIA FOR STUDIES
We included trials and observational studies evaluating association of PD with the risk of COPD or COPD-related events (exacerbation and mortality), with statistical adjustment for smoking.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently extracted data from selected studies using a standardised Excel file. Quality of studies was evaluated using the Newcastle-Ottawa Scale. OR with 95% CI was pooled in a random-effect model with inverse variance method.
RESULTS
22 observational studies with 51 704 participants were included. Pooled analysis of 18 studies suggested that PD was weakly associated with the risk of COPD (OR: 1.20, 95% CI 1.09 to 1.32). However, in stratified and subgroup analyses, with strict adjustment for smoking, PD no longer related to the risk of COPD (adjusting for smoking intensity: OR: 1.14, 95% CI 0.86 to 1.51; smokers only: OR: 1.46, 95% CI 0.92 to 2.31; never smokers only: OR: 0.93, 95% CI 0.72 to 1.21). Moreover, PD did not increase the risk of COPD-related exacerbation or mortality (OR: 1.18, 95% CI 0.71 to 1.97) in the pooled result of four studies.
CONCLUSIONS
This study demonstrates PD confers no risk for COPD and COPD-related events when strictly adjusted by smoking. Large-scale prospective cohort studies with control of potential confounding factors are warranted to validate the present findings.
Topics: Humans; Disease Progression; Quality of Life; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Periodontal Diseases
PubMed: 37369414
DOI: 10.1136/bmjopen-2022-067432 -
Journal of Clinical Pharmacology May 2022Anti-vascular endothelial growth factor (VEGF) therapy is used to slow the disease progression of neovascular age-related macular degeneration. Due to the treatment... (Meta-Analysis)
Meta-Analysis Review
Anti-vascular endothelial growth factor (VEGF) therapy is used to slow the disease progression of neovascular age-related macular degeneration. Due to the treatment burden of frequent intravitreal injections, anti-VEGFs are often used on treat and extend protocols rather than the labeled frequency. The current goal of anti-VEGF drug development is to minimize treatment burden by reducing the number of intravitreal injections. The purpose of this systemic review and model-based meta-analysis (MBMA) was to (1) perform modeling to describe the disease progression of neovascular age-related macular degeneration in the absence of treatment, as well as in the presence of abicipar, aflibercept, brolucizumab, or ranibizumab intervention; (2) and to simulate virtual head-to-head comparisons among the drugs with an extended dose schedule of once every 12 weeks (Q12). Data sources were PubMed, internal Allergan data, www.clinicaltrials.gov, and www.clinicaltrialsregister.eu. Eligibility assessment was performed by 2 independent review authors. Randomized, controlled trials that had at least 1 arm with an anti-VEGF (aflibercept, abicipar, bevacizumab, brolucizumab, pegaptanib, or ranibizumab), a control arm of placebo or anti-VEGF, a treatment duration of at least 4 months, reported best-corrected visual acuity data, and at least 20 patients were included. A total of 22 trials, consisting of 55 arms, from across 9500+ subjects and 500+ best-corrected visual acuity observations were used to develop the model. Consistent with reported data, results from the model showed that abicipar Q12 underperformed ranibizumab (every 4 weeks), aflibercept (every 4 weeks), and brolucizumab (every 8 weeks/Q12) labeled dosing schedules. However, when all drugs were virtually tested using the extended schedule, abicipar outperformed ranibizumab and aflibercept and produced a similar week 52 change from baseline as brolucizumab. Predicted week 52 changes from baseline were 5.92 ± 1.02, 3.04 ± 1.61, 6.61 ± 0.284, and 3.02 ± 2.35 best-corrected visual acuity letters for abicipar, aflibercept, brolucizumab, and ranibizumab, respectively, using the Q12 schedule. Results demonstrate the feasibility of Q12 dosing with clinically meaningful letter gains for abicipar and brolucizumab. The model developed under this MBMA has utility for exploring different regimens for existing or novel anti-VEGF agents.
Topics: Angiogenesis Inhibitors; Disease Progression; Humans; Infant, Newborn; Intravitreal Injections; Macular Degeneration; Randomized Controlled Trials as Topic; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Treatment Outcome; Visual Acuity
PubMed: 34783362
DOI: 10.1002/jcph.2002