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Journal of Cachexia, Sarcopenia and... Jun 2024Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate... (Review)
Review
Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2023) was completed. Eligible trials met the following criteria: adults (≥18 years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants = 6522) included biomarkers as endpoints. Most studies (n = 29, 55.7%) included a variety of cancer types. Pharmacological interventions (n = 27, 51.9%) were most evaluated, followed by nutritional interventions (n = 20, 38.4%). Ninety-nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n = 29, 55.8%) was assessed most often, followed by C-reactive protein (n = 22, 42.3%), interleukin-6 (n = 16, 30.8%) and tumour necrosis factor-α (n = 14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor 1 (IGF-1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP-3, IGF-1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.
Topics: Cachexia; Humans; Neoplasms; Biomarkers; Clinical Trials as Topic
PubMed: 38783477
DOI: 10.1002/jcsm.13491 -
Heart, Lung & Circulation Nov 2023We aimed to systematically compare literature on prevalence of modifiable and non-modifiable risk factors for early compared to late-onset coronary heart disease (CHD). (Meta-Analysis)
Meta-Analysis Review
AIM
We aimed to systematically compare literature on prevalence of modifiable and non-modifiable risk factors for early compared to late-onset coronary heart disease (CHD).
METHODS
PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol registered in PROSPERO CRD42020173216). Study quality was assessed using the National Heart, Lung and Blood Institute tool for observational and case-control studies. Review Manager 5.3 was used for meta-analysis. Effect sizes were expressed as odds ratio (OR) and mean differences (MD)/standardised MD (SMD) with 95% confidence intervals (CI) for categorical and continuous variables.
RESULTS
Individuals presenting with early-onset CHD (age <65 years) compared to late-onset CHD had higher mean body mass index (MD 1.07 kg/m; 95% CI 0.31-1.83), total cholesterol (SMD 0.43; 95% CI 0.23-0.62), low-density lipoprotein (SMD 0.26; 95% CI 0.15-0.36) and triglycerides (SMD 0.50; 95% CI 0.22-0.68) with lower high-density lipoprotein-cholesterol (SMD 0.26; 95% CI -0.42--0.11). They were more likely to be smokers (OR 1.76, 95% CI 1.39-2.22) and have a positive family history of CHD (OR 2.08, 95% CI 1.74-2.48). They had lower mean systolic blood pressure (MD 4.07 mmHg; 95% CI -7.36--0.78) and were less likely to have hypertension (OR 0.47, 95% CI 0.39-0.57), diabetes mellitus (OR 0.56, 95% CI 0.51-0.61) or stroke (OR 0.31, 95% CI 0.24-0.42).
CONCLUSION
A focus on weight management and smoking cessation and aggressive management of dyslipidaemia in young adults may reduce the risk of early-onset CHD.
Topics: Humans; Aged; Coronary Disease; Risk Factors; Hypertension; Smoking Cessation; Cholesterol
PubMed: 37777398
DOI: 10.1016/j.hlc.2023.07.010 -
Journal of Cachexia, Sarcopenia and... Jun 2024Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary... (Review)
Review
Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.
Topics: Humans; Cachexia; Neoplasms; Body Composition; Body Weight; Clinical Trials as Topic
PubMed: 38738581
DOI: 10.1002/jcsm.13478 -
Frontiers in Medicine 2023Obesity is a chronic medical condition that affects, among others, the cardiovascular and respiratory systems. Interventions for its treatment focus on sustained weight...
INTRODUCTION
Obesity is a chronic medical condition that affects, among others, the cardiovascular and respiratory systems. Interventions for its treatment focus on sustained weight reduction and general health improvement, leaving respiratory management aside. Our objective was to determine the effects of inspiratory muscle training (IMT) in patients with obesity.
METHODS
A systematic review was performed in Embase, Cochrane Library (CENTRAL), CINAHL, Web of Science, and PubMed/MEDLINE on June 26, 2023. Randomized clinical trials (RCTs), and quasi-randomized clinical trials investigating the effects of IMT in people with obesity were included. Selected studies were screened by two independent reviewers who extracted data and assessed the quality of the evidence.
RESULTS
The initial search returned 705 potential studies were included. Ultimately, eight studies met the criteria for eligibility and were included in the review. IMT improves physical capacity [6-minute walk test (6MWT): 44.5 m, 95% CI: 30.5 to 58.5; < 0.0001] and the strength of the inspiratory muscles [maximal inspiratory pressure (MIP): -28.4 cm HO, 95% CI: -41.9 to -14.8; < 0.0001] compared to the controls, without differences in the pulmonary function, body mass index (BMI) and metabolic parameters.
CONCLUSION
Inspiratory muscle training improves physical capacity and inspiratory muscle strength without significant changes in lung function, BMI, and metabolic parameters. PROSPERO, identifier CRD42023439625, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439625.
PubMed: 38089877
DOI: 10.3389/fmed.2023.1284689 -
Nutrients Jun 2024The purpose of our systematic review was to examine the effects of any physical activity/exercise intervention combined with any diet/nutrition intervention on any... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of our systematic review was to examine the effects of any physical activity/exercise intervention combined with any diet/nutrition intervention on any biological/biochemical index, quality of life (QoL), and depression in breast, lung, colon and rectum, prostate, stomach, and liver cancer patients and/or cancer survivors.
METHODS
A systematic review and meta-analysis were undertaken, using PRISMA guidelines and the Cochrane Handbook. The systematic review protocol can be found in the PROSPERO database; registration number: CRD42023481429.
RESULTS
We found moderate-quality evidence that a combined intervention of physical activity/exercise and nutrition/diet reduced body mass index, body weight, fat mass, insulin, homeostatic model assessment for insulin resistance, C-reactive protein, triglycerides, and depression, while it increased high-density lipoprotein, the physical component of QoL, and general functional assessment of cancer therapy.
CONCLUSIONS
We conclude that a combined intervention of physical activity/exercise and diet/nutrition may decrease body weight, fat mass, insulin levels, and inflammation, and improve lipidemic profile, the physical component of QoL, and depression in cancer patients and survivors. These outcomes indicate a lower risk for carcinogenesis; however, their applicability depends on the heterogeneity of the population and interventions, as well as the potential medical treatment of cancer patients and survivors.
Topics: Humans; Neoplasms; Exercise; Quality of Life; Cancer Survivors; Diet; Depression; Male; Body Mass Index; Female
PubMed: 38892682
DOI: 10.3390/nu16111749 -
Journal of Critical Care Oct 2023The optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19.
MATERIALS AND METHODS
We conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered.
RESULTS
Out of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90-1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61-1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21-0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08-2.53).
CONCLUSION
This systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.
Topics: Humans; Heparin; Heparin, Low-Molecular-Weight; Critical Illness; COVID-19; Neoplasms; Randomized Controlled Trials as Topic; Anticoagulants; Hemorrhage; Venous Thromboembolism
PubMed: 37244209
DOI: 10.1016/j.jcrc.2023.154344 -
Zeitschrift Fur Rheumatologie Mar 2024Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major driver of premature mortality in patients with rheumatoid arthritis (RA). Detection of... (Review)
Review
OBJECTIVE
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major driver of premature mortality in patients with rheumatoid arthritis (RA). Detection of RA-ILD is crucial but requires awareness among the treating physicians. To date, however, there is no international recommendation concerning screening for ILD in RA patients.
METHODS
After a systematic literature review, the modified Delphi technique in combination with the nominal group technique was used to provide a Delphi consensus statement elaborated by an expert panel of pneumonologists, rheumatologists, and a radiologist. Based on the available evidence, several clusters of questions were defined and discussed until consent was reached.
RESULTS
A screening algorithm for ILD in patients with RA based on clinical signs, respiratory symptoms, and risk factors has been developed. Further, the recommendations address diagnostic tools for RA-ILD and the follow-up of RA patients qualifying for ILD screening.
Topics: Humans; Arthritis, Rheumatoid; Lung Diseases, Interstitial; Risk Factors
PubMed: 38240817
DOI: 10.1007/s00393-023-01464-w -
Brain & Spine 2023To date, the available guidance on venous thromboembolism (VTE) prevention in elective lumbar fusion surgery is largely open to surgeon interpretation and preference... (Review)
Review
INTRODUCTION
To date, the available guidance on venous thromboembolism (VTE) prevention in elective lumbar fusion surgery is largely open to surgeon interpretation and preference without any specific suggested chemoprophylactic regimen.
RESEARCH QUESTION
This study aimed to comparatively analyze the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) with the use of commonly employed chemoprophylactic agents such as unfractionated heparin (UH) and low molecular weight heparin (LMWH) in lumbar fusion surgery.
MATERIAL AND METHODS
An independent systematic review of four scientific databases (PubMed, Scopus, clinicaltrials.gov, Web of Science) was performed to identify relevant articles as per the preferred reporting in systematic reviews and meta-analysis (PRISMA) guidelines. Studies reporting on DVT/PE outcomes of lumbar fusion surgery in adult patients with UH or LMWH chemoprophylaxis were included for analysis. Analysis was performed using the Stata software.
RESULTS
Twelve studies with 8495 patients were included in the analysis. A single-arm meta-analysis of the included studies found a DVT incidence of 14% (95%CI [8%-20%]) and 1% (95%CI [-6% - 8%]) with LMWH and UH respectively. Both the chemoprophylaxis agents prevented PE with a noted incidence of 0% (95%CI [0%-0.1%]) and 0% (95%CI [0%-1%]) with LMWH and UH respectively. The risk of bleeding-related complications with the usage of LMWH and UH was 0% (95% CI [0.0%-0.30%]) and 3% (95% CI [0.3%-5%]) respectively.
DISCUSSION AND CONCLUSION
Both LMWH and UH reduces the overall incidence of DVT/PE, but there is a paucity of evidence analyzing the comparative effectiveness of the chemoprophylaxis regimens in lumbar fusion procedures. The heterogeneity in data prevents any conclusions, as there remains an evidence gap. We recommend future high-quality randomized controlled trials to investigate in this regard to help develop recommendations on thromboprophylaxis usage.
PubMed: 38021015
DOI: 10.1016/j.bas.2023.102711 -
Clinical Microbiology and Infection :... Nov 2023Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI).
OBJECTIVES
To assess the risk of progression to active TB for indeterminate interferon-γ release assays (IGRA) results in immunocompromised individuals during screening for LTBI.
DATA SOURCES
PubMed, Embase, Web of Science, and the Cochrane Library were searched without start date or language restrictions on 18 April 2023.
STUDY ELIGIBILITY CRITERIA
Cohort study or randomized controlled trials that investigated the risk of progression to active TB for indeterminate IGRA during LTBI screening.
PARTICIPANTS
Immunocompromised individuals. TEST: IGRA (T-SPOT.TB and QuantiFERON).
REFERENCE STANDARD
None.
ASSESSMENT OF RISK OF BIAS
A modified version of the Newcastle-Ottawa Scale.
METHODS OF DATA SYNTHESIS
Fixed effects meta-analysis was used to obtain two pooled risk ratios (RRs). RR-ip represented disease progression rate in untreated individuals with indeterminate IGRA versus positive IGRA. RR-in represented disease progression rate in untreated individuals with indeterminate IGRA versus negative IGRA.
RESULTS
Among the 5102 identified studies, 28 (14 792 immunocompromised individuals) were included. The pooled RR-ip and RR-in for cumulative incidence were 0.51 (95% CI, 0.32-0.82; I = 0%) and 2.94 (95% CI, 1.78-4.85; I = 0%), respectively. In addition, 11 studies reporting person-year data were included to verify the reliability of cumulative incidence results. The pooled RR-ip and RR-in for person-year incidence were 0.40 (95% CI, 0.19-0.82; I = 13%) and 2.67 (95% CI, 1.24-5.79; I = 23%), respectively.
DISCUSSION
Indeterminate IGRA results in immunocompromised individuals may represent an intermediate risk of progression to active TB, with half the risk for positive results and three times for negative results. Proper follow-up and management of patients with indeterminate results are crucial for mitigating progression risk and improving patient outcomes.
Topics: Humans; Immunocompromised Host; Interferon-gamma Release Tests; Disease Progression; Latent Tuberculosis; Tuberculosis; Mass Screening
PubMed: 37422080
DOI: 10.1016/j.cmi.2023.07.003 -
Cureus Feb 2024The aim of this meta-analysis was to scrutinize the prevalence, characteristics, and outcomes of obstructive sleep apnea (OSA) in individuals with ideopathic pulmonary... (Review)
Review
The aim of this meta-analysis was to scrutinize the prevalence, characteristics, and outcomes of obstructive sleep apnea (OSA) in individuals with ideopathic pulmonary fibrosis (IPF). We carried out this systematic review and meta-analysis in accordance with the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement (PRISMA). Two independent researchers systematically searched major databases, including MEDLINE/PubMed, EMBASE, and the Cochrane Library, from January 1, 2000, until December 31, 2023. We included all studies involving adult patients (age >18 years) with IPF that assessed the prevalence and characteristics of OSA in IPF patients. A total of seven studies involving a pooled sample of 411 patients were included in this meta-analysis. The pooled prevalence of OSA among individuals with IPF was found to be 70% (95% CI: 59 to 82%). Individuals with OSA exhibited a significantly higher mean body mass index (BMI) compared to their counterparts. While individuals with both IPF and OSA exhibited higher scores on the Epworth Sleepiness Scale (ESS) compared to those with IPF alone, the OSA group also showed lower oxygen saturation during sleep in comparison to non-OSA patients. In summary, OSA is a prevalent coexisting condition among individuals with IPF. This presence could worsen the nighttime oxygen saturation. Consequently, there is a need for more extensive studies involving more uniform participant groups.
PubMed: 38516439
DOI: 10.7759/cureus.54562