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Cardiology Jul 2024The AIRCARD study is designed to investigate the relationship between long-term exposure to air and noise pollution and cardiovascular disease incidence and mortality....
Statistical Analysis Plan for the AIRCARD Study: Individual Long-term Air and Noise Pollution Exposure and Cardiovascular Disease Incidence and Mortality (AIRCARD): A Prospective Cohort Study Utilizing DANCAVAS and VIVA Screening Trials.
INTRODUCTION
The AIRCARD study is designed to investigate the relationship between long-term exposure to air and noise pollution and cardiovascular disease incidence and mortality. We aim to conduct a robust prospective cohort analysis assessing the cumulative and differential impacts of air and noise pollution exposure on cardiovascular disease and mortality. This study will adjust for relevant confounders, including traditional cardiovascular risk factors, socioeconomic indicators, and lipid-lowering agents.
METHODS
This prospective cohort study will include 27,022 male participants aged 65-74, recruited from the two large Danish DANCAVAS and VIVA trials, both population-based randomized, multicentered, clinically controlled studies. We will assess long-term exposure to air pollutants using the state-of-the-art DEHM/UBM/AirGIS modelling system and noise pollution through the Nord2000 and SoundPLAN models, covering data from 1979 to 2019. This statistical analysis plan is strictly formulated to predefine the analytical approach for all outcomes and key study variables before data access. The primary analysis will utilize Cox proportional hazards models, adjusted for confounders identified in our cohort (age, body mass index, hypertension, diabetes, smoking status, family history of heart disease, socioeconomic factors, and lipid-lowering agents). This statistical analysis plan further includes Spearman rank correlation to explore inter-pollutant associations.
CONCLUSION
The AIRCARD study addresses global concerns about the impact of air and noise pollution on cardiovascular disease. This research is important for understanding how the pollutants contribute to cardiovascular disease. We aim to provide insights into this area, emphasizing the need for public health measures to mitigate pollution exposure. Our goal is to provide policymakers and healthcare professionals with information on the role of environmental factors in cardiovascular health that could influence global strategies to reduce the cardiovascular disease burden associated with pollution. The design of this SAP ensures transparency and.
PubMed: 38952116
DOI: 10.1159/000539459 -
Parasites & Vectors Jul 2024Application of numerous malaria control interventions has led to reduction in clinical malaria cases and deaths but also the realisation that asymptomatic parasite...
BACKGROUND
Application of numerous malaria control interventions has led to reduction in clinical malaria cases and deaths but also the realisation that asymptomatic parasite carriers play a key role in sustaining transmission. This study assessed the effectiveness of using the Ultra-sensitive NxTek eliminate RDT (uRDT) and conventional SD Bioline HRP2 RDT (cRDT) in diagnosing asymptomatic parasitaemia while measuring the impact of mass testing, treatment and tracking (MTTT) on the prevalence of asymptomatic malaria over a 1-year period in Ghana.
METHODS
A total of 4000 targeted participants from two towns, Obom and Kofi Kwei, with their surrounding villages, were tested for asymptomatic malaria four times over the study period using uRDT (intervention) and the cRDT (control) respectively. Participants carrying malaria parasites were followed by home visit and phone calls for compliance to treatment, and filter paper blood blots collected from participants were used to determine true parasite carriage by PET-PCR. A mathematical model of the study site was developed and used to test the impact of test sensitivity and mass migration on the effect of MTTT.
RESULTS
The start and end point sensitivities of the cRDT were 48.8% and 41.7% and those for the uRDT were 52.9% and 59.9% respectively. After a year of MTTTs, asymptomatic parasite prevalence, as determined by PCR, did not differ statistically in the control site (40.6% to 40.1%, P = 0.730) but decreased at the intervention site (55.9% to 46.4%, P < 0.0001). Parasite prevalence by RDT, however, indicated statistical reduction in the control site (25.3% to 22.3%, P = 0.017) and no change in the intervention site (35.1% to 36.0%, P = 0.614). The model predicted a mild effect of both diagnostic sensitivity and human movement in diminishing the impact of MTTT in the study sites.
CONCLUSIONS
Asymptomatic parasite prevalence at the molecular level reduced significantly in the site where the uRDT was used but not where the cRDT was used. Overall, the uRDT exhibited higher sensitivity relative to the cRDT. Highly sensitive molecular techniques such as PET-PCR should be included in parasite prevalence estimation during MTTT exercises.
Topics: Ghana; Humans; Female; Male; Sensitivity and Specificity; Adult; Adolescent; Child, Preschool; Young Adult; Child; Diagnostic Tests, Routine; Parasitemia; Malaria, Falciparum; Middle Aged; Malaria; Plasmodium falciparum; Prevalence; Mass Screening; Infant
PubMed: 38951912
DOI: 10.1186/s13071-024-06354-x -
Journal of Cancer Research and Clinical... Jul 2024To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue.
BACKGROUND
Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC.
METHODS
Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC.
RESULTS
A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group.
CONCLUSION
Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.
Topics: Humans; Metabolomics; Esophageal Neoplasms; Stomach Neoplasms; Biomarkers, Tumor; Gastrointestinal Neoplasms; Metabolome; Case-Control Studies; Esophagogastric Junction
PubMed: 38951269
DOI: 10.1007/s00432-024-05857-5 -
Archives of Toxicology Jun 2024Natural toxins produced by Alternaria fungi include the mycotoxins alternariol, tenuazonic acid and altertoxins I and II. Several of these toxins have shown high...
Natural toxins produced by Alternaria fungi include the mycotoxins alternariol, tenuazonic acid and altertoxins I and II. Several of these toxins have shown high toxicity even at low levels including genotoxic, mutagenic, and estrogenic effects. However, the metabolic effects of toxin exposure from Alternaria are understudied, especially in the liver as a key target. To gain insight into the impact of Alternaria toxin exposure on the liver metabolome, rats (n = 21) were exposed to either (1) a complex culture extract with defined toxin profiles from Alternaria alternata (50 mg/kg body weight), (2) the isolated, highly genotoxic altertoxin-II (ATX-II) (0.7 mg/kg of body weight) or (3) a solvent control. The complex mixture contained a spectrum of Alternaria toxins including a controlled dose of ATX-II, matching the concentration of the isolated ATX-II. Liver samples were collected after 24 h and analyzed via liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Authentic reference standards (> 100) were used to identify endogenous metabolites and exogenous compounds from the administered exposures in tandem with SWATH-acquired MS/MS data which was used for non-targeted analysis/screening. Screening for metabolites produced by Alternaria revealed several compounds solely isolated in the liver of rats exposed to the complex culture, confirming results from a previously performed targeted biomonitoring study. This included the altersetin and altercrasin A that were tentatively identified. An untargeted metabolomics analysis found upregulation of acylcarnitines in rats receiving the complex Alternaria extract as well as downregulation of riboflavin in rats exposed to both ATX-II and the complex mixture. Taken together, this work provides a mechanistic view of Alternari toxin exposure and new suspect screening insights into hardly characterized Alternaria toxins.
PubMed: 38951189
DOI: 10.1007/s00204-024-03810-6 -
Journal of Cardiovascular Computed... 2024
Topics: Humans; Cardiovascular Diseases; Risk Assessment; Predictive Value of Tests; Mass Screening; Prognosis; Heart Disease Risk Factors; Risk Factors
PubMed: 38950936
DOI: 10.1016/j.jcct.2024.06.008 -
Acta Medica Portuguesa Jul 2024
Topics: Humans; Portugal; Sexually Transmitted Diseases; Male; Adolescent; Female; Young Adult
PubMed: 38950622
DOI: 10.20344/amp.21479 -
Oral Diseases Jul 2024To describe the epidemiological status of oral cancer (OC) in India along with updates on risk factors, advances and gaps in preventive measures, treatment, costs of... (Review)
Review
OBJECTIVES
To describe the epidemiological status of oral cancer (OC) in India along with updates on risk factors, advances and gaps in preventive measures, treatment, costs of care and monitoring.
METHODS
Two national estimates of incidence and mortality were cited, one for 2016 by the Global Burden of Disease India Study and one based on projections for 2020 by GLOBOCAN. The National Cancer Registry Project provided local and regional incidence and trends using data from 2012-2016. Scientific literature, reports of the NCRP, the IARC and government press releases were also consulted.
RESULTS
Tobacco and areca nut habits are the major risk factors for OC in India. In the 1980s, intervention studies on oral screening, awareness generation and habit cessation in rural areas reduced tobacco use and oral leukoplakia. Lately, adoption of the tobacco control law and mass media communications have resulted in decreased tobacco use. However, the increasing popularity of highly carcinogenic tobacco products containing areca nut, with evasion of their bans, is increasing OC incidence.
CONCLUSION
Despite advances in care, there is growing incidence of OC, persisting poor awareness about the need to quit tobacco/areca nut/alcohol use and go for screening. Major efforts are needed to implement preventive activities.
PubMed: 38950053
DOI: 10.1111/odi.14974 -
PloS One 2024The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal...
Acceptability of adding a non-contrast abdominal CT scan to screen for kidney cancer and other abdominal pathology within a community-based CT screening programme for lung cancer: A qualitative study.
OBJECTIVES
The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal malignancies to community-based CT screening for lung cancer within the Yorkshire Lung Screening Trial (YLST). This study explored the acceptability of the combined screening approach to participants and healthcare professionals (HCPs) involved in the trial.
METHODS
We conducted semi-structured interviews with eight HCPs and 25 participants returning for the second round of scanning within YLST, 20 who had taken up the offer of the additional abdominal CT scan and five who had declined. Transcripts were analysed using thematic analysis, guided by the Theoretical Framework of Acceptability.
RESULTS
Overall, combining the offer of a non-contrast abdominal CT scan alongside the low-dose thoracic CT was considered acceptable to participants, including those who had declined the abdominal scan. The offer of the additional scan made sense and fitted well within the process, and participants could see benefits in terms of efficiency, cost and convenience both for themselves as individuals and also more widely for the NHS. Almost all participants made an instant decision at the point of initial invitation based more on trust and emotions than the information provided. Despite this, there was a clear desire for more time to decide whether to accept the scan or not. HCPs also raised concerns about the burden on the study team and wider healthcare system arising from additional workload both within the screening process and downstream following findings on the abdominal CT scan.
CONCLUSIONS
Adding a non-contrast abdominal CT scan to community-based CT screening for lung cancer is acceptable to both participants and healthcare professionals. Giving potential participants prior notice and having clear pathways for downstream management of findings will be important if it is to be offered more widely.
Topics: Humans; Tomography, X-Ray Computed; Lung Neoplasms; Male; Female; Middle Aged; Early Detection of Cancer; Aged; Kidney Neoplasms; Qualitative Research; Patient Acceptance of Health Care; Mass Screening
PubMed: 38950010
DOI: 10.1371/journal.pone.0300313 -
Analytical and Bioanalytical Chemistry Jun 202417α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is...
Development and evaluation of a candidate reference measurement procedure for detecting 17α-hydroxyprogesterone in dried blood spots using isotope dilution liquid chromatography tandem mass spectrometry.
17α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is challenging due to its low physiological concentration. The high false-positive rates of immunoassays necessitate the development of more accurate methods. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers increased specificity and sensitivity, yet standardized procedures for 17α-OHP measurement are required for clinical application. A candidate reference measurement procedure (cRMP) using isotope dilution LC-MS/MS was developed for 17α-OHP quantification in DBS. By utilizing stable isotope-labeled D8-17α-OHP as an internal standard, the cRMP was optimized, covering sample preparation, calibration, and LC-MS/MS analysis. The method performance was validated across several parameters, including precision, accuracy, specificity, detection limits, and matrix effects. Clinical applicability was further assessed through the establishment of reference intervals for healthy newborns. The developed cRMP exhibited a linear range of 1.00 to 80.00 ng/mL for 17α-OHP, with detection and quantification limits of 0.14 ng/mL and 0.52 ng/mL, respectively. Inter- and intraday precision demonstrated coefficients of variation within 1.27 to 5.69%. The recovery rates and matrix effects were well within acceptable limits, ensuring method reliability. Clinical application showed distinct reference intervals for healthy newborns that were unaffected by sex but influenced by weight and gestational age. This method significantly enhances CAH diagnostic accuracy in newborns, providing a valuable tool for clinical laboratories and improving newborn screening program standardization and traceability.
PubMed: 38949681
DOI: 10.1007/s00216-024-05411-9 -
Curationis Jun 2024In South Africa, screening for tuberculosis during pregnancy is a serious challenge. Tuberculosis is one of the leading indirect causes of mortality in pregnant women.
BACKGROUND
In South Africa, screening for tuberculosis during pregnancy is a serious challenge. Tuberculosis is one of the leading indirect causes of mortality in pregnant women.
OBJECTIVES
The objective of the study was to explore the challenges experienced by midwives regarding tuberculosis in pregnant women.
METHOD
A qualitative exploratory research method was used to conduct the study. The study population comprised midwives who worked at primary healthcare clinics in the selected local area, Capricorn District, Limpopo province. Purposive non-probability sampling was used to select 10 participants. Data from participants were acquired using in-depth individual semi-structured interviews. Data analysis was carried out using manual thematic analysis following Tesch's technique.
RESULTS
The outcomes of this study included midwives knowing their roles regarding tuberculosis screening among pregnant women. They further highlighted their challenges while screening tuberculosis in pregnant women, such as shortage of screening tools, withholding of tuberculosis information, and language barrier.
CONCLUSION
Midwives should have the necessary equipment and be trained in various languages used in the province to improve tuberculosis screening among all pregnant women.Contribution: Infected pregnant women and their unborn children's health can be improved by tuberculosis screening.
Topics: Humans; South Africa; Female; Pregnancy; Mass Screening; Midwifery; Qualitative Research; Tuberculosis; Adult; Interviews as Topic
PubMed: 38949423
DOI: 10.4102/curationis.v47i1.2533