1,721,016 research outputs found
Associations of per- and polyfluoroalkyl substances, polychlorinated biphenyl, organochlorine pesticides, and polybrominated diphenyl ethers with oxidative stress markers: a systematic review and meta-analysis
No full textBackgroundPer- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are intentionally produced persistent organic pollutants (POPs) that are resistant to environmental degradation. Previous in-vitro and in-vivo studies have shown that POPs can induce oxidative stress, which is linked to neurodegenerative diseases, cardiovascular diseases, and cancer. However, findings in epidemiological studies are inconsistent and an evidence synthesis study is lacking to summarize the existing literature and explore research gaps.ObjectiveWe evaluated the effects of PFAS, PCBs, OCPs, and PBDEs, on oxidative stress biomarkers in epidemiological studies.MethodsA literature search was conducted in PubMed, Embase, and Cochrane CENTRAL to identify all published studies related to POPs and oxidative stress up to December 7th, 2022. We included human observational studies reporting at least one exposure to POPs and an oxidative stress biomarker of interest. Random-effects meta-analyses on standardized regression coefficients and effect direction plots with one-tailed sign tests were used for quantitative synthesis.ResultsWe identified 33 studies on OCPs, 35 on PCBs, 49 on PFAS, and 12 on PBDEs. Meta-analyses revealed significant positive associations of α-HCH with protein carbonyls (0.035 [0.017, 0.054]) and of 4′4-DDE with malondialdehyde (0.121 [0.056, 0.187]), as well as a significant negative association between 2′4-DDE and total antioxidant capacity (TAC) (-0.042 [-0.079, -0.004]), all β [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (pone-tailed = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (pone-tailed = 0.02) and paraoxonase-1 (pone-tailed = 0.03). However, there were inconsistent associations of OCPs with superoxide dismutase, glutathione peroxidase, and catalase.ConclusionsHigher levels of OCPs were associated with increased levels of oxidative stress through increased pro-oxidant biomarkers involving protein oxidation, DNA damage, and lipid peroxidation, as well as decreased TAC. These findings have the potential to reveal the underlying mechanisms of POPs toxicity
Trends of poisoning types in Sri Lanka: descriptive analysis of hospital admissions data 2004–2019
No full textBackgroundSri Lanka introduced national bans restricting access to highly hazardous pesticides (HHPs) in 2008-11, and in 2013-16. An immediate drop in pesticide poisoning cases was observed after the introduction of the first ban, but there was a simultaneous rise in hospital admissions due to drugs, medicines and biological substances. However, the long-term trends in hospital admissions and deaths due to poisoning in Sri Lanka have not been investigated. We aimed to determine whether there have been changes in types of poisoning presenting to hospitals and their associated case fatality (CF) following two distinct periods of implementation of national bans of HHPs in Sri Lanka.MethodsWe conducted a retrospective observational study using routinely collected national-level hospital admissions data from Sri Lanka between 2004 and 2019 to examine trends in hospital admissions, deaths, and CF of different poisoning types. We included the following types: drugs, medicines and biological substances; pesticides; and non-medicinal products; and an additional group for other external causes. We calculated type-specific number of in-hospital cases and deaths per 100,000 population and annual CF, stratified by sex and age group.ResultsWe found a reduction in hospital admission cases from both pesticide poisoning (58.5% between 2012 and 2017) and drugs, medicine, and biological substances following the implementation of the first HHPs bans in 2011. There was an increase in hospital admissions due to non-medicinal products and other external causes, but this did not translate into an increase in hospital deaths or CF. We observed a sharp decrease in CF due to pesticide poisoning following the first ban (50% between 2008 and 2012), with no concurrent rise in CF due to other types of poisoning and non-poisoning substances, which remained low throughout the study period.ConclusionsThe implementation of national bans of HHPs led to a reduction in number of admissions as well as CF due to pesticide poisoning in hospitals in Sri Lanka, with no evidence of substitution to other types of poisonings. The reversal of the upward trend in hospital admissions due to pesticide and medicinal poisonings suggests that the bans contributed to a reduction in admissions from these types of poisoning
Applications of mixture methods in epidemiological studies investigating the health impact of persistent organic pollutants exposures: a scoping review
No full textBackground: Persistent organic pollutants (POPs) are environmental chemicals characterized by long half-lives in nature and human bodies, posing significant health risks. The concept of the exposome, encompassing all lifetime environmental exposures, underscores the importance of studying POP as mixtures rather than in isolation. The increasing body of evidence on the health impacts of POP mixtures necessitates the proper application of statistical methods. Objectives: We aimed to summarize studies on the overall effects of POP mixtures, identify patterns in applications of mixture methods—statistical methods for investigating the association of mixtures—and highlight current challenges in synthesizing epidemiologic evidence of POP mixtures on health effects as illustrated through a case study. Methods: We conducted a systematic literature search on PubMed and Embase for epidemiological studies published between January 2011 and April 2023. Results: We included 240 studies that met our eligibility criteria. 126 studies focused on per- and polyfluoroalkyl substances (PFAS) mixtures only, while 40 analyzed three or more classes of POPs in mixture analyses. We identified 23 unique mixture methods used to estimate the overall effects of POP mixtures, with Bayesian Kernel Machine Regression (BKMR), a type of response-surface modeling, being the most common. Additionally, 22.9% of studies used a combination of methods, including response-surface modeling, index modeling, dimension reduction, and latent variable models. The most extensively explored health outcome category was body weight and birth sizes (n = 43), and neurological outcomes (n = 41). In the case study of PFAS mixtures and birth weight, 12 studies showed negative associations, while 4 showed null results, and 2 showed positive associations. Impact Statement: This scoping review consolidates the existing literature on the overall effects of POP mixtures using statistical methods. By providing a comprehensive overview, our study illuminates the present landscape of knowledge in this field and underscores the methodological hurdles prevalent in epidemiological studies focused on POP mixtures. Through this analysis, we aim to steer future research directions, fostering a more nuanced comprehension of the intricate dynamics involved in assessing the health effects of POP mixtures. Our work stands as a significant contribution to the ongoing exploration of the chemical exposome.</p
Delivering health care for patients with primary ciliary dyskinesia: diagnosis and life-long care
No full textPrimary ciliary dyskinesia (PCD) is a rare genetic disease that affects the function of cilia lining the upper and lower respiratory airways. High-speed video microscopy analysis (HSVA) is the only clinically available diagnostic test to assess ciliary function; however, European and North American diagnostic guidelines could not recommend its use as a confirmatory test due to insufficient evidence. The inability of cilia to beat in a coordinated manner can lead to varying degrees of progressive lung disease, recurrent otitis media with hearing loss and chronic rhinosinusitis. Disease expression is likely linked to genotype, with some genes responsible for a more severe phenotype. There is a lack of disease-specific validated clinical outcome measures to monitor disease progression and for use in clinical trials and prospective cohorts. Furthermore, service delivery models vary from country to country, yet there have been no comparisons on the effect of these differences in delivery of care for patients with PCD.Objectives: This work sets out to examine different aspects of diagnosis and management of PCD patients by determining: a) the accuracy and reliability of HSVA to diagnose PCD, b) genotype-phenotype associations, c) appropriate clinical outcome measures to monitor disease progression and for use in research, and d) differences in service delivery that could affect disease outcomes.Methods: We calculated the sensitivity, specificity, inter- and intra-observer reliability of HSVA to diagnose PCD compared to both European diagnostic guidelines and the multidisciplinary team clinical decisions (a). In order to investigate genotype-phenotype associations, we collected diagnostic, clinical and genetic data from three countries. We then applied a novel data-driven clustering method (i.e. topological data analysis) to generate models that would highlight underlying patterns in the phenotypic data and guide the selection of two genes for standard hypothesis testing (b). We conducted a scoping review in order to identify clinical outcome measures that have been used in PCD research and to recommend the use of a set of outcomes in future longitudinal studies (c). Finally, we performed interviews with PCD experts from various countries to develop a survey that would quantify similarities and differences between service delivery models. These were compared to results from a survey conducted ten years ago (d).Results: We found that HSVA was both sensitive and specific to diagnose PCD, with high inter- and intra-observer agreement when performed by experienced scientists (a). This was the first powered and blinded study to assess HSVA in isolation compared to the current evidence-based European diagnostic guidelines.Our topological models revealed a cluster of patients with mutations on the CCDC39 gene that had more severe respiratory phenotype, with statistically significantly lower FEV1 z-scores at diagnosis and higher proportion of history of neonatal respiratory distress (b). We also found a cluster of patients with DNAH11 mutations that had statistically significant milder respiratory phenotype. This was the first large scale multi-centred European study to investigate phenotype-genotype associations in PCD across multiple diagnostic and clinical parameters, using a novel data-driven approach.The scoping review identified a variety of clinical outcome measures that have been used in PCD research, with significant differences in measurement and reporting of outcomes between studies (c). It also highlighted the lack of standardisation in selection, definition and application of outcomes across studies. We recommended using disease-specific validated outcome measures such as QOL-PCD in future randomised controlled trials in order to generate comparable results.Comparisons between service delivery models revealed that diagnostic testing for PCD has become more standardised and centralised compared to ten years ago (d). However, management still varies considerably depending on geographical region and size of the PCD centre, with larger centres prioritising therapies that have been shown to be effective in PCD such as airway clearance and nasal rinsing.Discussion: The findings from these studies provide evidence to improve the delivery of health care for patients with PCD. We showed that HSVA can play an important part in the diagnostic pathway. Our genotype-phenotype association study provided evidence for early and more aggressive intervention in patients with specific genetic mutations. The adoption of a core set of clinical outcome measures will generate the evidence needed for the development of management guidelines, the importance of which were highlighted when comparing service delivery models between countries
Exposure to 4,4’-DDE in visceral adipose tissue and weight loss in adolescents from the Teen-LABS cohort
No full textObjective: dichlorodiphenyldichloroethylene (DDE), an obesogen accumulating in adipose tissue, is released into circulation with weight loss, although its impact is underexplored among adolescents. We tested the association using an integrative translational approach of epidemiological analysis among adolescents with obesity and in vitro measures exploring the impact of DDE on adipogenesis via preadipocytes.Methods: we included 63 participants from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. We assessed 4,4′-DDE in visceral adipose tissue at surgery and BMI and waist circumference at surgery and 0.5, 1, 3, and 5 years after. We conducted longitudinal analysis to estimate the interaction on weight loss between DDE and time since surgery. In vitro analysis quantified adipogenic differentiation in commercial human preadipocytes exposed to 4,4′-DDE via fluorescent staining and imaging.Results: a dose–response relationship was observed, with the low-exposure group having a greater reduction in BMI during the first year compared to higher-exposure groups and showing smaller regains compared to higher-exposure groups after the first year. In vitro analysis of preadipocytes treated with 4,4′-DDE during adipogenic differentiation for 12 days showed a concentration-dependent increase in lipid accumulation.Conclusions: DDE could contribute to weight trajectory among adolescents undergoing bariatric surgery, potentially mediated via promoted adipogenesis in preadipocytes
Clinical care for primary ciliary dyskinesia: current challenges and future directions
No full textPrimary ciliary dyskinesia (PCD) is a rare genetic disease that affects the motility of cilia, leading to impaired mucociliary clearance. It is estimated that the vast majority of patients with PCD have not been diagnosed as such, providing a major obstacle to delivering appropriate care. Challenges in diagnosing PCD include lack of disease-specific symptoms and absence of a single, “gold standard”, diagnostic test. Management of patients is currently not based on high-level evidence because research findings are mostly derived from small observational studies with limited follow-up period. In this review, we provide a critical overview of the available literature on clinical care for PCD patients, including recent advances. We identify barriers to PCD research and make suggestions for overcoming challenges
Management of primary ciliary dyskinesia: current practice and future perspectives
No full textPrimary ciliary dyskinesia (PCD) is an inherited disease, genetically and clinically heterogeneous, characterised by abnormal motile ciliary function. Although early symptoms predominantly effect the airways and most patients develop bronchiectasis, PCD is a multisystem disease and managementmust be multidisciplinary. Particularly relevant are chronic upper and lower respiratory tract symptoms, laterality disorders, cardiac manifestations and fertility. There is no strong evidence for the effectiveness of different therapies for PCD. This article highlights central aspects of PCD management, describes current practice and gives an overview on ongoing efforts to improve the evidenc
The patient's experience of primary ciliary dyskinesia: a systematic review
No full textBackground: primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by progressive sinopulmonary disease, with symptoms starting soon after birth. The aim of this study is to critically review, analyse, and synthesise the literature in order to understand the experiences of patients with primary ciliary dyskinesia (PCD) and the impact on health-related quality of life.Method: MEDLINE, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and EMBASE were searched according to the inclusion criteria. A qualitative analysis of 14 studies was conducted.Results: fourteen studies were included in the review, five with qualitative methodologies. Studies originated from the UK, USA, Italy, Denmark and Belgium, one study included a survey distributed internationally. Significant relationships were found between age and worsening of respiratory symptoms, physical, and mental domains of health-related quality of life, with a greater decline compared with reference populations. Variations between the UK and Italy were found for health-related quality of life and its correlation with time since diagnosis. PCD was found to have a physical impact in all age groups: patients found it difficult to keep up with others, and found energy levels were easily depleted compared to family or peers. In terms of social impact, symptoms lead to embarrassment and a sense of isolation, with patients concealing symptoms and/or their diagnosis. In turn, isolation was also linked with the lack of public and medical knowledge. In relation to emotional impact, anxiety was reported in a number of qualitative studies; patients were anxious about getting sick or when thinking about their future health. The burden of treatment and factors influencing adherence were also discussed in depth.Conclusion: health-related quality of life decreases with age in patients with PCD. For all age groups, PCD was found to greatly impact physical, emotional, social functioning, and treatment burden. More research is needed on the psychosocial impact of the illness, disease burden and its effect on quality of life
Variability of lung function in primary ciliary dyskinesia: longitudinal analysis from the PROVALF-PCD cohort
No full textBackground: the extent to which changes in lung function are due to natural variability in patients with primary ciliary dyskinesia (PCD) is unknown. We aimed to assess intra-individual variability in forced expiratory volume in 1s (FEV1) derived from spirometry to define the extent to which the observed changes were due to test variability in clinically stable PCD patients.Methods: PROVALF-PCD is a large international prospective cohort conducted in 2017-2019. We included patients ≥5 years who were clinically stable in ≥2 consecutive visits and provided spirometry-derived lung function measurements. To calculate the upper limit of normal (ULN), we fitted an unadjusted multilevel mixed effect model, and to determine the absolute change in FEV1 z-scores, we calculated the coefficient of repeatability (CR). We performed sensitivity analyses by stratifying relative change by age (adults versus children), number of measurements (≥4), and time between measurements (<4 months apart). Results: we included 252 participants from 12 countries with confirmed or highly likely PCD. We included 1028 FEV1 measurements from patients in stable state. The ULN for relative change between two measurements of FEV1 was 25%. Test variability remained high in all sensitivity analyses. The CR was 1.88 FEV1 z-score.Conclusions: changes in intra-individual FEV1 between visits greater than 25% in stable PCD patients lie beyond the expected test variability and therefore could be considered physiologically relevant. These findings inform the selection of endpoints for pulmonary intervention trials in PCD, as they suggest FEV1 is not a sensitive test for monitoring lung health in PCD
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