Two cosmoses, one universe: a narrative review exploring the gut microbiome's role in the effect of urban risk factors on vascular ageing.

In the face of rising global urbanisation, understanding how the associated environment and lifestyle impact public health is a cornerstone for prevention, research, and clinical practice. Cardiovascular disease is the leading cause of morbidity and mortality worldwide, with urban risk factors contributing greatly to its burden. The current narrative review adopts an exposome approach to explore the effect of urban-associated physical-chemical factors (such as air pollution) and lifestyle on cardiovascular health and ageing. In addition, we provide new insights into how these urban-related factors alter the gut microbiome, which has been associated with an increased risk of cardiovascular disease. We focus on vascular ageing, before disease onset, to promote preventative research and practice. We also discuss how urban ecosystems and social factors may interact with these pathways and provide suggestions for future research, precision prevention and management of vascular ageing. Most importantly, future research and decision-making would benefit from adopting an exposome approach and acknowledging the diverse and boundless universe of the microbiome.

An umbrella review of systematic reviews on the impact of the COVID-19 pandemic on cancer prevention and management, and patient needs.

The relocation and reconstruction of health care resources and systems during the coronavirus disease 2019 (COVID-19) pandemic may have affected cancer care. An umbrella review was undertaken to summarize the findings from systematic reviews on impact of the COVID-19 pandemic on cancer treatment modification, delays, and cancellations; delays or cancellations in screening and diagnosis; psychosocial well-being, financial distress, and use of telemedicine as well as on other aspects of cancer care. Bibliographic databases were searched for relevant systematic reviews with or without meta-analysis published before November 29th, 2022. Abstract, full- text screening, and data extraction were performed by two independent reviewers. AMSTAR-2 was used for critical appraisal of included systematic reviews. Fifty-one systematic reviews were included in our analysis. Most reviews were based on observational studies judged to be at medium and high risk of bias. Only two reviews had high or moderate scores based on AMSTAR-2. Findings suggest treatment modifications in cancer care during the pandemic versus the pre-pandemic period were based on low level of evidence. Different degrees of delays and cancellations in cancer treatment, screening, and diagnosis were observed, with low- and- middle- income countries and countries that implemented lockdowns being disproportionally affected. A shift from in-person appointments to telemedicine use was observed, but utility of telemedicine, challenges in implementation and cost-effectiveness in cancer care were little explored. Evidence was consistent in suggesting psychosocial well-being of patients with cancer deteriorated, and cancer patients experienced financial distress, albeit results were in general not compared to pre-pandemic levels. Impact of cancer care disruption during the pandemic on cancer prognosis was little explored. In conclusion, substantial but heterogenous impact of COVID-19 pandemic on cancer care has been observed.

The onset of the COVID-19 pandemic disrupted many aspects of human life, not least healthcare. As resources were redistributed towards the crisis, social isolation rules also limited access to medical professionals. In particular, these measures may have affected many aspects of cancer care, such as early detection or treatment. Many studies have aimed to capture the impact of these changes, but most have been observational, with researchers recording events without trying to impose a controlled design. These investigations also often faced limitations such as small sample sizes, or only focusing on one aspect of cancer care. Systemic reviews, which synthetize and assess existing research on a topic, have helped to bypass these constraints. However, they are themselves not devoid of biases. Overall, a clear, unified picture of the impact of COVID-19 on cancer care is yet to emerge. In response, Muka et al. carried an umbrella analysis of 51 systematic reviews on this topic. They used a well-known critical appraisal tool to assess the methodological rigor of each of these studies, while also summarising their findings. This work aimed to capture many aspects of the patients' experience, from diagnosis to treatment and the financial, psychological, physical and social impact of the disease. The results confirmed that the pandemic had a substantial impact on cancer care, including delays in screening, diagnosis and treatment. Throughout this period cancer patients experienced increased rates of depression, post-traumatic stress and fear of their cancer progressing. The long-term consequences of these disruptions remain to be uncovered. However, Muka et al. also showed that, overall, these conclusions rely on low-quality studies which may have introduced unaccountable biases. In addition, their review highlights that most of the data currently available has been collected in high- and middle-income countries, with evidence lacking from regions of the world with more limited resources. In the short-term, these results indicate that interventions may be needed to mitigate the negative impact of the pandemic on cancer care; in the long-term, they also demonstrate the importance of rigorous systematic reviews in guiding decision making. By shining a light on the ripple effects of certain decisions about healthcare resources, this work could also help to shape the response to future pandemics.

Global, Regional, and National Trends of Chagas Disease from 1990 to 2019: Comprehensive Analysis of the Global Burden of Disease Study.

Background: Chagas disease (CD) is a neglected tropical disease, endemic in Latin America, but due to migration and environmental changes it has become a global public health issue. Objectives: To assess the global prevalence and disability-adjusted life years due to CD using findings from the Global Burden of Disease Study 2019. Methods: The Global Burden of Disease data was obtained from the Global Burden of Disease Collaborative Network; results were provided by the Institute for Health Metrics and Evaluation. The prevalence and disability-adjusted life-years (DALYs) were described at a global, regional, and national level, including data from 1990 to 2019. Results: Globally, CD prevalence decreased by 11.3% during the study period, from 7,292,889 cases estimated in 1990 to 6,469,283 in 2019. Moreover, the global DALY rate of CD decreased by 23.7% during the evaluated period, from 360,872 in 1990 to 275,377 in 2019. In addition, significant differences in the burden by sex, being men the most affected, age, with the elderly having the highest burden of the disease, and sociodemographic index (SDI), with countries with the lowest SDI values having the highest prevalence of the disease, were observed. Finally, the prevalence trends have followed different patterns according to the region, with a sustained decrease in Latin America, compared to an increasing trend in North America and Europe until 2010. Conclusion: The global burden of CD has changed in recent decades, with a sustained decline in the number of cases. Although the majority of cases remain concentrated in Latin America, the increase observed in countries in North America and Europe highlights the importance of screening at-risk populations and raising awareness of this neglected tropical disease.

Cost-effectiveness analysis of alternative anticoagulation in suspected heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication associated with high medical costs. Factor Xa inhibitors gradually replace approved treatment with intravenous direct thrombin inhibitors despite their off-label indication, because of easier management and favorable economic profile. Whether they are cost-effective remains unclear. We evaluated the cost-effectiveness of approved and off-label anticoagulants in patients with suspected HIT, based on census data from the largest Swiss hospital between 2015 and 2018. We constructed a decision tree model that reflects important clinical events associated with HIT. Relevant cost data were obtained from the finance department or estimated based on the Swiss-wide cost tariff. We estimated averted adverse events (AEs) and incremental cost-effectiveness ratio as primary outcome parameters. We performed deterministic and probabilistic sensitivity analyses with 2000 simulations to assess the robustness of our results. In the base-case analysis, the total cost of averting 1 AE was 49 565 Swiss francs (CHF) for argatroban, 30 380 CHF for fondaparinux, and 30 610 CHF for rivaroxaban; after adjusting for 4Ts score: 41 152 CHF (argatroban), 27 710 CHF (fondaparinux), and 37 699 CHF (rivaroxaban). Fondaparinux and rivaroxaban were more clinically effective than argatroban, with AEs averted of 0.820, 0.834, and 0.917 for argatroban, fondaparinux, and rivaroxaban, respectively. Treatment with fondaparinux resulted in less cost and more AEs averted, hence dominating argatroban. Results were most sensitive to AE rates and prolongation of stay. Monte Carlo simulations affirmed our base-case analysis. This is the first cost-effectiveness analysis comparing argatroban with fondaparinux and rivaroxaban using primary data. Fondaparinux and rivaroxaban resulted in more averted AEs, but fondaparinux had greater cost savings. Fondaparinux could be a viable alternative to argatroban.

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis.

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Polyunsaturated fatty acids and serum C-reactive protein: the Rotterdam study.

We aimed to investigate whether dietary intake of total or individual (n-3, n-6, and n-3:n-6 ratio) polyunsaturated fatty acids (PUFAs) was prospectively associated with serum levels of C-reactive protein (CRP), a marker of inflammation. We analyzed 4,707 participants (1,943 men and 2,764 women) from the Rotterdam Study, a prospective follow-up study of subjects aged 55 years or older in the Netherlands. At baseline (1989-1993), dietary intake of PUFAs was assessed by validated food frequency questionnaire. CRP was measured at baseline and at the third study visit (1997-1999). Regression coefficients (ß) and 95% confidence intervals were obtained using linear generalized estimating equations. Dietary intake of butter and margarine explained most of the variance in PUFA intake. After adjustment for possible confounding factors, higher intake of total PUFAs was associated with lower CRP levels (fourth quartile vs. first quartile: ß = -0.08, 95% confidence interval: -0.15, -0.01). Similarly, intake of n-6 PUFAs was inversely related to CRP (fourth quartile vs. first: ß = -0.09, 95% confidence interval: -0.16, -0.01). No consistent trends were observed regarding n-3 PUFAs or n-3:n-6 PUFA ratio and CRP. These findings suggest that high intakes of total PUFAs are associated with lower levels of CRP, reflecting diminished chronic systemic inflammation, which in our study was mainly driven by n-6 PUFAs.

The global impact of non-communicable diseases on macro-economic productivity: a systematic review.

Non-communicable diseases (NCDs) have large economic impact at multiple levels. To systematically review the literature investigating the economic impact of NCDs [including coronary heart disease (CHD), stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on macro-economic productivity. Systematic search, up to November 6th 2014, of medical databases (Medline, Embase and Google Scholar) without language restrictions. To identify additional publications, we searched the reference lists of retrieved studies and contacted authors in the field. Randomized controlled trials, cohort, case-control, cross-sectional, ecological studies and modelling studies carried out in adults (>18 years old) were included. Two independent reviewers performed all abstract and full text selection. Disagreements were resolved through consensus or consulting a third reviewer. Two independent reviewers extracted data using a predesigned data collection form. Main outcome measure was the impact of the selected NCDs on productivity, measured in DALYs, productivity costs, and labor market participation, including unemployment, return to work and sick leave. From 4542 references, 126 studies met the inclusion criteria, many of which focused on the impact of more than one NCD on productivity. Breast cancer was the most common (n = 45), followed by stroke (n = 31), COPD (n = 24), colon cancer (n = 24), DM (n = 22), lung cancer (n = 16), CVD (n = 15), cervical cancer (n = 7) and CKD (n = 2). Four studies were from the WHO African Region, 52 from the European Region, 53 from the Region of the Americas and 16 from the Western Pacific Region, one from the Eastern Mediterranean Region and none from South East Asia. We found large regional differences in DALYs attributable to NCDs but especially for cervical and lung cancer. Productivity losses in the USA ranged from 88 million US dollars (USD) for COPD to 20.9 billion USD for colon cancer. CHD costs the Australian economy 13.2 billion USD per year. People with DM, COPD and survivors of breast and especially lung cancer are at a higher risk of reduced labor market participation. Overall NCDs generate a large impact on macro-economic productivity in most WHO regions irrespective of continent and income. The absolute global impact in terms of dollars and DALYs remains an elusive challenge due to the wide heterogeneity in the included studies as well as limited information from low- and middle-income countries.

The global impact of non-communicable diseases on healthcare spending and national income: a systematic review.

The impact of non-communicable diseases (NCDs) in populations extends beyond ill-health and mortality with large financial consequences. To systematically review and meta-analyze studies evaluating the impact of NCDs (including coronary heart disease, stroke, type 2 diabetes mellitus, cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease and chronic kidney disease) at the macro-economic level: healthcare spending and national income. Medical databases (Medline, Embase and Google Scholar) up to November 6th 2014. For further identification of suitable studies, we searched reference lists of included studies and contacted experts in the field. We included randomized controlled trials, systematic reviews, cohorts, case-control, cross-sectional, modeling and ecological studies carried out in adults assessing the economic consequences of NCDs on healthcare spending and national income without language restrictions. All abstracts and full text selection was done by two independent reviewers. Any disagreements were resolved through consensus or consultation of a third reviewer. Data were extracted by two independent reviewers using a pre-designed data collection form. Studies evaluating the impact of at least one of the selected NCDs on at least one of the following outcome measures: healthcare expenditure, national income, hospital spending, gross domestic product (GDP), gross national product, net national income, adjusted national income, total costs, direct costs, indirect costs, inpatient costs, outpatient costs, per capita healthcare spending, aggregate economic outcome, capital loss in production levels in a country, economic growth, GDP per capita (per capita income), percentage change in GDP, intensive growth, extensive growth, employment, direct governmental expenditure and non-governmental expenditure. From 4,364 references, 153 studies met our inclusion criteria. Most of the studies were focused on healthcare related costs of NCDs. 30 studies reported the economic impact of NCDs on healthcare budgets and 13 on national income. Healthcare expenditure for cardiovascular disease (12-16.5 %) was the highest; other NCDs ranged between 0.7 and 7.4 %. NCD-related health costs vary across the countries, regions, and according to type of NCD. Additionally, there is an increase in costs with increased severity and years lived with the disease. Low- and middle-income (LMI) countries were the focus of just 16 papers, which suggests an information shortage concerning the true economic burden of NCDs in these countries. NCDs pose a significant financial burden on healthcare budgets and nations' welfare, which is likely to increase over time. However further work is required to standardize more consistently the methods available to assess the economic impact of NCDs and to involve (hitherto under-addressed) LMI populations across the globe.

The global impact of non-communicable diseases on households and impoverishment: a systematic review.

The global economic impact of non-communicable diseases (NCDs) on household expenditures and poverty indicators remains less well understood. To conduct a systematic review and meta-analysis of the literature evaluating the global economic impact of six NCDs [including coronary heart disease, stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on households and impoverishment. Medline, Embase and Google Scholar databases were searched from inception to November 6th 2014. To identify additional publications, reference lists of retrieved studies were searched. Randomized controlled trials, systematic reviews, cohorts, case-control, cross-sectional, modeling and ecological studies carried out in adults and assessing the economic consequences of NCDs on households and impoverishment. No language restrictions. All abstract and full text selection was done by two independent reviewers. Data were extracted by two independent reviewers and checked by a third independent reviewer. Studies were included evaluating the impact of at least one of the selected NCDs and on at least one of the following measures: expenditure on medication, transport, co-morbidities, out-of-pocket (OOP) payments or other indirect costs; impoverishment, poverty line and catastrophic spending; household or individual financial cost. From 3,241 references, 64 studies met the inclusion criteria, 75% of which originated from the Americas and Western Pacific WHO region. Breast cancer and DM were the most studied NCDs (42 in total); CKD and COPD were the least represented (five and three studies respectively). OOP payments and financial catastrophe, mostly defined as OOP exceeding a certain proportion of household income, were the most studied outcomes. OOP expenditure as a proportion of family income, ranged between 2 and 158% across the different NCDs and countries. Financial catastrophe due to the selected NCDs was seen in all countries and at all income levels, and occurred in 6-84% of the households depending on the chosen catastrophe threshold. In 16 low- and middle-income countries (LMIC), 6-11% of the total population would be impoverished at a 1.25 US dollar/day poverty line if they would have to purchase lowest price generic diabetes medication. NCDs impose a large and growing global impact on households and impoverishment, in all continents and levels of income. The true extent, however, remains difficult to determine due to the heterogeneity across existing studies in terms of populations studied, outcomes reported and measures employed. The impact that NCDs exert on households and impoverishment is likely to be underestimated since important economic domains, such as coping strategies and the inclusion of marginalized and vulnerable people who do not seek health care due to financial reasons, are overlooked in literature. Given the scarcity of information on specific regions, further research to estimate impact of NCDs on households and impoverishment in LMIC, especially the Middle Eastern, African and Latin American regions is required.