Systems for rating bodies of evidence used in systematic reviews of air pollution exposure and reproductive and children's health: a methodological survey.

BACKGROUND: Translating findings from systematic reviews assessing associations between environmental exposures and reproductive and children's health into policy recommendations requires valid and transparent evidence grading. METHODS: We aimed to evaluate systems for grading bodies of evidence used in systematic reviews of environmental exposures and reproductive/ children's health outcomes, by conducting a methodological survey of air pollution research, comprising a comprehensive search for and assessment of all relevant systematic reviews. To evaluate the frameworks used for rating the internal validity of primary studies and for grading bodies of evidence (multiple studies), we considered whether and how specific criteria or domains were operationalized to address reproductive/children's environmental health, e.g., whether the timing of exposure assessment was evaluated with regard to vulnerable developmental stages. RESULTS: Eighteen out of 177 (9.8%) systematic reviews used formal systems for rating the body of evidence; 15 distinct internal validity assessment tools for primary studies, and nine different grading systems for bodies of evidence were used, with multiple modifications applied to the cited approaches. The Newcastle Ottawa Scale (NOS) and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework, neither developed specifically for this field, were the most commonly used approaches for rating individual studies and bodies of evidence, respectively. Overall, the identified approaches were highly heterogeneous in both their comprehensiveness and their applicability to reproductive/children's environmental health research. CONCLUSION: Establishing the wider use of more appropriate evidence grading methods is instrumental both for strengthening systematic review methodologies, and for the effective development and implementation of environmental public health policies, particularly for protecting pregnant persons and children.

How does gestational weight gain influence short- and long-term postpartum weight retention? An updated systematic review and meta-analysis.

This systematic review and meta-analysis provide an update of an earlier meta-analysis examining the impact of gestational weight gain (GWG) on postpartum weight retention (PPWR). Thirty-four observational studies were included, and results from 18 studies were combined in meta-analyses. We found that women with excessive GWG retained an additional 2.98 kg (95% CI: 0.59, 5.37 kg, I2  = 91%) at 0.5 years, 1.89 kg (95% CI: 0.90, 2.88 kg, I2  = 61%) at > 0.5-1 year and 2.89 kg (95% CI: 1.74, 4.04 kg, I 2  = 0%) at 2-4 years, compared to women who met the National Academy of Medicine GWG recommendations. Moreover, synthesis of confounder-adjusted regression coefficients showed that each 1 kg increase of GWG corresponded to 0.62 kg (95% CI: 0.22, 1.02 kg, I2  = 96%) additional PPWR at 6-9 months, 0.48 kg (95% CI: 0.14, 0.81 kg, I2  = 93%) at 1-3 years, and 0.31 kg (95% CI: -0.24, 0.86 kg, I2  = 89%) at 5-7 years postpartum. Findings suggest that higher GWG contributes to increased maternal body weight in the short- and long-term after childbirth, independent of prepregnancy body mass index. The heterogeneity of reported data and methodological differences across studies complicate the ability to synthesize data and interpret findings.

Prenatal exposure to ambient air pollutants and congenital heart defects: An umbrella review.

BACKGROUND: Prenatal exposure to ambient air pollutants has been linked to congenital heart defects (CHD), but findings of existing systematic reviews have been mixed. OBJECTIVE: To assess the epidemiological evidence on associations between prenatal exposure to ambient air pollutants and CHD subtypes, based on a systematic overview of reviews ("umbrella review"). METHODS: We conducted a systematic search for reviews assessing associations between prenatal exposure to criteria air pollutants and CHD. The risk of bias was evaluated using the Risk of Bias in Systematic Reviews (ROBIS) tool. The certainty of the systematic review findings was graded using the Navigation Guide methodology. RESULTS: We identified eleven systematic reviews, including eight with meta-analyses, assessing in total 35 primary studies of prenatal exposure to criteria air pollutants and various CHD subtypes. The certainty of the findings of four meta-analyses indicating an increased risk for coarctation of the aorta associated with nitrogen dioxide exposure was rated as moderate. The certainty of findings indicating positive, inverse, or null associations for other pollutant-subtype combinations was rated as very low to low, based on low precision and high statistical heterogeneity of summary odds ratios (SOR), substantial inconsistencies between review findings, and methodological limitations of the systematic reviews. DISCUSSION: The inconsistent findings and high statistical heterogeneity of many SOR of the included systematic reviews may partly be traced to differences in methodological approaches, and the risk of bias across included reviews (e.g., inclusion criteria, systematic search strategies, synthesis methods) and primary studies (e.g., exposure assessment, diagnostic criteria). Adherence to appropriate systematic review guidelines for environmental health research, as well as rigorous evaluation of risk of bias in primary studies, are essential for future risk assessments and policy-making. Still, our findings suggest that prenatal exposure to ambient air pollutants may increase risks for at least some CHD subtypes.

A natural experiment to assess how urban interventions in lower socioeconomic areas influence health behaviors: the UrbASanté study.

BACKGROUND: Mechanisms underlying the associations between changes in the urban environment and changes in health-related outcomes are complex and their study requires specific approaches. We describe the protocol of the interdisciplinary UrbASanté study, which aims to explore how urban interventions can modify environmental exposures (built, social, and food environments; air quality; noise), health-related behaviors, and self-reported health using a natural experiment approach. METHODS: The study is based on a natural experiment design using a before/after protocol with a control group to assess changes in environmental exposures, health-risk behaviors, and self-reported health outcomes of a resident adult population before and after the implementation of a time series of urban interventions in four contiguous neighborhoods in Paris (France). The changes in environmental exposures, health-related behaviors, and self-reported health outcomes of a resident adult population will be concurrently monitored in both intervention and control areas. We will develop a mixed-method framework combining substantial fieldwork with quantitative and qualitative analytical approaches. This study will make use of (i) data relating to exposures and health-related outcomes among all participants and in subsamples and (ii) interviews with residents regarding their perceptions of their neighborhoods and with key stakeholders regarding the urban change processing, and (iii) existing geodatabases and field observations to characterize the built, social, and food environments. The data collected will be analyzed with a focus on interrelationships between environmental exposures and health-related outcomes using appropriate approaches (e.g., interrupted time series, difference-in-differences method). DISCUSSION: Relying on a natural experiment approach, the research will provide new insights regarding issues such as close collaboration with urban/local stakeholders, recruitment and follow-up of participants, identification of control and intervention areas, timing of the planned urban interventions, and comparison of subjective and objective measurements. Through the collaborative work of a consortium ensuring complementarity between researchers from different disciplines and stakeholders, the UrbASanté study will provide evidence-based guidance for designing future urban planning and public health policies. TRIAL REGISTRATION: This research was registered at the ClinicalTrial.gov (NCT05743257).

Associations between circulating obesity-related biomarkers and prognosis in female breast cancer survivors: a systematic review of observational data in women enrolled in lifestyle intervention trials.

Obesity plays an important role in the development and progression of breast cancer via various oncogenic pathways. However, the biological mechanisms underlying this relationship are not fully understood. Moreover, it is unclear whether obesity-related and further associated biomarkers could be suitable targets for lifestyle interventions. This systematic review was conducted to examine relationships between obesity-related blood parameters and prognosis for breast cancer survivors enrolled in lifestyle intervention studies. A systematic, computerized literature search was conducted from inception through August 26th, 2020 in PubMed, EMBASE, and CENTRAL. The focus was on observational data from randomized controlled lifestyle intervention trials investigating associations between selected baseline biomarkers, measured in remission, and breast cancer recurrence, breast cancer mortality and/or all-cause mortality. Four studies with data from 5234 women met the inclusion criteria.Studies herein provide moderate evidence that bioavailable or serum testosterone may be positively linked to breast cancer recurrence and inversely linked to disease-free survival. Limited evidence suggests no associations with circulating estradiol or insulin levels on prognosis outcomes, whereas HDL cholesterol was inversely associated with breast cancer recurrence. For some other biomarkers, such as growth factors, adipokines, and CRP, the evidence for associations with disease prognosis was too weak to draw conclusions.Overall, despite potential candidates, there is insufficient evidence to confirm or refute that obesity-related biomarkers and sex hormones have a prognostic value for breast cancer survival. More longitudinal studies in breast cancer survivors to examine the clinical utility of obesity-related biomarkers are needed.

No Impact of Seasonality of Diagnoses on Baseline Tumor Immune Infiltration, Response to Treatment, and Prognosis in BC Patients Treated with NAC.

Breast cancer (BC) is the most common cancer in women worldwide. Neoadjuvant chemotherapy (NAC) makes it possible to monitor in vivo response to treatment. Several studies have investigated the impact of the seasons on the incidence and detection of BC, on tumor composition, and on the prognosis of BC. However, no evidence is available on their association with immune infiltration and the response to treatment. The objective of this study was to analyze pre- and post-NAC immune infiltration as assessed by TIL levels, the response to treatment as assessed by pathological complete response (pCR) rates, and oncological outcomes as assessed by relapse-free survival (RFS) or overall survival (OS) according to the seasonality of BC diagnoses in a clinical cohort of patients treated with neoadjuvant chemotherapy. Out of 1199 patients, the repartition of the season at BC diagnosis showed that 27.2% were diagnosed in fall, 25.4% in winter, 24% in spring, and 23.4% in summer. Baseline patient and tumor characteristics, including notable pre-NAC TIL levels, were not significantly different in terms of the season of BC diagnosis. Similarly, the pCR rates were not different. No association for oncological outcome was identified. Our data do not support the idea that the seasonality of diagnoses has a major impact on the natural history of BC treated with NAC.

The French Early Breast Cancer Cohort (FRESH): A Resource for Breast Cancer Research and Evaluations of Oncology Practices Based on the French National Healthcare System Database (SNDS).

BACKGROUND: Breast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death in women. The French National Cancer Institute has created a national cancer cohort to promote cancer research and improve our understanding of cancer using the National Health Data System (SNDS) and amalgamating all cancer sites. So far, no detailed separate data are available for early BC. OBJECTIVES: To describe the creation of the French Early Breast Cancer Cohort (FRESH). METHODS: All French women aged 18 years or over, with early-stage BC newly diagnosed between 1 January 2011 and 31 December 2017, treated by surgery, and registered in the general health insurance coverage plan were included in the cohort. Patients with suspected locoregional or distant metastases at diagnosis were excluded. BC treatments (surgery, chemotherapy, targeted therapy, radiotherapy, and endocrine therapy), and diagnostic procedures (biopsy, cytology, and imaging) were extracted from hospital discharge reports, outpatient care notes, or pharmacy drug delivery data. The BC subtype was inferred from the treatments received. RESULTS: We included 235,368 patients with early BC in the cohort (median age: 60 years). The BC subtype distribution was as follows: luminal (80.2%), triple-negative (TNBC, 9.5%); HER2+ (10.3%), or unidentifiable (n = 44,388, 18.9% of the cohort). Most patients underwent radiotherapy (n = 200,685, 85.3%) and endocrine therapy (n = 165,655, 70.4%), and 38.3% (n = 90,252) received chemotherapy. Treatments and care pathways are described. CONCLUSIONS: The FRESH Cohort is an unprecedented population-based resource facilitating future large-scale real-life studies aiming to improve care pathways and quality of care for BC patients.

Associations between lifestyle interventions during pregnancy and childhood weight and growth: a systematic review and meta-analysis.

BACKGROUND: Maternal health and lifestyle during pregnancy may be critical for the onset and progression of childhood obesity. Prenatal lifestyle interventions have been shown to positively affect maternal behaviors, gestational weight gain, and anthropometric outcomes in infants at birth. The influence of such interventions on child weight or growth beyond birth is unknown. We therefore examined the association between lifestyle interventions during pregnancy and anthropometric outcomes during childhood. METHODS: A systematic literature search was conducted in three electronic databases, two clinical trial registers and further sources, without language or publication status restrictions. Additionally, 110 study authors were contacted to obtain unpublished data. Randomized controlled trials comparing any antenatal lifestyle or behavioral intervention to standard prenatal care, in women of any body mass index (BMI), with offspring anthropometric data at 1 month of age or older, were considered. Two reviewers independently extracted data and assessed the risk of bias using the Cochrane Collaboration's updated tool. Data on weight, length, and BMI, and corresponding z-scores, were stratified into six age ranges and weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated in univariate and multivariate random-effects meta-analytical models. RESULTS: Twenty trials comprising 11,385 women were included in this systematic review, of which 19 were combined in meta-analyses. Overall, lifestyle interventions during pregnancy were not associated with differences in weight, length, BMI, or corresponding z-scores, in children aged 1 month to 7 years (e.g. weight in 5 to 6 month old children, WMD: 0.02 kg; 95% CI: - 0.05 to 0.10 kg, I2 = 38%; 13 studies, 6667 participants). Findings remained consistent when studies were stratified by maternal baseline BMI or other risk factors, and intervention content and duration. Based on the GRADE criteria, the strength of the body of evidence was considered moderate. CONCLUSION: Prenatal lifestyle interventions were not shown to influence childhood weight or growth. Nevertheless, women should be encouraged to pursue a healthy lifestyle during pregnancy. Further efforts to establish early prevention strategies for childhood obesity are urgently needed. Thus, large, high-quality studies with pre-planned, long-term follow-ups are warranted. TRIAL REGISTRATION: PROSPERO CRD42018118678 .

Hemostatis Analyzer-Supported Hemotherapy Algorithm in Cardiac Surgery: Protocol for a Randomized Controlled Monocentric Trial.

BACKGROUND: Point of care devices for performing targeted coagulation substitution in patients who are bleeding have become increasingly important in recent years. New on the market is the Quantra. It is a device that uses sonorheometry, a sonic estimation of elasticity via resonance, which is a novel ultrasound-based technology that measures viscoelastic properties of whole blood. Several studies have already shown the comparability of the Quantra with devices already established on the market, such as the rotational thromboelastometry (ROTEM) device. OBJECTIVE: In contrast to existing studies, this study is the first prospective interventional study using this new system in a cardiac surgical patient cohort. We will investigate the noninferiority between an already existing coagulation algorithm based on the ROTEM/Multiplate system and a new algorithm based on the Quantra system for the treatment of coagulopathic cardiac surgical patients. METHODS: The study is divided into two phases. In an initial observation phase, whole blood samples of 20 patients obtained at three defined time points (prior to surgery, after completion of cardiopulmonary bypass, and on arrival in the intensive care unit) will be analyzed using both the ROTEM/Multiplate and Quantra systems. The obtained threshold values will be used to develop a novel algorithm for hemotherapy. In a second intervention phase, the new algorithm will be tested for noninferiority against an algorithm used routinely for years in our department. RESULTS: The main objective of the examination is the cumulative loss of blood within 24 hours after surgery. Statistical calculations based on the literature and in-house data suggest that the new algorithm is not inferior if the difference in cumulative blood loss is <150 mL/24 hours. CONCLUSIONS: Because of the comparability of the Quantra sonorheometry system with the ROTEM measurement methods, the existing hemotherapy treatment algorithm can be adapted to the Quantra device with proof of noninferiority. TRIAL REGISTRATION: ClinicalTrials.gov NCT03902275; https://clinicaltrials.gov/ct2/show/NCT03902275. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17206.

Do lifestyle interventions during pregnancy have the potential to reduce long-term postpartum weight retention? A systematic review and meta-analysis.

Reducing postpartum weight retention is a promising strategy for addressing the rising prevalence of overweight and obesity in women. This systematic review and meta-analysis explored whether lifestyle interventions during pregnancy have the potential to reduce weight retention at 4 months postpartum and beyond. A search of five electronic databases for randomized controlled trials comparing the effect of weight-related lifestyle interventions beginning in pregnancy on postpartum weight retention to standard prenatal care groups was performed. Postpartum weight retention data was synthesized in a random-effects meta-analysis. Data from 14 studies of 7116 participants showed that the intervention group retained statistically significant less weight than the control group (weighted mean difference: -0.73 kg, 95% CI: -1.32 to -0.14, P = 0.015). Subgroup analysis showed this effect to be largest in studies with follow-ups from 4 to 6 months (weighted mean difference: -1.32 kg, 95% CI: -2.11 to -0.53, P = 0.001), but it remained significant until 12 months postpartum (weighted mean difference: -0.68 kg, 95% CI: -1.28 to -0.09, P = 0.023). In studies of women with a body mass index above 25.0 kg/m2 , no significant intervention effect was observed. More high-quality studies with a follow-up beyond 12 months postpartum are needed.

Adsorption of albumin on flax fibers increases endothelial cell adhesion and blood compatibility in vitro.

The physical and chemical properties of flax (linen) are attractive from the perspective of biomaterials science and engineering. Flax textiles uniquely combine hydrophilicity and strength, with the technical know-how to produce precisely engineered two- and three-dimensional knitted or woven structures. It is, however, extremely difficult to completely remove endotoxins from the flax, and this essentially precludes the use of linen for implant purposes. Herein, the potential utility of flax textiles for blood-contacting applications is investigated, using purified two-dimensional mesh specimens, with and without an albumin surface coating. It was hypothesized that the albumin coating will abolish the effect of adherent endotoxins at the flax's surface. In vitro cell viability assays showed that the flax mesh ± albumin is not cytotoxic. The albumin coating reduced (but not abolished) the effect of surface-exposed endotoxins (Limulus amebocyte lysate test). Under dynamic conditions, the albumin coating favors coverage with endothelial cells. Experiments with fresh human blood plasma (platelet-rich and platelet-free) showed that the albumin coating reduces the thrombogenicity in vitro. Platelets adhered to the albumin-coated flax mesh showed a less flattened structure. Although the results of this work cannot be extrapolated easily to in vivo situations, the data reveal that woven or knitted tubular structures produced from flax fibers may hold promise as implantable blood contacting devices like for instance vascular grafts.

Utilization of flax fibers for biomedical applications.

Over the past decades, a large number of animal-derived materials have been introduced for several biomedical applications. Surprisingly, the use of plant-based materials has lagged behind. To study the feasibility of plant-derived biomedical materials, we chose flax (Linum usitatissimum). Flax fibers possess excellent physical-mechanical properties, are nonbiodegradable, and there is extensive know-how on weaving/knitting of them. One area where they could be useful is as implantable mesh structures in surgery, in particular for the repair of incisional hernias of the abdominal wall. Starting with a bleached flax thread, a prototype mesh was specifically knitted for this study, and its cytocompatibility was studied in vitro and in vivo. The experimental data revealed that application of flax in surgery first requires a robust method to remove endotoxins and purify the flax fiber. Such a method was developed, and purified meshes did not cause loss of cell viability in vitro. In addition, endotoxins determined using limulus amebocyte lysate test were at acceptable levels. In vivo, the flax meshes showed only mild inflammation, comparable to commercial polypropylene meshes. This study revealed that plant-derived biomaterials can provide a new class of implantable materials that could be used as surgical meshes or for other biomedical applications.

Gaining a better understanding of respiratory health inequalities among cities: an ecological case study on elderly males in the larger French cities.

BACKGROUND: In recent years, there have been a growing number of studies on spatial inequalities in health covering a variety of scales, from small areas to metropolitan areas or regions, and for various health outcomes. However, few investigations have compared health status between cities with a view to gaining a better understanding of the relationships between such inequalities and the social, economic and physical characteristics. This paper focuses on disparities in respiratory health among the 55 largest French cities. The aim is to explore the relationships between inter-urban health patterns, city characteristics and regional context, and to determine how far a city's health status relates to the features observed on different geographical scales. METHODS: We used health data describing hospitalizations for Chronic Obstructive Pulmonary Disease (COPD) as a proxy for respiratory health, and the total number of hospitalizations (overall) as a proxy for general health. This last indicator was used as a benchmark. A large set of indicators relating to socioeconomic, physical and amenity aspects of the cities (urban units) was also constructed. Data were analyzed using linear correlations and multiple linear regression models. RESULTS: The results suggest that socioeconomic characteristics are major discriminators for inequalities in respiratory health status among urban units. Indeed, once combined to socioeconomic characteristics, only a climate indicator remained significant among the physical indicators. It appeared that the pollution indicators which were significantly correlated with COPD hospitalization rates loosed significance when associated to the socio-economic indicators in a multiple regression. The analysis showed that among the socio-economic indicators, an employment indicator derived at the regional scale, and two indicators reflecting the unequal intra-urban spatial distribution of population according to their education, were the most efficient to describe differences in the respiratory health status of urban units. CONCLUSION: In order to design effective urban policies, it is essential to gain a better understanding of the differences among cities in their entirety, rather than solely differences across small urban areas or individuals.

Respiratory protection during simulated emergency pediatric life support: a randomized, controlled, crossover study.

INTRODUCTION: Emergency pediatric life support (EPLS) of children infected with transmissible respiratory diseases requires adequate respiratory protection for medical first responders. Conventional air-purifying respirators (APR) and modern loose-fitting powered air-purifying respirator-hoods (PAPR-hood) may have a different impact during pediatric resuscitation and therefore require evaluation. OBJECTIVE: This study investigated the influence of APRs and PAPR-hoods during simulated pediatric cardiopulmonary resuscitation. METHODS: Study design was a randomized, controlled, crossover study. Sixteen paramedics carried out a standardized EPLS scenario inside an ambulance, either unprotected (control) or wearing a conventional APR or a PAPR-hood. Treatment times and wearer comfort were determined and compared. RESULTS: All paramedics completed the treatment objectives of the study arms without adverse events. Study subjects reported that communication, dexterity and mobility were significantly better in the APR group, whereas the heat-build-up was significantly less in the PAPR-hood group. Treatment times compared to the control group did not significantly differ for the APR group but did with the PAPR-hood group (261±12 seconds for the controls, 275±9 seconds for the conventional APR and 286±13 seconds for the PAPR-hood group, P < .05. CONCLUSIONS: APRs showed a trend to better treatment times compared to PAPR-hoods during simulated pediatric cardiopulmonary resuscitation. Study participants rated mobility, ease of communication and dexterity with the tight-fitting APR system significantly better compared to the loose-fitting PAPR-hood.

Variations in HSP70 genes associated with noise-induced hearing loss in two independent populations.

Noise-induced hearing loss (NIHL) is one of the most important occupational health hazards. Millions of people worldwide are exposed daily to harmful levels of noise. NIHL is a complex disease resulting from an interaction between genetic and environmental factors. Although the environmental risk factors have been studied extensively, little is known about the genetic factors. Heat-shock proteins (HSPs) are induced after exposure to severe noise. When first induced by exposure to moderate sound levels, they can protect the ear from damage from excessive noise exposure. This protection is highly variable between individuals. An association of HSP70 genes with NIHL has been described by Yang et al (2006) in a Chinese sample set of noise-exposed workers. In this study, three polymorphisms (rs1043618, rs1061581 and rs2227956) in HSP70-1, HSP70-2 and HSP70-hom, respectively, were genotyped in 206 Swedish and 238 Polish DNA samples of noise-exposed subjects and analyzed. One SNP, rs2227956 in HSP70-hom, resulted in a significant association with NIHL in both sample sets. In addition, rs1043618 and rs1061581 were significant in the Swedish sample set. Analysis of the haplotypes composed of the three SNPs revealed significant associations between NIHL and haplotype GAC in both sample sets and with haplotype CGT in the Swedish sample set. In conclusion, this study replicated the association of HSP70 genes with NIHL in a second and third independent noise-exposed sample set, hereby adding to the evidence that HSP70 genes may be NIHL susceptibility genes.

Cutaneous manifestations as initial presentation of Waldenstrom's macroglobulinemia.

Waldenstr m's Macroglobulinemia is a rare chronic lymphoproliferative disease. Clinical manifestations include usually weakness, weight loss, lymphadenopathy. Lung, kidney, heart, nervous system or bone may be involved. Cutaneous manifestations are unusual and misunderstood. Two different types of cutaneous lesions are described: non-specific and specific. They may reveal the disease or appear during the course of it. We report a case of a Waldenstr m's Macroglobulinemia with cutaneous involvement.