Computing the polytomous discrimination index.

Polytomous regression models generalize logistic models for the case of a categorical outcome variable with more than two distinct categories. These models are currently used in clinical research, and it is essential to measure their abilities to distinguish between the categories of the outcome. In 2012, van Calster et al proposed the polytomous discrimination index (PDI) as an extension of the binary discrimination c-statistic to unordered polytomous regression. The PDI is a summary of the simultaneous discrimination between all outcome categories. Previous implementations of the PDI are not capable of running on "big data." This article shows that the PDI formula can be manipulated to depend only on the distributions of the predicted probabilities evaluated for each outcome category and within each observed level of the outcome, which substantially improves the computation time. We present a SAS macro and R function that can rapidly evaluate the PDI and its components. The routines are evaluated on several simulated datasets after varying the number of categories of the outcome and size of the data and two real-world large administrative health datasets. We compare PDI with two other discrimination indices: M-index and hypervolume under the manifold (HUM) on simulated examples. We describe situations where the PDI and HUM, indices based on multiple comparisons, are superior to the M-index, an index based on pairwise comparisons, to detect predictions that are no different than random selection or erroneous due to incorrect ranking.

Dopamine receptor blockade improves pulmonary gas exchange but decreases exercise performance in healthy humans.

Pulmonary gas exchange, as evaluated by the alveolar-arterial oxygen difference (A-aDO2), is impaired during intense exercise, and has been correlated with recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) as measured by agitated saline contrast echocardiography. Previous work has shown that dopamine (DA) recruits IPAVA and increases venous admixture (Q̇s/Q̇t) at rest. As circulating DA increases during exercise, we hypothesized that A-aDO2 and IPAVA recruitment would be decreased with DA receptor blockade. Twelve healthy males (age: 25 ± 6 years, V̇O2 max : 58.6 ± 6.5 ml kg(-1) min(-1) ) performed two incremental staged cycling exercise sessions after ingestion of either placebo or a DA receptor blocker (metoclopramide 20 mg). Arterial blood gas, cardiorespiratory and IPAVA recruitment (evaluated by agitated saline contrast echocardiography) data were obtained at rest and during exercise up to 85% of V̇O2 max . On different days, participants also completed incremental exercise tests and exercise tolerance (time-to-exhaustion (TTE) at 85% of V̇O2 max ) with or without dopamine blockade. Compared to placebo, DA blockade did not change O2 consumption, CO2 production, or respiratory exchange ratio at any intensity. At 85% V̇O2 max , DA blockade decreased A-aDO2, increased arterial O2 saturation and minute ventilation, but did not reduce IPAVA recruitment, suggesting that positive saline contrast is unrelated to A-aDO2. Compared to placebo, DA blockade decreased maximal cardiac output, V̇O2 max and TTE. Despite improving pulmonary gas exchange, blocking dopamine receptors appears to be detrimental to exercise performance. These findings suggest that endogenous dopamine is important to the normal cardiopulmonary response to exercise and is necessary for optimal high-intensity exercise performance.

Assisted human reproduction and pregnancy outcomes in Alberta, 2009-2018: a population-based study.

BACKGROUND: Assisted human reproduction (AHR) can be used to help individuals and couples overcome infertility issues. We sought to describe trends in pregnancies using AHR and to evaluate the impact of AHR on perinatal outcomes in a large population-based cohort in Alberta, Canada. METHODS: We linked maternal and child administrative data for all live births occurring July 1, 2009, to Dec. 31, 2018, in Alberta, Canada, for this retrospective study. We identified AHR pregnancies from pharmaceutical claims or codes from the International Classification of Diseases and Related Health Problems (9th or 10th revision). Our main outcome measures were the incidence and temporal trends of live births in AHR pregnancies. We also compared maternal characteristics and perinatal outcomes of AHR and non-AHR pregnancies, and by maternal age group. RESULTS: Of 518 293 live births during the study period, 26 270 (5.1%) were conceived with AHR. The incidence of AHR pregnancies increased from 30.8 per 1000 pregnancies in 2009 to 54.7 per 1000 pregnancies in 2018. Females who used AHR were older (33.9 yr v. 30.1 yr, p < 0.001) and the number of females aged 30-35 years and older than 35 years who delivered following AHR increased over the study period (30-35 yr: 36.9 to 55.3 per 1000 pregnancies; > 35 yr: 79.1 to 95.2 per 1000 pregnancies). The proportion of live births with cesarean delivery (40.5% v. 23.3%, p < 0.001), low birth weight (26.9% v. 7.6%, p < 0.001), congenital malformation (0.5% v. 0.3%, p = 0.002) and admission to the neonatal intensive care unit (25.3% v. 9.7%, p < 0.001) was higher in the AHR group than the non-AHR group. INTERPRETATION: The incidence of live births following AHR pregnancies in Alberta was 5.1% between 2009 and 2018, and increased by 0.26% per year; newborns in the AHR group appeared smaller and showed signs of poorer health. This study provides insights on potential perinatal complications following AHR that may be important when caring for the newborn child.

Impacts of Wildfire Smoke and Air Pollution on a Pediatric Population with Asthma: A Population-Based Study.

Wildfires are increasing yearly in number and severity as a part of the evolving climate crisis. These fires are a significant source of air pollution, a common driver of flares in cardiorespiratory disease, including asthma, which is the most common chronic disease of childhood. Poorly controlled asthma leads to significant societal costs through morbidity, mortality, lost school and work time and healthcare utilization. This retrospective cohort study set in Calgary, Canada evaluates the relationship between asthma exacerbations during wildfire smoke events and equivalent low-pollution periods in a pediatric asthma population. Air pollution was based on daily average levels of PM2.5. Wildfire smoke events were determined by combining information from provincial databases and local monitors. Exposures were assumed using postal codes in the health record at the time of emergency department visits. Provincial claims data identified 27,501 asthma exacerbations in 57,375 children with asthma between 2010 to 2021. Wildfire smoke days demonstrated an increase in asthma exacerbations over the baseline (incidence rate ratio: 1.13; 95% CI: 1.02-1.24); this was not seen with air pollution in general. Increased rates of asthma exacerbations were also noted yearly in September. Asthma exacerbations were significantly decreased during periods of COVID-19 healthcare precautions.

Acceptance of and adherence with long-term positive airway pressure treatment in adults with chronic obstructive pulmonary disease: A systematic review protocol.

BACKGROUND: Long-term noninvasive positive airway pressure (PAP) treatment is effective treatment for sleep-related breathing disorders and chronic hypercarbic respiratory failure secondary to chronic obstructive pulmonary disease (COPD). PAP treatment may be delivered as continuous positive airway pressure or noninvasive ventilation. Success in initiating PAP treatment and barriers to its use in adult patients with COPD are largely unknown. This systematic review aims to identify the acceptance of and adherence to PAP treatment prescribed for long-term use in adult patients with COPD and to summarize variables associated with these measures. METHODS: Seven online electronic databases will be searched by an experienced medical librarian to identify records containing the concepts "obstructive airways disease" and "noninvasive positive airway pressure" and "acceptance" or "adherence". Randomized and non-randomized studies of interventions will be included. Citation lists from relevant articles will be reviewed, and experts will be contacted regarding unpublished studies. Abstracts from key conferences between 2018-2023 and Google Scholar search results will be reviewed for inclusion. Titles, abstracts and full texts will be reviewed independently for inclusion by two reviewers. Data extraction will be completed by one author using a pre-established form and primary outcomes confirmed by a second author. Methodological quality will be evaluated. If sufficient data are available for meta-analysis, a pooled summary statistic for the primary outcome will be calculated using a random-effects generic inverse-variance meta-analysis, weighted proportion or weighted medians-based approach. Subgroup analysis will explore clinically meaningful sources of heterogeneity. Variables that are associated with acceptance and adherence will be described. DISCUSSION: Long-term PAP treatment is a complex intervention prescribed to patients with COPD for several indications. Synthesis of the evidence on success with PAP treatment and variables associated with acceptance or adherence will inform program and policy development for supporting patients with COPD who are prescribed this therapy. TRIAL REGISTRATION: Systematic review registration: This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on July 13, 2021 (registration number CRD42021259262), with revisions submitted on April 17, 2023.

Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial.

BACKGROUND: People experiencing asthma exacerbations are at increased risk of cardiovascular events. To better understand the relationship between asthma exacerbations and cardiovascular risk, this randomized case-control, cross-over controlled trial assessed the immediate systemic inflammatory and vascular responses to acutely induced pulmonary inflammation and bronchoconstriction in people with asthma and controls. METHODS: Twenty-six people with asthma and 25 controls underwent three airway challenges (placebo, mannitol, and methacholine) in random order. Markers of cardiovascular risk, including serum C-reactive protein, interleukin-6, and tumor necrosis factor, endothelial function (flow-mediated dilation), microvascular function (blood-flow following reactive hyperemia), and arterial stiffness (pulse wave velocity) were evaluated at baseline and within one hour following each challenge. The systemic responses in a) asthma/control and b) positive airway challenges were analyzed. (ClinicalTrials.gov reg# NCT02630511). RESULTS: Both the mannitol and methacholine challenges resulted in clinically significant reductions in forced expiratory volume in 1 second (FEV1) in asthma (-7.6% and -17.9%, respectively). Following positive challenges, reduction in FEV1 was -27.6% for methacholine and -14.2% for mannitol. No meaningful differences in predictors of cardiovascular risk were observed between airway challenges regardless of bronchoconstrictor response. CONCLUSION: Neither acutely induced bronchoconstriction nor pulmonary inflammation and bronchoconstriction resulted in meaningful changes in systemic inflammatory or vascular function. These findings question whether the increased cardiovascular risk associated with asthma exacerbations is secondary to acute bronchoconstriction or inflammation, and suggest that other factors need to be further evaluated such as the cardiovascular impacts of short-acting inhaled beta-agonists.

Associations between social determinants of health and weight status in preschool children: a population-based study. / Associations entre les déterminants sociaux de la santé et le statut pondéral des enfants d'âge préscolaire : une étude de population.

INTRODUCTION: Social determinants of health (SDH) may influence children's weight status. Our objective was to examine relationships between SDH and preschoolers' weight status. METHODS: This retrospective cohort study included 169 465 children (aged 4-6 years) with anthropometric measurements taken at immunization visits from 2009 to 2017 in Edmonton and Calgary, Canada. Children were categorized by weight status based on WHO criteria. Maternal data were linked to child data. The Pampalon Material and Social Deprivation Indexes were used to assess deprivation. We used multinomial logistic regression to generate relative risk ratios (RRRs) to examine associations between ethnicity, maternal immigrant status, neighbourhood-level household income, urban/ rural residence and material and social deprivation with child weight status. RESULTS: Children of Chinese ethnicity were less likely than those in the General Population to have overweight (RRR = 0.64, 95% CI: 0.61-0.69) and obesity (RRR = 0.51, 0.42-0.62). Children of South Asian ethnicity were more likely than those in the General Population to have underweight (RRR = 4.14, 3.54-4.84) and more likely to have obesity (RRR = 1.39, 1.22-1.60). Children with maternal immigrant status were less likely than those without maternal immigrant status to have underweight (RRR = 0.72, 0.63-0.82) and obesity (RRR = 0.71, 0.66-0.77). Children were less likely to have overweight (RRR = 0.95, 0.94-0.95) and obesity (RRR = 0.88, 0.86-0.90) for every CAD 10 000 increase in income. Relative to the least deprived quintile, children in the most materially deprived quintile were more likely to have underweight (RRR = 1.36, 1.13-1.62), overweight (RRR = 1.52, 1.46-1.58) and obesity (RRR = 2.83, 2.54-3.15). Relative to the least deprived quintile, children in the most socially deprived quintile were more likely to have overweight (RRR = 1.21, 1.17-1.26) and obesity (RRR = 1.40, 1.26-1.56). All results are significant to p < 0.001. CONCLUSION: Our findings suggest the need for interventions and policies to address SDH in preschoolers to optimize their weight and health.

Reduced tidal volume-inflection point and elevated operating lung volumes during exercise in females with well-controlled asthma.

INTRODUCTION: Individuals with asthma breathe at higher operating lung volumes during exercise compared with healthy individuals, which contributes to increased exertional dyspnoea. In health, females are more likely to develop exertional dyspnoea than males at a given workload or ventilation, and therefore, it is possible that females with asthma may develop disproportional dyspnoea on exertion. The purpose of this study was to compare operating lung volume and dyspnoea responses during exercise in females with and without asthma. METHODS: Sixteen female controls and 16 females with asthma were recruited for the study along with 16 male controls and 16 males with asthma as a comparison group. Asthma was confirmed using American Thoracic Society criteria. Participants completed a cycle ergometry cardiopulmonary exercise test to volitional exhaustion. Inspiratory capacity manoeuvres were performed to estimate inspiratory reserve volume (IRV) and dyspnoea was evaluated using the Modified Borg Scale. RESULTS: Females with asthma exhibited elevated dyspnoea during submaximal exercise compared with female controls (p<0.05). Females with asthma obtained a similar IRV and dyspnoea at peak exercise compared with healthy females despite lower ventilatory demand, suggesting mechanical constraint to tidal volume (VT) expansion. VT-inflection point was observed at significantly lower ventilation and V̇O2 in females with asthma compared with female controls. Forced expired volume in 1 s was significantly associated with VT-inflection point in females with asthma (R2=0.401; p<0.01) but not female controls (R2=0.002; p=0.88). CONCLUSION: These results suggest that females with asthma are more prone to experience exertional dyspnoea, secondary to dynamic mechanical constraints during submaximal exercise when compared with females without asthma.

Perinatal and early life factors and asthma control among preschoolers: a population-based retrospective cohort study.

BACKGROUND: Preventing poor childhood asthma control is crucial for short-term and long-term respiratory health. This study evaluated associations between perinatal and early-life factors and early childhood asthma control. METHODS: This retrospective study used administrative health data from mothers and children born 2010-2012 with a diagnosis of asthma before age 5 years, in Alberta, Canada. The outcome was asthma control within 2 years after diagnosis. Associations between perinatal and early-life factors and risk of partly and uncontrolled asthma were evaluated by multinomial logistic regression. RESULTS: Of 7206 preschoolers with asthma, 52% had controlled, 37% partly controlled and 12% uncontrolled asthma 2 years after diagnosis. Compared with controlled asthma, prenatal antibiotics (adjusted risk ratio (aRR): 1.19; 95% CI 1.06 to 1.33) and smoking (aRR: 1.18; 95% CI 1.02 to 1.37), C-section delivery (aRR: 1.11; 95% CI 1.00 to 1.25), summer birth (aRR: 1.16; 95% CI 1.00 to 1.34) and early-life hospitalisation for respiratory illness (aRR: 2.24; 95% CI 1.81 to 2.76) increased the risk of partly controlled asthma. Gestational diabetes (aRR: 1.41; 95% CI 1.06 to 1.87), C-section delivery (aRR: 1.18; 95% CI 1.00 to 1.39), antibiotics (aRR: 1.32; 95% CI 1.08 to 1.61) and hospitalisation for early-life respiratory illness (aRR: 1.65; 95% CI 1.19 to 2.27) were associated with uncontrolled asthma. CONCLUSION: Maternal perinatal and early-life factors including antibiotics in pregnancy and childhood, gestational diabetes, prenatal smoking, C-section and summertime birth, and hospitalisations for respiratory illness are associated with partly or uncontrolled childhood asthma. These results underline the significance of perinatal health and the lasting effects of early-life experiences on lung development and disease programming.

Lack of tissue inhibitor of metalloproteinases 2 leads to exacerbated left ventricular dysfunction and adverse extracellular matrix remodeling in response to biomechanical stress.

BACKGROUND: Remodeling of the extracellular matrix (ECM) is a key aspect of myocardial response to biomechanical stress and heart failure. Tissue inhibitors of metalloproteinases (TIMPs) regulate the ECM turnover through negative regulation of matrix metalloproteinases (MMPs), which degrade the ECM structural proteins. Tissue inhibitor of metalloproteinases 2 is unique among TIMPs in activating pro-MMP2 in addition to inhibiting a number of MMPs. Given this dual role of TIMP2, we investigated whether TIMP2 serves a critical role in heart disease. METHODS AND RESULTS: Pressure overload by transverse aortic constriction (TAC) in 8-week-old male mice resulted in greater left ventricular hypertrophy, fibrosis, dilation, and dysfunction in TIMP2-deficient (TIMP2(-/-)) compared with wild-type mice at 2 weeks and 5 weeks post-TAC. Despite lack of MMP2 activation, total collagenase activity and specific membrane type MMP activity were greater in TIMP2(-/-)-TAC hearts. Loss of TIMP2 resulted in a marked reduction of integrin ß1D levels and compromised focal adhesion kinase phosphorylation, resulting in impaired adhesion of cardiomyocytes to ECM proteins, laminin, and fibronectin. Nonuniform ECM remodeling in TIMP2(-/-)-TAC hearts revealed degraded network structure as well as excess fibrillar deposition. Greater fibrosis in TIMP2(-/-)-TAC compared with wild-type TAC hearts was due to higher levels of SPARC (secreted protein acidic and rich in cysteine) and posttranslational stabilization of collagen fibers rather than increased collagen synthesis. Inhibition of MMPs including membrane type MMP significantly reduced left ventricular dilation and dysfunction, hypertrophy, and fibrosis in TIMP2(-/-)-TAC mice. CONCLUSIONS: Lack of TIMP2 leads to exacerbated cardiac dysfunction and remodeling after pressure overload because of excess activity of membrane type MMP and loss of integrin ß1D, leading to nonuniform ECM remodeling and impaired myocyte-ECM interaction.

Effect of the anti-oxidant tempol on fetal growth in a mouse model of fetal growth restriction.

Fetal growth restriction (FGR) greatly increases the risk of perinatal morbidity and mortality and is associated with increased uterine artery resistance and levels of oxidative stress. There are currently no available treatments for this condition. The hypothesis that the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol) would improve uterine artery function and rescue fetal growth was tested in a mouse model of FGR, using the endothelial nitric oxide synthase knockout mouse (Nos3(-/-)). Pregnant Nos3(-/-) and control C57BL/6J mice were treated with the superoxide dismutase-mimetic Tempol (1 mmol/L) or vehicle from Gestational Day 12.5 to 18.5. Tempol treatment significantly increased pup weight (P < 0.05) and crown-rump length (P < 0.01) in C57BL/6J and Nos3(-/-) mice. Uterine artery resistance was increased in Nos3(-/-) mice (P < 0.05); Tempol significantly increased end diastolic velocity in Nos3(-/-) mice (P < 0.05). Superoxide production in uterine arteries did not differ between C57BL/6J and Nos3(-/-) mice but was significantly increased in placentas from Nos3(-/-) mice (P < 0.05). This was not reduced by Tempol treatment. Placental System A activity was reduced in Nos3(-/-) mice (P < 0.01); this was not improved by treatment with Tempol. Treatment of Nos3(-/-) mice with Tempol, however, was associated with reduced vascular density in the placental bed (P < 0.05). This study demonstrated that treatment with the antioxidant Tempol is able to improve fetal growth in a mouse model of FGR. This was associated with an increase in uterine artery blood flow velocity but not an improvement in uterine artery function or placental System A activity.

Tissue inhibitor of metalloproteinases (TIMPs) in heart failure.

Remodeling of the myocardium and the extracellular matrix (ECM) occurs in heart failure irrespective of its initial cause. The ECM serves as a scaffold to provide structural support as well as housing a number of cytokines and growth factors. Hence, disruption of the ECM will result in structural instability as well as activation of a number of signaling pathways that could lead to fibrosis, hypertrophy, and apoptosis. The ECM is a dynamic entity that undergoes constant turnover, and the integrity of its network structure is maintained by a balance in the function of matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). In heart disease, levels of MMPs and TIMPs are altered resulting in an imbalance between these two families of proteins. In this review, we will discuss the structure, function, and regulation of TIMPs, their MMP-independent functions, and their role in heart failure. We will review the knowledge that we have gained from clinical studies and animal models on the contribution of TIMPs in the development and progression of heart disease. We will further discuss how ECM molecules and regulatory genes can be used as biomarkers of disease in heart failure patients.

An updated reference for age-sex-specific birth weight percentiles stratified for ethnicity based on data from all live birth infants between 2005 and 2014 in Alberta, Canada.

OBJECTIVE: This study aims to update the current reference for sex-specific birth weight percentiles by gestational age, overall and for specific ethnic groups, based on data from all singleton live-birth deliveries from 2005 to 2014 in Alberta, Canada. METHODS: Infant and maternal information were captured in the Alberta Vital Statistics-Births Database for 473,115 singleton infants born to 311,800 women between January 1, 2005 and December 31, 2014. Within each sex, and each sex-ethnic group, birth weights were modelled by gestational age using generalized additive models and natural cubic splines. Crude and corrected estimates for birth weight percentiles including cut-off values for large for gestational age (LGA) and small for gestational age (SGA) were calculated by sex and sex-ethnic group, and gestational age for singleton live births. RESULTS: LGA and SGA cut-offs were lower for females than for males for all gestational ages. The SGA and LGA percentiles were greater for both male and female very preterm infants in Alberta compared to previous national references. Ethnicity-specific LGA and SGA cut-offs for term Chinese and preterm and at-term South Asian infants were consistently lower than those for both the general population in Alberta and the previous national reference. South Asian infants had lower birth weights at almost all gestational ages compared with the other groups. CONCLUSION: The updated birth weight percentiles presented in this study highlight the differences in SGA and LGA cut-offs among infants from South Asian, Chinese, and the general population, which may be important for clinical perinatal care.

RéSUMé: OBJECTIFS: L'objectif de cette étude est d'actualiser la référence actuelle pour les percentiles de poids à la naissance spécifique au sexe par l'âge gestationnel, globalement et pour des groupes ethniques spécifiques, basé sur les données de tous les accouchements de naissances vivante uniques entre 2005 et 2014 en Alberta, au Canada. MéTHODES: L'information infantile et maternelle ont été capturées dans les statistiques de l'état civil ­ base de données sur les naissances, en Alberta, pour 473 115 nourrissons uniques nés de 311 800 femmes entre le 1er janvier 2005 et le 31 décembre 2014. Dans chaque sexe, et dans chaque groupe sexe-ethnique, les poids de naissances ont été modélisés par l'âge gestationnel grâce à l'utilisation de modèles additifs généralisés et de splines cubiques naturelles. Des estimations grossières et corrigées pour les percentiles de poids à la naissance, y compris les valeurs seuils pours les nourrissons gros pour l'âge gestationnel (GAG) et petits pour l'âge gestationnel (PAG), ont été calculées par sexe et groupe sexe-ethnique, et par l'âge gestationnel pour les naissances vivantes uniques. RéSULTATS: Les critères pour GAG et PAG étaient plus bas pour les femelles que pour les mâles pour tous les âges gestationnels. Les percentiles pour PAG et GAG étaient plus élevés pour les nourrissons mâles et femelles nés très prématurés en Alberta en comparaison avec les références nationales précédentes. Les critères pour GAG et PAG spécifiques à l'ethnicité chinoise, pour les nourrissons nés à termes, et sud-asiatiques, pour les nourrissons nés avant et à termes, étaient régulièrement plus basses que ceux de la population générale en Alberta et de la référence nationale précédente. Les nourrissons sud-asiatiques avaient des poids de naissances plus basses à presque tous les âges gestationnels en comparaison avec les autres groupes. CONCLUSION: Les percentiles de poids à la naissance actualisés présentés dans cette étude mettent en évidence les différences de PAG et GAG entre les nourrissons sud-asiatiques, chinoises et de la population générale, qui peuvent êtres importantes pour les soins cliniques périnatales.

Systemic vascular health is compromised in both confirmed and unconfirmed asthma.

INTRODUCTION: Asthma is associated with increased risk of cardiovascular diseases. Despite many presenting with symptoms of asthma, asthma cannot always be confirmed by physiological assessment. It is thus far unknown if the heightened cardiovascular risk applies to this group. The purpose of this study was to examine markers of cardiovascular risk, including endothelial function, arterial stiffness, and systemic inflammation, in individuals with confirmed asthma, unconfirmed asthma, and healthy controls. As short-acting beta agonist (SABA) use is associated with increased cardiovascular risk, a secondary analysis was conducted to investigate the impact of regular SABA use on vascular outcomes. METHODS: Individuals with confirmed asthma (n = 26), unconfirmed asthma (n = 15), and healthy controls (n = 26) were recruited for this cross-sectional study. Asthma was confirmed by FEV1 reversibility, methacholine challenge, or exercise challenge. Endothelial function was assessed using flow-mediated dilation (FMD), arterial stiffness using pulse wave velocity (PWV), and systemic inflammation by C-reactive protein (CRP) levels. RESULTS: FMD was significantly lower in both asthma groups compared to controls (confirmed: 7.7 ± 3.6%, unconfirmed: 7.3 ± 3.5%, controls: 10.4 ± 3.6%, p = 0.02). No difference was found in PWV nor CRP. Asthma participants who used SABA had increased arterial stiffness compared to those without SABA (9.2 ± 2.7 m/s, 7.7 ± 1.1 m/s respectively, p = 0.03). No difference was seen in FMD or CRP between SABA groups. CONCLUSION: Individuals with a clinical history of asthma symptoms demonstrate vascular impairments regardless of physiological confirmation of disease. Regular SABA use increases arterial stiffness. Avoiding potentially inappropriate SABA use among people without physiologically confirmed asthma may thus be beneficial in curbing cardiovascular risk.

Association between the antepartum oral glucose tolerance test and the risk of future diabetes mellitus among women with gestational diabetes: A systematic review and meta-analysis.

OBJECTIVES: The antepartum oral glucose tolerance test (OGTT) has re-emerged as associated with risk of diabetes among women with gestational diabetes (GDM). This systematic review summarized evidence on associations between antepartum OGTT and risk of diabetes in GDM (PROSPERO CRD42018100316). METHODS: MEDLINE, EMBASE, Web of Science, and CENTRAL were searched from January 1, 1982 to February 2020. Studies assessing associations between antepartum OGTT and risk of diabetes among women with GDM were included. Data on study characteristics, participants, OGTT values, and diabetes outcomes were extracted. Estimates on the association between antepartum OGTT and diabetes at follow-up were recorded. Pooled odds ratios for developing diabetes were calculated by study design. FINDINGS AND CONCLUSIONS: Of 6423 citations, 17 studies were included. Both elevated fasting blood glucose (FBG; OR: 3.62 ([95% CI 1.30, 10.12], I2 = 36%, p < 0.05)) and 2 h OGTT (OR: 3.96 [1.17, 13.40], I2 = 87%, p < 0.05) were associated with diabetes. These associations were attenuated (FBG: OR: 1.91 ([95% CI 0.80, 24.54], I2 = 83%, p = NS) and 1.58 ([95% CI 0.92, 2.74] I2 = 83%, p = NS) for prospective and retrospective data, respectively; 2 h OGTT: ORa: 1.95 ([95% CI 0.43, 8.93], I2 = 94%, p = NS)) after adjustments for common confounders. Further research is needed before clinical recommendations can be made.

The effect of pulmonary rehabilitation on carotid chemoreceptor activity and sensitivity in chronic obstructive pulmonary disease.

Recent work demonstrates that carotid chemoreceptor (CC) activity/sensitivity is elevated in patients with chronic obstructive pulmonary disease (COPD) compared with healthy controls, and this elevated chemoreception appears to contribute to increased cardiovascular risk. Exercise training has been shown to normalize CC activity/sensitivity in other populations, and therefore, the purpose of this study was to determine whether pulmonary rehabilitation (PR) can reduce CC activity/sensitivity in COPD. Forty-five COPD patients [mean FEV1 (forced expiratory volume in 1 s) = 56.6% predicted] completed PR, while 15 COPD patients (mean FEV1 = 74.6% predicted) served as non-PR controls. CC activity was determined by the reduction in ventilation while breathing transient hyperoxia ([Formula: see text] = 1.0); CC sensitivity was evaluated by the increase in ventilation relative to the drop in arterial saturation while breathing hypoxia. Dyspnea, six-minute walk and autonomic function data were also obtained. PR improved 6-minute walk distance (P < 0.001) and dyspnea (P = 0.04); however, there was no effect on CC activity (P = 0.60), sensitivity (P = 0.69), or autonomic function (P > 0.05 for all). Subgroup analyses indicated that PR reduced CC activity in those with elevated baseline CC activity, independent of changes in autonomic function. No change in dyspnea (P = 0.24), CC activity (P = 0.19), sensitivity (P = 0.80), or autonomic function (P > 0.05 for all) was observed in the control group. Despite improvements in exercise tolerance and dyspnea, PR appears to be generally ineffective at reducing CC sensitivity in stable COPD patients; while PR reduced CC activity in those with elevated basal CC activity, the physiological significance of this is unclear. Further investigations aimed at improving CC function in COPD are needed.NEW & NOTEWORTHY While work in other chronic diseases has shown that exercise training may help normalize carotid chemoreceptor (CC) activity/sensitivity, the current study found that exercise training through pulmonary rehabilitation did not consistently reduce CC activity/sensitivity in patients with chronic obstructive pulmonary disease (COPD). These results suggest that other interventions are needed to normalize CC activity/sensitivity in COPD.

Incidence of Syncope During Pregnancy: Temporal Trends and Outcomes.

Background We examined temporal trends, timing, and frequency, as well as adverse neonatal and maternal outcomes occurring in the first year postpartum among women experiencing syncope during pregnancy. Methods and Results This was a retrospective study of pregnancies between January 1, 2005, and December 31, 2014, in the province of Alberta, Canada. Of 481 930 pregnancies, 4667 had an episode of syncope. Poisson regression analysis found a 5% increase/year (rate ratio, 1.05; 95% CI, 1.04-1.06) in the age-adjusted incidence of syncope. Overall, 1506 (32.3%) of the syncope episodes first occurred in the first trimester, 2058 (44.1%) in the second trimester, and 1103 (23.6%) in the third trimester; and 8% (n=377) of pregnancies had >1 episode of syncope. Compared with women without syncope, women who experienced syncope were younger (age <25 years; 34.7% versus 20.8%; P<0.001), and primiparous (52.1% versus 42.4%; P<0.001). The rate of preterm birth was higher in pregnancies with syncope during the first trimester (18.3%), compared with the second (15.8%) and third trimesters (14.2%) and pregnancies without syncope (15.0%; P<0.01). The incidence of congenital anomalies among children born of pregnancies with multiple syncope episodes was significantly higher (4.9%) compared with children of pregnancies without syncope (2.9%; P<0.01). Within 1 year after delivery, women with syncope during pregnancy had higher rates of cardiac arrhythmias and syncope episodes than women with no syncope during pregnancy. Conclusions Pregnant women with syncope, especially when the syncopal event occurs during the first trimester, may be at a higher risk of adverse pregnancy outcomes as well as an increased incidence of cardiac arrhythmia and syncope postpartum.

Acute effects of salbutamol on systemic vascular function in people with asthma.

BACKGROUND: Asthmatics are at increased cardiovascular disease risk, which has been linked to beta2(ß2)-agonist use. Inhalation of ß2-agonists increases sympathetic nerve activity (SNA) in healthy individuals, however the systemic impact of salbutamol in asthmatics using ß2-agonists regularly is unknown. OBJECTIVES: This study compared the systemic vascular responses to a clinical dose of salbutamol (Phase I) and following an acute increase in SNA (Phase II) in asthmatics and controls. METHODS: Fourteen controls and 14 asthmatics were recruited for Phase I. On separate days, flow-mediated dilation (FMD) and peripheral arterial stiffness (pPWV) were evaluated at baseline and following either 400 µg inhaled salbutamol or a placebo inhaler. For Phase II, heart rate, blood pressure, vascular conductance, pPWV, and central (c)PWV were evaluated in response to a large increase in SNA brought on by cold-water hand immersion (i.e. cold-pressor test) or body-temperature water hand immersion (i.e. control) in 10 controls and 10 asthmatics. RESULTS: Following salbutamol, asthmatics demonstrated reduced FMD (-3.0%, p < 0.05) and increased pPWV (+0.7 m/s, p < 0.05); however, salbutamol had no effect in controls. The cold-pressor test resulted in similar increases in blood pressure, vascular flow rates and conductance, pPWV, and cPWV in both asthmatics and controls, suggesting similar neurovascular transduction in asthmatics and controls. CONCLUSION: Inhaled Salbutamol leads to increased arterial stiffness and reduced FMD in asthmatics. As asthmatics and controls had similar vascular responses to an increase in SNA, these findings suggest asthmatics have heightened sympathetic responses to ß2-agonists which may contribute to the increased cardiovascular risk in asthma.