Increase In Relative Risk Research Articles

Air quality and the risk of out-of-hospital cardiac arrest in Singapore (PAROS): a time series analysis

Previous studies have reported positive associations between out-of-hospital cardiac arrest (OHCA) and air pollutant concentrations, but there are inconsistencies across studies. We aimed to investigate the association between pollutant concentrations and the risk of OHCA in Singapore. We did a time series analysis of all cases of OHCA in Singapore reported between July 1, 2010, and Dec 31, 2018, to the Pan-Asian Resuscitation Outcomes Study (PAROS), a prospective, population-based registry. Using multivariable fractional polynomial modelling, we investigated the immediate (day 0) and lagged (up to 5 days after exposure) association between 10 μg/m³ increases in concentrations of particulate matter with a diameter of 2·5 μm or smaller (PM_2·5), particulate matter with a diameter of 10 μm or smaller (PM₁₀), ozone (O₃), nitrogen dioxide (NO₂), and sulphur dioxide (SO₂) and 1 mg/m³ increase in carbon monoxide (CO) and relative risk (RR) of OHCA. We extracted data for 18 131 cases of OHCA. The median age of this cohort of cases was 65 years (IQR 56-80), 6484 (35·8%) were female, 11 647 (64·2%) were male, 12 270 (67·7%) were Chinese, 2873 (15·8%) were Malay, and 2010 (11·1%) were Indian. Every 10 μg/m³ increase in PM_2·5 was associated with increased risk of OHCA (RR 1·022 [95% 1·002-1·043]) over the next 2 days, which decreased over the subsequent 3 days (3-5 days after exposure; 0·976 [0·955-0·998]). For PM₁₀, O₃, NO₂, and SO₂, we did not observe any associations between increased concentration and risk of OHCA on day 0 or cumulative risk over time (ie, at 0-1 days, 0-2 days, 0-3 days, 0-4 days, 0-5 days, and 3-5 days after exposure). For CO, we observed a cumulative decreased risk of OHCA across 0-5 days after exposure (0·876 [0·770-0·997]) and at days 3-5 after exposure (0·810 [0·690-0·949]). We observed effect modification of the association between increasing PM_2·5 concentration and OHCA 0-2 days after exposure by cardiac arrest rhythm (non-shockable 1·027 [1·004-1·050] vs shockable 1·002 [0·956-1·051]) and location of OHCA (at home: 1·033 [1·008-1·057] vs not at home 0·955 [0·957-1·035]). In hypothetical modelling, the number of OHCA events associated with PM_2·5 could be reduced by 8% with a 1 μg/m³ decrease in PM_2·5 concentrations and by 30% with a 3 μg/m³ decrease in PM_2·5 concentrations. Increases in PM_2·5 concentration were associated with an initial increased risk of OHCA and a subsequent reduced risk from 3-5 days after exposure, suggesting a short-term harvesting effect. A decrease in PM_2·5 concentrations could reduce population demand for emergency health services. National Medical Research Council, Singapore, under the Clinician Scientist Award, Singapore and the Singapore Translational Research Investigator Award (MOH-000982-01).

Increases in the Macrolide Resistance of Mycoplasma genitalium and the Emergence of the A2058T Mutation in the 23S rRNA Gene: Clonal Spread?

The management of Mycoplasma genitalium sexually transmitted infection (STI) is hindered by increasing resistance to the recommended antibiotics, macrolides and quinolones, worldwide. In Gipuzkoa (Basque Country, Spain), macrolide and quinolone resistance rates in 2014-2018 were reported as <20% and <10%, respectively. The aims of this study were to compare these rates with those in 2019-2021 and analyse the genetic and epidemiological features of the strains and cases associated with striking changes in the resistance trends. Resistance to macrolides (n = 1019) and quinolones (n = 958) was studied, analysing mutations in 23S rRNA and parC/gyrA genes, respectively. The rate of macrolide resistance increased from 17.3% in 2014-2018 to 32.1% in 2019-2021, as much in the more prevalent A2058/2059G mutations (16.6-27.8%) as in the emergent A2058T mutations (0.5-4.1%) but with differences in the odds ratios and the relative risk increase between A2058T and A2058/2059G mutations. MG191 adhesin and MG309 lipoprotein of the 27 emergent strains detected with A2058T mutations were amplified, sequenced, and typed using phylogenetic and variable number tandem repeat analysis, respectively. Genetic clonal spread was ruled out, but most of the A2058T cases were men who had sex with men (24/27) with a history of STI and antibiotic treatments (19/27). No changes were observed in quinolone resistance trends, but the rate of resistance to both antibiotics rose from 2.9% to 8.3%, especially in cases with A2058T mutations. The genetic characterisation of strains and epidemiological surveillance of cases are needed to detect populations at increased risk of treatment failure in this infection.

Circadian preference in young adults: Associations with sleep and mental health outcomes from a national survey of Norwegian university students

ABSTRACT Individual preferred timing of sleep and activity patterns, known as circadian preference, ranges from definitely morning types to definitely evening types. Being an evening type has been linked to adverse sleep and mental health outcomes. This study aimed to explore the associations between circadian preference and self-reported sleep, depression, anxiety, quality of life, loneliness, and self-harm/suicidal thoughts. Data stem from a national survey of students in higher education in Norway (the SHoT-study). All 169,572 students in Norway were invited to participate, and 59,554 students (66.5% women) accepted (response rate = 35.1%). Circadian preference was associated with sleep and mental health outcomes in a dose–response manner. For both genders, being an evening type (either definitely evening or more evening than morning) was associated with an increase in age-adjusted relative risk (RR-adjusted; range = 1.44 to 2.52 vs. 1.15 to 1.90, respectively) across all outcomes compared with definitely morning types. Overall, the present study provides further evidence that evening circadian preference is associated with adverse sleep and mental health outcomes in young adults. As such, future efforts to improve sleep and mental health in young adults should consider their circadian preferences.

Characterizing mild cognitive impairment to predict incident dementia in adults with bipolar disorder: What should the benchmark be?

Objective: Although mild cognitive impairment (MCI) is generally considered a risk state for dementia, its prevalence and association with dementia are impacted by the number of tests and cut-points used to assess cognition and define “impairment,” and sources of norms. Here, we investigate how these methodological variations impact estimates of incident dementia in adults with bipolar disorder (BD), a vulnerable population with pre-existing cognitive deficits and increased dementia risk. Method: Neuropsychological data from 148 adults with BD and 13,610 healthy controls (HC) were drawn from the National Alzheimer’s Coordinating Center. BD participants’ scores were standardized against published norms and again using regression-based norms generated from HC within the same catchment area as individual BD patients (“site-specific norms”), varying the number of within-domain tests (one vs. two) and the cut-points (−1 vs. −1.5 SD) used to operationalize MCI. Results: Site-specific norms were more sensitive to incident dementia (88.6%–94.3%) than published norms (74.3%–88.6%), but only when using a “single test” definition of impairment. Specificity (22.1%–74.3%), accuracy (37.8%–68.9%), and positive predictive values (26.1%–38.3%) were overall poor. Applying a “single test” definition of impairment resulted in better negative predictive values using site-specific (92.3%–93.3%) than published norms (83.6%–86.2%), and a substantial increase in relative risk of incident dementia relative to published norms. Conclusions: Neuropsychologists should define “impairment” as scores below −1.0 or −1.5 SD on at least two within-domain measures when using published norms to interpret cognitive performance in adults with BD.

Exploring the association between precipitation and population cases of ocular toxoplasmosis in Colombia.

Previous studies suggest a relationship between precipitation and ocular toxoplasmosis (OT) reactivation and congenital toxoplasmosis infection. We aimed to investigate the relationship between precipitation and the frequency of new OT cases in Colombia from 2015 to 2019. This retrospective cohort study analyzed data obtained from a claims-based database created by the Colombian Ministry of Health and national registries of precipitation of the Institute of Hydrology, Meteorology, and Environmental Studies. We estimated the daily number of OT cases, interpolating data from the average number of annual cases from 2015 to 2019. Then, we compared exposures (mean daily precipitation) in the case period in which the events (interpolated OT new cases) occurred by a quasi-Poisson regression, combined with a distributed lag non-linear model to estimate the non-linear and lag-response curve. In the 5-year analysis, there were 1,741 new OT cases. Most of the cases occurred in 2019, followed by 2015 and 2018. New OT cases among departments were significantly different (P< 0.01). The cumulative exposure-response curve was decreasing for most departments. Nevertheless, in Chocó, Bogotá, Cesar, Cauca, and Guajira, when a certain amount of precipitation accumulates, the relative risk (RR) increases, which was contrary to the pattern observed in the other regions. The response curves to the one-day lag showed that precipitation influences the RR; however, the trends vary by department. Finally, an increasing trend in the number of cases was directly proportional to precipitation in Guajira, Atlántico, Norte de Santander, Santander, Caquetá and Quindío (r = 0.84; P< 0.05). Precipitation influenced the RR for new OT cases. However, varying trends among geographical regions (departments) lead us to hypothesize that other sociodemographic, behavioral, and environmental variables, such as wind and water contamination, could influence the RR.

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations During the COVID-19 Pandemic, March to October 2020

ObjectiveTo compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. Patients and MethodsThe study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre–COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames. ResultsThe adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre–COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre–COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05). ConclusionThe findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre–COVID-19 time frame.

Overestimation of benefit when clinical trials stop early: a simulation study

BackgroundStopping trials early because of a favourable interim analysis can exaggerate benefit. This study simulated trials typical of those stopping early for benefit in the real world and estimated the degree to which early stopping likely overestimates benefit.MethodsFrom 1 million simulated trials, we selected those trials that exceeded interim stopping criteria, and compared apparent benefit when stopped with the true benefit used to generate the data. Each simulation randomly assigned period of observation, number of subjects, and control event rate using normal distributions centred on the same parameters in a template trial typical of real-world “truncated” (i.e. stopped for benefit) trials. The intervention’s true relative risk reduction (RRR) was also randomized, and assumed 1% of drugs have a warfarin-like effect (60% RRR), 5% a statin-like effect (35% RRR), 39% an ASA-like effect (15% RRR), 50% no effect (0% RRR), and that 5% would cause harm (modelled as a 20% relative risk increase). Trials had a single interim analysis and a z-value for stopping of 2.782 (O’Brien-Fleming threshold). We also modelled (1) a large truncated trial based on the SPRINT blood pressure trial (using SPRINT’s parameters and stopping criteria) and (2) the same typical truncated trials if they instead went to completion as planned with no interim analysis.ResultsFor typical truncated trials, the true RRR was roughly 2/3 the observed RRR at the time of stopping. RRR was overestimated by an absolute 14.9% (median, IQR 6.4–24.6) in typical truncated trials, by 5.3% (IQR −0.1 to 11.4) in the same trials if instead carried to completion, and by 2.3% (IQR 0.98–1.09) in large SPRINT-like trials. For all models, to keep the absolute RRR overestimate below 5%, 250 events were required.ConclusionSimulated trials typical of those stopping early for benefit overestimate the true relative risk reduction by roughly 50% (i.e. the true RRR was 2/3 of the observed value). Overestimation was much smaller, and likely unimportant, when simulating large SPRINT-like trials stopping early. Whether trials were large or small, stopped early or not, a minimum 250 events were needed to avoid overestimating relative risk reduction by an absolute 5% or more.

Looking beyond the Skin: Pathophysiology of Cardiovascular Comorbidity in Psoriasis and the Protective Role of Biologics.

Psoriasis is a chronic systemic inflammatory disease associated with a higher incidence of cardiovascular disease, especially in patients with moderate to severe psoriasis. It has been estimated that severe psoriasis confers a 25% increase in relative risk of cardiovascular disease, regardless of traditional risk factors. Although the underlying pathogenic mechanisms relating psoriasis to increased cardiovascular risk are not clear, atherosclerosis is emerging as a possible link between skin and vascular affection. The hypothesis that the inflammatory cascade activated in psoriasis contributes to the atherosclerotic process provides the underlying basis to suggest that an anti-inflammatory therapy that improved atherosclerosis would also reduce the risk of MACEs. In this sense, the introduction of biological drugs which specifically target cytokines implicated in the inflammatory cascade have increased the expectations of control over the cardiovascular comorbidity present in psoriasis patients, however, their role in vascular damage processes remains controversial. The aim of this paper is to review the mechanistic link between psoriasis and cardiovascular disease development, as well as analyzing which of the biological treatments could also reduce the cardiovascular risk in these patients, fueling a growing debate on the modification of the general algorithm of treatment.

P8.134: Advanced Cancers Treated With PD-L1 Inhibitors and CTLA-4 Antagonist in Transplanted Immunosuppressed Patients: Systematic Review of Graft Outcome

Background: Cancer is a major cause of morbidity and mortality in transplanted patients: its overall risk is increased two to three times compared to the general population, and it’s inversely related to age, with younger recipients experiencing a greater relative increase in risk compared to older recipients. Plus, the prognosis is worse for recipients diagnosed with cancer, compared to the general population, because of immunosuppressive drugs. The aim of this study is to demonstrate a correlation between use of CTLA-4 antagonist and PD-L1 inhibitors in transplanted patients with de novo malignancies and grafts outcome. Methods: A literature review concerning the use of anti PD-L1 and CTLA-4 antagonists in transplanted patients with advanced neoplasm was performed. The analyzed variables were: age, sex, transplanted solid organ, immunosuppressive induction and maintenance therapy performed, type of cancer developed, developmental latency time, anticancer drugs administered, possible rejection and related therapy administered, patient outcome. Results: A sample of 52 patients was sort from the literature review. The statistical analysis revealed that no variables had a significant correlation with graft rejection after the use of checkpoint inhibitors. The use of CTLA-4 antagonists seems to be associated with a less significant risk of development of graft rejection than PD-L1 inhibitors (OR = 4.00, p = 0.06). Conclusions: The available data suggest that CTLA-4 antagonists are safer in transplanted patients than PD-L1 inhibitors, which were associated with a higher risk of allograft rejection. This study didn’t identify an agent responsible for different outcomes between patients treated with PD-L1 inhibitors and CTLA-4 antagonists. Checkpoint inhibitors have proved to be valid for treatment of various malignancies, but transplanted cancer patients have never been included in clinical trials on their efficacy, because of the risk of graft rejection. Further studies and trials are needed to ensure these patients the best possible treatments.

Autoimmune diseases and atherothrombotic risk

Clinical investigators have long observed that patients with rheumatoid arthritis, inflammatory bowel disease, lupus, and psoriasis have increased rates of incident cardiovascular disease, often a decade earlier than among healthy individuals in the general population. 1 Solomon DH Karlson EW Rimm EB et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003; 107: 1303-1307 Crossref PubMed Scopus (1033) Google Scholar , 2 England BR Thiele GM Anderson DR Mikuls TR Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. BMJ. 2018; 361k1036 PubMed Google Scholar For example, psoriasis, a common T-helper cell type 1/17 immunological disorder, confers an increased risk of myocardial infarction over the life span with the greatest relative increase in risk among those with severe disease in their 30s and 40s. 3 Gelfand JM Neimann AL Shin DB Wang X Margolis DJ Troxel AB Risk of myocardial infarction in patients with psoriasis. JAMA. 2006; 296: 1735-1741 Crossref PubMed Scopus (1466) Google Scholar Yet, to date, most studies of chronic inflammatory disorders and cardiovascular risk have focused on one disease entity at a time and used sampling techniques of moderate sample size. Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UKThese findings warrant targeted cardiovascular prevention measures, in particular in younger patients with autoimmune diseases, and further research into pathophysiological mechanisms underlying these complications. Full-Text PDF

Severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Pregnancy in Ontario: A Matched Cohort Analysis.

Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than nonpregnant people to accept vaccination. We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy using a population-based SARS-CoV-2 case file from Ontario, Canada. Because of varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10-49 years old). Risk of severe SARS-CoV-2 outcomes was evaluated in pregnant women and time-matched nonpregnant controls using multivariable conditional logistic regression. Compared with the rest of the population, nonpregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio, 1.28), whereas risk of infection was reduced among pregnant women (standardized morbidity ratio, 0.43). After adjustment for confounding, pregnant women had a markedly elevated risk of hospitalization (adjusted odds ratio, 4.96; 95% confidence interval, 3.86-6.37) and intensive care unit admission (adjusted odds ratio, 6.58; 95% confidence interval, 3.29-13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity, .004). Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favors SARS-CoV-2 vaccination in pregnant women.

Weather impacts on various types of road crashes: a quantitative analysis using generalized additive models

Adverse weather conditions can have different effects on different types of road crashes. We quantify the combined effects of traffic volume and meteorological parameters on hourly probabilities of 78 different crash types using generalized additive models. Using tensor product bases, we model non-linear relationships and combined effects of different meteorological parameters. We evaluate the increase in relative risk of different crash types in case of precipitation, sun glare and high wind speeds. The largest effect of snow is found in case of single-truck crashes, while rain has a larger effect on single-car crashes. Sun glare increases the probability of multi-car crashes, in particular at higher speed limits and in case of rear-end crashes. High wind speeds increase the probability of single-truck crashes and, for all vehicle types, the risk of crashes with objects blown on the road. A comparison of the predictive power of models with and without meteorological variables shows an improvement of scores of up to 24%, which makes the models suitable for applications in real-time traffic management or impact-based warning systems. These could be used by authorities to issue weather-dependent driving restrictions or situation-specific on-board warnings to improve road safety.

Japanese school children's intake of selected food groups and meal quality due to differences in guardian's literacy of meal preparation for children during the COVID-19 pandemic

In 2020, a state of emergency (SOE) was enforced by the Japanese government, which included temporary school closures with the aim of overcoming COVID-19 spread, which prevented access to school lunches. We evaluated the relationship between meal quality and guardians' literacy of meal preparation for a nationally representative sample of 1107 Japanese schoolchildren (aged 10–14 years) before, during, and after the SOE on the basis of 7 questions scored using a 5-point Likert scale. The guardians' literacy of meal preparation for children was divided into quartiles, with Q1 and Q4 including participants with the lowest and highest scores on food literacy, respectively. School lunch menu was handed out monthly to each household by their classroom teacher. The consumption of (i) meat, fish, or eggs and (ii) vegetables at least twice a day indicated “well-balanced dietary intake”, which was less frequent in all four quartiles, especially for Q1 and Q2, during compared to before the SOE. The relative risk increases (95% CI) were Q1: −40.6% (−41.4% to −39.8%; p < 0.001), Q2: −34.0% (−34.7% to −33.3%; p < 0.001), Q3: −13.1% (−13.8% to −12.4%; p < 0.001), and Q4: −15.3% (−16.0% to −14.7%; p < 0.001), adjusted for sex, age, BMI, equivalent income adjusted for the number of household members, and educational level of parents. The interaction p was <0.001 for Q1–3 vs. Q4. Guardians with low total scores were significantly more likely to have less time, mental capacity, and financial ability to prepare meals after the SOE. Therefore, schoolchildren's meal quality deteriorated during the SOE, particularly among those with guardians with low food literacy even after adjustment for household income level and guardians' educational level.

De Novo Inflammatory Bowel Disease Following Bariatric Surgery: a Systematic Review and Meta-analysis.

The incidence of both obesity and inflammatory bowel disease (IBD) is rising globally. The influence of bariatric metabolic surgery (BMS) upon IBD development is largely unknown. This systematic review and meta-analysis aimed to evaluate the relationship between BMS and the risk of de novo IBD development following surgery. A systematic literature search and meta-analysis were performed using PubMed and Scopus databases. Inclusion criteria were any study reporting risk of de novo IBD development following BMS relative to an appropriate control cohort. Pooled odds ratios (POR) were calculated. A total of 31 articles were identified by the literature search. Four studies including 149,385 patients met the inclusion criteria and were included in the meta-analysis. Pooled estimation of a meta-analysis of risk ratios studies demonstrated a POR for the development of IBD following BMS of 1.17 (95% CI, 1.06-1.29). This indicates a 17% increase in relative risk of de novo IBD development for those patients receiving BMS compared to those treated by non-surgical methods. Based on the present data, there appears to be an association between BMS and risk of de novo IBD. Compared to the proven benefits of BMS on other aspects of patient health, this potential risk remains proportionally low but may be an important consideration for patients both pre- and post-operatively.

Modeling the impact of indoor relative humidity on the infection risk of five respiratory airborne viruses

With a modified version of the Wells-Riley model, we simulated the size distribution and dynamics of five airborne viruses (measles, influenza, SARS-CoV-2, human rhinovirus, and adenovirus) emitted from a speaking person in a typical residential setting over a relative humidity (RH) range of 20–80% and air temperature of 20–25 °C. Besides the size transformation of virus-containing droplets due to evaporation, respiratory absorption, and then removal by gravitational settling, the modified model also considered the removal mechanism by ventilation. The trend and magnitude of RH impact depended on the respiratory virus. For rhinovirus and adenovirus humidifying the indoor air from 20/30 to 50% will be increasing the relative infection risk, however, this relative infection risk increase will be negligible for rhinovirus and weak for adenovirus. Humidification will have a potential benefit in decreasing the infection risk only for influenza when there is a large infection risk decrease for humidifying from 20 to 50%. Regardless of the dry solution composition, humidification will overall increase the infection risk via long-range airborne transmission of SARS-CoV-2. Compared to humidification at a constant ventilation rate, increasing the ventilation rate to moderate levels 0.5 → 2.0 h−1 will have a more beneficial infection risk decrease for all viruses except for influenza. Increasing the ventilation rate from low values of 0.5 h−1 to higher levels of 6 h−1 will have a dominating effect on reducing the infection risk regardless of virus type.

Ultrasound Atherosclerosis Burden Score as a tool for predicting adverse cardiovascular events in patients with various cardiovascular risks aged 40-64 years

Aim. To investigate the prognostic significance of the Atherosclerosis Burden Score (ABS) in relation to the development of major adverse cardiovascular events in patients of different cardiovascular risks (CVR) aged 40 to 64 years.Material and methods. Men and women aged 40 to 64 years were included in the study. All the patients underwent duplex scanning of the carotid arteries and lower limb arteries. The total ABS was calculated by assessing the presence of plaque in the carotid and femoral bifurcations on both sides. The combined endpoint was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or peripheral artery revascularization.Results. The study included 232 patients who met the inclusion criteria, with a median age of 55,0 years. Very high CVR was established in 94 (40,5%) patients, while high CVR — in 48 (20,7%) patients, and low and intermediate CVR — in 90 (38,8%) patients. The follow-up period lasted 23,6 (15,5; 51,2) months, providing 632,6 patient-years of follow-up. Events within composite endpoint occurred in 28 (12,1%) patients. Increased cumulative risk of adverse cardiovascular events was observed for ABS ≥2, with a significant increase in relative risk (RR) for ABS ≥3. According to Cox regression analysis, ABS 3 was associated with a 3,71-fold (95% CI 1,18-11,6; p=0,025) increase in the RR of adverse cardiovascular events after adjustment for sex, age, baseline CVR, obesity, smoking, diabetes, CAD, a history of myocardial revascularization, type 2 diabetes, drug therapy, and levels of non-high density lipoprotein cholesterol, highly sensitive C-reactive protein, and glomerular filtration rate.Conclusion. In patients of various CVR aged 40-64 years, an ABS ≥3 was associated with a 3,71-fold (95% CI, 1,18-11,6; p=0,025) increase in relative risk of adverse cardiovascular events after adjusting for potential confounders, including sex, age, baseline CVR, CAD, and type 2 diabetes.

Monocyte subsets, T cell activation profiles, and stroke in men and women: The Multi-Ethnic Study of Atherosclerosis and Cardiovascular Health Study

Background and aimsDespite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes – key determinants of inflammation propagation versus resolution – and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke. MethodsWe investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models. ResultsWe observed associations of intermediate monocytes, early-activated CD4+ T cells, and both CD4+ and CD8+ T cells producing interleukin-4 after cytokine stimulation (Th2 and Tc2, respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women. ConclusionsCirculating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention.

Whole-Exome Sequencing in Congenital Hypothyroidism Due to Thyroid Dysgenesis.

Context:Congenital hypothyroidism due to thyroid dysgenesis (CHTD) is a predominantly sporadic and nonsyndromic (NS) condition of unknown etiology. NS-CHTD shows a 40-fold increase in relative risk among first-degree relatives (1 in 100 compared with a birth prevalence of 1 in 4000 in the general population), but a discordance rate between monozygotic (MZ) twins of 92%. This suggests a two-hit mechanism, combining a genetic predisposition (incomplete penetrance of inherited variants) with postzygotic events (accounting for MZ twin discordance).Objective:To evaluate whether whole-exome sequencing (WES) allows to identify new predisposing genes in NS-CHTD.Methods:We performed a case–control study by comparing the whole exome of 36 nonconsanguineous cases of NS-CHTD (33 with lingual thyroid ectopy and 3 with athyreosis, based on technetium pertechnetate scintigraphy at diagnosis) with that of 301 unaffected controls to assess for enrichment in rare protein-altering variants. We performed an unbiased approach using a gene-based burden with a false discovery rate correction. Moreover, we identified all rare pathogenic and likely pathogenic variants, based on in silico prediction tools, in 27 genes previously associated with congenital hypothyroidism (CH) (thyroid dysgenesis [TD] and dyshormonogenesis).Results:After correction for multiple testing, no enrichment in rare protein-altering variants was observed in NS-CHTD. Pathogenic or likely pathogenic variants (21 variants in 12 CH genes) were identified in 42% of cases. Eight percent of cases had variants in more than one gene (oligogenic group); these were not more severely affected than monogenic cases. Moreover, cases with protein-altering variants in dyshormonogenesis-related genes were not more severely affected than those without.Conclusions:No new predisposing genes were identified following an unbiased analysis of WES data in a well-characterized NS-CHTD cohort. Nonetheless, the discovery rate of rare pathogenic or likely pathogenic variants was 42%. Eight percent of the cases harbored multiple variants in genes associated with TD or dyshormonogenesis, but these variants did not explain the variability of hypothyroidism observed in dysgenesis. WES did not identify a genetic cause in NS-CHTD cases, confirming the complex etiology of this disease. Additional studies in larger cohorts and/or novel discovery approaches are required.

Ambient temperatures associated with increased risk of motor vehicle crashes in New York and Chicago

Motor Vehicle Crashes (MVC) are a major cause of death and disability worldwide. Yet it remains unknown to what extent changes in cold and hot temperatures affect the MVC. Here we quantify the linkage between ambient temperature exposure and the MVC risk of the driver in four cities of the United States. After adjusting for confounding factors, we find both a cold effect and a hot effect on MVC in New York, and a cold effect on MVC in Chicago. A 1 °C decrease in mean daily temperature below a cold threshold of −4.8 °C is associated with an increase in the overall cumulative relative risk of MVC by 11.59% (95% CI: 5.17%–16.43%) over 0–28 lag days for New York. The respective risk increase is 1.58% (95% CI: 0.36%–2.79%) over 0–2 lag days for a 1 °C increase in mean daily temperature above the hot threshold of 26.1 °C for New York. There is no significant heat wave or cold spell effects except for the heat wave effect on the consecutive heat wave days 7–10 in New York. Our study provides evidence of the association between driver exposure to low or high temperatures and the MVC risk. Improved public- administration preventive measures and policymaking are needed to minimize the negative consequences of abnormal temperatures on road safety driving.

Age-Associated Risk of Liver-Related Adverse Drug Reactions.

ObjectiveAging population is generally considered more sensitive to adverse drug reactions (ADRs). Yet, big data-based quantitative evidence currently does not exist to support this concept. This study aims to investigate age-associated risks of liver-related ADR (L-ADR).MethodsSpontaneous reporting data from 2012 to 2016 were retrieved from the China National ADR Monitoring System. The risk ratio (RR) was used to quantify the relative risk of L-ADR of each age group. The reporting odds ratio (ROR) was used to quantify the correlation with the risk of L-ADR of each drug category or drug in older adults.ResultsTotally, 64,702 L-ADR reports were retrieved, covering ages from 1 to 116, with a median age of 49. The RR values increased exponentially with the increase of age, which indicates that the relative risk of L-ADR increased by 33% for every 10-year increase in age. The age cutoff point for relative high risk of L-ADR was estimated at 52.0 years old (RR = 1). In 17 categories composed of 270 drugs, the top 3 drug categories with a high correlation to the risk of L-ADR in older adults were antiarrhythmic (ROR, 5.75; 95% CI: 4.45–7.42), antilipemic (ROR, 4.77; 95% CI: 4.53–5.02), and antihypertensive (ROR, 2.97; 95% CI: 2.59–3.41).ConclusionsThis research illustrates quantitatively that aging is a potential risk factor for L-ADR, with a 33% increase in relative risk for every 10-year increase in age. Risk management should be addressed for older adults when those drugs with a high correlation to the risk of L-ADR are used.