Middle Quintile Research Articles

Long-Term Mortality Implications of Maternal Weight Change in Pregnancy

ObjectivesHigh pregnancy weight gain is associated with greater postpartum weight retention; yet the long-term implications remain unknown. We examined associations of pregnancy weight change with mortality after ∼50 years of follow-up.MethodsThe Collaborative Perinatal Project (CPP) Mortality Linkage Study linked maternal participants in the CPP, a prospective pregnancy cohort (1959–1965), to the National Death Index and Social Security Death Master File for vital status through 2016 (n = 46,042). Total gestational weight change (gain or loss) in the index pregnancy (last CPP singleton pregnancy) was the difference in recorded delivery weight and self-reported pre-pregnancy weight. All-cause and cause-specific mortality associations with quintiles of gestational weight change were estimated using Cox regression adjusting for index pregnancy age, pre-pregnancy body mass index (BMI), race, parity, smoking, marital status, income, education, site, study year, prior chronic conditions, and gestational week at delivery.ResultsMajority of women (69%) had a healthy pre-pregnancy BMI and 46% were White and 45% were Black. Median (interquartile range) total gestational weight change was 9.5 kg (6.4–12.2), respectively; 2.5% lost weight in pregnancy. Over a median follow-up of 52 years (IQR 45–54), 38.9% of women died. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for mortality across quintiles 1 to 5 were 1.07 (95% CI 1.01–1.12), 1.03 (0.98–1.09), 1.00 (Reference), 1.01 (0.96–1.07), and 1.09 (1.03- 1.14), respectively. Compared to the middle quintile, HRs for the top four causes of death, cancer, cardiovascular disease, respiratory disease, and diabetes for the first quintile were 1.20 (0.99–1.46), 1.05 (0.96–1.15), 1.14 (0.96–1.37), and 0.92 (0.72–1.17), respectively; HRs for the fifth quintile were 1.19 (0.98–1.45), 1.14 (1.03–1.27), 0.95 (0.78–1.14), and 1.52 (1.20–1.92) respectively.ConclusionsThis study's novel findings extend the importance of healthy pregnancy weight gain beyond the pregnancy window to women's long mortality risk, particularly from cancer, cardiovascular disease, and diabetes.Funding SourcesThis work was funded by the Intramural Research Program of the NICHD.

The Association Between Serum Uric Acid and Mortality in Patients with Acute Coronary Syndrome After Percutaneous Coronary Intervention.

This study aims to explore the associations between uric acid (UA) and long-term outcomes among patients with acute coronary syndrome (ACS). A total of 1068 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI) were analyzed retrospectively. The patients were divided into 3 groups based on the levels of serum UA upon admission (bottom quintile, middle 3 quintiles, and top quintile). The primary endpoint was all-cause mortality. The patients in the higher UA groups were associated with younger age (71 ± 11 versus 68 ± 12 versus 67 ± 14 years; P < 0.05) and were more likely to be male (57.6 versus 76.9 versus 84.7%; P < 0.001). Furthermore, these patients had lower estimated glomerular filtration rates (83 ± 27 versus 74 ± 23 versus 59 ± 24 mL/minute/1.73 m2; P < 0.001) and lower left ventricular ejection fractions (58 ± 14 versus 57 ± 14 versus 53 ± 15%; P < 0.001). During the median 4-year follow-up, there were 158 incidents of all-cause death. Patients in the top quintile, followed by patients in the bottom quintile, had greater all-cause mortality compared with patients in the middle quintile (16.5 versus 11.4 versus 23.8%; P < 0.001). When the middle of the 3 quintiles was assigned as the reference group, the adjusted hazard ratios for all-cause mortality for the top and bottom quintiles were 1.72 (95% confidence interval [CI] 1.16-2.53, P < 0.05) and 1.57 (95% CI 1.03-2.36, P < 0.05), respectively. These results demonstrate that UA levels upon admission in patients with ACS who underwent PCI exhibited a 'J-shaped' association with all-cause mortality.

Size Matching by Height, Body Surface Area, and Body Mass Index in Infant Heart Transplantation

<h3>Purpose</h3> Congenital heart disease is the most common primary indication for transplantation in the infant population. Weight is the traditional metric for size-matching for infants but may fluctuate due to failure to thrive and fluid retention. We sought to analyze height, body surface area, and body mass index as possible alternative size-matching metrics in the infant population. <h3>Methods</h3> The UNOS database was retrospectively analyzed for infants (<1 years old) undergoing heart transplantation. 2115 infants were divided into quintiles (Q1-Q5) based on donor-to-recipient height ratio (DRHR), weight ratio (DRWR), Haycock body surface area ratio (BSAR), and body mass index ratio (BMIR). Multivariate Cox regression modeling was used to evaluate the risk of graft failure at 1-year. <h3>Results</h3> The bottom two DRWR quintiles were associated with higher risk compared to the middle DRWR quintile (Q1: 1.86 HR, p=0.002; Q2: 1.98, p=0.0004) (Table 1). The bottom two BSAR quintiles were also associated with higher risk compared to the middle BSAR quintile but to a lesser degree than DRWR (Q1: HR=1.74, p=0.005; Q2: HR=1.75, p=0.004). None of the DRHR quintiles or BMIR quintiles were associated with increased risk of 1-year graft failure compared to the middle quintile (Table 1). Ischemic time, retransplantation, ECMO at transplantation, and serum bilirubin were significant covariates associated with an increased risk of 1-year graft failure in each multivariate model. Later transplantation year was associated with lower risk of graft failure in each multivariate model. Serum creatinine, donor age, and recipient age were not associated with risk of graft failure in multivariate analysis. <h3>Conclusion</h3> Undersizing by DRWR or BSAR is associated with increased risk of graft failure in infant heart transplantation. Size mismatch by DRHR or BMIR is not predictive of graft failure when compared to modest oversizing (i.e., the middle quintile). Further investigation is needed to improve size-matching in infant heart transplantation.

Use of reusable menstrual management materials and associated factors among women of reproductive age in Ghana: analysis of the 2017/18 Multiple Indicator Cluster Survey

BackgroundThe use of unsafe materials to collect menstrual blood predisposes women and girls to infections. There is a paucity of literature on the utilization of reusable menstrual materials in sub-Saharan Africa. This study examined factors associated with the use of reusable menstrual management materials among women of reproductive age in Ghana. Findings from this study can inform menstrual health programmes and reproductive health policy to address menstrual hygiene and specific areas of emphasis.MethodsWe analysed secondary data from the 2017/18 Ghana Multiple Indicator Cluster Survey. Descriptive statistics were employed to compute frequencies and percentages, while Chi-square and complex sample Binomial Logistic Regression was conducted to identify factors associated with the use of reusable menstrual materials.ResultsHalf (52%) of the respondents were below 30 years old; mean (± sd) = 30.7(9.0). Thirteen percent used reusable materials to collect menstrual blood during their last period. Women aged 45–49 years (AOR = 5.34; 95% CI 3.47–8.19) were 5 times more likely to manage menstruation with reusable materials compared with those aged 15–19 years (p < 0.05). Women classified in the middle wealth quintile (AOR = 0.66; 95% CI 0.50–0.88) were 34% less likely to use reusable materials to collect menstrual blood compared with women in the poorest wealth quintile (p < 0.05). Also, women who were exposed to television (AOR = 0.78; 95% CI 0.61–0.99) had less odds of using reusable materials compared with women who were not exposed to television (p < 0.05).ConclusionThis study showed that the use of reusable menstrual materials was influenced by socio-demographic factors, economic factors and exposure to mass media. Therefore, policies and programmes aimed at promoting menstrual health should focus on less privileged women. The mass media presents an opportunity for communicating menstrual hygiene.

Factors associated with malaria care seeking among children under 5\xa0years of age in Mozambique: a secondary analysis of the 2018 Malaria Indicator Survey

BackgroundMozambique is ranked fourth in a list of the 29 countries that accounted for 95% of all malaria cases globally in 2019. The aim of this study was to identify factors associated with care seeking for fever, to determine the association between knowledge about malaria and care seeking and to describe the main reasons for not seeking care among children under five years of age in Mozambique.MethodsThis is a quantitative, observational study based on a secondary data analysis of the 2018 Malaria Indicator Survey. This weighted analysis was based on data reported by surveyed mothers or caregivers of children aged 0–59 months who had fever in the two weeks prior to the survey.ResultsCare was reportedly sought for 69.1% [95% CI 63.5–74.2] of children aged 0–59 months old with fever. Care-seeking was significantly higher among younger children, < 6 months old (AOR = 2.47 [95% CI 1.14–5.31]), 6–11 months old (AOR = 1.75 [95% CI 1.01–3.04]) and 12–23 months old (AOR = 1.85 [95% CI 1.19–2.89]), as compared with older children (48–59 months old). In adjusted analysis, mothers from the middle (AOR = 1.66 [95% CI 0.18–3.37]) and richest (AOR = 3.46 [95% CI 1.26–9.49]) wealth quintiles were more likely to report having sought care for their febrile children than mothers from the poorest wealth quintile. Additionally, mothers with secondary or higher education level were more likely to seek care (AOR = 2.16 [95% CI 1.19–3.93]) than mothers with no education. There was no association between maternal malaria knowledge or reported exposure to malaria messages and care-seeking behaviours. The main reasons reported for not seeking care included distance to health facility (46.3% of respondents), the perception that the fever was not severe (22.4%) and the perception that treatment was not available at the health facility (15%).ConclusionHealth facility access and socioeconomic barriers continue to be important constraints to malaria service utilization in Mozambique.

Individual and community-level factors of treatment-seeking behaviour among caregivers with febrile children in Ethiopia: A multilevel analysis

Early diagnosis and treatment of childhood fever are essential for controlling disease progression and death. However, the Treatment-seeking behaviour of caregivers is still a significant challenge in rural parts of the African region. This study aimed to assess individual and community-level factors associated with treatment-seeking behaviours among caregivers of febrile under-five age children in Ethiopia. The recent Ethiopian Demographic and Health Survey data (EDHS 2016) was used for the study. The survey collected information among 1,354 under-five children who had a fever within two weeks before the survey. The data were extracted, cleaned, and recoded using STATA version 14. Multilevel logistic regressions were used to determine the magnitude and associated factors of treatment-seeking behaviour among caregivers with febrile children in Ethiopia. Four models were built to estimate both fixed and random effects of individual and community-level factors between cluster variations on treatment-seeking behaviour. The Adjusted Odds Ratios with 95% Confidence Intervals (CI) of the best-fitted model were reported at p<0.05. This study revealed that 491 (36.26%) caregivers seek treatment for their febrile children. Living in metropolitan and small peripheral regions, delivery at health institutions, being poorer, middle and richer wealth quintiles, having a child with diarrhoea, cough, short rapid breathing, and wasting were positively associated with treatment-seeking behaviour of caregivers. The caregivers had poor treatment-seeking behaviour for their febrile children in Ethiopia. Health education programmers should emphasise the importance of seeking early treatment, taking action on childhood febrile illness signs.

International external validation of a stratification tool to identify branch-duct intraductal papillary mucinous neoplasms at lowest risk of progression.

BackgroundIdentifying branch‐duct intraductal papillary mucinous neoplasms (BD‐IPMNs) at lowest risk of progression may allow for a reduced intensity of surveillance.ObjectiveWe aimed to externally validate the previously developed Dutch‐American Risk stratification Tool (DART‐1; https://rtools.mayo.edu/DART/), which identifies cysts at low risk of developing worrisome features (WFs) or high‐risk stigmata (HRS).MethodsThree prospective cohorts of individuals under surveillance for BD‐IPMNs were combined, independent from the original development cohort. We assessed the performance (discrimination and calibration) of DART‐1, a multivariable Cox‐proportional logistic regression model with five predictors for the development of WFs or HRS.ResultsOf 832 individuals (mean age 77 years, SD 11.5) under surveillance for a median of 40 months (IQR 44), 163 (20%) developed WFs or HRS. DART‐1's discriminative ability (C‐statistic 0.68) was similar to that in the development cohort (0.64–0.72) and showed moderate calibration. DART‐1 adequately estimated the risk for patients in the middle risk quintile, and slightly underestimated it in the lowest quintiles. Their range of predicted versus observed 3‐year risk was 0%–0% versus 0%–3.7% for Q1; 0.3%–0.4% versus 3%–11% for Q2; and 2.6%–3% versus 2.4%–9.8% for Q3. The development of WFs or HRS was associated with pancreatic cancer (p < 0.001). Vice versa, in absence of WFs or HRS, the risk of malignancy was low (0.3%).ConclusionsThe performance of DART‐1 to predict the development of WFs or HRS in BD‐IPMN was validated in an external international cohort, with a discriminative ability equal as in the development cohort. Risk estimations were most accurate for patients with BD‐IPMNs in the middle risk quintile and slightly underestimated in the lowest quintiles.

Associations of Maternal Polyunsaturated Fatty Acids With Telomere Length in the Cord Blood and Placenta in Chinese Population.

Few studies have investigated the correlation between maternal polyunsaturated fatty acids (PUFAs) and telomeres in offspring, and the underlying influential mechanisms. In this study, we assessed the associations of maternal PUFAs with telomere length (TL) and DNA methylation of the telomerase reverse transcriptase (TERT) promoter in the cord blood and the placenta. A total of 274 pregnant women and their newborn babies were enrolled in this study. Maternal blood before delivery, the cord blood, and the placenta at birth were collected. Fatty acids in maternal erythrocytes and cord blood cells were measured by gas chromatography (GC). TL in the cord blood and the placenta was determined using real-time quantitative PCR (qPCR) by calculating the product ratio of telomeric DNA to the single-copy gene β-globin. The TERT promoter methylation was analyzed by DNA bisulfite sequencing. The associations of maternal fatty acids with TL were analyzed by univariate and multivariate regression. We found that low concentrations of docosapentaenoci acid (DPA, C22: 5n-3) and total n-3 PUFAs, adrenic acid (ADA, C22: 4n-6), and osbond acid (OA, C22: 5n-6) and high concentrations of linoleic acid (LA, C18: 2n-6) in maternal erythrocytes were associated with the shortened TL in cord blood cells (estimated difference in univariate analysis −0.36 to −0.46 for extreme quintile compared with middle quintile), and that low concentrations of cord blood docosahexaenoic acid (DHA, C22: 6n-3) were related to the shortened TL in cord blood cells. Differently, high concentrations of α-linolenic acid (LNA, C18: 3n-3), eicosatrienoic acid (EA, C20: 3n-3), DHA, and γ-linoleic acid (GLA, C18:3n-6) in maternal erythrocytes were associated with the shortened TL in the placenta (estimated difference in univariate analysis −0.36 to −0.45 for higher quintiles compared with the middle quintile). Further examination demonstrated that the concentrations of DHA and total n-3 PUFAs in maternal erythrocytes had positive associations with DNA methylation of the TERT promoter in the cord blood instead of the placenta. These data suggest that maternal PUFAs are closely correlated to infant TL and the TERT promoter methylation, which are differently affected by maternal n-3 PUFAs between the cord blood and the placenta. Therefore, keeping higher levels of maternal n-3 PUFAs during pregnancy may help to maintain TL in the offspring, which is beneficial to long-term health.

Factors associated with HIV testing among youth in a generalised hyperendemic setting: findings from a national survey in Eswatini

Aim: Even though Eswatini was the first country in Africa to achieve the UNAIDS 95-95-95 targets among people living with HIV nationally, youth aged 15–24 years lag behind in HIV testing. This study determined the overall prevalence of HIV testing among the youth and the factors associated with HIV testing. Methods: Data were analysed for 1 834 young people from the 2016–2017 Swaziland HIV Incidence Measurement Survey (SHIMS2) using multivariable logistic regression. Results: Overall, 66% of the young people had tested for HIV in the past 12 months before SHIMS2. Lower odds of HIV testing were observed among males, among those aged 15–17 years, the never married/cohabited, those with primary and secondary education, and among those who had high perceived stigma towards people living with HIV and AIDS. Youth from households classified in the poor and middle quintiles had higher odds of testing for HIV compared to those from rich households. Conclusion: Efforts to increase HIV testing should consider the sociodemographic and behavioural factors identified as determinants of HIV non-testing in this age group.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

County-level socio-economic disparities in COVID-19 mortality in the USA.

BackgroundPreliminary studies have suggested a link between socio-economic characteristics and COVID-19 mortality. Such studies have been carried out on particular geographies within the USA or selective data that do not represent the complete experience for 2020.MethodsWe estimated COVID-19 mortality rates, number of years of life lost to SARS-CoV-2 and reduction in life expectancy during each of the three pandemic waves in 2020 for 3144 US counties grouped into five socio-economic status categories, using daily death data from the Johns Hopkins University of Medicine and weekly mortality age structure from the Centers for Disease Control.ResultsDuring March–May 2020, COVID-19 mortality was highest in the most socio-economically advantaged quintile of counties and lowest in the two most-disadvantaged quintiles. The pattern reversed during June–August and widened by September–December, such that COVID-19 mortality rates were 2.58 times higher in the bottom than in the top quintile of counties. Differences in the number of years of life lost followed a similar pattern, ultimately resulting in 1.002 (1.000, 1.004) million years in the middle quintile to 1.381 (1.378, 1.384) million years of life lost in the first (most-disadvantaged) quintile during the whole year.ConclusionsDiverging trajectories of COVID-19 mortality among the poor and affluent counties indicated a progressively higher rate of loss of life among socio-economically disadvantaged communities. Accounting for socio-economic disparities when allocating resources to control the spread of the infection and to reinforce local public health infrastructure would reduce inequities in the mortality burden of the disease.

Cord Blood Thyroid Hormones and Neurodevelopment in 2-Year-Old Boys and Girls.

Objective: Thyroid hormones are essential for neurodevelopment in early life. However, the impact of mild alterations in neonatal thyroid hormones on infant neurodevelopment and its sex dimorphism is unclear. We aimed to assess whether mild variations in neonatal thyroid hormones of term-born newborns with maternal euthyroid are related to neurodevelopment in 2-year-old boys and girls.Methods: This study used data from 452 singleton term-born infants of mothers with normal thyroid function in Shanghai, China, and their follow-up measure at the age of 2 years. Cord serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured by chemiluminescent microparticle immunoassays and classified into three groups: the low (1st, Q1), middle (2nd−4th, Q2–Q4), and high (5th, Q5) quintiles. Neurodevelopment indices were assessed using the Ages and Stages Questionnaire, third edition (ASQ-3), at 24 months of age.Results: Compared to infants with thyroid hormones in the middle (Q2–Q4), boys with FT4 in the lowest quintile had 5.08 (95% CI: 1.37, 8.78) points lower scores in the communication domain, 3.25 (0.25,6.25) points lower scores in the fine motor domain, and 3.84 (0.04, 7.64) points lower scores in the personal-social domain, respectively. Boys with FT3 in the highest quintile had 4.46 (0.81, 8.11) points increase in the personal-social domain. These associations were not observed in girls. No associations were observed between cord blood serum TSH and ASQ-assessed neurodevelopment in the boys or the girls.Conclusions: Mild alterations in thyroid hormones of newborns were associated adversely with neurodevelopment in boys, suggesting the importance of optimal thyroid hormone status for neurodevelopment in early life.

Cardiac Remodeling According to the Nocturnal Fall of Blood Pressure in Hypertensive Subjects: The Whole Assessment of Cardiac Abnormalities in Non-Dipper Subjects with Arterial Hypertension (Wacanda) Study.

Objective: Several epidemiological studies suggest that the preservation of the physiological circadian rhythm of blood pressure or its disruption affects the extent of the organ damage developed by the patient. If we classify the circadian rhythm of blood pressure into four nocturnal profiles, significant differences emerge in terms of organ damage burden and prognosis: reverse dippers have the worst prognosis while dippers and mild dippers fall into an intermediate risk range. The risk profile of extreme dippers is still debated, and the available data are very conflicting and inconclusive. Starting from this gap of knowledge, we aimed to evaluate, retrospectively, in a cohort of hypertensive subjects, the degree of cardiac involvement in relation to the different nocturnal blood pressure profiles. Methods: We retrospectively evaluated 900 patients with essential hypertension, of whom 510 met our study criteria. We graded the 510 patients in relation to the percentage of reduction in mean systolic blood pressure (SBP) at night-time compared with day-time, considering this as a continuous variable, and then compared the extreme quintiles with each other and with the middle quintile (considered as reference). Results: Patients with less (or no) reduction in nocturnal SBP (reverse dipper) showed a higher level of organ damage and comorbidities. With regard to echocardiographic indexes, patients with maximum nocturnal pressure reduction (extreme dipper) showed a lower level of remodeling and/or impairment of E/e’ ratio, Right Atrium Area, Basal Right Ventricular Diameter, Inferior Vena Cava Average Diameter, and Tricuspidal Anular Plane Systolic Excursion compared also with hypertensive patients with a physiological nocturnal pressure reduction, even after correction for the main confounders. Conclusions: These data suggest that extreme dippers may constitute the subgroup of hypertensive patients with the lowest 24-h pressure load and, therefore, less cardiac remodeling.

Association between Teenage Pregnancy and Family Factors: An Analysis of the Philippine National Demographic and Health Survey 2017.

Adolescence is a key developmental period in one’s life course; health-related behaviors of adolescents can be linked to lifelong consequences, which affect their future health. Previous studies highlight the role of family and its significant association with adolescents’ health. In East Asia and the Pacific, the Philippines is the only country that is showing an upward trend of teenage pregnancy while other countries in the region have declining teenage pregnancy rates. Against this backdrop, this study investigated the association between teenage pregnancy and family factors, specifically parent structure. Data for the study were extracted from the Philippine National Demographic and Health Survey 2017. All adolescent women aged 15–19 years old (n = 5120) were included in the analyses. The dependent variable was teenage pregnancy, while parent structure, defined as a presence or absence of parents in the domicile, was the exposure variable. Multivariable logistic regression was utilized in assessing the association of teenage pregnancy and family factors after adjusting for several potential confounders. Adolescent women were more likely to become pregnant as a teenager when they lived with neither parent (aOR = 4.57, 95% CI = 2.56–8.15), were closer to 19 years of age (aOR = 2.17, 95% CI = 1.91–2.46), had knowledge of contraception (aOR = 1.27, 95% CI = 1.22–1.32) and lived in a big family (aOR = 1.14, 95% CI = 1.09, 1.20). Furthermore, adolescent women who lived with neither parent and belonged to the poorest wealth quintile were more likely to become pregnant as a teenager (aOR = 3.55, 95% CI = 1.67–7.55). Conversely, educational attainment higher than secondary education (aOR = 0.08, 95% CI = 0.01–0.49) and those who belonged to the richest wealth quintile (aOR = 0.40, 95% CI = 0.18–0.92) exhibited a statistically inverse association with teenage pregnancy compared with those with no education and from the middle wealth quintile, respectively. Living with neither parent was found as a risk factor for teenage pregnancy. Furthermore, we found that several sociodemographic factors exhibited a non-uniform increment and reduction in the risk of teenage pregnancy.

Association Between Dynamic Change of QT Interval and Long-Term Cardiovascular Outcomes: A Prospective Cohort Study.

Background: The prolongation or shortening of heart rate-corrected QT (QTc) predisposes patients to fatal ventricular arrhythmias and sudden cardiac death (SCD), but the association of dynamic change of QTc interval with mortality in the general population remains unclear.Methods: A total of 11,798 middle-aged subjects from the prospective, population-based cohort were included in this analysis. The QTc interval corrected for heart rate was measured on two occasions around 3 years apart in the Atherosclerosis Risk in Communities (ARIC) study. The ΔQTc interval was calculated by evaluating a change in QTc interval from visit 1 to visit 2.Results: After a median follow-up of 19.5 years, the association between the dynamic change of QTc interval and endpoints of death was U-shaped. The multivariate-adjusted hazard ratios (HRs) comparing subjects above the 95th percentile of Framingham–corrected ΔQTc (ΔQTcF) (≥32 ms) with subjects in the middle quintile (0–8 ms) were 2.69 (95% CI, 1.68–4.30) for SCD, 2.51 (1.68–3.74) for coronary heart disease death, 2.10 (1.50–2.94) for cardiovascular death, and 1.30 (1.11–1.55) for death from any cause. The corresponding HRs comparing subjects with a ΔQTcF below the fifth percentile (<-23 ms) with those in the middle quintile were 1.82 (1.09–3.05) for SCD, 1.83 (1.19–2.81) for coronary heart disease death, 2.14 (1.51–2.96) for cardiovascular death, and 1.31 (1.11–1.56) for death from any cause. Less extreme deviations of ΔQTcF were also associated with an increased risk of death. Similar, albeit weaker associations also were observed with ΔQTc corrected with Bazett's formula.Conclusions: A dynamic change of QTc interval is associated with increased mortality risk in the general population, indicating that repeated measurements of the QTc interval may be available to provide additional prognostic information.

Relationship of Ambient Temperature Parameters to Stroke Incidence in a Japanese Population - Takashima Stroke Registry, Japan, 1988-2010.

Using a population-based stroke registry system, we evaluated the relationship between ambient temperature parameters and stroke incidence in a Japanese population. We analyzed data from the Takashima Stroke Registry, which records all stroke occurrences in Takashima City, Japan. The study period of 8,401 days was divided into quintiles of daily weather parameters, and the middle quintile was used as the reference category. Incidence rates (IR per 100,000 person-years) were calculated across the quintiles. Poisson regression analysis was used to calculate the effect of temperature parameters on stroke incidence. There were 2,405 first-ever strokes (1,294 men), including 1,625 ischemic, 545 cerebral hemorrhages, 213 subarachnoid hemorrhages, and 22 unclassified strokes. The stroke IR was higher in the middle quintile of average temperature, 357.3 (328.4-388.8), and for other parameters. After adjustment for age and sex, for all stroke, the incidence rate ratio (IRR) in the highest (Q5: IRR 0.81, 95% confidence interval (CI) 0.71-0.92) and the second-highest (Q4: IRR 0.80, 95% CI 0.71-0.91) quintile was lower than that in the middle quintile (Q3: Reference). Analogous results were observed for the minimum, maximum, and lag-days temperatures, also in the subtypes and across ≥65 years of age, also in females. Higher temperatures, irrespective of the parameter (average, minimum, or maximum), had a protective effect against stroke occurrence in Japan.

Misconceptions and stigma against people living with HIV/AIDS: a cross-sectional study from the 2017 Indonesia Demographic and Health Survey.

OBJECTIVESData are not available in Indonesia to measure the main indicators of zero new infections, zero acquired immune deficiency syndrome (AIDS)-related deaths and zero discrimination. This study aimed to determine factors related to misconceptions about human immunodeficiency virus (HIV) transmission and the stigma against people living with HIV/AIDS (PLWHA) in IndonesiaMETHODSThis cross-sectional study used secondary data from the 2017 Indonesia Demographic and Health Survey (IDHS). The sample was women and men aged 17–45 years and married (n=3,023).RESULTSEducation and wealth index quintile were significantly related to misconceptions about HIV transmission. Respondents with low levels of education were more likely to have misconceptions about HIV transmission. Respondents who were in the poorest, poorer, middle, and richer quintiles of the wealth index were more likely to have misconceptions about HIV transmission than those in the richest quintile. Educational level, employment status, and wealth index quintile were predictors of stigma against PLWHA.CONCLUSIONSThere are still many Indonesian people with misconceptions about HIV transmission and stigma against PLWHA. Future studies should focus on educational programs or interventions aimed at increasing public knowledge and awareness, promoting compassion towards PLWHA, and emphasizing respect for the rights of PLWHA. These interventions are particularly important for populations who are uneducated and living in poverty.

Obesity-Induced Inflammation Co-Operates with Clonal Hematopoiesis of Indeterminate Potential (CHIP) Mutants to Promote Leukemia Development and Cardiovascular Disease

▪Obesity is an increasing epidemic world-wide responsible for enhancing the risk for developing Type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and cancer. However, it is unclear if and how obesity contributes to the transformation of pre-leukemic stem and progenitors (pre-LHSC/Ps) into full-blown leukemia such as acute myeloid leukemia (AML) or severe form of myeloproliferative neoplasm (MPN) or CVD. We hypothesized that obesity induced chronic inflammation might be responsible for clonal selection of pre-LHSC/Ps bearing pre-leukemic clonal hematopoiesis of indeterminate potential (CHIP) mutations such as DNMT3A, TET2, ASXL1, and JAK2 and for promoting the progression of early-onset MPN, AML/leukemia and CVD. To study the linkage between obesity and CHIP in humans, we first examined the UK biobank. After exclusions, the final study cohort included 47,466 unrelated participants free of T2DM at baseline and having valid CHIP measurements. The mean (SD) age at enrollment was 56.5 (8.0), 45.0% were male, 43.9% never smoked, and 82.6% self-reported as European decedents. At baseline, the mean (SD) body mass index (BMI) was 27.3 (4.7) kg/m 2, with 43.0% overweight and 23.6% obese, and the overall mean (SD) waist-to-hip ratio (WHR) was 0.87 (0.09). CHIP was present among 5.8% of the study population the most common mutations on the DNMT3A (3.7%) and TET2 (1.0%) genes; large CHIP clone defined as CHIP mutation with variant allele fraction >10% was present among 2.4% of the study population. Individuals with CHIP mutations on average had higher WHR. The presence of CHIP mutation was associated with a 0.0028 increase of WHR (p=0.03). Furthermore, CHIP prevalence increased with higher WHR: the percentage of participants with CHIP was 4.93%, 5.75%, 6.56% in the lowest, middle, and highest WHR quintiles respectively, signifying that dysfunctional metabolism may accelerate expansion of clonal hematopoiesis (CH). To better define the mechanism of obesity driven CH, we utilized several novel mouse models bearing Tet2 -/-, Dnmt3a +/-, Asxl1 +/- and Jak2 +/- mutations to mimic the human pre-LHSC/Ps condition and obesity, in the form of leptin deficient Lep Ob/Ob (Ob/Ob) mutation, which induces obesity and T2DM. We show that both the compound mutant (Tet2 -/-;Ob/Ob, Dnmt3a +/-;Ob/Ob, Asxl1 +/-;Ob/Ob and Jak2 +/-;Ob/Ob) and CHIP mutant bone marrow (BM; Tet2 -/-, Dnmt3a +/-, Asxl1 +/- and Jak2 +/-) transplanted into Ob/Ob mice develop rapid growth of mature myeloid cells and HSC/Ps leading to severe form of MPN/AML as well as CVD. This was associated with upregulation of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. Flow cytometry analysis of LSK and progenitor cells isolated from Tet2 -/-;Ob/Ob mice revealed an up-regulation of intracellular Ca2+ levels. We hypothesized that up-regulated Ca2+ signaling in Tet2 -/-; Ob/Ob HSC/Ps promotes aberrant signaling leading to an early-onset of severe MPN/AML. We performed a competitive transplantation experiment using, Tet2 -/-: Boy/J BM cells (1:1 ratio) into Ob/Ob and WT recipients. After 8 weeks post transplantation, we investigated the role of Ca2+ blockers in driving CH in Ob/Ob recipients using pharmacological inhibitors, either individually, or in combination, of metformin (100 mg/kg, orally), nifedipine (100 mg/kg, orally), MCC950 (30 mg/kg, orally) and anakinra (10 mg/kg, i.p). The combination treatment markedly reduced monocytes, neutrophils, WBC counts, and improved RBCs, hematocrits and platelets. The spleen and liver, heart, body weights and blood glucose levels were significantly reduced, along with a greater re-emergence of normal CD45.1 wild-type cells in the PB, BM, and spleen and a significant reduction in Tet2 mutant CD45.2 pre-LHSC/Ps and myeloid cells in the PB, BM, and spleen. Importantly, the frequency of leukemic blasts, LSK cells, ST-HSCs, LT-HSCs and granulocyte macrophage progenitors (GMP) were significantly reduced. Furthermore, the combination of drug treatment showed greater heart protective activity by reducing the atherosclerotic lesions in Ob/Ob recipients bearing CHIP by suppressing Ca2+ signaling. Taken together, these data suggest that obesity is highly associated with the presence of CHIP in humans and that targeting CHIP mutant cells with a combination of metformin/nifedipine/MCC950/anakinra is a safe and inexpensive way to rescue CH and its associated leukemic and cardiovascular defects. DisclosuresNatarajan: Amgen: Research Funding; Apple: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Boston Scientific: Research Funding; Blackstone Life Sciences: Consultancy; Genentech: Consultancy; Foresite Labs: Consultancy.

Health impacts of a more equal society: a microsimulation study

BackgroundSocioeconomic health inequalities persist in England. The gaps in life and healthy life expectancies are more than 15 years between the least and most deprived fifth of areas. The gaps can be explained largely by socioeconomic gradients in diet, smoking, alcohol, physical activity, and disease case fatalities. We aimed to quantify the health impact of a more equal society. MethodsWe used IMPACTNCD, a stochastic dynamic microsimulation that explicitly models the causal relations between exposures (fruit and vegetable consumption, smoking histories, environmental tobacco smoking, alcohol consumption, physical activity, body-mass index, systolic blood pressure, and total cholesterol) and diseases (cardiovascular disease, post-stroke dementia, type 2 diabetes, chronic obstructive pulmonary disease, and common cancers including lung, breast, and colon cancers). We simulated three theoretical scenarios for the years 2021–40 in England. (1) Recent trends in exposures and mortality continue (baseline); (2) in 2021, exposures in the most and second most deprived quintile groups (index of multiple deprivation) match those of the middle quintile (scenario A); and (3) as for scenario A, but additionally, case-fatality rates of the modelled diseases and mortality rates from any other cause match those of the middle quintile group (scenario B). FindingsPreliminary results suggest that under scenario A, approximately 250 000 (95% uncertainty intervals 220 000 to 280 000) disease events would be prevented or postponed, resulting in approximately 1·7 million (1·4 million to 1·9 million) case-years prevented or postponed and about 67 000 (44 000 to 88 000) fewer deaths. The aforementioned outcome equates to 1·7% (1·5 to 1·9) of all incident events, 0·80% (0·66 to 0·91) of all case-years, and 0·94% (0·61 to 1·20) of all deaths. Overall, 390 000 (300 000 to 490 000) quality-adjusted life-years would be gained. Under scenario B, the improved survival rates would prevent or postpone approximately 210 000 (180 000 to 220 000) disease events but would most likely lead to an increase in people living with the modelled diseases of approximately 330 000 (–110 000 to 690 000) case-years. Overall, 1·4 million (1·1 million to 1·7 million) quality-adjusted life-years would be gained. InterpretationSuccessful levelling-up policies would improve health but might increase health-care demand if they lead to improved survival despite the expected incidence reduction. Nevertheless, achieving these gains is politically and socially challenging and likely to be a multigeneration sustained effort. FundingThe Health Foundation.

How Income Inequality and Race/Ethnicity Drive Obesity in U.S. Adults: 1999-2016.

Obesity is a major public health problem both globally and within the U.S. It varies by multiple factors, including but not limited to income and sex. After controlling for potential covariates, there is little evidence to determine the association between income and obesity and how obesity may be moderated by sex and family income. We examined the association between income and obesity in U.S. adults aged 20 years and older, and tested whether this relationship differs by race or ethnicity groups. For this analysis, we used data from the 1999–2016 National Health and Nutrition Examination Surveys (NHANES). Obesity was determined using Body Mass Index ≥ 30 kg/m2; the Gini coefficient (GC) was calculated to measure income inequality using the Poverty Income Ratio (PIR). We categorized the PIR into five quintiles to examine the relationship between income inequality and obesity. For the first set of analyses, we used a modified Poisson regression in a sample of 36,665 adults, with an almost equal number of men and women (women’s ratio was 50.6%), including 17,303 white non-Hispanics (WNH), 7475 black non-Hispanics (BNHs), and 6281 Mexican Americans. The models included age, racial/ethnic groups, marital status, education, health behaviors (smoking and drinking status and physical activities), health insurance coverage, self-reported health, and household structure (live alone and size of household). Adjusting for potential confounders, our findings showed that the association between PIR and obesity was positive and significant more frequently among WNH and BNH in middle and top PIR quintiles than among lower-PIR quintiles; this association was not significant in Mexican Americans (MAs). Results of GC in obese women showed that in comparison with WNHs (GC: 0.34, S.E.: 0.002), BNHs (GC: 0.38, S.E.: 0.004) and MAs (GC: 0.41, S.E.: 0.006) experienced higher income inequality, and that BNH obese men experienced the highest income inequality (GC: 0.45, S.E.: 0.011). The association between PIR and obesity was significant among WNHs and BNHs men in the 3rd, 4th and 5th PIR quintiles. The same association was not found for women. In treating obesity, policymakers should consider not only race/ethnicity and sex, but also strategies to reduce inequality in income.