High Trajectory Research Articles

ASSOCIATION OF BLOOD PRESSURE TRAJECTORIES SINCE YOUNG ADULTHOOD WITH CARDIOVASCULAR DISEASES IN LATER LIFE

Objective: To identify blood pressure (BP) trajectories since young adulthood and to determine their association with risk of cardiovascular diseases (CVD) in later life. Design and method: This cohort study used data of young adults aged 18 to 39 years from the Kailuan Cohort, a prospective longitudinal study of Chinese men and women. Using group-based trajectory modeling, distinct BP trajectories from 2006 to 2010 were identified for 5 BP traits (mid-BP, SBP, DBP, MAP, and PP). Main outcomes were incident CVD (coronary revascularization, myocardial infarction, heart failure, or stroke), which were collected until 31 December 2020. Cox proportional hazards regression models were used to estimate the associations between BP trajectories and the risk of incident CVD. Results: Of the 11 535 adults included in the study (mean [SD] age, 32.6 [5.1] years), 8708 (75.5%) were men. We identified 3 trajectories for all BP traits (except for PP, which was 2). Among them, the mid-BP trajectory distribution was 4566 individuals (39.6%) with low-increasing, 5996 (52.0%) with moderate-increasing, and 973 (8.4%) with high-stable. Compared with the mid-BP low-increasing trajectory group, individuals in the moderate-increasing and high-stable groups had higher risk of CVD (moderate: HR, 2.44; 95% CI, 1.47 to 4.06; high: HR, 3.82; 95% CI, 1.98 to 7.39) after adjusting for socio-demographics and cardiovascular risk factors, as well as the baseline mid-BP level. Results were consistent after additionally adjusting for cumulative mid-BP exposure during 2006 to 2010 (moderate: HR, 2.31; 95% CI, 1.41 to 3.79; high: HR, 3.18; 95% CI, 1.72 to 5.90). Besides, the increased CVD risk associated with higher trajectories were also significant for SBP, DBP, MAP, and PP, and remained robust through several sensitivity analyses, which included excluding those who ever used antihypertensive drugs during 2006 to 2010, excluding events within the first year of follow-up, and considering death as competing risk. Conclusions: Higher BP trajectories since early adulthood were associated with an increased risk of CVD in later life. Early detection of BP trajectories may assist in more accurate identification of individuals with high risk of future CVD.

Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry

Brief Summary: Analysis of the multi-national SWEET diabetes registry showed that mean HbA1c in youth is highest at diagnosis and lowest at 4 to 5 months post-diagnosis. The HbA1c trajectory was lower in countries with nationalized health insurance. High gross domestic product (GDP) and high use of technology did not seem to protect from a higher trajectory.

Prenatal single and combined exposure to phthalates associated with girls’ BMI trajectory in the first six years

Evidence of the influence of prenatal phthalate exposure on childhood longitudinal obesity markers is limited. Nested on the Ma’anshan birth cohort study, 990 mother-daughter pairs were included. Seven phthalate metabolites were determined in urine collected in each trimester. Each child underwent a physical examination from birth to 6 years of age twelve times. Latent class growth models were used to identify three trajectories of girls’ body mass index (BMI). Logistic regression, quantile g-computation and Bayesian kernel machine regression models analyzed the relationships of prenatal exposure to individual and mixed phthalates with girls’ body mass index (BMI) trajectory. Compared to the “lowest trajectory” class, prenatal average concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP, ORcrude = 2.095, 95 % CI = 1.014–4.328) and di(2-ethylhexyl) phthalate (DEHP, ORcrude = 2.336, 95 % CI = 1.022–5.338) during pregnancy were associated with an increased probability of being in the “highest trajectory” class. The average concentration of DEHP (ORcrude = 1.879, 95 % CI = 1.002–3.522) was associated with an increased probability of being in the “moderate trajectory” class. Stratified analyses by trimester of pregnancy mainly showed that third-trimester exposure to monoethyl phthalate (MEP, ORadjusted = 1.584, 95 % CI = 1.094–2.292), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, ORadjusted = 2.885, 95 % CI = 1.367–6.088), MEHHP (ORadjusted = 2.425, 95 % CI = 1.335–4.407), DEHP (ORadjusted = 2.632, 95 % CI = 1.334–5.193) and high molecular weight phthalate (ORadjusted = 2.437, 95 % CI = 1.239–4.792) was associated with an increased probability of being in the “highest trajectory” class. However, the mixture of phthalates was not significantly related to the girl’s BMI trajectory. In conclusion, in utero exposure to phthalates, including MEP and DEHP metabolites (MEHHP and MEOHP), was significantly associated with early childhood high BMI trajectories in girls. The third trimester of pregnancy seemed to be the window of vulnerability to phthalate exposure for girls’ high BMI trajectory at periods of prenatal development. No evidence supported a significant relationship between combined exposure to phthalate metabolites and girls’ high BMI trajectory.

Trajectories of prenatal alcohol exposure and behavioral outcomes: Findings from a community-based sample

ObjectiveTo characterize patterns of prenatal alcohol exposure (PAE), and determine whether PAE trajectories were associated with behavior from a community-based sample of first-grade children. MethodsUsing data collected as part of the Collaboration of Fetal Alcohol Spectrum Disorders Prevalence study (n = 1663), we performed longitudinal cluster analysis on prenatal alcohol use reported for four time points around conception and pregnancy. From the sample, 638 respondents reported any alcohol use in pregnancy and were included in trajectories for average daily and maximum drinks per drinking day (max DDD). We then estimated the association with behavioral problems measured by the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF) with multivariable linear regression. The reference group had 1025 children with no reported PAE. ResultsFive trajectories were selected to describe max DDD patterns: very low/discontinuing (n = 186), low/discontinuing (n = 111), very low/continuing (n = 47), med/high (n = 245), and high (n = 49). Six trajectories best described average daily alcohol use: very low/discontinuing (n = 378), very low/continuing (n = 98), low/continuing (n = 56), low/discontinuing (n = 37), medium/high (n = 35), and high (n = 31). When assessing max DDD trajectories for both the CBCL and TRF, individuals with PAE in the two highest trajectories and the very low/continuing trajectory had more behavioral problems relative to children with no PAE, although confidence intervals for most estimates included the null. PAE modeled as average drinks per day did not predict behavior in any consistent pattern. ConclusionsIn this community-based sample, select PAE trajectories were associated with behavior, even at relatively low levels of PAE that continued later in gestation.

Estimated blood pressure trajectories and hypertension patterns among pregnant women living with HIV, Haiti, 2007-2017.

Hypertension in pregnancy is a key driver of mortality and morbidity among Haitian women. HIV infection and treatment may worsen hypertension and increase cardiovascular disease risk. The authors examined blood pressure and hypertension patterns among 1965 women (2306 pregnancies ending in live births) in a prevention of maternal‐to‐child transmission (PMTCT) program in Port‐au‐Prince, Haiti, between 2007 and 2017. Hypertension was defined as blood pressure ≥140/90 mm Hg on two consecutive visits. Latent class analysis assessed trajectories of mean arterial pressure (MAP) and multinomial ordinal logistic regression examined factors associated with higher trajectories. Between 2007–2009 and 2013–2016, hypertension at PMTCT entry increased from 1.3% to 3.8% (p = .005), while incidence at any time during PMTCT follow‐up increased from 5.0 to 16.1 per 100 person‐years (p < .001). Hypertension detected ≤20 weeks and > 20 weeks of gestation (possible gestational hypertension) increased from 1.1% to 3.5% (p = .003) and from 2.3% to 6.9% (p < .001), respectively. Five MAP trajectories ranged from low‐stable to high‐increasing. In multivariable analysis controlling for history of antiretroviral therapy, age, parity, and weight, program entry in more recent years was associated with greater odds of higher MAP trajectory (adjusted odds ratio for 2013–2016 vs. 2007–2009 = 3.1, 95% confidence interval: 1.7–5.6). The increasing prevalence and incidence of hypertension highlight a need for screening and management prior to PMTCT entry and during follow‐up. In a population with limited access to chronic disease care, and where many deliveries occur outside of a clinical setting, the period of PMTCT follow‐up represents an opportunity to diagnose and initiate management of preexisting and pregnancy‐related hypertension.

Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry.

A majority of youth with type 1 diabetes do not meet recommended hemoglobin A1c (HbA1c) targets. The SWEET diabetes registry is a multi-national registry of youth with diabetes. We used data from this registry to identify characteristics associated with glycemic control. Patients in the SWEET diabetes registry with at least one HbA1c value within 10 days of diagnosis and three follow up measurements in the first 18months of diagnosis were included (~10% of the SWEET diabetes registry). Locally weighted scatterplot smoothing was used to generate curves of HbA1c. Wilcoxon, Kruskal-Wallis, or χ2-tests were used to calculate differences between groups. The mean HbA1c of youth in the SWEET diabetes registry is highest at diagnosis and lowest between months 4 and 5 post-diabetes diagnosis. HbA1c continues to increase steadily through the first 18months of diagnosis. There are no differences in HbA1c trajectories based on sex or use of diabetes technology. Youth in North America/Australia/New Zealand had the highest HbA1c throughout the first 18months of diagnosis. The trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. Youth from countries with the highest gross domestic product (GDP) had the highest HbA1c throughout the first 18months of diagnosis. In this subset of patients, the trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. High GDP and high use of technology did not seem to protect from a higher trajectory.

Early life and socio-economic determinants of dietary trajectories in infancy and early childhood \u2013 results from the HSHK birth cohort study

BackgroundEarly childhood is a period when dietary behaviours are established. This study aimed to examine the longitudinal intake of core and discretionary foods and identify early life and socio-economic factors influencing those intakes.MethodsMother-infant dyads (n = 934) from the Healthy Smiles Healthy Kids study, an ongoing birth cohort study, were interviewed. The information on ‘weekly frequency of core and discretionary foods intake’ using a food frequency questionnaire was collected at 4 months, 8 months, 1 year, 2 years and 3 years age points. Group-based trajectory modelling analyses were performed to identify diet trajectories for ‘core’ and ‘discretionary’ foods respectively. A multinomial logistic regression was performed to identify the maternal and child-related predictors of resulting trajectories.ResultsThe intake of core and discretionary foods each showed distinct quadratic (n = 3) trajectories with age. Overall, core foods intake increased rapidly in the first year of life, followed by a decline after age two, whereas discretionary foods intake increased steadily across the five age points. Multiparity (Relative Risk (RR): 0.46, 95%CI: 0.27–0.77), non-English speaking ethnicity of mother (RR: 0.66, 95%CI: 0.47–0.91) and having a single mother (RR: 0.40, 95%CI: 0.18–0.85) were associated with low trajectories of core foods intake whereas older maternal age (RR: 1.05, 95%CI: 1.01–1.08) and longer breastfeeding duration (RR: 1.02, 95%CI: 1.00–1.03) were associated with higher trajectories of core foods intake. Also, multiparity (RR 2.63, 95%CI: 1.47–4.70), low maternal education (RR 3.01, 95%CI: 1.61–5.65), and socio-economic disadvantage (RR 2.69, 95%CI: 1.31–5.55) were associated with high trajectories of discretionary foods intake. Conversely, longer duration of breastfeeding (RR 0.99, 95%CI: 0.97–0.99), and timely introduction of complementary foods (RR 0.30, 95%CI: 0.15–0.61) had a protective effect against high discretionary foods consumption in infancy and early childhood.ConclusionChildren’s frequency of discretionary foods intake increases markedly as they transition from infancy to preschool age, and the trajectories of intake established during early childhood are strongly influenced by socio-demographic factors and infant feeding choices. Hence, there is a need for targeted strategies to improve nutrition in early childhood and ultimately prevent the incidence of chronic diseases in children.

Sediment transport characteristics above a gobi surface in northwestern China, and implications for aeolian environments

Gobis (gravel deserts) cover large areas in northwestern China and other parts of the world, but sediment transport above gobi surfaces has not been widely investigated; thus, there is insufficient empirical data to support dust source identification. In the present study, we used the LDDSEG vertically segmented sediment sampler to collect sediment transport data above a gobi surface. The results demonstrated that the sediment transport rate above the gobi surface was larger than that above a sandy surface, with rates as high as 9.7 kg m-1h−1. The transport flux can be expressed as a Gaussian peak function, with the maximum sediment transport at 0.05 to 0.09 m above the surface. Principal-components analysis (PCA) indicated that the mean grain size of the transported sediment was controlled mainly by the content of silt and clay (<63 μm) and fine sand (125 to 250 μm); this explains the inflection height for sediment transport. PCA also indicated that dry lacustrine deposits were the main sediment source in the study region. About 90% of the cumulative sediment transport occurs at a height below 0.65 m. Our results indicate that sediment transported over a gobi surface has higher trajectories and longer distances than above a sandy surface. The larger silt and clay component (about 30%) of the sediment transported over the gobi surface means that gobi surfaces are important dust sources in northern China, although the dust likely originated from dry lacustrine sites upwind of the study site.

Trajectories of phenotypical frailty over a decade in young–old community-dwelling adults: results from the Lc65+ study

BackgroundFew studies have examined the frailty trajectories of young–old adults using Fried frailty phenotype. Dropouts due to death were rarely taken into account. This longitudinal study aimed to identify trajectories...

Associations between body mass index trajectories in childhood and cardiovascular risk factors in adulthood

Background and aimsChildren with a growth trajectory of overweight have higher levels of cardiovascular disease (CVD) risk factors than children with a normal-weight trajectory. However, less is known about how trajectories of body mass index (BMI) across the rest of the BMI spectrum relate to CVD risk factors and whether adult BMI affects these associations. Our aim was to examine associations between childhood BMI trajectories and adult CVD risk factors. MethodsWe included 2466 individuals with childhood weights and heights (ages 6–14) from the Copenhagen School Health Records Register and adult CVD risk factors (ages 20–81) from the Copenhagen City Heart Study. Associations between childhood BMI trajectories identified by latent class modelling and CVD risk factors were examined using generalized linear regression analyses with and without adjustment for adult BMI. Normal-weight and overweight were defined by growth references from the Centers for Disease Control and Prevention. ResultsWe identified four childhood trajectories within the normal-weight spectrum and one trajectory of overweight. Compared to the trajectory with the lowest BMI level, several higher BMI trajectories were associated with worse circumference, HDL and glucose homeostasis in adulthood. The highest trajectory was additionally associated with higher total cholesterol and triglycerides. When adjusting for adult BMI, the higher BMI trajectories had lower waist circumference, blood pressure and triglycerides. ConclusionsTrajectories of BMI within the normal-weight range and in the overweight range are associated with a worse CVD risk profile than in the lowest BMI trajectory, and these associations are modifiable by growth after childhood.

Perbandingan trajectory tracking pada prototype excavator sistem pneumatic dengan sistem kontrol menggunakan joystick dan smartphone android

Trajectory tracking testing is mostly implemented both on vehicles, mobile robots, flying robots, and excavators to generate a small value of trajectory tracking to effectiveness and efficiency by the tasks and functions of each unit or product. This study aims to compare trajectory tracking on pneumatic excavator units with a manual control system with a joystick and a remote control system using an Android smartphone. Two tracks are used where the first track uses combine straight and radius shapes and the second track combines horizontal and vertical lines that form an angle of 90o. The results showed the use of remote control using an Android smartphone still has a higher trajectory tracking error when compared to manual control with a joystick even though on average the error results obtained are small, so more remote control is needed. Keywords: Pneumatic excavator system, joystick control system, remote control system, error trajectory tracking.

Emulating climate extreme indices

We use simple pattern scaling and time-shift to emulate changes in a set of climate extreme indices under future scenarios, and we evaluate the emulators’ accuracy. We propose an error metric that separates systematic emulation errors from discrepancies between emulated and target values due to internal variability, taking advantage of the availability of climate model simulations in the form of initial condition ensembles. We compute the error metric at grid-point scale, and we show geographically resolved results, or aggregate them as global averages. We use a range of scenarios spanning global temperature increases by the end of the century of 1.5 C and 2.0 C compared to a pre-industrial baseline, and two higher trajectories, RCP4.5 and RCP8.5. With this suite of scenarios we can test the effects on the error of the size of the temperature gap between emulation origin and target scenarios.We find that in the emulation of most indices the dominant source of discrepancy is internal variability. For at least one index, however, counting exceedances of a high temperature threshold, significant portions of the globally aggregated discrepancy and its regional pattern originate from the systematic emulation error. The metric also highlights a fundamental difference in the two methods related to the simulation of internal variability, which is significantly resized by simple pattern scaling. This aspect needs to be considered when using these methods in applications where preserving variability for uncertainty quantification is important.We propose our metric as a diagnostic tool, facilitating the formulation of scientific hypotheses on the reasons for the error. In the meantime, we show that for many impact relevant indices these two well established emulation techniques perform accurately when measured against internal variability, establishing the fundamental condition for using them to represent climate drivers in impact modeling.

Do body mass index and waist-to-height ratio over the preceding decade predict retinal microvasculature in 11-12 year olds and midlife adults?

Microvascular changes may contribute to obesity-associated cardiovascular disease. We examined whether body mass index (BMI) and waist-to-height ratio (WHtR) (1) at multiple earlier time points and (2) decade-long trajectories predicted retinal microvascular parameters in mid-childhood/adulthood. Participants/design: 1288 11-12 year olds (51% girls) and 1264 parents (87% mothers) in the population-based Child Health CheckPoint (CheckPoint) module within the Longitudinal Study of Australian Children (LSAC). LSAC exposure measures: biennial BMI z-score and WHtR for children at five time points from age 2-3 to 10-11 years and self-reported parent BMI at six time points from child age 0-1 years to 10-11 years. CheckPoint outcome measures: retinal arteriolar and venular caliber. BMI/WHtR trajectories were identified by group-based trajectory modeling; linear regression models estimated associations between BMI/WHtR at each time point/trajectories and later retinal vascular caliber, adjusted for age, sex, and family socioeconomic status. In time point analyses, higher child BMI/WHtR from age 4 to 5 years was associated with narrower arteriolar caliber at the age of 11-12 years, but not venular caliber. For example, each standard deviation higher in BMI z-score at 4-5 years was associated with narrower arteriolar caliber at 11-12 years (standardized mean difference (SMD): -0.05, 95% confidence interval (CI): -0.10 to 0.01); by 10-11 years, associations had doubled to -0.10 (95% CI: -0.16 to -0.05). In adults, these finding were similar, except the magnitude of BMI and arteriolar associations were similar across all time points (SMD: -0.11 to -0.13). In child and adult BMI trajectory analyses, less favorable trajectories predicted narrower arteriolar (p-trend < 0.05), but not venular (p-trend > 0.1), caliber. Compared with those in the average BMI trajectory, SMDs in arterial caliber for children and adults in the highest trajectory were -0.25 (95% CI: -0.44 to -0.07) and -0.42 (95% CI: -0.73 to -0.10), respectively. Venular caliber showed late associations with child WHtR, but not with BMI in children or adults. Associations of decade-long high BMI trajectories with narrowed retinal arteriolar caliber emerge in children, and are clearly evident by midlife. Adiposity appears to exert its early adverse life course impacts on the microcirculation more via arteriolar than venular mechanisms.

A Privacy-Preserving Trajectory Publication Method Based on Secure Start-Points and End-Points

By judging whether the start-point and end-point of a trajectory conform to the user’s behavioral habits, an attacker who possesses background knowledge can breach the anonymous trajectory. Traditional trajectory privacy preservation schemes often generate an anonymous set of trajectories without considering the security of the trajectory start- and end-points. To address this problem, this paper proposes a privacy-preserving trajectory publication method based on generating secure start- and end-points. First, a candidate set containing a secure start-point and end-point is generated according to the user’s habits. Second, k−1 anonymous trajectories are generated bidirectionally according to that secure candidate set. Finally, accessibility corrections are made for each anonymous trajectory. This method integrates features such as local geographic reachability and trajectory similarity when generating an anonymized set of trajectories. This provides users with privacy preservation at the k-anonymity level, without relying on the trusted third parties and with low algorithm complexity. Compared with existing methods such as trajectory rotation and unidirectional generation, theoretical analysis and experimental results on the datasets of real trajectories show that the anonymous trajectories generated by the proposed method can ensure the security of trajectory privacy while maintaining a higher trajectory similarity.

Modeling Variation in the Reproductive Lifespan of Female Adolescent and Young Adult Cancer Survivors Using AMH.

Many female survivors of adolescent and young adult cancers (AYA survivors) have shortened reproductive lifespans. However, the timing and duration of ovarian function after cancer treatment are largely unknown. To model the trajectory of ovarian function over two decades following cancer treatment and evaluate how trajectories vary by treatment gonadotoxicity and age. In a prospective cohort, AYA survivors aged 18-39 at variable times since cancer treatment completion provided dried blood spots (DBS) every 6 months for up to 18 months. Anti-Müllerian hormone (AMH) levels were measured using the Ansh DBS AMH enzyme-linked immunosorbent assay. The mean AMH trajectory was modeled for the entire cohort and separately by treatment gonadotoxicity and age using functional principal components analysis. 763 participants, mean (standard deviation) enrollment age 33.3 (4.7) and age at cancer diagnosis 25.9 (5.7) years, contributed 1905 DBS samples. The most common cancers were breast (26.9%), lymphoma (24.8%), and thyroid (18.0%). AMH trajectories differed among survivors by treatment gonadotoxicity (low, moderate, or high) (P < 0.001). Following low or moderately gonadotoxic treatments, AMH levels increased over 2-3 years and plateaued over 10-15 years before declining. In contrast, following highly gonadotoxic treatment, AMH levels were lower overall and declined shortly after peak at 2-3 years. Younger age at treatment was associated with higher trajectories, but a protective effect of younger age was not observed in survivors exposed to highly gonadotoxic treatments (Pinteraction < 0.001). In this large AYA survivor cohort, timing and duration of ovarian function strongly depended on treatment gonadotoxicity and age at treatment. The findings provide novel, more precise information to guide reproductive decision-making.

Bridging the Soft-skills Deficit Gap Among Secondary Students in the UAE

Educators are increasingly aware of the pivotal role that soft skills play in making sure students are adequately prepared to initiate collegiate education. Soft skills will be increasingly vital ingredient for success in postsecondary education and are very important for all students that need to develop their potential while in school. Soft skills are a valuable component and is a vital factor impacting the chances of student success in collegiate education. This indicates the importance and necessity of acquiring soft skills for the students while studying at schools. In this paper, five areas of soft skills namely communication skills, decision making and problem-solving skills, time management skills, teamwork and interpersonal skills , cultural competency skills are explored in an effort to find out the Soft-skills gap among secondary students in UAE . Though there are many other types of skills, the skills mentioned do provide a glimpse of the types of skills required for postsecondary success. The identified soft-skills gap need to be addressed rigorously to put the students in the higher trajectory for post-secondary success Keywords: Soft skills; Gap Analysis, secondary education; postsecondary success DOI : 10.7176/JLPG/89-05 Publication date :September 30 th 2019

Improved Linear Active Disturbance Rejection Control for Lever-Type Electric Erection System with Varying Loads and Low-Resolution Encoder

The lever-type electric erection system is a novel kind of erection system and the experimental platform in this paper operates with varying loads and low-resolution encoder. For high accuracy trajectory tracking, linear active disturbance rejection control (LADRC) is introduced. An approximate model, consisting of the servo system configured at velocity control mode and the lever-type erection mechanism, is built by means of system identification and curve fitting. Reduced-order LADRC based on the further simplified model is proposed to improve tracking accuracy and robustness. As comparisons, traditional LADRC and PID with high-gain tracking differentiator (HGTD) are designed. Simulation and experimental results indicate that reduced-order LADRC can realize higher trajectory tracking accuracy with low-resolution encoder and has better robustness to variation in erection loads, compared with traditional LADRC and PID with HGTD.

AUDIT-C and ICD codes as phenotypes for harmful alcohol use: association with ADH1B polymorphisms in two US populations.

Longitudinal electronic health record (EHR) data offer a large-scale, untapped source of phenotypical information on harmful alcohol use. Using established, alcohol-associated variants in the gene that encodes the enzyme alcohol dehydrogenase 1B (ADH1B) as criterion standards, we compared the individual and combined validity of three longitudinal EHR-based phenotypes of harmful alcohol use: Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) trajectories; mean age-adjusted AUDIT-C; and diagnoses of alcohol use disorder (AUD). With longitudinal EHR data from the Million Veteran Program (MVP) linked to genetic data, we used two population-specific polymorphisms in ADH1B that are associated strongly with AUD in African Americans (AAs) and European Americans (EAs): rs2066702 (Arg369Cys, AAs) and rs1229984 (Arg48His, EAs) as criterion measures. United States Department of Veterans Affairs Healthcare System. A total of 167 721 veterans (57 677 AAs and 110 044 EAs; 92% male, mean age=63years) took part in this study. Data were collected from 1 October 2007 to 1May 2017. Using all AUDIT-C scores and AUD diagnostic codes recorded in the EHR, we calculated age-adjusted mean AUDIT-C values, longitudinal statistical trajectories of AUDIT-C scores and ICD-9/10 diagnostic groupings for AUD. A total of 19 793 AAs (34.3%) had one or two minor alleles at rs2066702 [minor allele frequency (MAF)=0.190] and 6933 EAs (6.3%) had one or two minor alleles at rs1229984 (MAF=0.032). In both populations, trajectories and age-adjusted mean AUDIT-C were correlated (r=0.90) but, when considered separately, highest score (8+ versus 0) of age-adjusted mean AUDIT-C demonstrated a stronger association with the ADH1B variants [adjusted odds ratio (aOR) 0.54 in AAs and 0.37 in AAs] than did the highest trajectory (aOR 0.71 in AAs and 0.53 in EAs); combining AUDIT-C metrics did not improve discrimination. When age-adjusted mean AUDIT-C score and AUD diagnoses were considered together, age-adjusted mean AUDIT-C (8+ versus 0) was associated with lower odds of having the ADH1B minor allele than were AUD diagnostic codes: aOR=0.59 versus 0.86 in AAs and 0.48 versus 0.68 in EAs. These independent associations combine to yield an even lower aOR of 0.51 for AAs and 0.33 for EAs. The age-adjusted mean AUDIT-C score is associated more strongly with genetic polymorphisms of known risk for alcohol use disorder than are longitudinal trajectories of AUDIT-C or AUD diagnostic codes. AUD diagnostic codes modestly enhance this association.

Long-term BMI and growth profiles in offspring of women with gestational diabetes

Aims/hypothesisGestational diabetes mellitus (GDM) is reported to be associated with childhood obesity, however the magnitude of this association and relation to intrauterine growth is uncertain. We, therefore, aimed to assess whether the growth trajectories of large for gestational age (LGA) and non-LGA offspring of mothers with GDM (OGDM) are different until early adolescence. We also aimed to explore whether growth trajectories of OGDM differ from those of offspring of mothers with type 1 or 2 diabetes (ODM1, ODM2).MethodsWe studied height and BMI standard deviation score (SDS) of the OGDM group, up to the age of 14 years, with subgroup analysis comparing LGA with non-LGA at birth as a reflection of the intrauterine environment. All mothers with GDM who delivered at the University Medical Center Utrecht between 1990 and 2006 were contacted to participate; informed consent was received for 104 OGDM of 93 mothers. Offspring data were collected through Dutch infant welfare centres. Recorded height and weight were converted to BMI and age- and sex-specific SDS values for Dutch children. Additionally, we compared the OGDM group with ODM1 and ODM2 groups in order to identify those offspring with the highest risk of becoming overweight. Growth trajectories were compared between non-LGA and LGA OGDM and between OGDM, ODM1 and ODM2, using a random-effects model. In the longitudinal follow-up a mean of 7.4 ± 2 measurements per infant were available.ResultsMothers had a prepregnancy BMI of 25.8 kg/m2 and 24% of their infants were LGA at birth. Heights of OGDM were no different from those of the Dutch Growth Study. Non-LGA OGDM showed a BMI SDS comparable with that of the reference population, with a slight increase in early adolescence. LGA OGDM had a higher BMI SDS trajectory than non-LGA OGDM and the reference population, which plateaued at around 10 years of age. Comparison of growth trajectories of OGDM, ODM1 and ODM2 showed ODM2 to have the highest trajectory followed by ODM1 and OGDM, with the LGA counterparts of all three offspring groups in the highest BMI SDS ranges.Conclusions/interpretationUntil early adolescence, OGDM have a BMI that is 0.5 SDS higher than that of the Dutch background population. LGA OGDM appear to be at particularly higher risk of being overweight in adolescence compared with non-LGA OGDM, putting them also at a higher lifetime risk of being overweight and developing obesity. ODM2 showed the highest BMI SDS values and had an average BMI SDS of +1.6 until the age of 14, when it became +2 SD. These results emphasize the importance of adequate recognition and timely treatment of maternal gestational diabetes to prevent fetal macrosomia in obstetrics.

Pain and functional trajectories in symptomatic knee osteoarthritis over up to 12 weeks of exercise exposure

Exercise is the recommended treatment for knee osteoarthritis (OA). However, heterogeneous patterns in treatment response are poorly understood. Our purpose was to identify pain and functional trajectories from exercise interventions in knee OA, and to determine their association with baseline factors. Prospective cohort of 171 participants (mean age 61 years; BMI 32kg/m2, 71% female; 57% white) with symptomatic knee OA from a randomized trial comparing 12-week Tai Chi and Physical Therapy. We analyzed weekly Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain (0-500) and function (0-1700) scores using group-based trajectory models. Associations between baseline factors and trajectories were examined using multinomial logistic regression. We identified four pain trajectories: Lower-Early Improvement (43%), Moderate-Early Improvement (32%), Higher-Delayed Improvement (15%), and Higher-No Improvement (10%). We found similar trajectories for function, except that the lower function trajectories diverged into gradual (12%) or delayed-improvement (15%). Compared with the Lower-Early Improvement pain trajectory, moderate and higher trajectories were associated with poorer physical and psychosocial health. A similar pattern of associations were found among the function trajectories. We found four distinct trajectories for pain and function over up to 12-weeks of exercise interventions. While most participants experienced improvements over a short-term exposure, subgroups with greater baseline pain/physical disability had either gradual, delayed, or no improvements. These findings help disentangle the heterogeneity of treatment response and may advance patient-centered care in knee OA.