TY - JOUR AB - IMPORTANCE: The association between short-term exposure to air pollution and mortality has been widely documented worldwide; however, few studies have applied causal modeling approaches to account for unmeasured confounders that vary across time and space. OBJECTIVE: To estimate the association between short-term changes in fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations and changes in daily all-cause mortality rates using a causal modeling approach. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used air pollution and mortality data from Jiangsu, China; California; central-southern Italy; and Germany with interactive fixed-effects models to control for both measured and unmeasured spatiotemporal confounders. A total of 8 963 352 deaths in these 4 regions from January 1, 2015, to December 31, 2019, were included in the study. Data were analyzed from June 1, 2021, to October 30, 2023. EXPOSURE: Day-to-day changes in county- or municipality-level mean PM2.5 and NO2 concentrations. MAIN OUTCOMES AND MEASURES: Day-to-day changes in county- or municipality-level all-cause mortality rates. RESULTS: Among the 8 963 352 deaths in the 4 study regions, a 10-μg/m3 increase in daily PM2.5 concentration was associated with an increase in daily all-cause deaths per 100 000 people of 0.01 (95% CI, 0.001-0.01) in Jiangsu, 0.03 (95% CI, 0.004-0.05) in California, 0.10 (95% CI, 0.07-0.14) in central-southern Italy, and 0.04 (95% CI, 0.02- 0.05) in Germany. The corresponding increases in mortality rates for a 10-μg/m3 increase in NO2 concentration were 0.04 (95% CI, 0.03-0.05) in Jiangsu, 0.03 (95% CI, 0.01-0.04) in California, 0.10 (95% CI, 0.05-0.15) in central-southern Italy, and 0.05 (95% CI, 0.04-0.06) in Germany. Significant effect modifications by age were observed in all regions, by sex in Germany (eg, 0.05 [95% CI, 0.03-0.06] for females in the single-pollutant model of PM2.5), and by urbanicity in Jiangsu (0.07 [95% CI, 0.04-0.10] for rural counties in the 2-pollutant model of NO2). CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study contribute to the growing body of evidence that increases in short-term exposures to PM2.5 and NO2 may be associated with increases in all-cause mortality rates. The interactive fixed-effects model, which controls for unmeasured spatial and temporal confounders, including unmeasured time-varying confounders in different spatial units, can be used to estimate associations between changes in short-term exposure to air pollution and changes in health outcomes. AU - Ma, Y.* AU - Nobile, F.* AU - Marb, A. AU - Dubrow, R.* AU - Stafoggia, M.* AU - Breitner-Busch, S. AU - Kinney, P.L.* AU - Chen, K.* C1 - 70093 C2 - 55225 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa TI - Short-term exposure to fine particulate matter and nitrogen dioxide and mortality in 4 countries. JO - JAMA net. open VL - 7 IS - 3 PB - Amer Medical Assoc PY - 2024 SN - 2574-3805 ER - TY - JOUR AB - IMPORTANCE: Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. OBJECTIVE: To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. EXPOSURES: Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. MAIN OUTCOMES AND MEASURES: The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. RESULTS: In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. CONCLUSIONS AND RELEVANCE: This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT. AU - Zamboglou, C.* AU - Peeken, J.C. AU - Janbain, A.* AU - Katsahian, S.* AU - Strouthos, I.* AU - Ferentinos, K.* AU - Farolfi, A.* AU - Koerber, S.A.* AU - Debus, J.* AU - Vogel, M.M. AU - Combs, S.E. AU - Vrachimis, A.* AU - Morganti, A.G.* AU - Spohn, S.K.B.* AU - Shelan, M.* AU - Aebersold, D.M.* AU - Grosu, A.L.* AU - Ceci, F.* AU - Henkenberens, C.* AU - Kroeze, S.G.C.* AU - Guckenberger, M.* AU - Fanti, S.* AU - Belka, C.* AU - Bartenstein, P.* AU - Hruby, G.* AU - Scharl, S.* AU - Wiegel, T.* AU - Emmett, L.* AU - Arnoux, A.* AU - Schmidt-Hegemann, N.S.* C1 - 67906 C2 - 54384 TI - Development and validation of a multi-institutional nomogram of outcomes for PSMA-PET–based salvage radiotherapy in recurrent Prostate Cancer. JO - JAMA net. open VL - 6 IS - 5 PY - 2023 SN - 2574-3805 ER - TY - JOUR AU - Kullmann, S. C1 - 63098 C2 - 51291 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa TI - Nonnutritive sweeteners and neural reward response in women and Iidividuals with obesity. JO - JAMA net. open VL - 4 IS - 9 PB - Amer Medical Assoc PY - 2021 SN - 2574-3805 ER - TY - JOUR AB - Importance: People classified by a priori definitions as having metabolically healthy obesity have frequently been found to be at increased risk of mortality, compared with individuals with metabolically healthy normal weight, suggesting these definitions may be insufficient. Objectives: To systematically derive a new definition of metabolic health (MH) and investigate its association with cardiovascular disease (CVD) mortality and total mortality. Design, Setting, and Participants: In a cohort study using data from the third National Health and Nutrition Examination Survey (NHANES-III), a representative survey using complex multistage probability sampling, anthropometric factors, biomarkers, and blood pressure (BP) associated with total and CVD mortality among participants with obesity were identified with Cox proportional hazards regression. Area under the receiver operating characteristic was calculated to identify predictive factors for mortality to be used to define MH, cutoff levels were determined by the Youden index, and the findings were validated through comparison with the independent UK Biobank cohort, a population-based prospective study. All nonpregnant participants in the databases aged 18 to 75 years with no history of CVD, body mass index greater than or equal to 18.5, and who fasted 6 or more hours before examination in NHANES-III were included; participants in the UK Biobank cohort who did not have blood measurements were excluded. The study was conducted from 2015 to 2020. Exposures: Body mass index and MH were defined by the new definition and compared with 3 a priori definitions. Main Outcomes and Measures: Cardiovascular disease mortality and total mortality. Results: Within the NHANES-III (n = 12 341) cohort, mean (SD) age was 41.6 (29.2) years, 50.7% were women, and mean follow-up was 14.5 (2.7) years. Within the UK Biobank (n = 374 079) cohort, mean (SD) age was 56.2 (8.1) years, 55.1% were women, and mean follow-up was 7.8 (1.0) years. Use of blood pressure (BP)-lowering medication (hazard ratio [HR] for CVD mortality, 2.41; 95% CI, 1.50-3.87 and total mortality, 2.05; 95% CI, 1.47-2.84), diabetes, and several continuous factors were associated with mortality. Of all significant continuous factors, the combination of systolic BP and waist-to-hip ratio showed the highest area under the receiver operating characteristic (CVD mortality: 0.775; 95% CI, 0.770-0.781; total mortality: 0.696; 95% CI, 0.694-0.699). Thus, MH was defined as systolic BP less than 130 mm Hg, no BP-lowering medication, waist-to-hip ratio less than 0.95 for women and less than 1.03 for men, and no self-reported (ie, prevalent) diabetes. In both cohorts, metabolically healthy obesity was not associated with CVD and total mortality compared with metabolically healthy normal weight. For NHANES-III, the hazard ratio was 0.68 (95% CI, 0.30-1.54) for CVD mortality and 1.03 (95% CI, 0.70-1.51) for total mortality. For UK Biobank, the hazard ratio was 1.17 (95% CI, 0.81-1.69) for CVD mortality and 0.98 (95% CI, 0.87-1.10) for total mortality. Regardless of body mass index, all metabolically unhealthy groups displayed increased risks. Conclusions and Relevance: This newly proposed definition of MH may identify a subgroup of people with obesity without increased risk of mortality and stratify risks in people who are overweight or normal weight. AU - Zembic, A.* AU - Eckel, N.* AU - Stefan, N. AU - Baudry, J.* AU - Schulze, M.B.* C1 - 61928 C2 - 50510 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa TI - An empirically derived definition of metabolically healthy obesity based on risk of cardiovascular and total mortality. JO - JAMA net. open VL - 4 IS - 5 PB - Amer Medical Assoc PY - 2021 SN - 2574-3805 ER - TY - JOUR AB - Question Is a stepwise approach to identifying, delaying, and preventing diabetes in individuals with high risk in a low-income to middle-income country setting cost-effective? Findings In this economic evaluation study, conducted within a randomized clinical trial during a 3-year period, it would cost 145 international dollars to screen for and reduce diabetes incidence by 1 percentage point, 14 & x202f;539 international dollars per diabetes case prevented and/or delayed, and 14 & x202f;986 international dollars per quality-adjusted life-year gained. Meaning The findings of this study suggest that a stepwise approach for identification of high-risk individuals and diabetes prevention is likely cost-effective, even in a low-income to middle-income country setting.This economic evaluation estimates the cost-effectiveness of a stepwise approach to diabetes prevention among adults in India participating in the Diabetes Community Lifestyle Improvement Program.Importance A stepwise approach that includes screening and lifestyle modification followed by the addition of metformin for individuals with high risk of diabetes is recommended to delay progression to diabetes; however, there is scant evidence regarding whether this approach is cost-effective. Objective To estimate the cost-effectiveness of a stepwise approach in the Diabetes Community Lifestyle Improvement Program. Design, Setting, and Participants This economic evaluation study included 578 adults with impaired glucose tolerance, impaired fasting glucose, or both. Participants were enrolled in the Diabetes Community Lifestyle Improvement Program, a randomized clinical trial with 3-year follow-up conducted at a diabetes care and research center in Chennai, India. Interventions The intervention group underwent a 6-month lifestyle modification curriculum plus stepwise addition of metformin; the control group received standard lifestyle advice. Main Outcomes and Measures Cost, health benefits, and incremental cost-effectiveness ratios (ICERs) were estimated from multipayer (including direct medical costs) and societal (including direct medical and nonmedical costs) perspectives. Costs and ICERs were reported in 2019 Indian rupees (INR) and purchasing power parity-adjusted international dollars (INT $). Results The mean (SD) age of the 578 participants was 44.4 (9.3) years, and 364 (63.2%) were men. Mean (SD) body mass index was 27.9 (3.7), and the mean (SD) glycated hemoglobin level was 6.0% (0.5). Implementing lifestyle modification and metformin was associated with INR 10 & x202f;549 (95% CI, INR 10 & x202f;134-10 & x202f;964) (INT $803 [95% CI, INT $771-834]) higher direct costs; INR 5194 (95% CI, INR 3187-INR 7201) (INT $395; 95% CI, INT $65-147) higher direct nonmedical costs, an absolute diabetes risk reduction of 10.2% (95% CI, 1.9% to 18.5%), and an incremental gain of 0.099 (95% CI, 0.018 to 0.179) quality-adjusted life-years per participant. From a multipayer perspective (including screening costs), mean ICERs were INR 1912 (INT $145) per 1 percentage point diabetes risk reduction, INR 191 & x202f;090 (INT $14 & x202f;539) per diabetes case prevented and/or delayed, and INR 196 & x202f;960 (INT $14 & x202f;986) per quality-adjusted life-year gained. In the scenario of a 50% increase or decrease in screening and intervention costs, the mean ICERs varied from INR 855 (INT $65) to INR 2968 (INT $226) per 1 percentage point diabetes risk reduction, from INR 85 & x202f;495 (INT $6505) to INR 296 & x202f;681 (INT $22 & x202f;574) per diabetes case prevented, and from INR 88 & x202f;121 (INT $6705) to INR 305 & x202f;798 (INT $23 & x202f;267) per quality-adjusted life-year gained. Conclusions and Relevance The findings of this study suggest that a stepwise approach for diabetes prevention is likely to be cost-effective, even if screening costs for identifying high-risk individuals are added. AU - Islek, D.* AU - Weber, M.B.* AU - Ranjit Mohan, A.* AU - Mohan, V.* AU - Staimez, L.R.* AU - Harish, R.* AU - Narayan, K.M.V.* AU - Laxy, M. AU - Ali, M.K.* C1 - 59800 C2 - 49050 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa TI - Cost-effectiveness of a Stepwise Approach vs Standard Care for Diabetes Prevention in India. JO - JAMA net. open VL - 3 IS - 7 PB - Amer Medical Assoc PY - 2020 SN - 2574-3805 ER - TY - JOUR AB - This cross-sectional study uses the normalized difference vegetation index and the soil-adjusted vegetation index to examine the associations between the level of residential greenness, the presence of cardiometabolic disorders, and the prevalence of cardiovascular disease among adults in China.Question Is the general vegetation level of a residential area, referred to as residential greenness, associated with cardiovascular disease among adults, and does the presence of cardiometabolic disorders mediate or modify the association between residential greenness and cardiovascular disease? Findings In this cross-sectional study of 2445 adults in China, residential areas with higher greenness levels were associated with a lower likelihood of cardiovascular disease. The presence of cardiometabolic disorders partially mediated the association between residential greenness and cardiovascular disease. Meaning The study's findings may be helpful for health care professionals and policy makers in the development of strategies, such as planning for green spaces in residential areas, to mitigate the burden of cardiovascular disease.Importance Living in areas with more vegetation (referred to as residential greenness) may be associated with cardiovascular disease (CVD), but little data are available from low- and middle-income countries. In addition, it remains unclear whether the presence of cardiometabolic disorders modifies or mediates the association between residential greenness and CVD. Objective To evaluate the associations between residential greenness, cardiometabolic disorders, and CVD prevalence among adults in China. Design, Setting, and Participants This analysis was performed as part of the 33 Communities Chinese Health Study, a large population-based cross-sectional study that was conducted in 33 communities (ranging from 0.25-0.64 km(2)) in 3 cities within the Liaoning province of northeastern China between April 1 and December 31, 2009. Participants included adults aged 18 to 74 years who had resided in the study area for 5 years or more. Greenness levels surrounding each participant's residential community were assessed using the normalized difference vegetation index and the soil-adjusted vegetation index from 2010. Lifetime CVD status (including myocardial infarction, heart failure, coronary heart disease, cerebral thrombosis, cerebral hemorrhage, cerebral embolism, and subarachnoid hemorrhage) was defined as a self-report of a physician diagnosis of CVD at the time of the survey. Cardiometabolic disorders, including hypertension, diabetes, dyslipidemia, and overweight or obese status, were measured and defined clinically. Generalized linear mixed models were used to evaluate the association between residential greenness levels and CVD prevalence. A 3-way decomposition method was used to explore whether the presence of cardiometabolic disorders mediated or modified the association between residential greenness and CVD. Data were analyzed from October 10 to May 30, 2020. Main Outcomes and Measures Lifetime CVD status, the presence of cardiometabolic disorders, and residential greenness level. Results Among 24 845 participants, the mean (SD) age was 45.6 (13.3) years, and 12661 participants (51.0%) were men. A total of 1006 participants (4.1%) reported having a diagnosis of CVD. An interquartile range (1-IQR) increase in the normalized difference vegetation index within 500 m of a community was associated with a 27% lower likelihood (odds ratio [OR], 0.73; 95% CI, 0.65-0.83; P < .001) of CVD prevalence, and an IQR increase in the soil-adjusted vegetation index within 500 m of a community was associated with a 26% lower likelihood (OR, 0.74; 95% CI, 0.66-0.84; P < .001) of CVD prevalence. The presence of cardiometabolic disorders was found to mediate the association between residential greenness and CVD, with mediation effects of 4.5% for hypertension, 4.1% for type 2 diabetes, 3.1% for overweight or obese status, 12.7% for hypercholesterolemia, 8.7% for hypertriglyceridemia, and 11.1% for high low-density lipoprotein cholesterol levels. Conclusions and Relevance In this cross-sectional study, higher residential greenness levels were associated with lower CVD prevalence, and this association may be partially mediated by the presence of cardiometabolic disorders. Further studies, preferably longitudinal, are warranted to confirm these findings. AU - Yang, B.Y.* AU - Hu, L.W.* AU - Jalaludin, B.* AU - Knibbs, L.D.* AU - Markevych, I. AU - Heinrich, J.* AU - Bloom, M.S.* AU - Morawska, L.* AU - Lin, S.* AU - Jalava, P.* AU - Roponen, M.* AU - Gao, M.* AU - Chen, D.H.* AU - Zhou, Y.* AU - Yu, H.Y.* AU - Liu, R.Q.* AU - Zeng, X.W.* AU - Zeeshan, M.* AU - Guo, Y.* AU - Yu, Y.* AU - Dong, G.H.* C1 - 60159 C2 - 49280 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa TI - Association between residential greenness, cardiometabolic disorders, and cardiovascular disease among adults in China. JO - JAMA net. open VL - 3 IS - 9 PB - Amer Medical Assoc PY - 2020 SN - 2574-3805 ER - TY - JOUR AB - Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures: Type 2 diabetes and glycemic traits. Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms. AU - Huang, T.* AU - Wang, T.* AU - Zheng, Y.* AU - Ellervik, C.* AU - Li, X.* AU - Gao, M.* AU - Fang, Z.* AU - Chai, J.F.* AU - Ahluwalia, T.V.S.* AU - Wang, Y.* AU - Voortman, T.* AU - Noordam, R.* AU - Frazier-Wood, A.C.* AU - Scholz, M.* AU - Sonestedt, E.* AU - Akiyama, M.* AU - Dorajoo, R.* AU - Zhou, A.* AU - Kilpeläinen, T.O.* AU - Kleber, M.E.* AU - Crozier, S.R.* AU - Godfrey, K.M.* AU - Lemaitre, R.* AU - Felix, J.F.* AU - Shi, Y.* AU - Gupta, P.* AU - Khor, C.C.* AU - Lehtimäki, T.* AU - Wang, C.A.* AU - Tiesler, C.M. AU - Thiering, E. AU - Standl, M. AU - Rzehak, P.* AU - Marouli, E.* AU - He, M.* AU - Lecoeur, C.* AU - Corella, D.* AU - Lai, C.Q.* AU - Moreno, L.A.* AU - Pitkänen, N.* AU - Boreham, C.A.* AU - Zhang, T.* AU - Saw, S.M.* AU - Ridker, P.M.* AU - Graff, M.* AU - van Rooij, F.J.A.* AU - Uitterlinden, A.G.* AU - Hofman, A.* AU - van Heemst, D.* AU - Rosendaal, F.R.* AU - de Mutsert, R.* AU - Burkhardt, R.* AU - Schulz, C.A.* AU - Ericson, U.* AU - Kamatani, Y.* AU - Yuan, J.M.* AU - Power, C.* AU - Hansen, T.* AU - Sörensen, T.I.A.* AU - Tjönneland, A.* AU - Overvad, K.* AU - Delgado, G.* AU - Cooper, C.* AU - Djousse, L.* AU - Rivadeneira, F.* AU - Jameson, K.* AU - Zhao, W.* AU - Liu, J.* AU - Lee, N.R.* AU - Raitakari, O.* AU - Kähönen, M.* AU - Viikari, J.* AU - Grote, V.* AU - Langhendries, J.P.* AU - Koletzko, B.* AU - Escribano, J.* AU - Verduci, E.* AU - Dedoussis, G.* AU - Yu, C.* AU - Tham, Y.C.* AU - Lim, B.* AU - Lim, S.H.* AU - Froquel, P.* AU - Balkau, B.* AU - Fink, N.R.* AU - Vinding, R.K.* AU - Sevelsted, A.* AU - Bisgaard, H.* AU - Coltell, O.* AU - Dallongeville, J.* AU - Gottrand, F.* AU - Pahkala, K.* AU - Niinikoski, H.* AU - Hyppönen, E.* AU - Pedersen, O.* AU - März, W.* AU - Inskip, H.* AU - Jaddoe, V.W.V.* AU - Dennison, E.* AU - Wong, T.Y.* AU - Sabanayagam, C.* AU - Tai, E.S.* AU - Mohlke, K.L.* AU - Mackey, D.A.* AU - Gruszfeld, D.* AU - Deloukas, P.* AU - Tucker, K.L.* AU - Fumeron, F.* AU - Bønnelykke, K.* AU - Rossing, P.* AU - Estruch, R.* AU - Ordovas, J.M.* AU - Arnett, D.K.* AU - Meirhaeghe, A.* AU - Amouyel, P.* AU - Cheng, C.Y.* AU - Sim, X.* AU - Teo, Y.Y.* AU - van Dam, R.M.* AU - Koh, W.P.* AU - Orho-Melander, M.* AU - Loeffler, M.* AU - Kubo, M.* AU - Thiery, J.* AU - Mook-Kanamori, D.O.* AU - Mozaffarian, D.* AU - Psaty, B.M.* AU - Franco, O.H.* AU - Wu, T.* AU - North, K.E.* AU - Davey Smith, G.* AU - Chavarro, J.E.* AU - Chasman, D.I.* AU - Qi, L.* C1 - 56945 C2 - 47455 TI - Association of birth weight with Type 2 diabetes and glycemic traits: A mendelian randomization study. JO - JAMA net. open VL - 2 IS - 9 PY - 2019 SN - 2574-3805 ER - TY - JOUR AB - Importance: Lowering serum cholesterol levels is a well-established treatment for dyslipidemia in patients with type 2 diabetes (T2D). However, nerve lesions in patients with T2D increase with lower serum cholesterol levels, suggesting that lowering serum cholesterol levels is associated with diabetic polyneuropathy (DPN) in patients with T2D. Objective: To investigate whether there is an association between serum cholesterol levels and peripheral nerve lesions in patients with T2D with and without DPN. Design, Setting, and Participants: This single-center, cross-sectional, prospective cohort study was performed from June 1, 2015, to March 31, 2018. Observers were blinded to clinical data. A total of 256 participants were approached, of whom 156 were excluded. A total of 100 participants consented to undergo magnetic resonance neurography of the right leg at the Department of Neuroradiology and clinical, serologic, and electrophysiologic assessment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. Exposures: Quantification of the nerve's diameter and lipid equivalent lesion (LEL) load with a subsequent analysis of all acquired clinical and serologic data with use of 3.0-T magnetic resonance neurography of the right leg with 3-dimensional reconstruction of the sciatic nerve. Main Outcomes and Measures: The primary outcome was lesion load and extension. Secondary outcomes were clinical, serologic, and electrophysiologic findings. Results: A total of 100 participants with T2D (mean [SD] age, 64.6 [0.9] years; 68 [68.0%] male) participated in the study. The LEL load correlated positively with the nerve's mean cross-sectional area (r = 0.44; P < .001) and the maximum length of a lesion (r = 0.71; P < .001). The LEL load was negatively associated with total serum cholesterol level (r = -0.41; P < .001), high-density lipoprotein cholesterol level (r = -0.30; P = .006), low-density lipoprotein cholesterol level (r = -0.33; P = .003), nerve conduction velocities of the tibial (r = -0.33; P = .01) and peroneal (r = -0.51; P < .001) nerves, and nerve conduction amplitudes of the tibial (r = -0.31; P = .02) and peroneal (r = -0.28; P = .03) nerves. Conclusions and Relevance: The findings suggest that lowering serum cholesterol levels in patients with T2D and DPN is associated with a higher amount of nerve lesions and declining nerve conduction velocities and amplitudes. These findings may be relevant to emerging therapies that promote an aggressive lowering of serum cholesterol levels in patients with T2D. AU - Jende, J.M.E.* AU - Groener, J.B.* AU - Rother, C.* AU - Kender, Z.* AU - Hahn, A.* AU - Hilgenfeld, T.* AU - Juerchott, A.* AU - Preisner, F.* AU - Heiland, S.* AU - Kopf, S.* AU - Pham, M.* AU - Nawroth, P.P. AU - Bendszus, M.* AU - Kurz, F.T.* C1 - 56196 C2 - 46888 TI - Association of serum cholesterol levels with peripheral nerve damage in patients with type 2 diabetes. JO - JAMA net. open VL - 2 IS - 5 PY - 2019 SN - 2574-3805 ER - TY - JOUR AB - IMPORTANCE Increasing evidence suggests an important role of liver function in the pathophysiology of Alzheimer disease (AD). The liver is a major metabolic hub; therefore, investigating the association of liver function with AD, cognition, neuroimaging, and CSF biomarkers would improve the understanding of the role of metabolic dysfunction in AD.OBJECTIVE To examine whether liver function markers are associated with cognitive dysfunction and the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD.DESIGN, SETTING, AND PARTICIPANTS In this cohort study, serum-based liver function markers were measured from September 1, 2005, to August 31, 2013, in 1581 AD Neuroimaging Initiative participants along with cognitive measures, cerebrospinal fluid (CSF) biomarkers, brain atrophy, brain glucose metabolism, and amyloid-beta accumulation. Associations of liver function markers with AD-associated clinical and A/T/N biomarkers were assessed using generalized linear models adjusted for confounding variables and multiple comparisons. Statistical analysis was performed from November 1, 2017, to February 28, 2019.EXPOSURES Five serum-based liver function markers (total bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) from AD Neuroimaging Initiative participants were used as exposure variables.MAIN OUTCOMES AND MEASURES Primary outcomes included diagnosis of AD, composite scores for executive functioning and memory, CSF biomarkers, atrophy measured by magnetic resonance imaging, brain glucose metabolism measured by fludeoxyglucose F 18 (F-18) positron emission tomography, and amyloid-beta accumulation measured by [F-18]florbetapir positron emission tomography.RESULTS Participants in the AD Neuroimaging Initiative (n = 1581; 697 women and 884 men; mean [SD] age, 73.4 [7.2] years) included 407 cognitively normal older adults, 20 with significant memory concern, 298 with early mild cognitive impairment, 544 with late mild cognitive impairment, and 312 with AD. An elevated aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and lower levels of ALT were associated with AD diagnosis (AST to ALT ratio: odds ratio, 7.932 [95% CI, 1.673-37.617]; P = .03; ALT: odds ratio, 0.133 [95% CI, 0.042-0.422]; P = .004) and poor cognitive performance (AST to ALT ratio: beta [SE], -0.465 [0.180]; P = .02 for memory composite score; beta [SE], -0.679 [0.215]; P = .006 for executive function composite score; ALT: beta [SE], 0.397 [0.128]; P =.006 for memory composite score; beta [SE], 0.637 [0.152]; P < .001 for executive function composite score). Increased AST to ALT ratio values were associated with lower CSF amyloid-beta 1-42 levels (beta [SE], -0.170 [0.061]; P = .04) and increased amyloid-beta deposition (amyloid biomarkers), higher CSF phosphorylated tau(181) (beta [SE], 0.175 [0.055]; P = .02) (tau biomarkers) and higher CSF total tau levels (beta [SE], 0.160 [0.049]; P = .02) and reduced brain glucose metabolism (beta [SE], -0.123 [0.042]; P = .03) (neurodegeneration biomarkers). Lower levels of ALT were associated with increased amyloid-beta deposition (amyloid biomarkers), and reduced brain glucose metabolism (beta [SE], 0.096 [0.030]; P = .02) and greater atrophy (neurodegeneration biomarkers).CONCLUSIONS AND RELEVANCE Consistent associations of serum-based liver function markers with cognitive performance and A/T/N biomarkers for AD highlight the involvement of metabolic disturbances in the pathophysiology of AD. Further studies are needed to determine if these associations represent a causative or secondary role. Liver enzyme involvement in AD opens avenues for novel diagnostics and therapeutics. AU - Nho, K.* AU - Kueider-Paisley, A.* AU - Ahmad, S.* AU - MahmoudianDehkordi, S.* AU - Arnold, M. AU - Risacher, S.L.* AU - Louie, G.* AU - Blach, C.* AU - Baillie, R.* AU - Han, X.* AU - Kastenmüller, G. AU - Trojanowski, J.Q.* AU - Shaw, L.M.* AU - Weiner, M.W.* AU - Doraiswamy, P.M.* AU - van Duijn, M.* AU - Saykin, A.J.* AU - Kaddurah-Daouk, R.* C1 - 56682 C2 - 47222 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa TI - Association of altered liver enzymes with alzheimer disease diagnosis, cognition, neuroimaging measures, and cerebrospinal fluid biomarkers. JO - JAMA net. open VL - 2 IS - 7 PB - Amer Medical Assoc PY - 2019 SN - 2574-3805 ER - TY - JOUR AB - Importance: Which cardiometabolic risk factors (eg, hypertension, type 2 diabetes, overweight or obesity, and dyslipidemia) are more sensitive to long-term exposure to ambient air pollution and whether participants with these conditions are more susceptible to the cardiovascular effects of air pollution remain unclear. Objectives: To evaluate the associations among long-term exposure to air pollutants, cardiometabolic risk factors, and cardiovascular disease (CVD) prevalence. Design, Setting, and Participants: This population-based cross-sectional study was conducted from April 1 through December 31, 2009, in 3 cities in Northeastern China. Participants were adults aged 18 to 74 years who had lived in study area for 5 years or longer. Data analysis was performed from May 1 through December 31, 2018. Exposures: Long-term (2006-2008) exposure to air pollutants was measured using a spatiotemporal statistical model (particulate matter with an aerodynamic diameter of ≤2.5 μm [PM2.5] and ≤1.0 μm [PM1.0]) and data from air monitoring stations (particulate matter with an aerodynamic diameter of ≤10.0 μm [PM10.0], sulfur dioxide [SO2], nitrogen dioxide [NO2], and ozone [O3]). Main Outcomes and Measures: Cardiovascular disease was determined by self-report of physician-diagnosed CVD. Blood pressure, body mass index, and levels of triglycerides and low-density lipoprotein cholesterol were measured using standard methods. Results: Participants included 15 477 adults (47.3% women) with a mean (SD) age of 45.0 (13.5) years. The prevalence of CVD was 4.8%, and the prevalence of cardiometabolic risk factors ranged from 8.6% (hyperbetalipoproteinemia) to 40.5% (overweight or obesity). Mean (SD) air pollutant concentrations ranged from 35.3 (5.5) μg/m3 (for NO2) to 123.1 (14.6) μg/m3 (for PM10.0). Associations with air pollutants were identified for individuals with hyperbetalipoproteinemia (eg, odds ratio [OR], 1.36 [95% CI, 1.03-1.78] for a 10-μg/m3 increase in PM1.0) and the weakest association for those with for overweight or obesity (eg, OR, 1.06 [95% CI, 1.02-1.09] for a 10-μg/m3 increase in PM1.0). Cardiometabolic risk factors only partially mediated associations between air pollution and CVD. However, they modified the associations such that greater associations were found in participants with these cardiometabolic conditions (eg, ORs for CVD and per 10-μg/m3 increase in PM1.0, 1.22 [95% CI, 1.12-1.33] in participants with hyperbetalipoproteinemia and 1.07 [95% CI, 0.98-1.16] in participants without hyperbetalipoproteinemia). Conclusions and Relevance: In this population-based study of Chinese adults with CVD, long-term exposure to air pollution was associated with a higher prevalence of cardiometabolic risk factors, and the strongest associations were observed for hyperbetalipoproteinemia. In addition, participants with cardiometabolic risk factors may have been more vulnerable to the effects of air pollution on CVD. AU - Yang, B.-Y.* AU - Guo, Y.* AU - Markevych, I. AU - Qian, Z.M.* AU - Bloom, M.S.* AU - Heinrich, J.* AU - Dharmage, S.C.* AU - Rolling, C.A.* AU - Jordan, S.S.* AU - Komppula, M.* AU - Leskinen, A.* AU - Bowatte, G.* AU - Li, S.* AU - Chen, G.* AU - Liu, K.K.* AU - Zeng, X.W.* AU - Hu, L.W.* AU - Dong, G.H.* C1 - 55682 C2 - 46464 TI - Association of long-term exposure to ambient air pollutants with risk factors for cardiovascular disease in China. JO - JAMA net. open VL - 2 IS - 3 PY - 2019 SN - 2574-3805 ER - TY - JOUR AB - IMPORTANCE Few studies have investigated the association between greenness and childhood attention-deficit/hyperactivity disorder (ADHD).OBJECTIVE To evaluate the association between greenness surrounding schools or kindergartens and symptoms of ADHD in children.DESIGN, SETTING, AND PARTICIPANTS This population-based cross-sectional study was performed between April 2012 and January 2013 in 7 cities in northeastern China. This analysis included 59 754 children (aged 2-17 years) from 94 schools and kindergartens, who had resided in the study area for 2 years or longer. Data were analyzed from April 15, 2019, to October 10, 2019.EXPOSURES Greenness surrounding each child's school or kindergarten was estimated using 2 satellite image-derived vegetation indexes: the normalized difference vegetation index and the soil-adjusted vegetation index.MAIN OUTCOMES AND MEASURES Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) scales were used to measure ADHD symptoms (9 inattention symptoms and 9 hyperactivity-impulsivity symptoms). Parents or guardians rated the frequency of each of 18 ADHD symptoms during the preceding 6 months. Children with 6 or more symptoms of either inattention or hyperactivity-impulsivity were defined as having ADHD symptoms. Generalized linear mixed models were applied to estimate the association between greenness and ADHD symptoms.RESULTS The mean (SD) age of the 59 754 study participants was 10.3 (3.6) years, and 29 494 (49.4%) were girls. A total of 2566 participants (4.3%) had ADHD symptoms. Greenness levels differed substantially across schools and kindergartens. The normalized difference vegetation index within 500 m of a school or kindergarten ranged from -0.09 to 0.77. Greater greenness levels were associated with lower odds of ADHD symptoms. In covariate-adjusted models, a 0.1-unit increase in normalized difference vegetation index or soil-adjusted vegetation index within 500mof a school or kindergarten was significantly associated with lower odds of ADHD symptoms (odds ratios, 0.87 [95% CI, 0.83-0.91] and 0.80 [95% CI, 0.74-0.86], respectively; P < .001 for both). The associations were robust in a series of sensitivity analyses.CONCLUSIONS AND RELEVANCE These findings suggest that there may be a beneficial association between school-based greenness and ADHD symptoms in Chinese children. Future longitudinal and mechanistic studies are needed to confirm the findings of this cross-sectional analysis and further explore potential mechanisms of this association. AU - Yang, B.-Y.* AU - Zeng, X.-W.* AU - Markevych, I. AU - Bloom, M.S.* AU - Heinrich, J.* AU - Knibbs, L.D.* AU - Dharmage, S.C.* AU - Lin, S.* AU - Jalava, P.* AU - Guo, Y.* AU - Jalaludin, B.* AU - Morawska, L.* AU - Zhou, Y.* AU - Hu, L.-W.* AU - Yu, H.-Y.* AU - Yu, Y.* AU - Dong, G.-H.* C1 - 57657 C2 - 47911 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa TI - Association between greenness surrounding schools and kindergartens and attention-deficit/hyperactivity disorder in children in China. JO - JAMA net. open VL - 2 IS - 12 PB - Amer Medical Assoc PY - 2019 SN - 2574-3805 ER -