Tag: statistics

Brain. 2022 Jul 20:awac213. doi: 10.1093/brain/awac213. Online ahead of print.

ABSTRACT

Alzheimer’s disease biomarkers are becoming increasingly important for characterizing the longitudinal course of disease, predicting the timing of clinical and cognitive symptoms, and for recruitment and treatment monitoring in clinical trials. In this work, we develop and evaluate three methods for modelling the longitudinal course of amyloid accumulation in three cohorts using amyloid PET imaging. We then use these novel approaches to investigate factors that influence the timing of amyloid onset and the timing from amyloid onset to impairment onset in the Alzheimer’s disease continuum. Data were acquired from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the Baltimore Longitudinal Study of Aging (BLSA) and the Wisconsin Registry for Alzheimer’s Prevention (WRAP). Amyloid PET was used to assess global amyloid burden. Three methods were evaluated for modelling amyloid accumulation using 10-fold cross-validation and holdout validation where applicable. Estimated amyloid onset age was compared across all three modelling methods and cohorts. Cox regression and accelerated failure time models were used to investigate whether sex, apolipoprotein E genotype and e4 carriage were associated with amyloid onset age in all cohorts. Cox regression was used to investigate whether apolipoprotein E (e4 carriage and e3e3, e3e4, e4e4 genotypes), sex or age of amyloid onset were associated with the time from amyloid onset to impairment onset (global clinical dementia rating ≥1) in a subset of 595 ADNI participants that were not impaired before amyloid onset. Model prediction and estimated amyloid onset age were similar across all three amyloid modelling methods. Sex and apolipoprotein E e4 carriage were not associated with PET-measured amyloid accumulation rates. Apolipoprotein E genotype and e4 carriage, but not sex, were associated with amyloid onset age such that e4 carriers became amyloid positive at an earlier age compared to non-carriers, and greater e4 dosage was associated with an earlier amyloid onset age. In the ADNI, e4 carriage, being female and a later amyloid onset age were all associated with a shorter time from amyloid onset to impairment onset. The risk of impairment onset due to age of amyloid onset was non-linear and accelerated for amyloid onset age >65. These findings demonstrate the feasibility of modelling longitudinal amyloid accumulation to enable individualized estimates of amyloid onset age from amyloid PET imaging. These estimates provide a more direct way to investigate the role of amyloid and other factors that influence the timing of clinical impairment in Alzheimer’s disease.

PMID:35856240 | DOI:10.1093/brain/awac213

Zhonghua Liu Xing Bing Xue Za Zhi. 2022 Jul 10;43(7):1127-1133. doi: 10.3760/cma.j.cn112338-20211109-00871.

ABSTRACT

The National Health and Nutrition Examination Survey (NHANES) of America has been running for more than 60 years and has achieved many significant achievements with international influence. The application of modern information technologies in NHANES provides a supplementary tool for the project’s high quality and refined implementation. This paper introduces the information system of NHANES from seven aspects: project management, survey participant interview, physical examination, laboratory examination, field follow-up, data sharing, and social services. The construction and application prospects of the China National Health Survey Information System, suitable for China’s native conditions, are also discussed in this article.

PMID:35856210 | DOI:10.3760/cma.j.cn112338-20211109-00871

Zhonghua Liu Xing Bing Xue Za Zhi. 2022 Jul 10;43(7):1107-1111. doi: 10.3760/cma.j.cn112338-20220123-00065.

ABSTRACT

Objective: To describe the characteristics of molecular transmission network of newly diagnosed HIV-1 infected patients, analyze their risk factors related to network access and provide a scientific basis for precise prevention of HIV infection. Methods: For 340 blood samples collected from confirmed HIV-1 infection cases aged ≥50 years in Pengzhou city of Sichuan province from April 2019 to August 2021, nested PCR amplification was used to amplify, clean up and splice clips the pol gene region. The phylogenetic tree was constructed by multi-sequence comparison to distinguish subtypes, and the pairwise genetic distance was calculated. When the genetic distance threshold was 0.90%, the number of clusters was the largest (41), and the molecular transmission network was constructed.The χ² test and logistic regression analysis were performed.The software SPSS 19.0 was used for statistical analysis. Results: A total of 340 samples were successfully amplified (97.06%, 330/340) in 330 samples. 6 HIV-1 subtypes identified, including:CRF01_AE(56.67%,187/330), CRF07_BC(27.88%,92/330), B(11.21%,37/330), CRF08_BC(3.33%,11/330), CRF55_01B(0.61%,2/330) and C(0.30%,1/330).The network entry rate was 58.79% (194/330).The results of logistic regression analysis of the risk factors of HIV-1 molecular transmission network in the research subjects showed that compared with illiteracy, junior high school (OR=0.35, 95%CI:0.13-0.97) and high school/technical secondary school (OR=0.14, 95%CI: 0.02-0.97) had lower possibility of network entry. Compared with farmers, unknown occupations (OR=0.40,95%CI: 0.17-0.95) are less likely to enter the network .Compared with CRF01_AE, CRF07_BC (OR=0.20, 95%CI: 0.11-0.35) and CRF08_BC subtype (OR=0.09, 95%CI: 0.02-0.45) were less likely to enter the network. Conclusions: The sources of AIDS transmission among middle-aged and elderly people of rural areas are diversified in Pengzhou city of Sichuan province. AIDS intervention should focus on middle-aged and elderly farmers with low educational level, and strengthen detection and traceability investigation.

PMID:35856207 | DOI:10.3760/cma.j.cn112338-20220123-00065

Zhonghua Liu Xing Bing Xue Za Zhi. 2022 Jul 10;43(7):1087-1092. doi: 10.3760/cma.j.cn112338-20211214-00980.

ABSTRACT

Objective: To evaluate the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province. Methods: Information on the reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was collected through the National Population Health Science Data Center and the China Disease Prevention and Control Information System. In addition, the trend of Japanese encephalitis reported incidence rate in Gansu province before and after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program was analyzed using an interrupted time-series design. Results: The annual reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was 0.448/per 100 000. However, after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program in Gansu province in 2008, the amount of change in the level of Japanese encephalitis reported incidence rate was -2.223/per 100 000 (t=-2.90, P=0.007), the amount of change in the slope of Japanese encephalitis reported incidence rate was 0.082 (t=2.87, P=0.008) with the slope of Japanese encephalitis reported incidence rate as 0.071 (β₁+β₃=0.071). Conclusions: The Japanese encephalitis vaccine has achieved good prevention and control effects in Gansu province in the short term after its inclusion in the expanded immunization program, but outbreaks of Japanese encephalitis have still occurred. Therefore, in the future, Gansu province should promptly adjust the immunization strategy of the Japanese encephalitis vaccine, and strengthen the vaccination of the adult population, especially the rural adult population in the southeastern region of Gansu province, based on the continued focus on the works on Japanese encephalitis vaccination for children and adolescents.

PMID:35856204 | DOI:10.3760/cma.j.cn112338-20211214-00980

Zhonghua Liu Xing Bing Xue Za Zhi. 2022 Jul 10;43(7):1019-1029. doi: 10.3760/cma.j.cn112338-20211020-00806.

ABSTRACT

Objective: To explore the association of lifestyle and cardiometabolic risk factors with five epigenetic age acceleration (AA) indices. Methods: This study included 980 participants of China Kadoorie Biobank, for whom genome-wide DNA methylation of peripheral blood cells had been detected in baseline survey. Five indices of DNA methylation age (DNAm age) were calculated, i.e. Horvath clock, Hannum clock, DNAm PhenoAge, GrimAge and Li clock. Epigenetic AA was defined as the residual of regressing DNAm age on chronological age. Lifestyle factors studied included smoking status, alcohol consumption, eating habits, physical activity level and body shape defined by a combination of BMI and waist circumference. Cardiometabolic risk factors included blood pressure, blood glucose level and total cholesterol level. Linear regression model was used to analyze the association of lifestyle and cardiometabolic risk factors with AA (β). Results: GrimAge_AA was associated with smoking status, alcohol consumption, physical activity level and BMI. Compared with non-smokers, non-drinkers, or participants with BMI of 18.5- 23.9 kg/m², the smokers who smoked 1-14 cigarettes/day (β=0.71, 95%CI: 0.57-0.86), 15-24 cigarettes/day (β=0.88, 95%CI: 0.73-1.03), and ≥25 cigarettes/day (β=0.99, 95%CI: 0.81-1.18), respectively, heavy drinkers with daily pure alcohol consumption ≥60 g (β=0.33, 95%CI: 0.11-0.55) and participants with BMI<18.5 kg/m² (β=0.23, 95%CI: 0.03-0.43) showed accelerated aging. Compared with those in the lowest quintile of physical activity level, participants in the top three quintile of physical activity level showed decelerated aging (β=-0.13, 95%CI: -0.26-0.01, β=-0.12, 95%CI: -0.26-0.02, and β=-0.14, 95%CI: -0.27- -0.00, respectively). GrimAge_AA decreased with the increase of the number of healthy lifestyle factors (P<0.001). Compared with the participants with 0 to 1 healthy lifestyle factor, the β of those with 2, 3, or 4 to 5 healthy lifestyle factors were -0.30 (95%CI: -0.47- -0.12), -0.47 (95%CI: -0.65- -0.30) and -0.72 (95%CI: -0.90- -0.53), respectively. The other four indices were not statistically significantly associated with most lifestyle factors. None of the five indices of AA was associated with blood pressure, blood glucose level or total cholesterol level. Conclusion: People with unhealthy lifestyle showed accelerated epigenetic aging, that is, the predicted DNAm age is older than their own chronological age.

PMID:35856194 | DOI:10.3760/cma.j.cn112338-20211020-00806

Zhonghua Liu Xing Bing Xue Za Zhi. 2022 Jul 10;43(7):1079-1086. doi: 10.3760/cma.j.cn112338-20211227-01020.

ABSTRACT

Objective: To explore the changes of liver cancer mortality and the effect of liver cancer on life expectancy in key areas of four provinces in China from 2008 to 2018 and provide the basis for the evaluation of comprehensive prevention and control of cancer and promotion of the rational allocation of health resources. Methods: Based on the national cause-of-death surveillance in key areas of the 4 provinces from 2008 to 2018, we analyzed the mortality of liver cancer, cause eliminated life expectancy (CELE) and potential gains in life expectancy (PGLEs). Software Joinpoint 4.9.0.0 was used to calculate the average annual percentage change (AAPC). Arriaga’s decomposition method was used to estimate the contribution of the changes of liver cancer mortality in each age group to life expectancy. Results: The standardized mortality of liver cancer in key areas of the 4 provinces showed a downward trend from 2008 to 2018 (AAPC=-4.37%, P<0.001). The changes of liver cancer mortality had a positive effect on the increase of life expectancy, with a contribution value of 0.240 years and a contribution degree of 5.62%. The positive effect was greatest in age group 45-49 years (0.041 years, 0.96%), and the negative effect was greatest in age group 50-54 years (-0.015 years, -0.35%). Compared with 2008, the life expectancy increased by 4.27 years (AAPC=0.59%, P<0.001), the liver cancer CELE increased by 4.20 years (AAPC=0.58%, P<0.001), the PGLEs decreased by 0.07 years (AAPC=-0.62%,P<0.001), and life loss rate decreased by 0.13% (AAPC=-1.18%, P=0.001). The liver cancer PGLEs increased in Yongqiao district, Anhui province (0.09 years), and decreased in other districts (counties), with the largest decline was in Fugou county, Henan province (-0.21 years). Conclusions: From 2008 to 2018, the standardized mortality rate of liver cancer in key areas of the 4 provinces decreased gradually, contributing to the growth of life expectancy. The life loss caused by liver cancer decreased gradually, but the PGLEs varied with districts (counties).

PMID:35856203 | DOI:10.3760/cma.j.cn112338-20211227-01020

Zhonghua Liu Xing Bing Xue Za Zhi. 2022 Jul 10;43(7):1002-1009. doi: 10.3760/cma.j.cn112338-20210930-00760.

ABSTRACT

Objective: To analyze the associations between sleep status and the risk for kidney stone in Chinese adults. Methods: This study used baseline and long-term follow-up data of China Kadoorie Biobank. After excluding those with self-reporting of diagnosed chronic kidney disease and cancer and those with extreme values of sleep duration at baseline survey, 501 701 participants were included in this study. The information about their sleep status were collected, including insomnia symptoms, daytime sleepiness, nap habit, snoring and sleep duration. The sleep score was constructed based on insomnia symptoms, daytime sleepiness, and sleep duration, ranging from 0 to 3. Cox proportional hazards regression models were used to evaluate the association of sleep status with the risk for kidney stone, including individual sleep factors and combined sleep score. Results: During the follow-up for average (10.7±2.2) years, 12 381 cases of kidney stone were recorded for the first time. Compared with participants without insomnia symptoms, the multivariable-adjusted HR of kidney stone in those with difficulty falling asleep and waking up early were 1.12 (95%CI: 1.06-1.18) and 1.06 (95%CI: 1.00-1.12), respectively. There was no statistically significant association of kidney stone risk with sleeping pill use, daytime sleepiness, nap habit, or snoring. Compared with participants with sleep duration ≥7 hours per day, the HR of kidney stone in those with sleep duration <7 hours per day was 1.13 (95%CI: 1.08-1.18). Compared with participants with sleep score of 3 (highest sleep quality), the HR of kidney stone in those with sleep score of 2, 1, and 0 were 1.08 (95%CI: 1.03-1.13), 1.16 (95%CI: 1.10-1.23), and 1.19 (95%CI: 1.03-1.37), respectively. Conclusion: In China, adults with insomnia symptoms or short sleep duration have increased risk for kidney stone.

PMID:35856192 | DOI:10.3760/cma.j.cn112338-20210930-00760

J Cachexia Sarcopenia Muscle. 2022 Jul 20. doi: 10.1002/jcsm.13054. Online ahead of print.

ABSTRACT

BACKGROUND: The fat-to-muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk independent of overall obesity. However, little is known about the association between FMR and dementia risk. We aimed to prospectively investigate the sex-specific associations between total and regional FMR and incident dementia.

METHODS: A total of 491 420 participants (223 581 men and 267 839 women; mean age 56.7 ± 8.2 and 56.3 ± 8.0 years old, respectively) free of dementia at baseline from the UK Biobank were included. Fat mass and muscle mass were measured using a bioelectrical impedance assessment device. Cox regression analyses were used to examine the associations of total and regional FMR with incident all-cause dementia, Alzheimer’s disease (AD) and vascular dementia (VD). The shape of the associations of the continuous scale of FMR and incident dementia were examined using restricted cubic spline analysis.

RESULTS: During a median 8.65 years of follow-up, we documented 2 225 incident all-cause dementia cases, including 836 AD and 468 VD cases. There was an L-shaped association between whole body FMR and all-cause dementia risk in both sexes after adjusting body mass index (BMI) and other covariates (P for non-linear <0.001 in men and women), where all-cause dementia risk decreased steeply with increasing FMR and levelled off at around the medians (0.35 in men, 0.61 in women) with a hazard ratio (HR) of 0.78 (95% CI: 0.64, 0.96; P = 0.019) and 0.60 (0.47, 0.77; <0.001) per 1 standard deviation (SD) increase in men and women, respectively. Compared with other body parts, FMR of the leg showed the strongest inverse associations [HR (95% CI; P) per 1 SD below the medians: 0.60 (0.48, 0.75; <0.001); 0.61 (0.47, 0.79; <0.001) in men and women, respectively]. Specifically, the inverse associations of whole body FMR on all-cause dementia risk were significant only among participants over the age of 60 (P for trend <0.001). Multivariable adjusted Cox models showed inverse associations of whole body FMR with AD in men only (P for trend = 0.003), whereas no statistically significant decrease was detected in VD among men and women.

CONCLUSIONS: Our analyses provide strong evidence for L-shaped associations of total and regional FMR with the development of dementia among participants aged 60 years or older independent of overall obesity.

PMID:35856185 | DOI:10.1002/jcsm.13054

Minerva Med. 2022 Jun;113(3):497-505. doi: 10.23736/S0026-4806.22.07981-2.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease and activation of WNT and TGFβ mediated oncogenic pathways is frequently observed in this pathology. However, to date, limited reports have been published addressing the association of circadian clock with CRC pathogenesis and stratification. The current study aims at assessing the expression of important circadian markers, PER2, PER3 and NR1D1, in independent CRC cohorts and their associations with CRC-related pathways.

METHODS: Gene expression analysis was performed using available GEO (GSE39582) and TCGA datasets. Quantitative real time polymerase chain reaction was used to quantify the expression levels of PER2, PER3 and NRID1 in FFPE (formalin fixed paraffin embedded) CRC tissue samples. Furthermore, enrichment of circadian markers in WNT and TGFβ pathways-activated tumors was assessed.

RESULTS: Statistically significant downregulation of PER3 was found in tumor versus control samples in GEO (P<0.0001) and TCGA colon and rectal adenocarcinoma datasets (P<0.05). Analysis of GEO dataset revealed a statistically significant upregulation of PER2 (P<0.01), and NR1D1 in colon adenocarcinoma, which was confirmed by qRT-PCR in CRC tumor samples versus controls in FFPE validation cohort. Higher expression of NR1D1 was associated with poor prognosis in colon adenocarcinoma. Contrastingly, PER3 was significantly downregulated in tumors (P<0.001) compared to controls and was associated with high-grade CRC tumors versus low-grade tumors. Tumors with WNT pathway activation had significantly low PER3 and slightly upregulated PER2 (<0.0001) expression. Interestingly, differential expression of PER3 and NR1D1 was significantly correlated with TGFβ1-expressing tumors (P<0.0001). Moreover, MYC- amplified tumors exhibited decreased PER3 levels.

CONCLUSIONS: Thus, low PER3 expression in CRC and poor survival of patients with NR1D1-high tumors reveal that genes in the suppressor loop of circadian rhythm are dysregulated in CRC, hence pointing out to the importance of dissecting the circadian pathway in cancer.

PMID:35856182 | DOI:10.23736/S0026-4806.22.07981-2

Drugs Real World Outcomes. 2022 Jul 18. doi: 10.1007/s40801-022-00321-7. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular agents, including angiotensin-converting enzyme inhibitors, angiotensin II receptor inhibitors, acetylsalicylic acid, statins, and metformin, have demonstrated benefits for depression. However, there is scant evaluation of these drugs’ antidepressant properties in large population settings.

OBJECTIVE: This study aimed to examine cross-sectional associations between depression symptoms and the use of cardiovascular agents and metformin in populations with cardiovascular diseases or diabetes mellitus.

METHODS: Participants in the Trøndelag Health Study 2006-08 (HUNT3, n = 40,516) and 2017-19 (HUNT4, n = 42,103) were included and data on their drug use from 2006 to 2019 was retrieved from the Norwegian Prescription Database. The outcome was self-reported depression symptoms defined by the Hospital Anxiety and Depression Scale. Associations between cardiovascular agents or metformin use and self-reported depression were analyzed by multi-level logistic regression in sex-stratified samples.

RESULTS: Among men with cardiovascular diseases, use of acetylsalicylic acid was associated with reduced depression symptoms compared with acetylsalicylic acid non-users (reference) in HUNT3 and HUNT4 [risk ratio = 0.76; 95% confidence interval 0.59-0.94, risk ratio = 0.67; 95% CI 0.52-0.82, respectively]. Similarly, male statin users had a lower likelihood of reporting depression than statin non-users in HUNT3 (risk ratio = 0.70; 95% confidence interval 0.54-0.86) and HUNT4 (risk ratio = 0.67; 95% confidence interval 0.51-0.84). Associations between statins or acetylsalicylic acid use and reduced depression symptoms were detected in women with cardiovascular diseases in HUNT4. We found no statistical support for associations between other cardiovascular agents or metformin use and a reduced or increased depression symptom risk.

CONCLUSIONS: Results suggest negative associations between acetylsalicylic acid or statin use and depression symptoms. However, longitudinal cohort studies and randomized controlled trials are required to confirm the antidepressant effects of these drugs.

PMID:35856136 | DOI:10.1007/s40801-022-00321-7