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author:("Zhong, wendun")
1.  Time trends of antidepressant drug prescriptions in men versus women in a geographically defined US population 
Archives of women's mental health  2014;17(6):485-492.
To study time trends of antidepressant drug (AD) prescriptions in a geographically defined US population between 2005 and 2011 for men and women separately.
Using the Rochester Epidemiology Project medical records-linkage system, we identified all Olmsted County, MN residents who received AD outpatient prescriptions between 2005 and 2011 (seven years). We calculated the annual age-and sex-specific prevalence over seven years, and used generalized estimating equation models to test for time trends.
The prevalence of subjects receiving at least one AD prescription was approximately two times higher in women than men consistently across the seven years of the study. The standardized annual prevalence increased from 10.8% in 2005 to 14.4% in 2011 overall, from 7.0% in 2005 to 9.9% in 2011 for men, and from 14.4% in 2005 to 18.6% in 2011 for women. The absolute percent increase was greater in women (4.2% vs. 2.9%; standardized); however, the relative percent increase was greater in men (41.4% vs. 29.2%; standardized). The relative percent increase was greater in the age group 65+ years for both men and women.
AD prescriptions are increasing over time, especially in the elderly. Women receive more AD prescriptions than men. However, the relative increase in AD prescriptions over time is greater in men than women.
PMCID: PMC4239307  PMID: 25113318
antidepressants; drug prescriptions; population-based; time trends; pharmacoepidemiology; sex differences
2.  Pulse Wave Velocity and Cognitive Function in Older Adults 
Arterial stiffness may be associated with cognitive function. In this study, pulse wave velocity (PWV) was measured from the carotid to femoral (CF-PWV) and from the carotid to radial (CR-PWV) with the Complior SP System (Alam Medical, Vincennes, France). Cognitive function was measured by six tests of executive function, psychomotor speed, memory, and language fluency. A total of 1433 participants were included (mean age 75 years, 43% men). Adjusting for age, sex, education, pulse rate, hemoglobin A1C, HDL cholesterol, hypertension, CVD history, smoking ,drinking, and depression symptoms, a CF-PWV > 12 m/s was associated with a lower Mini-Mental State Examination score (coefficient: −0.31, se: 0.11, p=0.005), fewer words recalled on Auditory Verbal Learning Test (coefficient: −1.10, se: 0.43, p=0.01), and lower score on the composite cognition score (coefficient: −0.10, se: 0.05, p=0.04) and marginally significantly associated with longer time to complete Trail Making Test-B (coefficient: 6.30, se: 3.41, p=0.06), CF-PWV was not associated with Trail Making Test-A, Digit Symbol Substation Test, or Verbal Fluency Test. No associations were found between CR-PWV and cognitive performance measures. Higher large artery stiffness was associated with worse cognitive function, and longitudinal studies are needed to confirm these associations.
PMCID: PMC3778043  PMID: 23632267
pulse wave velocity; cognitive function; epidemiology; arterial stiffness
3.  Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation 
BMC Pediatrics  2014;14:199.
The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems.
The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset.
The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10.
PMCID: PMC4134331  PMID: 25102958
Pediatrics; Complex chronic conditions; Chronic disease; Classification; International classification of disease codes; Comorbidity; Mortality; Health services research
4.  Odor Identification and Cognitive Function in the Beaver Dam Offspring Study 
Olfactory impairment is associated with cognitive impairment in older adults but less is known about the association of olfactory impairment and cognitive function in middle-aged adults. The association between olfactory impairment and cognitive function tests of attention, processing speed and executive and psychomotor function was explored in 2837 participants (21–84 years; mean age 49 years) in the Beaver Dam Offspring Study. Among middle-aged participants (aged 35–64 years), those with impairment on an odor identification test took significantly longer to complete the Trail Making Test (TMT-A and TMT-B) and the Grooved Peg Board (GPB) test, than those without olfactory impairment in regression models adjusted for multiple factors. Similar results were found for the TMT-A and TMT-B, but not the GPB, in the whole cohort. Olfactory impairment was associated with poorer performance on cognitive function tests in a primarily middle-aged cohort.
PMCID: PMC3778079  PMID: 23789858
Olfaction; Odor Identification; Cognitive Function; Executive Function; Epidemiology
5.  Age and Sex Patterns of Drug Prescribing in a Defined American Population 
To describe age and sex patterns of drug prescribing in Olmsted County, MN. Prescription drugs are an important component of health care delivery, yet little is known about the prescribing patterns in the general population.
Patients and Methods
Population-based drug prescription records for the Olmsted County population in the year 2009 were obtained using the Rochester Epidemiology Project medical records-linkage system (n = 142,377). Drug prescriptions were classified using RxNorm codes and grouped using the National Drug File – Reference Terminology (NDF-RT).
Overall, 68% of the population received a prescription from at least one drug group, 52% received prescriptions from 2 or more groups, and 21% received prescriptions from 5 or more groups. The most commonly prescribed drug groups in the entire population were penicillins and beta-lactam antimicrobials (17%), antidepressants (13%), opioid analgesics (12%), antilipemic agents (11%), and vaccines/toxoids (11%). However, prescribing patterns differed by age and sex. Vaccines/toxoids, penicillins and beta-lactam antimicrobials, and anti-asthmatic drugs were most commonly prescribed in persons younger than 19 years. Antidepressants and opioid analgesics were most commonly prescribed in young and middle-aged adults. Cardiovascular drugs were most commonly prescribed in older adults. Women received more prescriptions than men for several groups of drugs, in particular for antidepressants. For several groups of drugs, the use increased with advancing age.
This study provides valuable baseline information for future studies of drug utilization and drug-related outcomes in this population.
PMCID: PMC3754826  PMID: 23790544
drug prescription; prevalence; population-based study; records-linkage system; age and sex differences in drug use; pharmacoepidemiology
6.  Carotid Atherosclerosis and 10-year Changes in Cognitive Function 
Atherosclerosis  2012;224(2):506-510.
Carotid atherosclerosis has been suggested to be involved in cognitive decline.
The Epidemiology of Hearing Loss Study is a longitudinal study of aging among Beaver Dam residents, WI. In 1998–2000, carotid intima-media thickness (IMT) and plaque were measured by ultrasound; cognitive function was measured by the Mini-Mental State Examination (MMSE). Follow-up examinations were conducted in 2003–2005 and 2009–2010. Incidence of cognitive impairment was defined as a MMSE score <24 or reported physician-diagnosed dementia during the follow-up. In the last examination, five additional cognitive tests were added. The associations of carotid atherosclerosis with incident cognitive impairment and cognitive test performance ten years later were evaluated.
A total of 1651 participants (mean age 66.8 years, 41% men) without cognitive impairment at baseline were included in the incidence analysis. IMT was associated with incidence of cognitive impairment after multiple adjustments (hazard ratio: 1.09, p=0.02 for each 0.1 mm increase in IMT). A total of 1311 participants with atherosclerosis data at baseline had the additional cognitive tests 10 years later. Larger IMT was associated with longer time to complete the Trail-Making Test-part B after multiple adjustments (0.1 mm IMT: 2.3 seconds longer, p=0.02). Plaque was not associated with incident cognitive impairment or cognitive test performance 10 years later.
In this population-based longitudinal study, carotid IMT was associated with a higher risk of developing cognitive impairment during the 10-year follow-up, and was associated with poorer performance in a test of executive function 10 years later.
PMCID: PMC3459157  PMID: 22854188
Carotid atherosclerosis; cognitive impairment; longitudinal; population-based; epidemiology
7.  Comparative proteomic and transcriptomic approaches to address the active role of GA4 in Japanese apricot flower bud dormancy release 
Journal of Experimental Botany  2013;64(16):4953-4966.
Hormones are closely associated with dormancy in deciduous fruit trees, and gibberellins (GAs) are known to be particularly important. In this study, we observed that GA4 treatment led to earlier bud break in Japanese apricot. To understand better the promoting effect of GA4 on the dormancy release of Japanese apricot flower buds, proteomic and transcriptomic approaches were used to analyse the mechanisms of dormancy release following GA4 treatment, based on two-dimensional gel electrophoresis (2-DE) and digital gene expression (DGE) profiling, respectively. More than 600 highly reproducible protein spots (P<0.05) were detected and, following GA4 treatment, 38 protein spots showed more than a 2-fold difference in expression, and 32 protein spots were confidently identified according to the databases. Compared with water treatment, many proteins that were associated with energy metabolism and oxidation–reduction showed significant changes after GA4 treatment, which might promote dormancy release. We observed that genes at the mRNA level associated with energy metabolism and oxidation–reduction also played an important role in this process. Analysis of the functions of the identified proteins and genes and the related metabolic pathways would provide a comprehensive proteomic and transcriptomic view of the coordination of dormancy release after GA4 treatment in Japanese apricot flower buds.
PMCID: PMC3830480  PMID: 24014872
2-DE; DGE; dormancy; GA4; Japanese apricot; proteomics; transcriptomics.
8.  Carotid Atherosclerosis and Cognitive Function in midlife: the Beaver Dam Offspring Study 
Atherosclerosis  2011;219(1):330-333.
Atherosclerosis may be associated with cognitive function; however the studies are few, especially among midlife adults.
Participants in the Beaver Dam Offspring Study who had cognitive test data and gradable carotid artery ultrasound scans were included (n=2794, mean age: 49 years). Atherosclerosis was measured by carotid intima-media thickness (IMT) and presence of plaque. Cognitive function was measured by the Trail Making Test (TMT), Grooved Pegboard Test (GPT) and Mini-Mental State Examination (MMSE). Generalized cognitive function was defined by a summary score calculated from the TMT and GPT. Linear regression was used to evaluate the associations between carotid atherosclerosis and cognitive function tests.
Larger IMT was associated with lower GPT, MMSE and the summary score adjusting for multiple factors, the coefficients were: 13.8 seconds (p<0.0001), −0.6 (p=0.007), and 0.47 (p=0.01), respectively for 1 mm increase in IMT. Plaque scores were significantly associated with TMT-B, GPT, MMSE, and the summary score adjusting for age, sex and education. The associations remained statistically significant after further adjustments except for the association with TMT-B, which was attenuated and no longer significant.
Our results show significant associations between markers of carotid atherosclerosis and cognitive function in a cohort of persons aged 21 to 84 years. Longitudinal studies are needed to further examine these associations.
PMCID: PMC3206159  PMID: 21831374
atherosclerosis; cognitive function; epidemiology
9.  Identification of Differentially-Expressed Genes Associated with Pistil Abortion in Japanese Apricot by Genome-Wide Transcriptional Analysis 
PLoS ONE  2012;7(10):e47810.
The phenomenon of pistil abortion widely occurs in Japanese apricot, and imperfect flowers with pistil abortion seriously decrease the yield in production. Although transcriptome analyses have been extensively studied in the past, a systematic study of differential gene expression has not been performed in Japanese apricot. To investigate genes related to the pistil development of Japanese apricot, high-throughput sequencing technology (Illumina) was employed to survey gene expression profiles from perfect and imperfect Japanese apricot flower buds. 3,476,249 and 3,580,677 tags were sequenced from two libraries constructed from perfect and imperfect flower buds of Japanese apricot, respectively. There were 689 significant differentially-expressed genes between the two libraries. GO annotation revealed that highly ranked genes were those implicated in small molecule metabolism, cellular component organisation or biogenesis at the cellular level and fatty acid metabolism. According to the results, we assumed that late embryogenesis abundant protein (LEA), Dicer-like 3 (DCL3) Xyloglucan endotransglucosylase/hydrolase 2 (XTH2), Pectin lyase-like superfamily protein (PPME1), Lipid transfer protein 3 (LTP3), Fatty acid biosynthesis 1 (FAB1) and Fatty acid desaturase 5 (FAD5) might have relationships with the pistil abortion in Japanese apricot. The expression patterns of 36 differentially expressed genes were confirmed by real-time (RT)-PCR. This is the first report of the Illumina RNA-seq technique being used for the analysis of differentially-expressed gene profiles related to pistil abortion that both computationally and experimentally provides valuable information for the further functional characterisation of genes associated with pistil development in woody plants.
PMCID: PMC3472986  PMID: 23091648
10.  Obesity and Depression Symptoms in the Beaver Dam Offspring Study Population 
Depression and anxiety  2010;27(9):846-851.
Depression and obesity are both important public health problems. However, it is not clear whether obesity contributes to depression. Our study aims to evaluate the association between obesity and possible depression.
During the Beaver Dam Offspring Study (BOSS) examination, participants’ body weight and height were measured with a Detecto 758C digital scale with height bar, and depression symptoms were measured with the Center for Epidemiological Studies-Depression Scale (CES-D). Other relevant information (such as demographic factors, lifestyle factors, comorbidities and use of anti-depressants) was also collected during the examination. There were 2641 participants included in the analyses.
Obesity was associated with possible depression measured by CES-D scale (OR =1.6, 95% CI: 1.3–2.0) after controlling for age and gender. The association remained similar after further adjustments. Obesity was significantly associated with all four domains measured by CES-D scale after controlling for age and sex, with the largest effect on “Somatic complaints” domain (beta 0.15, 95% CI: 0.0836–0.223). The association with “Interpersonal difficulties” was not significant after further adjustments.
Obesity was associated with a higher risk of possible depression, and had different influences on specific domains of depression symptoms measured by CES-D scale. These findings suggest the need for longitudinal studies on the effects of obesity on specific depression symptoms.
PMCID: PMC2891299  PMID: 20112247
obesity; depression; epidemiology
11.  Classification tree for detection of single-nucleotide polymorphism (SNP)-by-SNP interactions related to heart disease: Framingham Heart Study 
BMC Proceedings  2009;3(Suppl 7):S83.
The aim of this study was to detect the effect of interactions between single-nucleotide polymorphisms (SNPs) on incidence of heart diseases. For this purpose, 2912 subjects with 350,160 SNPs from the Framingham Heart Study (FHS) were analyzed. PLINK was used to control quality and to select the 10,000 most significant SNPs. A classification tree algorithm, Generalized, Unbiased, Interaction Detection and Estimation (GUIDE), was employed to build a classification tree to detect SNP-by-SNP interactions for the selected 10 k SNPs. The classes generated by GUIDE were reexamined by a generalized estimating equations (GEE) model with the empirical variance after accounting for potential familial correlation. Overall, 17 classes were generated based on the splitting criteria in GUIDE. The prevalence of coronary heart disease (CHD) in class 16 (determined by SNPs rs1894035, rs7955732, rs2212596, and rs1417507) was the lowest (0.23%). Compared to class 16, all other classes except for class 288 (prevalence of 1.2%) had a significantly greater risk when analyzed using GEE model. This suggests the interactions of SNPs on these node paths are significant.
PMCID: PMC2795986  PMID: 20018079

Results 1-11 (11)