Xiaoli Du

Studies of beta-lactam pharmacodynamics in infected patients are sparse. In this study, classification and regression tree (CART) and logistic regression analyses were used to identify which pharmacodynamic indices and magnitudes were significant predictors of meropenem efficacy for 101 adult patients with lower respiratory tract infections (LRTI). Using demographic data, a validated population pharmacokinetic model was employed to predict pharmacokinetic parameters and free serum concentrations in the studied patients. Pharmacodynamic indices [percentage of the dosing interval that free drug concentrations remain above the MIC (% fT > MIC), f(maximum concentration of drug in serum) (fC(max))/MIC, fC(min)/MIC, and f(area under the concentration-time curve) (fAUC)/MIC] were calculated based on the baseline pathogen with the highest drug MIC for each patient. The median (range) of percent fT > MIC, fC(max)/MIC, fC(min)/MIC, and fAUC/MIC were 100% (0 to 100%), 728.8 (0.8 to 15,777), 19.9 (0.01 to 278), and 3,605.4 (2.7 to 60,865.9), respectively. CART identified the following breakpoints as significant predictors for microbiological response: >54% fT > MIC, a fC(max)/MIC > 383, and a fC(min)/MIC > 5; fC(min)/MIC > 5 was the only significant predictor of clinical response. Due to 100% fT > MIC achieved in the majority of LRTI patients, fC(min)/MIC was the statistically significant parameter associated with meropenem clinical and microbiological response in the adults with LRTI. The findings for LRTI patients can be applied to optimize meropenem dose regimens to achieve clinical success and microbiological eradication in clinical practice.

BACKGROUND AND PURPOSE: To examine the incidence and trends of stroke and its major subtypes during the 1990s in 3 cities in China. METHODS: Stroke cases registered between 1991 to 2000 were initially identified through the stroke surveillance networks established in Beijing, Shanghai, and Changsha, and then confirmed by neurologists. RESULTS: The age-standardized incidence rates per 100,000 person years of overall first-ever stroke were 135.0 (95% CI, 126.5 to 144.6) in Beijing, 76.1 (70.6 to 82.6) in Shanghai, and 150.0 (141.3 to 160.0) in Changsha during the 1990s. Incidence of ischemic stroke (IS) was highest in Beijing, followed by Changsha and Shanghai; for intracerebral hemorrhage (ICH), the highest rate was found in Changsha, followed by Beijing and Shanghai. The same order as ICH was also observed for subarachnoid hemorrhage. The age-adjusted incidence of overall stroke and ICH for individuals > or =55 years of age in our populations was generally higher than that from Western populations. During the 1990s, ICH incidence decreased significantly at a rate of 12.0% per year in Beijing, 4.4% in Shanghai, and 7.7% in Changsha; in contrast, except for Changsha, IS incidence increased in Beijing (5.0% per year) and Shanghai (7.7%). CONCLUSIONS: There is a geographic variation in the incidence of stroke and its subtypes among these 3 cities, but the incidence of overall and hemorrhagic stroke in China is generally higher than that in the Western countries. Interestingly, the decrease in ICH and increase in IS during the past decade may reflect some underlying changes of risk factors in Chinese populations.

BACKGROUND AND PURPOSE: Incidence of stroke varies markedly in different world populations. In seven Chinese cities, the effect of a program of risk factor modification on the incidence and mortality of stroke was studied and compared with a control population. This article describes the incidence of stroke in the control populations for the years 1986 through 1990. METHODS: Incidence (first-ever strokes only) for 1986 was obtained by door-to-door interview with heads of households with subsequent verification on examination by a neurologist and review of medical and/or hospital records. In subsequent years, cases were ascertained with a three-tier monitoring system: by community health workers, local medical centers, and the Beijing Neurosurgical Institute. RESULTS: Average annual age-adjusted incidence per 100,000 was 215.6 (261.5 for males, 174.5 for females; P < .001). There was a significant drop in the total number of cases from 137 in 1986 to 106 in 1990, but the age-adjusted rate showed a significant drop for males only (322.3 to 182.5, P < .001). Marked differences in average annual age-adjusted rates existed among the seven cities, from 486.4 for Harbin to 80.9 for Shanghai. This difference in rate among cities was found for both sexes but was more pronounced in males. CONCLUSIONS: The stroke incidence rates in China, like those in Japan, are among the higher ones in the world. In recent years, there has been an apparent decline in stroke incidence. Marked differences in rates were found between males and females with decline in incidence occurring almost exclusively in males. There were also marked differences in stroke incidence among the cities studied. These differences may result in part from differences in diet, alcohol and cigarette consumption, or prevalence of hypertension.

Recent evidence suggests alterations in the gut microbiota-brain axis may drive cognitive impairment with aging. In the present study, we observed that prolonged administration of D-galactose to mice induced cognitive decline, gut microbial dysbiosis, peripheral inflammation, and oxidative stress. In this model of age-related cognitive decline, Cistanche deserticola polysaccharides (CDPS) improved cognitive function in D-galactose-treated mice by restoring gut microbial homeostasis, thereby reducing oxidative stress and peripheral inflammation. The beneficial effects of CDPS in these aging model mice were abolished through ablation of gut microbiota with antibiotics or immunosuppression with cyclophosphamide. Serum metabolomic profiling showed that levels of creatinine, valine, L-methionine, o-Toluidine, N-ethylaniline, uric acid and proline were all altered in the aging model mice, but were restored by CDPS. These findings demonstrated that CDPS improves cognitive function in a D-galactose-induced aging model in mice by restoring homeostasis of the gut microbiota-brain axis, which alleviated an amino acid imbalance, peripheral inflammation, and oxidative stress. CDPS thus shows therapeutic potential for patients with memory and learning disorders, especially those related to gut microbial dysbiosis.

A door-to-door two-phase study was used to investigate the prevalence of senile dementia in an urban community of Beijing. In the study population, 5,003 individuals aged 60 years and older (>/=65 years, n = 3,728) were screened at home with the Chinese version of the MMSE. Persons who screened positive for dementia, using different cutoff scores based on degree of literacy, were further evaluated using the criteria of DSM-III-R and ICD-10. Among subjects who screened positive in phase I, 134 were diagnosed as having dementia in phase II. The prevalence ratios of dementia were 2.68% in the population aged 60 years and older, and 3.49% in the population aged 65 years and older. The prevalence rates among those aged 65 years and older were 1.85% for Alzheimer's disease, 1.37% for vascular dementia and 0.27% for other dementia (including mixed dementia). The prevalence of all dementia and AD increased steeply with advancing age and was consistently higher in women, but it was not obviously higher for VaD in women. Alzheimer's disease was the commonest type of dementia. Our prevalence figures for dementia and AD are similar to those previously reported for China.