Direct Medical Expenses and Influencing Factors of MDR/RR-TB in Eastern China: Based on Data from Multi-Hospital Information Systems.

Background: Multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis (TB) is related to high healthcare costs. However, studies on direct healthcare expenditure in different settings remain inconclusive. Hence, we aimed to examine the direct medical expenses (DME) of patients with MDR/RR-TB and assessed which patient characteristics were associated with higher costs. Methods: DME was evaluated using records from the hospital information system in three cities with different economic levels in Zhejiang Province, Eastern China, matching with data (including socio-demographics, disease treatment status, etc.) collected in the Tuberculosis Management Information System. A logistic regression model was used to identify variables associated with higher costs. Results: Of 193 patients with MDR/RR-TB, the average DME was $10,491 (interquartile range (IQR) $4679-16,710), consisting of $2696 (IQR $1019-5100) out-of-pocket costs, medical reimbursement, and subsidies, accounting for 32%, 50.3% and 14%, respectively. A total of 74.2% and 56% of DME were for drugs and anti-TB drugs, respectively. Only 16.9% of the patients were treated with an all-oral regimen. Higher DME was significantly associated with local residents 7.29 (95% confidence interval (CI) [2.62-20.3]), hospitalization experience 7.63 (95% (CI) [2.54-22.95]), longer duration of treatment 6.63 (95% CI [2.27-19.35]), and lower health insurance reimbursement 5.65 (95% CI [1.90-16.79]). Conclusion: DME of patients with MDR/RR-TB was still significant, and domestic migrants, hospitalization, long treatment duration, and high health insurance rates increased the financial burden on MDR/RR-TB patients. Reasonable intervention programs should be developed to reduce the medical burden of patients with MDR/RR-TB, according to the DME and its component of MDR-TB patients, besides the economic status of their regions.

Mass Tuberculosis Screening Among the Elderly: A Population-Based Study in a Well-Confined, Rural County in Eastern China.

BACKGROUND: Mass tuberculosis (TB) screening has been recommended in certain high-risk populations. However, population-based screening interventions have rarely been implemented. Whether mass screening improves health equity is unknown. METHODS: We implemented a mass TB screening intervention among elderly persons (>60 years old) in Lanxi County, China. Standardized questionnaires, physical examinations, and chest radiographs (CXRs) were administered to all participants. Systematic testing with computed tomography, smear, culture, or Xpert was performed among persons with an abnormal CXR. We assessed TB prevalence per 100 000 persons and constructed multivariable regression models among subgroups that were and were not screened. Medical insurance was categorized as participation in either a basic program with limited coverage or a more comprehensive coverage program. RESULTS: In total, 49 339 individuals (32% of the elderly population in Lanxi) participated in the screening. One hundred fifteen screened persons were diagnosed with TB (233 cases per 100 000 persons), significantly higher than persons not screened (168 cases among 103 979 person-years; prevalence-to-case notification ratio, 1.44 [95% confidence interval {CI}, 1.14-1.83]). This increase was largely driven by diagnosis of asymptomatic disease during mass screening (n = 57 [50% of participants with TB]). Participants with basic medical insurance were much more likely to be diagnosed through mass screening than by passive detection (adjusted odds ratio, 4.52 [95% CI, 1.35-21.28]). CONCLUSIONS: In a population-based, mass TB screening intervention encompassing >30% of the elderly population in a county in rural China, case finding was 44% higher than background detection, driven by diagnosis of TB without recognized symptoms. Importantly, mass screening identified TB in people with limited healthcare options who were less likely to be found through background case detection.

Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load.

Despite extensive efforts, COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large. Vaccination is an effective approach to curb virus spread, but several variants (e.g., delta, delta plus, omicron, and IHU) appear to weaken or possibly escape immune protection. Thus, novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently needed. Multiple evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown mechanism. Here, we reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase (also known as nonstructural protein 12 (NSP12)) of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants, including omicron and IHU. Mechanistically, heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer. A mild daily heat treatment maintains low levels of both wild-type and P323L mutant of NSP12, suggesting clinical potential. Collectively, this novel mechanism, heat-induced NSP12 degradation, suggests a prospective heat-based intervention against SARS-CoV-2.

Research progress on approaches for detection of vitamin E in human blood / 预防医学

@#There are eight forms of vitamin E in human blood, including α-, β-, γ-, δ-tocopherols and α-, β-, γ-, δ-tocotrienols. As the most abundant and active form of vitamin E, α-tocopherol is widely accepted as a reliable indicator for nutritional assessment of body vitamin E status across the world. Considering that different vitamin E forms have diverse biological activities, separation and detection of different vitamin E forms in human blood facilitates the understanding of the association between vitamin E and diseases. In this review, the advances in sample-pretreatment techniques and detection techniques for vitamin E in human blood were presented. Currently, the sample-pretreatment techniques include solid-phase extraction, liquid-liquid extraction, dispersive liquid-phase microextraction, supported liquid extraction and direct protein precipitation; the detection techniques include automatic biochemical analysis, enzyme-linked immunosorbent assay, gas chromatography, liquid chromatography and ultra-high performance supercritical fluid chromatography mass spectrometry. This review summarizes the characteristics and scope of above-mentioned techniques used for detection of vitamin E in human blood, so as to provide insights into the selection of an appropriate method for inspection technicians.

Factors related to age at natural menopause in China: results from the China Kadoorie Biobank.

OBJECTIVES: The aim of this study was to investigate the potentially modifiable factors affecting age at natural menopause (ANM) in Chinese women. METHODS: We used cross-sectional data from the China Kadoorie Biobank study which that recruited 0.5 million (0.3 million women) Chinese adults aged 30 to 79 from 2004 to 2008. Multinomial logistic regression models were used to examine the relationships between ANM and various factors recorded at baseline. RESULTS: Among 87,349 postmenopausal women, the mean ANM (SD) was 48.7 (4.3) years. Older age, being a housewife, earlier menarche, and passive smoking were associated with both premature menopause (PM, ie, ANM <40 years) and early menopause (EM, ie, ANM between 40 and 44 years). A higher odds for EM was observed in women who were widowed (odds ratio: 1.10, 95% confidence interval: 1.04-1.16), had spontaneous abortions (1.33 [1.05-1.69]), current regular smoking (1.19 [1.07-1.37]), and frequent spicy food intake (1.11 [1.05-1.08]). Higher socioeconomic status; later first birth; more live births and induced abortions; longer breastfeeding; tea drinking, as well as intakes of meat, fruits, dairy, and soybean products; and increased body mass index gain were inversely associated with PM and/or EM. In contrast, women who had more pregnancies, occasional alcohol drinking, higher levels of physical activity or body mass index, vitamin intake, and hypertension were more likely to have a later age at menopause (LM, ie, ANM ≥53 years). CONCLUSIONS: This large epidemiological study found a wide range of sociodemographic, lifestyle, dietary, and reproductive factors related to PM, EM, and LM in Chinese women.

Association of dietary niacin intake with metabolic syndromeamong adults in Zhejiang Province / 预防医学

Objective @#To explore the association of dietary niacin intake and metabolic syndrome ( MS ) and its components among adults in Zhejiang Province, so as to provide the reference for dietary intervention of MS.@*Methods@#Using the multi-stage cluster random sampling method, the permanent residents aged 18 years and above were selected and investigated by a questionnaire developed by China Center for Disease Control and Prevention. Their waist circumference, blood pressure, glucose and lipid were measured. The daily dietary niacin intake of each person were calculated by "24-hour dietary review for 3 consecutive days", and divided into Q1, Q2, Q3 and Q4 groups according to quartiles. The multivariate logistic regression model was used to analyze the association of niacin intake with the risks of MS and its components. @*Results@#Among 2 438 participants, 871 cases with MS were detected, with a detection rate of 35.73%. The multivariate logistic regression analysis showed that compared with niacin intake Q1 group, Q2 ( OR=0.741, 95%CI: 0.561-0.978 ) and Q4 group ( OR=0.679, 95%CI: 0.487-0.947 ) had a lower risk of MS, Q2 ( OR=0.688, 95%CI: 0.516-0.919 ) and Q4 group ( OR=0.678, 95%CI: 0.479-0.960 ) had a lower risk of abdominal obesity, Q4 group ( OR=0.721, 95%CI: 0.536-0.969 ) had a lower risk of hyperglycemia. Further stratificating by gender, compared with niacin intake Q1 group, Q2 ( OR=0.664, 95%CI: 0.453-0.972 ) and Q3 group ( OR=0.646, 95%CI: 0.432-0.965 ) in women had a lower risk of MS, Q2 (OR=0.667, 95%CI: 0.460-0.967) and Q3 group ( OR=0.607, 95%CI: 0.408-0.902 ) had a lower risk of abdominal obesity; Q2 group ( OR=1.836, 95%CI: 1.202-2.805 ) in men had a higher risk of low high-density lipoprotein cholesterol.@*Conclusion@#Niacin intake is associated with an increased risk of MS, abdominal obesity and hyperglycemia.

Induction of peripheral blood T follicular helper cells expressing ICOS correlates with antibody response to hepatitis B vaccination.

T follicular helper (TFH) cells, a critical subset of CD4+ T cells, provide help to B cells during the procession of the humoral immune response in the germinal center (GC) and extrafollicular sites. CXCR5+ CD4+ T cells in human circulating blood, referred to herein as peripheral TFH (pTFH) cells, share phenotypes and functional properties with TFH cells in GC. Hepatitis B vaccine protects about 60% of the chronic hepatitis C patients from hepatitis B. The immunological bases that lead to the induction of protective antibody response is not well understood. In the present study, the pTFH cells subsets were determined in 18 healthy controls (anti-HBs ≥ 100 mIU/mL; HC), 21 nonresponders (anti-HBs < 10 mIU/mL; NR), and 23 weak responders (10 mIU/mL ≤ anti-HBs < 100 mIU/mL; WR) of chronic hepatitis patients upon routine hepatitis B vaccination. Though the frequency of the pTFH cell was equivalent in HC, WR, and NR, ICOS+ pTFH cells in HC underwent expansion with increased IL-21 secretion and production of serum anti-HBs response at 4 weeks after a full course of hepatitis B vaccination. These changes were not shown in both NR and WR. Analysis of ICOS+ pTFH cells represents a novel cellular determinant of the hepatitis B vaccine-induced humoral immune response, which may have relevance for design of hepatitis B vaccine.

Optimization of primary prevention strategies of birth defects in Zhejiang Province by Delphi method / 预防医学

Objective @#To optimize the primary prevention strategies of birth defects in Zhejiang Province by Delphi method, so as to promote the capacity of birth defects prevention. @*Methods@#The expert consultation questionnaire was developed based on the relevant policies of Zhejiang Province and literature. Ten experts from medical institutions and health administrative departments were employed for one round Delphi expert consultation. The weighted scores and priorities of ten measures for the primary prevention of birth defects in Zhejiang Province were determined, as well as the suggestions of optimizing the current policies. @*Results @# The response rate of the experts was 90.91%; the coefficient of authority was 0.92; the coefficients of variation of ten measures were all less than 0.25; the coefficient of coordination was 0.31 ( P<0.05 ) , which indicated the opinions of the experts tended to be consistent. In the order of priority, ten primary prevention measures of birth defects were the improvement of birth defects surveillance network ( province, city and county level ) , the training of birth defects prevention talents, the construction of genetic consultation clinics, health education and publicity, the reproduction outpatient service construction for older people, free premarital medical examination, free pre-pregnancy eugenics test, the construction of drug consultation clinics, career planning and training of birth defect prevention and control consultants and free folic acid supplement to the whole population. Nine experts suggested that the following policies need to be optimized: birth defects surveillance system, free premarital medical examination, and health education and publicity.@*Conclusion@#In the primary prevention of birth defects in Zhejiang Province, the most urgent problem to be solved is the improvement of the three-level birth defects surveillance network.

Residents' Awareness of Family Doctor Contract Services, Status of Contract with a Family Doctor, and Contract Service Needs in Zhejiang Province, China: A Cross-Sectional Study.

In China, family doctor services originated in 2009. After two years, the Chinese government proposed the establishment of a family doctor contract system suitable for China's national conditions. Then, in 2016, a multi-department jointly issued an important document, which further clarified the development goals of family doctor contract services in the next five years. Zhejiang Province has been exploring responsible doctor contract services since 2012, which was promoted throughout the province in 2015. OBJECTIVES: The aim of this study was to investigate the residents' awareness of Zhejiang Province, China, of family doctor contract services, the status of signing such a contract, and the demand for service items in the contracted service package. Further, we sought to explore the relevant influential factors in order to provide a reference and evidence-based recommendations for the further development of family doctor contract services. DESIGN: We enrolled 3960 residents from nine counties in Zhejiang Province using a multistage stratified random sampling method. A survey using a self-designed questionnaire was used to collect the demographic data, residents' awareness of family doctor contract services, the status of contracting, and demand for different items from October to December 2017. Data were analyzed by SPSS 21.0. RESULTS: In total, 3871 residents returned valid questionnaires, with a response rate of 97.75%. The awareness rate of residents of family doctor contract services was 71.58% (2771/3871). Age, education level, and chronic medical history status were the influencing factors affecting residents' awareness. The contracted rate was 50.43% (1952/3871). Age, education level, personal monthly income, chronic disease history, and awareness of family doctor contract services were the influencing factors. Residents who have a contract with family doctors have a higher demand for family doctor contract services, and different residents have different needs for the project because of their physical condition, education level, marital status, household registration, and personal monthly income level. The top three needs of the residents for contracted services were health consultation (84.64%), regular physical examination (81.71%), and increasing the proportion of medical insurance reimbursements (80.06%). CONCLUSIONS: The awareness rate of family doctor contract services and the contracting rate are unsatisfactory among residents of Zhejiang Province. It is suggested that the government should more heavily publicize family doctor contract services, expand the coverage, introduce personalized contract schemes to meet the needs of different groups, and promote the rapid development of family doctor contract services in Zhejiang Province.

An adult gerbil model for evaluating potential coxsackievirus A16 vaccine candidates.

A suitable animal model of CVA16 infection is crucial in order to understand its pathogenesis and to help develop antiviral vaccines or screen therapeutic drugs. The neonatal mouse model has a short sensitivity period to CA16 infection, which is a major limitation. In this study, we demonstrate that adult (60-day-old) gerbils are susceptible to CVA16 infection at high doses (108.0 TCID50). A clinical isolate strain of CVA16 was inoculated intraperitoneally into adult gerbils, which subsequently developed significant clinical symptoms, including hind limb weakness, paralysis of one or both hind limbs, tremors, and eventual death from neurological disorders. Real-time RT-PCR revealed that viral loads in the spinal cord and brainstem were higher than those in other organs/tissues. Histopathological changes, such as neuronal degeneration, neuronal loss, and neuronophagia, were observed in the spinal cord, brainstem, and heart muscle, along with necrotizing myositis. Gerbils receiving both prime and boost immunizations of alum adjuvant inactivated vaccine exhibited no clinical signs of disease or mortality following challenge by CVA16, whereas 80% of control animals showed obvious clinical signs, including slowness, paralysis of one or both hind limbs, and eventual death, suggesting that the CVA16 vaccine can fully protect gerbils against CVA16 challenge. These results demonstrate that an adult gerbil model provides us with a useful tool for studying the pathogenesis and evaluating antiviral reagents of CVA16 infection. The development of this animal model would also be conducive to screening promising CVA16 vaccine candidates as well as further vaccination evaluation.

Prevalence, types, and malformations in congenital anomalies of the kidney and urinary tract in newborns: a retrospective hospital-based study.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUTs) are some of the most common birth defects affecting newborns. CAKUTs often have poor birth outcomes owing to the limited experience of physicians in developing countries regarding antenatal and postnatal diagnosis. We aimed to estimate the epidemiology of CAKUTs using data from a hospital-based registry in Zhejiang Province, China. METHODS: We included a total of 2790 newborns with CAKUTs, identified among 1,748,038 births during 2010-2016. The prevalence and type of CAKUTs, maternal and neonatal characteristics, and associated malformations were analyzed. RESULTS: The average prevalence of CAKUTs born to mothers overall and mothers aged ≥35 years were both around 1.60 per 1000 births (95% confidence interval (CI), 1.54-1.66; 95% CI, 1.44-1.83, respectively) during the study period. The prevalence of CAKUTs changed over time among all women and women of advanced maternal age, although no significant trends were observed. CAKUTs were more likely to occur in male than female newborns (odds ratio (OR) 1.28, 95% CI 1.18-1.38), in multiple births than singletons (OR 1.53, 95% CI 1.21-1.92) and in urban areas than rural areas (OR 1.27, 95% CI 1.18-1.37). The overall prenatal detection rate of CAKUTs was 73.87%. The average gestational age at antenatal diagnosis was 26.57 ± 8.70 weeks. A total 22.69% CAKUTs had associated malformations. Congenital heart defects were the most common anomalies, accounting for 8.89% of the whole population. The main proportion in subgroups was hydronephrosis, representing 31.79% of registered CAKUTs. CONCLUSIONS: There was a nearly twofold increase in the prevalence of CAKUTs from 2010 to 2016 in Zhejiang Province. CAKUTs are strongly associated with male sex, multiple births, urban areas, and other nonurinary congenital malformations.

Factors Correlating to the Development of Hepatitis C Virus Infection in Hemodialysis Patients-Findings Mainly from Asiatic Populations: A Systematic Review and Meta-Analysis.

Hemodialysis is an effective replacement therapy for chronic renal failure patients. In recent decades, the number of hemodialysis patients has grown rapidly and some measures for preventing blood-borne diseases have been implemented, but hepatitis C virus (HCV) infection remains a significant problem. The meta-analysis published in 2009 on HCV infection-related factors was based on localized study objects, and some additional studies have been published since 2009; however, the contribution of these factors remains under dispute. Our study pooled the odds ratios (ORs) or mean standard deviations (MDs) with 95% confidence intervals (CIs) and analyzed sensitivity using Review Manager 5.1 software (5.1 version Copenhagen: The Nordic Cochrane Centre; 2011) by searching data in the PubMed, Elsevier, Springer, Wiley, and EBSCO databases. Spearman correlation analysis was performed using the SPSS package. In our meta-analysis, 1715 HCV-infected hemodialysis patients and 7093 non-HCV-infected hemodialysis patients from 44 studies were analyzed. The pooled ORs with 95% CIs were: histories of blood transfusion, 4.30 (3.11, 5.96); weekly hemodialysis times > 2, 6.00 (3.25, 11.06); kidney transplantation, 5.80 (3.95, 8.52); hemodialysis units > 2, 6.90 (2.42, 19.68); shared hemodialysis devices, 5.00 (2.35, 10.65); and drug addiction, 4.73 (1.54, 14.47). The pooled MDs with 95% CIs were duration of hemodialysis (months) 27.48 (21.67, 33.30). There was a positive correlation between duration of hemodialysis and the HCV infection rate (p < 0.01). Hemodialysis patients, especially from Asia, with shared hemodialysis devices, hemodialysis units > 2, blood transfusion, kidney transplantation, and drug addiction were at increased risk of HCV infection. The HCV infection rate increased with the duration of hemodialysis. High-risk hemodialysis patients should be monitored and receive timely screening.

[Analysis of the incidence and perinatal outcomes of multiple births in Zhejiang Province from 2008 to 2013].

OBJECTIVE: To analyze the trends of multiple births rates and their perinatal outcomes in Zhejiang province from 2008 to 2013. METHODS: Data were obtained from hospital-based perinatal mortality surveillance system in Zhejiang, including all the hospitals in 30 monitoring counties (districts). All births (28 or more weeks of gestation) born in the monitoring hospitals were included in our study within 7 days after delivery from 2008 to 2013. Chi-square test was performed for statistical analyses for comparisons between regions. Trends in the incidence of multiple births and causes of perinatal death were analyzed using chi-square test for trend. RESULTS: From 2008 to 2013, the multiple births rate in Zhejiang province was increased and the rates were 2.32% (5 551/239 636), 2.49% (6 053/243 452), 2.61% (6 549/250 594), 2.82% (7 758/275 105), 2.91% (8 803/302 447) and 3.06% (9 051/295 709), respectively. And the perinatal mortality rates for multiple births were 4.32% (240/5 551), 3.45% (209/6 053), 3.76% (246/6 549), 2.86% (222/7 758), 2.77% (244/8 803) and 2.11% (191/9 051), respectively. A significant drop in the perinatal mortality rates for multiple births was observed between 2008 and 2013 (χ(2) trend = 66.52, P < 0.001). There was a significantly greater risk for perinatal death to multiple births when compared with single birth (OR = 3.62, 95% CI: 3.42-3.83). The three leading causes of perinatal death for multiple births were birth defect, premature and/or low birth weight, and twin-twin transfusion syndrome. CONCLUSION: The multiple births rates in Zhejiang province showed an increasing trend. The perinatal mortality rates for multiple births were decreased annually, however, it was still higher than those in developed countries.