[Research progress on the role of hepatitis B virus DNA integration in chronic hepatitis B].

Chronic hepatitis B virus (HBV) infection will greatly contribute to raising the occurrence probability of cirrhosis and hepatocellular carcinoma in patients. Although existing antiviral treatment regimens have a certain effect on delaying disease progression and improving prognosis, it is still not effective in attaining functional cures. Hepatitis B virus DNA integration may be one of the reasons for this phenomenon. Therefore, this paper reviews the possible mechanisms of HBV DNA integration in maintaining chronic inflammation of the liver, evading existing antiviral treatment methods, and inducing hepatocellular carcinoma so as to further deepen the understanding of the role of HBV DNA integration in the occurrence and development of chronic hepatitis B, providing ideas and references for formulating better treatment strategies.

Mail and Telephone Outreach from Electronic Health Records for Research Participation on Cognitive Health and Aging.

OBJECTIVES: This report describes the efficacy and utility of recruiting older individuals by mail to participate in research on cognitive health and aging using Electronic Health Records (EHR). METHODS: Individuals age 65 or older identified by EHR in the Mount Sinai Health System as likely to have Mild Cognitive Impairment (MCI) were sent a general recruitment letter (N=12,951). A comparison group of individuals with comparable age and matched for gender also received the letter (N=3,001). RESULTS: Of the 15,952 individuals who received the mailing, 953 (6.0%) responded. 215 (1.3%) declined further contact. Overall rate of expression of interest was 4.6%. Of the 738 individuals who responded positively to further contact, 321 indicated preference for further contact by telephone. Follow-up of these individuals yielded 30 enrollments (0.2% of 15,952). No differences in response rate were noted between MCI and comparison groups, but the comparison group yielded higher enrollment. 6 individuals who were not the intended recipients of mailing but nevertheless contacted our study were also enrolled. CONCLUSIONS: Mailings to individuals identified through a trusted source, such as a medical center from which they have received clinical care, may be a viable means of reaching individuals within this age group as this effort yielded a low rejection rate. However, EHR information did not enhance study enrollment. Implications for improving recruitment are discussed.

[Effect of vanadium exposure on neurobehavioral function in workers].

OBJECTIVE: To establish the comprehensive indicators for neurobehavioral function test, and to investigate the possible adverse effect of long-time vanadium exposure on neurobehavioral function and its features in workers. METHODS: From July to November, 2012, The Neurobehavioral Core Test Battery(NCTB) recommended by WHO was used to conduct tests for 128 workers in vanadium exposure group and 128 workers in control group. The t-test and analysis of covariance were used to compare the differences in each indicator in NCTB between different populations, and the principal component analysis was used to establish the comprehensive neurobehavioral index(NBI) and investigate the effect of vanadium on workers' neurobehavioral function. RESULTS: The vanadium exposure group had significantly lower visual retention score(6.9±1.9), digit span(order) score(8.9±2.9), lifting and turning dexterity(the non-handed hand) score (14.1±3.6), pursuit aiming test(the number of correct dots) score(65.7±24.8), and digit symbol score (31.1±15.0) than the control group (8.2±1.3, 9.4±2.7, 15.5±3.0, 76.5±23.8, and 33.7±9.5)(all P<0.05). The vanadium exposure group also had a significantly lower NBI than the control group(-0.167±0.602 vs 0.168±0.564, P<0.05). CONCLUSION: Long-term vanadium exposure can influence the workers' neurobehavioral function, with the manifestations of decreased hearing and visual memory, movement velocity, accuracy, and coordination.

Are there sensitive time periods for dementia caregivers? The occurrence of behavioral and psychological symptoms in the early stages of dementia.

BACKGROUND: The behavioral and psychological symptoms associated with dementia (BPSD) can be burdensome to informal/family caregivers, negatively affecting mental health and expediting the institutionalization of patients. Because the dementia patient-caregiver relationship extends over long periods of time, it is useful to examine how BPSD impact caregiver depressive symptoms at varied stages of illness. The goal of this study was to assess the association of BPSD that occur during early stage dementia with subsequent caregiver depressive symptoms. METHODS: Patients were followed from the early stages of dementia every six months for up to 12 years or until death (n = 160). Caregiver symptoms were assessed on average 4.5 years following patient's early dementia behaviors. A generalized estimating equation (GEE) extension of the logistic regression model was used to determine the association between informal caregiver depressive symptoms and BPSD symptoms that occurred at the earliest stages dementia, including those persistent during the first year of dementia diagnosis. RESULTS: BPSD were common in early dementia. None of the individual symptoms observed during the first year of early stage dementia significantly impacted subsequent caregiver depressive symptoms. Only patient agitation/aggression was associated with subsequent caregiver depressive symptoms (OR = 1.76; 95% CI = 1.04-2.97) after controlling for concurrent BPSD, although not in fully adjusted models. CONCLUSIONS: Persistent agitation/aggression early in dementia diagnosis may be associated with subsequent depressive symptoms in caregivers. Future longitudinal analyses of the dementia caregiving relationship should continue to examine the negative impact of persistent agitation/aggression in the diagnosis of early stage dementia on caregivers.

Bridging from clinical endpoints to estimates of treatment value for external decision makers.

AIM: While clinical endpoints provide important information on the efficacy of treatment in controlled conditions, they often are not relevant to decision makers trying to gauge the potential economic impact or value of new treatments. Therefore, it is often necessary to translate changes in cognition, function or behavior into changes in cost or other measures, which can be problematic if not conducted in a transparent manner. The Dependence Scale (DS), which measures the level of assistance a patient requires due to AD-related deficits, may provide a useful measure of the impact of AD progression in a way that is relevant to patients, providers and payers, by linking clinical endpoints to estimates of cost effectiveness or value. The aim of this analysis was to test the association of the DS to clinical endpoints and AD-related costs. METHOD: The relationship between DS score and other endpoints was explored using the Predictors Study, a large, multi-center cohort of patients with probable AD followed annually for four years. Enrollment required a modified Mini-Mental State Examination (mMMS) score >or= 30, equivalent to a score of approximately >or= 16 on the MMSE. DS summated scores (range: 0- 15) were compared to measures of cognition (MMSE), function (Blessed Dementia Rating Scale, BDRS, 0-17), behavior, extrapyramidal symptoms (EPS), and psychotic symptoms (illusions, delusions or hallucinations). Also, estimates for total cost (sum of direct medical cost, direct non-medical cost, and cost of informal caregivers' time) were compared to DS scores. RESULTS: For the 172 patients in the analysis, mean baseline scores were: DS: 5.2 (SD: 2.0), MMSE: 23.0 (SD: 3.5), BDRS: 2.9 (SD: 1.3), EPS: 10.8%, behavior: 28.9% psychotic symptoms: 21.1%. After 4 years, mean scores were: DS: 8.9 (SD: 2.9), MMSE: 17.2 (SD: 4.7), BDRS: 5.2 (SD: 1.4), EPS: 37.5%, behavior: 60.0%, psychotic symptoms: 46.7%. At baseline, DS scores were significantly correlated with MMSE (r=-0.299, p < 0.01), BDRS (r=0.610, p < 0.01), behavior (r=.2633, p=0.0005), EPS (r=0.1910, p=0.0137) and psychotic symptoms (r=0.253, p < 0.01); and at 4-year follow-up, DS scores were significantly correlated with MMSE (r=-0.3705, p=0.017), BDRS (r=0.6982, p < 0.001). Correlations between DS and behavior (-0.0085, p=0.96), EPS (r=0.3824, p=0.0794), psychotic symptoms (r=0.130, ns) were not statistically significant at follow-up. DS scores were also significantly correlated with total costs at baseline (r=0.2615, p=0.0003) and follow-up (r=0.3359, p=0.0318). DISCUSSION: AD is associated with deficits in cognition, function and behavior, thus it is imperative that these constructs are assessed in trials of AD treatment. However, assessing multiple endpoints can lead to confusion for decision makers if treatments do not impact all endpoints similarly, especially if the measures are not used typically in practice. One potential method for translating these deficits into a more meaningful outcome would be to identify a separate construct, one that takes a broader view of the overall impact of the disease. Patient dependence, as measured by the DS, would appear to be a reasonable choice - it is associated with the three clinical endpoints, as well as measures of cost (medical and informal), thereby providing a bridge between measures of clinical efficacy and value in a single, transparent measure.

Longitudinal study of effects of patient characteristics on direct costs in Alzheimer disease.

OBJECTIVES: To estimate long-term trajectories of direct cost of caring for patients with Alzheimer disease (AD) and examine the effects of patients' characteristics on cost longitudinally. METHODS: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed up annually for up to 7 years in three university-based AD centers in the United States. Random effects models estimated the effects of patients' clinical and sociodemographic characteristics on direct cost of care. Direct cost included cost associated with medical and nonmedical care. Clinical characteristics included cognitive status (measured by Mini-Mental State Examination), functional capacity (measured by Blessed Dementia Rating Scale [BDRS]), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, and comorbidities. The model also controlled for patients' sex, age, and living arrangements. RESULTS: Total direct cost increased from approximately 9,239 dollars per patient per year at baseline, when all patients were at the early stages of the disease, to 19,925 dollars by year 4. After controlling for other variables, a one-point increase in the BDRS score increased total direct cost by 7.7%. One more comorbid condition increased total direct cost by 14.3%. Total direct cost was 20.8% lower for patients living at home compared with those living in an institutional setting. CONCLUSIONS: Total direct cost of caring for patients with Alzheimer disease increased substantially over time. Much of the cost increases were explained by patients' clinical and demographic variables. Comorbidities and functional capacity were associated with higher direct cost over time.

Clinical features associated with costs in early AD: baseline data from the Predictors Study.

BACKGROUND: Few studies on cost of caring for patients with Alzheimer disease (AD) have simultaneously considered multiple dimensions of disease costs and detailed clinical characteristics. OBJECTIVE: To estimate empirically the incremental effects of patients' clinical characteristics on disease costs. METHODS: Data are derived from the baseline visit of 180 patients in the Predictors Study, a large, multicenter cohort of patients with probable AD followed from early stages of the disease. All patients initially lived at home, in retirement homes, or in assisted living facilities. Costs of direct medical care included hospitalizations, outpatient treatment and procedures, assistive devices, and medications. Costs of direct nonmedical care included home health aides, respite care, and adult day care. Indirect costs were measured by caregiving time. Patients' clinical characteristics included cognitive status, functional capacity, psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, and duration of illness. RESULTS: A 1-point increase in the Blessed Dementia Rating Scale score was associated with a $1,411 increase in direct medical costs and a $2,718 increase in unpaid caregiving costs. Direct medical costs also were $3,777 higher among subjects with depressive symptoms than among those who were not depressed. CONCLUSIONS: Medical care costs and unpaid caregiving costs relate differently to patients' clinical characteristics. Poorer functional status is associated with higher medical care costs and unpaid caregiving costs. Interventions may be particularly useful if targeted in the areas of basic and instrumental activities of daily living.

Do United States-based Medicaid spend-down programmes make public sense for persons with HIV/AIDS?

Medicaid is a US government insurance programme designed primarily for poor individuals, with expenditures that rose more than 13% in 2002. Thirty-five states have programmes allowing individuals to incur medical expenses at a rate that would make them poor enough to meet Medicaid eligibility criteria. This paper examines the cost of providing care to those spending-down to Medicaid compared to those eligible without spending-down. This longitudinal cohort study compiled inpatient, outpatient and Medicaid data from three academic Infectious Diseases clinics serving approximately 40% of the reported HIV-positive population in North Carolina. Participants included all HIV-positive patients who received care in one of three clinics and received Medicaid coverage at any time from 1996 to 2000 (1,495 individuals). Overall, those who needed to spend-down to Medicaid incurred higher medical costs, following a distinctive pattern of high costs when initially qualified and when ending coverage, and low costs while on spend-down. US states may wish to consider expanding Medicaid's categorically eligible criteria or significantly reducing the frequency with which persons must spend-down to become eligible for Medicaid.

Informal costs of dementia care: estimates from the National Longitudinal Caregiver Study.

OBJECTIVES: The purpose of the study was to examine on a national level the informal costs of caring for elderly community-dwelling male veterans with dementia by female caregivers and the relationships between informal costs and disease severity, and between informal costs and dementia problem behaviors. METHODS: Female primary caregivers were drawn from the first wave (N = 2043) of the National Longitudinal Caregiver Study, a survey of informal caregivers of elderly male veterans diagnosed with probable Alzheimer's disease or vascular dementia. Cost measures include the following four items: value of caregiving time, caregiver's lost income, out-of-pocket expenditures for formal caregiving services, and caregiver's excess health costs. Disease severity was indexed by the number of impairments in activities of daily living. Patient's problem behaviors were measured using the Behavior Rating Scale-Dementia. RESULTS: The annual cost of providing informal care to elderly community-dwelling veterans with dementia was estimated to be $18,385 per patient in 1998. The larger components of this cost are caregiving time ($6,295) and caregiver's lost earnings ($10,709). All aspects of costs increase with disease severity and problem behavior. Most of this cost increase derives from the increased caregiving time required for the provision of physical care. DISCUSSION: This study provides a comprehensive estimate of the excess costs that result from providing informal dementia care in the community. Unlike previous studies, our estimates excluded costs that caregivers would have incurred if they had not been caregivers. Therefore, results reported here reflect only costs due to informal dementia care.

SDS-PAGE protein pattern and its antigenicity analysis of different isolates of Schistosoma japonicum in China.

Homogenates prepared from S. japonicum adult worms of different isolates from Anhui, Hubei, Guangxi, Yunnan and Sichuan Provinces were analyzed by SDS-PAGE and enzyme linked immunoelectrotransfer blot (EITB) tested with rabbit anti-snails antibody. The results of SDS-PAGE indicated that with silver staining both male and female worms of Guangxi isolate showed some definite differences in their protein profile, namely, absence of one band between 50-75 kDa in male worms and marked reduction in quantity of > 110 and 30 kDa bands in female worms. There was no obvious difference among other isolates both in male and female worms. The EITB patterns were similar in S. japonicum of Anhui and Hubei, and it was also the case with isolates from Yunnan and Sichuan, except that Yunnan female worms had a distinct band at 84 kDa which could hardly be seen in EITB pattern of Sichuan female worms; female worms of Guangxi isolates also showed a distinct 84 kDa band. The EITB pattern of male worms from Guangxi isolates showed 2 main bands of MW > 130 kDa against anti-Anhui snail antiserum which corresponded with the result of male worms of Anhui isolates. But these bands could not be seen with male worms from isolates of Yunnan and Sichuan.

[Characterization of Echinococcus granulosus and Echinococcus multilocularis by DNA probe].

Cloned DNA fragments pHD5, pSM889 and pEG18 have been used as DNA probes in the restriction endonuclease analysis and southern blot hybridization to characterize E. granulosus and E. multilocularis protoscolices from China. Southern blot hybridization method is sensitive, specific and has the advantage in identification over microscopic examination. The authors deem that it can be used in the base-line epidemiological survey and surveillance of hydatid disease to provide data for hydatid disease control.

[RFLP analysis of DNA from Echinococcus granulosus collected from four provinces/autonomous region in China].

A fragment of the ribosomal RNA gene of Schistosoma mansoni pSM889 and two DNA fragments specific to Echinococcus granulosus pHD5 and pEG18 have been used as DNA probes to assess the extent of genetic variability within E. granulosus. The DNA analysis, including restriction endonuclease digestion and Southern blot hybridization with the probes, did not demonstrate any genetic variation among E. granulosus collected from sheep in Xinjiang, Qinghai, Gansu and Ninxia. Similarly, there was no genetic variation among E. granulosus isolates collected from yak in Qinghai and Gansu provinces. The authors deemed that the yak isolates and the sheep isolates of E. granulosus appear to belong to a same strain.

[Studies on the strain differences of Schistosoma japonicum in the mainland of China. XI. Enzyme linked immunoelectrotransfer blot analysis].

Antigens prepared from S. japonicum adult worms of different isolates i. e. Anhui, Hubei, Guangxi, Yunnan and Sichuan by origin were analyzed by enzyme linked immunoelectrotransfer blot (EITB) probed with rabbit anti-snail antibody (Figs 1,2). Anti-sera against Oncomelania h. hupensis from Anhui, Hubei, Yunnan and Sichuan localities were prepared separately and used in the tests. The EITB patterns were similar in S. j. isolates of Anhui and Hubei, and it was also the case among S. j. isolates of Yunnan and Sichuan except Yunnan female worms with a marked band of 84 kDa but it was almost invisible in EITB pattern of Sichuan female worms. Like Yunnan isolate, female worms of Guangxi isolate also showed marked 84 kDa bands. The EITB pattern of male worms from Guangxi isolate showed 2 main bands of mw > 130 kDa against anti-Anhui snail anti-serum, which corresponded with the male worms of Anhui isolate whereas the color of the bands was darker and denser in the former isolates, and these bands can not be seen in the male worms from isolates of Yunnan and Sichuan. Based on the above mentioned results in connection with the information about the susceptibility between different isolates of schistosomes and their snail hosts which we have reported before, some preliminary analysis and discussion were made.

[Studies on the strain differences of Schistosoma japonicum in the mainland of China. X. Comparison of SDS-page protein patterns].

The purpose of the present study was to investigate the SDS-PAGE separation of proteins of the 5 different isolates of Schistosoma japonicum from the mainland of China to determine their similarities and/or differences and to gain additional data which could give an added insight into the degree of relationship. Soluble proteins of freshly sonicated adult worm extract of the 5 different isolates (i.e., Anhui, Hubei, Guangxi, Sichuan and Yunnan) were compared by SDS-polyacrylamide gel electrophoresis. The results indicated that no marked difference could be observed among the isolates after gels were stained by Coomassie blue white both male and female worms of Guangxi isolate showed some definite differences in their protein profile, i.e., lack of 50-75 kDa band in male worms and a marked reduction in the quantity of > 110 and 30 kDa bands in female worms as shown by silver stain.

[Detection of human cytomegalovirus DNA by in situ hybridization].

A biotin labelled human cytomegalovirus (HCMV) DNA probe of EcoRI D fragment (17kb) from HCMV AD 169 strain was prepared. In situ hybridization of HCMV was performed in paraffin section of tissues collected from an autopsy case of congenital and combined immunodeficiency syndrome associated with systemic HCMV and pneumocystis carinii infections. The pathological lesions of HCMV infection showed three different patterns: 1, necrotic granuloma type, 2, diffuse type, and 3, scattered type. HCMV DNA was identified in all the inclusion bodies and piled or granular positive material was found in the nuclei or cytoplasms of some giant cells. In addition, some morphologically intact cells might be observed positive for CMV DNA either in nuclei or in cytoplasms.

[Detection of circulating membrane antigen of schistosome in schistosomiasis by dot-ELISA and idiotype/antiidiotype interaction inhibition test].

A monoclonal antibody (designated 8SE) against membrane antigen of adult Schistosoma japonicum labeled with HRP was used in dot-ELISA (direct method) to detect schistosomal circulating membrane antigen. Sera from 48 parasitologically confirmed schistosomiasis cases were tested, 39 (81.3%) were positive. No false positive reaction was found in sera from 24 healthy controls. No cross reaction was detected in sera from clonorchiasis or paragonimiasis in 18 cases each. This results suggest that circulating membrane antigen does exist in patients with schistosomiasis and it might be used as a complementary method for diagnosis of schistosomiasis. A preliminary result of idiotype/antiidiotype interaction inhibition reaction for detecting circulating membrane antigen was also presented.

Relation between changes of TXB2 and PGF1 alpha and the severity of the disease and pathological lesions in cases of severe icteric hepatitis.

Clinically, 32 cases of intrahepatic cholestasis and 30 cases of severe chronic hepatitis with a bilirubin level higher than 171 mumol/L were studied. The results showed that bilirubin was 420 mumol/L in the first group, and 480 mumol/L in the second group (P greater than 0.05); TXB2 was 306 pg/ml and 271 pg/ml (P greater than 0.05) while PGF1 alpha was 253 pg/ml and 494 pg/ml (P less than 0.05) respectively, both were higher than their normal values (P less than 0.01). The cases were divided into acute, moderate and severe types according to their pathological lesions. Experimentally, intra- and extrahepatic cholestasis and necrotic liver tissues were induced by ANIT, ligation of common bile duct, and carbon tetrachloride respectively. Bilirubin was 629 mumol/L, 124.8 mumol/L, and lower than 17.1 mumol/L (P less than 0.01); plasma TXB2 was 634 pg/ml, 1036 pg/ml, and 239 pg/ml (P less than 0.01); PGF1 alpha was 186 pg/ml, 218 pg/ml, and 868 pg/ml (P less than 0.01) in the three groups respectively. No statistic difference was found in their TXB2 and PGF1 alpha. Our studies suggested that plasma TXB2 and PGF1 alpha in the liver was not related to the severity of liver lesions. TXB2 and PGF1 alpha are positively correlated with the increase of bilirubin while TXB2 is negatively correlated with PGF1 alpha, which might serve as an index for cholestasis, and be a cause for deepening jaundice.