[Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention].

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Cost and related factors analysis for patients undergoing colon polyp surgery based on DRG mode.

OBJECTIVE: The aim of the study was to analyze the hospitalization costs of patients with intestinal polyps undergoing colonic polyp surgery and associated influencing factors and to explore the entry point of cost control and the way of fine management. PATIENTS AND METHODS: One year before (2021) and one year after (2022) the implementation of the Diagnosis Related Grouping (DRG), the patients receiving APC, CSP and EMR in GK39 (colonoscopy operation) group were included in a second Affiliated Hospital in Nanjing according to the Nanjing grouping scheme. Descriptive analysis method and multiple linear regression method were used for analysis. RESULTS: After the implementation of DRG in 2022, the average hospitalization cost of patients decreased by 19.46% compared with the same period last year. Before and after the implementation of DRG, medical technology costs accounted for the highest proportion of hospitalization costs. Age, hospitalization days, number of polyps, number of clamps and clinical pathway had statistically significant effects on hospitalization cost (p<0.05), among which hospitalization days, number of polyps, and number of clamps had the greatest impact on hospitalization cost, followed by age and clinical pathway. CONCLUSIONS: The implementation of DRG has a positive effect on guiding hospitalization cost control. It is suggested to realize accurate cost control by analyzing the cost structure of the disease group. Clinical pathway completion rate has a direct impact on the implementation effect of DRG, including cost control. It is suggested to refine clinical pathway management and achieve scientific cost control through continuous optimization and improvement of clinical pathway management.

Serum metabolomics assessment of etiological processes predisposing ketosis in water buffalo during early lactation.

Metabolic disorders as ketosis are manifestations of the animal's inability to manage the increase in energy requirement during early lactation. Generally, buffaloes show a different response to higher metabolic demands than other ruminants with a lower incidence of metabolic problems, although ketosis is one of the major diseases that may decrease the productivity in buffaloes. The aim of this study was to characterize the metabolic profile of Mediterranean buffaloes (MB) associated with 2 different levels of ß-hydroxybutyrate (BHB). Sixty-two MB within 50 days in milk (DIM) were enrolled and divided into 2 groups according to serum BHB concentration: healthy group (37 MB; BHB <0.70 mmol/L; body condition score: 5.00; parity: 3.78; and DIM: 30.70) and group at risk of hyperketonemia (25 MB; BHB ≥0.70 mmol/L; body condition score: 4.50; parity: 3.76; and DIM: 33.20). The statistical analysis was conducted by one-way ANOVA and unpaired 2-sample Wilcoxon tests. Fifty-seven metabolites were identified and among them, 12 were significant or tended to be significant. These metabolites were related to different metabolic changes such as mobilization of body resources, ruminal fermentations, urea cycle, thyroid hormone synthesis, inflammation, and oxidative stress status. These findings are suggestive of metabolic changes related to subclinical ketosis status that should be further investigated to better characterize this disease in the MB.

Air quality improvement assessment and exposure risk of Shandong Province in China during 2014 to 2020.

As one of the most polluted provinces in China, air pollution events occur frequently in Shandong. Based on the hourly (or daily) concentrations of six air pollutants (PM2.5, PM10, O3, NO2, SO2 and CO), the situations of air quality improvement in three kinds of cities (key cities, coastal cities and general cities) are assessed comprehensively during 2014-2020. Contrary to the daily maximum 8-h average ozone (MDA8 O3), the annual average concentrations of other pollutants show the downward trends during 2014-2020. Therein, the improvement rates of annual average concentrations of air pollutants in key cities are highest. By 2020, the day proportions of O3 as the primary pollutant are up to 38% in three kinds of cities. Besides, due to the impact of COVID-19, the monthly average concentrations of PM2.5, PM10, NO2, SO2 and CO in February 2020 decrease by 32.1-49.5% year-on-year. There are still about 50% of population exposed to high-risk regions (R i > 2), which are mainly concentrated in main urban areas and industrial areas. Thus, the adjustment of industrial structure and energy composition in the context of carbon peak and carbon neutrality should be implemented in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-022-04651-5.

Image-Quality Assessment of 3D Intracranial Vessel Wall MRI Using DANTE or DANTE-CAIPI for Blood Suppression and Imaging Acceleration.

BACKGROUND AND PURPOSE: 3D intracranial vessel wall MRI techniques are time consuming and prone to artifacts, especially flow artifacts. Our aim was to compare the image quality of accelerated and flow-suppressed 3D intracranial vessel wall MR imaging techniques relative to conventional acquisitions. MATERIALS AND METHODS: Consecutive patients undergoing MR imaging had conventional postcontrast 3D T1-sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) and either postcontrast delay alternating with nutation for tailored excitation (DANTE) flow-suppressed or DANTE-controlled aliasing in parallel imaging results in higher acceleration (CAIPI) flow-suppressed and accelerated T1-SPACE sequences performed. The sequences were evaluated using 4- or 5-point Likert scales for overall image quality, SNR, extent/severity of artifacts, motion, blood suppression, sharpness, and lesion assessment. Quantitative assessment of lumen and wall-to-lumen contrast ratios was performed. RESULTS: Eighty-nine patients were included. T1-DANTE-SPACE had significantly better qualitative ratings relative to T1-SPACE for image quality, SNR, artifact impact, arterial and venous suppression, and lesion assessment (P < .001 for each, respectively), with the exception of motion (P = .16). T1-DANTE-CAIPI-SPACE had significantly better image quality, lesion assessment, arterial and venous blood suppression, less artifact impact, and less motion compared with T1-SPACE (P < .001 for each, respectively). The SNR was higher with T1-SPACE compared with T1-DANTE-CAIPI-SPACE (P < .001). T1-DANTE-CAIPI-SPACE showed significantly worse lumen (P = .005) and wall-to-lumen contrast ratios (P = .001) compared with T1-SPACE, without a significant difference between T1-SPACE and T1-DANTE-SPACE. T1-DANTE-CAIPI-SPACE scan time was 5:11 minutes compared with 8:08 and 8:41 minutes for conventional T1-SPACE and T1-DANTE-SPACE, respectively. CONCLUSIONS: Accelerated postcontrast T1-DANTE-CAIPI-SPACE had fewer image artifacts, less motion, improved blood suppression, and a shorter scan time, but lower qualitative and quantitative SNR ratings relative to conventional T1-SPACE intracranial vessel wall MR imaging. Postcontrast T1-DANTE-SPACE had superior SNR, blood suppression, higher image quality, and fewer image artifacts, but slightly longer scan times relative to T1-SPACE.

[Results and cost-effectiveness of colorectal cancer screening program among urban residents in Zhejiang province, 2013-2018].

Objective: To analyze the results and cost-effectiveness of colorectal cancer (CRC) screening program among Zhejiang urban residents so as to provide evidence for further optimization of CRC screening strategies. Methods: Based on the Cancer Screening Program in Urban China which was conducted in Zhejiang province from 2013-2018, data related to the rates on compliance and detection through the CRC screening program among the 40-74 year-old residents were analyzed. Chi-square tests were used to compare the differences among groups, and multivariate logistic regression models were applied to explore the potential risk factors. Cost-effectiveness ratio (CER) was calculated by using the cost per lesion detected as the indicator. Results: Among all the 166 285 participants who completed the risk assessment questionnaire, 21 975 (13.2%) were recognized as under the high risk of CRC and 4 389 (20.0%) of them received the colonoscopy. The detection rates of CRC, advanced adenoma, and non-advance adenoma were 0.3% (11 cases), 2.7% (119 cases), and 5.2% (229 cases), respectively. Results from the multivariate logistic regression analyses showed that factors as age, gender, education level, smoking, drinking alcohol, previous fecal occult blood test (FOBT), polyp history, and family history of CRC were significantly associated with the compliance rate of colonoscopy while age, smoking and polyp history were significantly associated with the detection rate of advanced neoplasms (CRC and advanced adenoma). The costs were ï¿¥22 355.74 Yuan for every CER advanced neoplasm detection and ï¿¥264 204.18 Yuan per CRC detection, respectively. The CER decreased along with ageing. Sensitivity analysis showed that CERs were expected to decrease when the compliance rate of colonoscopy was increasing. Conclusions: The current screening program seems effective in detecting the precancerous colorectal lesions, but the relatively low compliance rate of colonoscopy restricting both the diagnostic yields and economic benefits. It is necessary to improve the awareness and acceptance of colonoscopy among the high-risk CRC population.

[Technological innovation and patent transformation in rectal cancer surgery].

Surgery for rectal cancer has obtained quick improvement in techniques and concepts in recent years but still has challenging areas. Colorectal surgeons always seek to make operations clearer and easier, so that surgery can be safer and less time-consuming while guaranteeing surgical goals. With this purpose, our team have explored to make innovations in operations for rectal cancer and translate relevant patents from 2009. We summarize our achievements in this article as follows: (1) Reverse Miles operation (perineal operation first then laparoscopic abdominal operation) with two relevant patents-specialized instruments bag for laparoscopic operations (patent number ZL201520442331.0) and accessory spotlight for ultrasound scalpel (patent number ZL20102 0137689.X). (2) Laparoscopic sphincter-saving surgery for low rectal cancer through marker meeting approach with two patents-vacuum rectal drainage tube with functions of irrigation and ventilation (patent number ZL201520374385.8) and sterile sleeve cover of ultrasound scalpel handle (patent number ZL201920648102.2). (3) Laparoscopic radical resection of colorectal cancer and natural orifice specimen extraction. Different methods were designed according to the location of the tumor that classified as 20-40 cm, 10-20 cm and 5-10 cm to anus. Two relevant patents were specialized instruments for natural orifice specimen extraction (patent application number ZL2017101480141) and plastic film sleeve for natural orifice specimen extraction (patent application number ZL 201921169857.0). Reformation of surgical technique and innovation of surgical instruments should be conducted by surgeons with innovative thinking who always seek the way to translate ideas to patents and then real products to promote surgical treatment.

Prevalence and Potential Associated Factors of Depression among Chinese Older Inpatients.

INTRODUCTION: Little is known about the current representative depression situation among Chinese older inpatients. The aim of this study is to examine prevalence of depression and associated risk factors among Chinese older inpatients by a large-scale cross-sectional national survey. METHODS: This study is based on baseline survey data from a large-scale cohort study in a representative sample of Chinese older inpatients. The procedure of this study involves physical examination and face-to-face questionnaire interviews. Depression was assessed based on the Geriatric Depression Scale 15. Mixed-effect Poisson regression model was used to examine the relationship between depression and covariates by controlling the cluster effect of hospital wards. RESULTS: Of all 9727 respondents, the mean age of all respondents was 72.4±5.7 years, from 65 to 97. The average GDS score was 2 (1, 4). The prevalence rate of depression was 16.7% (95%CI: 15.8-17.4%) among older inpatients. The prevalence rates were 14.6% for males and 19.5% for females respectively. After controlling the cluster effect of hospital wards, age, gender, ADL score, educational level, BMI, frail, marriage, falls, alcohol drinking, cognitive function, living conditions, vision, hearing, sleep and defecation function were associated with depression. Emaciation (OR=1.176, 95%CI: 1.107-1.249), frail (OR=1.562, 95%CI: 1.489-1.639), divorced or widowed (OR=1.083 95%CI: 1.017-1.153), living in the bungalow (OR=1.075, 95%CI: 1.023-1.130), falls (OR=1.078, 95%CI: 1.030-1.128), cognitive function (OR=1.142, 95%CI: 1.091-1.195), vision dysfunction (OR=1.125, 95%CI: 1.076-1.177), hearing dysfunction (OR=1.061, 95%CI: 1.011-1.113), sleep dysfunction (OR=1.237, 95%CI: 1.194-1.282), defecation dysfunction (OR=1.160, 95%CI: 1.103-1.221) could increase prevalence risk of depression. CONCLUSIONS: There was a high prevalence of depression among Chinese older inpatients. Demographic characteristics, physical and mental conditions indicators have strong effect on prevalence and strength of depression. Therefore, it is essential to assess depression and perform comprehensive measures to improve physical and mental conditions in order to manage depressive symptoms in older inpatients.

Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection.

Transient elastography (TE) is accurate in staging fibrosis noninvasively. However, a reliable serum biomarker with comparable accuracy is also important, especially when TE is unreliable/unavailable. Therefore, we aimed to evaluate the diagnostic performance of serum Golgi protein 73 (GP73) for significant fibrosis in patients with chronic HBV infection. A total of 801 patients with chronic liver disease (CLD; 492 chronic HBV infection and 309 non-HBV liver disease) with liver biopsy performance were enrolled. Healthy controls (n = 180) and hepatocellular carcinoma (HCC) patients (n = 85) were included for comparisons. Liver biopsy was used as the reference method for fibrosis staging. Serum GP73 level was measured in duplicate in double-blind fashion. Serum GP73 was highest in HCC but also significantly higher in chronic hepatitis B than in healthy controls. The elevation of serum GP73 in non-HCC patients was significantly associated with the presence of significant fibrosis independently of ALT level, liver stiffness (LS) value, inflammation grade and other confounding factors. The diagnostic performance of serum GP73 was accurate in antiviral-naïve HBV patients (area under the receiver operating curve [AUROC], 0.76 95% CI: 0.72-0.81) but not in patients with ongoing antiviral treatment (AUROC, 0.60). The utility of serum GP73 was also confirmed in non-HBV CLD (AUROC, 0.80 95% CI: 0.75-0.85). Serum GP73 was comparable to LS (AUROC, 0.78 95% CI: 0.73-0.82) and significantly better than AST to platelet ratio index (APRI) (AUROC, 0.67 95% CI: 0.62-0.72) and FIB-4 (AUROC, 0.68 95% CI: 0.63-0.73). In conclusion, serum GP73 is an accurate serum marker for significant fibrosis in chronic HBV infection, with higher accuracy than APRI and FIB-4. Serum GP73 is potentially a complementary tool for TE when evaluating the necessity of antiviral treatment, particularly in patients without definite antiviral indication.

Identification and Quantitative Assessment of Different Components of Intracranial Atherosclerotic Plaque by Ex Vivo 3T High-Resolution Multicontrast MRI.

BACKGROUND AND PURPOSE: High-resolution 3T MR imaging can visualize intracranial atherosclerotic plaque. However, histologic validation is still lacking. This study aimed to evaluate the ability of 3T MR imaging to identify and quantitatively assess intracranial atherosclerotic plaque components ex vivo with histologic validation. MATERIALS AND METHODS: Fifty-three intracranial arterial specimens with atherosclerotic plaques from 20 cadavers were imaged by 3T MR imaging with T1, T2, and proton-density-weighted FSE and STIR sequences. The signal characteristics and areas of fibrous cap, lipid core, calcification, fibrous tissue, and healthy vessel wall were recorded on MR images and compared with histology. Fibrous cap thickness and maximum wall thickness were also quantified. The percentage of areas of the main plaque components, the ratio of fibrous cap thickness to maximum wall thickness, and plaque burden were calculated and compared. RESULTS: The signal intensity of the lipid core was significantly lower than that of the fibrous cap on T2-weighted, proton-density, and STIR sequences (P < .01) and was comparable on T1-weighted sequences (P = 1.00). Optimal contrast between the lipid core and fibrous cap was found on T2-weighted images. Plaque component mean percentages were comparable between MR imaging and histology: fibrous component (81.86% ± 10.59% versus 81.87% ± 11.59%, P = .999), lipid core (19.51% ± 10.76% versus 19.86% ± 11.56%, P = .863), and fibrous cap (31.10% ± 11.28% versus 30.83% ± 8.51%, P = .463). However, MR imaging overestimated mean calcification (9.68% ± 5.21% versus 8.83% ± 5.67%, P = .030) and plaque burden (65.18% ± 9.01% versus 52.71% ± 14.58%, P < .001). CONCLUSIONS: Ex vivo 3T MR imaging can accurately identify and quantitatively assess intracranial atherosclerotic plaque components, providing a direct reference for in vivo intracranial plaque imaging.

Naturalistic assessment of the learner license period.

The purpose of this study was to describe the characteristics and progression of practice driving during the learner license period in a sample of teenagers. During the first and last 10h of practice driving, we examined (1) the amount, variety and complexity of conditions of practice; (2) the nature of parental instruction; and (3) errors that teens made while driving. Data were collected from 90 teens and 131 parents living in Virginia, USA, using in-vehicle cameras, audio recorders, GPS and trip recorders. Based on data collected from the instrumented vehicles, teens practiced for 46.6h on average, slightly higher than the GDL requirement for their jurisdiction, though half did not complete the required 45h of practice and only 17% completed the required 15h of night time driving. Exposure to diverse roadways increased over the practice driving period, which averaged 10.6 months. Most driving instruction occurred in reaction to specific driving situations, such as navigating and identifying hazards, and could be characterized as co-driving. Higher order instruction, which relates to the tactics or strategies for safe driving, was less frequent, but remained stable through the practice driving period. Instruction of all forms was more likely following an elevated gravitational force (g-force) event. Errors decreased over time, suggesting improvements in manual and judgment skills, but engagement in potentially distracting secondary tasks increased (when an adult was in the vehicle). A small percentage of trips occurred with no passenger in the front seat, and the g-force rate during these trips was almost 5 times higher than trips with an adult front-seat passenger. Taken collectively, these findings indicate (1) most teens got at least the required amount of supervised practice, but some did not; (2) instruction was mainly reactive and included some higher order instruction; (3) teens driving skills improved despite increased exposure to complex driving conditions, but secondary tasks also increased. Opportunities remained for improving the quality and variability in supervision and enhancing the development of skills during the lengthy period of practice.

An update of the Hong Kong Epilepsy Guideline: consensus statement on the use of antiepileptic drugs in Hong Kong.

OBJECTIVE: New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong. PARTICIPANTS: Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society. EVIDENCE: A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution. CONSENSUS PROCESS: Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature. CONCLUSIONS: Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine, pregabalin, and perampanel were made. The consensus statements may provide a reference to physicians in their daily practice. Controversy exists over the use of generic products among patients who are currently taking brand medications. In this regard, approvals from prescriber and patient are pivotal. Good communication between doctors and patients is essential, as well as enlisting the assistance of doctors, nurses, and pharmacists, therapeutic blood monitoring if available, and the option of brand antiepileptic drug as a self-financed item. The physical appearance of generic drugs should be considered as it may hamper drug compliance. Support from medical services is recommended. In the longer term, the benefit of flexibility and the options to have a balance between the generic and brand drug market may need to be addressed by institutions and regulatory bodies.

Assessment of dentinal tubule invasion capacity of Enterococcus faecalis under stress conditions ex vivo.

AIM: To investigate the dentinal tubule invasion capacity of Enterococcus faecalis under alkaline and energy starvation stress conditions. METHODOLOGY: The root canals from human single-rooted teeth (n = 40) were infected with E. faecalis under alkaline (pH 9, 10, 11 and 12) and energy starvation (no glucose, 0.05% glucose and 0.15% glucose) stress conditions. The root canals were prepared in a standard manner and treated to remove the smear layer before incubation. After 4 weeks of cultivation, the roots were split vertically into two halves: one half was processed for biofilm formation analysis using a scanning electron microscope; the other half was stained with fluorescent DNA-binding reagents, washed thoroughly and sectioned (100 µm thick), and the depth of tubule invasion by the microorganism was examined by confocal laser-scanning microscopy. The extent of dentine tubule invasion was analysed statistically. RESULTS: The E. faecalis strain resulted in biofilm formation and dentine tubules invasion under all of the stress conditions, except for pH 11 and 12 conditions. However, the tubule penetration distance was markedly reduced in these stress conditions (P < 0.01) compared with in tryptic soy broth (TSB) or pH 7 medium. The invasion depth in the middle root dentine was significantly higher than in the apical sections in TSB and energy starvation medium (P < 0.01). CONCLUSIONS: Ex vivo E. faecalis formed biofilms and colonized dentine under alkaline and glucose starvation stress conditions, but its ability to invade dentine tubules was significantly decreased.

Development of a low-dose fast-dissolving tablet formulation of Newcastle disease vaccine for low-cost backyard poultry immunisation.

The immunisation of backyard poultry is critical for maintaining healthy flocks to provide nutrition and income for low-resource farmers worldwide. A vaccine presentation for flocks of less than 50 birds could make it more affordable and accessible, increasing uptake and impact. Fast-dissolving tablets (FDT) of Newcastle disease virus (NDV) vaccine were produced by freeze drying the LaSota NDV strain combined with excipients into tablets containing a small number of doses and packaged in polymer blister sheets. The NDV-FDT vaccine maintained virus stability for more than six months at 4°C, based on plaque assay and egg infectivity dose data. Stability was further confirmed in a challenge study, where the tablet vaccine elicited a strong immune response and provided 100 per cent protection to vaccinated chickens infected with a virulent strain of NDV. The vaccine tablet can be diluted in water (no needle or syringe required) and administered either in drinking water or with a dropper via an intraocular and/or intransal route. Results indicate that FDTs containing a small number of doses are a feasible presentation for backyard poultry farmers. The compact packaging of the FDTs will also provide cost savings in storing and distributing the vaccine in the cold chain.

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.

Diffusion tensor imaging in the assessment of normal-appearing brain tissue damage in relapsing neuromyelitis optica.

BACKGROUND AND PURPOSE: Normal-appearing brain tissue (NABT) damage was established in multiple sclerosis by histology, MR spectroscopy, magnetization transfer imaging and diffusion tensor imaging (DTI). However, whether this phenomenon can be detected in relapsing neuromyelitis optica (RNMO) remains unclear. The aim of this study was to use DTI to investigate the presence of NABT damage in RNMO patients and its possible mechanism. METHODS: Conventional MR imaging and DTI scans were performed in 16 patients with RNMO without visible lesions on brain MR imaging and in 16 sex- and age-matched healthy control subjects. Histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA) was performed in the entire brain tissue (BT), white matter (WM), and gray matter (GM). Region of interest (ROI) analysis of MD and FA was also performed in WM regions connected with the spinal white matter tracts or optic nerve (including medulla oblongata, cerebral peduncle, internal capsule, and optic radiation), in corpus callosum without direct connection with them, and in some GM regions. RESULTS: From histogram analysis, we found the RNMO group had a higher average MD of the BT, WM, and GM, a lower average MD peak height and a higher average MD peak location of the GM, and a higher average FA peak height of the WM than did the control group. From ROI analysis, compared with control subjects, RNMO patients had a higher average MD and a lower average FA in ROIs of WM connected with the spinal white matter tracts or optic nerve and a normal average MD and FA in corpus callosum without direct connection with them. In addition, a high average MD was found in parietal GM in these patients. CONCLUSIONS: Our findings confirm the presence of abnormal diffusion in brain tissue in patients with RNMO and suggest that secondary degeneration caused by lesions in the spinal cord and optic nerve might be an important mechanism for this abnormality.

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.