Inhibition of orthotopic castration-resistant prostate cancer growth and metastasis in mice by JC VLPs carrying a suicide gene driven by the PSA promoter.

Metastatic castration-resistant prostate cancer (mCRPC) is challenging to treat. Virus-like particles (VLPs), originating from JC polyomavirus (JCPyV) and carrying a suicide gene driven by the PSA promoter (PSAtk-VLPs), can inhibit tumor growth in animal models of human prostate cancer. However, the efficacy of suppression of orthotopic PCa growth and metastasis by PSAtk-VLPs remains undetermined. Here, we established an iRFP stable expression CRPC cell line suitable for deep-tissue observation using fluorescence molecular tomography (FMT). These cells were implanted into murine prostate tissue, and PSAtk-VLPs were systemically administered via the tail vein along with the prodrug ganciclovir (GCV), allowing for the real-time observation of orthotopic prostate tumor growth and CRPC tumor metastasis. Our findings demonstrated that systemic PSAtk-VLPs administration with GCV and subsequent FMT scanning facilitated real-time observation of the suppressed growth in mouse iRFP CRPC orthotopic tumors, which further revealed a notable metastasis rate reduction. Systemic PSAtk-VLPs and GCV administration effectively inhibited orthotopic prostate cancer growth and metastasis. These findings suggest the potential of JCPyV VLPs as a promising vector for mCRPC gene therapy. Conclusively, systemically administered JCPyV VLPs carrying a tissue-specific promoter, JCPyV VLPs can protect genes within the bloodstream to be specifically expressed in specific organs.

Suppression of bone metastatic castration-resistant prostate cancer cell growth by a suicide gene delivered by JC polyomavirus-like particles.

Prostate cancer is one of the most common cancers in men. The heterogeneity and mutations exhibited by prostate cancer cells often results in the progression to incurable metastatic castration-resistant prostate cancer (mCRPC). Our previous investigations demonstrated that the virus-like particles (VLPs) of JC polyomavirus (JCPyV) can deliver exogenous genes to prostate cancer cells for expression. JCPyV VLPs packaging pPSAtk (PSAtk-VLPs) possess the ability to transcriptionally target and selectively induce cytotoxicity in prostate cancer cells in vitro and in vivo, as pPSAtk can only express the thymidine kinase gene, a suicide gene, in androgen receptor-positive cells. To further investigate whether PSAtk-VLPs inhibit the growth of metastasized prostate cancer cells, we established an animal model of bone-metastatic prostate cancer to compare PSAtk-VLPs with leuprorelin acetate and enzalutamide, hormonal agents commonly used in clinical settings, and investigated the effectiveness of PSAtk-VLPs. In the present study, we observed that PSAtk-VLPs effectively inhibited the growth of prostate cancer cells that had metastasized to the bone in the metastatic animal model. In addition, PSAtk-VLPs showed a higher effectiveness than hormone therapy in this animal model study. These results suggest that PSAtk-VLPs may serve as a treatment option for mCRPC therapy in the future.

Fear of falling as a potential complication of Ramsay Hunt syndrome in older adults: a case report.

BACKGROUND: Fear of falling (FOF) is a common and major health concern in older adults. The consequences of FOF include reduced physical performance, social activity, and health-related quality of life. Ramsay Hunt syndrome (RHS) is a herpes zoster-related facial nerve dysfunction accompanied by an erythematous vesicular rash on the ear or mouth that may complicate ipsilateral facial paralysis and otalgia, vertigo, tinnitus, hearing loss, and meningoencephalitis. However, repeated falls and subsequent FOF due to RHS have not been reported in older adults. CASE PRESENTATION: A 65-year-old woman diagnosed with RHS experienced repeated falls during hospital admission and after discharge. Despite recovery of balance and no subsequent falls, the patient presented with persistent FOF at the geriatric outpatient follow-up visit 1 year after the RHS episode. The fear sensation impaired the patient's instrumental daily activities and was confirmed by documentation of serial comprehensive geriatric assessments, especially the Timed Up and Go test scores. CONCLUSIONS: RHS may cause repeated falls and FOF, leading to impairment in daily activities and psychosocial function in older adults. Therefore, clinicians should be mindful of falls and FOF when caring for older patients with RHS and should develop multidimensional strategies for fall prevention and FOF.

Difference of antihypertensive prescribing between office- and hospital-based clinics in Taiwan.

BACKGROUND: The geographical location and medical facility may affect the pattern of antihypertensive prescriptions. Information regarding the correlation between the prescription and health care faculties in different geographical locations was lacking. OBJECTIVE: The aim of this study was to compare differences in the prescribing of antihypertensives between hospital-based clinics (hospital arm) and office-based clinics (office arm) in different geographical locations in Taiwan. METHOD: We collected data from the National Health Insurance database of Taiwan to carry out a population-based, retrospective cohort analysis of 3,218,794 patients newly diagnosed with hypertension in the period January 1, 1997 to December 31, 2004. Eligible participants were classified into either of two groups based on the level of health care faculty: hospital arm and office arm. The covariates composed of age, gender, antihypertensive regimens, urbanization status, comorbidity, and Charlson comorbidity index. RESULTS: There were 2,028,784 cases (63.0 %) for the hospital arm and 1,190,010 (37 %) for the office arm. In the hospital-based arm, there were 168,933 (8.3 %) patients diagnosed with diabetes mellitus, 166,110 (8.2 %) patients diagnosed with coronary artery disease, 147,465 (7.3 %) patients diagnosed with cerebrovascular accident, 86,866 (4.3 %) patients diagnosed with chronic kidney disease, 74,525 (3.7 %) patients diagnosed with benign prostatic hyperplasia, 55,517 (2.7 %) patients diagnosed with congestive heart failure. The all comorbidities in the hospital arm had significantly higher proportions than those in the office arm (p < 0.001). The Charlson comorbidity index in the hospital arm was higher than that in the office arm (p < 0.001). Physicians who practiced in the office arm prescribed polytherapy less often than those in the hospital arm (OR = 0.68, 95 % CI: 0.67-0.68). For overall urbanization status, the adjusted OR of polytherapy prescriptions in the aging city (OR = 1.08, 95 % CI: 1.05-1.12) was higher than other type cities. The highest urbanization-specific OR of polytherapy prescriptions was observed for highly urbanized city in the hospital arm (OR = 1.20, 95 % CI: 1.18-1.23) and aging city in the office arm (OR = 1.42, 95 % CI: 1.21-1.67). In the both arm, patients with lower CCI showed decreased risk of polytherapy prescription. CONCLUSION: The antihypertensive prescriptions in the clinical practices were different between the hospital arm and the office arm in the different health care, comorbidity, and urbanization status. During the study period, the proportion of antihypertensive polytherapy had declined.

Depression as a predictor of falls amongst institutionalized elders.

OBJECTIVE: In this study, we set out to examine the combined effects of medical condition and depression status on fall incidents amongst institutionalized elderly people. METHODS: A cross-sectional study was carried out to investigate the fall history of institutionalized elders involving 286 subjects. Experiences of falls over the previous year were recorded, with at least two falls during the prior one-year period, or one injurious fall defined as 'fallers'. The Geriatric Depression Scale-15 was used as a screening instrument for depression status. RESULTS: Based on a multivariate logistic regression and stratification analysis, depression was found to have enhanced effects with various medical conditions on fall risk. As compared with the non-depressive reference group, a five-fold fall risk was discernible amongst depressed elders with multiple medications, whilst a six-fold risk was found amongst depressive elders using ancillary devices, along with a 11-fold amongst depressive elders with neural system diseases. CONCLUSIONS: This study provides the evidence of enhancing effects between depression and medical conditions on the risk of falls amongst institutionalized elderly people. Thus, depressed elders with neural system diseases, using ancillary devices or multiple medications, should be specifically listed as very high risk of falling amongst institutionalized elderly, and strictly prevent them from falls. Screening and treatment of depression could also be a useful strategy in the prevention of falls amongst institutionalized elderly with poor medical condition.

Adherence to available clinical practice guidelines for initiation of antihypertensive medication in patients with or without diabetes mellitus and other comorbidities in Taiwan.

The aim of the study is to explore the prescribing trends for antihypertensive medications in newly diagnosed hypertensive subjects with different comorbidities with or without diabetes in Taiwan. Factors for prescribing angiotensin receptor blockers (ARBs) are also investigated. The study design is a secondary data analysis of Taiwanese population from the National Health Insurance, from 1997, to 2004. A total of 3 218 187 patients were included in the statistical analysis; there were 2 963 861 cases without diabetes and 254 326 with diabetes. From 1998 to 2004, in both arms, there were significant trends for increasing ARB use (ρ = 0.964, P < .001). Patients with preexisting diabetes were more likely to be prescribed ARBs than those without preexisting diabetes (OR = 1.68; 95% CI, 1.65-1.70). A similar situation was noted for patients with the comorbidities of cerebrovascular accident (OR = 1.61), congestive heart failure (OR = 2.20), coronary artery disease (OR = 1.63), and chronic kidney disease (OR = 2.23). Although diuretics were not the most commonly prescribed antihypertensive for nondiabetics during the study period, physicians' prescribing practices were within the range of published clinical practice guidelines for hypertension management. Further comprehensive studies are needed to explore the impact of prescription patterns, especially ARBs, on the allocation of health care resources and therapeutic efficacy in Taiwan.

Incidence of cardiovascular events in which 2 thiazolidinediones are used as add-on treatments for type 2 diabetes mellitus in a Taiwanese population.

BACKGROUND: Thiazolidinediones (TZDs) are oral antihyperglycemic drugs that are used to treat insulin resistance. Rosiglitazone is a TZD that has been found to increase the risk of cardiovascular events, especially of myocardial ischemic events. OBJECTIVE: The aim of this study was to conduct a direct comparison of TZDs (pioglitazone and rosiglitazone) and their relationship to cardiovascular events (myocardial infarction [MI], angina, congestive heart failure [CHF], and cerebral vascular accident [CVA]) in Taiwanese patients with type 2 diabetes mellitus (DM). METHODS: A retrospective study with second data analysis was performed from January 1, 1998, to December 31, 2006. We selected those who were prescribed only 1 kind of TZD for at least 120 days in the 180-day period; those who switched to another TZD during the above-mentioned periods and had cardiovascular events before the use of TZD were excluded. Stringent definitions for MI, angina, CHF, and CVA were set, and survival analysis was performed. RESULTS: A total of 7725 type 2 DM cases were included in the final analysis. In our model, the hazard ratio (HR) for development of MI in rosiglitazone-treated patients was 0.539 (95% CI, 0.327-0.889; P = 0.015) compared with pioglitazone-treated patients for whom age, gender, medical specialist, duration of DM, and histories of antihypertensive, statin, and fibrate medications were controlled. There were no significant differences in HRs among angina (HR = 0.543; 95% CI, 0.293-1.006; P = 0.052), CHF (HR = 0.820; 95% CI, 0.619-1.086; P = 0.166), and CVA (HR = 0.949; 95% CI, 0.724-1.244; P = 0.705) groups. Antihypertensive and statin therapy led to significantly different HRs for cardiovascular events depending on when they were first prescribed. If statins were prescribed after TZD, the HR relative to patients who never used statins was 3.896 for MI (95% CI, 2.071-7.328; P < 0.001), 3.194 for angina (95% CI, 1.514-6.737; P = 0.002), and 1.303 for CHF (95% CI, 1.011-1.678; P = 0.041). If antihypertensives were prescribed after TZD, the HR relative to patients never treated with antihypertensives was 7.654 for angina (95% CI, 1.922-32.921; P = 0.004), 3.900 for CHF (95% CI, 2.437-6.242; P < 0.001), 2.242 for CVA (95% CI, 1.613-3.116; P < 0.001), and 2.325 for MI (95% CI, 1.109-4.873; P = 0.026). CONCLUSIONS: Our data suggested that, as an add-on treatment for diabetic patients, rosiglitazone had significantly lower HRs for MI compared with those for pioglitazone. Diabetic hypertensive patients treated with TZD were at a high risk for angina, CHF, CVA, and MI, whereas statin use increased the risk for MI, angina, and CHF. There are some potential limitations to this study owing to the analysis methodology and retrospective design. In addition, all enrolled type 2 DM patients were treated with TZD medications, but diabetes patients treated with nonpharmacologic therapy, including lifestyle modifications, were not included.

White blood cell count and psychomotor cognitive performance in the elderly.

BACKGROUND: White blood cell (WBC) count is associated with many inflammatory diseases such as cardiovascular disease, diabetes and hypertension. Research on the relationship of WBC count and cognition in the elderly is relatively sparse. This study examined the association between WBC count and cognitive performance in older adults. METHODS: Data from the National Health and Nutrition Examination Survey (1999-2002) containing 1670 older adults were analysed. Every subject completed a household interview, examination of digit symbol substitution test (DSST) scores, WBC count measurement and a questionnaire regarding personal health. WBC count was restricted to the normal range and divided into quartiles, using a multiple hierarchical regression model to estimate the relationship between WBC counts and DSST scores. Quartile-based analysis with an extended-model approach was used for further covariates adjustment. Trends test examining the associations across increasing quartiles of WBC counts and DSST scores were also conducted. RESULTS: In the multiple hierarchical regression model, the ß coefficient, representing the change of DSST scores for each 1000 cells uL(-1) increase in WBC count, was -0·097 (R(2) = 0·343, P < 0·001). After additional competent covariates adjustment, the negative correlation remained (all P < 0·001). In quartile-based multiple linear regression, the negative trends between DSST scores and WBC count quartiles in the stratified comparison with extended-model approach were all statistically significant (P for trends <0·001). CONCLUSIONS: Higher WBC counts, even within the normal range, were associated with poor psychomotor cognitive performance in the elderly.

Pheochromocytoma presented as intestinal pseudo-obstruction and hyperamylasemia.

Pheochromocytoma has wide variations in alimentary presentations and complications. Here, we report a patient with pheochromocytoma who developed intestinal pseudo-obstruction and hyperamylasemia. The intestinal pseudo-obstruction responded promptly to intravenous infusions of phentolamine, an alpha-adrenergic blocker managed to control hypertensive crisis. The hyperamylasemia regressed gradually after resection of the tumor. The role of catecholamines liberated from the tumor is discussed in the associated pathogenesis. Early recognition of pheochromocytoma with gastrointestinal manifestations will facilitate proper management and prevent possible lethal outcome.

Changes in drug prescription utilization for diabetic and hypertensive outpatients after initiation of the National Health Insurance's Global Budget Program in Taiwan.

BACKGROUND: To examine changes in medicine utilization and prescription trends for diabetic (DM) and hypertensive (HT) patients upon initiation of the National Health Insurance (NHI) global budget (GB) program in Taiwan. MATERIAL/METHODS: Data on hospital-based outpatient prescriptions for DM and HT from the Taipei branch before and after the GB were analyzed from January 2002 to December 2004. A secondary analysis of reimbursed data, with descriptive and trend analyses of the four indicators, daily oral medication cost, daily tablets used, medicine items per prescription, and tablet cost, was conducted. RESULTS: The comparisons of before and after the GB were as follows: Daily oral medication cost increased from US $0.585 to $0.956 (64%) for the DM group and from $1.01 to $1.07 (6.12%) for the HT group. The increments for daily used tablets, medicine items per prescription, and tablet cost were 33.3%, 17.9%, and 26.5% for the DM group and 6.65%, 3.31%, and 0.27% for the HT group. Indicators for the DM group not only increased significantly compared with those of the HT group, but also had higher adjusted beta coefficients. The comparisons of before and after the GB showed that the increments for the DM group decreased slightly, but not those for the HT group. CONCLUSIONS: The indicators for DM were significantly higher than those of HT group during the implementation phase of the GB. The GB program implemented by the NHI in Taiwan slightly slowed the trend of hospital-based ambulatory prescription costs of DM, but not HT.

Bell's palsy associated with influenza vaccination: two case reports.

The etiology of Bell's palsy is often unknown. We present herein two cases of adults who developed a Bell's palsy following the administration of an influenza vaccine. While the incidence is low, with the widespread recommendation for annual influenza vaccines, patients should be apprised of the possibility of this complication and the benefit of early treatment.

Cost benefits of targeting the pneumococcal vaccination program to the elderly population in Taiwan.

BACKGROUND: Because of the continuing rise in pneumococcal vaccine costs and limits on funding of such costs, vaccination priorities in Taiwan were assessed. METHODS: Data of a randomly selected sample of 200,448 people were analyzed to identify the highest risk groups. Patients were subgrouped on the basis of age and gender, and estimates were made of cumulative admissions, pneumonia recurrence rate, and associated costs of hospital care and medical treatment over the period 1997-2002 for each subgroup. RESULTS: The per capita costs of medical treatment for pneumonia in those aged 65 years or above were found to be highest in those with chronic lung disease (19,906,086 US dollars), heart disease (19,692,769 US dollars), and diabetes mellitus (8,613,973 US dollars). CONCLUSION: Elderly adults over age 65 years with these chronic diseases should be considered high-priority candidates for pneumococcal vaccination.

Preferences of the elderly and their primary family caregivers in the arrangement of long-term care.

BACKGROUND AND PURPOSE: Long-term care policies and networks in Taiwan are still in the early stages of development and as such it is important to establish comprehensive care models which clearly define the needs of the elderly and their family members. This study examined the preferences of the elderly and their primary family caregivers in long-term care arrangements. METHODS: Using multi-stage sampling, a total of 1180 subjects (n = 593 elderly people [age > or = 65 years] and n = 587 caregivers) from 7 counties/cities in the north of Taiwan were interviewed by local public health nurses. RESULTS: Home care was the first choice for both elderly people and their primary caregivers (59.2% of both groups combined). Institutional care was considered the second choice; however, only 9.2% found this choice acceptable. Community-based care was the least preferred mode of long-term care (4.2%). Among the sample subjects, elderly people born in China, those not living in the Taipei metropolitan area, and those not receiving a financial subsidy from the government, indicated that they would be more inclined to accept institutional care. All other elderly people between the ages of 65 and 74 years indicated greater preference for community-based care. Primary caregivers born in China, those with only an elementary school level of education, and those with previous unpleasant experiences in caring for the elderly were more inclined to accept community and institutional care. CONCLUSIONS: Most elderly people and their primary family caregivers preferred home care. This study also revealed that previous experiences with care for the elderly, educational level, and socioeconomic status were important factors influencing preferences for long-term care arrangements.

Influenza and pneumococcal vaccination of the elderly in Taiwan.

In 1998, Taiwan became the first country in Asia to provide free influenza vaccination to high-risk groups, mainly the elderly. The purpose of this study is to determine: (1) the annual mortality rate from influenza and pneumococcal-related illnesses such as pneumonia, chronic bronchitis, pulmonary emphysema and asthma and (2) the effectiveness of and adverse events associated with the influenza vaccination. In the elderly, influenza vaccination caused the annual death rate due chronic bronchitis, pulmonary emphysema, and asthma to decline steadily but had no effect on the annual pneumonia death rate. The only adverse effect of concern was vertigo (in approximately 2-3%).

Prescription patterns of hypertension--National Health Insurance in Taiwan.

BACKGROUND: Hypertension is a universal disease. Treatment patterns of hypertension provide valuable information for clinicians. Therefore, we present the patterns of antihypertensive medications in Taiwan by their pharmacological classifications, breaking down by patients' ages and genders. METHODS: A descriptive and cross-sectional analysis was performed. Claims from the National Health Insurance of Taiwan were used and included all ambulatory cares of 21 million people from July 1, 1997 to June 30, 1998. A total of 9,717,960 visits with 16,595,030 matched records of antihypertensive medications were obtained. Hypertensive medications were divided into 5 main categories; monotherapy and multiple therapy were defined and discussed separately. Frequency and proportion of utilization of antihypertensive medication were charted and figured. RESULTS: The most frequently prescribed antihypertensive medications were: calcium antagonists: 5,332,527 records (54.9% of enrolled visits); beta-blockers: 4,230,843 records (43.5%); angiotensin converting enzyme inhibitors (ACEIs): 3,057,009 records (31.5%); diuretics: 2,255,838 records (23.2%); and "others": 1,647,100 records (16.9%). Regardless of gender, the top 2 prescription patterns were calcium antagonists and beta-blockers for monotherapy, beta-blockers + calcium antagonists and ACEIs + calcium antagonists for multiple therapy. CONCLUSIONS: Although Taiwan is a country with National Health Insurance, patterns of pharmacologic treatment of hypertension in Taiwan are close to those in the US, not to those of countries in Europe. Also, these treatments were tailored to the conditions of the patients.