The utility of a non-verbal prospective memory measure as a sensitive marker for early-stage Alzheimer's disease in Hong Kong.

ABSTRACT Background: With the proportion of older adults in Hong Kong projected to double in size in the next 30 years, it is important to develop measures for detecting individuals in the earliest stage of Alzheimer's disease (AD, 0.5 in Clinical Dementia Rating, CDR). We tested the utility of a non-verbal prospective memory task (PM, ability to remember what one has to do when a specific event occurs in the future) as an early marker for AD in Hong Kong Chinese. Methods: A large community dwelling sample of older adults who are healthy controls (CDR 0, N = 125), in the earliest stage of AD (CDR 0.5, N = 125), or with mild AD (CDR 1, N = 30) participated in this study. Their reaction time/accuracy data were analyzed by mixed-factor analyses of variance to compare the performance of the three CDR groups. Logistic regression analyses were performed to test the discriminative power of these measures for CDR 0 versus 0.5 participants. Results: Prospective memory performance declined as a function of AD severity: CDR 0 > CDR 0.5 > CDR 1, suggesting the effects of early-stage AD and AD progression on PM. After partialling out the variance explained by psychometric measures (e.g., ADAS-Cog), reaction time/accuracy measures that reflected the PM still significantly discriminated between CDR 0 versus 0.5 participants in most of the cases. Conclusion: The effectiveness of PM measures in discriminating individuals in the earliest stage of AD from healthy older adults suggests that these measures should be further developed as tools for early-stage AD discrimination.

Effects of education on very mild dementia among Chinese people in Hong Kong: potential mediators in the Cantonese Mini-Mental State Examination tasks.

BACKGROUND: In Hong Kong, older Chinese adults generally have a low level of education. This study examined the effect of education on very mild Alzheimer's disease (AD), as quantified by Clinical Dementia Rating (CDR) scale (CDR 0.5 versus 0), in a Chinese community. The Cantonese version of the Mini-Mental State Examination (C-MMSE) was used to estimate cognitive abilities that were related to the level of education, and that in turn serve as protective factors for AD. METHODS: A total of 788 community-dwelling older adults (383 CDR 0 and 405 CDR 0.5) were recruited in this cross-sectional study, which was derived from a population-based prevalence project. The participants' number of years of education and C-MMSE scores were used to predict their CDR scores using logistic regression and the mediation effects of C-MMSE scores were analyzed. RESULTS: Consistent with previous studies, the chance of being rated as having very mild AD increased with age, but decreased with years of education, among the older adult community of Hong Kong. The effect of education on very mild dementia was weakened substantially when C-MMSE scores were included as mediating variables. CONCLUSIONS: The findings indicate that the protective effects of education on dementia were mediated by an enhancement of older adults' performance on some C-MMSE items, including attention and orientation to time and place.

Postoperative outcomes in vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.

BACKGROUND: Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM: We sought to compare 30-day postoperative infectious complication rate among vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS: A retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS: One hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). CONCLUSIONS: Twenty-six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.

Effects of vedolizumab, adalimumab and infliximab on biliary inflammation in individuals with primary sclerosing cholangitis and inflammatory bowel disease.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure. AIM: To evaluate the effect of biological therapies on PSC progression in IBD patients. METHODS: We performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017. Hepatic biochemistries were compared using the paired t-test (patients served as their own controls) ≤3 months before and 6-8 and 12-14 months after biological initiation. Radiographic information of biliary stenosis and liver fibrosis were obtained via abdominal ultrasound, abdominal magnetic resonance imaging and magnetic resonance elastography. RESULTS: Use of adalimumab was associated with a significant decrease in alkaline phosphatase (ALP) after 6-8 months (P = 0.03; mean change -70 U/L, standard deviation [SD] 88 U/L) compared to vedolizumab (mean change +50 U/L, SD 142 U/L) or infliximab (mean change +37 U/L, SD 183 U/L) but the change was not significant after 12-14 months (P = 0.24). No significant decreases were observed with AST, ALT, total or direct bilirubin, elastography score or radiographic imaging of biliary tree dilation/strictures with any biological therapy after 6-8 or 12-14 months. CONCLUSIONS: Current evidence suggests that biological therapies used for the treatment of IBD are not effective treatments for PSC. Further study is needed to elucidate any potential beneficial effect of adalimumab on PSC.

Central nervous system control of hyperphagia in hypothalamic obesity: dependence on adrenal glucocorticoids.

Gold thioglucose (GTG)-treated hyperphagic obese mice exhibit a pronounced anorexia upon adrenalectomy which is reversed by the systemic administration of adrenal glucocorticoids. To determine whether the return of hyperphagia was mediated by an action of the hormones on the central nervous system, food intake and body weight were monitored in anorexic GTG-treated obese adrenalectomized mice which received a single intracerebroventricular (icv) injection of very small amounts of adrenal glucocorticoids, including cortisone, corticosterone, and dexamethasone. The responses of untreated controls and adrenalectomized control mice were also studied. To rule out possible systemic effects of icv injections of adrenal glucocorticoids, food intake and body weight were also monitored in similar mice given a single ip injection of the hormones. We found that hyperphagia was restored and weight loss abolished in anorexic GTG-treated obese adrenalectomized mice after a single icv injection of adrenal glucocorticoids; the dose of cortisone required was found to be 1/60th of that previously shown to be needed systemically to restore hyperphagia. A single ip injection of these adrenal hormones in the small amounts given icv failed to induce hyperphagia in these mice. The icv and ip injections of the adrenal glucocorticoids did not significantly affect food intake or body weight of untreated controls and adrenalectomized control mice. These findings indicate that adrenal glucocorticoids act via the central nervous system in restoring hyperphagia in anorexic GTG-treated obese adrenalectomized mice.

Corticosteroid aerosols in the treatment of asthma.

Since the 1950s, corticosteroid aerosols have proved useful in the treatment of asthma. Although their precise mechanism of action is not known, these topical agents have beneficial antiinflammatory and decongestive effects on the bronchial tree in both the allergic and nonallergic forms of this disease. Four of the newer aerosolized steroids--beclomethasone dipropionate, triamcinolone acetonide, flunisolide and budesonide--have been evaluated in clinical trials. The last drug is still investigational. Their side effects are minimal, the major ones being oral candidiasis and dysphonia. They are most effective when used prophylactically and should not be administered during acute asthmatic attacks, as insufficient amounts of drug are inhaled when the airways are obstructed. Patients must be instructed in the correct techniques of administering steroid aerosols to ensure optimal therapy.

Anorexia after adrenalectomy in gold thioglucose-treated obese mice: role of adipose tissue mass.

We have previously shown that following adrenalectomy, gold thioglucose (GTG)-treated hyperphagic obese mice exhibit anorexia, weight loss and a pronounced hypoglycemia which leads ultimately to their death. In the present study, we sought to determine whether the increased adipose tissue mass which is characteristic of GTG-treated obese mice exerted a role in the onset and development of anorexia after adrenalectomy. Accordingly, the effects of adrenalectomy on food intake, weight gain, plasma glucose and corticosterone levels were investigated in normal untreated controls, GTG-treated hyperphagic obese mice and GTG-treated non obese mice. The GTG-treated non obese mice were prepared by restricting their daily intake of chow (pair-feeding) to that consumed by normal untreated mice. After adrenalectomy, all mice were allowed free access to food. As expected, all GTG-treated hyperphagic obese mice exhibited anorexia and weight loss following adrenalectomy. In contrast, about half (52%) of the GTG-treated non obese mice exhibited anorexia and weight loss after adrenalectomy. The response of the GTG-treated non obese adrenalectomized mice was not due to differences in adrenal insufficiency since all adrenalectomized mice had blood levels of corticosterone of less than 0.5 microgram%. These findings indicate that whereas the increased adipose tissue mass of the GTG-treated obese mice appears to be associated with an increased incidence of anorexia following adrenalectomy, increased adipose tissue mass alone does not appear to be essential for the occurrence of anorexia.

Adrenalectomy induced anorexia in gold thioglucose-treated obese mice: metabolic and hormonal changes.

Adrenalectomy of gold thioglucose (GTG)-treated hyperphagic obese mice had been shown by us earlier to result in anorexia, weight loss, hypoglycemia and subsequent death of all mice. More recent studies suggest that adipose tissue mass may not be the critical determinant of anorexia since a large proportion of GTG-treated non obese (pair-fed to curb obesity) mice when challenged with adrenalectomy also developed anorexia. The aim of the present studies was to determine whether the changes in circulating metabolites, namely, glucose, free fatty acids and hormones, including insulin, glucagon and ACTH, which accompany adrenalectomy, might provide a clue to the causative agent for the onset of anorexia in GTG obese and non obese mice. Accordingly, plasma levels of glucose, free fatty acids, insulin, glucagon and ACTH were measured in GTG-treated obese, non obese and in normal untreated mice following adrenalectomy or a sham operation. Preoperatively, plasma insulin levels were significantly elevated in GTG obese mice whereas plasma glucose, free fatty acids and glucagon levels were not appreciably different than those of untreated controls. Upon adrenalectomy and onset of anorexia, GTG obese mice exhibited a progressive decline in blood glucose and insulin levels; plasma free fatty acids increased precipitously but only after the first day. Plasma glucagon levels declined immediately following adrenalectomy, however, by the 6th day postoperatively they were significantly elevated above the sham operated obese and untreated controls. Prior to adrenalectomy, the pair-fed GTG non obese mice exhibited blood glucose and insulin levels well below the levels of untreated controls and GTG obese mice whereas plasma free fatty acids and glucagon levels were markedly elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcomes measurement across the continuum of care.

Outcomes management can only be truly achieved if it is conducted using data obtained from every possible care delivery site--the entire continuum of care. The author emphasizes that designing the most appropriate information infrastructure for an integrated health system requires a thorough understanding of the needs of the organization as reflected in its strategic business goals and objectives.

A model for developing longitudinal health records.

The future of population health management will focus on treatment of chronic diseases and avoidance of acute disorders for targeted populations. The key tools for managing population health must involve outcomes measurement and management, wellness/preventive programs, care management programs, and cost management. This can be achieved by the implementation of a computerized patient health record for longitudinal health information (lifetime) recording and management.

An adverse drug reaction reporting program in a community hospital.

An adverse drug reaction (ADR) surveillance program implemented in a 472-bed acute care community hospital consists of three components: specific indicators that nurses and pharmacists can use to evaluate reactions for reporting, an ADR reporting form and procedure, and innovative computerized screening for ADRs. In the program's first year, ADR reporting has increased 13-fold, and an important ADR to an antibiotic has been detected and publicized, resulting in modified prescribing patterns. Careful planning and frequent, intensive in-service training are key to the program's success.

Inhibition of human endothelial cell proliferation in vitro in response to n-butyrate and propionate.

The study aimed to investigate the effects of n-butyrate and propionate on the proliferation and viability of human endothelial cells in culture. Proliferation was assessed by a 24-hour bromodeoxyuridine pulse labelling and immunoperoxidase method and viability was assessed by a colorimetric viability (MTT) assay. Endothelial cells were isolated from human umbilical vein by collagenase digestion. Experiments were performed on 96-well plates and cultures were exposed to different concentrations of n-butyrate and propionate for 2 days. n-butyrate and propionate caused significant reductions in the proliferation of endothelial cells at concentrations of 1.25 mM and 10 mM respectively (p less than 0.05); the reduction in proliferation was dose-dependent for both agents. n-butyrate was a more potent inhibitor of proliferation than propionate. However, there were no significant effects on the viability of the cells with both agents up to the highest concentrations tested (25 mM). The data indicate that n-butyrate and propionate inhibit endothelial cell proliferation which may contribute to the pathogenic effects of dental plaque in periodontal disease.

Baker's asthma (grain-dust-induced asthma).

A 48-year-old black male with no underlying atopy developed asthma after working nine years at a bakery. The attacks of wheezing were preceded by nasal symptoms and usually occurred after several hours of work. Skin testing revealed reactivity to dust, molds, and wheat extracts; serum level of IgE was normal, and a RAST screen to common allergens was negative. A bronchial provocation test using commercial wheat extract was negative, but the same test using the patient's own bakery flour resulted in an immediate positive reaction. The pathogenesis and management of grain-dust-induced asthma are discussed.