Production of prostaglandin e(2) by iridial melanocytes exposed to latanoprost acid, a prostaglandin F(2 alpha) analogue.

Several prostaglandin analogues used for glaucoma treatment cause increased pigmentation of the iris. The purpose of the present study was investigate whether latanoprost, a PGF(2 alpha) analogue, has any effect on the production of endogenous prostaglandins in iridial melanocytes, which could be important in the mechanism leading to increased pigmentation. Bovine and human iridial melanocytes in culture were used for the experiments. Production of endogenous prostaglandins was measured by enzyme immunoassay, and the melanin content was measured spectrophotometrically. In bovine iridial melanocytes, latanoprost acid caused a significant increase of the PGE(2) production, which could be blocked by indomethacin and NS398, indicating an involvement of cyclo-oxygenase 2. In order to study the selectivity of the phenomenon other endogenous substances/drugs were tested, e.g., acetylcholine, carbachol, noradrenaline, neuropeptide Y, substance P and alpha-MSH, but none was found to have any significant effect. Human iridial melanocytes also responded to latanoprost acid with increased production of PGE(2) and in 1 out of 5 individuals increased melanogenesis coincided with increased PGE(2) production. In bovine iridial melanocytes, latanoprost acid did not stimulate melanogenesis. These results indicate that latanoprost acid cause enhanced formation of endogenous prostaglandins that may have auto- and/or paracrine effects in the melanocytes, possibly associated with melanogenesis.     

The Methodological Quality of Economic Evaluations of Guideline Implementation into Clinical Practice: A Systematic Review of Empiric Studies

OBJECTIVES: Despite the emphasis on efficiency of health-care services delivery, there is an imperfect evidence base to inform decisions about whether and how to develop and implement guidelines into clinical practice. In general, studies evaluating the economics of guideline implementation lack methodological rigor. We conducted a systematic review of empiric studies to assess advances in the economic evaluations of guideline implementation. METHODS: The Cochrane Effective Professional and Organisational Change Group specialized register and the MEDLINE database were searched for English publications between January 1998 and July 2004 that reported objective effect measures and implementation costs. We extracted data on study characteristics, quality of study design, and economic methodology. It was assessed whether the economic evaluations followed methodological guidance. RESULTS: We included 24 economic evaluations, involving 21 controlled trials and three interrupted time series designs. The studies involved varying settings, targeted professionals, targeted behaviors, clinical guidelines, and implementation strategies. Overall, it was difficult to determine the quality of study designs owing to poor reporting. In addition, most economic evaluations were methodologically flawed: studies did not follow guidelines for evaluation design, data collection, and data analysis. CONCLUSIONS: The increasing importance of the value for money of providing health care seems to be reflected by an increase in empiric economic evaluations of guideline implementation. Because of the heterogeneity and poor methodological quality of these studies, however, the resulting evidence is still of limited use in decision-making. There seems to be a need for more methodological guidance, especially in terms of data collection and data synthesis, to appropriately evaluate the economics of developing and implementing guidelines into clinical practice.     

Fatal disseminated Acanthamoeba lenticulata infection in a heart transplant patient

We report a fatal case of disseminated acanthamebiasis caused by Acanthamoeba lenticulata (genotype T5) in a 39-year-old heart transplant recipient. The diagnosis was based on skin histopathologic results and confirmed by isolation of the ameba from involved skin and molecular analysis of a partial 18S rRNA gene sequence (DF3).     

Reported versus measured body weight and height of 4-year-old children and the prevalence of overweight

BACKGROUND: In adults, body weight tends to be underestimated when based on self-reported data. Whether this discrepancy between measured and reported data exists in healthy young children is unclear. We studied whether parental reported body weight and height of 4-year-old children corresponded with measured body weight and height. In addition, we studied the determinants and the consequences of differences between reported and measured data. METHODS: Data on body weight and height of 864 4-year-old Dutch children born in 1996/1997 enrolled in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study were collected via a questionnaire and a medical examination. Overweight was defined according to standard international age and gender specific definitions. RESULTS: Mean differences between measured and reported body weight, height, and body mass index (BMI) were small. Parents of children with a low BMI tended to over report body weight while parents of children with a high BMI tended to underreport body weight. Whereas 9.5% of the children were overweight according to reported BMI, the prevalence of overweight was 13.4% based on measured BMI. Over 45% of the overweight children according to measured BMI were missed when reported BMI was used. CONCLUSION: These findings suggest that overweight prevalence rates in children are underestimated when based on reported weight and height.     

Aging, retirement, and changes in physical activity: prospective cohort findings from the GLOBE study

There is increased recognition that determinants of health should be investigated in a life-course perspective. Retirement is a major transition in the life course and offers opportunities for changes in physical activity that may improve health in the aging population. The authors examined the effect of retirement on changes in physical activity in the GLOBE Study, a prospective cohort study known by the Dutch acronym for "Health and Living Conditions of the Population of Eindhoven and surroundings," 1991-2004. They followed respondents (n = 971) by postal questionnaire who were employed and aged 40-65 years in 1991 for 13 years, after which they were still employed (n = 287) or had retired (n = 684). Physical activity included 1) work-related transportation, 2) sports participation, and 3) nonsports leisure-time physical activity. Multinomial logistic regression analyses indicated that retirement was associated with a significantly higher odds for a decline in physical activity from work-related transportation (odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.97, 4.65), adjusted for sex, age, marital status, chronic diseases, and education, compared with remaining employed. Retirement was not associated with an increase in sports participation (OR = 1.12, 95% CI: 0.71, 1.75) or nonsports leisure-time physical activity (OR = 0.80, 95% CI: 0.54, 1.19). In conclusion, retirement introduces a reduction in physical activity from work-related transportation that is not compensated for by an increase in sports participation or an increase in nonsports leisure-time physical activity.     

Changes in medical end-of-life practices during the legalization process of euthanasia in Belgium

Changes in medical practices during transitions in regulating healthcare are rarely investigated. In this study, we investigated changes in medical end-of-life decisions with a possible or certain life-shortening effect (ELDs) that occurred during the legalization process of euthanasia in Belgium. We took representative random samples from deaths reported to registries in Flanders, Belgium in 1998 (n=3999) at the beginning of the process and in 2001 (N=5005), at the end of the process. The reporting physicians received an anonymous mail questionnaire about possible ELDs preceding the death involved. We found no significant shifts in the epidemiology of diseases between 1998 and 2001. The overall incidence of ELDs did not change. The incidence decreased for euthanasia, administering life-ending drugs without patient's explicit request, and alleviation of pain and symptoms with life-shortening co-intention. Incidence increased for alleviation of pain and symptom without life-shortening intention, and remained stable for non-treatment decisions. All decisions in 2001 were more often discussed with patients, their relatives and nurses. In 2001, continuous deep sedation was reported in 8.3% of deaths. We can conclude that physicians' end-of-life practices have substantially changed during the short but tumultuous legalization process of euthanasia in Belgium. Although follow-up research is needed to investigate the continuance of these changes, it is important for policy makers to keep in mind that social factors related to transitions in healthcare regulation may play an important role in the physicians' actual behaviour.     

Use of Medications of Questionable Benefit During the Last Year of Life of Older Adults With Dementia

Objectives

To investigate the prevalence and factors associated with the use of medications of questionable benefit throughout the final year of life of older adults who died with dementia.

Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: insight into the role of structure and size

Purpose

The direct effects of galacto-oligosaccharides (GOS), including Vivinal^® GOS syrup (VGOS) and purified Vivinal^® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure–activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin.

Methods

Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA.

Results

In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release.

Conclusions

This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.

     

Socioeconomic inequalities in homicide mortality: a population-based comparative study of 12 European countries

Recent research has suggested that violent mortality may be socially patterned and a potentially important source of health inequalities within and between countries. Against this background the current study assessed socioeconomic inequalities in homicide mortality across Europe. To do this, longitudinal and cross-sectional data were obtained from mortality registers and population censuses in 12 European countries. Educational level was used to indicate socioeconomic position. Age-standardized mortality rates were calculated for post, upper and lower secondary or less educational groups. The magnitude of inequalities was assessed using the relative and slope index of inequality. The analysis focused on the 35–64 age group. Educational inequalities in homicide mortality were present in all countries. Absolute inequalities in homicide mortality were larger in the eastern part of Europe and in Finland, consistent with their higher overall homicide rates. They contributed 2.5?% at most (in Estonia) to the inequalities in total mortality. Relative inequalities were high in the northern and eastern part of Europe, but were low in Belgium, Switzerland and Slovenia. Patterns were less consistent among women. Socioeconomic inequalities in homicide are thus a universal phenomenon in Europe. Wide-ranging social and inter-sectoral health policies are now needed to address the risk of violent victimization that target both potential offenders and victims.     

Cultural differences affecting euthanasia practice in Belgium: one law but different attitudes and practices in Flanders and Wallonia

Since 2002, Belgium has had a national law legalising euthanasia. The law prescribes several substantive due care requirements and two procedural due care requirements, i.e. consultation with an independent physician and reporting of euthanasia to a Federal Control Committee. A large discrepancy in reporting rates between the Dutch-speaking (Flanders) and the French-speaking (Wallonia) parts of Belgium has led to speculation about cultural differences affecting the practice of euthanasia in both regions. Using Belgian data from the European Values Study conducted in 2008 among a representative sample of the general public and data from a large-scale mail questionnaire survey on euthanasia of 480 physicians from Flanders and 305 from Wallonia (conducted in 2009), this study presents empirical evidence of differences between both regions in attitudes towards and practice of euthanasia. Acceptance of euthanasia by the general population was found to be slightly higher in Flanders than in Wallonia. Compared with their Flemish counterparts, Walloon physicians held more negative attitudes towards performing euthanasia and towards the reporting obligation, less often labelled hypothetical cases correctly as euthanasia, and less often defined a case of euthanasia having to be reported. A higher proportion of Flemish physicians had received a euthanasia request since the introduction of the law. In cases of a euthanasia request, Walloon physicians consulted less often with an independent physician. Requests were more often granted in Flanders than in Wallonia (51% vs 38%), and performed euthanasia cases were more often reported (73% vs 58%). The study points out some significant differences between Flanders and Wallonia in practice, knowledge and attitudes regarding euthanasia and its legal requirements which are likely to explain the discrepancy between Wallonia and Flanders in the number of euthanasia cases reported. Cultural factors seem to play an important role in the practice of (legal) euthanasia and the extent to which legal safeguards are followed.