Spatial distribution of avoidable cancer deaths in Germany

Aim

To investigate the spatial distribution of avoidable cancer mortality (ACM) rates in Germany and to identify small areas with exceptionally high rates using districts (Landkreise/Kreise and kreisfreie St?dte) as a unit of analysis. Avoidable cancer mortality reflects deaths from cancer that should not occur in the presence of effective and timely health care.

Methods

Age-standardised, average ACM rates were calculated for the period from 2000 through 2004 for each of the 439 districts in Germany using unit-record mortality data. The spatial distribution of ACM was subsequently analysed using country maps, interval estimates and regression analysis. Data on mortality and age distribution were obtained from the German Federal Statistical Office (DESTATIS) and the Federal Office for Building and Regional Planning (INKAR).

Results

We found that in women under 70?years, the highest ACM rates were seen for cancer of the breast and for cancer of the trachea, bronchus and lung, whereas in men under 70?years, the highest ACM rates were seen for cancer of the trachea, bronchus and lung, and for cancer of the colon, rectosigmoid junction, rectum, anus and anal canal. The statistically lowest mean ACM rates could be found in the south of Germany for men and women. Although the mean ACM rates in men in former East Germany were significantly higher than elsewhere in the country, they were not substantially higher than those in the west and northwest. The mean ACM rates in women were even lower in the east than in the northwest and west.

Conclusion

The spatial distribution of ACM rates in women in Germany showed a north-south gradient rather than the east-west gradient that often appears or, for sociohistorical reasons, is even assumed in the German context. When applying measures of ACM, we suggest using districts with statistically lower ACM rates than the nationwide average as a benchmark for the maximum number of excess deaths that should be considered preventable, whether within the current German context or beyond.     

Differential effects of the adenosine A1 receptor agonist adenosine amine congener on renal, femoral and carotid vascular conductance in preterm fetal sheep

1. Adenosine A(1) receptor activation is critical for endogenous neuroprotection from hypoxia-ischaemia, raising the possibility that treatment with A(1) receptor agonists may be an effective physiological protection strategy for vulnerable preterm infants. However, the A(1) receptor can mediate unwanted systemic effects, including vasoconstriction of the afferent glomerular arteriole. There is limited information on whether this occurs at doses that improve cerebral perfusion in the immature brain. 2. Therefore, in the present study, we examined whether infusion of the selective A(1) receptor agonist adenosine amine congener (ADAC) is associated with reduced renal perfusion in chronically instrumented preterm (0.7 gestation) fetal sheep. In the present study, ADAC was given in successive doses of 2.5, 5.0 and 15.0 microg, 45 min apart. 3. Treatment with ADAC was associated with a marked reduction in renal vascular conductance (and blood flow), whereas carotid conductance was increased and there was no significant effect on femoral conductance. In contrast with the stable effects of increasing ADAC dose on vascular conductance, there was a significant dose-related fall in fetal heart rate and blood pressure. 4. In conclusion, these short-term data support the concern that A(1) receptor agonist infusion can selectively impair renal perfusion, even at low doses.     

Use of an arginine‐enriched oral nutrition supplement in the healing of pressure ulcers in patients with spinal cord injuries: An observational study

Aim: Pressure ulcers are a serious secondary consequence of spinal cord injuries. The objective of the present study was to determine whether an arginine‐containing nutritional supplement can reduce the healing time of pressure ulcers in people with spinal cord injuries compared with those not consuming the supplement until full wound healing. Methods: Thirty‐four spinal cord injured patients with a grade 2, 3 or 4 pressure ulcer were prescribed two 237 mL tetrapaks/day of a supplement containing additional protein, arginine, zinc and vitamin C. Pressure ulcer healing was assessed with the Pressure Ulcer Scale for Healing tool. Results: Twenty patients consumed the nutritional supplement until full pressure ulcer healing had occurred, while 14 patients ceased consuming the supplement before full healing occurred because of intolerance, compliance or taste issues. A 2.5‐fold greater rate of healing was observed in patients consuming the supplement until full healing compared with those who ceased taking the supplement (8.5 ± 1.1 weeks vs 20.9 ± 7.0 weeks respectively; P= 0.04). There were no significant differences in age, nutritional status, gender or reason for admission between groups. Comparison of healing rates in the group consuming the supplement to full wound healing against expected rates derived from the medical literature showed a significantly shorter time‐to‐healing (grade 3 pressure ulcer: 6.5 ± 0.8 weeks vs 18.2 weeks; grade 4: 11.4 ± 2.0 weeks vs 22.1 weeks; P < 0.001). Conclusion: The present small‐scale study demonstrated the potential for specialised wound healing nutritional supplements to shorten the time to pressure ulcer healing in spinal cord injured patients.     

Beyond the barriers: family medicine residents' attitudes towards providing Aboriginal health care

Medical Education 2011: 45 : 400–406 Context Health care is one of many under‐resourced areas in Aboriginal communities in Canada. Aboriginal people have substandard health compared with the general population, yet have less access to health care services. Not only is there a paucity of Aboriginal doctors, but it also appears that few non‐Aboriginal doctors are willing or able to work in Aboriginal contexts. Objectives This study examines the attitudes of family medicine residents towards providing health care to Aboriginal patients. The goal of this study was to assess the willingness of family medicine residents to work in Aboriginal health care and to elucidate the major factors that inform these attitudes. Methods We conducted a cross‐sectional survey of an urban cohort of family medicine residents using a convenience sample. Our survey instrument consisted of a questionnaire comprising a mixture of open‐ended and closed questions. Results Although a majority (52%, n = 27) of the family medicine residents were willing to work in Aboriginal contexts, many felt underprepared to do so (40%, n = 21). Residents who have had some exposure to Aboriginal issues and have had community experiences are more likely to state an intention to work in Aboriginal settings. Conclusions The results of this study encourage the creation of educational experiences for medical residents that may promote a desire to work in Aboriginal communities.     

Valuing child health utility 9D health states with a young adolescent sample

QALYs are increasingly being utilized as a health outcome measure to calculate the benefits of new treatments and interventions within cost-utility analyses for economic evaluation. Cost-utility analyses of adolescent-specific treatment programmes are scant in comparison with those reported upon for adults and tend to incorporate the views of clinicians or adults as the main source of preferences. However, it is not clear that the views of adults are in accordance with those of adolescents on this issue. Hence, the treatments and interventions most highly valued by adults may not correspond with those most highly valued by adolescents. Ordinal methods for health state valuation may be more easily understood and interpreted by young adolescent samples than conventional approaches. The availability of young adolescent-specific health state values for the estimation of QALYs will provide new insights into the types of treatment programmes and health services that are most highly valued by young adolescents. The first objective of this study was to assess the feasibility of applying best-worst scaling (BWS) discrete-choice experiment (DCE) methods in a young adolescent sample to value health states defined by the Child Health Utility 9D (CHU9D) instrument, a new generic preference-based measure of health-related quality of life developed specifically for application in young people. The second objective was to compare BWS DCE questions (where respondents are asked to indicate the best and worst attribute for each of a number of health states, presented one at a time) with conventional time trade-off (TTO) and standard gamble (SG) questions in terms of ease of understanding and completeness. A feasibility study sample of consenting young adolescent school children (n = 16) aged 11-13 years participated in a face-to-face interview in which they were asked to indicate the best and worst attribute levels from a series of health states defined by the CHU9D, presented one at a time. Participants were also randomly allocated to receive additional conventional TTO or SG questions and prompted to indicate how difficult they found them to complete. The results indicate that participants were able to readily choose 'best' and 'worst' dimension levels in each of the CHU9D health states presented to them and provide justification for their choices. Furthermore, when presented with TTO or SG questions and prompted to make comparisons, participants found the BWS DCE task easier to understand and complete. The results of this feasibility study suggest that BWS DCE methods are potentially more readily understood and interpretable by vulnerable populations (e.g. young adolescents). These findings lend support to the potential application of BWS DCE methods to undertake large-scale health state valuation studies directly with young adolescent population samples.     

A simple and sensitive fully validated HPLC-UV method for the determination of 5-fluorouracil and its metabolite 5,6-dihydrofluorouracil in plasma

The authors developed a simple and sensitive, fully validated HPLC-UV method for the determination of both 5-FU and its metabolite DHFU in small-volume plasma samples. The analytes were separated on a 4.6 x 250 mm ID Atlantis dC18 5-microm column with isocratic elution at room temperature. Chlorouracil was used as internal standard. The analytes were detected with an UV diode array detector. DHFU was detected at 205 nm, 5-FU at 266 nm, and chlorouracil at both wavelengths. The limits of quantification in plasma were 0.040 mug /mL for 5-FU and 0.075 microg/mL for DHFU. Linearity, accuracy, precision, recovery, dilution, freeze-thaw stability, and stability in the sample compartment were evaluated. The method appeared linear over a range from 0.04 to 15.90 microg/mL for 5-FU and from 0.075 to 3.84 microg/mL for DHFU. The method appeared very suitable for therapeutic drug monitoring and pharmacokinetic studies of 5-FU because of its simple extraction and small sample volume. Problems in earlier published methods with interfering peaks and variable retention times were overcome. The method appeared also to be suitable for detection of uracil and its metabolite dihydrouracil in plasma.     

The association of hypertensive disorders of pregnancy with weight gain over the subsequent 21 years: findings from a prospective cohort study

Obesity is an important risk factor for hypertensive disorders of pregnancy, but most cases of hypertensive disorders of pregnancy occur in women of normal weight. There may be predisposing factors to both hypertensive disorders of pregnancy and obesity. To test this hypothesis, the authors compared changes in body mass index (weight (kg)/height (m)2) over time in women with and without hypertensive disorders of pregnancy. They used data from 3,572 women who received antenatal care at a major public hospital in Brisbane, Australia, between 1981 and 1984 and who were followed up for 21 years. A total of 318 women (8.9%) had experienced hypertensive disorders in the index pregnancy, and 233 of them (73.3%) had a baseline body mass index of or=5 kg/m2 were 59% greater for women who experienced hypertensive disorders of pregnancy compared with those who did not (odds ratio=1.59, 95% confidence interval: 1.24, 2.04). The authors concluded that hypertensive disorders of pregnancy are associated with increased weight gain over 21 years.     

Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting

OBJECTIVE: Alternate day fasting may extend lifespan in rodents and is feasible for short periods in nonobese humans. The aim of this study was to examine the effects of 3 weeks of alternate day fasting on glucose tolerance and skeletal muscle expression of genes involved in fatty acid transport/oxidation, mitochondrial biogenesis, and stress response. RESEARCH METHODS AND PROCEDURES: Glucose and insulin responses to a standard meal were tested in nonobese subjects (eight men and eight women; BMI, 20 to 30 kg/m(2)) at baseline and after 22 days of alternate day fasting (36 hour fast). Muscle biopsies were obtained from a subset of subjects (n = 11) at baseline and on day 21 (12-hour fast). RESULTS: Glucose response to a meal was slightly impaired in women after 3 weeks of treatment (p < 0.01), but insulin response was unchanged. However, men had no change in glucose response and a significant reduction in insulin response (p < 0.03). There were no significant changes in the expression of genes involved in mitochondrial biogenesis or fatty acid transport/oxidation, although a trend toward increased CPT1 expression was observed (p < 0.08). SIRT1 mRNA expression was increased after alternate day fasting (p = 0.01). DISCUSSION: Alternate day fasting may adversely affect glucose tolerance in nonobese women but not in nonobese men. The gene expression results indicate that fatty acid oxidation and mitochondrial biogenesis are unaffected by alternate day fasting. However, the increased expression in SIRT1 suggests that alternate day fasting may improve stress resistance, a commonly observed feature of calorie-restricted rodents.     

Food advertising on Australian television: the extent of children's exposure

The objective of this study was to investigate the extent and nature of food advertising during Australian children's television (TV) viewing hours and programs, and to determine whether confectionery and fast food restaurant advertisements were more likely to be broadcast during children's programs than during adults' programs on Sydney television stations. One week (390 h) of Australian advertising data broadcast during children's TV viewing hours over 15 television stations were analysed to determine the proportion of food advertisements and, in turn, the proportion of those advertisements promoting foods high in fat and/or sugar. One week (346 h) of confectionery and fast food restaurant advertisements broadcast over three Sydney television stations were analysed to determine whether these types of advertisements were more likely to be advertised during children's programs than adults' programs. Half of all food advertisements promoted foods high in fat and/or sugar. 'Confectionery' and 'fast food restaurants' were the most advertised food categories during children's TV viewing hours. Confectionery advertisements were three times as likely, and fast food restaurant advertisements twice as likely, to be broadcast during children's programs than adults' programs. It can be concluded that foods most advertised during children's viewing hours are not those foods that contribute to a healthy diet for children. Confectionery and fast food restaurant advertising appears to target children. Australian children need protection from the targeted promotion of unhealthy foods on television, but currently little exists.     

Uptake of Clostridium botulinum C3 Exoenzyme into Intact HT22 and J774A.1 Cells

The Clostridium botulinum C3 exoenzyme selectively ADP-ribosylates low molecular weight GTP-binding proteins RhoA, B and C. This covalent modification inhibits Rho signaling activity, resulting in distinct actin cytoskeleton changes. Although C3 exoenzyme has no binding, the translocation domain assures that C3 enters cells and acts intracellularly. C3 uptake is thought to occur due to the high concentration of the C3 enzyme. However, recent work indicates that C3 is selectively endocytosed, suggesting a specific endocytotic pathway, which is not yet understood. In this study, we show that the C3 exoenzyme binds to cell surfaces and is internalized in a time-dependent manner. We show that the intermediate filament, vimentin, is involved in C3 uptake, as indicated by the inhibition of C3 internalization by acrylamide, a known vimentin disruption agent. Inhibition of C3 internalization was not observed by chemical inhibitors, like bafilomycin A, methyl-β-cyclodextrin, nocodazole or latrunculin B. Furthermore, the internalization of C3 exoenzyme was markedly inhibited in dynasore-treated HT22 cells. Our results indicate that C3 internalization depends on vimentin and does not depend strictly on both clathrin and caveolae.