Ethnic Health Care Advisors: A Good Strategy to Improve the Access to Health Care and Social Welfare Services for Ethnic Minorities?

Empirical studies indicate that ethnic minorities have limited access to health care and welfare services compared with the host population. To improve this access, ethnic health care (HC) advisors were introduced in four districts in Amsterdam, the Netherlands. HC advisors work for all health care and welfare services and their main task is to provide information on health care and welfare to individuals and groups and refer individuals to services. Action research was carried out over a period of 2 years to find out whether and how this function can contribute to improve access to services for ethnic minorities. Information was gathered by semi-structured interviews, analysing registration forms and reports, and attending meetings. The function’s implementation and characteristics differed per district. The ethnicity of the health care advisors corresponded to the main ethnic groups in the district: Moroccan and Turkish (three districts) and sub-Sahara African and Surinamese (one district). HC advisors reached many ethnic inhabitants (n = 2,224) through individual contacts. Half of them were referred to health care and welfare services. In total, 576 group classes were given. These were mostly attended by Moroccan and Turkish females. Outreach activities and office hours at popular locations appeared to be important characteristics for actually reaching ethnic minorities. Furthermore, direct contact with a well-organized back office seems to be important. HC advisors were able to reach many ethnic minorities, provide information about the health care and welfare system, and refer them to services. Besides adapting the function to the local situation, some general aspects for success can be indicated: the ethnic background of the HC advisor should correspond to the main ethnic minority groups in the district, HC advisors need to conduct outreach work, there must be a well-organized back office to refer clients to, and there needs to be enough commitment among professionals of local health and welfare services

Effects of Dual Targeting of Tumor Cells and Stroma in Human Glioblastoma Xenografts with a Tyrosine Kinase Inhibitor against c-MET and VEGFR2

Contains fulltext : 118357.pdf (publisher's version ) (Open Access)Anti-angiogenic treatment of glioblastoma with Vascular Endothelial Growth Factor (VEGF)- or VEGF Receptor 2 (VEGFR2) inhibitors normalizes tumor vessels, resulting in a profound radiologic response and improved quality of life. This approach however does not halt tumor progression by diffuse infiltration, as this phenotype is less angiogenesis dependent. Combined inhibition of angiogenesis and diffuse infiltrative growth would therefore be a more effective treatment approach in these tumors. The HGF/c-MET axis is important in both angiogenesis and cell migration in several tumor types including glioma. We therefore analyzed the effects of the c-MET- and VEGFR2 tyrosine kinase inhibitor cabozantinib (XL184, Exelixis) on c-MET positive orthotopic E98 glioblastoma xenografts, which routinely present with angiogenesis-dependent areas of tumor growth, as well as diffuse infiltrative growth. In cultures of E98 cells, cabozantinib effectively inhibited c-MET phosphorylation, concomitant with inhibitory effects on AKT and ERK1/2 phosphorylation, and cell proliferation and migration. VEGFR2 activation in endothelial cells was also effectively inhibited . Treatment of BALB/c nu/nu mice carrying orthotopic E98 xenografts resulted in a significant increase in overall survival. Cabozantinib effectively inhibited angiogenesis, resulting in increased hypoxia in angiogenesis-dependent tumor areas, and induced vessel normalization. Yet, tumors ultimately escaped cabozantinib therapy by diffuse infiltrative outgrowth via vessel co-option. Of importance, in contrast to the results from experiments, blockade of c-MET activation was incomplete, possibly due to multiple factors including restoration of the blood-brain barrier resulting from cabozantinib-induced VEGFR2 inhibition. In conclusion, cabozantinib is a promising therapy for c-MET positive glioma, but improving delivery of the drug to the tumor and/or the surrounding tissue may be needed for full activity

Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias

Robert Clarke and colleagues conduct a meta-analysis of unpublished datasets to examine the causal relationship between elevation of homocysteine levels in the blood and the risk of coronary heart disease. Their data suggest that an increase in homocysteine levels is not likely to result in an increase in risk of coronary heart disease

De invloed van omgevingsfactoren op de infectiviteit van niet-delende cultures van Campylobacter jejuni

Campylobacter jejuni is de meest frequente bacteriele veroorzaker van voedselinfecties. Onder omstandigheden waarbij C. jejuni niet kan groeien, bijvoorbeeld bij temperaturen lager dan 30 graden C, verliest de bacterie zijn kweekbaarheid, maar lijkt de bacterie niet dood te gaan. In deze studie is onderzocht of een niet-kweekbare C. jejuni een infectie kan veroorzaken, en of de omstandigheden waaronder de kweekbaarheid verloren is gegaan van invloed zijn op een eventuele infectie. Gedurende 40 dagen zijn kweekbaarheid, levensvatbaarheid en vermogen om een infectie te veroorzaken bepaald van C. jejuni die was opgeslagen in twee verschillende media bij drie verschillende temperaturen. Wanneer opgeslagen in een nutrient-arm medium bij lage temperatuur (4 graden C) bleek C. jejuni langer zijn kweekbaarheid te behouden dan bij hogere temperaturen (12 graden C, 25 graden C) of in een rijk medium. Bacterien bleven onder alle condities levensvatbaar. De mate van adhesie en invasie van de opgeslagen cultures nam af in de tijd; bij lage temperatuur in buffer behielden de bacterien het langst hun vermogen om aan darmepitheel- cellen te hechten of om erin binnen te dringen. Terwijl de infectiviteit van de totale cultuur afnam, nam de infectiviteit per kweekbare bacterie in die cultuur toe gedurende de eerste 5 dagen om daarna weer af te nemen. Dit resultaat suggereert dat een niet-kweekbare C. jejuni infectieus kan zijn. Echter, er kan ook een alternatieve verklaring zijn, namelijk dat er slechts een beperkt aantal specifieke bindingsplaatsen voor de hechting van C. jejuni aanwezig zijn. De eventuele aanwezigheid van specifieke bindingsplaatsen voor Campylobacter heeft mogelijk grote gevolgen voor onderzoek aan de invloed van niet-kweekbare cellen. Als niet-kweekbare cellen niet meer infectief zijn, maar wel kunnen hechten aan een bindingsplaats, dan kunnen zij met kweekbare cellen concurreren om een bindingsplaats. Dit zou een geheel nieuw rol betekenen voor niet-kweekbare cellen: niet-kweekbare cellen zouden dan de kans op een infectie verlagen!Campylobacter (C.) jejuni is a causative agent of gastro-enteritis. Growth of this Gram negative bacterium is restricted to a limited number of environmental conditions. Under conditions where growth of C. jejuni is not possible, e.g. at temperatures below 30 degrees C, C. jejuni can remain viable for a certain period of time, but its culturability decreases. In this study we examined the effect of this loss of culturability on the infectivity in cell-lines. We hypothesised that if non-culturable cells affect the process of infection then the infectivity per culturable cell used in the infection assay is not constant, whereas if only culturable cell are infectious then the infectivity per culturable cell is. C. jejuni was stored for 40 days in nutrient poor and nutrient rich medium at three temperatures. During this period we monitored its culturability, viability and infectivity. A decrease in culturability in time was observed. At low temperature (4 degrees C) and in nutrient poor medium cells remained culturable for longer periods than at higher temperatures (12 degrees C, 25 degrees C) or in nutrient rich medium. Non-culturable cells remained viable, as determined by tetrazolium chloride staining. The absolute level of adhesion and invasion showed a decrease in time. At low temperatures and in nutrient poor medium cells retained their capability to adhere and invade longer than at higher temperatures or in nutrient rich medium. While the absolute level of adhesion and invasion decreased, the infectivity per culturable cell added seemed to increase during the first 5 days of storage at 4 degrees C. This result confirmed our hypothesis that non-culturable C. jejuni can affect the process of infection. However, the result can also be explained by the presence of a limited number of bindingsites for C. jejuni in our testmodel. This suggested existence of bindingsites has great importance for the research into the influence of non-culturable cells on the infectivity. If non-culturable cells are not infectious but can block bindingsites, then they can play a protective role by competing with the culturable cells for the limited number of bindingsites.RIV

De invloed van omgevingsfactoren op de infectiviteit van niet-delende cultures van Campylobacter jejuni

Campylobacter (C.) jejuni is a causative agent of gastro-enteritis. Growth of this Gram negative bacterium is restricted to a limited number of environmental conditions. Under conditions where growth of C. jejuni is not possible, e.g. at temperatures below 30 degrees C, C. jejuni can remain viable for a certain period of time, but its culturability decreases. In this study we examined the effect of this loss of culturability on the infectivity in cell-lines. We hypothesised that if non-culturable cells affect the process of infection then the infectivity per culturable cell used in the infection assay is not constant, whereas if only culturable cell are infectious then the infectivity per culturable cell is. C. jejuni was stored for 40 days in nutrient poor and nutrient rich medium at three temperatures. During this period we monitored its culturability, viability and infectivity. A decrease in culturability in time was observed. At low temperature (4 degrees C) and in nutrient poor medium cells remained culturable for longer periods than at higher temperatures (12 degrees C, 25 degrees C) or in nutrient rich medium. Non-culturable cells remained viable, as determined by tetrazolium chloride staining. The absolute level of adhesion and invasion showed a decrease in time. At low temperatures and in nutrient poor medium cells retained their capability to adhere and invade longer than at higher temperatures or in nutrient rich medium. While the absolute level of adhesion and invasion decreased, the infectivity per culturable cell added seemed to increase during the first 5 days of storage at 4 degrees C. This result confirmed our hypothesis that non-culturable C. jejuni can affect the process of infection. However, the result can also be explained by the presence of a limited number of bindingsites for C. jejuni in our testmodel. This suggested existence of bindingsites has great importance for the research into the influence of non-culturable cells on the infectivity. If non-culturable cells are not infectious but can block bindingsites, then they can play a protective role by competing with the culturable cells for the limited number of bindingsites.Campylobacter jejuni is de meest frequente bacteriele veroorzaker van voedselinfecties. Onder omstandigheden waarbij C. jejuni niet kan groeien, bijvoorbeeld bij temperaturen lager dan 30 graden C, verliest de bacterie zijn kweekbaarheid, maar lijkt de bacterie niet dood te gaan. In deze studie is onderzocht of een niet-kweekbare C. jejuni een infectie kan veroorzaken, en of de omstandigheden waaronder de kweekbaarheid verloren is gegaan van invloed zijn op een eventuele infectie. Gedurende 40 dagen zijn kweekbaarheid, levensvatbaarheid en vermogen om een infectie te veroorzaken bepaald van C. jejuni die was opgeslagen in twee verschillende media bij drie verschillende temperaturen. Wanneer opgeslagen in een nutrient-arm medium bij lage temperatuur (4 graden C) bleek C. jejuni langer zijn kweekbaarheid te behouden dan bij hogere temperaturen (12 graden C, 25 graden C) of in een rijk medium. Bacterien bleven onder alle condities levensvatbaar. De mate van adhesie en invasie van de opgeslagen cultures nam af in de tijd; bij lage temperatuur in buffer behielden de bacterien het langst hun vermogen om aan darmepitheel- cellen te hechten of om erin binnen te dringen. Terwijl de infectiviteit van de totale cultuur afnam, nam de infectiviteit per kweekbare bacterie in die cultuur toe gedurende de eerste 5 dagen om daarna weer af te nemen. Dit resultaat suggereert dat een niet-kweekbare C. jejuni infectieus kan zijn. Echter, er kan ook een alternatieve verklaring zijn, namelijk dat er slechts een beperkt aantal specifieke bindingsplaatsen voor de hechting van C. jejuni aanwezig zijn. De eventuele aanwezigheid van specifieke bindingsplaatsen voor Campylobacter heeft mogelijk grote gevolgen voor onderzoek aan de invloed van niet-kweekbare cellen. Als niet-kweekbare cellen niet meer infectief zijn, maar wel kunnen hechten aan een bindingsplaats, dan kunnen zij met kweekbare cellen concurreren om een bindingsplaats. Dit zou een geheel nieuw rol betekenen voor niet-kweekbare cellen: niet-kweekbare cellen zouden dan de kans op een infectie verlagen

The influence of environmental conditions on the infectivity of non-growing Campylobacter jejuni

Campylobacter jejuni is de meest frequente bacteriele veroorzaker van voedselinfecties. Onder omstandigheden waarbij C. jejuni niet kan groeien, bijvoorbeeld bij temperaturen lager dan 30 graden C, verliest de bacterie zijn kweekbaarheid, maar lijkt de bacterie niet dood te gaan. In deze studie is onderzocht of een niet-kweekbare C. jejuni een infectie kan veroorzaken, en of de omstandigheden waaronder de kweekbaarheid verloren is gegaan van invloed zijn op een eventuele infectie. Gedurende 40 dagen zijn kweekbaarheid, levensvatbaarheid en vermogen om een infectie te veroorzaken bepaald van C. jejuni die was opgeslagen in twee verschillende media bij drie verschillende temperaturen. Wanneer opgeslagen in een nutrient-arm medium bij lage temperatuur (4 graden C) bleek C. jejuni langer zijn kweekbaarheid te behouden dan bij hogere temperaturen (12 graden C, 25 graden C) of in een rijk medium. Bacterien bleven onder alle condities levensvatbaar. De mate van adhesie en invasie van de opgeslagen cultures nam af in de tijd; bij lage temperatuur in buffer behielden de bacterien het langst hun vermogen om aan darmepitheel- cellen te hechten of om erin binnen te dringen. Terwijl de infectiviteit van de totale cultuur afnam, nam de infectiviteit per kweekbare bacterie in die cultuur toe gedurende de eerste 5 dagen om daarna weer af te nemen. Dit resultaat suggereert dat een niet-kweekbare C. jejuni infectieus kan zijn. Echter, er kan ook een alternatieve verklaring zijn, namelijk dat er slechts een beperkt aantal specifieke bindingsplaatsen voor de hechting van C. jejuni aanwezig zijn. De eventuele aanwezigheid van specifieke bindingsplaatsen voor Campylobacter heeft mogelijk grote gevolgen voor onderzoek aan de invloed van niet-kweekbare cellen. Als niet-kweekbare cellen niet meer infectief zijn, maar wel kunnen hechten aan een bindingsplaats, dan kunnen zij met kweekbare cellen concurreren om een bindingsplaats. Dit zou een geheel nieuw rol betekenen voor niet-kweekbare cellen: niet-kweekbare cellen zouden dan de kans op een infectie verlagen

Patterns of progression in malignant glioma following anti-VEGF therapy: perceptions and evidence

Antiangiogenic treatment has recently become an integral part of modern cancer therapy targeting the vasculature of numerous aggressive malignancies including glioblastoma. There is preclinical evidence that antiangiogenic therapies promote glioma cell invasiveness. In clinical series, upon progression on antiangiogenic therapy with the vascular endothelial growth factor-directed antibody bevacizumab (BEV), glioblastoma has been reported to display a more infiltrative pattern of recurrence. This distant spread at recurrence or progression and a gliomatosis cerebri-like growth pattern is best detectable on fluid-attenuated inversion recovery MRI. The frequency of up to 20% to 30% of such a pattern in BEV-treated patients is higher than expected to occur without BEV. Older reports and common clinical knowledge estimate the frequency of diffuse or distant spread in recurrent glioblastoma at 10%. This observation stimulated two streams of research. One is to overcome this often insidious adverse effect of antiangiogenic treatment, to optimize antiangiogenic therapies and to face this major challenge, integrating antiangiogenic with anti-invasive mechanisms into one combined treatment concept. The second is questioning a specific property of antiangiogenic therapy to induce diffuse or distant spread. Here, alternative hypotheses of increased awareness and better imaging as well as invasiveness being part of the natural course of the disease have been tested. Without doubt, migration and invasiveness are major obstacles to successful glioma therapy, notably local therapies, both in the natural course of the disease and in the concept of "evasive resistance." However, clinical analyses of case series, matched pairs analyses, and follow-up on the BRAIN trial (A Study to Evaluate Bevacizumab Alone or in Combination with Irinotecan for Treatment of Glioblastoma Multiforme), which led to accelerated approval of BEV for recurrent glioblastoma in the United States, have not supported a specific propensity of BEV to induce diffuse growth or distant spread at recurrence