Exceptions to the rule: healthy deprived areas and unhealthy wealthy areas

In general, inhabitants of low socio-economic areas are unhealthier than inhabitants of high socio-economic areas, but some areas are an exception to this rule. These exceptions imply that other factors besides the socio-economic level of an area contribute to the health of the inhabitants of an area, e.g. environmental factors. In our study we concentrate on areas within the Netherlands that are healthier or unhealthier than could be expected based on their socio-economic level. This study first identifies these areas and secondly determines which area characteristics distinguish these areas from those areas where the level of health is in agreement with their socio-economic level. We used nation-wide data on neighbourhood differences in population composition (gender, age, marital status and ethnicity), urbanisation and two health indicators: mortality and hospitalisation rates. In the Netherlands, many areas are healthier or unhealthier than could be expected based on their income level alone. Areas with higher mortality rates than expected are mainly urban areas with high percentages of elderly people and persons living alone. Similar but opposite associations are observed for areas with lower mortality rates than expected, which are further characterised by a low percentage of non-western immigrants. Areas with lower hospitalisation rates than expected are mainly rural areas with few non-western immigrants. From these results, we conclude that urbanisation and residential segregation based on age, ethnicity and marital status might be important contributors to geographical health inequalities.     

Comparing Approaches to Normalize,Quantify, and Characterize Urinary Extracellular Vesicles

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A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole

The development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-β-cyclodextrin (HPβCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPβCD. After pH adjustment, the itraconazole/HPβCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPβCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis.