[Guideline conform diagnostics for dysphagia : A representative survey of speech therapists at certified stroke units in Germany]. / Leitlinienkonforme Dysphagiediagnostik : Eine repräsentative Befragung von Logopäden an zertifizierten Stroke-Units.

BACKGROUND: Almost 260,000 people in Germany suffer from a stroke each year. As a consequence, for more than 60% this leads to dysphagia. In order to prevent secondary diseases, such as pneumonia, malnutrition and dehydration, a differentiated diagnosis by a multiprofessional team in a stroke unit is required. The guidelines in 2015 for diagnosing neurologic dysphagia by the German Society of Neurology recommend a detailed anamnesis, a standardized screening, a clinical swallowing examination and additional instrumental diagnostics. OBJECTIVE: This study examined whether dysphagia is diagnosed by speech therapists at certified stroke units according to the recommended guidelines. MATERIAL AND METHODS: An online questionnaire was compiled and sent to 1 speech therapist at each of the 195 certified stoke units and 112 participants responded to the questionnaire. The questionnaire consisted of questions about anamnesis, clinical swallowing diagnostics and the instrumental diagnostics. Of the speech therapists working on a stroke unit 57% participated in this study. RESULTS: The results show that 50% of the participants elaborated a detailed and differentiated anamnesis, 64% used a standardized screening (Daniels test) and 66% implemented a guideline conform swallowing test. As technical instruments, 35% of the respondents used video fluoroscopy and 71% of the respondents a fiber endoscopy. CONCLUSION: The implementation of a detailed and differentiated anamnesis, standardized screening, and a clinical swallowing examination with testing of different food consistencies suggests a high quality of the dysphagia diagnostics at stroke units in Germany. The increasing availability of technical instruments, especially fiber endoscopy, substantiates this view.

Treat-to-target (T2T) recommendations for gout.

OBJECTIVES: The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. METHODS: A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. CONCLUSIONS: This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon.

Development of novel quinone phosphorodiamidate prodrugs targeted to DT-diaphorase.

A series of naphthoquinone and benzimidazolequinone phosphorodiamidates has been synthesized and studied as potential cytotoxic prodrugs activated by DT-diaphorase. Reduction of the quinone moiety in the target compounds was expected to provide a pathway for expulsion of the phosphoramide mustard alkylating agent. All of the compounds synthesized were excellent substrates for purified human DT-diaphorase (k(cat)/K(m) = 3 x 10(7) - 3 x 10(8) M(-1) s(-1)). The naphthoquinones were toxic to both HT-29 and BE human colon cancer cell lines in a clonogenic assay; however, cytotoxicity did not correlate with DT-diaphorase activity in these cell lines. The benzimidazolequinone analogues were 1-2 orders of magnitude less cytotoxic than the naphthoquinone analogues. Chemical reduction of the naphthoquinone led to rapid expulsion of the phosphorodiamidate anion; in contrast, the benzimidazole reduction product was stable. Michael addition of glutathione and other sulfur nucleophiles provides an alternate mechanism for activation of the naphthoquinone phosphorodiamidates, and this mechanism may contribute to the cytotoxicity of these compounds.