Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Heteromeric Kv1 potassium channel expression: amino acid determinants involved in processing and trafficking to the cell surface.

Kv1.4 and Kv1.1 potassium channels are expressed in brain as mature glycoproteins that are trans-Golgi glycosylated. When expressed in cell lines these homomers had very different trans-Golgi glycosylation efficiencies and cell surface expression levels with Kv1.4 > Kv1.1 for both parameters (Zhu, J., Watanabe, I., Gomez, B., and Thornhill, W. B. (2001) J. Biol. Chem. 276, 39419-39427). This previous study identified determinants in the outer pore region of Kv1.4 and Kv1.1 that positively and negatively, respectively, affected these events when expressed as homomers. Here we investigated which subunit exhibited positive or negative effects on these processes when expressed as heteromers. Kv1.4/Kv1.1 heteromers, by coexpression or expression as tandem-linked heteromers, were expressed on the cell surface at approximately 20-fold lower levels versus Kv1.4 homomers but they were trans-Golgi glycosylated. The lower Kv1.4/Kv1.1 expression level was not rescued by Kvbeta 2.1 subunits. Thus Kv1.1 inhibited high cell surface expression and partially retained the heteromer in the endoplasmic reticulum, whereas Kv1.4 stimulated trans-Golgi glycosylation. The subunit determinants and cellular events responsible for these differences were investigated. In a Kv1.4/Kv1.1 heteromer, the Kv1.1 pore was a major negative determinant, and it inhibited high cell surface expression because it induced high partial endoplasmic reticulum retention and it decreased protein stability. Other Kv1.1 regions also inhibited high surface expression of heteromers. The Kv1.1 C terminus induced partial Golgi retention and contributed to a decreased protein stability, whereas the Kv1.1 N terminus contributed to only a decreased protein stability. Thus a neuron may regulate its cell surface K+ channel protein levels by different Kv1 subfamily homomeric and heteromeric combinations that affect intracellular retention characteristics and protein stability.