Prescriptive variability of drugs by general practitioners

<div><p>Prescription drug spending is growing faster than any other sector of healthcare. However, very little is known about patterns of prescribing and cost of prescribing between general practices. In this study, we examined variation in prescription rates and prescription costs through time for 55 GP surgeries in Northern Ireland Western Health and Social Care Trust. Temporal changes in variability of prescribing rates and costs were assessed using the Mann–Kendall test. Outlier practices contributing to between practice variation in prescribing rates were identified with the interquartile range outlier detection method. The relationship between rates and cost of prescribing was explored with Spearman's statistics. The differences in variability and mean number of prescribing rates associated with the practice setting and socioeconomic deprivation were tested using t-test and <i>F</i>-test respectively. The largest between-practice difference in prescribing rates was observed for Apr-Jun 2015, with the number of prescriptions ranging from 3.34 to 8.36 per patient. We showed that practices with outlier prescribing rates greatly contributed to between-practice variability. The largest difference in prescribing costs was reported for Apr-Jun 2014, with the prescription cost per patient ranging from £26.4 to £64.5. In addition, the temporal changes in variability of prescribing rates and costs were shown to undergo an upward trend. We demonstrated that practice setting and socio-economic deprivation accounted for some of the between-practice variation in prescribing. Rural practices had higher between practice variability than urban practices at all time points. Practices situated in more deprived areas had higher prescribing rates but lower variability than those located in less deprived areas. Further analysis is recommended to assess if variation in prescribing can be explained by demographic characteristics of patient population and practice features. Identification of other factors contributing to prescribing variability can help us better address potential inappropriateness of prescribing.</p></div

Endoscopic ultrasonography features of gastric mucosal cobblestone-like changes from a proton-pump inhibitor

A 68-year-old man with no symptoms presented to Hokkaido University Hospital for esophagogastroduodenoscopy screening. He had a history of Helicobacter pylori eradication. Initial esophagogastroduodenoscopy showed no gastric cobblestone-like mucosa or gastric cracked mucosa. After 1 year, he received esomeprazole (20 mg) once daily for heartburn at another hospital. Esophagogastroduodenoscopy was performed after 2 years of esomeprazole administration. Endoscopic findings showed that after H. pylori eradication, according to the Kyoto classification, gastric cobblestone-like mucosa presented in the gastric body area. Dilation of the oval crypt opening and intervening part in the gastric cobblestone-like mucosa was detected by endoscopy with narrow band imaging. Endoscopic ultrasonography revealed a thick gastric second layer and sporadic small a-echoic lesions in the low-echoic thickened second layer in the gastric cobblestone-like mucosa. The gastric cobblestone-like mucosa biopsy specimen showed parietal cell protrusions and oxyntic gland dilatations. Recently, we reported that gastric mucosal changes such as gastric cracked mucosa and gastric cobblestone-like mucosa were caused by protonpump inhibitors; however, the gastric cobblestone-like mucosa was not examined by endoscopic ultrasonography. In this case, endoscopic ultrasonography findings suggested that oxyntic gland dilatations caused the elevated gastric mucosa, such as gastric cobblestone-like mucosa, from the use of proton-pump inhibitors

Lansoprazole inhibits the cysteine protease legumain by binding to the active site

Proton pump inhibitors (PPIs) are prodrugs used in the treatment of peptic ulcer diseases. Once activated by acidic pH, the PPIs subsequently inhibit the secretion of gastric acid by covalently forming disulphide bonds with the SH groups of the parietal proton pump, that is the H + /K + -ATPase. Long-term use of PPIs has been associated with numerous adverse effects, including bone fractures. Considering the mechanism of activation, PPIs could also be active in acidic micro-environments such as in lysosomes, tumours and bone resorption sites. We suggested that the SH group in the active site of cysteine proteases could be susceptible for inhibition by PPIs. In this study, the inhibition by lansoprazole was shown on the cysteine proteases legumain and cathepsin B by incubating purified proteases or cell lysates with lansoprazole at different concentrations and pH conditions. The mechanism of legumain inhibition was shown to be a direct interaction of lansoprazole with the SH group in the active site, and thus blocking binding of the legumain-selective activity-based probe MP-L01. Lansoprazole was also shown to inhibit both legumain and cathepsin B in various cell models like HEK293, monoclonal legumain over-expressing HEK293 cells (M38L) and RAW264.7 macrophages, but not in human bone marrow-derived skeletal (mesenchymal) stem cells (hBMSC-TERT). During hBMSC-TERT differentiation to osteoblasts, lansoprazole inhibited legumain secretion, alkaline phosphatase activity, but had no effects on in vitro mineralization capacity. In conclusion, lansoprazole acts as a direct covalent inhibitor of cysteine proteases via disulphide bonds with the SH group in the protease active site. Such inhibition of cysteine proteases could explain some of the off-target effects of PPIs. </p