Visualization of the photodegradation of a therapeutic drug by chemometric-assisted fluorescence spectroscopy

The fluorescence spectral fingerprint, also known as the excitation-emission matrix (EEM), is used to assess and visualize therapeutic drug photodegradation in combination with chemometrics. Examination of EEM-parallel factor analysis (PARAFAC) data showed that an individual component was easily separated from a mixture of photogenerated products of a heterocyclic pharmacophore, in this case, phenothiazine drugs (PTZs). Detailed investigations of both structure–EEM relationships and kinetics revealed that the components extracted from EEM–PARAFAC could be quantitatively attributed to such photogenerated products as phenothiazine sulfoxide and carbazole derivatives. EEM in combination with principal component analysis (PCA) could be used as a mapping tool to visualize information of the photodegradation process of PTZs. We also assessed the photostability of various types of PTZs containing side chains by using validated EEM–PARAFAC methodology.

Drug quality and assurance changes with time under the influence of a variety of environmental factors, such as light, temperature, and moisture.     

Elements Influencing Recruitment and Retention of Millennial Hospitalists Born in or after 1982: a Survey-Based Study

BackgroundHospitalist turnover is exceedingly high, placing financial burdens on hospital medicine groups (HMGs). Following training, many begin their employment in medicine as early-career hospitalists, the majority being millennials.ObjectiveTo understand what elements influence millennial hospitalists’ recruitment and retention.DesignWe developed a survey that asked participants to rate the level of importance of 18 elements (4-point Likert scale) in their decision to choose or remain at an HMG.ParticipantsThe survey was electronically distributed to hospitalists born in or after 1982 across 7 HMGs in the USA.Main MeasuresElements were grouped into four major categories: culture of practice, work-life balance, financial considerations, and career advancement. We calculated the means for all 18 elements reported as important across the sample. We then calculated means by averaging elements within each category. We used unpaired t-tests to compare differences in means for categories for choosing vs. remaining at an HMG.Key ResultsOne hundred forty-four of 235 hospitalists (61%) responded to the survey. 49.6% were females. Culture of practice category was the most frequently rated as important for choosing (mean 96%, SD 12%) and remaining (mean 96%, SD 13%) at an HMG. The category least frequently rated as important for both choosing (mean 69%, SD 35%) and remaining (mean 76%, SD 32%) at an HMG was career advancement. There were no significant differences between respondent gender, race, or parental status and ratings of elements for choosing or remaining with HMGs.ConclusionCulture of practice at an HMG may be highly important in influencing millennial hospitalists’ decision to choose and stay at an HMG. HMGs can implement strategies to create a millennial-friendly culture which may help improve recruitment and retention.KEY WORDS: Hospitalist, Hospital medicine group (HMG), Recruitment, Retention, Culture of practice, Millennial     

Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type 2 diabetes by baseline age and body mass index

Aims/IntroductionMany East Asians with type 2 diabetes are elderly and have a low body mass index (BMI), especially in ''super‐aged'' populations, such as Japan. This post‐hoc analysis assessed once‐weekly semaglutide efficacy and safety in Japanese individuals with type 2 diabetes across baseline age and BMI subgroups.Materials and MethodsData were derived from the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) Japan monotherapy and SUSTAIN Japan oral antidiabetes drug (OAD) combination trials comparing once‐weekly semaglutide with sitagliptin or OADs, respectively. Participants were grouped by baseline age (<65 and ≥65 years) and/or BMI (<25 and ≥25 kg/m²). Reductions from baseline in glycosylated hemoglobin and bodyweight (efficacy), and adverse events (safety) were assessed.ResultsIn this analysis, participants from the SUSTAIN Japan monotherapy trial (n = 308; n per subgroup; range, 8–73) and SUSTAIN Japan OAD combination trial (n = 601; n per subgroup; range, 20–168) were included. Reductions in glycosylated hemoglobin and bodyweight were numerically greater with semaglutide versus comparators across all age and BMI subgroups. Reductions from baseline in glycosylated hemoglobin ranged from –1.7 to –2.1 with semaglutide 0.5 mg, –1.8 to –2.4 with semaglutide 1.0 mg and –0.6 to –1.0 with comparators. Corresponding ranges for bodyweight (kg) were –1.0 to –2.5, –2.4 to –4.3 and 1.0 to –1.0 kg, respectively. The safety profile of semaglutide was broadly similar across BMI and age subgroups.ConclusionsIn this post‐hoc analysis with modest subgroup numbers, once‐weekly semaglutide appeared consistently more efficacious versus comparators across age and BMI subgroups in Japanese patients, with a similar safety profile.     

Pelvic insufficiency fracture after definitive radiotherapy for uterine cervical cancer: retrospective analysis of risk factors

The purpose of this study is to determine the incidence, clinical characteristics and risk factors of postradiation pelvic insufficiency fracture (PIF) in women with uterine cervical cancer. We reviewed the medical records of 126 patients who received definitive radiotherapy (RT) for uterine cervical cancer between 2003 and 2009 at our institution. Among them, 99 patients who underwent at least one computed tomography (CT) or magnetic resonance imaging of the pelvis during their follow-up at more than 6 months were included in this analysis. The relationship between the incidence of PIF and several patient- and treatment-related factors was analyzed. The median follow-up period was 21 months. Of the 126 patients, 33 (with a total of 50 lesions) were diagnosed with PIF. The 2-year cumulative incidence was 32%. Univariate analysis showed that age ≥70 years (P= 0.0010), postmenopausal state (P = 0.0013), and lower CT density of bone and bone marrow (P= 0.020) significantly related to PIF. In a multivariate analysis, of the 59 patients whose CT densities were evaluable, lower CT density was the only significant factor associated with PIF (P = 0.0026). In conclusion, postradiation PIFs were detected in a considerable number of patients after definitive RT for cervical cancer. Predisposing factors were older age, postmenopausal state, and decreased density of bone and bone marrow on CT.     

Persistent primitive hypoglossal artery associated with cerebral aneurysm and cervical internal carotid artery stenosis--case report.

A 71-year-old female had vertigo attacks once or twice a day secondary to vertebrobasilar insufficiency. Left carotid angiography revealed persistent primitive hypoglossal artery (PPHA) associated with a large internal carotid artery (ICA) aneurysm and severe stenosis of the ICA. The bilateral vertebral arteries were hypoplastic. The basilar artery was opacified via the PPHA but not via vertebral arteries. Clipping of the aneurysm was performed first because the risk of rupture of the aneurysm was not negligible. One month after clipping, carotid endarterectomy using a T-shaped shunt system was successfully performed. The postoperative course was uneventful and the vertebrobasilar ischemic attacks did not recur. Left carotid angiography demonstrated complete obliteration of the aneurysm and disappearance of the carotid artery stenosis. Low ICA flow (70 ml/min) and low stump pressure of the PPHA (25 mmHg) strongly suggested low perfusion of the posterior circulation. Carotid endarterectomy may be essential for augmentation of the posterior circulation in patients with PPHA associated with ICA stenosis.     

A preliminary study of microcapsule suspension for hemolysis evaluation of artificial organs

A microcapsule suspension, a substitute for animal blood in hemolysis tests, has been developed for evaluation of the absolute hemolytic properties of circulatory artificial organs. The microcapsule suspension was made by dispersing microcapsule slurry into an ethylene glycol sodium chloride solution. The microcapsule slurry was composed of a leuco dye solution and polyurethane membrane made by the reaction between aliphatic poly-isocyanate and polyamine by interfacial polycondensation. The microcapsule was a small particle containing dye inside. The microcapsule suspension was white; the diameter of the microcapsules was from 5 to 100 microns. The specific gravity of the suspension was 1.024, and the membrane was elastic. The fluid showed Newtonian characteristics, different from animal blood, and its viscosity was approximately 5.8 mPa.s. After the microcapsules were destroyed, the leuco dye was extracted with n-hexane from the suspension and was measured by spectroscopy after being colored with acid ethanol. Hemolysis can be regarded as a fatigue fracture of cell membranes rather than a static fracture. The destruction of microcapsules by a Potter type tissue grinder was observed at a low stroke number region and was compared to rat blood. Moreover, hemolysis tests of a commercially available centrifugal blood pump and the prototype of our centrifugal pump for mechanism checks were carried out with bovine blood. The hemolysis level of the prototype pump increased with time while the hemolysis level of the commercial blood pump did not change as much as that of the control when both pumps were tested with the microcapsule suspension. These results are similar to tests utilizing bovine blood. Therefore, hemolysis tests of circulatory artificial organs completed with microcapsule suspension are expected to provide results similar to tests with animal blood.     

No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer

BACKGROUND: It remains unknown whether extended surgery improves the survival rate of patients with gastric cancer. This study was a review of combined pancreaticosplenectomy with total gastrectomy for gastric cancer. METHODS: The clinicopathological details of 190 patients who underwent combined pancreaticosplenectomy with total gastrectomy between 1969 and 1996 were compared retrospectively with those of 206 patients who underwent total gastrectomy with splenectomy alone. RESULTS: There was no statistical difference in the survival rate when pancreaticosplenectomy was added to total gastrectomy. The mortality rate was similar, but the morbidity rate was higher in patients who had pancreaticosplenectomy. Six patients who had direct pancreatic invasion and two thought to have involved lymph nodes along the splenic artery survived for more than 5 years after operation. In the latter group, the metastatic lymph nodes along the splenic artery could have been resected without pancreatectomy. CONCLUSION: Since a combined pancreaticosplenectomy adds no survival advantage to total gastrectomy for gastric cancer, this procedure should no longer be regarded as routine.