Hypolipidemic Agents of Phthalimide Derivatives 6. Effects of Aromatic vs. Non-Aromatic Imides

A number of substituted phthalimide, 1, 8-naphthalimide, succinimide and glutarimide derivatives demonstrated significant hypolipidemic activity at 20 mg/kg/ day, I.P. after 16 days dosing. The N-(n-pentyl) succinimide proved to be the most potent analogue of the new compounds, lowering serum triglyceride levels 51 % and serum cholesterol 47 % after 16 days dosing in mice. For the N-substituted derivatives, i. e., n-butyl, butanone, and propionic acid, of these four cyclic imides, there appeared to be no obvious trend in ability to reduce serum lipid levels. In general, the 1,8-naphthalimide and glutarimide derivatives appeared to be less active than phthalimide and succinimide. However, the -phenylsuccinimide afforded less activity than the -phenylglutarimide. Most of the derivatives at 20mg/kg/day demonstrated improved activity over clofibrate at 150mg/kg/day.     

Disability-Adjusted Life Years Averted Versus Quality-Adjusted Life Years Gained: A Model Analysis for Breast Cancer Screening

ObjectivesTo quantify the impact of mammography-based screening on the quality of life, disability-adjusted life years (DALYs) averted or quality-adjusted life years (QALYs) gained can be used. We aimed to assess whether the use of DALYs averted or QALYs gained will lead to different cost-effective screening strategies.MethodsUsing the microsimulation model MISCAN, we simulated different breast cancer screening strategies varying in starting age (starting at 45, 47, and 50 years), stopping age (stopping at 69, 72, and 74 years), and frequency (annual [A], biennial [B], combination of both [A + B], and triennial [T]). In total, we defined 24 different breast cancer screening strategies, including no screening as a reference strategy. We calculated incremental cost-effectiveness ratios (ICERs) and compared which strategies were on the efficiency frontiers for DALYs and QALYs.ResultsBreast cancer screening averted between 46.00 and 105.58 DALYs and gained between 28.69 and 64.50 QALYs per 1000 women. For DALYs there were 5 strategies on the efficiency frontier (T50-69, T50-74, T45-74, B45-74, and A45-74). The same strategies plus one (B45-72) were on the efficiency frontier for QALYs.ConclusionsUsing DALYs averted instead of QALYs gained to assess the effects on quality of life from breast cancer screening in the Dutch population yields differences in ICERs, but almost the same strategies were on the efficiency frontiers. Whether the choice in outcome measure leads to a difference in optimal policy depends on the cost-effectiveness threshold.     

Epidemiologische Ansätze zur Klärung wichtiger Forschungsfragen zu COVID-19 – eine Übersicht

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Epidemiologie als wissenschaftliche Disziplin ist prädestiniert dafür, Kernfragen der COVID-19-Pandemie zu...     

Comparison of nutritional and hydration status in patients undergoing twice and thrice-weekly hemodialysis: a silent drama in developing countries

International Urology and Nephrology - In low and middle- income countries, due to lack of financial resources, the number of patients receiving one or two hemodialysis (HD) sessions a week has...     

Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients

BackgroundProtroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT).Patients and MethodsOf the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed.ResultsNine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim.ConclusionsApplication of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.     

Prevalence of rotavirus antibodies in a non-human primate colony

A total of 51 monkeys maintained in a colony at the Institute of Primate Research (Kenya) and housed in doors with natural lighting in a group cage were used in this study. Monkeys belonging to 3 species were selected at random and blood samples collected. The serum samples were screened for presence of neutralizing antibodies (VTN) to rhesus rotavirus (RRV) by virus neutralization assay. Virus neutralization was determined by 60% reduction in fluorescent focus units (ffu). 96% of the animals screened had naturally occurring antibodies to rhesus rotavirus. Another group of 11 lactating monkeys (5 baboons, 6 vervets) and their infants were screened further for presence of IgG and IgA antibodies in serum and breast milk (mothers). Overall, the mothers had higher titres of both IgG and IgA than the infants. Taken together, these results demonstrate rotavirus infection is endemic in this primate colony. This mimics the human situation, hence, captive non human primates (such as the baboons) could be a suitable model for testing rotavirus candidate vaccines and for investigating the possible application in humans of passive-active immunization strategy.     

Thrombocytopenia After Isolated Limb or Hepatic Perfusions with Melphalan: The Risk of Heparin-Induced Thrombocytopenia

Background: Three cases of heparin-induced thrombocytopenia (HIT) were observed in patients undergoing isolated limb perfusion (ILP) with melphalan. This occurrence prompted the discontinuation of prophylactic postoperative heparin in ILP patients and its avoidance in patients undergoing isolated hepatic perfusion (IHP). The need to reassess these decisions led to a review of thrombocytopenia in both patient populations.Methods: Records of all patients treated with ILP or IHP at our institution from July 1992 through November 1996, were reviewed. Nine IHP patients were tested prospectively for heparinrelated antibodies using serum samples obtained perioperatively and during the second postoperative week.Results: Thrombocytopenia (<100,000 platelets/L) developed postoperatively in 30% of 131 ILP patients and in 77% of 56 IHP patients. No cases of HIT were identified other than the three who had been previously diagnosed. The prevalence of HIT in heparinized ILP patients was 2.8% (3/108). All nine IHP patients developed heparin-related antibodies postoperatively.Conclusions: Because the prevalence of HIT following ILP is in the range observed in other clinical settings, postoperative heparin prophylaxis is an option. However, it probably should be limited to the first week, and daily platelet counts should be reviewed for a pattern of thrombocytopenia consistent with HIT. The prevalence of heparin-related antibodies after IHP is so high that prophylactic heparin should be avoided in this setting.     

Combined vascular endothelial growth factor and TP53 status predicts poor response to tamoxifen therapy in estrogen receptor-positive advanced breast cancer.

PURPOSE: In recent studies, we showed that TP53 gene mutation or high levels of cytosolic vascular endothelial growth factor (VEGF) in estrogen receptor (ER)-alpha-positive primary breast tumors predict a poor disease outcome for patients treated with first-line tamoxifen for advanced disease. Mutant TP53 may up-regulate VEGF, whereas, on the other hand, wild-type TP53 may decrease VEGF production. EXPERIMENTAL DESIGN: In the present study, we aimed to assess the combined predictive value of TP53 gene mutation and VEGF status of 160 advanced breast cancer patients with ER-positive tumors who were treated with tamoxifen (median follow-up from start of tamoxifen treatment, 64 months). To assess TP53 gene mutation status, the entire open reading frame was sequenced; for VEGF status, an ELISA was used. RESULTS: In univariate analysis, both TP53 gene mutation (28% of the tumors) and a VEGF level above the median value were significantly associated with a short progression-free survival, post-relapse overall survival, and a poor rate of response to tamoxifen. In Cox multivariate regression analysis including the traditional predictive factors, the addition of TP53 gene mutation and VEGF status, alone or in combination, significantly predicted a poor efficacy of tamoxifen treatment. When the two factors were combined, a significantly decreased odds ratio was seen for the rate of response (odds ratio, 0.27). Similarly, an increased hazard ratio (HR) was seen for progression-free survival (HR, 2.32) and post-relapse overall survival (HR, 1.68) in the group with mutant TP53 and high VEGF compared with the group with both risk factors absent. CONCLUSIONS: Combined TP53 gene mutation status and high VEGF levels of ER-positive primary breast tumors independently predict a poor course of the disease of patients with advanced breast cancer treated with tamoxifen. These patients, having unfavorable tumor characteristics, might benefit more from other types of (individualized) treatment protocols.