Polyisoprenylated benzophenones and xanthones from the pericarp of Garcinia planchonii Pierre.

Two new polyisoprenylated benzophenones, planchoniones A (1) and B (2), together with two known benzophenones (3, 4) and six known xanthones (5-10), were isolated from an ethyl acetate extract of the pericarp of Garcinia planchonii Pierre. Their structures were established using spectroscopic methods, mainly 1D and 2D NMR. The four benzophenones were evaluated for their cytotoxicity against MCF-7 human breast cancer cells, and showed almost no activity. Meanwhile, compounds 5-10 were investigated for their inhibitory effects towards α-glucosidase, and γ-mangostin (5) exhibited the most remarkable effect with IC50 value of 15.3 ± 0.9 µM (compared with acarbose, IC50 = 224.9 ± 3.6 µM).

An Umbrella Review of the Cost Effectiveness of Human Papillomavirus Vaccines.

BACKGROUND AND OBJECTIVES: Although many systematic reviews for the human papillomavirus vaccines cost effectiveness have been published, they vary in perspectives, methods, and quality. We aimed to condense systematically such evidence to facilitate locating, processing, and learning, not only about the consensus of findings but also how models were built and their evolution over time and across settings. METHODS: We conducted an umbrella review of cost-effectiveness studies for human papillomavirus vaccines using three databases (PubMed, Embase, and Cochrane). Based on their objectives, we classified studies into three groups (human papillomavirus vaccines cost effectiveness, model characteristics, and all-type vaccines, including human papillomavirus vaccines). We used the AMTAR2 to assess the quality of the studies. Additionally, we provided a summary of study findings, discussions, and evidence gaps in the literature. RESULTS: Though most studies were critically low quality and had a low quality of reporting, the human papillomavirus vaccine was consistently cost effective in young girls and men who have sex with men. Stratified analyses by rated quality did not change the results. The quality assessment of the reviews did not necessarily reflect the quality assessment of underlying studies. The human papillomavirus vaccine models became more complex over time, capturing more realistic disease transmission with different human papillomavirus strains and herd immunities. CONCLUSIONS: Additional evidence is needed for vulnerable populations (e.g., childhood cancer survivors) who are at high risk for human papillomavirus vaccine-related cancers and, therefore, may be more cost effective when receiving human papillomavirus vaccines. Quantifying human papillomavirus vaccine cost effectiveness via meta-analyses is feasible if investigators can increase the homogeneity of their populations.

Mitigation of indoor human exposure to airborne particles of outdoor origin in an urban environment during haze and non-haze periods.

During the 2019 smoke haze episode in Singapore, elevated levels of fine particulate matter (PM2.5) were observed, deteriorating both ambient and indoor air quality (IAQ). We investigated the mitigation of indoor human exposure to PM2.5 of outdoor origin under diverse exposure scenarios with and without filtration of PM2.5 during both hazy and non-hazy days. The key objective of our study was to make a comparative evaluation of the effectiveness of portable air cleaners (PACs) and air conditioning (AC) systems equipped with particle filters in improving IAQ and to assess related long-term carcinogenic and non-carcinogenic health risks. We conducted real-time measurements of PM2.5, black carbon mass concentrations and particle number concentrations in both indoor and outdoor areas, quantified the relative concentrations of the water-soluble fraction of toxic trace elements in PM2.5 for health risk assessment, and estimated the levels of thermal comfort. In addition, we calculated the total estimated cost of indoor air pollution control. Our findings suggest that indoor air cleaners are more effective at mitigating human exposure to airborne particles and reducing health risk with less consumption of electricity and better cost-effectiveness compared to AC. This information would be beneficial for public health interventions during major air pollution events.

Incidence and Risk Factors for 30-Day Readmission after Inpatient Chemotherapy among Acute Lymphoblastic Leukemia Patients.

Chemotherapy for acute lymphoblastic leukemia (ALL) patients is complex and intense, resulting in a high readmission rate. We aimed to identify the incidence, causes, and risk factors of readmission following inpatient chemotherapy among ALL patients, using 2016 National Readmission Database. We applied three different definitions of 30-day readmission: (1) nonelective readmission based on readmission type, (2) unplanned readmission defined by CMS, and (3) unintentional readmission, combining (1) and (2). We used unweighted multivariable Poisson regression with robust variance estimates for risk factors analysis, including patient-, hospital-, and admission-related characteristics. Percentage for nonelective, unplanned, and unintentional readmission were 33.3%, 22.4%, and 18.5%, respectively. The top three causes for unplanned readmissions were neutropenia/agranulocytosis (27.8%), septicemia (15.3%), and pancytopenia (11.5%). Risk ratios for unintentional readmission were 1.21 (1.08-1.36) for nonelective vs. elective admission, 1.19 (1.06-1.33) for public vs. private insurance enrollees, 0.96 (0.95-0.98) for each day of hospital stay, 0.77 (0.62-0.95) for large teaching and 0.87 (0.70-1.08) for small teaching vs. nonteaching hospitals. Possible strategies to reduce readmission among ALL patients could be shortening the gap in quality of care among teaching vs. non-teaching hospitals, understanding the difference between privately vs. publicly insured patients, and avoiding aggressive discharge after chemotherapy.

Cost-Effectiveness Analysis of Adjuvant Neratinib Following Trastuzumab in Early-Stage HER2-Positive Breast Cancer.

DISCLOSURES: No funding supported the writing of this letter. The authors report no conflicts of interest related to the subject of this letter.

Appropriateness of Otic Quinolone Use among Privately Insured US Patients.

OBJECTIVE: Considering emerging safety concerns involving otic quinolones, we assessed the extent of otic quinolone use for questionable indications. STUDY DESIGN: Descriptive cross-sectional study of a national sample of privately insured patients. SETTING: Outpatient encounters in the United States. SUBJECTS AND METHODS: Children and adults with outpatient pharmacy-dispensing claims for new prescriptions of otic or ophthalmic quinolones in 2017 were identified within the IBM MarketScan Commercial Claims & Encounters and the Medicare Supplemental Database. Each dispensing ≥30 days apart constituted a unique episode. Only claims with supporting ear-related diagnoses on outpatient encounters ±3 days of dispensing were considered. Ophthalmic drops were excluded if eye-related diagnoses were found ±30 days. Prescribing was classified as appropriate, questionable, or undetermined. RESULTS: We found 214,897 episodes in 200,270 patients. Adults were twice as likely as children to have otic treatment with questionable indications (6.2% vs 3.0%). Sensitivity analyses with broader time windows to ascertain diagnoses showed similar proportions of questionable use. Otalgia and cerumen impaction constituted 90% of questionable indications. Family physicians (6.8%) and internists (8.0%) had higher percentages of questionable use than other specialties. CONCLUSION: Based on the demonstrated risks of quinolone ear drops, opportunities exist to decrease otic quinolone use, especially in adults.

Association between statin drug use and peripheral blood leukocyte telomere length in the National Health and Nutrition Examination Survey 1999-2002: a cross-sectional study.

PURPOSE: To evaluate the association between statin drug use and peripheral blood leukocyte telomere length in a U.S. nationally representative sample of adults. METHODS: We conducted a cross-sectional analysis of data from National Health and Nutrition Examination Survey 1999-2002, representative of the noninstitutionalized U.S. POPULATION: The analytic study population included 3496 men and women aged 40-84 years without a history of cancer and who had information of telomere length and statin use. RESULTS: Compared with nonusers, statin users were more likely to be former smokers, older, white, male, and had more comorbidities. Statin users did not have longer telomeres than nonusers after age (coefficient -0.013, p = .30) and multivariable (0.0003, p = .98) adjustment. After multivariable adjustment, log-transformed telomere length nonstatistically significantly increased with increasing duration of use (0.003, p-trend = .11), which did not differ by number of comorbidities (p-interaction = 0.18). Compared with nonuse, more than 5 years of use had an odds ratio of telomere length above the 75th percentile of 1.62 (95% confidence interval 0.90-2.92; p-trend = .10). CONCLUSIONS: Although telomere length appeared to be longer with longer duration of use of a statin, this association was not statistically significant, and we could not rule out bias as the explanation.

Synthesis, molecular modeling and biological evaluation of potent analogs of 2-methoxyestradiol.

The endogenous steroid 2-methoxyestradiol (1) has attracted a great interest as a lead compound towards the development of new anti-cancer drugs. Herein, the synthesis, molecular modeling, anti-proliferative and anti-angiogenic effects of ten 2-ethyl and four 2-methoxy analogs of estradiol are reported. The ethyl group was introduced to the steroid A-ring using a novel Friedel-Crafts alkylation protocol. Several analogs displayed potent anti-proliferative activity with IC50-values in the submicromolar range towards the CEM human leukemia cancer cell line. As such, all of these compounds proved to be more active than the lead compound 2-methoxyestradiol (1) in these cells. The six most cytostatic analogs were also tested as anti-angiogenic agents using an in vitro tube formation assay. The IC50-values were determined to be in the range of 0.1 µM ±â€¯0.03 and 1.1 µM ±â€¯0.2. These six compounds were also modest inhibitors against tubulin polymerization with the most potent inhibitor was 14b (IC50 = 2.1 ±â€¯0.1 µM). Binding studies using N,N'-ethylene-bis(iodoacetamide) revealed that neither14a or 14b binds to the colchicine binding site in the tubulin protein, in contrast to 2-methoxyestradiol (1). These observations were supported by molecular modeling studies. Results from a MDA-MB-231 cell cycle assay showed that both 10e and 14b gave accumulation in the G2/M phase resulting in induction of apoptosis. The results presented herein shows that the novel analogs reported exhibit their anticancer effects via several modes of action.