Impact of Regional Systems of Care on Disparities in Care Among Female and Black Patients Presenting With ST‐Segment–Elevation Myocardial Infarction

BACKGROUND: The American Heart Association Mission: Lifeline STEMI (ST-segment-elevation myocardial infarction) Systems Accelerator program, conducted in 16 regions across the United States to improve key care processes, resulted in more patients being treated within national guideline goals (time from first medical contact to device: <90 minutes for direct presenters to hospitals capable of performing percutaneous coronary intervention; <120 minutes for transfers). We examined whether the effort reduced reperfusion disparities in the proportions of female versus male and black versus white patients. METHODS AND RESULTS: In total, 23 809 patients (29.3% female, 82.3% white, and 10.7% black) presented with acute STEMI between July 2012 and March 2014. Change in the proportion of patients treated within guideline goals was compared between sex and race subgroups for patients presenting directly to hospitals capable of performing percutaneous coronary intervention (n=18 267) and patients requiring transfer (n=5542). The intervention was associated with an increase in the proportion of men treated within guideline goals that presented directly (58.7-62.1%, P=0.01) or were transferred (43.3-50.7%, P<0.01). An increase was also seen among white patients who presented directly (57.7-59.9%, P=0.02) or were transferred (43.9-48.8%, P<0.01). There was no change in the proportion of female or black patients treated within guideline goals, including both those presenting directly and transferred. CONCLUSION: The STEMI Systems Accelerator project was associated with an increase in the proportion of patients meeting guideline reperfusion targets for male and white patients but not for female or black patients. Efforts to organize systems of STEMI care should implement additional processes targeting barriers to timely reperfusion among female and black patients

The effect of pre-pregnancy body mass index on breastfeeding initiation, intention and duration:A systematic review and dose-response meta-analysis

Overweight and obesity not only are major risk factors for number of chronic diseases, but also a risk factor for pregnancy complications in women. The present study aims to investigate the association between pre-pregnancy BMI and the persistence and duration of BF. The electronic databases including Medline (PubMed), Scopus, Embase, Web of Science and Google Scholar were searched for papers with titles and/or abstracts including one of our keywords and published up to 15 April 2019. For dose-response relationship, the two-stage random-effects meta-analysis was performed using the �dosresmeta� function in R software. Thirty-two studies with the effect of pre-pregnancy BMI on BF initiation, intention and duration were included in the present study. Based on crude and adjusted OR models, the risk of BF cessation increased by 4 (OR = 1.04; 95 CI: 1.02�1.05) with an increase in a unit of BMI. In addition, based on crude and adjusted RR models, the risk of BF cessation increases by 2 and 1 (crude RR = 1.02; 95 CI: 1.01�1.03 and adjusted RR = 1.01; 95 CI: 0.99�1.02) with an increase in one unit of BMI. Based on the result, the health care professionals and other key stakeholders should be aware of the impact excess weight, and that women who are overweight or obese should be encouraged with continued access to guidance, counseling and support, starting from conception, to maximize BF outcomes. © 2020 The Authors Public health; Women's health; Reproductive medicine; Obstetrics and gynecology; Reproductive system; Clinical research; Pre-pregnancy, Body mass index, Breastfeeding, Initiation, Duration. © 2020 The Author

Nomenclature for alleles of the thiopurine methyltransferase gene

The drug-metabolizing enzyme thiopurine methyltransferase (TPMT) has become one of the best examples of pharmacogenomics to be translated into routine clinical practice. TPMT metabolizes the thiopurines 6-mercaptopurine, 6-thioguanine, and azathioprine, drugs that are widely used for treatment of acute leukemias, inflammatory bowel diseases, and other disorders of immune regulation. Since the discovery of genetic polymorphisms in the TPMT gene, many sequence variants that cause a decreased enzyme activity have been identified and characterized. Increasingly, to optimize dose, pretreatment determination of TPMT status before commencing thiopurine therapy is now routine in many countries. Novel TPMT sequence variants are currently numbered sequentially using PubMed as a source of information; however, this has caused some problems as exemplified by two instances in which authors' articles appeared on PubMed at the same time, resulting in the same allele numbers given to different polymorphisms. Hence, there is an urgent need to establish an order and consensus to the numbering of known and novel TPMT sequence variants. To address this problem, a TPMT nomenclature committee was formed in 2010, to define the nomenclature and numbering of novel variants for the TPMT gene. A website (http://www.imh.liu.se/tpmtalleles) serves as a platform for this work. Researchers are encouraged to submit novel TPMT alleles to the committee for designation and reservation of unique allele numbers. The committee has decided to renumber two alleles: nucleotide position 106 (G>A) from TPMT*24 to TPMT*30 and position 611 (T>C, rs79901429) from TPMT*28 to TPMT*31. Nomenclature for all other known alleles remains unchanged

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines

Identification of genes associated with platinum drug sensitivity and resistance in human ovarian cancer cells

Platinum-based chemotherapeutic regimens are ultimately unsuccessful due to intrinsic or acquired drug resistance. Understanding the molecular basis for platinum drug sensitivity/resistance is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 4000 genes using cDNA microarray screening in a panel of 14 unrelated human ovarian cancer cell lines derived from patients who were either untreated or treated with platinum-based chemotherapy. These data were analysed relative to the sensitivities of the cells to four platinum drugs (cis-diamminedichloroplatinum (cisplatin), carboplatin, DACH-(oxalato)platinum (II) (oxaliplatin) and cis-diamminedichloro (2-methylpyridine) platinum (II) (AMD473)) as well as the proliferation rate of the cells. Correlation analysis of the microarray data with respect to drug sensitivity and resistance revealed a significant association of Stat1 expression with decreased sensitivity to cisplatin (r=0.65) and AMD473 (r=0.76). These results were confirmed by quantitative RT–PCR and Western blot analyses. To study the functional significance of these findings, the full-length Stat1 cDNA was transfected into drug-sensitive A2780 human ovarian cancer cells. The resulting clones that exhibited increased Stat1 expression were three- to five-fold resistant to cisplatin and AMD473 as compared to the parental cells. The effect of inhibiting Jak/Stat signalling on platinum drug sensitivity was investigated using the Janus kinase inhibitor, AG490. Pretreatment of platinum-resistant cells with AG490 resulted in significant increased sensitivity to AMD473, but not to cisplatin or oxaliplatin. Overall, the results indicate that cDNA microarray analysis may be used successfully to identify determinants of drug sensitivity/resistance and future functional studies of other candidate genes from this database may lead to an increased understanding of the drug resistance phenotype

Neo-appreciation pedagogy: the pragmatics of reading aesthetic affect in the undergraduate classroom

textThis dissertation offers collegiate literary instructors a theoretical foundation and pedagogical method for teaching their students how to analyze aesthetic affect: a theory and practice termed here "neo-appreciation pedagogy." While the dissertation outlines a general theory of literary reading, it only does so to provide the basis for classroom methods that directly confront archaic, text-immanent models of meaning production. While preserving much of the method and terminology of the traditional literary classroom, neo- appreciation pedagogy offers students an overt admission that literary study is at least partially a transmission of particular cultural biases; however, it also teaches them ways to critique those cultural biases, beginning with their own responses to "great" literature. In other words, neo-literary appreciation pedagogy seeks to teach students why certain cultural artifacts have been valued in the past (particularly works which they themselves typically do not value) by expanding their repertoire of reading or "lectical" strategies. In pursuit of this goal, this dissertation outlines a taxonomy of conventional reading strategies simple enough to teach to undergraduate students. This taxonomy is articulated into a heuristic - "the lectical triangle" - used to teach students first how to analyze the lectical strategies they already use then how to deploy those and other lectical strategies (with which they may be less familiar) in increasingly sophisticated - i.e. academic - ways. Building upon post-structuralist, linguistic theory and American Pragmatism in general (along with significant elaboration s upon the work of Wolfgang Iser and Wayne Booth in particular), lectical analysis helps students explore how different textual patterns can "invite" certain lectical responses and only "tolerate" or even "resist" others while never requiring any particular response. Neo-appreciation pedagogy, therefore, does not seek to reinforce conventional or canonical readings of literary works, much less reproduce any particular aesthetic affect; instead, it seeks to give students the tools to understand the lectical conventions by which such works have been valued in the past, while giving them more lectical resources for readings they might perform in the future.Englis