Quintilian on Memory and Delivery

This chapter discusses Quintilian’s account of delivery and memory, especially (though not solely) with regard to his extended treatment of them in Book 11. With delivery, it surveys such issues as his discussion of the appropriate gesture and voice to be adopted by the orator, and the pragmatics of delivering a speech before a Roman audience. It discusses Quintilian’s heavily gendered and class-based account of appropriate delivery, where the orator has to adopt manners appropriate for a high-status male and eschew the contrary; it also considers the uneasy relationship between high-status oratory and low-status acting. It focuses above all on the highly textualized account of performance in Quintilian, where delivery is closely linked to an assumed written text, and argues that this is the consequence of Quintilian’s classicism, where oratory is associated with an established literary canon on a par with other literary genres. With memory, it briefly discusses his mnemotechnics, but argues that Quintilian is pulled between two incompatible desires: the classicism which leads him to want to associate memorization with fidelity to a written text, but also the pragmatism which requires a large measure of spontaneity and improvisation, which may be hindered if the orator has prepared a memorized text in advance.

Adverse effects and duration of treatment of TB in Canterbury, New Zealand

BACKGROUND Treatment of TB is often extended beyond the recommended duration. The aim of this study was to assess prevalence of extended treatment and to identify associated risk factors. We also aimed to determine the frequency and type of adverse drug reactions (ADR) experienced by this study population.METHODS We performed a retrospective cohort study of all patients treated for active TB at Christchurch Hospital, Christchurch, New Zealand, between 1 March 2012 and 31 December 2018. Data for 192 patients were collected on patient demographics, disease characteristics and treatment characteristics, including planned and actual duration of treatment and ADRs.RESULTS Of 192 patients, 35 (18.2%) had treatment extended, and 85 (46.5%) of 183 with fully drug-susceptible TB received ≥9 months treatment. The most common reasons for extension were persistent or extensive disease and ADR. Extended treatment duration was not associated with any patient or disease characteristics. We found 35 (18.2%) patients experienced at least one ADR. The most common ADRs were hepatitis, rash and peripheral neuropathy.CONCLUSION TB treatment extension beyond WHO guidelines is common. Further research is needed to guide management of those with slow response to treatment. Methods for early detection of ADR, systems to improve adherence and therapeutic drug monitoring are potentially useful strategies.

Predictors of slow clinical response and extended treatment in patients with extra-pulmonary tuberculosis in Pakistan, A hospital-based prospective study

The optimal duration of treatment in different forms of extrapulmonary tuberculosis (EPTB) is not clearly defined. This study aimed to identify predictors of slow clinical response and extended anti-TB treatment in EPTB patients. Socio-demographic, clinical, and microbiological characteristics of EPTB patients registered for anti-TB treatment at a tertiary care hospital, were analysed for identification of predictors of extended treatment. A total of 251 patients (137 lymphadenitis, and 114 pleuritis) were included in the analysis. Treatment was extended to more than 6 months in 58/251 (23%) patients. In the multivariate regression analysis, culture-positive EPTB (p = 0.007) [OR (95% CI) = 3.81 (1.43, 10.11)], history of diabetes (p = 0.014) [OR (95% CI) = 25.18 (1.94, 325.83)], smokeless tobacco use (p = 0.002) [OR (95% CI) = 17.69 (2.80, 111.72)], and slow regression of local signs and symptoms after 2 months of treatment (p < 0.001) [OR (95% CI) = 17.09 [(5.79, 50.39)] were seen to be significantly associated with treatment extension. Identification of predictors of extended treatment can help clinical decisions regarding optimal duration of treatment. Further studies are needed to identify subgroups of EPTB patients who can benefit from a shorter or longer treatment regimen.

Place, Being, and Agency

Chapter 3 identifies the special world of Shakespearean comedy in terms of the multiple dimensions of place, something that seems especially pertinent to the comic genre. Shakespeare’s comedies deploy the Renaissance sense of place as capable of being either mundane or magical. Reflecting that dialectic, the association of place with Italy in the comedies calls upon popular notions of that locale as full of contradictions yet open to the possibility of transformation. The comedies often organize locale in terms of a contrast between “regulative” and “protean” places (the latter recalling Frye’s “green world”). Protean environs are enchanted and can enchant, as in As You Like It (which receives extended treatment); they make change and transformative experience possible; and yet they exhibit different degrees of agency in different plays. Notwithstanding its power, the protean world is a nice place to visit, but one would not want to live there. The chapter concludes by assessing the power of place to affect action and meaning in a range of comedies.

Comparative Effectiveness and Safety of Extended Anticoagulant Therapy Among Medicare Beneficiaries with Venous Thromboembolism

Introduction: Approximately 30% of patients with venous thromboembolism (VTE) experience a recurrence within 10 years of the initial event with their recurrence risk peaking during the first 6-12 months. Two large randomized clinical trials AMPLIFY-EXT and PADIS-PE reported that extended treatment with apixaban and warfarin beyond 6 months of initial treatment reduced recurrent VTE without increasing the rate of major bleeding compared to placebo, respectively. Little is known about real-world effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment for Medicare beneficiaries with VTE, despite the fact that VTE disproportionately affects the elderly. We assessed the effectiveness and safety of extended use of apixaban and warfarin beyond 6 months of initial treatment for prevention of recurrent VTE and adverse major bleeding events among Medicare beneficiaries with newly diagnosed VTE. Methods: A retrospective cohort study using 2014-2018 Medicare data (5% samples in 2014-2016 and 15% samples of Medicare beneficiaries in 2017-2018) was conducted for patients aged ≥18 years with a diagnosis of deep vein thrombosis or pulmonary embolism ascertained from inpatient claims. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy defined as ≥83% proportion days covered with oral anticoagulants during the initial 6-month period, and received extended treatment with either apixaban or warfarin or no extended therapy. We compared the risks of recurrent VTE and major bleeding between apixaban, warfarin, and no treatment groups. To adjust for differences in baseline characteristics and clinical factors (e.g., HAS-BLED score, active cancer, and provoked VTE) between groups, we used the stabilized inverse probability treatment weighting (IPTW) method. Follow-up continued until the occurrence of the first event, switch to the comparator, disenrollment, death, or end of the study period. Multivariable Cox proportional hazards modeling with IPTW was used to obtain adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI). Results: The study cohort (mean age=74 ±12 years, 40% male, 76% White) consisted of 2,315 users of extended apixaban treatment (83% with 5 mg twice a day and 17% with 2.5 mg twice a day; mean duration=6.2 months), 2,757 users of extended warfarin treatment (mean duration=8.2 months), and 2,328 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The incidence rates of recurrent VTE were 0.42, 1.73, and 1.72 per 100 person-years, and those of major bleeding were 2.28, 3.62, and 1.43 per 100 person-years in the apixaban, warfarin, and no treatment groups, respectively (Table 1). Compared to no extended treatment, the use of apixaban was associated with an 80% decreased risk of recurrent VTE (aHR=0.19, 95%CI=0.06-0.55) without increasing the risk of major bleeding (aHR=1.19, 95%CI=0.65-2.19); the use of warfarin did not lower the risk of recurrent VTE (aHR=0.75, 95%CI=0.42-1.37) but increased the risk of major bleeding (aHR=1.92, 95%CI=1.13-3.25). Compared to the use of warfarin, the use of apixaban was associated with a decreased risk of recurrent VTE (aHR=0.26, 95% CI=0.09-0.76) and no difference in major bleeding risk (aHR=0.61, 95%CI=0.36-1.06). These findings remained consistent in subgroup (e.g., patients with provoked vs. unprovoked VTE, patients with active cancer vs. those without, and patients with chronic kidney diseases vs. those without) and sensitivity analyses (e.g., ≥92% proportion days covered with oral anticoagulants during the initial 6-month period). Conclusions: Compared to no extended therapy, extended anticoagulation with apixaban was associated with a reduced risk of recurrent VTE without increasing the risk of major bleeding, whereas warfarin did not lower risk of recurrent VTE but increased the risk of major bleeding among Medicare beneficiaries with VTE. In the head-to-head comparison, the use of apixaban was more effective than warfarin in preventing recurrent VTE, without increasing the risk of major bleeding events. Our findings suggest that apixaban is an effective and safer option for extended treatment of VTE when compared to warfarin or no treatment among Medicare beneficiaries with VTE. Figure 1 Figure 1. Disclosures Park: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Kang: BMS/Pfizer Alliance American Thrombosis InvestigatorInitiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: MERCK: Research Funding; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. DeRemer: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS advisory board attendee: Honoraria.

Adherence Trajectories of Extended Direct-Acting Oral Anticoagulants and Risk of Recurrent Venous Thromboembolism and Major Bleeding: A Retrospective Cohort Study

Introduction: The optimal duration of extended oral anticoagulant treatment for patients with venous thromboembolism (VTE) beyond the initial 3 to 6 months of the treatment remains undetermined. Group-based trajectory modeling (GBTM) is a data-driven method that can categorize patients with similar longitudinal adherence patterns over time into distinct subgroups. This study identified distinct patient subgroups with similar adherence trajectories of extended treatment of direct-acting oral anticoagulants (DOACs), and then examined the association between adherence trajectories and the risk of recurrent VTE and major bleeding among patients with VTE. Methods: We identified patients ≥18 years with a diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) from inpatient claims using 2013-2019 Truven Commercial and Medicare Supplemental database. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy-defined as ≥83% proportion days covered (PDC) with oral anticoagulants during the initial 6-month treatment period, and had extended treatment with any DOACs or no extended therapy. Based on the monthly PDC as the DOAC adherence measure, we used GBTM to identify DOAC adherence trajectories during 6 months of the extended treatment. The final trajectory model was chosen by assessing the Bayesian information criteria, Nagin's criteria, and having at least 10% of patients in each trajectory group for improving clinical utility. We compared recurrent VTE and major bleeding among adherence trajectory subgroups. Patients were followed up from the initiation of the extended treatment until the occurrence of the study outcomes, discontinuation of DOACs, switching to warfarin, end of study period, or end of enrollment, whichever occurred first. Cox proportional hazard modeling with inverse probability treatment weighting (IPTW) was used to obtain hazard ratios (HR) and 95% confidence intervals (95% CI). Results: The study cohort (mean age=58.7 years and 51.1% males) consisted of 10,960 patients with extended treatment of DOACs (4,294 apixaban, 6,409 rivaroxaban, 238 dabigatran, and 19 edoxaban users) with a mean treatment duration of 7.7 months and 5,133 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The final GBTM models identified four distinct adherence trajectories for extended therapy including (1) patients with consistent adherence (group 1, 40.7%), (2) patients with gradually declining adherence (group 2, 14.3%), (3) patients with rapidly declining adherence (group 3, 13.1%), and (4) patients with no extended treatment (reference group, 31.9%) (Figure 1). The incidence rates of recurrent VTE were 18.6, 46.9, 84.1, and 160.7 per 10,000 person-years, and those of major bleeding were 61.0, 125.1, 168.3, and 48.7 per 10,000 person-years in group 1, group 2, group 3, and the reference group, respectively. After IPTW, demographics and clinical characteristics (e.g., HAS-BLED bleeding risk score, provoked VTE) were comparable across the four trajectory groups with &lt;0.1 of the standardized mean difference for each pairwise comparison. Compared to the reference group, group 1 (HR=0.09, 95% CI=0.05-0.17) and group 2 (HR=0.16, 95% CI=0.04-0.58) had decreased risk of recurrent VTE without increasing risk of major bleeding (HR=1.26, 95% CI=0.76-2.10 in group 1, HR=2.28, 95% CI=0.96-5.36 in group 2). There was no difference in the risk of recurrent VTE (HR=0.32, 95% CI=0.09-1.16) in group 3 but they had an increased risk of major bleeding (HR=2.69, 95% CI=1.00-7.23). The findings were consistent across different types of DOACs, suggesting a class effect of DOACs as extended therapy. Conclusions: We identified 4 distinct trajectories of DOAC adherence during the 6 months of extended therapy among patients who completed 6 months of initial treatment. Compared to no extended treatment, persistent use of DOACs during extended treatment was associated with a lower risk of recurrent VTE without increasing major bleeding risk, whereas a rapid decline in adherence was associated with an increased risk of major bleeding with no difference in the risk of recurrence. Our findings provide evidence on the benefits of continuing and being adherent to extended anticoagulant treatment in patients with VTE without increasing the risk of major bleeding. Figure 1 Figure 1. Disclosures Kang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Jones: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; MERCK: Research Funding. DeRemer: BMS advisory board attendee: Honoraria; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. Park: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding.