Функції реалій в інтертекстах американських гумористичних новел

Актуальность работы связана с изучением текста в "диалоге" с другими текстами, т.е. в рамках теории интертекстуальности. Реалия рассматривается как элемент интертекста, где она функционируюет в составе аллюзии, цитаты, заголовочного комплекса и является составным элементом американских юмористических новелл 19-20 вв.Актуальність роботи пов'язана з вивченням тексту у "діалозі" з іншими текстами, тобто в рамках теорії інтертекстуальності. Реалія розглядається як елемент інтертексту, де вона функціонує у складі алюзії, цитати, заголовкового комплексу, і є складовим елементом американських гумористичних новел 19-20 ст.The actuality of the work is connected with the study of the text in "in dialogue" with other texts, i.e. within the limits of the intertextuality theory. A piece of realia is examined as an element of intertext where it functions in the structure of allusion, quotation, headline complex, and is a constituent part of the 19th-20th c. American humour short stories

Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis

BACKGROUND: The current World Health Organization (WHO) pediatric tuberculosis dosing guidelines lead to suboptimal drug exposures. Identifying factors altering the exposure of these drugs in children is essential for dose optimization. Pediatric pharmacokinetic studies are usually small, leading to high variability and uncertainty in pharmacokinetic results between studies. We pooled data from large pharmacokinetic studies to identify key covariates influencing drug exposure to optimize tuberculosis dosing in children. METHODS AND FINDINGS: We used nonlinear mixed-effects modeling to characterize the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide, and investigated the association of human immunodeficiency virus (HIV), antiretroviral therapy (ART), drug formulation, age, and body size with their pharmacokinetics. Data from 387 children from South Africa, Zambia, Malawi, and India were available for analysis; 47% were female and 39% living with HIV (95% on ART). Median (range) age was 2.2 (0.2 to 15.0) years and weight 10.9 (3.2 to 59.3) kg. Body size (allometry) was used to scale clearance and volume of distribution of all 3 drugs. Age affected the bioavailability of rifampicin and isoniazid; at birth, children had 48.9% (95% confidence interval (CI) [36.0%, 61.8%]; p 25 kg could improve rifampicin exposures. Our analysis was limited by the differences in availability of covariates among the pooled studies. CONCLUSIONS: Children older than 3 months have lower rifampicin exposures than adults and increasing their dose by 75 or 150 mg could improve therapy. Altered exposures in children with HIV is most likely caused by concomitant ART and not HIV per se. The importance of the drug-drug interactions with lopinavir/ritonavir and efavirenz should be evaluated further and considered in future dosing guidance. TRIAL REGISTRATION: ClinicalTrials.gov registration numbers; NCT02348177, NCT01637558, ISRCTN63579542

'I saw it as a second chance': A qualitative exploration of experiences of treatment failure and regimen change among people living with HIV on second- and third-line antiretroviral therapy in Kenya, Malawi and Mozambique.

Increasing numbers of people living with HIV (PLHIV) in sub-Saharan Africa are experiencing failure of first-line antiretroviral therapy and transitioning onto second-line regimens. However, there is a dearth of research on their treatment experiences. We conducted in-depth interviews with 43 PLHIV on second- or third-line antiretroviral therapy and 15 HIV health workers in Kenya, Malawi and Mozambique to explore patients' and health workers' perspectives on these transitions. Interviews were audio-recorded, transcribed and translated into English. Data were coded inductively and analysed thematically. In all settings, experiences of treatment failure and associated episodes of ill-health disrupted daily social and economic activities, and recalled earlier fears of dying from HIV. Transitioning onto more effective regimens often represented a second (or third) chance to (re-)engage with HIV care, with patients prioritising their health over other aspects of their lives. However, many patients struggled to maintain these transformations, particularly when faced with persistent social challenges to pill-taking, alongside the burden of more complex regimens and an inability to mobilise sufficient resources to accommodate change. Efforts to identify treatment failure and support regimen change must account for these patients' unique illness and treatment histories, and interventions should incorporate tailored counselling and social and economic support

Low levels of viral suppression among refugees and host nationals accessing antiretroviral therapy in a Kenyan refugee camp.

BACKGROUND: Refugees and host nationals who accessed antiretroviral therapy (ART) in a remote refugee camp in Kakuma, Kenya (2011-2013) were compared on outcome measures that included viral suppression and adherence to ART. METHODS: This study used a repeated cross-sectional design (Round One and Round Two). All adults (≥18 years) receiving care from the refugee camp clinic and taking antiretroviral therapy (ART) for ≥30 days were invited to participate. Adherence was measured by self-report and monthly pharmacy refills. Whole blood was measured on dried blood spots. HIV-1 RNA was quantified and treatment failures were submitted for drug resistance testing. A remedial intervention was implemented in response to baseline testing. The primary outcome was viral load <5000 copies/mL. The two study rounds took place in 2011-2013. RESULTS: Among eligible adults, 86% (73/85) of refugees and 84% (86/102) of Kenyan host nationals participated in the Round One survey; 60% (44/73) and 58% (50/86) of Round One participants were recruited for Round Two follow-up viral load testing. In Round One, refugees were older than host nationals (median age 36 years, interquartile range, IQR 31, 41 vs 32 years, IQR 27, 38); the groups had similar time on ART (median 147 weeks, IQR 38, 64 vs 139 weeks, IQR 39, 225). There was weak evidence for a difference between proportions of refugees and host nationals who were virologically suppressed (<5000 copies/mL) after 25 weeks on ART (58% vs 43%, p = 0.10) and no difference in the proportions suppressed at Round Two (74% vs 70%, p = 0.66). Mean adherence within each group in Round One was similar. Refugee status was not associated with viral suppression in multivariable analysis (adjusted odds ratio: 1.69, 95% CI 0.79, 3.57; p = 0.17). Among those not suppressed at either timepoint, 69% (9/13) exhibited resistance mutations. CONCLUSIONS: Virologic outcomes among refugees and host nationals were similar but unacceptably low. Slight improvements were observed after a remedial intervention. Virologic monitoring was important for identifying an underperforming ART program in a remote facility that serves refugees alongside host nationals. This work highlights the importance of careful laboratory monitoring of vulnerable populations accessing ART in remote settings

Novel approaches to postnatal prophylaxis to eliminate vertical transmission of HIV

No abstract available.Support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) is provided by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health, all components of the National Institutes of Health and by NICHD.http://www.ghspjournal.orgam2024Paediatrics and Child HealthSDG-03:Good heatlh and well-bein

Casting a Wide Net: HIV Drug Resistance Monitoring in Pre-Exposure Prophylaxis Seroconverters in the Global Evaluation of Microbicide Sensitivity Project.

BACKGROUND: Evidence of HIV drug resistance (HIVDR) in individuals using oral pre-exposure prophylaxis (PrEP) who acquire HIV is limited to clinical trials and case studies. More data are needed to understand the risk of HIVDR with oral PrEP during PrEP rollout. Mechanisms to collect these data vary, and are dependent on cost, scale of PrEP distribution, and in-country infrastructure for the identification, collection, and testing of samples from PrEP seroconverters. METHODS: The Global Evaluation of Microbicide Sensitivity (GEMS) project, in collaboration with country stakeholders, initiated HIVDR monitoring among new HIV seroconverters with prior PrEP use in Eswatini, Kenya, South Africa, and Zimbabwe. Standalone protocols were developed to assess HIVDR among a national sample of PrEP users. In addition, HIVDR testing was incorporated into existing demonstration projects for key populations. LESSONS LEARNED: Countries are supportive of conducting a time-limited evaluation of HIVDR during the early stages of PrEP rollout. As PrEP rollout expands, the need for long-term HIVDR monitoring with PrEP will need to be balanced with maintaining national HIV drug resistance surveillance for pretreatment and acquired drug resistance. Laboratory capacity is a common obstacle to setting up a monitoring system. CONCLUSIONS: Establishing HIV resistance monitoring within PrEP programs is feasible. Approaches to drug resistance monitoring may evolve as the PrEP programs mature and expand. The methods and implementation support offered by GEMS assisted countries in developing methods to monitor for drug resistance that best fit their PrEP program needs and resources

Cost-effectiveness of easy-access, risk-informed oral pre-exposure prophylaxis in HIV epidemics in sub-Saharan Africa: a modelling study.

BACKGROUND: Approaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective. METHODS: We applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug$11, HIV test $4, and$14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3$100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP. FINDINGS: In the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished. INTERPRETATION: Under the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation. FUNDING: US Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation

Antiretroviral Medication Prescription Errors and Associated Factors among HIV Infected Children in Selected Health Facilities in Nairobi, Kenya

Thesis (Master's)--University of Washington, 2018University of Washington Abstract Antiretroviral Medication Prescription Errors and Associated Factors among HIV Infected Children in Selected Health Facilities in Nairobi, Kenya Irene Njahira Mukui Chair of Committee: Carey Farquhar Background: Access to life saving antiretroviral therapy (ART) in many resource-limited settings has increased, yet more than 30% of children on ART do not achieve viral suppression. Multiple factors contribute to viral suppression including patient, drug and health system factors. Infants and children require continuous medication dose adjustments in response to changing pharmacodynamics and inappropriate dosing may contribute to viral non-suppression. This study sought to determine the magnitude of prescription dosing errors and associated factors. Methods: We conducted a cross sectional study among HIV Infected children aged ≤11 years receiving ART in four public health facilities. Demographic, clinical and prescription data were abstracted from the medical charts of children receiving ART for the last clinical visit. Descriptive statistics were used to summarize participant characteristics. Logistic regression was conducted to determine factors associated with prescription dosing errors. Results: A total of 196 children were included in the study; among these, 52.6% were male and the median age was 7.9 years (IQR 4.8, 10.0). The most commonly used ART regimen was abacavir/lamivudine/lopinavir/ritonavir taken by 31.1% (61/196) of children. Overall, 43.6% (85/196), 45.9% (90/196) and 46.9% (92/196) of children lacked data on specific ARV formulation, dosage and frequency of dosing, respectively. Among 104 children with complete prescription information, the dosing error rate was 36.5% (38/104). In a multivariable model, being on non-nucleoside reverse transcriptase inhibitors was independently associated with prescription dosing errors (adjusted odds ratio 8.8; 95% confidence interval 2.1-36.3). Conclusion: Half of children receiving antiretroviral therapy had inadequate prescription information and among those with adequate information, one third had prescription dosing errors. These findings calls for urgent measures to address health care prescribing practices and knowledge. In addition, further evaluation should be conducted to determine associations with viral suppression

Challenges to and opportunities for the adoption and routine use of early warning indicators to monitor pediatric HIV drug resistance in Kenya

Abstract Background Pediatric non-adherence to antiretroviral therapy (ART), loss to follow-up, and HIV drug resistance (HIVDR) are challenges to achieving UNAIDS’ targets of 90% of those diagnosed HIV-positive receiving treatment, and 90% of those receiving treatment achieving viral suppression. In Kenya, the pediatric population represents 8% of total HIV infections and pediatric virological failure is estimated at 33%. The monitoring of early warning indicators (EWIs) for HIVDR can help to identify and correct gaps in ART program functioning to improve HIV care and treatment outcomes. However, EWIs have not been integrated into health systems. We assessed challenges to the use of EWIs and solutions to challenges identified by frontline health administrators. Methods We conducted key informant interviews with health administrators who were fully knowledgeable of the ART program at 23 pediatric ART sites in 18 counties across Kenya from May to June 2015. Thematic content analysis identified themes for three EWIs: on-time pill pick-up, retention in care, and virological suppression. Results Nine themes—six at the facility level and three at the patient level—emerged as major challenges to EWI monitoring. At the facility level, themes centered on system issues (e.g., slow return of viral load results), staff shortages and inadequate adherence counseling skills, lack of effective patient tracking and linkage systems, and lack of support for health personnel. At the patient level, themes focused on stigma, non-disclosure of HIV status to children who are age eligible, and little engagement of guardians in the children’s care. Practical solutions identified included the use of lay health workers (e.g., peer educators, community health workers) to implement a variety of care and treatment tasks, whole facility approaches to adherence counseling, adolescent peer support groups, and working with children directly as soon as they are age eligible. Discussion The monitoring of EWIs has not been routine in health facilities in Kenya due to several challenges. However, facilities have implemented novel strategies to address some of these barriers. Future work is needed to assess whether scale-up of some of these approaches can aid in the effective use of EWIs and improving HIV care outcomes among the pediatric population