Implication of antiretrovival therapy on children's health-related quality of life in conflict situation = Gesundheitsbezogene Auswirkungen der antiretroviralen Therapie auf die Lebensqualität bei Kindern in Konfliktsituationen ; eine Untersuchung aus dem Bezirk Gulu, Uganda

Diese Studie beschäftigt sich mit den Auswirkungen der Verabreichung von antiretroviralen Medikamenten an Kinder, die mit HIV infiziert sind und in der semi-urbanen Umgebung im Bezirk Gulu, Norduganda, leben. Ziel war es, die Lebensqualität hinsichtlich der gesundheitlichen Entwicklung dieser Kinder, die eine antiretrovirale Therapie erhalten, unter Berücksichtigung der Folgen des Bürgerkriegs, zu untersuchen. Die Studie erfolgte anhand eines Begriffsmodels auf Basis von Literatur. Es wird angenommen, dass die vorgeschlagenen Faktoren in diesem Begriffsmodel interagieren und die Einstellung zu Therapien der Betroffenen, allgemeinem Zugang zu medizinischer Versorgung und zur Einhaltung der Behandlungsmethoden, um die Lebensqualität zu verbessern, beeinflussen. Die Faktoren, welche innerhalb der Bürgerkriegssituation interagieren, beinhalten: Die Rolle der Politik und NGOs, gesundheitsbeeinflußende Faktoren, soziokulturelle Charakteristika, Gesundheitssysteme, Einstellungen zu Gesundheit, psychosoziale Faktoren, Indikatoren zur Belastbarkeit einer Familie und gesundheitsbezogene Parameter über Lebensqualität und Gesamtgesundheit. Zur qualitativen Datenerhebung wurden ethnographische Forschungsmethoden angewandt um den Alltag der Kinder, welche eine antiretrovirale Therapie erhalten, in ihrem Haushaltsumfeld zu untersuchen. Die Datensammlung wurde mit dem Instrument des triangularen Forschungsinstruments – Sekundärdaten, Tiefeninterviews mit Informanten in Schlüsselpositionen, den Müttern der Kinder, Gruppendiskussionen und teilnehmender Beobachtung erarbeitet. Die Datenerhebung fand in zwei sechsmonatigen Perioden statt, in welchen 19 Tiefeninterviews mit Müttern, fünf mit Informanten in Schlüsselpositionen und vier Gruppendiskussionen mit teilnehmender Beobachtung durchgeführt wurden. Für die thematische Datenanalyse wurde offenes, axiales und selektives Kodieren unter Anwendung von Atlas.ti 6 (eine Software zur Textanalyse) angewendet. Die Netzwerkanalyse der Codes generierte Themen, welche in der Dissertation diskutiert wurden. Ergebnisse der Analyse wurden mit den Informanten gegengeprüft und ein Nachweis wurde im Validationsprozess erbracht. Durch die Studie wurde bewiesen, dass, trotz gegenteiliger Argumente, der Bürgerkrieg negativen Einfluss auf die HIV/AIDS Epidemiologie in Form von erhöhter Armut, Verlust von Eigentum und Leben, Zerstörung der Gesundheitsinfrastruktur und geschwächten Haushalten hat. Trotz aller Herausforderungen kann unter bestimmten Bedingungen die Lebensqualität der Kinder unter antiretroviraler Therapie wesentlich verbessert werden obwohl die Haushalte nicht voll belastbar sind, das Gesundheitssystem inadequat ist, sowie die nationalen und internationalen Gelder gekürzt werden. Die erzielten Erfolge sind in Gefahr, weil viele Kinder noch gar nicht mit der antiretroviralen Therapie begonnen haben. Die Studie brachte ebenso hervor, dass Best Practices wie Kindertage und das Präventionsprojekt von lokalen Organisationen wie TASO und Health Alert-Uganda nachhaltig positive Resultate im Rahmen der antiretroviralen Therapie erbringen. Aufgrund der mangelnden qualitativen Daten über die Lebensqualität HIV-infizierter Menschen in ökonomisch benachteiligten Gebieten, möchte die Studie auch zu mehr Forschung in diesem Gebiet auffordern. Da die Finanzierung das Hauptproblem darstellt, ist eine bessere Unterstützung durch die Regierung notwendig. Die Erstellung von Richtlinien zur Kosteneffizienz dieser Best Practices, welche derzeit von regionalen Hilfsorganisationen durchgeführt werden, ist notwendig.This study explored the response to Antiretroviral (ARV) drug use by children living with HIV among communities within the vicinity of Gulu district municipality in northern Uganda. The aim was to look at the quality of life as the health outcomes of treatment for these children accessing ART in the context of civil conflict. The study was guided by an annotated conceptual framework informed by literature, where by suggested factors are thought to interact to influence the health seeking behaviour, general treatment access and adherence practices which results in better quality of life. These factors operating within the conflict environment include government policies and NGO functions, health determinants, sociocultural characteristics, health systems, health behaviour and psychosocial factors, family resilience indicators, health-related quality of life parameters and quality of life outcomes. The exploratory qualitative study employed ethnographic research method to look at the daily life experience of children living with HIV/AIDS and are undergoing antiretroviral therapy (ART) within their households’ living environment. Data collection was done using triangulated study tools of document reviews, in-depth interviews with respondents and key informants, focus group discussions and participants’ observation. Data collection was done in two phases of six months each in which nineteen in-depth interviews, five key informants’ interviews, and four focus group discussions were done. Thematic data analysis was used in which open, axial and selective coding for data reduction and analysis was done aided by Atlas.ti 6 computer software for text analysis. The thematic network analysis of the codes generated key themes that were used to discuss the thesis. Outcomes from the analysis were crosschecked with respondents and an audit trail made as a validation process. The study findings have revealed that despite major arguments about the impact of conflict on the spread of HIV/AIDS, the LRA conflict indeed negatively impacted on the HIV/AIDS epidemiology through increase in poverty, loss of property and lives, destruction of health infrastructure, as well as increased households’ vulnerability. However amidst all these challenges, within certain conditions, treatment outcomes shown by the quality of life of these children on ART have yielded pretty good results; yet with poor social resilience, health systems inadequacy, limited government funding of the health sector couple with dwindling donor funds, the gains are seriously threatened, considering that many more children are yet to even start on the ART. The study also found that best practices such as children’s days and positive prevention project by local community based organisations like TASO and Health Alert-Uganda are yielding positive results in the scale up of ART. Due to lack of data on quality of life related to HIV in resource limited settings, the study calls for more research in this field and as funds remain a major problem to policy makers, better government support are urged to make guidelines that incorporate cost effective, best practices that are currently being used by grass root organisations

Oxygen in Unevolved Metal-Poor Stars from Keck Ultraviolet HIRES Spectra

The determination of the abundance of oxygen (O) is important in our understanding of mass–spectrum of previous generations of stars, the evolution of the Galaxy, stellar evolution, and the age-metallicity relation. We have measured O in 24 unevolved stars with Keck HIRES observations of the OH lines in the ultraviolet spectral region at a spectral resolution of ~45,000. The spectra have high signal-to-noise ratios, typically 60–110, and high dispersion, 0.022 Å per pixel. Very special care has been taken in determining the stellar parameters in a consistent way and we have done this for two different, plausible temperature scales. The O abundance from OH has been computed by spectrum synthesis techniques for all 24 stars plus the Sun for which we have a Keck spectrum of the daytime sky. In addition, we determined O abundances from the O I triplet with our stellar parameters and the published equivalent widths of the three O I lines from six sources. The comparison of data analyzed with the same, consistently determined, parameter sets show generally excellent agreement in the O abundances; differences in the origin of the models (not the parameters) may result in abundance differences of 0.07 to 0.11 dex. We show that the O abundances from OH and from O I are reliable and independent and average the two for the adopted O. This averaging has the great benefit of neutralizing uncertainties in the parameters since OH and O I strengths depend on effective temperature and gravity in opposite directions. For these cool, unevolved stars we find that O is enhanced relative to Fe with a completely linear relation between [O/H] and [Fe/H] over 3 orders of magnitude with very little scatter; taking the errors into account in determining the fits, we find [O/H] = +0.66 (±0.02) [Fe/H] + 0.05 (±0.04). The O abundances from 76 disk stars of Edvardsson et al. have a measured slope of 0.66 (identical to our halo dwarf stars) and fit this relationship smoothly. The relation between [O/Fe] and [Fe/H] is robustly linear and shows no sign of a break at metallicities between -1.0 and -2.0, as has been discussed by others. At low metallicities, [Fe/H] \u3c -3.0, [O/Fe] \u3e +1.0. The fit to this relationship (taking the errors into account) is [O/Fe] = -0.35 (±0.03) [Fe/H] + 0.03 (±0.05). The enrichment of O is probably still from massive stars and Type II supernovae; however, the absence of a break in [O/Fe] versus [Fe/H] runs counter to traditional galactic evolution models, and the interplay of Type II and Type Ia supernovae in the production of O and Fe should be reexamined. It appears that either Fe or O can be used as a chronometer in studies of galactic evolution

The Confluence of Stereotactic Ablative Radiotherapy and Tumor Immunology

Stereotactic radiation approaches are gaining more popularity for the treatment of intracranial as well as extracranial tumors in organs such as the liver and lung. Technology, rather than biology, is driving the rapid adoption of stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), in the clinic due to advances in precise positioning and targeting. Dramatic improvements in tumor control have been demonstrated; however, our knowledge of normal tissue biology response mechanisms to large fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular expression of MHC I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors to enhance antitumor immune responses

NASA’s Terabyte Infrared Delivery (TBIRD) Program: Large-Volume Data Transfer from LEO

Satellites in low-Earth orbit (LEO) have on-board sensors that can generate large amounts of data to be delivered to a ground user. Direct-to-Earth delivery from LEO is challenging because of the sparse contact with a ground terminal, but the short link distances involved can enable very high data rates by exploiting the abundance of spectrum available at optical frequencies. We provide an overview and update of NASA’s Terabyte Infrared Delivery (TBIRD) program, which will demonstrate a direct-to-Earth laser communication link from a small satellite platform to a small ground terminal at burst rates up to 200Gbps. Such a link is capable of transferring several terabytes per day to a single ground terminal. The high burst rates are achieved by leveraging off-the-shelf fiber-telecommunications transceivers for use in space applications. A 2U TBIRD payload is currently being developed for flight on a 6U NASA CubeSat

The confluence of stereotactic ablative radiotherapy and tumor

Stereotactic radiation approaches are gaining more popularity for the treatment of intracranial as well as extracranial tumors in organs such as the liver and lung. Technology, rather than biology, is driving the rapid adoption of stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), in the clinic due to advances in precise positioning and targeting. Dramatic improvements in tumor control have been demonstrated; however, our knowledge of normal tissue biology response mechanisms to large fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular expression of MHC I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors to enhance antitumor immune responses

False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women

Objective: Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). Design: To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. Methods: Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. Results: HIV prevalence was 0.06 % among 921,438 pregnant women and 1.34 % among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14 % vs. 0.21%, odds ratio 0.65 [95 % confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p,0.01) to have Western blot-negative (52.9 % vs. 9.8%) and indeterminate results (17.0 % vs. 3.7%) and lower PPV (30 % vs. 87%). The p24 band was detected more often among pregnant women (p,0.01). Conclusions: False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others

Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström’s Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study

[Purpose]: The double-blind, randomized, placebo-controlled phase III iNNOVATE study showed sustained efficacy of ibrutinib-rituximab in Waldenström's macroglobulinemia (WM). Here, we present the final analysis from iNNOVATE. [Methods]: Patients had confirmed symptomatic WM, either previously untreated or previously treated; patients with prior rituximab had at least a minor response to their last rituximab-based regimen. Patients were randomly assigned to once-daily ibrutinib 420 mg plus rituximab or placebo plus rituximab (n = 75 per arm). The primary end point was progression-free survival (PFS). Secondary end points included response rate, time to next treatment, hemoglobin improvement, overall survival, and safety. [Results]: With a median follow-up of 50 (range, 0.5-63) months, median (95% CI) PFS was not reached (57.7 months to not evaluable) with ibrutinib-rituximab versus 20.3 months (13.0 to 27.6) with placebo-rituximab (hazard ratio, 0.250; P < .0001). PFS benefit was regardless of prior treatment status, MYD88 and CXCR4 mutation status, or key patient characteristics. Higher response rates (partial response or better) were observed with ibrutinib-rituximab (76% v 31% with placebo-rituximab; P < .0001) and were sustained over time. Median time to next treatment was not reached with ibrutinib-rituximab versus 18 months with placebo-rituximab. More patients receiving ibrutinib-rituximab versus placebo-rituximab had sustained hemoglobin improvement (77% v 43%; P < .0001). Median overall survival was not reached in either arm. Ibrutinib-rituximab maintained a manageable safety profile; the prevalence of grade ≥ 3 adverse events of clinical interest generally decreased over time. [Conclusion]: In the final analysis of iNNOVATE with a median follow-up of 50 months, ibrutinib-rituximab showed ongoing superiority across clinical outcomes in patients with WM regardless of MYD88 or CXCR4 mutation status, prior treatment, and key patient characteristics.Supported by Pharmacyclics LLC, an AbbVie Company. Pharmacyclics LLC sponsored and designed the study.Peer reviewe

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Greece

<p>Abstract</p> <p>Background</p> <p>Inheritance of a mutation in either <it>BRCA1 </it>or <it>BRCA2 </it>accounts for approximately 5% of all breast cancer cases, but varies by country. Investigations into the contribution of <it>BRCA </it>mutations to breast cancer incidence in Greece have been, for the most part, limited by small sample sizes and by the use of cases selected for their family history of cancer. The aim of the current study was to estimate <it>BRCA </it>mutation frequencies in breast cancer patients unselected for family history.</p> <p>Methods</p> <p>To do so, we enrolled 127 unselected women with breast cancer from the Alexandra Hospital in Athens, Greece, a large public hospital in the city. Mutations in <it>BRCA1 </it>and <it>BRCA2 </it>were detected using a combination of techniques and were confirmed by direct sequencing. Two large genomic deletions were sought using mutation-specific assays. A detailed family history of cancer was obtained from each patient.</p> <p>Results</p> <p>We were able to successfully complete testing on samples from 127 women. Among these, six mutations were identified (four in <it>BRCA1 </it>and two in <it>BRCA2</it>) representing 4.7% of the total or 9.5% of cases diagnosed before age forty. None of the mutation carriers had a family history of breast or ovarian cancer. Three of the four <it>BRCA1 </it>mutations were in exon 20: two were a G5331A mutation and the third was a 3.2 kb deletion. The fourth <it>BRCA1 </it>mutation was the 3819delGTAAA in exon 11. The two <it>BRCA2 </it>mutations were in exon 11 (3782del10 and 4512insT).</p> <p>Conclusions</p> <p>The G5331A mutation in <it>BRCA1 </it>appears to be a founder mutation in the Greek population.</p