bluuebunny/crossref_metadata_2025 huggingface dataset:
The destruction of the nations and the promise of return: hermeneutical observations on the book of Deuteronomy
Authors: Braulik G
Published: November 2012

Many Israelis, but also many Christian Palestinians, today understand the current conflict around the possession of the land in a Bible-oriented way. They associate it with the radical destruction of all inhabitants of the land and its subsequent occupation as it is formulated in Deuteronomy, namely as an instruction of God, and as portrayed in the book of Joshua, namely as an historical event. This typologising form of  common hermeneutics contradicts both modern historiography on ancient Israel and the historic-critical exegesis of the two books as well as their interpretation in Jewish tradition. The campaign of the twelve-tribe nation under Joshua and the destruction of the peoples of Canaan is a  theological,  fictitious  image of radical trust in God, which was designed under King Josiah for mythical ancient times. Neither the laws on warfare nor the promises of return in a synchronically read Deuteronomy know about any future violent conquest of  the  land of Canaan. The article analyses Israel's relation to the inhabitants of the land, especially in  chapters 29-30, which are decisive for Moses’ vision of the  future.  Based on this analysis, it develops the hermeneutics of Deuteronomy  for  the directives on the destruction of the nations. Applying these directives typologically proves to  be  ruled  out, both for the wars following the conquest of the land and for the return of Israel from exile.
Veranderingen in samenleving en kerk en de gevolgen voor het beroep van pastor
Authors: Heitink Gerben
Published: November 2012

This article is an attempt to open up a new perspective on the crisis of christianity and church in the context of Western Europe, especially The Netherlands. Since half a century the secularisation paradigm has  been the dominant perspective to explain  this development. But a long-term historical perspective offers a wider horizon. Through the ages there have been different  types of christianity (E.Troeltsch): the public church in relation to the civil society, the free church emphasizing church membership (the priesthood of the believers) and the more individualized mystic type of faith. Since the  separation  of church and state untill totday the second type had been the dominant one. A consequence of  the cultural  shift from modernity to postmodernity is the rise of ‘wild devotion’ conform the third type of a more individualized way of life. This article pays attention to the challenges of these  developments  to the practice of church life and the pastoral profession.
New politics, new stories, new history: the Chronicler as historian for a new generation
Authors: Boshoff W
Published: November 2012

The Chronistic History, consisting of I and II chronicles, Ezra and Nehemiah, constitutes a new history for the post-exilic Judaean community. These people faced new  social and political relities and had to make sense of their history and situation. Central features of the Chronistic History are (in I and II  Chronicles) the review of king David’s genealogies, the centrality of David’s reign and cultic arrangements, which resulted in Solomon’s building of the temple, and the history of the kingdom of Judah, with the reigns of Hesekiah and Josiah as focal points. In Ezra and Nehemiah the focal points are the Persian king Cyrus’ decree, allowing the Judaeans to return to Jerusalem, the conflict with the people of the land, and the rebuilding of the city walls and temple. The  Chronicler’s use of history to constitute a new reality for its readers, helped them to visualise a new Judaean community by inclusion and exclusion. This process was not only healing and reconciliatory, but also entailed conflict and animosity.
Drivers for the writing of a sermon about reconciliation
Authors: Vos C J A
Published: November 2012

This article focuses on the energy that must fill the homiletic space, in order for an effective sermon about reconciliation, to be created. Of concern is the liturgical situation in which, sermons about reconciliation take place – the  homiletic process through which a homiletic theory is established, the sermon as a work of art and its structure. All these liturgical and homiletic motivators release energy, which enables preaching about reconciliation to take place in a way that moves the listener. Reconciliation means to overcome the divide between the rich and the poor and looking at other people the other person through different eyes.
Kruispunte in Christene se besluitneming oor homoseksualiteit
Authors: De Villiers DE
Published: November 2012

The article demonstrates that the present differences Christians have in morally evaluating homosexuality in general and steady homosexual relationships in articular, can be related to the decisions they take at four pivotal crossroads.  Two one-sided and opposite approaches to this evaluation that follow from different decisions at these crossroads are discussed. They are contrasted with a reforming Christian approach that would enable Christians to take a more nuanced and substantiated stance to the moral issues with regard to homosexuality.
Family (oikos) Evangelism for reaching forward caste Hindus in India
Authors: Fowlkes DW , Verster P
Published: November 2012

This article acknowledges the need for Church Planting Movements among the unreached peoples of India. Of particular concern to this study is the application of Church Planting Movement strategy to forward caste Hindus of India. It is shown that evangelizing households (family or “oikos” evangelism) is a New Testament strategy and the most appropriate strategy for reaching forward caste Hindus. It is concluded that Christian disciples remaining within Hindu culture and familial systems hold the potential for the most indigenous approach to evangelizing forward caste Hindus.
Prospects of a Christian Ethics of responsibility (Part 1): An assessment of an American version
Authors: De Villiers DE
Published: November 2012

In his book Das Prinzip  Verantwortung, published in 1979, the philosopher Hans Jonas argued that all existing approaches in philosophical ethics are inadequate, because they do not effectively address the serious issues caused by the rapid expansion of modern technology. He proposed a completely new approach to ethics based on the principle of responsibility. His book – among others – inspired a number of theologians in Germany and the USA to develop their own versions of a Christian ethics of responsibility. In this article Jonas’ s version of an ethics of responsibility and the attempt of the American theologian William Schweiker to develop a Christian version of such an ethics in close proximity to Jonas’ s are critically discussed. It is pointed out that Jonas does not succeed in making out a convincing case for elevating responsibility to the fundamental principal of ethics. It  is also argued that Schweiker’ s ambivalent stance in this regard does not support his claim that Christian ethics, in order to adequately respond to the serious ethical issues of our time, should be developed as an ethics of responsibility. The question “Can and should Christian ethics today be developed as ethics of responsibility?” is therefore left open.
Natuurrampe en die voorsienigheid van God, met besondere verwysing na die beskouing van Johannes Calvyn
Authors: Potgieter P C
Published: November 2012

It stands to reason that many of those believing in the providence of God will look for theological guidance when natural disasters of a catastrophic magnitude strike. This paper explores the reasoning of well-known theologians, and particularly John Calvin, in this regard endeavouring to develop a relevant contribution towards deeper insight in the extremely difficult issue of a theodicy. Contrary to a popular idea that Calvin adopted an extremely harsh line on providence by which God becomes responsible for every kind of disaster, it is argued that he maintains a fine balance between the loving grace of our heavenly Father and his righteous judgment over mankind who undermined his intended order of nature by sin. Argued from a Christological perspective, the faithful should respect both God's revelation and his hidden plan, which they will not be able to fathom in this life. Whatever happens, they should be pastorally guided to humble patience and perseverance in sincere hope on God’ s unquestionable faithfulness, and the firm belief that he will guide his creation to its true destination.
Riglyne vir ‘n verantwoordelike Nuwe Testamentiese verstaan in die homoseksualiteitsdebat. Deel 1: ’n Komplekse Saak
Authors: Steyn Gert J
Published: November 2012

This is the first of two contributions that are asking how the New Testament can be used in a responsible manner in the debate about homosexuality. It is clear that this is a complex issue which is driven by subjective opinions about the phenomenon itself, and by the selection and analysis of passages chosen for the chosen viewpoint of the individual. Different arguments are steering the debate: emotional, societal pressure, biological-psychological, biblical, theological, and technical arguments all find their way in different contexts.  The fact of the existence of deviations in nature, the occurrence of the phenomenon in  different primitive and ancient cultures, and the use and application of a single term for a variety of aspects, are all contributing to this complex labyrinth. A responsible use of the New Testament in the debate on homosexuality can only happen when it is done in a diversified and qualified manner .
In het teken van Kaïn. Een theologische exegese van Genesis 4
Authors: Peels H G L
Published: November 2012

Present day reflection upon the burning questions of evil an violence increasingly dominate the agenda of modern society. Biblical scholarship can contribute meaningfully to this discourse by analysing biblical narratives in which the themes of violence and animocity occur. In this regard it becomes necessary to unmask the mechanisms of violence, and to examine the judgement of violence from a biblical-theological perspective. Violence and animocity are displayed very soon in the Old Testament. Genesis 4 recounts the well-known story of Cain and Abel. The story of the world’s first children turns out to be the story of the world’s firs murder. YHWH’s role in this process is of particular interest: his warnings (vss 6-7), his interrogation (vss 9-10), his sentence (vss 11-12) and his promise (vs 15). This article investigates Genesis 4:1-16 and focuses especially on the remarkable promise to Cain, the nature of Cain’s mark (vs 15) and the theological significance of YHWH as the keeper of Abel’s brother. Genesis 4 turns out to be a chapter with paradigmatic value for today.
Faith to faith – Missiology as encounterology
Authors: Kritzinger J N J
Published: November 2012

This article responds to a book edited by Prof PGJ Meiring in 1996 on the religions of South Africa. It appreciates the integration between the fields of Religious Studies and Theology of Religions in the book, but suggests that a missiological approach should explore the inter-religious encounter, rather than merely what others believe or what we believe about the possibility of their being saved. An approach of “encounterology” requires: a) a holistic and reflexive process that considers seven different dimensions of the encounter; b) a dialogical approach in which a Christian enters into a journey of mutual witness with a follower of another faith. The article uses a seven-point praxis cycle to indicate what such an encounterology could look like.
The pastoral care of preaching and the trauma of HIV and AIDS
Authors: Streets F J
Published: November 2012

There is within the history of Christian worship practices a long tradition of someone offering a sermon to those gathered for worship. The primary means for many Christians throughout the world of receiving Christian education and guidance is by listening to sermons. There is generally embedded in all Christian preaching some attempt on the part of the preacher to share a worldview based upon the his or her biblical and theological interpretation of the meaning of faith and their application to daily living. This article explores how the sermon can be a source of religious instruction and aspect of pastoral caring for those infected and affected by HIV and AIDS. The article also suggests that such sermons can be a form of advocating social justice for those who are stigmatized because of their HIV status. Note: The people mentioned in this article, are real but, their names, Rob, Inspiration and Pastor Able are fictitious for reasons of confidentiality.“My Africa is fading and no one sees or cares that it is happening.”
Karl Barth�s understanding of mission: The Church in relationship
Authors: Bentley W.
Published: November 2012

As the Church is moving towards its 21st century of existence, it is confronted by challenges it has never known before. This changing world demands self-reflection within the Church. It has to consider its place, identity and function, thereby giving rise to the exploration of its mission. In this article, the ecclesiology of Karl Barth is explored. By considering Barth�s understanding of the Church�s relationship with different parties such as God, other religions, those outside the Christian faith, the State and its own inner dynamics, the Church will be reminded of its missionary function in the world.
Constructing Protestant and Catholic Peters: A comparative study in the literary use of the New Testament and ecclesiastical tradition
Authors: Hale F.
Published: November 2012

Just as literary authors have long taken liberties with the biblical accounts of Jesus Christ and shaped Him to fit their own agendas, they have also appropriated considerable artistic licence in enhancing the meagre information about Peter in the New Testament when constructing fictional narratives about him. A comparison of The Big Fisherman by the theologically liberal American Congregationalist Lloyd C Douglas and Simon Peter the Fisherman by the Austrian Catholic Kurt Frieberger illustrates how two accomplished novelists, drawing in part on similar sources, created markedly different and to some extent predictable images of this apostle. Neither novel is fully faithful to the New Testament evidence; both evince the influence of extrabiblical sources.
Safety and Efficacy of Sunitinib in Patients with Unresectable Pancreatic Neuroendocrine Tumors
Authors: Wiedmann Marcus W. , Mössner Joachim
Published: November 2012

Pancreatic neuroendocrine tumors (PNETs) are becoming increasingly common, with the majority of patients presenting with either lymph node involvement or metastatic disease, thus requiring systemic therapy. Targeted therapy is a type of medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth rather than by simply interfering with rapidly dividing cells (eg, with traditional chemotherapy). In this review article, pharmacologic inhibition of multiple targets including vascular endothelial growth factor receptor (VEGF-R), platelet-derived growth factor receptor (PDGF-R), stem cell factor receptor (c-KIT-R), FML-like tyrosine kinase-3 receptor (FLT3-R), colony stimulating factor 1 receptor (CSF1-R), and glial cell-line derived neurotrophic factor receptor (RET-R) with sunitinib in patients with unresectable PNETs is discussed. Phase III data indicate that additional treatment with sunitinib can improve prognosis in these patients.
The Effect of Woman Leadership Style and Organizational Culture on Locus of Control, Work Achievement, and Work Satisfaction of Employee
Authors: Lantara Andi Niniek Fariaty , Haming Murdifing , Mus Abdul Rahman , Alam Roslina
Published: November 2012

Research begins from May to August of 2011 at The Governor Office of South Sulawesi Province. The objective of research is to understand and to analyze the direct and indirect effect of woman leadership style and organizational culture on locus of control, work achievement, and work satisfaction of employee. Research type is explanatory with survey method. The respondent is the work unit under the leadership of woman. Sampling technique is minimized sample method which results in 135 respondents. Data analysis method is Structure Equation Modeling (SEM). Result of analysis indicates that women leadership style is having positive and significant effect on locus of control, work achievement, and work satisfaction of employee.
A Multi-center, Dose-escalation Study of Human type I Pancreatic Elastase (PRT-201) Administered after Arteriovenous Fistula Creation
Authors: Peden Eric K. , Leeser David B. , Dixon Bradley S. , El-Khatib Mahmoud T. , Roy-Chaudhury Prabir , Lawson Jeffrey H. , Menard Matthew T. , Dember Laura M. , Glickman Marc H. , Gustafson Pamela N. , Blair Andrew T. , Magill Marianne , Franano F. Nicholas , Burke Steven K.
Published: November 2012

Purpose

To explore the safety and efficacy of PRT-201.

Methods

Randomized, double-blind, placebo-controlled, single-dose escalation study of PRT-201 (0.0033 to 9 mg) applied after arteriovenous fistula (AVF) creation. Participants were followed for one year. The primary outcome measure was safety. Efficacy measures were the proportion with intra-operative increases in AVF outflow vein diameter or blood flow ≥25% (primary), changes in outflow vein diameter and blood flow, AVF maturation and lumen stenosis by ultrasound criteria and AVF patency.

Results

The adverse events in the PRT-201 group (n=45) were similar to those in the placebo group (n=21). There were no differences in the proportion with ≥25% increase in vein diameter or blood flow, successful maturation or lumen stenosis. There was no statistically significant difference in primary patency between the dose groups (placebo n=21, Low Dose n=16, Medium Dose n=17 and High Dose n=12). In a subgroup analysis that excluded three participants with early surgical failures, the hazard ratio (HR) for primary patency loss of Low Dose compared with placebo was 0.38 (95% CI 0.10-1.41, P=0.15). In a Cox model, Low Dose (HR 0.27, 95% CI 0.04-0.79, P=0.09), white race (HR 0.17, 95% CI 0.03-0.79, P=0.02), and age <65 years (HR 0.25, CI 0.05-1.15, P=0.08) were associated (P<0.10) with a decreased risk of primary patency loss.

Conclusions

PRT-201 was not different from placebo for safety or efficacy measures. There was a suggestion for improved AVF primary patency with Low Dose PRT-201 that is now being studied in a larger clinical trial.
NGAL as a Renai Injury Marker: A Prospective Randomized Trial using Wolf Piezolith 3000
Authors: Varisco Daniela , Gelosa Marco , Grasso Angelica , Rastaldi Maria Pia , Croci Daniela , Messa Piergiorgio , Zanetti Giampaolo , Ferruti Mario , Rocco Francesco
Published: November 2012

Background

Shock wave lithotripsy (SWL) has proven to be safe and effective for renal stone treatment. The shock wave rate used during the SWL procedure causes cavitation, which is the phenomenon responsible for stone fragmentation and may be responsible for tissue and vascular damages ascribed to lithotripsy. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been shown to be one of the earliest and most overexpressed markers in case of cellular damage in the kidney.

Objective

Using a new generation piezoelectric lithotripter, we evaluated the relation between renal damage, stone fragmentation rate, pain and shock wave rate delivered during SWL.

Materials and Methods

80 patients suffering from a single renal stone were included in our clinical trial and underwent SWL with Wolf PiezoLith 300 lithotripter. A urine sample was collected in 54 patients (30 belonging to Group A, 24 to Group B) before treatment, within 2 hours and 72 hours after SWL, for NGAL measurement.

Results

The stone fragmentation rate obtained in the 2 groups was practically the same 30 days after SWL, with an efficacy rate of 72.7% in Group A and of 73.3% in Group B. NGAL increased after treatment, but was not statistically different in the two groups, and returned to the baseline value after 72 h. Furthermore, NGAL was always well below the threshold value of 350 ng/mL, indicative of acute renal failure.

Conclusions

The best stone fragmentation rate achievable with a piezoelectric lithotripter can be reached with a higher shock wave rate without significant renal damage, thus optimizing the treatment time.
Fully Programmable Gaussian Function Generator Using Floating Gate MOS Transistor
Authors: Srivastava Richa , Gupta Maneesha , Singh Urvashi
Published: November 2012

Floating gate MOS (FGMOS) based fully programmable Gaussian function generator is presented. The circuit combines the tunable property of FGMOS transistor, exponential characteristics of MOS transistor in weak inversion, and its square law characteristic in strong inversion region to implement the function. Two-quadrant current mode squarer is the core subcircuit of Gaussian function generator that helps to implement full Gaussian function for positive as well as negative input current. FGMOS implementation of the circuit reduces the current mismatching error and increases the tunability of the circuit. The performance of circuit is verified at 1.8 V in TSMC 0.18 μm CMOS, BSIM3, and Level 49 technology by using Cadence Spectre simulator.
Assembly of theβ-Barrel Outer Membrane Proteins in Gram-Negative Bacteria, Mitochondria, and Chloroplasts
Authors: Misra Rajeev
Published: November 2012

In the last decade, there has been an explosion of publications on the assembly ofβ-barrel outer membrane proteins (OMPs), which carry out diverse cellular functions, including solute transport, protein secretion, and assembly of protein and lipid components of the outer membrane. Of the three outer membrane model systems—Gram-negative bacteria, mitochondria and chloroplasts—research on bacterial and mitochondrial systems has so far led the way in dissecting theβ-barrel OMP assembly pathways. Many exciting discoveries have been made, including the identification ofβ-barrel OMP assembly machineries in bacteria and mitochondria, and potentially the core assembly component in chloroplasts. The atomic structures of all five components of the bacterialβ-barrel assembly machinery (BAM) complex, except theβ-barrel domain of the core BamA protein, have been solved. Structures reveal that these proteins contain domains/motifs known to facilitate protein-protein interactions, which are at the heart of the assembly pathways. While structural information has been valuable, most of our current understanding of theβ-barrel OMP assembly pathways has come from genetic, molecular biology, and biochemical analyses. This paper provides a comparative account of theβ-barrel OMP assembly pathways in Gram-negative bacteria, mitochondria, and chloroplasts.
Diabetic and Metabolic Programming: Mechanisms Altering the Intrauterine Milieu
Authors: Eberle Claudia , Ament Christoph
Published: November 2012

A wealth of epidemiological, clinical, and experimental studies have been linked to poor intrauterine conditions as well as metabolic and associated cardiovascular changes postnatal. These are novel perspectives connecting the altered intrauterine milieu to a rising number of metabolic diseases, such as diabetes, obesity, and hypercholesterolemia as well as the Metabolic Syndrome (Met S). Moreover, metabolic associated atherosclerotic diseases are connected to perigestational maternal health. The “Thrifty Phenotype Hypothesis” introduced cross-generational links between poor conditions during gestation and metabolic as well as cardiovascular alterations postnatal. Still, mechanisms altering the intrauterine milieu causing metabolic and associated atherosclerotic diseases are currently poorly understood. This paper will give novel insights in fundamental concepts connected to specific molecular mechanisms “programming” diabetes and associated metabolic as well as cardiovascular diseases.
Neuropsychiatric Features of a Cohort of Patients with Systemic Lupus Erythematosus
Authors: Moraes-Fontes Maria Francisca , Lúcio Isabel , Santos Céu , Campos Maria Manuel , Riso Nuno , Vaz Riscado Manuel
Published: November 2012

In order to establish if neuropsychiatric systemic lupus erythematosus (NPSLE) can be identified by any characteristic other than those used to diagnose the neuropsychiatric (NP) disease itself, we retrospectively reviewed 98 systemic lupus erythematosus (SLE) patients followed over a mean period of 10 years. NPSLE was identified in 22 patients. Stroke and generalized seizures were the most frequent NP manifestations. The NPSLE and non-NPSLE groups were similar with regard to demographic characteristics, ACR criteria, serum autoantibodies, and frequency of hypertension and hypercholesterolemia. Of note, compared to the non-NPSLE group, NPSLE was associated with a higher frequency of smoking (78 versus 26%), organ damage (73 versus 34%), and cumulative mortality rate (14 versus 7%). The series of patients was further analysed according to the presence of antiphospholipid syndrome (APS). Significantly, the interval between the onset of NP disease and SLE diagnosis was shorter in the APS− (0.3±1 years) than in the APS+ (5±7 years) groups. Recurrence and/or persistence of NP events were only documented in the APS− group. Overall cumulative mortality was highest in NPSLE and in APS+ patients with inadequate anticoagulation control, identifying an aspect that requires improved vigilance and the development of novel therapeutic modalities.
Plasma Membrane Transporters in Modern Liver Pharmacology
Authors: Marin Jose J. G.
Published: November 2012

The liver plays a crucial role in the detoxification of drugs used in the treatment of many diseases. The liver itself is the target for drugs aimed to modify its function or to treat infections and tumours affecting this organ. Both detoxification and pharmacological processes occurring in the liver require the uptake of the drug by hepatic cells and, in some cases, the elimination into bile. These steps have been classified as detoxification phase 0 and phase III, respectively. Since most drugs cannot cross the plasma membrane by simple diffusion, the involvement of transporters is mandatory. Several members of the superfamilies of solute carriers (SLC) and ATP-binding cassette (ABC) proteins, with a minor participation of other families of transporters, account for the uptake and efflux, respectively, of endobiotic and xenobiotic compounds across the basolateral and apical membranes of hepatocytes and cholangiocytes. These transporters are also involved in the sensitivity and refractoriness to the pharmacological treatment of liver tumours. An additional interesting aspect of the role of plasma membrane transporters in liver pharmacology regards the promiscuity of many of these carriers, which accounts for a variety of drug-drug, endogenous substances-drug and food components-drug interactions with clinical relevance.
Quantifying and addressing losses along the continuum of care for people living with HIV infection in sub‐Saharan Africa: a systematic review
Authors: Kranzer Katharina , Govindasamy Darshini , Ford Nathan , Johnston Victoria , Lawn Stephen D
Published: November 2012

Introduction

Recent years have seen an increasing recognition of the need to improve access and retention in care for people living with HIV/AIDS. This review aims to quantify patients along the continuum of care in sub‐Saharan Africa and review possible interventions.

Methods

We defined the different steps making up the care pathway and quantified losses at each step between acquisition of HIV infection and retention in care on antiretroviral therapy (ART). We conducted a systematic review of data from studies conducted in sub‐Saharan Africa and published between 2000 and June 2011 for four of these steps and performed a meta‐analysis when indicated; existing data syntheses were used for the remaining two steps.

Results

The World Health Organization estimates that only 39% of HIV‐positive individuals are aware of their status. Among patients who know their HIV‐positive status, just 57% (95% CI, 48 to 66%) completed assessment of ART eligibility. Of eight studies using an ART eligibility threshold of≤200 cells/µL, 41% of patients (95% CI, 27% to 55%) were eligible for treatment, while of six studies using an ART eligibility threshold of≤350 cells/µL, 57% of patients (95% CI, 50 to 63%) were eligible. Of those not yet eligible for ART, the median proportion remaining in pre‐ART care was 45%. Of eligible individuals, just 66% (95% CI, 58 to 73%) started ART and the proportion remaining on therapy after three years has previously been estimated as 65%. However, recent studies highlight that this is not a simple linear pathway, as patients cycle in and out of care. Published studies of interventions have mainly focused on reducing losses at HIV testing and during ART care, whereas few have addressed linkage and retention during the pre‐ART period.

Conclusions

Losses occur throughout the care pathway, especially prior to ART initiation, and for some patients this is a transient event, as they may re‐engage in care at a later time. However, data regarding interventions to address this issue are scarce. Research is urgently needed to identify effective solutions so that a far greater proportion of infected individuals can benefit from long‐term ART.
Cost‐effectiveness evaluation of initial HAART regimens for managing HIV‐infected patients according to real clinical practice
Authors: Castagna A , Colombo G , Salpietro S , Galli L , Poli A , Lazzarin A
Published: November 2012

We evaluated the single‐tablet regimen (STR) versus multiple‐tablet regimen (MTR) strategies through an incremental cost‐effectiveness analysis in a large cohort of patients starting their first HAART. Adult HIV‐1‐naïve patients, followed at the San Raffaele Hospital, starting their first‐line regimen from June 2008 to April 2012, were included in the analysis. First‐line HAART regimens more frequently used (>10%) were grouped into two classes as follows: a) single‐tablet regimen (STR) of TDF + FTC + EFV; b) multiple‐tablet regimen (MTR) including TDF + FTC + EFV, TDF + FTC + ATV/r, TDF + FTC + DRV/r TDF + FTC + LPV/r. The incremental cost‐effectiveness analysis was carried out by means of a Markov model calculating quality of life and costs for each patient, according to the given regimen (including any subsequent switch if occurred), through 1‐year cycles. The outcome measure was quality‐adjusted life‐years (QALYs). Data were analysed from the point of view of the Lombardy Regional Health Service (RHS): HAART, hospitalisations, visits, examinations and other concomitant non‐HAART drugs costs were evaluated, price variations included. 474 naïve patients: 90% males, mean age 42.2 years, mean baseline HIV‐RNA 4.50 log10copies/ml and CD4+ count of 310 cells/µL with a mean follow‐up of 28 months. Patients starting with an STR treatment were less frequently HCVAb positive (4% vs 11%, P=0.040), had higher mean CD4+ values [351 vs 297, P=0.004] as compared to MTR patients. The mean year cost/patient was €9,213 (range: €6,574.71–€33,570.00) with a mean per patient QALYs of 0.986 (range: 0.878–0.999) among STR patients; the mean year cost/patient was €14,277 (range: €5,908.89–€82,310.30) with a mean QALY of 0.933 (0.830–0.976) among MTR patients. STR dominates (i.e. is more effective and less costly) compared to MTR. (Fig. 1) At multivariable analysis, after adjustment for age, gender, HCVAb status, HIV risk factor, baseline CD4+ and HIV‐RNA, the cost‐effectiveness ratio was significantly lower among patients starting an STR treatment as compared to a MTR regimen (adjusted mean: €12,096 vs. €16,106; P=0.0001). The incremental cost‐effectiveness ratio (ICER) values comparing the two treatment strategies reported in the table. Starting with a first‐line STR regimen compared to multiple‐tablet regimens resulted cost‐effective showing lower costs and better efficacy as measured by QALYs.

Incremental Cost Effectiveness Ratio of HAART Regimens.

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Loss to follow up within an HIV cohort
Authors: Wood H , Dhar J
Published: November 2012

BHIVA guidelines recommend that all ARV‐naïve and stable on‐treatment patients are monitored at least 6 monthly [1]. Studies have shown that loss to follow up (LFU) not only worsens outcomes [2] but has increased potential for onward transmission. Case notes of 1275 HIV patients registered under our care up to January 2011 were examined for attendance within the previous 6 months. 788 (61%) patients had not been seen within the previous 6 months. Reasons for non attendance were identified. These are outlined below:

Patient group
Number

Deceased
61

Transferred care to another HIV clinic
455

Moved out of the UK
54

Lost to follow up ‐ no means to contact
130

Lost to follow up ‐ eligible for recall
88

76% of the 130 LFU whose demographics were further examined were of Black African ethnicity, 54% female, 51% of single marital status and 48% of patients had been taking ARVs at the time of LFU. Interestingly, 53% of patients were lost to follow up within 1 year of diagnosis. The LFU patients (88) that had a local GP and a registered current address were sent recall letters. A small number of patients reengaged with care as a result of this action, some having not attended for over 5 years. Partner notification led to a number of new diagnoses in these cases. Failure to respond led to subsequent letters inviting them to clinic and finally a letter to their GP informing them of non attendance. In September 2011, a new recall system using Lillie Electronic Patient Records (EPR) was introduced to promptly recognise if a patient had not attended for care as planned. Prior to this, recall was a manual process carried out by the Health Advising Team. We conclude that within our cohort we had a particularly mobile group of patients; 455 (36%) transferring care to another clinic within the UK, 54 (4%) moving out of UK. 76% of the LFU group being of Black African ethnicity highlights the ongoing problem of retention of care in this group. Further exploration is needed to identify additional issues besides housing and immigration that lead to LFU. Furthermore, the disportionate number of patients (53%) disengaging with services within 1 year of diagnosis should encourage HIV services to provide additional support within this time period to reduce LFU. This study highlights the need for robust recall systems within clinics to identify those individuals not engaging with services or not attending for routine monitoring. These may be easier to implement with the increasing use of EPR. An audit of the recall system is planned in September 2012 to re‐examine loss to follow up rates after its implementation.
The Australian experiment: general practitioner care of HIV
Authors: Baker D
Published: November 2012

Over 20,000 people are living with HIV infection in Australia. From the early days of the epidemic general practitioners (GPs) have been closely involved in providing HIV care including antiretroviral therapy (ART). Training programs began in 1990 with about 200 GPs currently trained to provide ART. However there are limited data available on uptake and outcomes of GP HIV care. This review will present data on current GP involvement in providing HIV care as well as treatment outcomes. A Medline search was conducted using the terms general practice, HIV and Australia. Abstracts from local conferences were also reviewed. The major identified study of treatment uptake is HIV Futures [1], a national survey of approximately 1000 HIV+ve people performed every 2 years. Over the last 10 years this study consistently reports that about 50% of all HIV specific care is provided by GPs. One study describes an audit of 500 HIV+ve patients starting treatment in primary and hospital sites [2]. This found that there were comparable and high levels of adherence to guidelines on ART initiation in both general and specialist practice. A cohort of 168 patients followed for over 10 years in an Australian GP reported that 24% had been lost to follow‐up, 7% died and 68% continued in care with 98% receiving ART with 96% having an undetectable viral load (<400) [3]. These outcomes were similar to those reported in the long‐running national Australian HIV Observational Database (AHOD). Robust data show that about half of all HIV care in Australia is provided by GPs. Limited published data on adherence to guideline and treatment outcomes suggest comparable result in general practice versus specialist settings. GP care appears to be an acceptable and effective approach to HIV management although more research on treatment outcomes is needed.
Hospital admissions of HIV‐infected patients at a Lisbon reference centre: comparison among previously known and in‐ward HIV‐diagnosed patients
Authors: Miranda A , Fernandes D , Peres S , Biague Q , Salvado R , Faria M , Mansinho K
Published: November 2012

Comparison of hospital admission causes for previously known (group A) and HIV‐infected patients diagnosed during in‐ward stay (group B), from 2009 to 2011. Retrospective evaluation of demographic, epidemiologic, clinical, immunologic, virologic and treatment parameters at time of admission. 1167 patients were admitted; of those 617 (52,9%) were HIV‐infected: 92% HIV‐1 and 8% HIV‐2. 83% had previously known HIV infection and 15% were diagnosed during hospital stay (missing data in 2%). 66% were male, mean age was 46 years and 52% were Portuguese. The most frequent transmission routes were heterosexual exposure (36%) and iv drug use (29%). Mean length of hospital stay was 17 days (group A) and 28 days (group B) (p = 0,004). At admission, the mean TCD4+ count was 280 cells/mm3 in group A, and 132 cells/mm3 in group B (p<0,001). The majority of group B patients had clinical or immunological AIDS criteria at admission (84%) while group A presented a 71% rate for the same parameter (p=0,011). In group A, 52% of patients were on antiretroviral therapy but of those only 33% presented undetectable HIV plasma RNA, non‐adherence being an important cause of therapeutic failure identified in 40% of cases. Respiratory infection was the principal cause of hospital admission in both groups (33% in group A vs. 35% in group B). The most prevalent nosological entities were community acquired pneumonia in group A (18,1% vs. 11,5%‐p=0,118) and Pneumocystis jirovecii pneumonia in group B (4% vs. 18%‐p<0,001). Mycobacterium tuberculosis was frequently identified as an agent of opportunistic infection (10% in group A vs. 24% in group B‐p=<0,001). HCV coinfection was a comorbidity found in 37% in group A vs. 11% in group B (p<0,001). Other relevant comorbidities were psychiatric disturbances (16% vs. 3%‐p=0,001) and neoplastic conditions (11% vs. 0%‐p=0,001), mostly present in group A. Mortality rate was not significantly different between groups (10% group A vs. 11% group B) (p=0,773). This analysis evidenced that, a significant percentage of HIV patients diagnosed at admission were late presenters. Slightly a half of patients with previous known HIV infection were prescribed cARV and only a third presented undetectable HIV viral load. Non‐adherence was a major concern in this population. Respiratory infections had a significant clinical impact in both groups, justifying the importance of vaccination prevention strategies in immunocompromised individuals.
CYP2B6 G516T and ABCB‐1 C3435T polymorphisms: implications for efavirenz‐associated liver toxicity in HIV/tuberculosis co‐infected Thai adults
Authors: Uttayamakul S , Manosuthi W , Likanonsakul S , Shioda T , Khusmith S
Published: November 2012

Cytochrome P450 2B6 (CYP2B6) and ATP‐binding cassette, sub‐family B (ABCB‐1) play an important role in metabolism and transport of anti‐retroviral therapy (ART) agents. CYP2B6 516TT and ABCB‐1 3435CT polymorphisms affected plasma efavirenz levels. Efavirenz‐based ART was proofed to be beneficial in HIV/tuberculosis co‐infection management; however, the drug‐drug interactions and toxicity are major concerns. Factors affecting adverse drug events and liver toxicity were investigated in this study. Seventy‐one HIV patients with tuberculosis receiving efavirenz (600 mg/day)‐based ART were enrolled in the randomized trial: the N2R study in Bamrasnaradura Infectious Diseases Institute, Thailand. After 12 weeks of ART, 65 rifampicin recipients continued in the analysis of the factors influenced drug toxicity. Plasma efavirenz, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubins were determined. CYP2B6 and ABCB‐1 polymorphisms were genotyped. Mann‐Whitney U test was used to compare genotypes and laboratory parameters. CYP2B6 516TT and ABCB‐1 3435CT genotypes were found in 9 (13.85%) and 33 (50.77%) patients, respectively, while six (9.23%) carry both ‐516TT and ‐3435CT genotypes. Patients with 516TT genotype had significantly higher mean rank plasma efavirenz than GT and GG genotypes (54.78 vs. 29.50, p=1.97x10−4) while those carrying 3435CT had slightly higher than CC and TT genotypes. Patients carrying both ‐516TT and ‐3435CT had higher mean rank efavirenz levels than those without these two genotypes (60.17 vs. 30.24, p=2.21x10−4), and had significantly different ALT, total and direct bilirubin levels (p=0.044, 0.009, 0.021, respectively). CYP2B6 516TT and ABCB‐1 3435CT influenced plasma efavirenz levels and related to higher levels of ALT, total and direct bilirubin in patients implication for drug toxicity. The results might be useful for personalized therapy due to their impact on ART adherence related to drug resistance and treatment failure.
Raltegravir switch improves hepatitis C transaminitis in HIV‐1 and hepatitis C (HCV) co‐infected individuals
Authors: Cevik M , Jagjit Singh G , Dickinson L , Nelson M
Published: November 2012

Purpose of the study

HCV is one of the most relevant co‐morbidities seen in HIV‐infected individuals as evidenced by the negative impact that HIV exerts on the course of HCV infection. Despite remarkable results on HIV infection alone, the impact of highly active antiretroviral therapy (HAART) on liver disease in co‐infection remains unknown. We sought to explore the impact of raltegravir (RAL) on amino transferase (ALT) in HIV/HCV co‐infected individuals.

Methods

HIV‐infected individuals co‐infected with HCV within the last 5 years receiving non‐integrase inhibitor containing HAART with a subsequent switch to RAL‐containing HAART were identified from a retrospectively maintained outpatient database. Patient demographics were extracted. Biochemical, virological and immunological parameters were collated and individuals received pegylated interferon with ribavirin were excluded. ALT levels at switch and post switch were compared using Kruskal‐Wallis test. Spearman's Rank correlation was used to assess the relationship between ALT and HCV‐RNA.

Summary of results

Twenty‐seven HIV‐HCV co‐infected individuals were identified between January 2007 and January 2012 and seven individuals were excluded. Median age was 44 years (range: 31–68). Five had acute and fifteen had chronic HCV infection during the switch. Twenty (100%) had HIV‐RNA‐1<40 copies/mL at time of RAL switch. In chronic HCV infected individuals, median ALT levels at the time of switch were 465 IU/L, decreased significantly to 179 IU/L 1 month following switch (p=0.0261) and to 140 IU/L 6 months later (p=0.0225). On the other hand, in acute HCV infected individuals median ALT levels were 1005 IU/L at time of switch but decreased significantly to 220 IU/L 1 month later (p=0.0034) and to 35 IU/L 6 month later (p=0.0026). Sustained improvement in ALT levels from baseline to 1 month and up to 24 weeks after switch to RAL was observed in both groups but the reduction in ALT levels was statistically more significant in acutely infected individuals. ALT and HCV‐RNA levels showed a positive correlation at 6 months pre, post and at time of switch both in acute and chronic HCV‐infected individuals (Spearman's Rank correlation).

Conclusion

In our study, RAL had a favourable effect on the liver up to 24 weeks after switch in HIV/HCV infected individuals.

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Hepatitis B virus infection in adolescents and young adults with human immunodeficiency virus infection in an urban clinic in a resource‐limited setting
Authors: Katusiime C , Kambugu A
Published: November 2012

Purpose of the study

Patients with HBV/HIV co‐infection are at an increased risk of progression to hepatic cirrhosis and eventual liver‐related death. There is limited data on HBV/HIV co‐infection prevalence in adolescents and young adults in developing countries. The objective of the study was to estimate the prevalence of hepatitis B virus co‐infection among HIV‐positive adolescents and young adults attending an urban clinic in Kampala, Uganda.

Methods

Prospective study in HIV‐infected adolescents and young adults aged from 15–24 years.

Summary of results

From the adolescent/young adult HIV clinic, we purposively selected a sample of 148 adolescents and young adults who had been diagnosed with sexually transmitted infections between April 2011 and March 2012. A total of 148 HIV‐positive adolescents and young adults, 10 males and 138 females, aged between 15 and 24 years, were examined. Nine participants (6.1%) were HBsAg‐positive and were diagnosed with hepatitis B. Hepatitis B was predominant amongst the female participants compared to the male participants: 6.1% vs 0%. The median age of the participants diagnosed with hepatitis B was 22 years (IQR: 18.5–24.0). Of the 9 HBV/HIV co‐infected participants, 7 (77.8%) had CD4+counts of>250 cells/µl while 2 (22.2%) had CD4+counts<250 cells/µl (p<0.001). The median CD4+counts for the HBV/HIV co‐infected participants whose CD4+counts>250 cells/µl was 434 cells/µl (IQR: 289–577). On the other hand, the participants whose CD4+counts<250 cells/µl had a median CD4+count of 120 cells/µl. There was very strong evidence to show that the 8 (88.9%) HBV/HIV co‐infected participants who were in WHO stage I and II were more as compared to 1 (11.1%) HBV/HIV co‐infected patients who was in WHO stage III and IV (p<0.001).

Conclusion

Only 6.1% of the HIV‐positive adolescents/young adults had hepatitis B co‐infection. HIV/HBV co‐infection was predominant among female adolescents/young adults and there was very strong evidence to show that HIV/HBV co‐infection was largely associated with WHO stage I and II disease.
The Vesicular Transport Assay: Validated In Vitro Methods to Study Drug‐Mediated Inhibition of Canalicular Efflux Transporters ABCB11/BSEP and ABCC2/MRP2
Authors: Herédi‐Szabó Krisztina , Kis Emese , Krajcsi Peter
Published: November 2012

The canalicular membrane of hepatocytes contains several transport proteins that use the energy of ATP to efflux potentially toxic molecules to the bile. Probably the two most important proteins at this location are MRP2 and BSEP, which transport phase II conjugates of xenobiotics and endobiotics and conjugated bile salts, respectively. The impaired function of either of these transporter proteins reduces the clearance of the toxic conjugates, resulting in their accumulation in the hepatocytes and eventually the plasma. Conjugated bile salts and phase II metabolites are compounds with low passive permeability; therefore, the most commonly used test system to investigate MRP2‐ and BSEP‐mediated transport processes is the vesicular transport assay. The concentration of probe substrates and inhibitors used in the experiment is close to their free concentration in the hepatocytes, providing an advantage when calculating kinetic parameters (Km, Ki, Vmax). The protocols aim to assist scientists to set up a transport assay for a known or potential substrate and test small molecule inhibition of the transporters. Curr. Protoc. Toxicol. 54:23.4.1‐23.4.16. © 2012 by John Wiley & Sons, Inc.