bluuebunny/crossref_metadata_2025 huggingface dataset:
Distal Tourniquet-Facilitated Radial Arterial Cannulation in Adults—a Double-Blinded, Prospective, Randomized and Controlled Study
Authors: Zhou Quanhong , Yao Jun , Chen Yongzhu , Lu Jie , Zhang Xiaoli , Jiang Wei
Published: November 2014

Purpose

Relatively small radial artery may be challenging for cannulation. We investigated whether a distal tourniquet would inflate the proximal radial artery and therefore facilitate cannulation in adults.

Methods

There were two stages of the study. The first was to measure the characteristics of radial artery by ultrasound imaging before and after tourniquet in volunteers. The second was a prospective, randomized, double blind study. Forty patients (American Society of Anesthesiologists I-III) who needed artery cannulation during operation were enrolled. Patients were assigned into two groups: loosen or tightened tourniquet for proximal radial artery cannulation by traditional palpation technique. The primary endpoints were the success rates and time of first attempt success by traditional palpation technique. The time of success after two to three attempts, failure rates and complications were collected.

Results

For volunteers, the distal tourniquet significantly expanded the cross-sectional up-forward diameter (p<0.001) and the area (p<0.05), but had no effect on cross-sectional lateral-lateral diameter or circumference of proximal radial artery (p>0.05). The success rate of first attempt was higher in the tighten group (75%) than in the loosen group (15%, p<0.05), but the time for success of first attempt/two to three attempts was similar (19.33 ± 1.12/62.11 ± 37.03 sec loosen group vs. 19.07 ± 12.75/45.55 ± 8.98 sec tightened group, p>0.05). Both groups had same failure rates of 10%. No complication was observed.

Conclusions

Distal tourniquet could inflate the proximal radial artery and facilitate palpation of radial artery cannulation.
Barriers to Adopting a Fistula-First Policy in Europe: An International Survey among National Experts
Authors: van der Veer Sabine N. , Ravani Pietro , Coentrão Luis , Fluck Richard , Kleophas Werner , Labriola Laura , Hoischen Susanne H. , Noordzij Marlies , Jager Kitty J. , van Biesen Wim
Published: November 2014

Purpose

The purpose of this study is to explore how vascular access care was reimbursed, promoted, and organised at the national level in European and neighbouring countries.

Methods

An electronic survey among national experts to collect country-level data.

Results

Forty-seven experts (response rate, 76%) from 37 countries participated. Experts from 23 countries reported that 50% or less of patients received routine pre-operative imaging of vessels. Nephrologists placed catheters and created fistulas in 26 and 8 countries, respectively. Twenty-one countries had a fee per created access; the reported fee for catheter placement was never higher than for fistula creation. As the number of haemodialysis patients in a centre increased, more countries had a dedicated coordinator or multidisciplinary team responsible for vascular access maintenance at the centre-level; in 11 countries, responsibility was always with individual nephrologists, independent of a centre's size. In 23 countries, dialysis centres shared vascular access care resources, with facilitation from a service provider in 4. In most countries, national campaigns (n = 35) or educational programmes (n = 29) had addressed vascular access-related topics; 19 countries had some form of training for creating fistulas. Forty experts considered the current evidence base robust enough to justify a fistula-first policy, but only 13 believed that more than 80% of nephrologists in their country would attempt a fistula in a 75-year-old woman with comorbidities.

Conclusions

Suboptimal access to surgical resources, lack of dedicated training of clinicians, limited routine use of pre-operative diagnostic imaging and patient characteristics primarily emerged as potential barriers to adopting a fistula-first policy in Europe.
Chemotherapy Drug Extravasation in Totally Implantable Venous Access Port Systems: How Effective is Early Surgical Lavage?
Authors: Azaïs Henri , Bresson Lucie , Bassil Alfred , Katdare Ninad , Merlot Benjamin , Houpeau Jean-Louis , Bedoui Sophie El , Meurant Jean-Pierre , Tresch Emmanuelle , Narducci Fabrice
Published: November 2014

Purpose

Totally implantable venous access port systems (TIVAPS) are a widely used and an essential tool in the efficient delivery of chemotherapy. Chemotherapy drug extravasation (CDE) can have dire consequences and will delay treatment. The purpose of this study is to both clarify the management of CDE and show the effectiveness of early surgical lavage (ESL).

Methods

Patients who had presented to the Cancer Center of Lille (France) with TIVAPS inserted between January 2004 and April 2013 and CDE had their medical records reviewed retrospectively.

Results

Thirty patients and 33 events were analyzed. Implicated agents were vesicants (51.5%), irritants (45.5%) and non-vesicants (3%). Huber needle malpositionning was involved in 27 cases. Surgery was performed in 97% of cases, 87.5% of which were for ESL with 53.1% of the latter requiring TIVAPS extraction. Six patients required a second intervention due to adverse outcomes (severe cases). Vesicants were found to be implicated in four out of six severe cases and oxaliplatin in two others. Extravasated volume was above 50 ml in 80% of cases. Only one patient required a skin graft.

Conclusions

CDEs should be managed in specialized centers. ESL allows for limited tissue contact of the chemotherapy drug whilst using a simple, widely accessible technique. The two main factors that correlate with adverse outcome seem to be the nature of the implicated agent (vesicants) and the extravasated volume (above 50 ml) leading to worse outcomes. Oxaliplatin should be considered as a vesicant.
Een kansloze minderheid in de marge?
Authors: Vermeersch P.
Published: November 2014

An underprivileged minority in the margin? The socio-economic and political situation of the Roma in Europe

This article provides an overview of the current socio-economic and political situation of the Roma in Europe, the continent's largest and most marginalized minority. While a host of new regulations and initiatives on different levels of government have been issued in order to foster the social inclusion of the Roma in various areas of life, the situation on the ground remains far from hopeful. Poverty and discrimination continue to be huge problems in most of the countries where Roma live. New avenues for political and social mobilization have become available to Roma activists and politicians. Yet also in this area important challenges remain. The recent popularity of extreme right-wing populist responses to Roma mobilization and migration has created important obstacles to the full participation and equal citizenship of Roma in our contemporary societies.
Participatie, veiligheid en beeldvorming van Romaminderheden
Authors: van Baar H.
Published: November 2014

Participation, security and representation of Roma minority groups. A critical reflection on Dutch policies

This article critically evaluates the recent developments in Dutch policy formation regarding Roma minorities from the perspective of the increased attention paid to their position at European level. First, the author discusses the so-called ‘Europeanization of Roma representation’, that is the post-1989 representation of the Roma as a European minority and the simultaneous large-scale, Europe-wide devising of development, inclusion, and empowerment programs meant for them. Thereafter, the author argues that some of the risks of the Roma’s Europeanization – such as the isolation and culturalization of policy formation and the diminishing of democratic accountability – have also and ambiguously affected Dutch policies meant for Roma, Sinti and caravan dwellers. By means of a brief analysis of recent policy developments, the author demonstrates that the Dutch shift towards a policy that, at least in name, encourages social participation, has actually tended to result into a one-sided focus on the Roma as a ‘problem group’ and ‘security threat’.
Scripts, de voertuigen van kennis
Authors: Weyers Heleen , van Tol Donald
Published: November 2014

Scripts, the hidden cargo of stories

This article presents the results of a study into the knowledge of doctors regarding three kinds medical treatment regulation at the end of life, the so-called KOPPEL study. One of the findings of this study is that most doctors know the law that regulates ending life at request (euthanasia) and guideline for palliative sedation quite well. However, hardly any of them know Book 7, Section 450.3 of the Dutch Civil Code, the section that regulates written treatment refusals. Apart from the description of the findings, we elaborate on three reasons that Aubert distinguishes for knowledge of the law: the period the regulation exists, the congruence between habits and norms of the law, and experience with the law. We conclude that Aubert’s factors do indeed explain the differences in knowledge of the doctors. In the discussion we come to the conclusion that sociology of law should not only pay attention to ‘what knowledge of the law is’ (Griffiths, Van Tol) and ‘which factors influence this knowledge’ (Aubert) but also to ‘how knowledge of law can be ascertained’. In our opinion the idea of scripts, as introduced by Schank and Abelson, can be of great help in this respect.
Making Sense of Integers through Storytelling
Authors: Wessman-Enzinger Nicole M. , Mooney Edward S.
Published: November 2014

Students process open-number problems through various ways of thinking. The patterns emerged from the authors' research on student thinking about integers and are connected to teaching tips for the classroom.
Revisiting Mr. Tall and Mr. Short
Authors: Riehl Suzanne M. , Steinthorsdottir Olof Bjorg
Published: November 2014

While students are solving a proportion problem, their work in a measure space will enable teachers to take the measure of their thinking.
Taxicab Geometry in New York City
Authors: Cho Hoyun
Published: November 2014

A discussion of taxicab geometry provides the real-life tie-in to this computation activity.
Charles-Marius Barbeau et l’étude des collections ethnographiques franco-américaines d’Europe de l’Ouest (1931-1956)
Authors: Ferey Vanessa
Published: November 2014

Cette note est issue de recherches menées sur les archives du fonds Marius Barbeau préservées au Musée canadien de l’histoire. Les travaux du folkloriste québécois menés à partir de 1931 au Musée d’ethnographie du Trocadéro participent à l’actualisation des connaissances d’une partie des collections françaises issues de ses anciennes colonies d’Amérique du Nord. Grâce à sa vive collaboration avec le muséologue français Georges-Henri Rivière, le musée parisien est désormais en mesure de valoriser une culture matérielle méconnue en prévision de l’inauguration du Musée de l’Homme en 1937. Malgré une retraite prise en 1948, l’infatigable Marius Barbeau entretient une correspondance scientifique avec Georges-Henri Rivière et revient à Paris en 1953. Il analyse ainsi plusieurs collections amérindiennes dont les résultats apportent un nouveau regard sur le patrimoine franco-américain des musées d’Europe de l’Ouest.
Dolores Turmel-Rodrigue, peintre de la vie populaire en Beauce
Authors: Genest Bernard
Published: November 2014

Décédée en 2011 à l’âge de 82 ans, Dolores Turmel-Rodrigue, artiste peintre, s’était donné pour mission de faire revivre dans ses tableaux les personnes, les lieux et les pratiques de la société traditionnelle de sa région natale, la Beauce. Pour nous la présenter et commenter son oeuvre, Bernard Genest a ressorti ses notes de terrain et des enregistrements réalisés dans le cadre de recherches menées dans les années 1982-1985. Il commence par situer l’artiste dans ses contextes géographique, social et culturel, puis s’attarde à décrire la technique et les thématiques qui caractérisent la production de l’artiste. Sans avoir au départ de plan préconçu, celle-ci voyait comme un devoir de mémoire le fait de témoigner de pratiques et d’un mode de vie pour lesquels elle éprouvait un vif attachement et la conviction profonde d’un héritage à préserver et à transmettre. Son oeuvre, selon l’auteur de l’article, est une contribution importante au patrimoine culturel des Beaucerons et pour l’ensemble des Québécois.
Developing a New Surrogate Safety Indicator Based on Motion Equations
Authors: Behbahani Hamid , Nadimi Navid , Alenoori Hooman , Sayadi Mina
Published: November 2014

Collision avoidance system (CAS), with the help of surrogate safety measures is a beneficial tool for reducing driver errors and preventing rear-end collisions. One of the most well-known surrogate safety measures to detect rear-end conflicts is Time-to-collision (TTC). TTC refers to the time remaining before the rear-end accident if the course and the speed of vehicles are maintained constant. Different surrogate measures have been derived from TTC; however, the most important are Time Exposed Time-to-collision (TET) and Time Integrated Time-to-collision (TIT). In this paper a new surrogate safety measure based on TTC notion has been developed. This new indicator merges TET and TIT into one measure and gives a score between 0 and 100%, as the probability of collision. Applying this indicator in CAS as a safety measure will be more useful than TET&TIT, to reduce driver errors and rear-end collisions.
Traffic Flow Prediction Using MI Algorithm and Considering Noisy and Data Loss Conditions: An Application to Minnesota Traffic Flow Prediction
Authors: Hosseini Seyed Hadi , Moshiri Behzad , Rahimi-Kian Ashkan , Araabi Babak Nadjar
Published: November 2014

Traffic flow forecasting is useful for controlling traffic flow, traffic lights, and travel times. This study uses a multi-layer perceptron neural network and the mutual information (MI) technique to forecast traffic flow and compares the prediction results with conventional traffic flow forecasting methods. The MI method is used to calculate the interdependency of historical traffic data and future traffic flow. In numerical case studies, the proposed traffic flow forecasting method was tested against data loss, changes in weather conditions, traffic congestion, and accidents. The outcomes were highly acceptable for all cases and showed the robustness of the proposed flow forecasting method.
Curbing the epidemic on both sides of the Atlantic: a public health perspective
Authors: Fenton Kevin
Published: November 2014

HIV/AIDS continues to place a devastating toll on individuals, families and communities globally, and western industrialized countries are by no means exempt. Today, there are more than 1 million Americans and 100,000 Britons living with HIV, with a disproportionate burden of new and prevalent HIV infections borne by gay, bisexual and other men who have sex with men (MSM), racial/ethnic minorities, migrants and persons who use drugs. Epidemic concentration in urban areas, especially among: population sub‐groups with high prevalence of risk behaviours; the socio‐economically marginalized; or those with poor access to services, has been well documented. Recent increases in HIV incidence in the rural south US, and in MSM in both countries, reflect the dynamic and evolving nature of these epidemics. New national HIV prevention strategies in both countries have refocused attention on these domestic epidemics, prioritizing HIV testing scaling up, linkage to quality care and tackling long‐standing health inequalities. There are also significant differences between the two countries – in part a reflection of the different health and social care systems; historical approaches to the funding and coordination of HIV prevention; and underlying patterns of health inequalities and their social and structural determinants. In addition, the social–political acceptability of using the sexual health frame to guide more holistic and integrated approaches to HIV prevention efforts remains a key difference. This presentation will compare and contrast HIV prevention responses in the US and UK over the past decade, identifying opportunities for enhancing the prevention response in these and other western industrialized countries in the 21st century.
Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection
Authors: Thornhill John , Inshaw Jamie , Oomeer Soonita , Kaleebu Pontiano , Cooper David , Ramjee Gita , Schechter Mauro , Tambussi Giuseppe , Fox Julie , Maria Miro Jose , Weber Jonathan , Babiker Abdel , Porter Kholoud , Fidler Sarah
Published: November 2014

Introduction

Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART). Low CD4/CD8 ratio is associated with a high risk of AIDS and non‐AIDS events and may act as a marker of immune senescence [1]. This ratio is improved by ART although normalization is uncommon (~7%) [2]. The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI) [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI.

Material and Methods

Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (≥1) adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiated>six months after SC: deferred). We also considered time to CD4 count normalization (≥900 cells/mm3).

Results

In total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45%) early ART had normalized CD4/8 ratio, compared with 11/99 (11%) in the deferred group, whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99 (3%) in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.75 – 5.01, p<0.001). The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.96 – 0.99 for each 30‐day increase). CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.001 – 1.002, p<0.001). There was an association between normal CD4/CD8 ratio and being virally suppressed (<400 copies HIV RNA/ml) p<0.001. CD4 count normalization was also significantly more likely for those initiating early (HR 5.00, 95% CI 1.52 – 16.41, p=0.008).

Conclusions

The likelihood of achieving normalization of CD4/CD8 ratios was increased if ART was initiated within six months of PHI. Higher CD4/CD8 ratio may reflect a more “normal” immune phenotype conferring enhanced prognosis and predict post‐treatment control.
Determinants of IL‐6 levels during HIV infection
Authors: Borges Álvaro H , O'Connor Jemma L , Phillips Andrew N , Rönsholt Frederikke F , Pett Sarah , Vjecha Michael J , French Martyn A , Lundgren Jens D
Published: November 2014

Introduction

Elevated IL‐6 levels have been linked to increased risk of cardiovascular disease (CVD), cancer and death. Compared to the general population, treated HIV+ persons have 50–100% higher IL‐6 levels, but few data on the determinants of IL‐6 levels during HIV infection currently exist.

Material and Methods

Participants in three international HIV trials (SMART, ESPRIT and SILCAAT) with IL‐6 plasma levels measured at baseline were included (N=9864). Factors independently associated with log2‐transformed IL‐6 level were identified by multivariate linear regression; exponentiated estimates corresponding to fold differences (FDs) in IL‐6 were calculated. Demographics (age, gender, race, BMI) and HIV‐specific variables (nadir and entry CD4 counts, HIV‐RNA, use of different ART regimens) were investigated in all three trials. In SMART (N=4498), smoking, comorbidities (CVD, diabetes, hepatitis B/C [HBV/HCV]), HDL‐cholesterol, renal function (eGFR) and educational level were also assessed.

Results

Demographics associated with higher IL‐6 were older age (FD [95% CI]: 1.09 [1.08–1.11] per 10 yr) and higher BMI (1.02 [1.01–1.04] per 5 kg/m2), whereas black race was associated with reduced IL‐6 (0.96 [0.93–0.99]). As for HIV variables, patients not receiving ART (1.36 [1.29–1.43]) and with higher HIV‐RNA (1.24 [1.01–1.52] for >100,000 vs. ≤500 copies/mL) had increased IL‐6. Participants taking protease inhibitors (PI) had higher IL‐6 (1.14[1.09–1.19]). Higher nadir CD4 count (0.98 [0.97–0.99]/100 cells/µL) was related to lower IL‐6. All evaluated comorbidities were related to higher IL‐6; FDs in IL‐6 were 1.08 [1.04–1.12] for smoking, 1.12 [1.02–1.24] for CVD, 1.07 [1.00–1.16] for diabetes and 1.12 [1.02–1.24] for HBV (1.15 [1.02–1.30]) and 1.53 [1.45–1.62] for HCV. IL‐6 increased with decreasing eGFR (0.98 [0.97–1.00]/10 mL/min) and HDL‐cholesterol (0.98 [0.96–0.99]/10 mg/mL). Lower education was related to higher IL‐6 (1.09 [1.03–1.15] for high school vs. bachelor's degree).

Conclusions

Higher IL‐6 levels were associated with older age and non‐black race, higher BMI and lower HDL‐cholesterol, ongoing HIV replication, low nadir CD4 counts, comorbidities and decreased renal function. This suggests that there are multiple causes of inflammation in treated HIV infection. A possible contribution from PI use was also observed. Contribution from inflammation to explain variation in clinical outcomes for these factors should be investigated.
Once‐daily dolutegravir is superior to once‐daily darunavir/ritonavir in treatment‐naïve HIV‐1‐positive individuals: 96 week results from FLAMINGO
Authors: Molina Jean‐Michel , Clotet Bonaventura , van Lunzen Jan , Lazzarin Adriano , Cavassini Matthias , Henry Keith , Kulagin Valeriv , Givens Naomi , Brennan Clare , de Oliveira Carlos Fernando
Published: November 2014

Introduction

Dolutegravir (DTG) 50 mg once daily was superior to darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily through Week 48, with 90% vs. 83% of participants achieving HIV RNA 50 c/mL (p=0.025) [1]. We present data through Week 96.

Material and Methods

FLAMINGO is a multicentre, randomized, open‐label, Phase IIIb non‐inferiority study, in which HIV‐1‐positive ART‐naïve adults with HIV‐1 RNA≥1000 c/mL and no evidence of viral resistance were randomized 1:1 to receive DTG or DRV/r, with investigator‐selected backbone NRTIs (TDF/FTC or ABC/3TC). Participants were stratified by screening HIV‐1 RNA (≤100K c/mL) and NRTI backbone.

Results

A total of 484 adults were randomized and treated; 25% had baseline HIV RNA 100K c/mL. At Week 96, the proportion of participants with HIV RNA 50 c/mL was 80% in the DTG arm vs. 68% in the DRV/r arm (adjusted difference 12.4%; 95% CI 4.7, 20.2%; p=0.002). Secondary analyses supported primary results: per‐protocol [(DTG 83% vs. DRV/r 70%), 95% CI 12.9 (5.3, 20.6)] and treatment‐related discontinuation = failure [(98% vs. 95%), 95% CI 3.2 (−0.3, 6.7)]. Overall virologic non‐response (DTG 8%; DRV/r 12%) and non‐response due to other reasons (DTG 12%; DRV/r 21%) occurred less frequently on DTG. As at Week 48, the difference between arms was most pronounced in participants with high baseline viral load (82% vs. 52% response through Week 96) and in the TDF/FTC stratum (79% vs. 64%); consistent responses were seen in the ABC/3TC stratum (82% vs. 75%). Six participants (DTG 2, none post‐Week 48; DRV/r 4, two post‐Week 48) experienced protocol‐defined virologic failure (PDVF; confirmed viral load 200 c/mL on or after Week 24); none had treatment‐emergent resistance to study drugs. Most frequent drug‐related adverse events (AEs) were diarrhoea, nausea and headache, with diarrhoea significantly more common on DRV/r (24%) than DTG (10%). Significantly more participants had Grade 2 fasting LDL toxicities on DRV/r (22%) vs. DTG (7%), p<0.001; mean changes in creatinine for DTG (~0.18 mg/dL) observed at Week 2 were stable through Week 96.

Conclusions

Once‐daily DTG was superior to once‐daily DRV/r in treatment‐naïve HIV‐1‐positive individuals, with no evidence of emergent resistance to DTG in virologic failure and relatively similar safety profiles for DTG and DRV/r through 96 Weeks.
Models of care and delivery
Authors: Lundgren Jens
Published: November 2014

Marked regional differences in HIV‐related clinical outcomes exist across Europe. Models of outpatient HIV care, including HIV testing, linkage and retention for positive persons, also differ across the continent, including examples of sub‐optimal care. Even in settings with reasonably good outcomes, existing models are scrutinized for simplification and/or reduced cost. Outpatient HIV care models across Europe may be centralized to specialized clinics only, primarily handled by general practitioners (GP), or a mixture of the two, depending on the setting. Key factors explaining this diversity include differences in health policy, health insurance structures, case load and the prevalence of HIV‐related morbidity. In clinical stable populations, the current trend is to gradually extend intervals between HIV‐specific visits in a shared care model with GPs. A similar shared‐model approach with community clinics for injecting drug‐dependent persons is also being implemented. Shared care models require oversight to ensure that primary responsibility is defined for the persons overall health situation, for screening of co‐morbidities, defining indication to treat comorbidities, prescription of non‐HIV medicines, etc. Intelligent bioinformatics platforms (i.e. generation of alerts if course of care deviates from a prior defined normality) are being developed to assist in providing this oversight and to provide measure of quality. Although consensus exists to assess basic quality indicators of care, a comprehensive set of harmonized indicators are urgently needed to define best practise standards via benchmarking. Such a tool will be central to guide ongoing discussions on restructuring of models, as quality of care should not be compromised in this process.
Predicted savings to the UK National Health Service from switching to generic antiretrovirals, 2014–2018
Authors: Hill Andrew , Hill Teresa , Jose Sophie , Pozniak Anton
Published: November 2014

Introduction

In other disease areas, generic drugs are normally used after patent expiry. Patents on zidovudine, lamivudine, nevirapine and efavirenz have already expired. Patents will expire for abacavir in late 2014, lopinavir/r in 2016, and tenofovir, darunavir and atazanavir in 2017. However, patents on single‐tablet regimens do not expire until after 2026.

Methods

The number of people taking each antiretroviral in the UK was estimated from 23,655 individuals in the UK CHIC cohort (2012 database). Costs of patented drugs were taken from the British National Formulary database, assuming a 30% discount. Costs of generic antiretrovirals were estimated using an 80% discount from patented prices, or actual costs where available. Two options were analysed: 1 – all patients use single‐tablet regimens and patented versions of drugs; prices remain stable over time; 2 – all people switch from patented to generic drugs when available, after patent expiry (dates shown above).

Results

There were an estimated 67,000 people taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until 2018 (in line with previous rises). The most widely used antiretrovirals in the CHIC cohort were tenofovir (TDF) (75%), emtricitabine (FTC) (69%), efavirenz (EFV) (39%), lamivudine (3TC) (23%), abacavir (ABC) (18%), darunavir (DRV) (21%) and atazanavir (ATV) (16%). The predicted annual UK cost of generic ABC/3TC/EFV (three generic tablets once daily) was £1018 per person‐year. Costs of patented single‐tablet regimens ranged from £5000 to £7500 per person‐year. Assuming continued use of patented antiretrovirals in the UK, the predicted total national costs of antiretroviral treatment were predicted to rise from £425 million in 2014 to £459 m in 2015, £495 m in 2016, £536 m in 2017 and £578 m in 2018. With a 100% switch to generics, total predicted costs were £337 m in 2014, £364 m in 2015, £382 m in 2016, £144 m in 2017 and £169 m in 2018. The total predicted saving over five years from a switch to generics was £1.1 billion.

Conclusions

Systematic switching from patented to generic antiretrovirals could potentially save approximately £1.1 billion in the UK over the next five years, compared with continued use of patented versions: this money could be spent on urgently needed HIV prevention programmes. Similar savings are feasible for other European countries, given parallel patent expiry dates. More detailed economic evaluation is required to show when patented single‐tablet regimens provide value for money, compared to bioequivalent generic versions of 3–4 pills once daily.
Treatment and care of TB across Europe
Authors: Kirk Ole
Published: November 2014

There continues to be profound differences in TB incidences as well as in TB treatment and care across Europe in recent years. High TB incidences are observed in Eastern Europe and especially among injecting drug users (IDUs), and there are large overlaps with a HIV epidemic, which is also far from being under control in this region. Further, mortality rates among HIV‐positive patients with TB in Eastern Europe were in the 2000s 3–5 fold higher compared with other parts of Europe. As of 2014, there remain many challenges in the organizational set‐up of TB care in Eastern Europe and often only limited possibilities of support for the vulnerable IDU populations, including in particular opioid substitution therapy. Further, high prevalences of multi‐drug‐resistant TB (MR‐TB) are an increasing problem in Eastern Europe which in several settings reached beyond 50% among patients previously treated for TB. Obviously, this causes problems for immediate therapy of the individual patients and for development of secondary resistance during therapy. The panel of TB drugs available in TB clinics in Eastern Europe is often limited, and a quick TB diagnosis and acknowledgement of the resistance pattern to guide initial therapy seems to be a priority. For HIV‐positive patients in particular, better access to cART may also be an important tool to reduce the TB incidence among these patients. Thus, treatment and care of TB patients in especially Eastern Europe are facing a variety of diagnostic and therapeutic challenges in the coming years.
Efavirenz 400 mg daily remains non‐inferior to 600 mg: 96 week data from the double‐blind, placebo‐controlled ENCORE1 study
Authors: Carey Dianne
Published: November 2014

Introduction

ENCORE1 compared the efficacy and safety of reduced versus standard dose efavirenz (EFV) with tenofovir/emtricitabine (TDF/FTC) as first‐line HIV therapy. The primary analysis at 48 weeks showed 400 mg EFV was safe and virologically non‐inferior to 600 mg. This analysis explores over 96 weeks the durability of efficacy and safety.

Materials and Methods

A multinational, double‐blind, placebo‐controlled, non‐inferiority trial in treatment‐naïve HIV‐positive adults randomized to TDF/FTC plus reduced (400 mg, EFV400) or standard dose (600 mg, EFV600) EFV. The difference between proportions of participants with plasma HIV RNA (VL) <200 log10 copies/mL by intention‐to‐treat (ITT missing=failure) was compared using a non‐inferiority margin of −10%. Non‐inferiority was also examined in per protocol (PP) and non‐completer = failure (NC=F) populations. Adverse events (AEs) and serious adverse events (SAEs) were summarized by treatment arm.

Results

The ITT population comprised 630 patients (EFV400 = 321; EFV600 = 309); 32% were female; 37%, 33% and 30% were African, Asian and Caucasian, respectively. A total of 585 (EFV400 = 299; EFV600 = 286) completed 96 weeks on randomized therapy. At 96 weeks, proportions with VL <200 copies/mL were EFV400 (90.0%) and EFV600 (90.6%) (difference −0.6; 95% CI −5.2 to 4.0; p=0.72) demonstrating continued non‐inferiority. Non‐inferior efficacy was also observed for VL thresholds of <50 and <400 copies/mL irrespective of baseline VL (<100,000 versus ≥100,000 copies/mL). There was no between‐arm difference in time to loss of virological response (>200 copies/mL) (p=0.47) or mean change from baseline VL (p=0.74). Mean change from baseline in CD4 T‐cell counts at week 96 remained significantly higher for EFV400 than EFV600 (difference 25 cells/µL; 95% CI 2–48; p=0.03). There was no difference in the frequency or severity of AEs (EFV400 = 89.4%, EFV600 = 89.3%; difference 0.09; 95% CI −4.73 to 4.90; p=0.97). The proportions ever reporting an AE definitely or probably EFV‐related were EFV400 (37.7%) and EFV600 (47.9%) (difference −10.2%; 95% CI −17.9 to −2.51; p=0.01). SAEs did not differ in frequency (EFV400 = 7.5%, EFV600 = 10.4%; difference −2.9%; 95% CI −7.3 to 1.6; p=0.20).

Conclusions

Non‐inferiority of EFV 400 mg to EFV 600 mg when combined with TDF/FTC as initial HIV therapy was confirmed at week 96. Both doses demonstrated similar safety profiles. These results support the use of a lower EFV dose as part of routine HIV management.
Patients’ willingness to take separate component antiretroviral therapy regimens for HIV in the Netherlands
Authors: Engelhard Esther , Smith Colette , Vervoort Sigrid , Kroon Frank , Brinkman Kees , Nieuwkerk Pythia , Reiss Peter , Geerlings Suzanne
Published: November 2014

Introduction

The costs of combination antiretroviral therapy (cART) consisting of separate, particularly generic, components are generally much lower than of a single tablet regimen (STR) including the same active ingredients. Our aim was to evaluate whether patients in care in the Netherlands would be willing to take separate component regimens (SCR) instead of an STR and to examine whether willingness was associated with particular patient characteristics.

Materials and Methods

Data from the HIV Monitoring Foundation of all adult HIV‐1‐infected patients in care taking cART>6 months were used to randomly select 1000 patients. As part of a questionnaire developed for a study assessing patient experience, patients were asked whether they were willing to take an SCR instead of an STR. Logistic regression was used to examine associations between age, gender, region of origin, mode of HIV transmission, socioeconomic status, duration of cART and answering “yes” to the question versus “maybe” or “no.” Variables with p<0.1 in the univariate analysis were entered in a multivariate model.

Results

Of the 300 patients who completed the questionnaire, 49% answered “yes,” 24% “maybe” and 27% “no” to the question whether they would be willing to use a SCR. Reasons for answering “no” included difficulties swallowing pills, convenience of STR (especially when travelling/at work), and concerns about side effects. Respondents who answered “maybe” often indicated that they preferred STRs, emphasized the importance of taking the pills once daily, and pointed out that efficacy/safety of an SCR should not be less. Having to pay for medication was reported as a reason to consider switching to an SCR. In the multivariate analysis, respondents who were born outside the Netherlands were less likely; and those with cART use ≥15 yrs were more likely to answer “yes” (Table 1).

Conclusions

Half of the respondents were willing to take SCRs instead of an STR. The likelihood of accepting to switch to SCR seems less for migrants and for those who have commenced treatment more recently. Duration of cART use and region of origin may therefore be factors to take into account when considering to prescribe SCR. Future studies should investigate whether an expressed willingness to switch will translate into maintained high levels of adherence and viral suppression.
Long‐term fat redistribution in ARV‐naïve HIV+ patients initiating a non‐thymidine containing regimen in clinical practice
Authors: Ferrer Elena , Navarro Antonio , Curto Jordi , Medina Pilar , Rozas Nerea , Barrera Gladys , Saumoy Maria , Manuel Tiraboschi Juan , Gomez Carmen , Podzamczer Daniel
Published: November 2014

Introduction

Lipodystrophy is still a matter of concern in HIV+ patients receiving ART. However, long‐term fat change in patients taking non‐thymidine regimens is not well known.

Materials and Methods

A prospective ongoing fat change assessment including clinical evaluation and dexa scans (Hologic QDR 4500) is being conducted in all consecutive patients initiating ART from January 2008. Arm, leg, trunk and total fat as well as fat mass ratio (FMR=% trunk fat/% leg fat) were determined. Patients with data at baseline (BL), 12 and 36 m are included in this analysis. ITT and OT were performed. Multivariate general linear models were used to assess changes in fat measures.

Results

One hundred patients were included. 81% men, 42.9 years, 18% AIDS, CD4 218.5 (6‐756), viral load 5 log (2.9‐6.8), leg fat 4644g, trunk fat 6693g, FMR 0.94. Around 40 patients (40%) initiated a PIr (17 LPVr, 11 ATVr, 9 DRVr, 3 FPVr), 34 (34%) NVP and 21 (21%) EFV. About 83% received TDF/FTC and 10% ABC/3TC. Groups were comparable at BL except for a lower viral load in NVP patients (p=0.047) and lower c‐LDL in PI patients (p=0.043). After 36 m, no patient presented a clinically evident lipodystrophy. At 12 m, an overall significant increase was found from baseline in trunk, leg and FMR (median 759 g, 479.4 g and 0.03, respectively, p<0.05) and at 36 m in trunk and leg fat (median 989.9 g, 566 g, respectively, p<0.05). According to ART, at 12 m a significant increase in trunk and leg fat was observed in EFV and PIr. At 36 m, in NVP patients trunk and leg fat as well as FMR increased, whereas in PIr patients only leg fat increased (see figure). In ITT analysis, adjusted by age, sex, risk practice and BL CD4, EFV was associated with a greater increase in FMR (p=0.036) at 36 m vs PIr. In OT analysis, at 12 m, NVP was associated with a smaller percentage increase in trunk fat (vs PIr and EFV, p=0.006) and in leg fat (vs PIr, p=0.046). These differences did not persist at 36 m.

Conclusions

In this cohort of patients taking non‐thymidine‐based regimens, after 36 m without a clinically evident lipodystrophy, no significant changes in FMR were observed. However, some differences in fat redistribution according to ART were present: PIr was associated with an initial and continuous increase in trunk and leg fat, NVP with a slower and progressive increase in both fat compartments, while in EFV patients, the initial fat increase was followed by a decrease in peripheral fat at 36 m. Longer follow up will help to confirm these trends.
Polymorphisms in LPL, CETP, and HL protect HIV‐infected patients from atherogenic dyslipidemia in an allele‐dose‐dependent manner
Authors: Echeverría Patricia , Guardiola Montse , González Marta , Carles Vallvé Joan , Puig Jordi , Bonjoch Anna , Clotet Bonaventura , Ribalta Josep , Negredo Eugenia
Published: November 2014

Introduction

HIV‐infected patients treated with Highly Active Antiretroviral Therapy (HAART) may be predisposed to hypertriglyceridemia, which gives rise to a highly atherogenic lipid profile known as atherogenic dyslipidemia (AD). We propose that genetic variability leaves some HIV‐infected patients more predisposed to AD than others [1, 2].

Methods

This was a cross‐sectional, observational study conducted in 468 antiretroviral‐treated HIV‐infected patients attending at the outpatient clinic of a tertiary hospital over a 6‐month period, who were classified as normolipidemic (n=173) or presenting with AD (triglycerides: 1.7 mmol/L and HDLc < 1.02 [men] or 1.28 mmol/L [women]) (n=148). Polymorphisms were identified in the APOA5, APOC3, LPL, CETP, HL, MTP, APOE, LRP5 and VLDLR genes.

Results

Atherogenic dyslipidemia was detected in 31% of patients, most of whom were men (77%). This group was also older and had higher levels of remnant lipoprotein cholesterol (RLPc) than normolipidemic patients. The polymorphisms rs328 in LPL, rs708272 in CETP and rs1800588 in HL were 10–40% significantly more frequent in normolipidemic patients. At least 1 of these polymorphisms was detected in 90% of normolipidemic patients; in AD patients, the percentage decreased to 75% (p=0.003). This effect was dependent on both the allele and the dose of HAART and independent of the regimen administered. The protective combination showed a trend towards higher HDLc (1.13 [0.40] vs 1.24 [0.23] mmol/L), lower triglycerides (2.23 [2.34] vs 1.89 [1.24] mmol/L) and lower RLPc (16.41 [11.42] vs 12.99 [11.69] mmol/L).

Conclusions

Polymorphisms in LPL, CETP and HL protect HIV‐infected patients from developing AD in a dose‐dependent manner [3].
Clinical significance of the UGT1A1*28 allele detection in HIV‐infected patients
Authors: Kanestri Veronika , Mironov Konstantin , Kravchenko Alexey , Pokrovskaya Anastasiya , Dribnohodova Olga , Dunayeva Elena , Tsiganova Galina , Harbutly Marina , Goliusova Marina , Konnov Vladislav , Kozirina Nadezhda , Shahgildyan Vasiliy , Kuimova Ulyana , Popova Anna , Efremova Oksana , Konnov Danila
Published: November 2014

Introduction

The UGT1A1*28 (rs8175347) polymorphism is associated with hyperbilirubinemia. The presence of 6 TA‐repeats in the UGT1A1 gene promoter region corresponds to normal UGT1TA1 activity. A detection of 7 TA‐repeats in hetero‐ or homozygous individuals [(TA)6/(TA)7 and (TA)7/(TA)7] is associated with lower UGT1TA1 activity, which may eventually result in the development of Gilbert syndrome and/or modified individual response to drugs metabolized by this enzyme. ATV contributes to the decreased levels of UGT1A1, which may lead to elevations of indirect bilirubin, jaundice and even to therapy discontinuation. We evaluated the prevalence of the UGT1A1*28 among HIV‐infected patients and the dependence of the frequency and severity of AE during ATV treatment on individual genetic characteristics.

Materials and Methods

47 HIV‐infected patients was screen for UGT1A1 genotype and the presence of UGT1A1*28. All patients received ATV in the HAART regimen for 48 weeks. Changes in the total, direct and indirect bilirubin, ALT, AST, GGT and jaundice were evaluated. Statistical analysis was performed using Microsoft Office Excel for Windows XP Professional 2007 and Biostat.

Results

All patients were followed up in the AIDS Center (males 72.3%, median age 33 years, median CD4+ count‐282 cells/µl (19.5%)). HBV/HCV was in 36.2% patients. Ten patients had risk factors that could affect bilirubin turnover (chronic cholecystitis, biliary dyskinesia, etc.). Genotype (TA)6/(TA)6 was found in 42.6% patients, (TA)6/(TA)7‐42.6% and (TA)7/(TA)7‐14.9%. Overall prevalence of UGT1A1*28 was 57.4%, and homozygous allele frequency was 14.9%. G3/4 of indirect bilirubin were detected in 36.2% patients [(TA)6/(TA)6 in 10–20%, (TA)6/(TA)7‐25‐40%, (TA)7/(TA)7‐72‐86%], and significant jaundice in 10.6% [80% with (TA)7/(TA)7]. The OR for hyperbilirubinemia>40 µmol/L in patients with heterozygous UGT1A1*28 was increased 3 times over patients without this allele (OR 3.07, 95% CI 1.54–4.6) and 34 times as compared with homozygotes (OR 33.9, 95% CI 31.45–36.35). The presence of additional risk factors increased the probability of G3/4 hyperbilirubinemia. No significant changes in the ALT, AST, and GGT levels were observed.

Conclusions

The risk of severe hyperbilirubinemia during ATV treatment is minimal for patients without UGT1A1*28 and no more than one additional risk factor and for patients with UGT1A1*28 and no additional risk factors; patients with homozygous genotype UGT1A1*28 are at the highest risk.
Using social network methods to reach out‐of‐care or ART‐nonadherent HIV+ injection drug users in Russia: addressing a gap in the treatment cascade
Authors: Amirkhanian Yuri , Kelly Jeffrey , Kuznetsova Anna , Meylakhs Anastasia , Yakovlev Alexey , Musatov Vladimir , Chaika Nikolay
Published: November 2014

Introduction

HIV treatment to reduce downstream HIV incidence and to decrease disease mortality and morbidity at a population level both require that hidden, out‐of‐care people living with HIV (PLH) in the community be reached and engaged to enter care. This research evaluated the feasibility of reaching out‐of‐care or non‐adherent PLH through members of their social networks in St Petersburg, Russia.

Materials and Methods

To recruit a social network sample of HIV‐positive injection drug users, 16 HIV+ seeds were enrolled into the study through PLH‐oriented websites and online forums using recruitment ads or approached in needle exchange sites. Interested persons called the study phone number and completed a brief eligibility interview. Seed inclusion criteria were HIV+ status, being 18 years or older, having ever injected drugs, and having not visited an HIV doctor in the past 6 months. Seeds provided blood specimens tested for HIV to confirm their self‐reported status. Eligible seeds were enrolled, completed brief network elicitation interview, and were asked to invite their own HIV+ friends into the study. Incentives were provided as compensation for participants’ time and additional smaller incentives were provided for inviting each HIV+ network member to also participate. The seed's PLH friends established the first ring of participants who, in turn were asked to invite their own PLH friends (second ring). All study participants completed assessment of psychosocial wellbeing and sexual and injection‐related HIV risk behaviour. Blood samples were collected from all participants to confirm their HIV+ status.

Results

Through this chain referral process, the initial 16 seeds led to the enrolment of a total of 66 PLH from the community (mean=4 per initial seed), most of whom – like the seed – were not presently in HIV care or were ART non‐adherent.

Conclusions

Implementation of treatment cascade goals requires complementing conventional paths of identifying PLH with feasible and effective community‐based approaches such as described in this study. This research establishes that PLH are connected in their day‐to‐day social networks with other HIV+ persons and shows that social network methods can be employed to reach infected persons through their connections with other PLH. This method has the potential to expand the reach of medical care efforts and ART uptake.