bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Gender Classification Using an Extended Set of Local Binary Patterns
Authors: Ardakany Abbas Roayaei , Nicolescu Mircea , Nicolescu Monica
Published: November 2014

In this article, the authors designed and implemented an efficient gender recognition system with high classification accuracy. In this regard, they proposed a novel local binary descriptor capable of extracting more informative and discriminative local features for the purpose of gender classification. Traditional Local binary patterns include information about the relationship between a central pixel value and those of its neighboring pixels in a very compact manner. In the proposed method the authors incorporate into the descriptor more information from the neighborhood by using extra patterns. They have evaluated their approach on the standard FERET and CAS-PEAL databases and the experiments show that the proposed approach offers superior results compared to techniques using state-of-the-art descriptors such as LBP, LDP and HoG. The results demonstrate the effectiveness and robustness of the proposed system with 98.33% classification accuracy.
Weighing the costs: Implementing the SLMTA programme in Zimbabwe using internal versus external facilitators
Authors: Shumba Edwin , Nzombe Phoebe , Mbinda Absolom , Simbi Raiva , Mangwanya Douglas , Kilmarx Peter H. , Luman Elizabeth T. , Zimuto Sibongile N.
Published: November 2014

Background: In 2010, the Zimbabwe Ministry of Health and Child Welfare (MoHCW) adopted the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme as a tool for laboratory quality systems strengthening.Objectives: To evaluate the financial costs of SLMTA implementation using two models (external facilitators; and internal local or MoHCW facilitators) from the perspective of the implementing partner and to estimate resources needed to scale up the programme nationally in all 10 provinces.Methods: The average expenditure per laboratory was calculated based on accounting records; calculations included implementing partner expenses but excluded in-kind contributions and salaries of local facilitators and trainees. We also estimated theoretical financial costs, keeping all contextual variables constant across the two models. Resource needs for future national expansion were estimated based on a two-phase implementation plan, in which 12 laboratories in each of five provinces would implement SLMTA per phase; for the internal facilitator model, 20 facilitators would be trained at the beginning of each phase.Results: The average expenditure to implement SLMTA in 11 laboratories using external facilitators was approximately US$5800 per laboratory; expenditure in 19 laboratories using internal facilitators was approximately $6000 per laboratory. The theoretical financial cost of implementing a 12-laboratory SLMTA cohort keeping all contextual variables constant would be approximately $58 000 using external facilitators; or $15 000 using internal facilitators, plus $86 000 to train 20 facilitators. The financial cost for subsequent SLMTA cohorts using the previously-trained internal facilitators would be approximately $15 000, yielding a break-even point of 2 cohorts, at $116 000 for either model. Estimated resources required for national implementation in 120 laboratories would therefore be $580 000 using external facilitators ($58 000 per province) and $322 000 using internal facilitators ($86 000 for facilitator training in each of two phases plus $15 000 for SLMTA implementation in each province).Conclusion: Investing in training of internal facilitators will result in substantial savings over the scale-up of the programme. Our study provides information to assist policy makers to develop strategic plans for investing in laboratory strengthening.
Making great strides in medical laboratory quality
Authors: Noble Michael , Martin Robert , Ndihokubwayo Jean-Bosco
Published: November 2014

No abstract
Evidence from 617 laboratories in 47 countries for SLMTA-driven improvement in quality management systems
Authors: Yao Katy , Luman Elizabeth T. , Collaborating Authors SLMTA
Published: November 2014

Background: The Strengthening Laboratory Management Toward Accreditation (SLMTA) programme is a large-scale effort to improve the quality of laboratories in resource-limitedcountries.Objectives: This study sought to evaluate the first four years (2010–2013) of SLMTA implementation.Methods: Country-level data were submitted by SLMTA programme leads and compiledglobally. Performance was measured before (baseline) and after (exit) SLMTA implementation using an audit checklist which results in a percentage score and a rating of zero to five stars. Some laboratories continued to monitor performance in post-exit surveillance audits. We evaluated score improvements using two-tailed t-tests for equal variances and estimated the number of tests performed by SLMTA laboratories based on star level.Results: SLMTA was implemented in 617 laboratories in 47 countries in Africa, the Caribbean, Latin America and Southeast Asia. At the baseline audit, the laboratories scored an average of 39% on the checklist and 84% of them were rated below one star. As of December 2013, 302 laboratories had completed the SLMTA programme; mean checklist scores increased from39% at baseline to 64% at exit (p < 0.001) over an average 16-month programme duration. Ninety-two laboratories conducted a surveillance audit at a median of 11 months after their exit audit; 62% further increased their performance. Six SLMTA laboratories have achieved accreditation status. In total, the 617 SLMTA laboratories conduct an estimated 111 milliontests annually. Only 16% of these tests were conducted by laboratories with at least one star at baseline, which increased to 68% of tests after SLMTA training. Thus, approximately 23 million tests are conducted annually by laboratories previously at zero stars that now have one to five stars; this number is projected to increase to 58 million when currently-enrolled laboratories complete the programme.Conclusion: SLMTA has transformed the laboratory landscape in resource-limited countries worldwide and has the potential to make a substantial and sustainable impact on the qualityof laboratory testing and patient care.
A comprehensive review of the SLMTA literature part 1: Content analysis and future priorities
Authors: Luman Elizabeth T. , Yao Katy , Nkengasong John N.
Published: November 2014

Background: Since its introduction in 2009, the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme has been implemented widely throughout Africa, as well as in the Caribbean, Central and South America, and Southeast Asia.Objective: We compiled results from local, national and global studies to provide a broad view of the programme and identify directions for the future. The review consists of two companion papers; this paper focuses on content analysis, examining various thematic components of the SLMTA programme and future priorities.Methods: A systematic literature search identified 28 published articles about implementing the SLMTA programme. Results for various components of the SLMTA programme were reviewed and summarised.Results: Local and national studies provide substantial information on previous experiences with quality management systems; variations on SLMTA implementation; building human resource capacity for trainers, mentors and auditors; the benefits and effectiveness of various types of mentorship; the importance of management buy-in to ensure country ownership; the need to instill a culture of quality in the laboratory; success factors and challenges; and future directions for the programme.Conclusions: Local, national and global results suggest that the SLMTA programme has been overwhelmingly successful in transforming laboratory quality management. There is an urgent need to move forward in four strategic directions: progression (continued improvement in SLMTA laboratories), saturation (additional laboratories within countries that have implemented SLMTA), expansion (implementation in additional countries), and extension (adapting SLMTA for implementation beyond the laboratory), to lead to transformation of overall health systems and patient care.
Imaging of complications from hematopoietic stem cell transplant
Authors: Pandey Tarun , Maximin Suresh , Bhargava Puneet
Published: November 2014

Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT) is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in treamtent of genetic, immunological, and solid tumors like neuroblastoma, lymphoma, and germ cell tumors. In spite of the rapid advances in stem cell technology, success rate with this technique has not been universal and many complications have also been seen with this form of therapy. The key to a successful HSCT therapy lies in early diagnosis and effective management of complications associated with this treatment. Our article aims to review the role of imaging in diagnosis and management of stem cell transplant complications associated with HSCT.
Neonatal neurosonography: A pictorial essay
Authors: Bhat Venkatraman , Bhat Varun
Published: November 2014

Neurosonography is a simple, established non-invasive technique for the intracranial assessment of preterm neonate. Apart from established indication in the evaluation of periventricular haemorrhage, it provides clue to wide range of pathology. This presentation provides a quick roadmap to the technique, imaging anatomy and spectrum of pathological imaging appearances encountered in neonates.
MRI and MR tractography in bilateral hypertrophic olivary degeneration
Authors: Sen Debraj , Gulati Yoginder S , Malik Virender , Mohimen Aneesh , Sibi Eranki , Reddy Deepak Chandra
Published: November 2014

Hypertrophic olivary degeneration is a trans-synaptic neuronal degeneration associated with hypertrophy of the inferior olivary nucleus due to a lesion in the triangle of Guillain-Mollaret. Familiarity with this entity on magnetic resonance imaging (MRI) is essential to avoid other erroneous ominous diagnoses. We present a case of bilateral hypertrophic olivary degeneration and discuss the etiopathogenesis and MRI findings in this entity. The contributory role of MR tractography in the diagnosis is also highlighted.
Shoulder to Shoulder? Masculinities and Informal Learning in Later Life
Authors: Fragoso António , Ricardo Rute , Tavares Nélia , Coelho Aurora
Published: November 2014

Although Portuguese researchers are increasingly interested in studying ageing processes, adult education has not been giving older citizen's learning the attention it deserves. At the same time, while discourse on informal learning has been present for a long time, not many investigations have chosen it as a central theme. During the OMAL project, we wanted to first have an exploratory approach to older men's learning in the community which, at a certain point, needs a theoretical focus on masculinities. In this article, we present the results of two case studies related to fishing. Our findings point to some interesting comments both on the importance of informal learning and of symbolic spaces in the community, as well as promising results on the issue of masculinities. Our provisional conclusions allow us to redirect our future investigational efforts.
"Druženje, vedoželjnost, širina …", učinki neformalnega izobraževanja odraslih v projektu Bell
Authors: Vrečer Natalija
Published: November 2014

V članku so predstavljeni rezultati kvalitativne raziskave, ki je bila opravljena v Sloveniji v okviru projekta Bell. V tem projektu smo raziskovali učinke neformalnega izobraževanja, pri čemer smo izhajali iz predpostavke, da ima neformalno izobraževanje številne pozitivne učinke. Predpostavka se je v raziskavi potrdila. Vsi intervjuvanci so omenjali številne pozitivne učinke kot posledico njihove udeležbe v neformalnem izobraževanju. Rezultati intervjujev potrjujejo rezultate statistične analize, saj so bili tako pri kvalitativni kot pri kvantitativni analizi najpogostejši učinki razširjena socialna mreža, osebna učinkovitost (zlasti okrepitev samozavesti), duševno zdravje, kompetence (zlasti kompetence IKT in splošno znanje) in sprememba izobraževalne izkušnje (zlasti večja motivacija za učenje). Prav tako rezultati intervjujev potrjujejo rezultate analize literature, intervjuvanci so omenjali skoraj vse pozitivne učinke neformalnega izobraževanja, ki so bili ugotovljeni v navedeni literaturi.
Parada učenja - Dnevi učečih se skupnosti
Authors: Pangerc Pahernik Zvonka
Published: November 2014

Članek predstavlja nekatere vidike 19-letnega razvoja projekta Teden vseživljenjskega uče-nja, ki so pripeljali do novega pristopa k promociji izobraževanja odraslih in vseživljenjskega učenja v Sloveniji. Ta nosi zveneče ime Parada učenja (PU) s podnaslovom, ki daje vedeti, da je učenje že vraščeno v okolja, v katerih je bil pristop uporabljen, in obenem spodbuja (nadaljnji) razvoj učečih se skupnosti. Opisani so primer in nekatere značilnosti dozdajšnjih 14 Parad učenja ter njihova vpetost v prakso, stroko in politiko izobraževanja odraslih. Slednja je na evropski ravni zagotovila strateške pa tudi finančne spodbude za opisana prizadevanja v obliki Resolucije o prenovljenem Evropskem programu za učenje odraslih. Uresničevanje tega programa bo teklo tudi v prihodnje in bo podpiralo razvoj učeče se družbe.
Kaj lahko med študijem naredim za svojo večjo zaposljivost?
Authors: Jurček Andreja , Radusinović Aleksandra
Published: November 2014

V nenehno spreminjajoči se družbi se potreba po fleksibilnosti jasno kaže predvsem na trgu dela. V ospredje vse bolj prihajata koncepta vseživljenjskega učenja in vseživljenjske karierne orientacije, kar pomeni, da pri iskalcih zaposlitve ne gre več za statično pridobitev izobrazbe in eno izbiro kariere, temveč za dinamično, kontinuirano pridobivanje kompetenc in prilaganje poklicne poti trenutnim razmeram na trgu dela ob upoštevanju posameznikovih želja, sposobnosti in interesov. Vloga kariernih centrov Univerze v Ljubljani je izvajanje svetovanj, delavnic in različnih dogodkov, kar našim študentom in diplomantom omogoča prvi stik z morebitnimi delodajalci ter pridobitev veščin, potrebnih za uspešen vstop in predvsem obstoj na trgu dela.
“A força da liderança com ideias” ou “Thatcher, Hayek e o Brasil”
Authors: Cavalieri Marco Antonio , Passos Marcelo De Oliveira
Published: November 2014

Recentemente, Margaret Thatcher, uma das principais líderes do liberalismo econômico no âmbito político, faleceu, suscitando uma série de reavaliações sobre o significado de sua passagem pelo cargo de primeira-ministra da Grã-Bretanha. Thatcher era admiradora da obra de um dos grandes líderes do liberalismo econômico no âmbito acadêmico, o economista austríaco Friedrich Hayek. Em nossa opinião, a relação entre as ideias de Hayek e a atuação política de Margaret Thatcher é um excelente exemplo da interação entre o meio acadêmico e a adoção das suas recomendações na prática política. Desse modo, aproveitamos para realizar três esforços de síntese nesse artigo. Primeiro, revisitar o núcleo duro das ideias econômicas e da abordagem teórica de Hayek. Em segundo lugar, analisar como o economista austríaco influenciou não somente Thatcher, mas seu contemporâneo Ronald Reagan. Por fim, algumas notas conclusivas analisam a relação entre o mundo acadêmico e a prática, fazendo algumas ilações a partir disso. Vale mencionar, a título de alerta, que o artigo tem um caráter ensaístico.
Polygon Area and Perimeter
Authors: Cady JoAnn , Bair Sherry L.
Published: November 2014

To elicit creative student thinking, this open-ended problem asks solvers to analyze area and perimeter.
Picking and Packing Strawberries
Authors: Bair Sherry L. , Cady JoAnn
Published: November 2014

This Solve It problem, about packaging various numbers of fruit, originally appeared in the March 2014 issue.
Web 2.0 in the Mathematics Classroom
Authors: McCoy Leah P.
Published: November 2014

To promote creativity, collaboration, and communication, look to interactive applications, broadly called Web 2.0.
Maximizing Volume with Solids and Nets
Authors: Miles Victoria L.
Published: November 2014

This month's activity explores rectangular prisms (e.g., cereal boxes) to ascertain why it is such a popular shape. An activity sheet is included.
Lovely Math
Authors: Hall Anna H.
Published: November 2014

Math by the Month is a regular department of the journal featuring collections of short activities focused on a monthly theme. The articles aim for an inquiry or problem-solving orientation that includes four activities each for grade bands K–2, 3–4, and 5–6. The writings of Roald Dahl inspired the problems in this issue.
Enriching Addition and Subtraction Fact Mastery through Games
Authors: Bay-Williams Jennifer M. , Kling- Gina
Published: November 2014

Becoming fluent with basic facts is developmental. Use games infused with a focus on acquisition of strategies to help students in the early grades progress to computational fluency.
Investigation of Bicycle Travel Time Estimation Using Bluetooth Sensors for Low Sampling Rates
Authors: Mei Zhenyu , Wang Dianhai , Chen Jun , Wang Wei
Published: November 2014

Filtering the data for bicycle travel time using Bluetooth sensors is crucial to the estimation of link travel times on a corridor. The current paper describes an adaptive filtering algorithm for estimating bicycle travel times using Bluetooth data, with consideration of low sampling rates. The data for bicycle travel time using Bluetooth sensors has two characteristics. First, the bicycle flow contains stable and unstable conditions. Second, the collected data have low sampling rates (less than 1%). To avoid erroneous inference, filters are introduced to “purify” multiple time series. The valid data are identified within a dynamically varying validity window with the use of a robust data-filtering procedure. The size of the validity window varies based on the number of preceding sampling intervals without a Bluetooth record. Applications of the proposed algorithm to the dataset from Genshan East Road and Moganshan Road in Hangzhou demonstrate its ability to track typical variations in bicycle travel time efficiently, while suppressing high frequency noise signals.
Regional differences in self‐reported HIV care and management in the EuroSIDA study
Authors: Grønborg Laut Kamilla , Mocroft Amanda , Lazarus Jeffrey , Reiss Peter , Rockstroh Jürgen , Karpov Igor , Rakhmanova Aza , Knysz Brygida , Moreno Santiago , Gargalianos Panagiotis , Lundgren Jens , Kirk Ole ,   on behalf of Eurosida in Eurocoord
Published: November 2014

Introduction

EuroSIDA has previously reported a poorer clinical prognosis for HIV‐positive individuals in Eastern Europe (EE) as compared with patients from other parts of Europe, not solely explained by differences in patient characteristics. We explored regional variability in self‐reported HIV management at individual EuroSIDA clinics, with a goal of identifying opportunities to reduce the apparent inequalities in health.

Methods

A survey (www.chip.dk/eurosida/csurvey) on HIV management was conducted in early 2014 in all currently active EuroSIDA clinics. Responders in EE were compared with clinics in all other EuroSIDA regions combined (non‐EE). Characteristics were compared between regions using Fishers exact test.

Results

A total of 80/97 clinics responded (82.5%, 12/15 in EE, 68/82 in non‐EE). Participating clinics reported seeing a total of 133,532 patients [a median of 1300 per clinic (IQR 700–2399)]. The majority of clinics requested viral load and CD4 measurements at least every six months for patients on as well as off ART (EE 66.7%, non‐EE 75%, p=0,72). Significantly fewer EE clinics performed resistance tests before ART as well as upon treatment failure (Figure 1). Half of the EE clinics indicated following WHO guidelines (EE 50%, non‐EE 7.4%, p<0.0001), whereas most non‐EE clinics followed EACS guidelines (non‐EE 76.5%, EE 41.7%, p=0.017). The majority of EE clinics and ¼ non‐EE clinics indicated deferral of ART initiation in asymptomatic individuals until CD4 ≤350 cells/mm3 (Figure 1). There were no significant regional differences in screening haematology, liver or renal function, which the majority of clinics reported to do routinely. However, EE clinics reported screening significantly less for cardiovascular disease (CVD), and only about half screened for tobacco use, alcohol consumption and drug use (Figure 1). Screening for cervical cancer and for anorectal cancer was low in both regions (Figure 1).

Conclusions

We found significant regional variability in self‐reported HIV management across Europe, with less resistance testing, screening for CVD and substance use in EE. EE clinics indicated deferral of ART initiation for longer than non‐EE clinics. Adherence to international guidelines for cervical cancer screening was poor in both regions. Whether differences in HIV management are reflected in clinical outcomes deserves further investigation.
Major challenges in clinical management of TB/HIV co‐infected patients in Eastern Europe compared with Western Europe and Latin America
Authors: Efsen Anne Marie , Schultze Anna , Post Frank , Panteleev Alexander , Furrer Hansjakob , Miller Robert , Skrahin Aliaksandr , Losso Marcelo H , Toibaro Javier , Girardi Enrico , Miro José , Bruyand Mathias , Obel Niels , Caylá Joan , Podlekareva Daria , Lundgren Jens , Mocroft Amanda , Kirk Ole ,   EuroCoord TB/HIV Study Group
Published: November 2014

Introduction

Rates of both TB/HIV co‐infection and multi‐drug‐resistant (MDR) TB are increasing in Eastern Europe (EE). Data on the clinical management of TB/HIV co‐infected patients are scarce. Our aim was to study the clinical characteristics of TB/HIV patients in Europe and Latin America (LA) at TB diagnosis, identify factors associated with MDR‐TB and assess the activity of initial TB treatment regimens given the results of drug‐susceptibility tests (DST).

Material and Methods

We enrolled 1413 TB/HIV patients from 62 clinics in 19 countries in EE, Western Europe (WE), Southern Europe (SE) and LA from January 2011 to December 2013. Among patients who completed DST within the first month of TB therapy, we linked initial TB treatment regimens to the DST results and calculated the distribution of patients receiving 0, 1, 2, 3 and ≥4 active drugs in each region. Risk factors for MDR‐TB were identified in logistic regression models.

Results

Significant differences were observed between EE (n=844), WE (n=152), SE (n=164) and LA (n=253) for use of combination antiretroviral therapy (cART) at TB diagnosis (17%, 40%, 44% and 35%, p<0.0001), a definite TB diagnosis (culture and/or PCR positive for Mycobacterium tuberculosis; 47%, 71%, 72% and 40%, p<0.0001) and MDR‐TB prevalence (34%, 3%, 3% and 11%, p <0.0001 among those with DST results). The history of injecting drug use [adjusted OR (aOR) = 2.03, (95% CI 1.00–4.09)], prior TB treatment (aOR = 3.42, 95% CI 1.88–6.22) and living in EE (aOR = 7.19, 95% CI 3.28–15.78) were associated with MDR‐TB. For 569 patients with available DST, the initial TB treatment contained ≥3 active drugs in 64% of patients in EE compared with 90–94% of patients in other regions (Figure 1a). Had the patients received initial therapy with standard therapy [Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RHZE)], the corresponding proportions would have been 64% vs. 86–97%, respectively (Figure 1b).

Conclusions

In EE, TB/HIV patients had poorer exposure to cART, less often a definitive TB diagnosis and more often MDR‐TB compared to other parts of Europe and LA. Initial TB therapy in EE was sub‐optimal, with less than two‐thirds of patients receiving at least three active drugs, and improved compliance with standard RHZE treatment does not seem to be the solution. Improved management of TB/HIV patients requires routine use of DST, initial TB therapy according to prevailing resistance patterns and more widespread use of cART.
Lack of association between use of efavirenz and death from suicide: evidence from the D:A:D study
Authors: Smith Colette , Ryom Lene , d'Arminio Monforte Antonella , Reiss Peter , Mocroft Amanda , El‐Sadr Wafaa , Weber Rainer , Law Matthew , Sabin Caroline , Lundgren Jens
Published: November 2014

Introduction

A recent meta‐analysis of 4 RCTs showed an increased rate of suicidality events (suicidal ideation or attempted/completed suicide) associated with efavirenz (EFV) compared to other regimens, but only a trend towards a higher rate of completed/attempted suicides, as only 17 events occurred. We investigated the association between EFV use and completed suicide.

Materials and Methods

All D:A:D participants were followed from study entry to the first of death, last study visit or 1 February 2013. Deaths are centrally validated using cause of death methodology, which assigns underlying, immediate and up to four contributing causes of death. Two endpoints were considered: 1) suicide or psychiatric disease as the underlying cause, and 2) suicide or psychiatric disease mentioned as an underlying, immediate or contributing cause of death (anywhere). Adjusted rate ratios were calculated using Poisson regression.

Results

A total of 4420 deaths occurred in 49,717 people over 371,333 person‐years (PY) (rate 11.9 per 1000 PY; 95% CI 11.6–12.3). A total of 193 deaths (rate 0.52; 0.45–0.59) had an underlying cause of suicide or psychiatric disease, and 482 deaths (1.30; 1.18–1.41) had suicide or psychiatric disease mentioned anywhere. A strong association with current CD4 count was seen: for suicide or psychiatric disease mentioned anywhere, rates were: 3.18 (2.55–3.80) for <200 cells/uL, 1.60 (1.29–1.90) for 201–350 cells/uL, 1.07 (0.86–1.29) for 351–500 cells/uL, 0.95 (0.80–1.09) for >500 cells/uL and 1.30 (1.18–1.41) for unknown. Highest rate of suicide or psychiatric deaths were seen in ART‐experienced people currently off ART, but no differences were seen according to current ART regimen, which remained after adjustment (Table 1). Consistent results were obtained when considering additional endpoints of suicide alone as the underlying cause and death from suicide or any possibly related cause (psychiatric disease, drug overdose, alcohol related, accidental or violent), as well as considering recent EFV use in the previous 3 and 6 months.

Conclusions

The finding of no higher death rates from suicide amongst those receiving EFV is reassuring. However, there is likely confounding by indication in our observational study. In light of conflicting results from RCTs, this potentially could suggest that in clinical practice EFV may be less frequently prescribed in those with underlying psychiatric conditions.
A clinically useful risk‐score for chronic kidney disease in HIV infection
Authors: Mocroft Amanda , Lundgren Jens , Ross Michael , Law Matthew , Reiss Peter , Kirk Ole , Smith Colette , Wentworth Debbie , Heuhaus Jacquie , Fux Christophe , Moranne Olivier , Morlat Phillipe , Johnson Margaret , Ryom Lene ,   on behalf of the Data on Adverse Events (D:A:D) study group,the Royal Free Hospital Clinic Cohort and the INSIGHT study group
Published: November 2014

Introduction

Development of a simple, widely applicable risk score for chronic kidney disease (CKD) allows comparisons of risks or benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen.

Materials and Methods

A total of 18,055 HIV‐positive persons from the Data on Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs) >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73 m2 after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months apart) eGFR <60. Poisson regression was used to develop a score predicting low (<0 points), medium (1–4 points) and high (>5 points) risk of developing CKD. Increased incidence of CKD associated with starting ARVs was modelled by including ARVs as time‐updated variables. The risk score was externally validated on two independent cohorts.

Results

A total of 641 persons developed CKD during 103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7–6.7). Older age, intravenous drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (Figure 1). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6–1.0), 5.6 (95% CI 4.5–6.7) and 37.4 (95% CI 34.0–40.7) (Figure 1). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90–0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.1–6.1) and 2013 persons from the control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5–5.1). External validation showed consistent CKD rates across risk groups (Figure 2).

Interpretation

Traditional and HIV‐related risk factors were predictive of CKD; all are routinely available, making the risk score easy to incorporate into clinical practise and of direct relevance for clinical decision making. NNTH in persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and alternative ARVs may be more appropriate.
Effectiveness of a team intervention in reducing modifiable cardiovascular disease risk in HIV‐infected subjects on antiretroviral therapy
Authors: Bloch Mark , Jayewardene Avindra , Vincent Trina , Linton Natalie , Quan Dick , Gowers Andrew
Published: November 2014

Introduction

The increasing age, higher modifiable and inherent cardiovascular disease (CVD) risk of HIV‐infected patients [1] necessitates improved approaches to reducing co‐morbidities. We aimed to assess the effectiveness of a team intervention in reducing modifiable CVD risk.

Materials and Methods

HIV‐infected patients ≥50 years attending a large HIV caseload primary‐care practice, who were virologically suppressed on antiretroviral therapy (ART), with moderate or severe 10‐year CVD Framingham risk (≥10%) were recruited for this prospective case‐control study. Intervention participants were provided a team approach to care, which involved treatment by study doctors for lipid, hypertension and ART management, and monthly review by a team of research nurses and dieticians for smoking cessation, exercise and dietary advice over 12 months. Controls were matched on age and smoking status, and were given standard of care (SOC) by non‐study doctors. Outcomes included CVD risk factors, body composition and CVD risk assessment, including Framingham 10‐yr risk [2] and D:A:D 5‐year estimated risk of coronary heart disease (CHD) [3]. Repeated measures analysis of variance was used to examine pre‐ and post‐intervention differences, with p‐values used to assess time and main effects of approach to care (Intervention, SOC).

Results

A total of 33 patients completed the intervention, with 33 controls (58.0±6.8 and 59.1±6.9 years, respectively). Smoking cessation occurred in 25% cases versus nil controls. There was a significant change in CVD risk between intervention and control groups, in both Framingham scores (time and group×time interaction) and D:A:D scores (group×time interaction only) (Table 1). There was also a significant difference in change in total cholesterol over the study period (time and group×time interaction). Body composition was only measured in intervention patients, with a significant loss in % body fat observed in pre‐ and post‐intervention.

Conclusions

Team intervention was significantly more effective than standard of care in reducing CVD risk in HIV‐infected patients on ART. A team approach to care may be an important component of reducing CVD risk in this population.
Early changes in coagulation but not inflammatory biomarkers under intermittent ART: the randomized ANRS 106 WINDOW trial
Authors: Gallien Sébastien , Charreau Isabelle , Fonsart Julien , Mourah Samia , Kalidi Issa , Delobel Pierre , Marchou Bruno , Aboulker Jean‐Pierre , Molina Jean‐Michel
Published: November 2014

Introduction

In the SMART trial, baseline plasma hsCRP, IL6 and D‐dimer levels were strongly correlated to all‐cause mortality. A case‐control study has shown an increase of IL‐6 and D‐dimer levels after one month of antiretroviral therapy (ART) interruption, which was correlated to viral load. Restarting ART was associated to a decrease in D‐dimer but not IL‐6 or hsCRP levels. We assessed biomarkers levels up to 96 weeks in ART‐experienced adults with plasma HIV RNA levels <400 c/mL randomized in the ANRS 106 WINDOW trial to intermittent ART (IT: six cycles of eight weeks of ART interruption followed by eight weeks of ART) versus continuous treatment (CT).

Methods

Stored plasma for 160 participants (80 IT and 80 CT), matched by age, sex and CDC classification, were analyzed blinded for IL‐6, sCD‐14, hsCRP and D‐dimer levels at baseline, week 8 (IT group only), week 16 and week 96. Lower levels of detection for IL‐6, sCD14, hsCRP and D‐Dimer were 1.5 pg/mL, 250 ng/mL, 0.03 µg/mL and 0.21 µg/mL, respectively. The primary objective was to compare changes in IL‐6, hsCRP, sCD14 and D‐dimer plasma levels from baseline to week 8, 16 and 96 in the IT and CT arms. Biomarkers levels were log10 transformed prior to analysis.

Results

At baseline, patients were mostly men (86%), with a median age of 40 years, a CD4+ T‐cell count of 768/mm3, have received a median of 4.7 years of ART and 85% had HIV RNA <50 c/mL. Proportion of patients with plasma HIV RNA levels<400 c/mL were 6% and 99%, 81% and 97%, 86% and 92% at weeks 8, 16 and 96 in the IT and CT arms, respectively. Plasma biomarkers levels are shown in the Table 1.

Compared to baseline, D‐dimer levels significantly increased 8 weeks after ART interruption in the IT arm (+23% fold change, 95% CI +9% to +39%) but reverted to baseline levels at week 16 and remained unchanged at week 96. There was no significant change from baseline in the other biomarker levels in the IT arm. Similarly, no significant change from baseline in biomarker levels was seen in the CT arm up to 96 weeks.

Conclusion

Coagulation and inflammatory biomarkers levels remained stable over 96 weeks in well‐suppressed HIV‐infected patient on ART. Following ART interruption there was a significant increase in D‐dimer but not in inflammatory biomarkers levels. This increase was reversed upon reintroduction of ART. These data suggest that ART interruption increases coagulation rather than inflammatory biomarkers.
Changes in lipid levels after 48 weeks of dual versus triple therapy observed in the GARDEL study
Authors: Cahn Pedro , Andrade Villanueva Jaime , Arribas Jose , Gatell Jose , Lama Javier , Norton Michel , Patterson Patricia , Sierra Madero Juan , Sued Omar , Ines Figueroa Maria , Jose Rolón Maria
Published: November 2014

Introduction

Treatment with ritonavir‐boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study.

Materials and Methods

The GARDEL study compared the efficacy and safety of a dual therapy (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT) with LPV/r 400/100 mg BID+3TC or FTC and a third investigator‐selected NRTI in fixed‐dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms.

Results

Patient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL‐C (94 mg/dL DT, 91 mg/dL TT) and HDL‐C (36 mg/dL DT, 35 mg/dL TT). Changes in total cholesterol, LDL‐C and HDL‐C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL). Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL‐C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC.

Conclusion

Changes in lipid parameters were observed in both arms. Albeit the increase was numerically higher for cholesterol (total and LDL‐C) in DT arm while TT arm had higher increases in TG; no difference was observed when week 48 values were compared with the NCEP ATP III goals for cardiovascular risk reduction [1]. So, the DT strategy, even missing the lipid‐lowering effect observed with tenofovir, does not seem to add significant risk to patients treated with this novel strategy.
The prevalence and predictive value of dipstick urine protein in HIV‐positive persons in Europe
Authors: Mocroft Amanda , Ryom Lene , Lapadula Giuseppe , Reiss Peter , Blaxhult Anders , Furrer Hansjakob , Kutsyna Galyna , Gatell Jose , Begovac Josep , Kirk Ole , Lundgren Jens ,   for EuroSIDA in EuroCoord
Published: November 2014

Introduction

Proteinuria (PTU) is an important marker for the development and progression of renal disease, cardiovascular disease and death, but there is limited information about the prevalence and factors associated with confirmed PTU in predominantly white European HIV+ persons, especially in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2.

Patients and methods

Baseline was defined as the first of two consecutive dipstick urine protein (DPU) measurements during prospective follow‐up >1/6/2011 (when systematic data collection began). PTU was defined as two consecutive DUP >1+ (>30 mg/dL) >3 months apart; persons with eGFR <60 at either DPU measurement were excluded. Logistic regression investigated factors associated with PTU.

Results

A total of 1,640 persons were included, participants were mainly white (n=1,517, 92.5%), male (n=1296, 79.0%) and men having sex with men (n=809; 49.3%). Median age at baseline was 45 (IQR 37–52 years), and CD4 was 570 (IQR 406–760/mm3). The median baseline date was 2/12 (IQR 11/11–6/12), and median eGFR was 99 (IQR 88–109 mL/min/1.73 m2). Sixty‐nine persons had PTU (4.2%, 95% CI 3.2–4.7%). Persons with diabetes had increased odds of PTU, as were those with a prior non‐AIDS [1] or AIDS event and those with prior exposure to indinavir. Among females, those with a normal eGFR (>90) and those with prior abacavir use had lower odds of PTU (Figure 1).

There was no significant association between past or current use of tenofovir, lopinavir, atazanvir (boosted or unboosted) or any other boosted PI and PTU (p>0.2). During 688.2 person‐years of follow up (PYFU), three persons developed chronic kidney disease (CKD; confirmed [>3 months apart] eGFR<60); 2/685 (0.3%) without PTU and 1/38 (2.8%) with PTU (p=0.032). The crude incidence of CKD in those with baseline PTU and eGFR>60 was almost 10 times higher than in those without baseline PTU and eGFR>60 (rate ratio 9.61; 95% CI 0.87–105.9, p=0.065).

Conclusions

One in 25 persons with eGFR>60 had confirmed proteinuria at baseline. Factors associated with PTU were similar to those associated with CKD. The lack of association with antiretrovirals, particularly tenofovir, may be due to the cross‐sectional design of this study, and additional follow‐up is required to address progression to PTU in those without PTU at baseline. It may also suggest other markers are needed to capture the deteriorating renal function associated with antiretrovirals may be needed at higher eGFRs. Our findings suggest PTU is an early marker for impaired renal function.
Incremental cost per newly diagnosed HIV infection (NDHI): routine (RTS), targeted (TTS), and current clinical practice testing strategies (CPTS)
Authors: Gomez‐Ayerbe Cristina , Jesús Pérez Elías María , Muriel Alfonso , Pérez Elías Pilar , Cano Agustina , Diaz Alberto , Moreno Ana , Luis Casado Jose , Santos Cristina , Martinez‐Colubi María , Uranga Almudena , Dronda Fernando , Moreno Santiago
Published: November 2014

Introduction

Although RTS as HIV Diagnosis was considered cost effectiveness [1], overall budget may be unaffordable for some countries. We explore Incremental cost per NDHI associated with different TS.

Materials and Methods

From a health care perspective, using direct costs and Euros currency, we calculated budget and cost per NDHI of RTS (all patients were tested), TTS (Universal risk practices and clinical conditions‐RP&CC ‐ only positive were tested), and CPTS (Only patients physicians considered were tested). We considered DRIVE (Spanish acronym of HIV infection Rapid Diagnosis) study and clinical Practice outcomes. Population between 18–60 years, attending to a Hospital Emergency Room or to a Primary Care Center performed an HIV RP&CC questionnaire (Q) and an HIV rapid test (HIV RT). Unitary costs considered were: HIV RT, nurse, registry, transport and HIV confirmation when necessary, imputed to all population in RTS and CPTS and only in HIV RP&CC‐Q positive in TTS analysis, while HIV RP&CC‐Q costs were added to all population in TTS. Sensitivity analyses were performed with varying rates of NDHI and of positive HIV RP&CC‐Q population, and different RP&CC Q sensitivity (SE) to predict HIV infection.

Results

5,329 HIV RP&CC‐Q and HIV RT were performed to 49.64% women, median age 37 years old, 74.9% Spaniards. In DRIVE and CP, NDHI were 4.1‰, and 1.6‰, while HIV RP&CC‐Q was positive in 51.2%. HIV RP&CC‐Q SE was 100%. Overall budget employed in HIV testing was in RTS 43,503€, in TTS 24,472€ and in CPTS 5,032€. Cost per 1 NDHI was 1,977€, 1,112€ and 5,032€, respectively. A reduction in cost of 865€, favouring TTS vs. RTS, while an increased cost of 824€ in CPTS vs. RTS was obtained. Considering NDHI rate of 2.6‰ saving costs increased to 1379€ in TTS, while were reduced to 576€ if NDHI rate increases 6.2‰. Effect of RP&CC‐Q positivity rate was similar, if 25% saving costs were 1368€, while if 75% were reduced to 399€. Varying SE of RP&CC‐Q to 95%, 91% and 50% cost saving was 810€, 754€, and 208€, and number of MHI one, two and 11.

Conclusions

In DRIVE study Targeted TS with universal screening of RP&CC before an HIV rapid test is cost saving, without missing NDHI, with respect to Routine TS. Lower rates of HIV infection and RP&CC in the population, increase costs savings.
Hepatitis B virus (HBV) status of children born to HIV/HBV co‐infected women in a French hospital: a cross‐sectional study
Authors: Sellier Pierre , Schnepf Nathalie , Amarsy Rishma , Maylin Sarah , Coutellier Martin , Lopes Amanda , Mazeron Marie‐Christine , Flateau Clara , Morgand Marjolaine , Ciraru‐Vigneron Nicole , Berthe Aurore , Ricbourg Aude , Dolores‐Moreno Anne‐Marie , Simoneau Guy , Evans John , Souak Safia , Matheron Sophie , Mouly Stephane , Benifla Jean‐Louis , Simon François , Bergmann Jean‐François
Published: November 2014

Introduction

Human Immunodeficiency Virus (HIV) Mother‐To‐Child‐Transmission (MTCT) and prevention by combined antiretroviral therapy (cART) have been extensively studied. Hepatitis B Virus (HBV) MTCT from HIV/HBV co‐infected women and prevention by antiretroviral therapy with dual activity have been poorly studied. The aim of the study was to assess HBV MTCT from HIV/HBV co‐infected women in a developed country with a large access to cART.

Materials and Methods

HIV/HBV co‐infected pregnant women attending the Obstetrics Department from 1st January 2000 to 1st January 2012 could be included in the study (NCT02044068). Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or vaccine to newborns was retrospectively recorded. We assessed HBV status of children at least as old as two years.

Results

Forty nine (9.2%) from 530 HIV‐infected women followed in the hospital were HIV/HBV co‐infected. 34 (69.4%) had given birth to 57 children in the hospital. 13 of these women (22 children) were lost‐to‐follow‐up, 21 women (35 children) could be studied. Twenty six children (74.3%) had HBs Ab at a protective level, 22 of them had received immunoglobulin at birth; 24 had received a complete vaccine schedule during the first six months of life (with immunoglobulin in 21 cases). The women had been given lamivudine or tenofovir/emtricitabine during eight and nine pregnancies respectively. Eight children (22.8%) were tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%) had received immunoglobulin and a complete vaccine schedule; in two children, immunoglobulin was uncertain; in one child, the vaccine schedule was incomplete; in the last one, data about immunoglobulin and the vaccine schedule were lacking. The women had been given lamivudine or tenofovir/emtricitabine during five and two pregnancies respectively. One child had HBc Ab and HBs Ab, immunoglobulin was uncertain and the vaccine schedule was incomplete. The woman had been given lamivudine during the last trimester.

Conclusions

Three quarters of the children were protected. HBs Ab were negative in more than a tenth of the children who had received immunoglobulin and a complete vaccine schedule, questioning on long‐term protection and underlining the need of control.
Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan
Authors: Su Yi‐Ching , Liu Wen‐Chun , Chang Lan‐Hsin , Wu Pei‐Ying , Luo Yu‐Zhen , Wu Cheng‐Hsin , Sun Hsin‐Yun , Chang Sui‐Yuan , Hung Chien‐Ching
Published: November 2014

Introduction

The incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource‐rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person‐years of follow‐up (PYFU) in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT) service at a University Hospital.

Methods

Between May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third‐generation enzyme immunoassay. A nested case‐control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013.

Results

During the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV‐negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76–4.94); the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05–4.51) in 2006–2009, to 3.33 per 1000 PYFU (95% CI, 0.86–5.80) in 2010–2011, to 4.94 per 1000 PYFU (95% CI, 0.99–8.99) in 2012–2013. In case‐control study, HCV seroconverters were more likely to have HIV‐infected partners, recent syphilis and a Rapid Plasma Reagin (RPR) titre of 4 or greater. In multivariate analysis, having HIV‐infected partners remained as the only independent associated factors with HCV seroconversion (AOR, 6.931; 95% CI, 1.064–45.163). Phylogenetic analysis revealed transmission pairs and clusters, with most clustered sequences derived from MSM.

Conclusions

Similar to the observation among HIV‐infected patients who are not IDUs, increasing trends of recent HCV infection also occur among the individuals who sought VCT services in Taiwan. Having HIV‐infected partners is independently associated with recent HCV seroconversion.