A formação de professores de química na UFPA: a história de um curso de graduação e sua evolução curricular

Este trabalho constitui-se num estudo sobre o curso de formação de professores de Química da UFPA, contando sua história a partir dos desenhos curriculares que o nortearam nos seus 30 anos de existência e inserindo tal história no contexto maior da construção da ciência moderna. O estudo prossegue analisando, à luz da literatura, o projeto político-pedagógico recém aprovado pelo Colegiado do Curso visando detectar possíveis avanços e conclui respondendo, a partir do quadro delineado pela história do Curso e pelo momento presente, à questão: em função das demandas impostas pela sociedade moderna, como deve ser formado, hoje, um professor de química? Foram usados como principais métodos de pesquisa, coleta de depoimentos mediante entrevistas semi-estruturadas e pesquisa documental e bibliográfica, com maior ênfase a esta última.

Um método para determinação de pontos de operação com diversidade em linha digital de assinante usando balanceamento de espectro e algoritmo evolucionário

Este trabalho apresenta um método para encontrar um conjunto de pontos de operação, os quais são ótimos de Pareto com diversidade, para linhas digitais de assinante (DSL - digital subscriber line). Em diversos trabalhos encontrados na literatura, têm sido propostos algoritmos para otimização da transmissão de dados em linhas DSL, que fornecem como resultado apenas um ponto de operação para os modems. Esses trabalhos utilizam, em geral, algoritmos de balanceamento de espectro para resolver um problema de alocação de potência, o que difere da abordagem apresentada neste trabalho. O método proposto, chamado de diverseSB , utiliza um processo híbrido composto de um algoritmo evolucionário multiobjetivo (MOEA - multi-objective evolutionary algorithm), mais precisamente, um algoritmo genético com ordenamento por não-dominância (NSGA-II - Non-Dominated Sorting Genetic Algorithm II), e usando ainda, um algoritmo de balanceamento de espectro. Os resultados obtidos por simulações mostram que, para uma dada diversidade, o custo computacional para determinar os pontos de operação com diversidade usando o algoritmo diverseSB proposto é muito menor que métodos de busca de “força bruta”. No método proposto, o NSGA-II executa chamadas ao algoritmo de balanceamento de espectro adotado, por isso, diversos testes envolvendo o mesmo número de chamadas ao algoritmo foram realizadas com o método diverseSB proposto e o método de busca por força bruta, onde os resultados obtidos pelo método diverseSB proposto foram bem superiores do que os resultados do método de busca por força bruta. Por exemplo, o método de força bruta realizando 1600 chamadas ao algoritmo de balanceamento de espectro, obtém um conjunto de pontos de operação com diversidade semelhante ao do método diverseSB proposto com 535 chamadas.

Cogeneration design problem Computational complexity analysis and solution through an expert system

Purpose - The purpose of this paper is twofold: to analyze the computational complexity of the cogeneration design problem; to present an expert system to solve the proposed problem, comparing such an approach with the traditional searching methods available.Design/methodology/approach - The complexity of the cogeneration problem is analyzed through the transformation of the well-known knapsack problem. Both problems are formulated as decision problems and it is proven that the cogeneration problem is np-complete. Thus, several searching approaches, such as population heuristics and dynamic programming, could be used to solve the problem. Alternatively, a knowledge-based approach is proposed by presenting an expert system and its knowledge representation scheme.Findings - The expert system is executed considering two case-studies. First, a cogeneration plant should meet power, steam, chilled water and hot water demands. The expert system presented two different solutions based on high complexity thermodynamic cycles. In the second case-study the plant should meet just power and steam demands. The system presents three different solutions, and one of them was never considered before by our consultant expert.Originality/value - The expert system approach is not a "blind" method, i.e. it generates solutions based on actual engineering knowledge instead of the searching strategies from traditional methods. It means that the system is able to explain its choices, making available the design rationale for each solution. This is the main advantage of the expert system approach over the traditional search methods. On the other hand, the expert system quite likely does not provide an actual optimal solution. All it can provide is one or more acceptable solutions.

Utilização de metaheurísticas combinada a diferentes métodos de aglutinação para a otimização de um processo de torneamento com múltiplas respostas

Pós-graduação em Engenharia Mecânica - FEG

Surgical interventions for treating pectus excavatum

Background: Pectus excavatum is characterized by a depression of the anterior chest wall (sternum and lower costal cartilages) and is the most frequently occurring chest wall deformity. The prevalence ranges from 6.28 to 12 cases per 1000 around the world. Generally pectus excavatum is present at birth or is identified after a few weeks or months; however, sometimes it becomes evident only at puberty. The consequence of the condition on a individual's life is variable, some live a normal life and others have physical and psychological symptoms such as: precordial pain after exercises; impairments of pulmonary and cardiac function; shyness and social isolation. For many years, sub-perichondrial resection of the costal cartilages, with or without transverse cuneiform osteotomy of the sternum and placement of a substernal support, called conventional surgery, was the most accepted option for surgical repair of these patients. From 1997 a new surgical repair called, minimally invasive surgery, became available. This less invasive surgical option consists of the retrosternal placement of a curved metal bar, without resections of the costal cartilages or sternum osteotomy, and is performed by videothoracoscopy. However, many aspects that relate to the benefits and harms of both techniques have not been defined. Objectives: To evaluate the effectiveness and safety of the conventional surgery compared with minimally invasive surgery for treating people with pectus excavatum. Search methods: With the aim of increasing the sensitivity of the search strategy we used only terms related to the individual's condition (pectus excavatum); terms related to the interventions, outcomes and types of studies were not included. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, LILACS, and ICTPR. Additionally we searched yet reference lists of articles and conference proceedings. All searches were done without language restriction. Date of the most recent searches: 14 January 2014. Selection criteria: We considered randomized or quasi-randomized controlled trials that compared traditional surgery with minimally invasive surgery for treating pectus excavatum. Data collection and analysis: Two review authors independently assessed the eligibility of the trials identified and agreed trial eligibility after a consensus meeting. The authors also assessed the risk of bias of the eligible trials. Main results: Initially we located 4111 trials from the electronic searches and two further trials from other resources. All trials were added into reference management software and the duplicates were excluded, leaving 2517 studies. The titles and abstracts of these 2517 studies were independently analyzed by two authors and finally eight trials were selected for full text analysis, after which they were all excluded, as they did not fulfil the inclusion criteria. Authors' conclusions: There is no evidence from randomized controlled trials to conclude what is the best surgical option to treat people with pectus excavatum.

Surgical interventions for treating pectus excavatum

Pectus excavatum is characterized by a depression of the anterior chest wall (sternum and lower costal cartilages) and is the most frequently occurring chest wall deformity. The prevalence ranges from 6.28 to 12 cases per 1000 around the world. Generally pectus excavatum is present at birth or is identified after a few weeks or months; however, sometimes it becomes evident only at puberty. The consequence of the condition on a individual’s life is variable, some live a normal life and others have physical and psychological symptoms such as: precordial pain after exercises; impairments of pulmonary and cardiac function; shyness and social isolation. For many years, sub-perichondrial resection of the costal cartilages, with or without transverse cuneiform osteotomy of the sternum and placement of a substernal support, called conventional surgery, was the most accepted option for surgical repair of these patients. From 1997 a new surgical repair called, minimally invasive surgery, became available. This less invasive surgical option consists of the retrosternal placement of a curved metal bar, without resections of the costal cartilages or sternum osteotomy, and is performed by videothoracoscopy. However, many aspects that relate to the benefits and harms of both techniques have not been defined. Objectives To evaluate the effectiveness and safety of the conventional surgery compared with minimally invasive surgery for treating people with pectus excavatum. Search methods With the aim of increasing the sensitivity of the search strategy we used only terms related to the individual’s condition (pectus excavatum); terms related to the interventions, outcomes and types of studies were not included. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, LILACS, and ICTPR. Additionally we searched yet reference lists of articles and conference proceedings. All searches were done without language restriction.

A new method for calculating the convergent point of a moving group

Context. Convergent point (CP) search methods are important tools for studying the kinematic properties of open clusters and young associations whose members share the same spatial motion. Aims. We present a new CP search strategy based on proper motion data. We test the new algorithm on synthetic data and compare it with previous versions of the CP search method. As an illustration and validation of the new method we also present an application to the Hyades open cluster and a comparison with independent results. Methods. The new algorithm rests on the idea of representing the stellar proper motions by great circles over the celestial sphere and visualizing their intersections as the CP of the moving group. The new strategy combines a maximum-likelihood analysis for simultaneously determining the CP and selecting the most likely group members and a minimization procedure that returns a refined CP position and its uncertainties. The method allows one to correct for internal motions within the group and takes into account that the stars in the group lie at different distances. Results. Based on Monte Carlo simulations, we find that the new CP search method in many cases returns a more precise solution than its previous versions. The new method is able to find and eliminate more field stars in the sample and is not biased towards distant stars. The CP solution for the Hyades open cluster is in excellent agreement with previous determinations.

High precision radial velocities with giano spectra

Radial velocities measured from near-infrared (NIR) spectra are a potential tool to search for extrasolar planets around cool stars. High resolution infrared spectrographs now available reach the high precision of visible instruments, with a constant improvement over time. GIANO is an infrared echelle spectrograph and it is a powerful tool to provide high resolution spectra for accurate radial velocity measurements of exo-planets and for chemical and dynamical studies of stellar or extragalactic objects. No other IR instruments have the GIANO's capability to cover the entire NIR wavelength range. In this work we develop an ensemble of IDL procedures to measure high precision radial velocities on a few GIANO spectra acquired during the commissioning run, using the telluric lines as wevelength reference. In Section 1.1 various exoplanet search methods are described. They exploit different properties of the planetary system. In Section 1.2 we describe the exoplanet population discovered trough the different methods. In Section 1.3 we explain motivations for NIR radial velocities and the challenges related the main issue that has limited the pursuit of high-precision NIR radial velocity, that is, the lack of a suitable calibration method. We briefly describe calibration methods in the visible and the solutions for IR calibration, for instance, the use of telluric lines. The latter has advantages and problems, described in detail. In this work we use telluric lines as wavelength reference. In Section 1.4 the Cross Correlation Function (CCF) method is described. This method is widely used to measure the radial velocities.In Section 1.5 we describe GIANO and its main science targets. In Chapter 2 observational data obtained with GIANO spectrograph are presented and the choice criteria are reported. In Chapter 3 we describe the detail of the analysis and examine in depth the flow chart reported in Section 3.1. In Chapter 4 we give the radial velocities measured with our IDL procedure for all available targets. We obtain an rms scatter in radial velocities of about 7 m/s. Finally, we conclude that GIANO can be used to measure radial velocities of late type stars with an accuracy close to or better than 10 m/s, using telluric lines as wevelength reference. In 2014 September GIANO is being operative at TNG for Science Verification and more observational data will allow to further refine this analysis.

Il linguaggio valutativo nel bilancio di sostenibilità: analisi trilingue basata su corpora

The aim of this dissertation is to analyze the language of evaluation in Italian, English and French sustainability reports in order to observe how firms build their corporate image and to investigate the kind of relationship they develop with their stakeholders. The analysis is carried out by applying Martin & White's Appraisal theory and corpus linguistics methods. For the purposes of this research, a multilingual specialized corpus of sustainability reports has been created, which is the result of two different levels of compilation. At the first level, three sub-corpora have been created with the aim of representing three different languages (Italian, English and French): at this level, the research on evaluative language will show that a standardization process of sustainability reports is underway. At the second level of compilation, each of the three sub-corpora has been split in two further sub-corpora, representative of two different business sectors: at this level, the research will show how the sector where firms operate directly influences the choice of the topics to be discussed. The first chapter of this dissertation introduces the concept of evaluative language, with a particular focus on the framework of Appraisal theory. The second chapter deals with corpus linguistics and describes different types of corpora, the search methods and the criteria for the compilation of corpora. The third chapter discusses the concepts of Corporate Social Responsibility and sustainability reports, focusing mainly on the reporting principles and the linguistic patterns of this genre, and provides an overview of the main guidelines and certifications for the reporting of sustainability actions. Chapter four is dedicated to the description of the methodology used for this research, while the last chapter presents and discusses the results of the analysis, in an attempt to draw generalizations on the use of evaluative language in this emerging genre.

Joint lavage for osteoarthritis of the knee

Background Osteoarthritis is the most common form of joint disorder and a leading cause of pain and physical disability. Observational studies suggested a benefit for joint lavage, but recent, sham-controlled trials yielded conflicting results, suggesting joint lavage not to be effective. Objectives To compare joint lavage with sham intervention, placebo or non-intervention control in terms of effects on pain, function and safety outcomes in patients with knee osteoarthritis. Search methods We searched CENTRAL, MEDLINE, EMBASE, and CINAHL up to 3 August 2009, checked conference proceedings, reference lists, and contacted authors. Selection criteria We included studies if they were randomised or quasi-randomised trials that compared arthroscopic and non-arthroscopic joint lavage with a control intervention in patients with osteoarthritis of the knee. We did not apply any language restrictions. Data collection and analysis Two independent review authors extracted data using standardised forms. We contacted investigators to obtain missing outcome information. We calculated standardised mean differences (SMDs) for pain and function, and risk ratios for safety outcomes. We combined trials using inverse-variance random-effects meta-analysis. Main results We included seven trials with 567 patients. Three trials examined arthroscopic joint lavage, two non-arthroscopic joint lavage and two tidal irrigation. The methodological quality and the quality of reporting was poor and we identified a moderate to large degree of heterogeneity among the trials (I2 = 65%). We found little evidence for a benefit of joint lavage in terms of pain relief at three months (SMD -0.11, 95% CI -0.42 to 0.21), corresponding to a difference in pain scores between joint lavage and control of 0.3 cm on a 10-cm visual analogue scale (VAS). Results for improvement in function at three months were similar (SMD -0.10, 95% CI -0.30 to 0.11), corresponding to a difference in function scores between joint lavage and control of 0.2 cm on a WOMAC disability sub-scale from 0 to 10. For pain, estimates of effect sizes varied to some degree depending on the type of lavage, but this variation was likely to be explained by differences in the credibility of control interventions: trials using sham interventions to closely mimic the process of joint lavage showed a null-effect. Reporting on adverse events and drop out rates was unsatisfactory, and we were unable to draw conclusions for these secondary outcomes. Authors' conclusions Joint lavage does not result in a relevant benefit for patients with knee osteoarthritis in terms of pain relief or improvement of function.

Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

Background Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. Objectives We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) comparing chemotherapy alone with CMT in patients with early stage Hodgkin lymphoma with respect to response rate, progression-free survival (alternatively tumour control) and overall survival (OS). Search methods We searched MEDLINE, EMBASE and CENTRAL as well as conference proceedings from January 1980 to November 2010 for randomised controlled trials comparing chemotherapy alone to the same chemotherapy regimen plus radiotherapy. Selection criteria Randomised controlled trials comparing chemotherapy alone with CMT in patients with early stage HL. Trials in which the chemotherapy differed between treatment arms were excluded. Trials with more than 20% of patients in advanced stage were also excluded. Data collection and analysis Effect measures used were hazard ratios (HR) for tumour control and OS as well as relative risks for response rates. Two review authors independently extracted data and assessed quality of trials. We contacted study authors to obtain missing information. Since none of the trials reported progression-free survival according to our definitions, all similar outcomes were evaluated as tumour control. Main results Five RCTs involving 1245 patients were included. The HR was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumour control and 0.40 (95% CI 0.27 to 0.61) for OS for patients receiving CMT compared to chemotherapy alone. Complete response rates were similar between treatment groups. In sensitivity analyses another six trials were included that did not fulfil the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. Authors' conclusions Adding radiotherapy to chemotherapy improves tumour control and overall survival in patients with early stage Hodgkin lymphoma.

Thymic peptides for treatment of cancer patients

Background Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour cells and to resist infections due to immunosuppression induced by the disease and antineoplastic therapy. Objectives To evaluate the effectiveness of pTE and sTP for the management of cancer. Search methods We searched CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE, EMBASE, AMED, BIOETHICSLINE, BIOSIS, CATLINE, CISCOM, HEALTHSTAR, HTA, SOMED and LILACS (to February 2010). Selection criteria Randomised trials of pTE or sTP in addition to chemotherapy or radiotherapy, or both, compared to the same regimen with placebo or no additional treatment in adult cancer patients. Data collection and analysis Two authors independently extracted data from published trials. We derived odds ratios (OR) from overall survival (OS) and disease-free survival (DFS) rates, tumour response (TR) rates, and rates of adverse effects (AE) related to antineoplastic treatments. We used a random-effects model for meta-analysis. Main results We identified 26 trials (2736 patients). Twenty trials investigated pTE (thymostimulin or thymosin fraction 5) and six trials investigated sTP (thymopentin or thymosin α1). Twenty-one trials reported results for OS, six for DFS, 14 for TR, nine for AE and 10 for safety of pTE and sTP. Addition of pTE conferred no benefit on OS (RR 1.00, 95% CI 0.79 to 1.25); DFS (RR 0.97, 95% CI 0.82 to 1.16); or TR (RR 1.07, 95% CI 0.92 to 1.25). Heterogeneity was moderate to high for all these outcomes. For thymosin α1 the pooled RR for OS was 1.21 (95% CI 0.94 to 1.56, P = 0.14), with low heterogeneity; and 3.37 (95% CI 0.66 to 17.30, P = 0.15) for DFS, with moderate heterogeneity. The pTE reduced the risk of severe infectious complications (RR 0.54, 95% CI 0.38 to 0.78, P = 0.0008; I² = 0%). The RR for severe neutropenia in patients treated with thymostimulin was 0.55 (95% CI 0.25 to 1.23, P = 0.15). Tolerability of pTE and sTP was good. Most of the trials had at least a moderate risk of bias. Authors' conclusions Overall, we found neither evidence that the addition of pTE to antineoplastic treatment reduced the risk of death or disease progression nor that it improved the rate of tumour responses to antineoplastic treatment. For thymosin α1, there was a trend for a reduced risk of dying and of improved DFS. There was preliminary evidence that pTE lowered the risk of severe infectious complications in patients undergoing chemotherapy or radiotherapy.

Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

BACKGROUND Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). OBJECTIVES To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. SEARCH METHODS We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. SELECTION CRITERIA Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART DATA COLLECTION AND ANALYSIS: Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. MAIN RESULTS One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I(2)=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95% CI 0.17, 0.75] with substantial heterogeneity (I(2)=62%). We also performed subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had ≥350 CD4 cells/µL, we estimated a rate ratio of 0.12 [95% CI 0.01, 1.99]. In this subgroup, there were 247 transmissions in untreated couples and 30 in treated couples. AUTHORS' CONCLUSIONS ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has ≤550 CD4 cells/µL. A recent multicentre RCT confirms the suspected benefit seen in earlier observational studies and reported in more recent ones. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed.Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.

Interventions for the management of mandibular fractures

BACKGROUND Fractures of the mandible (lower jaw) are a common occurrence and usually related to interpersonal violence or road traffic accidents. Mandibular fractures may be treated using open (surgical) and closed (non-surgical) techniques. Fracture sites are immobilized with intermaxillary fixation (IMF) or other external or internal devices (i.e. plates and screws) to allow bone healing. Various techniques have been used, however uncertainty exists with respect to the specific indications for each approach. OBJECTIVES The objective of this review is to provide reliable evidence of the effects of any interventions either open (surgical) or closed (non-surgical) that can be used in the management of mandibular fractures, excluding the condyles, in adult patients. SEARCH METHODS We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 28 February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1), MEDLINE via OVID (1950 to 28 February 2013), EMBASE via OVID (1980 to 28 February 2013), metaRegister of Controlled Trials (to 7 April 2013), ClinicalTrials.gov (to 7 April 2013) and the WHO International Clinical Trials Registry Platform (to 7 April 2013). The reference lists of all trials identified were checked for further studies. There were no restrictions regarding language or date of publication. SELECTION CRITERIA Randomised controlled trials evaluating the management of mandibular fractures without condylar involvement. Any studies that compared different treatment approaches were included. DATA COLLECTION AND ANALYSIS At least two review authors independently assessed trial quality and extracted data. Results were to be expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated to include both clinical and methodological factors. MAIN RESULTS Twelve studies, assessed as high (six) and unclear (six) risk of bias, comprising 689 participants (830 fractures), were included. Interventions examined different plate materials and morphology; use of one or two lag screws; microplate versus miniplate; early and delayed mobilization; eyelet wires versus Rapid IMF™ and the management of angle fractures with intraoral access alone or combined with a transbuccal approach. Patient-oriented outcomes were largely ignored and post-operative pain scores were inadequately reported. Unfortunately, only one or two trials with small sample sizes were conducted for each comparison and outcome. Our results and conclusions should therefore be interpreted with caution. We were able to pool the results for two comparisons assessing one outcome. Pooled data from two studies comparing two miniplates versus one miniplate revealed no significant difference in the risk of post-operative infection of surgical site (risk ratio (RR) 1.32, 95% CI 0.41 to 4.22, P = 0.64, I(2) = 0%). Similarly, no difference in post-operative infection between the use of two 3-dimensional (3D) and standard (2D) miniplates was determined (RR 1.26, 95% CI 0.19 to 8.13, P = 0.81, I(2) = 27%). The included studies involved a small number of participants with a low number of events. AUTHORS' CONCLUSIONS This review illustrates that there is currently inadequate evidence to support the effectiveness of a single approach in the management of mandibular fractures without condylar involvement. The lack of high quality evidence may be explained by clinical diversity, variability in assessment tools used and difficulty in grading outcomes with existing measurement tools. Until high level evidence is available, treatment decisions should continue to be based on the clinician's prior experience and the individual circumstances.

Optimal time for initiating antiretroviral therapy (ART) in HIV-infected, treatment-naive children aged 2 to 5 years old

BACKGROUND The use of combination antiretroviral therapy (cART) comprising three antiretroviral medications from at least two classes of drugs is the current standard treatment for HIV infection in adults and children. Current World Health Organization (WHO) guidelines for antiretroviral therapy recommend early treatment regardless of immunologic thresholds or the clinical condition for all infants (less than one years of age) and children under the age of two years. For children aged two to five years current WHO guidelines recommend (based on low quality evidence) that clinical and immunological thresholds be used to identify those who need to start cART (advanced clinical stage or CD4 counts ≤ 750 cells/mm(3) or per cent CD4 ≤ 25%). This Cochrane review will inform the current available evidence regarding the optimal time for treatment initiation in children aged two to five years with the goal of informing the revision of WHO 2013 recommendations on when to initiate cART in children. OBJECTIVES To assess the evidence for the optimal time to initiate cART in treatment-naive, HIV-infected children aged 2 to 5 years. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS conference database, specific relevant conferences, www.clinicaltrials.gov, the World Health Organization International Clinical Trials Registry platform and reference lists of articles. The date of the most recent search was 30 September 2012. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART, and prospective cohort studies which followed children from enrolment to start of cART and on cART. DATA COLLECTION AND ANALYSIS Two review authors considered studies for inclusion in the review, assessed the risk of bias, and extracted data on the primary outcome of death from all causes and several secondary outcomes, including incidence of CDC category C and B clinical events and per cent CD4 cells (CD4%) at study end. For RCTs we calculated relative risks (RR) or mean differences with 95% confidence intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from adjusted analyses. We combined results from RCTs using a random effects model and examined statistical heterogeneity. MAIN RESULTS Two RCTs in HIV-positive children aged 1 to 12 years were identified. One trial was the pilot study for the larger second trial and both compared initiation of cART regardless of clinical-immunological conditions with deferred initiation until per cent CD4 dropped to <15%. The two trials were conducted in Thailand, and Thailand and Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages 2 to 5 years were included in this review. There was one death in the immediate cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In the subgroup analysis of children aged 24 to 59 months, there was one CDC C event in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI 2.7 to 9.1). One cohort study from South Africa, which compared the effect of delaying cART for up to 60 days in 573 HIV-positive children starting tuberculosis treatment (median age 3.5 years), was also included. The adjusted hazard ratios for the effect on mortality of delaying ART for more than 60 days was 1.32 (95% CI 0.55 to 3.16). AUTHORS' CONCLUSIONS This systematic review shows that there is insufficient evidence from clinical trials in support of either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5 years. Programmatic issues such as the retention in care of children in ART programmes in resource-limited settings will need to be considered when formulating WHO 2013 recommendations.