Joint optimization of headway and number of stops for bilateral bus rapid transit.

The bilateral Bus Rapid Transit (BRT) system is a kind of BRT system in which the stops are located in the middle of the transit lane. By simultaneously serving transit lines in opposite directions, it is particularly designed to save space resources and enhance service quality. To improve the operational efficiency of the bilateral BRT, this paper optimizes the operational performance of bilateral BRT with elastic demand. The objective is to minimize the generalized time cost per passenger of the system by jointly optimizing the headway and number of stops of bilateral BRT. The cost includes the agency operating and user travel. The optimal design model is formulated as a mixed-integer program and solved using a fuzzy analytic hierarchy process (FAHP) and a genetic algorithm (GA). We conduct a case study and sensitivity analysis to show the effectiveness and reliability of the proposed approach. We conclude that the optimized minimum generalized cost per passenger is lower than the actual case for all demand levels, especially at off-peak hours, by about 22.5%. In addition, we find that the weights of agency and user costs have the most significant impact on headway, whereas the influence of walking, vehicle speed, and route length is minimal. In contrast, the optimal number of BRT stops is mostly influenced by the route length, and walking speed has essentially no effect on the optimal number of stops. Finally, we find that the generalized cost per passenger at peak hours is 10% to 15% smaller than at off-peak hours in various scenarios.

Home-Based Rehabilitation Following Subtalar Dislocation: A Case Report.

The demand for physical medicine and rehabilitation services has risen significantly. Immediate rehabilitation is not always readily available which may compromise patients' functional recovery. Here, we describe a rare subtalar dislocation case and how an unsupervised home-based rehabilitation program allowed functional recovery. A 49-year-old male presented to the emergency department with an injury to the right ankle which resulted from a 3-meter height fall with his foot in plantar flexion and inversion. Clinical and imaging findings confirmed a diagnosis of a rare case of subtalar dislocation. The post-injury AOFAS Ankle-Hindfoot Scale score was 24/100 points. After six weeks of immobilization, a patient-tailored home-based rehabilitation program was prescribed. Adherence to our home-based rehabilitation program was critical to allow a range-of-motion improvement and functional recovery. Delaying rehabilitation may lead to long-term functional impairments. Thus, acknowledging the post-acute period as critical to initiate rehabilitation is mandatory. When outpatient rehabilitation settings are not readily available due to high demand, comprehensive patient education, and home-based rehabilitation programs may constitute effective alternative interventions. We demonstrate the significant improvement obtained with an early patient-tailored home-based rehabilitation program in range-of-motion and functional outcomes in a case of medial subtalar dislocation.

Enhancing decision-making support by mining social media data with social network analysis.

This paper explores the use of social network analysis (SNA) on airlines' online social networks (OSNs) to extract valuable information for decision support, by analyzing interactions and discursive exchanges between users. The research is focused on fostering customer service of an airline company during a strike period, namely by detecting influential customers (whether satisfied or dissatisfied), address pending requests, and enhancing customer satisfaction, thus promoting issue-solving, and increasing responsiveness. The methodology involves analyzing data from the Facebook account of an airline company, using SNA to structure the data, and calculating metrics to detect possible situations to be addressed by customer service. The research concludes that it is possible to extract valuable information for decision support by analyzing the metrics that were built over the interactions and discursive exchanges between OSN users. SNA metrics enable to measure airline's call-center performance in terms of speed of answer and customer satisfaction, to identify active users requiring additional support, as well as highly influential customers who may impact on the overall customer satisfaction, thus helping to resolve issues more efficiently. This study provides both theoretical and practical implications: it contributes to the existing literature by integrating social interaction and SNA for decision support in airline's service context; and it provides practical insights into how companies can use SNA metrics to improve customer service. The research also highlights and corroborates the importance of monitoring social media interactions for decision-making and improving customer service.

[Evaluation of the Knowledge of Women of Childbearing Age with Epilepsy about the Impact of Their Disease in Contraception, Pregnancy and Breastfeeding: A Multicenter Cross-Sectional Study]. / Avaliação do Conhecimento das Mulheres com Epilepsia em Idade Fértil sobre o Impacto da sua Doença na Contraceção, Gravidez e Amamentação: Um Estudo Transversal Multicêntrico.

INTRODUCTION: The interaction of antiseizure medication with contraceptives, its potential teratogenicity and implications in pregnancy and breastfeeding are aspects to consider in the neurological care of women with epilepsy of childbearing age. To ensure the commitment in therapeutic decisions and the appropriate planning of maternity, it is essential that women are informed about the implications of their disease in these domains. The main aim of this study was to assess the knowledge of women of childbearing age with epilepsy concerning the impact of epilepsy in contraception, pregnancy and breastfeeding. As secondary aims we defined (1) the demographic, clinical and therapeutic characterization of this group of patients, (2) the identification of variables that correlated with the level of knowledge of women with epilepsy, and (3) the identification of preferential methods to acquire new knowledge about epilepsy. MATERIAL AND METHODS: The study was observational, cross-sectional and multicentric, and was carried out in five hospitals of the Lisbon metropolitan area. After identifying all women of childbearing age with epilepsy followed in the epilepsy clinic of each center, we applied an electronic questionnaire based on a non-systematic review of the literature. RESULTS: One hundred and fourteen participants were validated, with a median age of 33 years. Half of the participants were on monotherapy, and the majority had no seizures in the last six months. We identified important gaps in the participants' knowledge. Sections about complications and administration of antiseizure medication during pregnancy were the ones with the worst results. None of the clinical and demographic variables correlated with the final questionnaire score. Having had a previous pregnancy and the desire to breastfeed in a future pregnancy were positively correlated with the performance in breastfeeding section. Face-to-face discussion during medical outpatient visits was selected as the preferential method to learn about epilepsy, and the internet and social media were the least preferred ones. CONCLUSION: The knowledge of women of childbearing age with epilepsy in the Lisbon metropolitan area concerning the impact of epilepsy in contraception, pregnancy and breastfeeding seems to have significant gaps. Medical teams should consider engaging in patient education particularly during outpatient clinics.

Introdução: A interação dos fármacos anticrise epilética com os métodos contracetivos, a sua potencial teratogenicidade e as implicações na gravidez e amamentação são aspetos a considerar no acompanhamento de mulheres com epilepsia em idade fértil. Para o seu desejado envolvimento nas decisões terapêuticas e o adequado planeamento da maternidade, é essencial que as mulheres estejam corretamente informadas acerca das implicações da sua doença. O objetivo principal do presente estudo foi avaliar o conhecimento das mulheres com epilepsia em idade fértil sobre o impacto da epilepsia na contraceção, gravidez e amamentação. Como objetivos secundários definiram-se (1) a caracterização demográfica, clínica e terapêutica deste grupo de doentes, (2) a identificação de variáveis correlacionadas com o nível de conhecimento das mulheres com epilepsia, e (3) a identificação de meios e suportes preferenciais para aquisição de novos conhecimentos sobre epilepsia. Material e Métodos: O estudo foi observacional, transversal e multicêntrico, tendo decorrido em cinco centros hospitalares da região metropolitana de Lisboa. Após identificação das mulheres com epilepsia em idade fértil seguidas na Consulta de Epilepsia de cada centro, aplicou-se um questionário eletrónico construído após revisão não sistemática da literatura. Resultados: Foram validadas 114 participantes, com uma idade mediana de 33 anos. Metade das participantes apresentavam-se sob monoterapia, tendo a maioria a epilepsia controlada há pelo menos seis meses. Identificaram-se importantes lacunas no conhecimento das participantes. Conceitos sobre complicações dos fármacos anticrise epilética e a sua administração durante a gravidez motivaram piores resultados. Não houve correlação entre variáveis clinico-demográficas e o resultado no questionário. A ocorrência de gravidez prévia e o desejo de amamentar numa gravidez futura correlacionaram-se com o desempenho na secção sobre amamentação. A discussão oral na consulta foi a forma preferencial para aquisição de novos conhecimentos sobre epilepsia, tendo a internet e as redes sociais sido os meios menos escolhidos. Conclusão: O conhecimento das mulheres com epilepsia em idade fértil na área metropolitana de Lisboa sobre o impacto da sua doença na contraceção, gravidez e amamentação parece apresentar lacunas importantes. A educação para a saúde deste grupo deverá constituir uma preocupação por parte das equipas médicas, devendo privilegiar-se a consulta como local de ensino.

Monkeypox Mysteries of the New Outbreak in Non-Endemic Areas.

Monkeypox virus (MPXV) was declared by the World Health Organization (WHO) in mid-2022 to be a public health emergency of international concern, following its spread around the world after circulating in Western and Central Africa. This new outbreak is concentrated in men who have sex with men (MSM). Moreover, beyond the epidemiological change, compared with endemic countries, differences in clinical features and many other aspects have also been detected. These and other characteristics are unusual and still unclear. Based on the available data, the authors try to help to clarify some of the current major gaps in monkeypox knowledge to strengthen the outbreak response.

Monkeypox: From A Neglected Tropical Disease to a Public Health Threat.

Since the first case of human monkeypox was diagnosed in 1970, the disease remained endemic in several countries in West and Central Africa. In 1996, there was a sudden increase in cases in the Democratic Republic of Congo (DRC), and since 2017 an ongoing outbreak in Nigeria took place, probably related to the population growth, human invasion of MPXV animal habitat reservoirs, and the waning of the cross-protection offered from smallpox immunization, later ending in 1980. Since May 2022, an unprecedented outbreak of human monkeypox has rapidly spread around the world, outside endemic regions of Africa, through new modes of transmission, showing differences in clinical features compared with previous reports. The 2022 MPXV strain belongs to the clade of West Africa but diverges from the original strain, making the virus more transmissible. The authors review the main milestones in more than 50 years of history of human monkeypox, from a rare viral zoonotic infection to a public health emergency.

Hepatitis C antibody prevalence and behavioral correlates in people who inject drugs attending harm reduction services in Lisbon, Portugal.

The hepatitis C virus (HCV) infection is an important public health problem, affecting millions of people worldwide. People who inject drugs (PWID) are at increased risk of HCV infection due to, among other factors, widespread unsafe injecting practices, such as sharing of infected equipment or unprotected sexual practices. In Portugal, there is a lack of data regarding the proportion of infected persons through injecting drug use. This study aimed to evaluate the anti-HCV prevalence and behavioral correlates of infection in PWID attending harm reduction services in the Metropolitan Area of Lisbon, Portugal. A cross-sectional study with a purposive sample of PWID was undertaken between March 2018 and March 2020. Participants were recruited through the harm-reduction services of a nongovernmental organization. A rapid diagnostic test for anti-HCV screening was performed. Data on drug consumption history and current practices, past HCV testing, care and treatment history, and knowledge regarding hepatitis C were also collected through a questionnaire applied by trained inquirers. A total of 176 PWID participated in this study. An overall prevalence of 70.5% of anti-HCV positive in this population was found. Those with an anti-HCV positive testing result tended to start consuming at a younger age and have a higher consumption of benzodiazepines in the last 30 days. Sharing needles and other injecting material is a frequent risk behavior among this group. Also, they are more likely to have attended an opioid agonist treatment and to have undertaken previous hepatitis C and HIV tests in the past. This study represents an important effort to better understand the HCV prevalence and behavioral correlates of infection among PWID in Portugal, as well as to better estimate those in need of HCV treatment.

Persistence of IgG COVID-19 antibodies: A longitudinal analysis.

Background and aim: The kinetics of antibody production in response to coronavirus disease 2019 (COVID-19) infection is not well-defined yet. This study aimed to evaluate the antibody responses to SARS-CoV-2 and its dynamics during 9-months in a cohort of patients infected during the first phase of the pandemic. As a secondary aim, it was intended to evaluate the factors associated with different concentrations of IgG antibodies. Methods: A prospective cohort study was conducted from June 2020 to January 2021. This study recruited a convenience sample of adult individuals who where recently diagnosed with COVID-19 and were living in mainland Portugal. A total of 1,695 blood samples were collected from 585 recovered COVID-19 patients up to 9 months after SARS-CoV-2 acute infection. A blood sample was collected at baseline and three, 6 and 9 months after SARS-CoV-2 acute infection to assess the concentration of IgG antibody against SARS-CoV-2. Results: The positivity rate of IgG reached 77.7% in the first 3 months after symptom onset. The IgG persists at all subsequent follow-up time-points, which was 87.7 and 89.2% in the 6th and 9th months after symptom onset, respectively. Three distinct kinetics of antibody response were found within the 9 months after infection. Kinetic 1 (K1) was characterized by a constant low IgG antibody concentration kinetic (group size: 65.2%); kinetic 2 (K2), composed by constant moderate IgG kinetic (group size: 27.5%) and kinetic 3 (K3) characterized by higher IgG kinetic (group size: 7.3%). People with ≥56 years old (OR: 3.33; CI 95%: [1.64; 6.67]; p-value: 0.001) and symptomatic COVID-19 (OR: 2.08; CI 95%: [1.08; 4.00]; p-value: 0.031) had higher odds of a "Moderate IgG kinetic." No significant association were found regarding the "Higher IgG kinetic." Conclusion: Our results demonstrate a lasting anti-spike (anti-S) IgG antibody response at least 9 months after infection in the majority of patients with COVID-19. Younger participants with asymptomatic disease have lower IgG antibody positivity and possibly more susceptible to reinfection. This information contributes to expanding knowledge of SARS-CoV-2 immune response and has direct implications in the adoption of preventive strategies and public health policies.

HIV Infection: Time from Diagnosis to Initiation of Antiretroviral Therapy in Portugal, a Multicentric Study.

The benefits of antiretroviral therapy (ART) for persons living with HIV (PLWH) are well established. Rapid ART initiation can lead to improved clinical outcomes. Portugal has one of the highest rates of new HIV diagnoses in the European Union, and an average time until ART initiation above the recommendations established by the national guideline according to data from the first two years after its implementation in 2015, with no more recent data available after that. This study aimed to evaluate time from the first hospital appointment until ART initiation among newly diagnosed HIV patients in Portugal between 2017 and 2018, to investigate differences between hospitals, and to understand the experience of patient associations in supporting the navigation of PLWH throughout referral and linkage to the therapeutic process. To answer to these objectives, a twofold design was followed: a quantitative approach, with an analysis of records from five Portuguese hospitals, and a qualitative approach, with individual interviews with three representatives of patient associations. Overall, 847 and 840 PLWH initiated ART in 2017 and in 2018, respectively, 21 days (median of the two years) after the first appointment, with nearly half coming outside the mainstream service for hospital referral, and with observed differences between hospitals. In 2017-2018, only 38.0% of PLWH initiated ART in less than 14 days after the first hospital appointment. From the interviews, barriers of administrative and psychosocial nature were identified that may hinder access to ART. Patient associations work to offer a tailored support to patients' navigation within the health system, which can help to reduce or overcome those potential barriers. Indicators related to time until ART initiation can be used to monitor and improve access to specialized care of PLWH.

Sighs during sleep in multiple system atrophy.

Sighs are physiological phenomena and may occasionally occur during sleep in healthy young adults. Although inspiratory sighs are considered a diagnostic red flag for the parkinsonian form of multiple system atrophy (MSA), its frequency and characteristics are unclear. We aimed to define sigh frequency during sleep recordings in patients with MSA compared to Parkinson's disease (PD) patients, as well as evaluate possible associated breathing disorders or autonomic changes. We analyzed 9 polysomnography's from patients with MSA and 9 from matched PD patients. The proportion of MSA patients (both MSA-P and MSA-C) with sleep-related sighs was significantly higher than that of PD patients, and these occurred predominantly in stages N1 and N2. The median sigh index in sleep and wakefulness were also significantly higher in MSA, although with a significant inter-subject variability. Higher sigh indexes were not associated to other breathing disturbances or with longer disease duration. In MSA, 12% of sighs were associated with oxygen desaturation, while none of the events in PD patients presented with significant changes in oxygen saturation. Respiratory events followed 45% of sighs in MSA, predominantly central sleep apneas, and 29% of sighs in PD, predominantly hypopneas. Our data suggests that high sigh frequencies during sleep should also be considered a red flag for MSA, and future studies should aim to determine whether increased sighing frequency during sleep is specific for this disorder.

[Candida auris: The Recent Emergence of a Multiresistant Pathogenic Fungi]. / Candida auris: Emergência Recente de um Fungo Patogénico Multirresistente.

Candida auris was first described as a new species back in 2009. Although it differs markedly from other Candida species, this species can be misidentified as other yeasts in the routine microbiology laboratories. Therefore, its identification to species level should be confirmed by reference laboratories. Candida auris exhibits potential to cause invasive infections, and frequently shows a multidrugresistance pattern, and it is associated with high mortality rates. Outbreaks caused by Candida auris and associated with health care institutions have been reported in several countries around the world, including some European countries, such as the United Kingdom and Spain. In Portugal, to our knowledge, there are no known infections or colonization cases caused by Candida auris. This species can survive in the environment for several weeks and once introduced into the hospital environment, the risk of transmission is high, requiring strict infection control measures in order to prevent transmission. This paper intends to raise the awareness of the emergence of this fungal species, as well as to discuss the consequences of this situation.

Candida auris foi descrita pela primeira vez em 2009, como uma espécie distinta das outras leveduras do género Candida. Este fungo é difícil de se distinguir de outras espécies com que se correlaciona, sendo, atualmente, aconselhada a confirmação da sua identificação por laboratórios de referência. Esta levedura tem a capacidade de causar infeções invasivas, podendo ser resistente às três classes de antifúngicos, sendo a mortalidade elevada. Candida auris tem sido detetada em vários países do Mundo, incluindo alguns países da Europa, tais como Reino Unido e Espanha. Até à data, em Portugal, não há registo de qualquer caso de infeção/colonização por Candida auris. Esta espécie pode sobreviver no ambiente durante várias semanas e uma vez introduzida no ambiente hospitalar, o risco de transmissão é elevado, obrigando à implementação de medidas rigorosas de controlo da infeção, por forma a prevenir a transmissão. Este artigo pretende dar a conhecer e discutir a problemática da emergência deste fungo e as suas eventuais consequências.

Handling of Fresh Vegetables: Knowledge, Hygienic Behavior of Vendors, Public Health in Maputo Markets, Mozambique.

In developing countries, markets are the main supply of horticultural products to populations, but this can pose a public health challenge due to the risk of the fecal-oral transmission of gut pathogens. This transmission is strongly associated with inadequate public sanitation or low standards of personal and domestic hygiene, and their prevalence can cause gastrointestinal diseases, which are the third leading cause of death in Mozambique. This study aims at assessing the risk for public health of horticultural products supply chain, from the farmers-vendors to the consumers, in municipal markets in Maputo-City, Mozambique. Surveys (75) were conducted on vendors and an observational analysis was performed in the markets under study. The results showed that 62% of the vendors had access to water from boreholes or artisanal sources and the issue "access to water" was significantly different between markets (p = 0.004). Of the vendors who wash their products (53.3%), only 7.5% use tap-water for this purpose, with the difference in attitudes being statistically significant between vendors in the markets (p = 0.035). The majority (60.4%) said that vegetables and fruits can cause diseases due to pesticides and only 31.3% believe that the diseases may be related to poor hygiene. Despite the vendors' low knowledge of Good Hygiene Practices (GHP), we noticed that women have better practical assimilation of GHP when compared to men (p = 0.008). Although Maputo's markets are struggling to achieve quality hygiene standards in a reliable and sustainable manner, their resources are limited and significantly different (p = 0.044) from market to market, and this problem remains a concern for the public-health authorities of the city. In conclusion, the provision of adequate drinking water and sewage disposal systems, together with education for health of vendors, can reduce the risk of contamination of fresh food by the more common organisms causing diarrhea in children, including intestinal parasites.

Candida auris, an Agent of Hospital-Associated Outbreaks: Which Challenging Issues Do We Need to Have in Mind?

The emergence of Candida auris is considered as one of the most serious problems associated with nosocomial transmission and with infection control practices in hospital environment. This multidrug resistant species is rapidly spreading worldwide, with several described outbreaks. Until now, this species has been isolated from different hospital surfaces, where it can survive for long periods. There are multiple unanswered questions regarding C. auris, such as prevalence in population, environmental contamination, effectiveness of infection prevention and control, and impact on patient mortality. In order to understand how it spreads and discover possible reservoirs, it is essential to know the ecology, natural environment, and distribution of this species. It is also important to explore possible reasons to this recent emergence, namely the environmental presence of azoles or the possible effect of climate change on this sudden emergence. This review aims to discuss some of the most challenging issues that we need to have in mind in the management of C. auris and to raise the awareness to its presence in specific indoor environments as hospital settings.

Sleep-related hypermotor epilepsy and peri-ictal hypotension in a patient with syntaxin-1B mutation.

STX1B is a gene that encodes syntaxin-1B. STX1B mutations have recently been implicated in fever-associated epilepsy syndromes. However, these have not previously been reported in sleep-related hypermotor epilepsy. A 20-year-old man with a strong family history of epilepsy was investigated in our epilepsy monitoring unit due to uncontrolled epilepsy, compatible with sleep-related hypermotor epilepsy. Electroclinical and polygraphic physiological recordings revealed left frontal epileptiform discharges and prominent peri-ictal hypotension. Normal MRI using an epilepsy protocol prompted a search for a genetic epilepsy, which revealed a likely pathogenic mutation in the STX1B gene. The patient remained seizure-free after treatment optimization with carbamazepine. This case suggests that a sleep-related hypermotor epilepsy phenotype can be associated with syntaxin-1B gene mutation, and testing for this gene should be considered in such patients. Furthermore, it may also be concluded that autonomic dysfunction, characterized by peri-ictal hypotension, can also occur in this discorder. [Published with video sequences on www.epilepticdisorders.com].

First report of occult hepatitis B infection among ART naïve HIV seropositive individuals in Maputo, Mozambique.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection and human immunodeficiency virus (HIV) infection in Mozambique is one of the highest in the world, though in spite of this the prevalence of occult hepatitis B infection (OBI) is unknown. OBJECTIVES: This study was conducted with the aim to investigate the prevalence of OBI and frequency of isolated hepatitis B core antibody (anti-HBc alone) among antiretroviral (ART) naïve HIV-positive patients in Mozambique. METHODS: A cross-sectional study was conducted in two health facilities within Maputo city. All ART-naive HIV seropositive patients attending outpatient clinics between June and October 2012 were consecutively enrolled. Blood samples were drawn from each participant and used for serological measurement of HBV surface antigen (HBsAg), antibodies against HBV surface antigen (anti-HBs) and antibodies against core antigen (anti-HBc) using ELISA. Quantification of HBV DNA was performed by real time PCR. A questionnaire was used to obtain demographics and clinical data. RESULTS: Of the 518 ART-naive HIV-positive subjects enrolled in the study, 90.9% (471/518) were HBsAg negative. Among HBsAg negative, 45.2% (213/471) had isolated anti-HBc antibodies, and the frequency of OBI among patients with anti-HBc alone was 8.3% (17/206). OBI was not correlated either with CD4+ T cells count or transaminases levels. A total of 11.8% of patients with OBI presented elevated HBV DNA level. Frequency of individuals with APRI score > 2 and FIB-4 score > 3.25 was higher in patients with OBI as compared not exposed, immune and anti-HBc alone patients. CONCLUSION: Our data demonstrate for the first time that OBI is prevalent among HIV patients in Mozambique, and will be missed using the commonly available serological assays that measures HBsAg.

Correction: HBV infection in untreated HIV-infected adults in Maputo, Mozambique.

[This corrects the article DOI: 10.1371/journal.pone.0181836.].

Familial cerebral cavernous malformation: Report of a novel KRIT1 mutation in a Portuguese family.

Cerebral cavernous malformations (CCMs) are vascular malformations which may occur in familial forms which have autosomal dominant inheritance. Mutations have been identified in three genes: KRIT1, MGC4607 and PDCD10. We have documented a novel mutation on KRIT1 gene, and the second to be reported in a Portuguese family. This mutation consists in a two nucleotide insertion (c.947_948insAC) within the exon 10, resulting in premature protein termination (p.Leu317Argfs*2). These findings will hopefully contribute to a better clinical, imaging and genetic characterisation of this disease, particularly while trying to identify the factors that influence its treatment and prognosis.

HBV infection in untreated HIV-infected adults in Maputo, Mozambique.

BACKGROUND: HIV/ HBV coinfected patients are at high risk of developing chronic HBV infection, liver cirrhosis and hepatocellular carcinoma. In Mozambique, where HIV prevalence is one of the highest in the world, HIV-infected patients are scarcely characterized in terms of HBV coinfection and 3TC-resistance mutations profile. METHODS: To characterize ART-naïve HIV-infected adults, with and without HBV coinfection, a cross-sectional study was conducted between May and November 2012 in two health centers from Maputo city, Mozambique. Subjects were consecutively enrolled in the study and, then, tested for hepatitis B surface antigen (HBsAg). Moreover, CD4+ T cells count, HBV DNA in plasma, HBV genotyping and 3TC-resistance mutations profile of HBV were assessed in HIV/HBV coinfected patients. RESULTS: In total, 518 patients were enrolled in the study. The median age was 33 years old and 66.8% were women. The median CD4+ T cells count was 361 cells/mm3 and 47 (9.1%) were coinfected with HBV. Out of 46 coinfected patients, 24 (55.2%) had HBV DNA ≥ 20 - < 20 000 and 12 (26.1%) had HBV-DNA ≥20 000. APRI > 2.0 was reported in 4.3% of coinfected and 1.7% of monoinfected patients (p = 0.228), while FIB-4 > 3.25 was reported in 4.4% of coinfected and 1.3% of monoinfected patients (p = 0.112). Genotype A was the most frequent, identified in 25/27 (92.6%) patients, whereas genotype E was present in 2/27 (7.4%) patients. No patient had 3TC-resistance mutations. CONCLUSIONS: This study showed that HBV coinfection was prevalent among ART-naïve HIV-infected adults in Mozambique. Overall, these data highlight the importance of screening HBV coinfection as an integrated measure of HIV routine care to improve health conditions and treatment of HIV/HBV coinfected patients.

Population Approach to Efavirenz Therapy.

Efavirenz (EFV) is a nonnucleoside reverse transcriptase inhibitor commonly used as first-line therapy in the treatment of human immunodeficiency virus (HIV), with a narrow therapeutic range and a high between-subject variability which can lead to central nervous system toxicity or therapeutic failure. To characterize the sources of variability and better predict EFV steady-state plasma concentrations, a population pharmacokinetic model was developed from 96 HIV-positive individuals, using a nonlinear mixed-effect method with Monolix® software. A one-compartment with first-order absorption and elimination model adequately described the data. To explain between-subject variability, demographic characteristics, biochemical parameters, hepatitis C virus-HIV coinfection, and genetic polymorphisms were tested. A combination of the single-nucleotide polymorphisms rs2279343 and rs3745274, both in the CYP2B6 gene, were the only covariates influencing clearance, included in the final model. Oral clearance was estimated to be 19.6 L/h, 14.15 L/h, and 6.08 L/h for wild-type, heterozygous mutated and homozygous mutated individuals, respectively. These results are in accordance with the current knowledge of EFV metabolism and also suggest that in homozygous mutated individuals, a dose adjustment is necessary. Hepatitis C virus-HIV coinfection does not seem to be a predictive indicator of EFV pharmacokinetic disposition.

[Multidrug-Resistant Tuberculosis by Strains of Beijing Family, in Patients from Lisbon, Portugal: Preliminary Report]. / Tuberculose Multirresistente por Estirpes da Família Beijing, em Doentes de Lisboa, Portugal: Estudo Preliminar.

INTRODUCTION: Beijing family strains of Mycobacterium tuberculosis are associated with multidrug-resistance. Although strains of the Lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the Beijing family. However, the features of patients from whom they were isolated, are not yet known. MATERIAL AND METHODS: Retrospective study involving 104 multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, from the same number of patients, isolated and genotyped between 1993 and 2015 in Lisbon. We assessed the prevalence of strains of both families and the epidemiologic and clinical features of those infected with Beijing family strains. RESULTS: Seventy-four strains (71.2%) belonged to the Lisboa family, 25 (24.0%) showed a unique genotypic pattern and five (4.8%) belonged to the Beijing family, the latter identified after 2009. Those infected with Beijing family strains were angolan (n = 1), ukrainian (n = 2) and portuguese (n = 2), mainly young-aged and, four of five immunocompetent and with no past history of tuberculosis. All had multidrug-resistant tuberculosis. We did not find any distinctive clinical or radiological features, neither a predominant resistance pattern. Cure rate was high (four patients). DISCUSSION: Although the number of infected patients with Beijing strains was small, it suggests an important proportion of primary tuberculosis, a potential for transmission in the community but also a better clinical outcome when compared to other reported strains, such as W-Beijing and Lisboa. CONCLUSION: Although Lisboa family strains account for most of the multidrug and extensively drug-resistant tuberculosis cases in Lisbon area, Beijing strains are transmitted in the city and might change the local characteristics of the epidemics.

Introdução: As estirpes de Mycobacterium tuberculosis da família Beijing estão associadas à multirresistência. As estirpes da família Lisboa prevalecem entre os doentes com tuberculose multirresistente e extensivamente resistente desta região, mas vários estudos documentam  a presença da família Beijing, embora desconhecendo-se as características dos doentes donde foram isoladas. Material e Métodos: Estudo retrospectivo de 104 estirpes multirresistentes e extensivamente resistentes de Mycobacterium tuberculosis, isoladas e genotipadas, de 1993 a 2015, de igual número de doentes de Lisboa. Avaliámos a prevalência de ambas as famílias de estirpes e as características epidemiológicas e clínicas, dos infectados por estirpes Beijing. Resultados: Setenta e quatro estirpes (71,2%) pertenciam à família Lisboa, 25 (24,0%) apresentavam padrão genotípico único e cinco (4,8%) pertenciam à família Beijing, estas identificadas depois de 2009. Os infectados pela estirpe Beijing eram de nacionalidade angolana (n = 1), ucraniana (n = 2) e portuguesa (n = 2), na maioria jovens, quatro em cinco imunocompetentes e sem história de tuberculose anterior. Todos tinham tuberculose multirresistente. Não detectámos apresentações clínicas ou radiológicas diferenciadoras, nem padrão de resistências predominante. A taxa de cura foi alta (quatro doentes). Discussão: Apesar do número de doentes infectados pela estirpe Beijing ser reduzido, sugere proporção importante de tuberculose primária, potencial de transmissão na comunidade, mas, também, melhor evolução clínica do que a descrita para outras estirpes, como a W-Beijing ou a Lisboa. Conclusão: Apesar das estirpes da família Lisboa serem as principais responsáveis pelos casos de tuberculose multirresistente e extensivamente resistente na região de Lisboa, as estirpes Beijing transmitem-se na cidade e poderão modificar as características locais da epidemia.