Search

Background: HIV-exposed uninfected (HEU) infants show a high rate of morbidity. We aimed to investigate on biomarkers of immune activation/microbial translocation in HEU infants, evaluating the impact that infections/malnutrition can have on biomarker levels during the first year of life.Methods: Clinical data of 72 Malawian infants were recorded monthly and correlated with levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FABP), analyzed longitudinally.Results: Levels of sCD14 and LBP showed a significant age-related increase. Higher levels of LBP (19.4 vs. 15.2 μg/ml) were associated with stunting, affecting 30% of the infants. The association remained statistically significant after adjusting for cytomegalovirus acquisition, malaria and respiratory infections (p = 0.031). I-FABP levels were significantly increased in infants experiencing gastrointestinal infections (1442.8 vs. 860.0 pg/ml, p = 0.018).Conclusion: We provide evidence that stunting is associated with an enhanced inflammatory response to microbial products in HEU children, suggesting that malnutrition status should be taken into consideration to better understand the alteration of the immune profile of HEU infants living in poor socioeconomic settings. [ABSTRACT FROM AUTHOR]

Background Frailty is associated with a prodromal stage called pre-frailty, a potentially reversible and highly prevalent condition before frailty becomes established. Despite this, there is no widely accepted definition of pre-frailty to support its early identification and management. This study applied an international consensus approach to define and better understand pre-frailty. Methods A modified electronic two-round Delphi Consensus study was conducted. In all, 23 experts from 12 countries with different backgrounds participated. The questionnaire was developed following a systematic literature review. An online consensus meeting was conducted with eight Delphi participants and two external experts. Qualitative and quantitative methods were employed for data analysis. An agreement level of 70% was applied for accepting statements. Results A total of 71 statements were circulated in Round 1. Of these, 52.8% were accepted. Fifty-one statements were re-circulated in Round 2, of which 92.1% were accepted. The online consensus meeting produced a consensus statement describing the concept, multi-factorial nature, and mechanism of pre-frailty as well as assessment, prevention and management approaches. All experts agreed that physical and non-physical factors such as psychological and social capacity are involved in the development of pre-frailty, potentially adversely affecting health and health-related quality of life outcomes. Practitioners should regard pre-frailty as a multi-factorial, multi-dimensional, and non-linear process that does not inevitably lead to frailty. It might be reversed or attenuated by targeted interventions. Brief, feasible and validated tools are recommended for opportunistic screening or case-finding followed by confirmation with multi-dimensional assessment. Conclusion It is difficult to establish consensus on one compact definition of pre-frailty, which is a multi-dimensional concept not only associated with physical impairment, but also with cognitive, nutritional, socioeconomic and other aspects of frailty. However, it may be too early to agree on an operational definition of pre-frailty since none yet exists for frailty. [ABSTRACT FROM AUTHOR]

Background Lowering mortality and hospitalization of older adults is one of the main goals of public health to improve both health systems' sustainability and older adults' quality of life. The aim of this study is to identify the determinants associated with mortality and the use of hospital services in the population older than 64 years of age. Methods A randomized sample from the population of the Lazio region (Italy) above the age of 64 was enrolled in 2014 by the administration of a questionnaire to assess frailty; the rates of use of hospital services and mortality in the year following the enrolment have been retrieved by the regional database. Univariable and multivariable analyses addressed the association of health status, social and economic variables with health outcomes. Results One thousand two hundred and eighty persons were recruited; 52 deaths were reported at 1 year of follow-up (robust 1.8%, frail 10.1% and very frail 19.1%, P < 0.001). The mean rate of use of hospital services was 692.2 per 1000 observation/year (robust 589.5, frail 1191.1 and very frail 848.4, P < 0.001). In the multivariate analysis, the higher rate of use of hospital services was independently associated with functional status, social support, psychological/psychiatric discomfort, availability of home care services and physical health. Conclusions Frailty, as a multidimensional issue, is also a strong predictor of survival in the short term. The use of the hospital services by older adults is associated mainly with functional status, social resources, psycho-physical status and health service organization factors. [ABSTRACT FROM AUTHOR]

We study the problem of computing drawings of planar graphs in sub-quadratic area, by allowing edge crossings. We first prove that sub-quadratic area cannot be achieved if only a constant number of crossings per edge is allowed. More precisely, we show that the same area lower bounds as in the crossing-free case hold for straight-line and poly-line drawings of planar graphs and seriesparallel graphs. Motivated by this result, we study straight-line drawings of planar graphs where the number of crossings per edge is not bounded by a constant. In this case, we prove that every planar graph admits a straight-line drawing with sub-quadratic area and sub-linear thickness (the thickness of a drawing is the minimum number of colors that can be assigned to the edges so that each color class induces a planar drawing). We also prove that every partial 2-tree (and hence every series-parallel graph) admits a linear-area straight-line drawing with thickness at most 10. It is worth remarking that a drawing with thickness h - 1 is h-quasi planar, i.e. it does not contain h-mutually crossing edges. The main ingredient to prove our results is (c, t)-track layouts, a combinatorial tool that can be represented as a drawing where: (i) each vertex is assigned to one of t horizontal layers (tracks), (ii) no two adjacent vertices are on the same track, (iii) each edge receives one of c colors, so that no two edges of the same color (u, v) and (w, z) cross if u, w are on the same track, and v, z are on the same track. [ABSTRACT FROM AUTHOR]

Objectives: No data are available on bone metabolism in infants exposed to tenofovir during breastfeeding. We investigated bone metabolism markers in the first year of life in infants from mothers who received tenofovir, lamivudine and efavirenz during pregnancy and 12 months of breastfeeding in a national Option B+ programme in Malawi.Methods: Serum samples collected at 6 and 12 months in tenofovir-exposed infants and in a small sample of tenofovir-unexposed infants from the same clinical centre were analysed in batches for levels of bone-specific alkaline phosphatase (BAP; marker of bone formation) and of C-terminal telopeptide of type I collagen (CTX; marker of bone resorption).Results: Overall, 136 tenofovir-exposed infants were evaluated. No infant had at either timepoint CTX values above the upper normal limit, while most of them had at 6 and 12 months levels of BAP above the upper normal limit for the age range. Levels of bone markers showed no differences by gender and no association with growth parameters. Tenofovir-unexposed and -exposed children had similar mean levels of bone markers at 6 months (CTX: 0.62 versus 0.55 ng/mL, P = 0.122; BAP: 384 versus 362 U/L, P = 0.631).Conclusions: No significant association between treatment with tenofovir and CTX or BAP levels was found. The high levels of BAP, coupled to the normal levels observed for CTX, might reflect primarily skeletal growth. Potential negative effects of prolonged exposure to tenofovir through breastfeeding cannot however be excluded and longitudinal studies that evaluate bone mineralization status in children enrolled in Option B+ programmes are warranted. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate antiretroviral drug concentrations in mothers and infants enrolled under the Option B-Plus approach for the prevention of HIV mother-to-child transmission in Malawi and to assess the maternal virological response after 1 year of treatment.Patients and Methods: Forty-seven women and 25 children were studied. Mothers were administered during pregnancy a combination of tenofovir, lamivudine and efavirenz and continued it during breastfeeding (up to 2 years) and thereafter. Drug concentrations were evaluated in mothers (plasma and breast milk) at 1 and 12 months post-partum and in infants (plasma) at 6 and 12 months of age. Drug concentrations were determined using an LC-MS/MS validated methodology.Results: In breast milk, tenofovir concentrations were very low (breast milk/maternal plasma ratio = 0.08), while lamivudine was concentrated (breast milk/plasma ratio = 3) and efavirenz levels were 80% of those found in plasma. In infants, median levels at 6 months were 24 ng/mL tenofovir, 2.5 ng/mL lamivudine and 86.4 ng/mL efavirenz. At month 12, median levels were below the limit of quantification for the three drugs. No correlation was found between drug concentrations and laboratory parameters or indices of growth. HIV-RNA >1000 copies/mL was seen at month 1 in 15% of the women and at month 12 in 8.5%. Resistance was found in half of the women with detectable viral load.Conclusions: Breastfeeding infants under Option B-Plus are exposed to low concentrations of antiretroviral drugs. With this strategy, mothers had a good virological response 1 year after delivery. [ABSTRACT FROM AUTHOR]

A simultaneous geometric embedding (SGE) of two planar graphs G1 and G2 with the same vertex set is a pair of straight-line planar drawings Γ1 of G1 and Γ2 of G2 such that each vertex is drawn at the same point in Γ1 Γ2. Many papers have been devoted to the study of which pairs of graphs admit a SGE, and both positive and negative results have been proved. We extend the study of SGE, by introducing and characterizing a new class of planar graphs that makes it possible to immediately extend several positive results that rely on the property of strictly monotone paths. Moreover, we introduce a relaxation of the SGE setting where Γ1 and Γ2 are required to be quasi-planar (i.e. they can have crossings provided that there are no three mutually crossing edges). This relaxation allows for the simultaneous embedding of pairs of planar graphs that are not simultaneously embeddable in the classical SGE setting and opens up several new interesting research questions. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to determine the prevalence of drug resistance mutations among HIV-positive women in Malawi 18 months after discontinuing nevirapine-based ART for the prevention of mother-to-child transmission.Patients and Methods: HIV-infected antiretroviral-naive (except for single-dose nevirapine) pregnant Malawian women receiving a nevirapine-based triple antiretroviral regimen from Week 25 of gestation until 6 months of breastfeeding were included in this analysis. Drug resistance was assessed in HIV-DNA 24 months post-partum and at baseline (before the initiation of treatment). In patients with resistance, the presence of mutations was also evaluated in the corresponding plasma samples.Results: Seven out of 42 (16.7%) women studied had archived drug resistance at Month 24 [six cases had NNRTI-associated mutations and two cases the M184I mutation]. In four cases, resistance mutations were already present at baseline (all NNRTI mutations). In three cases, there was an emergence of 'new' resistance (also present in the plasma in one case). Of the 35 women without resistance mutations at Month 24, only one subject had resistance mutations at baseline. Baseline resistance was significantly more common among women with mutations at 24 months compared with those harbouring a WT virus (4/7 versus 1/35, P < 0.001).Conclusions: Among women who had discontinued drugs 6 months post-partum, only 3/42 (7.1%) had accumulated new resistance mutations in HIV-DNA 2 years after delivery. These findings are reassuring in terms of the safety of the Option B strategy for the prevention of HIV mother-to-child transmission. [ABSTRACT FROM AUTHOR]

A2-layer drawing of a bipartite graph G is a drawing such that the vertices of each partition set are drawn as points of a distinct horizontal line (called a layer) and the edges are drawn as straight-line segments. We study 2-layer drawings where edges can cross only at right angles; these drawings are called 2-layer right angle crossing drawings (2-layer RAC drawings for short). We focus on the following problem, which we call the maximum 2-layer RAC subgraph (M2LRacS) problem. Given a bipartite graph G, compute a subgraph H of G such that: (i) H admits a 2-layer RAC drawing and (ii) H has the maximum number of edges among the subgraphs of G that satisfy (i). We study this problem both in the no-fixed-layer setting, where no restriction is given on the vertex ordering on each layer, and in the 1-?xed-layer setting, where the ordering of the vertices of one of the two layers is given as part of the input and cannot be changed. The M2LRacS problem is known to be NP-hard in the no-fixed-layer setting (Di Giacomo, E., Didimo, W., Eades, P. and Liotta, G. (2011) 2-Layer Right Angle Crossing Drawings. Proc. IWOCA 2011, Lecturer Notes in Computer Science 7056, pp. 156-169; Di Giacomo, E., Didimo, W., Eades, P. and Liotta, G. (2014) 2-layer right angle crossing drawings. Algorithmica, 68, 954-997), but no algorithm has been proposed so far to solve it. We prove that the M2LRacS problem remains NP-hard even in the 1-?xed-layer setting, and provide different heuristics to solve it in the two settings; one of these heuristics is a 3-approximation algorithm for the no-fixed-layer setting. Also, we present the results of an experimental study that compares our heuristics and shows the effectiveness of the 3-approximation algorithm in practice. [ABSTRACT FROM AUTHOR]

Objectives To identify factors associated with detectable viral load and the emergence of drug resistance in a cohort of HIV-infected pregnant women in Malawi receiving antiretroviral combination regimens for the prevention of mother-to-infant transmission. Methods The study included 260 treatment-naive women who had received a three-drug nevirapine-based regimen from week 25 of gestational age until 6 months after delivery. HIV RNA was determined at month 6 and drug resistance was assessed if viral load was >50 copies/mL. Attendance at the scheduled follow-up visits was used as an indirect measure of treatment adherence. Results The rate of detectable HIV RNA at 6 months was 9.6% (25/260). The only significant predictor of this occurrence was the presence of ≥1 missed visit during follow-up (P = 0.012). Resistance was assessed in 19 of these women: 7 (37%) had a wild-type virus and the other 12 (63%) had resistance-associated mutations (nucleoside reverse transcriptase inhibitor, 7/12; non-nucleoside reverse transcriptase inhibitor, 11/12). Three of 12 cases (25%) in which mutations were detected had a viral load <1000 copies/mL. The emergence of resistance was not correlated with the presence of baseline mutations in either plasma or archived DNA. Conclusions In this cohort of women, detectable HIV RNA 6 months post-partum was infrequent and associated with low adherence to the treatment programme. Mutations were present in 63% of the women with detectable viral load at 6 months who had samples available for resistance testing. The impact of resistance on treatment re-initiation in women discontinuing drugs after the risk of transmission has ceased can be limited. [ABSTRACT FROM PUBLISHER]

Universal human immunodeficiency virus (HIV) test-and-treat approaches have been evaluated in mathematical models. We developed a district-level model based on actual data from 26-patients in the Drug Resource Enhancement Against AIDS and Malnutrition Program in sub-Saharan Africa. Rapid decreases were observed in the incidence of HIV infection and population infectivity.Background. The use of antiretrovirals to reduce the incidence of human immunodeficiency virus (HIV) infection has been evaluated in mathematical models as potential strategies for curtailing the epidemic. Cohort data from the Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) Program was used to generate a realistic model for the HIV epidemic in sub-Saharan Africa.Methods. Two combined stochastic models were developed: patient and epidemic models. Models were combined using virus load as a parameter of infectivity. DREAM data that assessed patient care in Mozambique and Malawi were used to generate measures of infectivity, survival, and adherence. The Markov chain prediction model was used for the analysis of disease progression in treated and untreated patients. A partnership model was used to assess the probability that an infected individual would transmit HIV.Results. Data from 26 565 patients followed up from January 2002 through July 2009 were analyzed with the model; 63% of patients were female, the median age was 35 years, and the median observation time was 25 months. In the model, a 5-fold reduction in infectivity (from 1.6% to 0.3%) occurred within 3 years when triple ART was used. The annual incidence of HIV infection declined from 7% to 2% in 2 years, and the prevalence was halved, from 12% to 6%, in 11 years. Mortality in HIV-infected individuals declined by 50% in 5 years. A cost analysis demonstrated economic efficiency after 4 years.Conclusions. Our model, based on patient data, supports the hypothesis that treatment of all infected individuals translates into a drastic reduction in incident HIV infections. A targeted implementation strategy with massive population coverage is feasible in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]