To investigate the accuracy of electrical cardiometry (EC) to measure stroke volume (SV) and cardiac output (CO) and to provide gestational age (GA) and birth weight (BW)-based reference data for SV ...and CO in hemodynamically stable preterm neonates.
Prospective observational blinded study. Paired measurements of SV and CO on stable preterm infants without any hemodynamic compromise were carried out using EC (SVEC) and echocardiography (SVECHO).
Seventy-nine preterm neonates (mean GA: 31±3.2 weeks) were enrolled. A good correlation was found for SV (r=0.743; P<0.0001) and CO (r=0.7; P<0.0001) measured by EC and echocardiography. These correlations remained significant after adjusting for GA, patent ductus arteriosus and type of respiratory support (SV: St.β=0.48, P<0.0001 and CO: St.β=0.69, P<0.0001). Mean biases (and variabilities) were -1.1 (from 0.7 to -2.9) ml and -0.21 (from 0.15 to -0.55) l min(-1) for SV and CO, respectively. Local regression shows a tendency for EC to overestimate SV and CO especially at higher values (at about >2 ml and >0.4 l min(-1), respectively). Coefficient of variation of SV was 48.9% and 52%, for EC and echocardiography. SV and CO rose with increasing GA and BW following an exponential equation (R(2)>0.8).
Measuring SV and CO with EC in hemodynamically stable preterm infants shows good correlation and variability similar to that of echocardiography. A trend to overestimation exists at highest values, but it is unlikely to be clinically significant. Reference GA and BW-based nomograms for SV and CO are provided.
A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are ...clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown.
We randomly assigned 1844 women in Thailand who received zidovudine during the third trimester of pregnancy to receive intrapartum nevirapine or placebo. In the postpartum period, 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapine-containing antiretroviral regimen. Plasma samples were obtained 10 days post partum and analyzed for resistance mutations. Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of therapy and three and six months thereafter.
After six months of therapy, the HIV-1 RNA level was less than 50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine, as compared with 68 percent of the women who had not received intrapartum nevirapine (P=0.03). Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations were K103N, G190A, and Y181C. Among the women who had received intrapartum nevirapine, viral suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of those without resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53 log10 copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated with virologic failure. After six months of therapy, there was no significant difference between groups in the CD4 count (P=0.65).
Women who received intrapartum nevirapine were less likely to have virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen. Our data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral therapy for mothers.
Background. The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)–infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. ...Methods. We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged <16 years at cART initiation from 1996 onward. We used Cox models to calculate hazard ratios (HRs), adjusted for region and origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation. Results. We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval CI, 55–133), 11 in southern Africa (95% CI, 4–35), and 81 (95% CI, 26–252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0–50) and in Asia (95% CI, 0–27). KS risk was lower in girls than in boys (adjusted HR aHR, 0.3; 95% CI, .1–.9) and increased with age (10–15 vs 0–4 years; aHR, 3.4; 95% CI, 1.2–10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8–7.3) at cART initiation. Conclusions. HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk.
The aims of the paper are to examine the role of burnout in the relationship between stress factors related to nurses’ work and social environment and intention to leave the profession and to ...investigate the nature of the relationship between burnout and intention to leave the nursing profession.
A postulate of the job demands–resources model is that two distinct yet related processes contribute to the development of burnout. The energetic process originates from demands and is
mainly centered on emotional exhaustion; the motivational process originates from resources and is
mainly centered on depersonalization. Moreover, we postulated that the two components of burnout are linked indirectly to intention to leave the profession via psychosomatic complaints, associated with the energetic process, and via professional commitment, associated with the motivational process.
The research model was tested on cross-sectional data collected in 2005 from 1636 registered nurses working in hospitals who responded to a self-administrated questionnaire.
Demands are the most important determinants of emotional exhaustion and indirectly induce depersonalization via emotional exhaustion, whereas resources mainly predict depersonalization. Moreover, emotional exhaustion and depersonalization are linked to psychosomatic complaints and professional commitment, which are in turn associated with intention to leave the profession.
The results suggest that a dual strategy is needed in order to retain nurses within the profession: a decrease in job demands, coupled with an increase in available job resources. In particular, nurses’ tasks and role should be restructured to reduce work overload and increase the meaning of their work.
Objectives
The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART).
Methods
Data from ...paediatric HIV‐infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r‐ART) and in the long term (up to 24 months after r‐ART) following the first TI was modelled using asymptotic regression.
Results
In 779 children with at least one TI, the median age at first TI was 10.1 interquartile range (IQR) 6.4, 13.6 years and the mean CD4% was 27.3% standard deviation (SD) 11.0%; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% 95% confidence interval (CI) 18.3, 20.1% at r‐ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r‐ART and long‐term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long‐term CD4% was highest in those with a TI lasting 1 to <3 months, those with r‐ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%.
Conclusions
After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.
Objectives To investigate the association of single nucleotide polymorphisms (SNPs) with nevirapine concentrations following intra-partum single-dose nevirapine. Methods Plasma and DNA samples were ...obtained from 330 HIV-infected Thai women who received intra-partum single-dose nevirapine in the PHPT-2 clinical trial to prevent perinatal HIV transmission. Nine SNPs within CYP2B6, CYP3A4 and ABCB1 were genotyped by real-time PCR. Nevirapine plasma concentrations were determined by HPLC and used in a population pharmacokinetic analysis. Results Higher nevirapine exposure was observed in women carrying the CYP2B6 516G>T polymorphism, but this did not reach statistical significance (P = 0.054). The TGATC CYP2B6 haplotype (g.3003T, 516G, 785A, g.18492T and g.21563C) was associated with increased nevirapine clearance and lower exposure (P = 0.0029). The median time for nevirapine concentrations to reach 10 ng/mL post-partum (nevirapine IC50 for HIV-1) was 14 days interquartile range (IQR, 14–18) for TGATC homozygotes, 16 days (14–20) for TGATC heterozygotes and 18 days (14–20) for non-TGATC homozygotes (P = 0.020). Conclusions The CYP2B6 516G>T impact on nevirapine concentrations was less pronounced after intra-partum single-dose nevirapine than reported under steady-state conditions, perhaps due to lack of enzyme auto-induction at the time of dosing. Although the TGATC CYP2B6 haplotype may shorten the persistence of nevirapine post-partum, its practical implications for the prevention of HIV transmission or selection of resistance mutations are likely limited.
Introduction
The clinical relevance of low‐level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV ...on virological failure (VF) among Asian CLHIV on first‐line combination antiretroviral therapy (cART).
Methods
CLHIV aged <18 years, who were on first‐line cART for ≥12 months, and had virological suppression (two consecutive plasma viral load pVL <50 copies/mL) were included. Those who started treatment with mono/dual antiretroviral therapy, had a history of treatment interruption >14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF.
Results
From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non‐nucleoside reverse transcriptase inhibitor‐based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow‐up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person‐years of follow‐up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU; p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60).
Conclusions
LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first‐line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF.
Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil.
To describe the incidence, presentation, treatment and treatment outcomes of ...tuberculosis (TB) in human immunodeficiency virus (HIV) infected children.
Observational study of TB diagnosed in HIV-infected children in 2011-2013.
Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0-11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes.
Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention.
Objectives
The aim of the study was to assess the prevalence, predictors and patterns of genotypic resistance mutations in children after failure of World Health Organization‐recommended initial ...nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based treatment regimens.
Methods
We carried out a multicentre retrospective study of genotyping tests performed for all HIV‐infected children at eight paediatric centres in Thailand who experienced failure of NNRTI therapy at a time when virological monitoring was not routinely available.
Results
One hundred and twenty children were included in the study. Their median age (interquartile range) was 9.1 (6.8–11.0) years, the median duration of their NNRTI regimens was 23.7 (15.7–32.6) months, their median CD4 percentage was 12% (4–20%), and their median plasma HIV RNA at the time of genotype testing was 4.8 (4.3–5.2) log10 HIV‐1 RNA copies/mL. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the Q151M complex, 5% had K65R, and 1% had the 69 insertion. Ninety‐eight per cent of the children had at least one NNRTI resistance mutation, and 48% had etravirine mutation‐weighted scores ≥4. CD4 percentage <15% prior to switching regimens odds ratio (OR) 5.49; 95% confidence interval (CI) 2.02–14.93 and plasma HIV RNA>5 log10 copies/mL (OR 2.46; 95% CI 1.04–5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion.
Conclusions
In settings without routine viral load monitoring, second‐line antiretroviral therapy regimens should be designed assuming that clinical or immunological failure is associated with high rates of multi‐NRTI resistance and NNRTI resistance, including resistance to etravirine.
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