Vocal emotion processing deficits in HIV-infected individuals.

We aimed to explore the brain imaging correlates of vocal emotion processing in a group of HIV+ individuals and to compare the vocal emotion processing of HIV+ individuals with a group of healthy adults. We conducted multiple linear regressions to determine the cerebral correlates of a newly designed vocal emotion processing test in a sub-group of HIV+ individuals who completed the cerebral magnetic resonance scan (n = 36). Separately, we test whether the association between our test scores and each cerebral measure persisted regardless of the presence of neurocognitive impairment. We also calculated differences in average test scores between the total HIV+ group (n = 100) and a healthy adult group (n = 46). We found a positive association between the test scores and several brain area volumes: right frontal, temporal and parietal lobes, bilateral thalamus, and left hippocampus. We found a negative association between inflammatory markers in frontal white matter and the test scores. After controlling by neurocognitive impairment, several brain area volumes remained positively associated to the prosody test scores. Moreover, the whole HIV+ sample had significantly poorer test scores than healthy adults, but only in the subset of HIV+ individuals with neurocognitive impairment. For the first time, our results suggest that cerebral dysfunctions in particular brain areas involved in the processing of emotional auditory stimuli may occur in HIV+ individuals. These results highlight the need for broad characterization of the neuropsychological consequence of HIV brain damages.

Diffusion Model for Describing the Regional Spread of Huanglongbing from First-Reported Outbreaks and Basing an Area Wide Disease Management Strategy.

Huanglongbing (HLB), a recent worldwide spreading disease on citrus, was detected in July 2009 in Yucatan State of Mexico. The objective of this study was to evaluate the fit of diffusion and classic disease gradient models to large-scale HLB spatial data originated from initial foci to improve sampling, monitoring, and control strategies for Diaphorina citri, vector of Candidatus Liberibacter asiaticus (CLas), putative agent of HLB. Four transect routes were selected: Yuc-1, Yuc-2, QRoo-1, and QRoo-2, based on the directionality of the prevailing winds and foci location of HLB infected plants. In these routes, 35 sites, 5 to 20 km apart, were selected for monthly evaluation during a 12-month period. A 10-insect sample and disease incidence and severity of HLB, further confirmed by PCR, were assessed per site. Mexican lime was more vulnerable (67.5%) than sweet orange (14%). Also, leaf symptoms were mostly found with homogeneous distribution but rarely reaching 100% of the tree canopy during the 12-month period. The diffusion model provided the best fit among the family of time-gradient curves (r2 = 0.90 to 0.99) due to the flexibility of a three-parameter model. The gradients were well conformed to the model in a 25 to 82.6 km range, having the east-west direction the longest effect. Yuc-2 and QRoo-2 transects showed 82.6 and 43.9 km gradients with a diffusion coefficient (Do) of 0.15 and 0.09, respectively. This study constitutes the first quantitative evidence of the regional spread of CLas from a single focus and the application of a flexible model that improved the fit and allowed to better compare different gradients. These results are useful to determine the size of Regional Areas of Diaphorina citri Control (ARCO), a management program currently implemented in Mexico to combat HLB.

Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.

OBJECTIVES: Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). METHODS: A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. RESULTS: After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. CONCLUSIONS: When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.

Decreasing prevalence of HCV coinfection in all risk groups for HIV infection between 2004 and 2011 in Spain.

While hepatitis C virus (HCV) infection seems to be expanding among HIV-infected men who have sex with men (MSM), the rate of coinfection in intravenous drug users (IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV-infected Patients (CoRIS) between 2004 and 2011. We analysed risk factors for HIV/HCV coinfection by logistic regression analyses. The prevalence of HIV/HCV coinfection decreased from 25.3% (95% CI, 23.1-27.5) in 2004-2005 to 8.2% (95% CI, 6.9-9.5) in 2010-2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0-8.9%; and heterosexual women, 14.5-4.0% (all P < 0.05). Strongest risk factors for HIV/HCV coinfection were IDU (OR, 54.9; 95% CI, 39.4-76.4), birth decade 1961-1970 (OR, 2.1; 95% CI, 1.1-3.7) and low educational level (OR, 2.4; 95% CI, 1.6-3.5). Hence, the prevalence of HIV/HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population.

Inequalities in HIV disease management and progression in migrants from Latin America and sub-Saharan Africa living in Spain.

OBJECTIVES: The objective of the study was to analyse key HIV-related outcomes in migrants originating from Latin America and the Spanish-speaking Caribbean (LAC) or sub-Saharan Africa (SSA) living in Spain compared with native Spaniards (NSP). METHODS: The Cohort of the Spanish AIDS Research Network (CoRIS) is an open, prospective, multicentre cohort of antiretroviral-naïve patients representing 13 of the 17 Spanish regions. The study period was 2004-2010. Multivariate logistic or Fine and Gray regression models were fitted as appropriate to estimate the adjusted effect of region of origin on the different outcomes. RESULTS: Of the 6811 subjects in CoRIS, 6278 were NSP (74.2%), LAC (19.4%) or SSA (6.4%). For these patients, the follow-up time was 15870 person-years. Compared with NSP, SSA and LAC under 35 years of age had a higher risk of delayed diagnosis [odds ratio (OR) 2.0 (95% confidence interval (CI) 1.5-2.8) and OR 1.7 (95% CI 1.4-2.1), respectively], as did LAC aged 35-50 years [OR 1.3 (95% CI 1.0-1.6)]. There were no major differences in time to antiretroviral therapy (ART) requirement or initiation. SSA exhibited a poorer immunological and virological response [hazard ratio (HR) [corrected] 0.8 (95% CI 0.7-1.0) and HR [corrected] 0.7 (95% CI 0.6-0.9), respectively], while no difference was found for LAC. SSA and LAC showed an increased risk of AIDS for ages between 35 and 50 years [HR 2.0 (95% CI 1.1-3.7) and HR [corrected] 1.6 (95% CI 1.1-2.4), respectively], which was attributable to a higher incidence of tuberculosis. However, no statistically significant differences were observed in mortality. CONCLUSIONS: Migrants experience a disproportionate diagnostic delay, but no meaningful inequalities were identified regarding initiation of treatment after diagnosis. A poorer virological and immunological response was observed in SSA. Migrants had an increased risk of AIDS, which was mainly attributable to tuberculosis.

Removal of metal ions from aqueous effluents involving new thermosensitive polymeric sorbent.

In this work, new thermosensitive copolymers bearing phosphonated groups were synthesized and used to remove metal pollution. Sorption properties are brought by hydrolyzed (dimethoxyphosphoryl)methyl 2-methylacrylate (hMAPC1) monomer. N-n-propylacrylamide (NnPAAm) led to the thermoresponsive properties of the copolymers. Low lower critical solution temperature (LCST) values were observed, ranging between 20 and 25 °C depending on the molar ratio of each monomer in the copolymer. Sorption properties of these copolymers towards nickel ions were evaluated for increasing temperatures (10-40 °C), Ni ion concentrations of 20 mg L(-1) and pH values between 3 and 7. Best results were observed for temperatures just lower than the LCST (20 °C), when the copolymer was fully soluble in water solution. For temperature higher than the LCST, phosphonic diacid groups accessibility was considerably reduced by the precipitation of the thermosensitive part of the copolymer leading to lower sorption properties. In these conditions, the highest Ni removal by the copolymer was observed for pH = 7, when there was almost no competition between the sorption of H(+) and Ni(2+) ions on the phosphonic acid groups. These optimal conditions enabled removal of about 70% of the nickel in the synthetic effluent.

Specificity and sensibility of the Spanish version of the COMFORT Behaviour Scale for assessing pain, grade of sedation and withdrawal syndrome in the critically ill paediatric patient. Multicentre COSAIP study (Phase 1).

AIM: The main aim of this investigation was to analyse the specificity and sensibility of the COMFORT Behaviour Scale (CBS-S) in assessing grade of pain, sedation, and withdrawal syndrome in paediatric critical care patients. METHOD: An observational, analytical, cross-sectional and multicentre study conducted in Level III Intensive Care Areas of 5 children's university hospitals. Grade of sedation was assessed using the Spanish version of the CBS-S and the Bispectral Index on sedation, once per shift over one day. Grade of withdrawal was determined using the CBS-S and the Withdrawal Assessment Tool-1, once per shift over three days. RESULTS: A total of 261 critically ill paediatric patients with a median age of 5.07 years (P25:0.9-P75:11.7) were included in this study. In terms of the predictive capacity of the CBS-S, it obtained a Receiver Operation Curve of .84 (sensitivity of 81% and specificity of 76%) in relation to pain; .62 (sensitivity of 21% and specificity of 78%) in relation to sedation grade, and .73% (sensitivity of 40% and specificity of 74%) in determining withdrawal syndrome. CONCLUSIONS: The Spanish version of the COMFORT Behaviour Scale could be a useful, sensible and easy scale to assess the degree of pain, sedation and pharmacological withdrawal of critically ill paediatric patients.

Comparative analysis of environmental noise levels in two paediatric intensive care units. / Niveles de ruido ambiental en dos unidades de cuidados intensivos pediátricos con diferente infraestructura.

AIMS: 1) To determine noise levels in two paediatric intensive care units (PICU) of a tertiary hospital and 2) to analyse whether these values comply with the current standards. METHOD: Observational, descriptive and cross-sectional study carried out in two PICU with different infrastructure: bays separated by curtains and individual bedrooms. A PCE-999 sound level meter was used to determine noise levels, which were registered in decibels (dB). At the same time, an ad hoc data recording document was designed in which we differentiated between each unit (open concept or closed), time of recording. RESULTS: A total of 330 tests, 72 from open PICUs and 258 from closed PICUs were collected. The noise in the open PICU was 56.74 ± 3.61 decibels versus 50.36 ± 4.71 in the closed PICU, obtaining the highest levels during the morning. DISCUSSION: As it occurs in other studies, noise levels exceed the allowed limits. At the same time, the main sources of noise in the PICU came from alarms, medical equipment, such as monitors or respirators, and conversations between health professional. CONCLUSIONS: This investigation has shown high levels of environmental noise in the two PICUs analysed. The data obtained indicate that the architectural concept of individual bedrooms may have an impact in decreasing this environmental input.

Specificity and sensibility of the Spanish version of the COMFORT Behaviour Scale for assessing pain, grade of sedation and withdrawal syndrome in the critically ill paediatric patient. Multicentre COSAIP study (Phase 1). / Especificidad y sensibilidad de la COMFORT Behavior Scale-Versión española para valorar el dolor, el grado de sedación y síndrome de abstinencia en el paciente crítico pediátrico. Estudio multicéntrico COSAIP (Fase 1).

AIM: The main aim of this investigation was to analyse the specificity and sensibility of the COMFORT Behaviour Scale (CBS-S) in assessing grade of pain, sedation, and withdrawal syndrome in paediatric critical care patients. METHOD: An observational, analytical, cross-sectional and multicentre study conducted in Level III Intensive Care Areas of 5 children's university hospitals. Grade of sedation was assessed using the Spanish version of the CBS-S and the Bispectral Index on sedation, once per shift over one day. Grade of withdrawal was determined using the CBS-S and the Withdrawal Assessment Tool-1, once per shift over three days. RESULTS: A total of 261 critically ill paediatric patients with a median age of 5.07 years (P25:0.9-P75:11.7) were included in this study. In terms of the predictive capacity of the CBS-S, it obtained a Receiver Operation Curve of .84 (sensitivity of 81% and specificity of 76%) in relation to pain; .62 (sensitivity of 21% and specificity of 78%) in relation to sedation grade, and .73% (sensitivity of 40% and specificity of 74%) in determining withdrawal syndrome. CONCLUSIONS: The Spanish version of the COMFORT Behaviour Scale could be a useful, sensible and easy scale to assess the degree of pain, sedation and pharmacological withdrawal of critically ill paediatric patients.

Grade of sedation in the critically ill pediatric patient and its correlation with sociodemographic and clinical variables. Multicentre COSAIP study.

AIMS: To determine the grade of sedation in the critically ill paediatric patient using Biespectral Index Sensor (BIS) and to analyse its relationship with sociodemographic and clinical patient variables. METHODS: Observational, analytical, cross-sectional and multicentre study performed from May 2018 to January 2020 in 5 Spanish paediatric critical care units. Sex, age, reason for admission, presence of a chronic pathology, type and number of drugs and length of stay were the sociodemographic and clinical variables registered. Furthermore, the grade of sedation was assessed using BIS, once per shift over 24 h. RESULTS: A total of 261 paediatric patients, 53.64% of whom were male, with a median age of 1.61 years (0.35-6.55), were included in the study. Of the patients, 70.11% (n = 183) were under analgosedation and monitored using the BIS sensor. A median of BIS values of 51.24 ±â€¯14.96 during the morning and 50.75 ±â€¯15.55 during the night were observed. When comparing BIS values and sociodemographic and clinical paediatric variables no statistical significance was detected. CONCLUSIONS: Despite the limitations of the BIS, investigations and the present study show that BIS could be a useful instrument to assess grade of sedation in critically ill paediatric patients. However, further investigations which determine the sociodemographic and clinical variables involved in the grade of paediatric analgosedation, as well as studies that contrast the efficacy of clinical scales like the COMFORT Behaviour Scale-Spanish version, are required.

Grade of sedation in the critically ill paediatric patient and its correlation with sociodemographic and clinical variables. Multicentre COSAIP study. / Grado de sedación del paciente crítico pediátrico y variables sociodemográficas y clínicas correlacionadas. Estudio multicéntrico COSAIP.

AIMS: To determine the grade of sedation in the critically ill paediatric patient using Biespectral Index Sensor (BIS) and to analyse its relationship with sociodemographic and clinical patient variables. METHODS: Observational, analytical, cross-sectional and multicentre study performed from May 2018 to January 2020 in 5 Spanish paediatric critical care units. Sex, age, reason for admission, presence of a chronic pathology, type and number of drugs and length of stay were the sociodemographic and clinical variables registered. Furthermore, the grade of sedation was assessed using BIS, 11per shift over 24hours. RESULTS: A total of 261 paediatric patients, 53.64% of whom were male, with a median age of 1.61 years (0.35-6.55), were included in the study. Of the patients, 70.11% (n=183) were under analgosedation and monitored using the BIS sensor. A median of BIS values of 51.24±14.96 during the morning and 50.75±15.55 during the night were observed. When comparing BIS values and sociodemographic and clinical paediatric variables no statistical significance was detected. CONCLUSIONS: Despite the limitations of the BIS, investigations and the present study show that BIS could be a useful instrument to assess grade of sedation in critically ill paediatric patients. However, further investigations which determine the sociodemographic and clinical variables involved in the grade of paediatric analgosedation, as well as studies that contrast the efficacy of clinical scales like the COMFORT Behaviour Scale-Spanish version, are required.

Validity of contents of a paediatric critical comfort scale using mixed methodology. / Validez de contenido de una escala de confort crítico pediátrico mediante una metodología mixta.

INTRODUCTION: Critical illness in paediatric patients includes acute conditions in a healthy child as well as exacerbations of chronic disease, and therefore these situations must be clinically managed in Critical Care Units. The role of the paediatric nurse is to ensure the comfort of these critically ill patients. To that end, instruments are required that correctly assess critical comfort. OBJECTIVE: To describe the process for validating the content of a paediatric critical comfort scale using mixed-method research. MATERIAL AND METHODS: Initially, a cross-cultural adaptation of the Comfort Behavior Scale from English to Spanish using the translation and back-translation method was made. After that, its content was evaluated using mixed method research. This second step was divided into a quantitative stage in which an ad hoc questionnaire was used in order to assess each scale's item relevance and wording and a qualitative stage with two meetings with health professionals, patients and a family member following the Delphi Method recommendations. RESULTS: All scale items obtained a content validity index >0.80, except physical movement in its relevance, which obtained 0.76. Global content scale validity was 0.87 (high). During the qualitative stage, items from each of the scale domains were reformulated or eliminated in order to make the scale more comprehensible and applicable. CONCLUSIONS: The use of a mixed-method research methodology during the scale content validity phase allows the design of a richer and more assessment-sensitive instrument.

Construction and feasibility study of the SOFMER Activity Score (SAS), a new assessment of physical and cognitive activity.

OBJECTIVES: For hospitalizations in rehabilitation centers (RCs) in France, the quantification of healthcare givers' activity is based on the dependency of the patients, defined as a total or partial inability to perform activities required for daily living without help. The tools currently used to quantify dependency are not sufficiently precise. Here we describe the construction of a new tool, the SOFMER Activity Score (SAS scoring), which allows for a good description of the level of activity of patients hospitalized in RCs, and a feasibility study of the tool. METHODS: After a study group proposed the first version of the SAS, the validity of its content was studied by the Delphi consensus method: 26 physicians or healthcare professionals known for their expertise in PMR responded to the first round. The feasibility study was prospective and involved multi-site professionals. Data related to the SAS determined by a multidisciplinary team were collected and compared to the Activité de la Vie Quotidienne (AVQ) scale, which is administered to all patients and included in medical and administrative data. RESULTS: We included 81 patients in the feasibility study. The mean (SD) time to obtain the SAS was 4.5 (3.3) min. For 97.5% of scorings, the participating professionals judged that the SAS was compatible or fairly compatible with clinical practice. The internal structure of the SAS scale seemed better than that of the AVQ scale, for which the present study confirmed a floor effect for all items. CONCLUSIONS: The SAS allows for measuring the level of physical and cognitive activity of a patient hospitalized in an RC. If validation studies for the SAS, exploring its reliability, construct validity or criterion validity, confirm the tool's good metrological qualities, the SAS will allow for a good quantification of the burden of care.

Especificidad y sensibilidad de la COMFORT Behavior Scale-Versión española para valorar el dolor, el grado de sedación y síndrome de abstinencia en el paciente crítico pediátrico. Estudio multicéntrico COSAIP (Fase 1) / Specificity and sensibility of the Spanish version of the COMFORT Behaviour Scale for assessing pain, grade of sedation and withdrawal syndrome in the critically ill paediatric patient. Multicentre COSAIP study (Phase 1)

Objetivo: El objetivo principal de la investigación fue analizar la especificidad y sensibilidad de la escala COMFORT Behavior Scale-Versión española (CBS-ES) en la determinación del grado de dolor, sedación y síndrome de abstinencia.Método: Se llevó a cabo un estudio observacional, analítico y transversal y multicéntrico en unidades de cuidados intensivos pediátricas de 5 hospitales españoles. Se valoró el grado de sedación del paciente crítico pediátrico de forma simultánea empleando para ello la CBS-ES y registrando los valores del Bispectral Index Sedation, una vez por turno durante un día. El grado de abstinencia se determinó una vez por turno, durante 3 días, empleando de forma simultánea la CBS-ES y la Withdrawal Assessment Tool-1.Resultados: Se incluyeron en el estudio un total de 261 pacientes críticos pediátricos con una mediana de 1,61 años (P25: 0,35-P75: 6,55). Por lo que a la capacidad predictiva de la CBS-ES se refiere se obtuvo un área bajo la curva de 0,84 (sensibilidad del 81% y especificidad del 76%) con relación al dolor; de 0,62 (sensibilidad del 27% y especificidad del 78%) en el caso de la sedación, y de 0,73 (sensibilidad del 40% y especificidad del 74%) en el del síndrome de abstinencia.Conclusiones: Se ha podido contrastar que la CBS-ES podría ser un instrumento sensible, útil y fácil de emplear para valorar el grado de dolor, sedación y síndrome de abstinencia farmacológico del paciente crítico pediátrico.

Aim: The main aim of this investigation was to analyse the specificity and sensibility of the COMFORT Behaviour Scale (CBS-S) in assessing grade of pain, sedation, and withdrawal syndrome in paediatric critical care patients.Method: An observational, analytical, cross-sectional and multicentre study conducted in Level III Intensive Care Areas of 5 children's university hospitals. Grade of sedation was assessed using the Spanish version of the CBS-S and the Bispectral Index on sedation, once per shift over one day. Grade of withdrawal was determined using the CBS-S and the Withdrawal Assessment Tool-1, once per shift over three days.Results: A total of 261 critically ill paediatric patients with a median age of 5.07 years (P25:0.9-P75:11.7) were included in this study. In terms of the predictive capacity of the CBS-S, it obtained a Receiver Operation Curve of .84 (sensitivity of 81% and specificity of 76%) in relation to pain; .62 (sensitivity of 21% and specificity of 78%) in relation to sedation grade, and .73% (sensitivity of 40% and specificity of 74%) in determining withdrawal syndrome.Conclusions: The Spanish version of the COMFORT Behaviour Scale could be a useful, sensible and easy scale to assess the degree of pain, sedation and pharmacological withdrawal of critically ill paediatric patients.

Functionalization of titanium oxide surfaces by means of poly(alkyl-phosphonates).

The use of a multiple attachment sites strategy is considered in order to improve the stability of monomolecular adlayers. The hypothesis was tested in the case of PEG-ylated compounds carrying phosphonate groups, known for their affinity toward titanium oxide surfaces. As a result, a new class of co- and terpolymers were synthesized by free-radical polymerization of three different monomers: dialkyl(methacryloyloxyalkyl)phosphonates, PEG methyl ether methacrylate, and/or butyl methacrylate monomers. Adlayers were formed following a simple dip-and-rinse protocol using diluted aqueous polymer solutions and were characterized by evaluating their thicknesses with variable angle spectroscopic ellipsometry (VASE) and their elemental compositions with X-ray photoelectron spectroscopy (XPS). The same techniques were used to determine changes of the adlayer as a function of exposure to electrolytes at different pH values and to monitor nonspecific protein adsorption upon serum exposures. The results indicated that the poly(alkyl-phosphonate)-based adlayers combine multiple site attachment of phosphonic groups and presentation of PEG side chains to the aqueous environment, resulting in both improved stability over a wide pH range in comparison to the tested reference surfaces and excellent resistance to protein adsorption when exposed to full human serum.

Transmitted drug resistance to rilpivirine in newly diagnosed antiretroviral naive adults.

We characterized transmitted drug resistance to rilpivirine and the predicted efficacy of first-line rilpivirine-containing regimens in antiretroviral-naive Spanish patients. International Antiviral Society-USA mutations were detected in 138 of 2781 patients (4.9%), E138A (3.4%) being the most prevalent. Using the Stanford Algorithm, 121 patients (4.4%) showed low-level or intermediate resistance. No differences in the predicted efficacy of first-line non-nucleoside reverse transcriptase inhibitor-based regimens were observed. As rilpivirine becomes more widely used in clinical practice, the evolution of its transmitted drug resistance will need to be monitored. In addition, the exact role of E138A singletons on rilpivirine activity as part of first-line regimens merits further evaluation.

Use of cohort data to estimate national prevalence of transmitted drug resistance to antiretroviral drugs in Spain (2007-2012).

Prevalence of transmitted drug resistance (pTDR) to antiretroviral drugs in Spain (2007-2012) was estimated using the CoRIS cohort, adjusting its territorial distribution and transmission route to the reference population from the Spanish Information System on New human immunodeficiency virus diagnoses. A total of 2702 patients from ten autonomous communities and with naive FASTA sequence within 6 months of human immunodeficiency virus diagnosis were selected. Weighted pTDR, estimated using the inverse probability of selection in the sample by autonomous communities and transmission group, was 8.12% (95% CI 6.44-9.80), not significantly different from unweighted pTDR. We illustrate how proportional weighting can maximize representativeness of cohort-based data, and its value to monitor pTDR at country level.

Contribution of the anomeric effect to the solution and crystal structure of [1S,2S,6S,7s]-1,6-diaza-4,9-dioxa-2,7-dimethoxycarbonylbicyclo[4.4.1]undecane, a condensation product of L-serine methyl ester with formaldehyde.

The reaction of L-serine methyl ester hydrochloride (1) with paraformaldehyde (2) in dichloromethane in the presence of triethylamine afforded a novel compound: [lS,2S,6S,7S]-1,6-diaza-4,9-dioxa-2,7-dimethoxycarbonylbicyclo[4.4.1]undecane (4) as a 2:3 adduct of 1 with 2. 1H and 13C NMR spectroscopy were unable to discriminate between two possible symmetrical structures. The latter was unambiguously proved by X-ray crystallography. The crystal structure established: (i) the existence of two identical seven-membered rings each containing a N-C-O grouping; (ii) the existence of a long C-O-C-N-C-N-C-O-C sequence in which each nitrogen belongs simultaneously to a N-C-O (oxazolidine) and to a N-C-N (aminal) motifs; (iii) the existence of a chair-like conformation for both seven-membered rings; (iv) the antiperiplanar geometry of pN-C-O and consequently the manifestation of a strong anomeric effect in both N-C-O groupings, whereas anomeric effect was virtually absent in the N-C-N sequence, as corroborated by bond distances and bond angles. Chemical shifts, coupling constants and NOE effects confirm that the conformational features of 4 are preserved in solution.

Anomeric effects in non-carbohydrate compounds: conformational differences between the oxazolidine rings of a cis-fused bicyclic system.

Tris(hydroxymethyl)aminomethane (Tris) can react with benzaldehyde (1:2 molar ratio) to produce cis-2,8-diphenyl-5-hydroxymethyl-1-aza-3,7-dioxabicyclo[3.3.0]octa ne, the structure of which has been confirmed by nuclear magnetic resonance spectroscopy and X-ray crystallography. The crystal structure showed that both oxazolidine rings A and B are puckered in opposite directions. Ring A exists in an E3 envelope form with 0-3 noticeably down (0.65 A) the plane of the remaining atoms, whereas ring B adopts the 7E envelope conformation with the 0-7 atom displaced up from the mean reference plane by 0.70 A. Comparison of bond angles and bond distances showed that both oxazolidine rings A and B exhibit cross endo-anomeric effects resulting from electron delocalization over the bond sequence O-3-C-2-N-1-C-8-O-7.

Tuberculosis in a cohort of HIV-positive patients: epidemiology, clinical practice and treatment outcomes.

OBJECTIVE: To describe tuberculosis (TB) incidence, risk factors, clinical presentation, disease management and outcomes in human immunodeficiency virus (HIV) infected patients from the CoRIS cohort, Spain, 2004-2010. DESIGN: Open multicentre cohort of antiretroviral treatment (ART) naïve patients at entry. Incidence and risk factors were evaluated using multivariate Poisson regression. RESULTS: Among 6811 patients, 271 were eligible for the study and 198 for the estimation of the incidence rate; TB incidence ranged from 12.1 to 14.1/1000 person-years. TB was associated with low education level (rate ratio [RR] 2.65, 95%CI 1.73-4.07), being sub-Saharan African (RR 3.14, 95%CI 1.81-5.45), heterosexual (RR 2.01, 95%CI 1.22-3.29) or an injecting drug user (RR 2.11, 95%CI 1.20-3.69), not undergoing ART (RR 3.33, 95%CI 2.22-4.76), CD4 <200 cells/mm(3) (RR 5.20, 95%CI 3.25-8.33) and log-viral load of 4-5 (RR 5.44, 95%CI 3.28-9.02) or >5 (RR 13.10, 95%CI 8.27-20.76). Overall, 87% were new cases and 13% were previously treated cases; 175 (65%) were bacteriologically confirmed. Drug susceptibility testing was performed in 146 (83%) patients: resistance to first-line drugs was 11.1% in new and 36.4% in previously treated cases. Standard anti-tuberculosis treatment with four or three drugs was prescribed in respectively 55% and 36% of cases. Treatment default was 11%, and was higher among previously treated cases; 80% received ART during anti-tuberculosis treatment, 80% of new and 50% of previously treated cases were cured or completed treatment, and 18 (6.6%) died. CONCLUSION: TB incidence in HIV-infected patients remains high. Interventions should include early HIV diagnosis and access to ART, enhanced bacteriological confirmation, wider use of four-drug regimens and reduction in treatment default.