A comprehensive assessment of care competence and maternal experience of first antenatal care visits in Mexico: Insights from the baseline survey of an observational cohort study.

BACKGROUND: Comprehensive antenatal care (ANC) must prioritize competent, evidence-based medical attention to ensure a positive experience and value for its users. Unfortunately, there is scarce evidence of implementing this holistic approach to ANC in low- and middle-income countries, leading to gaps in quality and accountability. This study assessed care competence, women's experiences during the first ANC visit, and the factors associated with these care attributes. METHODS AND FINDINGS: The study analyzed cross-sectional baseline data from the maternal eCohort study conducted in Mexico from August to December 2023. The study adapted the Quality Evidence for Health System Transformation (QuEST) network questionnaires to the Mexican context and validated them through expert group and cognitive interviews with women. Pregnant women aged 18 to 49 who had their first ANC visit with a family physician were enrolled in 48 primary clinics of the Instituto Mexicano del Seguro Social across 8 states. Care competence and women's experiences with care were the primary outcomes. The statistical analysis comprised descriptive statistics, multivariable linear and Poisson regressions. A total of 1,390 pregnant women were included in the study. During their first ANC visit, women received only 67.7% of necessary clinical actions on average, and 52% rated their ANC experience as fair or poor. Women with previous pregnancies (adjusted regression coefficient [aCoef.] -3.55; (95% confidence intervals [95% CIs]): -4.88, -2.22, p < 0.001), at risk of depression (aCoef. -3.02; 95% CIs: -5.61, -0.43, p = 0.023), those with warning signs (aCoef. -2.84; 95% CIs: -4.65, -1.03, p = 0.003), common pregnancy discomforts (aCoef. -1.91; 95% CIs: -3.81, -0.02, p = 0.048), or those who had a visit duration of less than 20 minutes (<15 minutes: aCoef. -7.58; 95% CIs: -10.21, -4.95, p < 0.001 and 15 to 19 minutes: aCoef. -2.73; 95% CIs: -4.79, -0.67, p = 0.010) and received ANC in the West and Southeast regions (aCoef. -5.15; 95% CIs: -7.64, -2.66, p < 0.001 and aCoef. -5.33; 95% CIs: -7.85, -2.82, p < 0.001, respectively) had a higher probability of experiencing poorer care competence. Higher care competence (adjusted prevalence ratio [aPR] 1.004; 95% CIs:1.002, 1.005, p < 0.001) and receiving care in a small clinic (aPR 1.19; 95% CIs: 1.06, 1.34, p = 0.003) compared to a medium-sized clinic were associated with a better first ANC visit experience, while common pregnancy discomforts (aPR 0.94; 95% CIs: 0.89, 0.98, p = 0.005) and shorter visit length (aPR 0.94; 95% CIs: 0.88, 0.99, p = 0.039) were associated with lower women's experience. The primary limitation of the study is that participants' responses may be influenced by social desirability bias, leading them to provide socially acceptable responses. CONCLUSIONS: We found important gaps in adherence to ANC standards and that care competence during the first ANC visit is an important predictor of positive user experience. To inform quality improvement efforts, IMSS should institutionalize the routine monitoring of ANC competencies and ANC user experience. This will help identify poorly performing facilities and providers and address gaps in the provision of evidence-based and women-centered care.

A comprehensive, predictive mortality score for patients with bloodstream infections (PROBAC): a prospective, multicentre cohort study.

OBJECTIVES: Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort. METHODS: A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC. RESULTS: Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70 mmHg and PaO2/FiO2 ≤ 300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%-14% for 3-7 points, 26%-45% for 8-12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79-0.83) in the DC and 0.80 (0.78-0.83) in the VC. CONCLUSIONS: A 30 day mortality predictive score in BSI with good discrimination ability was developed and internally validated.

Prevalence of people living with multidrug-resistant HIV and limited treatment options in Spain.

OBJECTIVES: Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) with multidrug resistance (MDR; confirmed resistance to three or more [or resistance to two or more plus contraindication to one or more] core ART classes) and limited treatment options (LTOs) in Spain. METHODS: This was an observational, retrospective, multicentre, cross-sectional chart review study undertaken in five reference Spanish centres. Participants were people with HIV on ART with MDR and LTOs (detectable viral load [HIV-RNA >200 copies/mL], treatment-limiting drug-drug interaction [DDI], or intolerance precluding the use of one or more ART classes). Prevalence, demographic/clinical characteristics, and treatment options were assessed. Logistic regression analyses were used to identify MDR-associated variables. RESULTS: Of 14 955 screened people with HIV, 69 (0.46%) presented with MDR and 23 (0.15%) had LTOs. The population analysed was 73.9% male with a median age of 54.0 years; the median time since HIV diagnosis was 26.5 years, and median CD4+ cell count was 511.0 cells/µL. The only factor significantly associated with MDR (univariate analysis) was CD4+ cell count. Injection drug use was the most common transmission route. Comorbidities (mainly endocrine and cardiovascular disorders; 34.8% affecting HIV management) and concomitant treatments were frequent. No recent opportunistic infections were reported. Patients had been exposed to the following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease inhibitors (95.6%), non-nucleoside analogue reverse transcriptase inhibitors (87.0%), and integrase strand transfer inhibitors (82.6%). The available fully active drugs were dolutegravir (39.1%), bictegravir (30.4%), and raltegravir (21.7%). CONCLUSIONS: The prevalence of people with HIV with MDR and LTOs in Spain is very low, with approximately half of those studied not exhibiting virological suppression. Low CD4+ cell counts were associated with MDR. These findings may help address the impact and treatment needs of these patients and prevent clinical progression and transmission of MDR HIV.

Clinical characteristics, predisposing factors and outcomes for Enterococcus faecalis versus Enterococcus faecium bloodstream infections: a prospective multicentre cohort study.

PURPOSES: Enterococcal BSI is associated with significant morbidity and mortality, with fatality rates of approximately 20-30%. There are microbiological and clinical differences between E. faecalis and E. faecium infections. The aim of this study was to investigate differences in predisposing factors for E. faecalis and E. faecium BSI and to explore prognostic factors. METHODS: This study was a post-hoc analysis of PROBAC, a Spanish prospective, multicenter, cohort in 2016-2017. Patients with E. faecalis or E. faecium BSI were eligible. Independent predictors for BSI development in polymicrobial and monomicrobial BSI and in-hospital mortality in the monomicrobial group were identified by logistic regression. RESULTS: A total of 431 patients were included. Independent factors associated with E. faecium BSI were previous use of penicillins (aOR 1.99 (95% CI 1.20-3.32)) or carbapenems (2.35 (1.12-4.93)), hospital-acquired BSI (2.58 (1.61-4.12)), and biliary tract source (3.36 (1.84-6.13)), while congestive heart failure (0.51 (0.27-0.97)), cerebrovascular disease (0.45 (0.21-0.98)), and urinary tract source (0.49 (0.26-0.92)) were associated with E. faecalis BSI. Independent prognostic factors for in-hospital mortality in E. faecalis BSI were Charlson Comorbidity Index (1.27 (1.08-1.51)), SOFA score (1.47 (1.24-1.73)), age (1.06 (1.02-1.10)), and urinary/biliary source (0.29 (0.09-0.90)). For E. faecium BSI, only SOFA score (1.34 (1.14-1.58) was associated with in-hospital mortality. CONCLUSIONS: The factors associated with E. faecium and E. faecalis BSI are different. These variables may be helpful in the suspicion of one or other species for empiric therapeutic decisions and provide valuable information on prognosis.

Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study.

BACKGROUND: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. METHODS: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. RESULTS: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. CONCLUSIONS: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.

May Measurement Month 2021: an analysis of blood pressure screening results from Mexico.

May Measurement Month 2021 (MMM21) in Mexico was an opportunistic survey that aimed to improve blood pressure awareness at the individual and population levels and to analyse the impact of the COVID-19 pandemic on the prevalence, knowledge, and rates of hypertension in the country. This survey followed the methodology of MMM, previously published. The total number of participants screened was 77 547, of which 47 793 (61.6%) were female and 29 178 (37.6%) were male. The mean age (SD) was 46.2 (16.6) years. Of all 77 547 participants, 14 939 (19.3%) had hypertension, of which 48% were aware. The frequency and awareness of hypertension in this survey are similar to those reported before the pandemic (MMM19-Mexico and the 2019 National Health Survey), suggesting that the impact of the COVID-19 pandemic in these parameters of arterial hypertension was not as important as expected. These data are concordant with the official reports in Mexico that showed that the pandemic had a severe impact on cardiovascular mortality but did not modify mortality due to hypertension or stroke.

Decay kinetics of HIV-1-RNA in seminal plasma with dolutegravir/lamivudine versus dolutegravir plus emtricitabine/tenofovir alafenamide in treatment-naive people living with HIV.

BACKGROUND: This was a substudy of a Phase IV, randomized clinical trial (ClinicalTrials.gov identifier: NCT04295460) aiming to compare the activity of dolutegravir/lamivudine versus dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) in the male genital tract. METHODS: Participants were asymptomatic adults without sexually transmitted diseases, treatment-naive people living with HIV (PLWH), with CD4+ T cell counts >200 cells/mm3 and plasma HIV-1-RNA levels >5000 and <500 000 copies/mL, randomized (1:1) to DTG + TAF/FTC or dolutegravir/lamivudine. Blood plasma (BP) and seminal plasma (SP) were collected at baseline and Weeks 4, 8, 12 and 24. HIV-1-RNA was measured in BP and SP using the Cobas 6800 system (Roche Diagnostics) with a lower detection limit of 20 copies/mL. The primary efficacy endpoint was the proportion of subjects with undetectable SP HIV-1-RNA at Week 12 by intention-to-treat analysis. RESULTS: Fifteen participants in the DTG + TAF/FTC and 16 in the dolutegravir/lamivudine arms were analysed, with basal SP viral load of 4.81 (4.30-5.43) and 4.76 (4.09-5.23), P = 0.469, respectively. At Week 12, only one participant in each treatment arm had a detectable SP HIV-1-RNA (DTG + TAF/FTC, 141 copies/mL; dolutegravir/lamivudine, 61 copies/mL). Based on the estimated means, there was no significant difference in the decay of HIV-1-RNA in both BP and SP over time between the two arms of treatment (F = 0.452, P = 0.662, and F = 1.147, P = 0.185, respectively). CONCLUSIONS: After 12 weeks of treatment, there were no differences in the percentage of undetectable SP HIV-1-RNA in naive PLWH who started dolutegravir/lamivudine compared with DTG + TAF/FTC.

Stability of temocillin in outpatient parenteral antimicrobial therapy: is it a real option?

BACKGROUND: Temocillin is an interesting alternative to carbapenems for susceptible Enterobacteriaceae. Although its use in outpatient parenteral antimicrobial therapy (OPAT) programmes has generated interest, this has been hampered by the lack of stability data. OBJECTIVES: The purpose of the present study was to evaluate the physical and chemical stability of temocillin at the recommended dose for its use in OPAT programmes, contained in polypropylene infusion bags or polyisoprene elastomeric devices at different temperatures, and to describe a novel LC-MS/MS developed for the quantification of temocillin. METHODS: Temocillin daily dose (6 g) was diluted in 500 mL of 0.9% sodium chloride to obtain a final concentration of 12 g/L. This solution was stored at 4°C, 25°C, 32°C and 37°C for 72 h, both in polypropylene infusion bags and in polyisoprene elastomeric pumps. Physical and chemical stability were evaluated during 72 h after manufacturing. Solutions were considered stable if colour, clearness and pH remained unchanged and if the percentage of intact drug was ≥90%. RESULTS: Temocillin attained the chemical stability criterion of ≥90% of the original concentration for the whole experiment in both devices at 4°C, 25°C and 32°C. At 37°C, temocillin was stable for 24 h but its concentration dropped below 90% from that timepoint. No precipitation occurred and minor colour changes were observed. CONCLUSIONS: Temocillin is stable under OPAT conditions and it would be an appropriate candidate for the treatment of patients who can be discharged to complete therapy in an OPAT programme. For this study, an LC-MS/MS method was developed.

On-chip generation of high-dimensional entangled quantum states and their coherent control.

Optical quantum states based on entangled photons are essential for solving questions in fundamental physics and are at the heart of quantum information science. Specifically, the realization of high-dimensional states (D-level quantum systems, that is, qudits, with D > 2) and their control are necessary for fundamental investigations of quantum mechanics, for increasing the sensitivity of quantum imaging schemes, for improving the robustness and key rate of quantum communication protocols, for enabling a richer variety of quantum simulations, and for achieving more efficient and error-tolerant quantum computation. Integrated photonics has recently become a leading platform for the compact, cost-efficient, and stable generation and processing of non-classical optical states. However, so far, integrated entangled quantum sources have been limited to qubits (D = 2). Here we demonstrate on-chip generation of entangled qudit states, where the photons are created in a coherent superposition of multiple high-purity frequency modes. In particular, we confirm the realization of a quantum system with at least one hundred dimensions, formed by two entangled qudits with D = 10. Furthermore, using state-of-the-art, yet off-the-shelf telecommunications components, we introduce a coherent manipulation platform with which to control frequency-entangled states, capable of performing deterministic high-dimensional gate operations. We validate this platform by measuring Bell inequality violations and performing quantum state tomography. Our work enables the generation and processing of high-dimensional quantum states in a single spatial mode.

Extensive Expression of the Virulome Related to Antibiotic Genotyping in Nosocomial Strains of Klebsiella pneumoniae.

The emergence of hyper-virulent and multidrug-resistant (MDR) strains of Klebsiella pneumoniae isolated from patients with hospital- and community-acquired infections is a serious health problem that increases mortality. The molecular analysis of virulome expression related to antimicrobial-resistant genotype and infection type in K. pneumoniae strains isolated from patients with hospital- and community-acquired infections has been poorly studied. In this study, we analyzed the overall expression of the virulence genotype associated with the antimicrobial resistance genotype and pulse field gel electrophoresis (PFGE) type (PFtype) in K. pneumoniae. We studied 25 strains of K. pneumoniae isolated from patients who developed bacteremia and pneumonia during their hospital stay and 125 strains from outpatients who acquired community-acquired infections. Susceptibility to 12 antimicrobials was determined by Kirby-Bauer. The identification of K. pneumoniae and antibiotic-resistance genes was performed using polymerase chain reaction (PCR). To promote the expression of the virulence genes of K. pneumoniae, an in vitro infection model was used in human epithelial cell lines A549 and A431. Bacterial RNA was extracted with the QIAcube robotic workstation, and reverse transcription to cDNA was performed with the Reverse Transcription QuantiTect kit (Qiagen). The determination of the expression of the virulence genes was performed by real-time PCR. In addition, 57.3% (n = 86) of the strains isolated from patients with hospital- and community-acquired infections were multidrug-resistant (MDR), mainly to beta-lactam antibiotics (CB, AM, CFX, and CF), aminoglycosides (GE), quinolones (CPF and NOF), nitrofurantoin (NF), and sulfamethoxazole/trimethoprim (SXT). The most frequently expressed genes among strains isolated from hospital- and community-acquired infections were adhesion-type, ycfm (80%), mrkD (51.3%), and fimH (30.7%); iron uptake, irp2 (84%), fyuA (68.7%), entB (64.7%), and irp1 (56.7%); and protectins, rpmA (26%), which were related to antibiotic-resistance genes, blaTEM (96%), blaSHV (64%), blaCITM (52.6%), blaCTXM-1 (44.7%), tetA (74%), sul1 (57.3%), aac(3)-IV (40.7%), and aadA1 (36%). The results showed the existence of different patterns of expression of virulome related to the genotype of resistance to antimicrobials and to the PFtypes in the strains of K. pneumoniae that cause hospital- and community-acquired infections. These findings are important and may contribute to improving medical treatment strategies against infections caused by K. pneumoniae.

Patients and nursing-related factors associated with switching from peritoneal dialysis to hemodialysis: A cross-sectional survey.

The study aimed at analyzing patients and nursing-related factors associated with switching from peritoneal dialysis to hemodialysis. A telephone survey with 574 patients receiving care at six peritoneal dialysis centers of the Mexican Institute of Social Security was conducted: 64.3% were on peritoneal dialysis, and 35.7% had transitioned from peritoneal dialysis to hemodialysis. Data were collected on participants' sociodemographic and clinical characteristics, peritoneal dialysis center size, and nursing workload. Descriptive, bivariate, and multiple Poisson regression analyses were performed. Factors associated with an increased probability of switching from peritoneal dialysis to hemodialysis were a history of catheter dysfunction, peritonitis, and being treated in a large peritoneal dialysis center with a low (<50 patients per nurse per month) or high nursing workload (>70 patients per nurse per month) located in the State of Mexico, compared to a medium-size peritoneal dialysis center with a moderate workload (50-70 patients per nurse per month). To decrease the odds of switching from peritoneal dialysis to hemodialysis, improvement programs should aim to limit nurses' workload to 50-70 patients per nurse per month and implement evidence-based nursing interventions to prevent, detect, and manage peritonitis and peritoneal catheter dysfunction.

Combining Solid-State NMR with Structural and Biophysical Techniques to Design Challenging Protein-Drug Conjugates.

Several protein-drug conjugates are currently being used in cancer therapy. These conjugates rely on cytotoxic organic compounds that are covalently attached to the carrier proteins or that interact with them via non-covalent interactions. Human transthyretin (TTR), a physiological protein, has already been identified as a possible carrier protein for the delivery of cytotoxic drugs. Here we show the structure-guided development of a new stable cytotoxic molecule based on a known strong binder of TTR and a well-established anticancer drug. This example is used to demonstrate the importance of the integration of multiple biophysical and structural techniques, encompassing microscale thermophoresis, X-ray crystallography and NMR. In particular, we show that solid-state NMR has the ability to reveal effects caused by ligand binding which are more easily relatable to structural and dynamical alterations that impact the stability of macromolecular complexes.

Relevance of intra-hospital patient movements for the spread of healthcare-associated infections within hospitals - a mathematical modeling study.

The aim of this study is to analyze patient movement patterns between hospital departments to derive the underlying intra-hospital movement network, and to assess if movement patterns differ between patients at high or low risk of colonization. For that purpose, we analyzed patient electronic medical record data from five hospitals to extract information on risk stratification and patient intra-hospital movements. Movement patterns were visualized as networks, and network centrality measures were calculated. Next, using an agent-based model where agents represent patients and intra-hospital patient movements were explicitly modeled, we simulated the spread of multidrug resistant enterobacteriacae (MDR-E) inside a hospital. Risk stratification of patients according to certain ICD-10 codes revealed that length of stay, patient age, and mean number of movements per admission were higher in the high-risk groups. Movement networks in all hospitals displayed a high variability among departments concerning their network centrality and connectedness with a few highly connected departments and many weakly connected peripheral departments. Simulating the spread of a pathogen in one hospital network showed positive correlation between department prevalence and network centrality measures. This study highlights the importance of intra-hospital patient movements and their possible impact on pathogen spread. Targeting interventions to departments of higher (weighted) degree may help to control the spread of MDR-E. Moreover, when the colonization status of patients coming from different departments is unknown, a ranking system based on department centralities may be used to design more effective interventions that mitigate pathogen spread.

Incidence Rate and Risk Factors for Anal Squamous Cell Carcinoma in a Cohort of People Living With HIV from 2004 to 2017: Implementation of a Screening Program.

BACKGROUND: Anal squamous cell carcinoma is rare, in general, but considerably higher in HIV-infected men who have sex with men. There is no consensus on the screening of at-risk populations. OBJECTIVE: This study aimed to determine the incidence rates of anal squamous cell carcinoma and the efficacy of a screening program. DESIGN: This is a cohort study (SeVIHanal/NCT03713229). SETTING: This study was conducted at an HIV outpatient clinic in Seville, Spain. PATIENTS: From 2004 to 2017, all patients with at least 1 follow-up visit were analyzed (follow-up group), including a subgroup of men who have sex with men who participated in a specialized program for screening and treating anal neoplasia (SCAN group) from 2011 onward. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence rate of anal squamous cell carcinoma. RESULTS: Of the 3878 people living with HIV included in the follow-up group, 897 were transferred to the SCAN group; 1584 (41%) were men who have sex with men. Total follow-up was 29,228 person-years with an overall incidence rate for anal squamous cell carcinoma of 68.4/100,000 person-years (95% CI, 46.7-97.4). The changes in the incidence rate/100,000 person-years (95% CI) over time was 20.7 (3.40-80.5) for 2004 to 2006, 37.3 (13.4-87.3) for 2007 to 2010, and 97.8 (63.8-144.9) for 2011 to 2017 (p < 0.001). The strongest impact on the incidence of anal squamous cell carcinoma was made by the lack of immune restoration (adjusted incidence rate ratio (95% CI): 6.59 (4.24-10); p < 0.001), the Centers for Disease Control and Prevention category C (adjusted incidence rate ratio (95% CI): 7.49 (5.69-9.85); p < 0.001), and non-men who have sex with men (adjusted incidence rate ratio (95% CI): 0.07 (0.05-0.10); p < 0.001) in a Poisson analysis. From 2010 to 2017, incidence rates (95% CI) of anal squamous cell carcinoma within the SCAN group and the men who have sex with men of the follow-up group were 95.7 (39.6-202) and 201 (101-386)/100,000 person-years (adjusted incidence rate ratio (95% CI): 0.30 (0.23-0.39); p<0.001). The incidence rate ratio (95% CI) including non-men who have sex with men in the follow-up group was 0.87 (0.69-1.11); p = 0.269. LIMITATIONS: Adherence to the visits could not be quantified. CONCLUSION: Incidence rates of anal squamous cell carcinoma in people living with HIV increased significantly from 2004 to 2017, especially in men who have sex with men who were not being screened. Participation in the SCAN program significantly reduced the incidence of anal squamous cell carcinoma in men who have sex with men, in whom focus should be placed, especially on those presenting with Centers for Disease Control and Prevention category C and advanced immune suppression. See Video Abstract at http://links.lww.com/DCR/B734. TASA DE INCIDENCIA Y FACTORES DE RIESGO DEL CARCINOMA ANAL A CLULAS ESCAMOSAS EN UNA COHORTE DE PERSONAS QUE VIVEN CON EL VIH DE A IMPLEMENTACIN DE UN PROGRAMA DE DETECCIN: ANTECEDENTES:El carcinoma anal a células escamosas es generalmente raro, pero considerablemente más alto en hombres infectados por el VIH que tienen relaciones sexuales con hombres. No hay consenso sobre el cribado de poblaciones en riesgo.OBJETIVO:Este estudio tuvo como objetivo determinar las tasas de incidencia del carcinoma anal a células escamosas y la eficacia de un programa de detección.DISEÑO:Estudio de cohorte (SeVIHanal / NCT03713229).AJUSTE:Clínica ambulatoria de VIH en Sevilla, España.PACIENTES:De 2004 a 2017, se analizaron todos los pacientes con al menos una visita de seguimiento (grupo F / U), incluido un subgrupo de hombres que tenían relaciones sexuales con hombres que participaron en un programa especializado de cribado y tratamiento de neoplasias anales (SCAN-group) a partir de 2011.PRINCIPALES MEDIDAS DE RESULTADO:Tasas de incidencia del carcinoma anal a células escamosas.RESULTADOS:De las 3878 personas que viven con el VIH incluidas en el grupo F / U, 897 fueron transferidas al grupo SCAN, 1584 (41%) eran hombres que tenían relaciones sexuales con hombres. El seguimiento total fue de 29228 personas-año con una tasa de incidencia general de carcinoma anal a células escamosas de 68,4 / 100000 personas-año [intervalo de confianza del 95%: 46,7-97,4]. El cambio en las tasas de incidencia / 100000 personas-año (intervalo de confianza del 95%) a lo largo del tiempo fue 20,7 (3,40-80,5) para 2004-2006, 37,3 (13,4-87,3) para 2007-2010 y 97,8 (63,8-144,9) para 2011-2017, p <0,001. El impacto más fuerte en la incidencia del carcinoma a células escamosas anal fue la falta de restauración inmunológica [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 6,59 (4,24-10); p <0,001], categoría C de los Centros de Control de Enfermedades [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 7,49 (5,69-9,85); p <0,001] y no hombres que tenían relaciones sexuales con hombres [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,07 (0,05-0,10); p <0,001] en el análisis de Poisson. Desde 2010-2017, las tasas de incidencia (intervalo de confianza del 95%) de carcinoma anal a células escamosas dentro del grupo SCAN y los hombres que tienen relaciones sexuales con hombres del grupo F / U fueron 95,7 (39,6-202) y 201 (101- 386) / 100000 personas-año [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,30 (0,23-0,39); p <0,001]. La razón de la tasa de incidencia (intervalo de confianza del 95%), incluidos los no hombres que tenían relaciones sexuales con hombres en F / U, fue de 0,87 [0,69-1,11); p = 0,269].LIMITACIONES:No se pudo cuantificar la adherencia a las visitas.CONCLUSIÓNES:La tasa de incidencia del carcinoma anal a células escamosas en personas que viven con el VIH aumentó significativamente de 2004 a 2017, especialmente en hombres que tenían relaciones sexuales con hombres que no se someten a pruebas de detección. La participación en el programa SCAN redujo significativamente la incidencia de carcinoma anal a células escamosas en hombres que tenían relaciones sexuales con hombres, en quienes se debe prestar una especial atención, sobre todo en aquellos que se presentan en la categoría C de los Centros de Control de Enfermedades con inmunodeficiencia avanzada. Consulte Video Resumen en http://links.lww.com/DCR/B734.

Low CD4/CD8 ratio is associated with increased morbidity and mortality in late and non-late presenters: results from a multicentre cohort study, 2004-2018.

BACKGROUND: To study whether the association between the CD4/CD8 ratio variation over time and the development of clinical outcomes vary in late presenters (CD4 count < 350/µL or AIDS event at enrolment) or advanced presenters (CD4 count < 200/µL or AIDS event at enrolment). METHODS: We included ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) enrolled between January 2004 up to November 2018 and with at least 6 months of follow-up. We used extended Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between CD4/CD8 ratio over time and a composite endpoint of the occurrence of the first AIDS event, first serious non-AIDS event or overall mortality occurring from 6 months after enrolment. HRs in non-late, late and advanced presenters were obtained by including an interaction term between late presentation status and CD4/CD8 ratio over time. RESULTS: Of 10,018 participants, 55.6% were late presenters and 26.5% were advanced presenters. Compared with CD4/CD8 ratio > 0.4, CD4/CD8 ratio ≤ 0.4 over time was associated with an increased risk of experiencing the composite endpoint in non-late (HR 1.90; 95%CI 1.48, 2.43), late (HR 1.94; 1.46, 2.57) and advanced presenters (HR 1.72; 1.26, 2.34). Similarly, CD4/CD8 ratio ≤ 0.4 over time was associated with a higher risk of developing an AIDS event (HR 3.31; 2.23, 4.93 in non-late; HR 2.75; 1.78, 4.27 in late and HR 2.25; 1.34, 3.76 in advanced presenters) or serious non-AIDS event (HR 1.39; 0.96, 2.02 in non-late, HR 1.62; 1.10, 2.40 in late and HR 1.49; 0.97, 2.29 in advanced presenters) as well as with a higher risk of overall mortality (HR 1.49; 0.92, 2.41 in non-late, HR 1.80; 1.04, 3.11 in late and HR 1.61; 0.92, 2.83 in advanced presenters) compared to CD4/CD8 > 0.4, regardless of the late presentation status. CONCLUSIONS: A low CD4/CD8 measured over time is associated with increased risk of morbidity and mortality in people living with HIV independently of their late presentation status. These data support the prognostic role of CD4/CD8 over time and can help defining a subgroup of patients who need closer monitoring to avoid comorbidities.

Mortality and Causes of Death After Liver Transplantation: Analysis of Sex Differences in a Large Nationwide Cohort.

In the last few years, several studies have analyzed sex and gender differences in liver transplantation (LT), but none have performed a disaggregated analysis of both mortality and causes of death. Data from 15,998 patients, 11,914 (74.5%) males and 4,069 (25.5%) females, transplanted between 2000 and 2016 were obtained from the Liver Transplantation Spanish Registry. Survival analysis was applied to explore recipient sex as a risk factor for death. The causes of death at different follow-up duration were disaggregated by recipient sex for analysis. Short-term survival was higher in males, whereas long-term survival was higher in females. Survival at 1, 5 and 10 years post-transplant was 87.43%, 73.83%, and 61.23%, respectively, in males and 86.28%, 74.19%, and 65.10%, respectively, in females (p = 0.05). Post-LT mortality related to previous liver disease also presented sex differences. Males had 37% increased overall mortality from acute liver failure (p = 0.035) and 37% from HCV-negative cirrhosis (p < 0.001). Females had approximately 16% increased mortality when the liver disease was HCV-positive cirrhosis (p = 0.003). Regarding causes of death, non-malignancy HCV+ recurrence (6.3% vs. 3.9% of patients; p < 0.001), was more frequently reported in females. By contrast, death because of malignancy recurrence (3.9% vs. 2.2% of patients; p = 0.003) and de novo malignancy (4.8% vs. 2.5% of patients; p < 0.001) were significantly more frequent in male recipients. Cardiovascular disease, renal failure, and surgical complications were similar in both. In summary, male patients have lower short-term mortality than females but higher long-term and overall mortality. In addition, the post-LT mortality risk related to previous liver disease and the causes of mortality differ between males and females.

Prediction of Heat Transfer and Fluid Flow Effects on Entropy Generation in a Monolithic Catalytic Converter Using Large-Eddy Simulation.

In the present work, heat transfer and fluid flow and their effects on entropy generation in a realistic catalytic converter of a Lada Niva 21214 vehicle are studied using large eddy simulation. At first, the pressure drop over the catalytic converter is measured for dry air at constant temperature (T=298 K), different volumetric flow rates, and extrapolated to large volumetric flow rates for dry air (T=298 K) and for the exhaust gas under realistic engine conditions (T=900 K) using the Darcy-Forchheimer relation. Then, coupled heat and fluid flow phenomena inside the catalytic converter are analyzed for nonreacting isothermal conditions and nonreacting conditions with conjugate heat transfer by using the large-eddy simulation. The predicted pressure drop agrees well with the measured and extrapolated data. Based on the obtained numerical results, the characteristic flow features are identified, namely: the impinging flow with stagnation, recirculation, flow separation and laminarization within the fine ducts of the monolith, which depends on the heat transfer through temperature-dependent thermophysical properties of exhaust gas. Moreover, due to high-velocity gradients at the wall of the narrow ducts in the monolith, entropy production by viscous dissipation is observed predominantly in the monolith region. In contrast, entropy production due to heat transport is relatively small in the monolith region, while it overwhelms viscous dissipation effects in the pipe regions.

Impact of Immunosuppressive Agents on Clinical Manifestations and Outcome of Staphylococcus aureus Bloodstream Infection: A Propensity Score-Matched Analysis in 2 Large, Prospectively Evaluated Cohorts.

BACKGROUND: Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. METHODS: Data from 2 large prospective, international, multicenter cohort studies (Invasive Staphylococcus aureus Infections Cohort [INSTINCT] and International Staphylococcus aureus Collaboration [ISAC]) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score-matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroid monotherapy and immunosuppressive agents other than steroids [IMOTS]). RESULTS: Of 3188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 nonimmunosuppressed patients. After propensity score matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the 2 groups (death during follow-up: 105/309 [33.9%] immunosuppressed vs 94/309 [30.4%] nonimmunosuppressed; hazard ratio [HR], 1.20 [95% confidence interval {CI}, .84-1.71]). Competing risk analysis showed a cause-specific HR of 1.81 (95% CI, .85-3.87) for SAB-related late complications in patients receiving immunosuppressive agents. The cause-specific HR was higher in patients taking IMOTS (3.69 [95% CI, 1.41-9.68]). CONCLUSIONS: Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTS warrants further investigations.

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial.

BACKGROUND: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. METHODS: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. RESULTS: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). CONCLUSIONS: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338.

Group-velocity dispersion emulator using a time lens.

We report a novel method to continuously track the temporal evolution of an arbitrary complex waveform as it propagates through a group-velocity dispersion medium by using a single-frequency-driven phase modulator. The proposed method exploits the fact that the frequency spectrum of a given (input) waveform, following a suitable sinusoidal temporal phase modulation, exhibits the same shape as that of a dispersed version of the same temporal waveform after propagation through a prescribed amount of dispersion. In experiments, we track the dispersion-induced temporal evolution of different optical picosecond pulsed waveforms by tuning the frequency and/or amplitude of the phase modulation signal and observing the resulting shapes in the optical frequency domain. A good agreement is obtained between the measured spectra and predicted temporal shapes of the propagating waveform for different amounts of dispersion. Moreover, the method is successfully applied on a chirped optical pulse to find the optimal pulse compression conditions.