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Most prior research characterizes information-seeking behaviors as serving utilitarian purposes, such as whether the obtained information can help solve practical problems. However, information-seeking behaviors are sensitive to different contexts (i.e., threat vs. curiosity), despite having equivalent utility. Furthermore, these search behaviors can be modulated by individuals' life history and personality traits. Yet the emphasis on utilitarian utility has precluded the development of a unified model, which explains when and how individuals actively seek information. To account for this variability and flexibility, we propose a unified information-seeking framework that examines information-seeking through the lens of motivation. This unified model accounts for integration across individuals' internal goal states and the salient features of the environment to influence information-seeking behavior. We propose that information-seeking is determined by motivation for information, invigorated either by instrumental utility or hedonic utility, wherein one's personal or environmental context moderates this relationship. Furthermore, we speculate that the final common denominator in guiding information-seeking is the engagement of different neuromodulatory circuits centered on dopaminergic and noradrenergic tone. Our framework provides a unified framework for information-seeking behaviors and generates several testable predictions for future studies.
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Conducta en la Búsqueda de Información , Motivación , Humanos , Conducta Exploratoria , DopaminaRESUMEN
The objective of this study was to evaluate blood cells and metabolites, insulin-like growth factor-1 (IGF-1), digestibility, internal organs weight and histology, gene expression, and spleen cell proliferation of pre-weaned bull calves supplemented with a blend of essential oils in milk replacer (MR). Sixteen newborn Holstein × Gyr crossbred dairy bull calves, with body weight at birth of 33.3 ± 3.7 kg, were housed in individual sand bedded pens, blocked by genetic composition, and randomly assigned to 1 of 2 treatments in a randomized complete block design: Control (CON, n = 8) and blend of essential oils supplementation (BEO, n = 8, 1 g/day/calf, Apex Calf, Adisseo, China). The commercial blend was composed by plant extracts derived from anise, cinnamon, garlic, rosemary, and thyme. Animals were fed 5 L of MR/day reconstituted at 15% (dry matter basis), divided into two equal meals. Water and starter were provided ad libitum. ß-hydroxybutyrate, urea, and glucose were evaluated weekly, IGF-1 was evaluated biweekly, and total blood cell count was performed every four weeks until the end of the trial at eight weeks of age. Feed samples were collected three times a week and polled for weekly analysis. Apparent total nutrient digestibility was determined from d 56 to 60 of age. On d 60 ± 1, animals were euthanized for organ weight, histology, spleen cell proliferation, and intestinal gene expression analysis. Data were analyzed independently using linear mixed models using the REML method in the nlme package in R for continuous outcomes. A non-parametric test was used for ordered categorical outcomes using the Artools package in R. There were no differences between groups for blood evaluations, digestibility, gene expression, and a spleen cell proliferation assay. However, BEO calves presented a heavier pancreas, heavier intestines, bigger ileum villi, and higher cecum butyrate levels (P < 0.05), demonstrating that the EO supplementation helped intestinal development and symbiotic bacteria. It was also observed in CON animals' heavier respiratory tract and a higher eosinophil count (P < 0.05). Therefore, the organs where eosinophils are more active had a better response for BEO animals. No differences were found in the intestinal gene expression in the immune context. These results demonstrate that supplementing essential oils in MR could contribute to gut development and immune function. However, more research is needed to understand its impact on body development and define the best dosage and route of administration.
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Ajo , Factor I del Crecimiento Similar a la Insulina , Aceites de Plantas , Animales , Bovinos , Masculino , Antioxidantes , Expresión Génica , Factor I del Crecimiento Similar a la Insulina/genética , Bazo , Aceites de Plantas/farmacologíaRESUMEN
With the objective of characterizing the composition and spatial distribution of plastic fragments in a subtropical lagoon system, five sample areas affected by various anthropogenic impacts were chosen in the southern part of the Estuarine Lagoon System in Laguna, Santa Catarina, Brazil. The total density of the floating meso- and microplastics encountered was 7.32/m3, with the greatest density in the access channel and external area of the lagoon. Plastic filament was the most abundant and mainly comprised polyester (PET), polypropylene (PP) and polyethylene (PE) from 0.05 to 0.71 mm2. Fishing and urbanization were the main sources of the meso- and microplastics in the environment. This is the first study to evaluate contamination by meso- and microplastics in the southern part of the Estuarine Lagoon System and provides information about the nature and extent of contamination by plastics in this estuarine ecosystem.
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Plásticos , Contaminantes Químicos del Agua , Ecosistema , Monitoreo del Ambiente , Microplásticos , Contaminantes Químicos del Agua/análisisRESUMEN
A surgical video can improve patient care, surgical education, as well as scientific presentations and publications. Previous authors have outlined a basic understanding of how to produce high-quality surgical videos. With continuous technological improvements in video-filming hardware and editing software, multiple options for producing high-quality surgical videos are available. This article described important aspects of filming and editing videos to create a video that the surgeon can watch before performing the procedure. The authors reviewed camera terminology, including resolution, optical and digital zoom, shutter speed, and frame rate, as well as equipment options or setup for recording high-quality surgical videos. We provided information regarding computer requirements and editing on Windows and Macintosh operating systems, optimizing educational value for the viewer.
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Mano , Cirujanos , Mano/cirugía , Humanos , Programas Informáticos , Extremidad Superior/cirugía , Grabación en VideoRESUMEN
It is well established that mantle plumes are the main conduits for upwelling geochemically enriched material from Earth's deep interior. The fashion and extent to which lateral flow processes at shallow depths may disperse enriched mantle material far (>1,000 km) from vertical plume conduits, however, remain poorly constrained. Here, we report He and C isotope data from 65 hydrothermal fluids from the southern Central America Margin (CAM) which reveal strikingly high 3He/4He (up to 8.9RA) in low-temperature (≤50 °C) geothermal springs of central Panama that are not associated with active volcanism. Following radiogenic correction, these data imply a mantle source 3He/4He >10.3RA (and potentially up to 26RA, similar to Galápagos hotspot lavas) markedly greater than the upper mantle range (8 ± 1RA). Lava geochemistry (Pb isotopes, Nb/U, and Ce/Pb) and geophysical constraints show that high 3He/4He values in central Panama are likely derived from the infiltration of a Galápagos plume-like mantle through a slab window that opened â¼8 Mya. Two potential transport mechanisms can explain the connection between the Galápagos plume and the slab window: 1) sublithospheric transport of Galápagos plume material channeled by lithosphere thinning along the Panama Fracture Zone or 2) active upwelling of Galápagos plume material blown by a "mantle wind" toward the CAM. We present a model of global mantle flow that supports the second mechanism, whereby most of the eastward transport of Galápagos plume material occurs in the shallow asthenosphere. These findings underscore the potential for lateral mantle flow to transport mantle geochemical heterogeneities thousands of kilometers away from plume conduits.
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Mutations in the cardiac myosin regulatory light chain (RLC, MYL2 gene) are known to cause inherited cardiomyopathies with variable phenotypes. In this study, we investigated the impact of a mutation in the RLC (K104E) that is associated with hypertrophic cardiomyopathy (HCM). Previously in a mouse model of K104E, older animals were found to develop cardiac hypertrophy, fibrosis, and diastolic dysfunction, suggesting a slow development of HCM. However, variable penetrance of the mutation in human populations suggests that the impact of K104E may be subtle. Therefore, we generated human cardiac myosin subfragment-1 (M2ß-S1) and exchanged on either the wild type (WT) or K104E human ventricular RLC in order to assess the impact of the mutation on the mechanochemical properties of cardiac myosin. The maximum actin-activated ATPase activity and actin sliding velocities in the in vitro motility assay were similar in M2ß-S1 WT and K104E, as were the detachment kinetic parameters, including the rate of ATP-induced dissociation and the ADP release rate constant. We also examined the mechanical performance of α-cardiac myosin extracted from transgenic (Tg) mice expressing human wild type RLC (Tg WT) or mutant RLC (Tg K104E). We found that α-cardiac myosin from Tg K104E animals demonstrated enhanced actin sliding velocities in the motility assay compared with its Tg WT counterpart. Furthermore, the degree of incorporation of the mutant RLC into α-cardiac myosin in the transgenic animals was significantly reduced compared with wild type. Therefore, we conclude that the impact of the K104E mutation depends on either the length or the isoform of the myosin heavy chain backbone and that the mutation may disrupt RLC interactions with the myosin lever arm domain.
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Miosinas Cardíacas , Cardiomiopatía Hipertrófica , Actinas/genética , Actinas/metabolismo , Adenosina Trifosfatasas , Animales , Miosinas Cardíacas/genética , Miosinas Cardíacas/metabolismo , Cardiomiopatía Hipertrófica/genética , Ratones , Mutación , Cadenas Ligeras de Miosina/genética , Cadenas Ligeras de Miosina/metabolismoRESUMEN
OBJECTIVE: To study the effects of disability, cognitive impairment, and neuropsychiatric disturbance among older Mexican Americans on depressive symptoms in their children caregivers. METHODS: This study utilizes data from Wave 7 (2010-2011) of the Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE). The final sample included 200 adult children caregivers that provided direct personal care with activities of daily living (ADL) (e.g. bathing, toileting, dressing, etc.) to their older parents (average age = 87). We analyzed the influence of ADL disability, cognition (MMSE), and neuropsychiatric symptoms (NPI) of the care recipient on depressive symptoms of the adult child caregiver. A cross-sectional multivariable linear regression analysis was conducted to examine the effect of neuropsychiatric disturbance on caregiver depressive symptoms. RESULTS: Presence of care recipient NPI symptoms was associated with higher depressive symptoms for caregivers. Additional characteristics associated with caregiver depressive symptoms were not being married, and higher perceived social stress. ADL disability of the care recipient, cognitive functioning of the care recipient, or caregiver health status alone did not have a significant effect on depressive symptoms of the caregiver. CONCLUSIONS: In a Mexican American familistic culture, disability and cognitive impairment might be better tolerated by families but neuropsychiatric behavioral symptoms related to dementia may take an increased toll on family member caregivers. The need to provide respite services, mental health resources and community services for caregivers of care recipients with neuropsychiatric symptoms is of paramount importance to alleviate depressive symptoms and burden among caregivers.
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Cuidadores , Americanos Mexicanos , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Estudios Transversales , Depresión/epidemiología , Familia , HumanosRESUMEN
BACKGROUND: Cleft is one of the most common birth defects globally and the lack of access to surgery means millions are living untreated. Smoke exposure from cooking occurs infrequently in developed countries but represents a high-proportion of smoke exposure in less-developed regions. We aimed to study if smoke exposure from cooking is associated with an increased risk in cleft, while accounting for other smoke sources. METHODS: We conducted a population-sampled case-control study of children with cleft lip and/or palate and healthy newborns from Vietnam, Philippines, Honduras, Nicaragua, Morocco, Congo, and Madagascar. Multivariable regression models were used to assess associations between maternal cooking during pregnancy, parental smoking, and household tobacco smoke with cleft. RESULTS: 2137 cases and 2014 controls recruited between 2012-2017 were included. While maternal smoking was uncommon (<1%), 58.3% case and 36.1% control mothers cooked over an open fire inside. Children whose mothers reported cook smoke exposure were 49% (95% confidence interval (CI) = 1.2-1.8) more likely to have a child with a cleft. This was consistent in five of seven countries. No significant associations were found for any other smoke exposure. CONCLUSIONS: Our finding of maternal cook smoke and cleft in low-resource countries, similar to maternal tobacco smoke in high-resource countries, may reflect a common etiology. This relationship was present across geographically diverse countries with variable socioeconomic statuses and access to care. Exposures specific to low-resource settings must be considered to develop public health strategies that address the populations at increased risk of living with cleft and inform the mechanisms leading to cleft development.
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Labio Leporino , Fisura del Paladar , Humo/efectos adversos , Fumar/efectos adversos , Estudios de Casos y Controles , Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Congo , Culinaria , Femenino , Honduras , Humanos , Recién Nacido , Madagascar , Marruecos , Madres , Nicaragua , Filipinas , Embarazo , Factores de Riesgo , VietnamRESUMEN
The aim was to describe a methodology developed to study the relationship among the spatio-temporal patterns of habitat utilization, feeding ecology and microplastics (MPs) contamination across the different ontogenetic phases of fishes belonging to different trophic levels and living along the riverine-estuarine-coastal food web. The Goiana Estuary's water column was examined for the seasonal and spatial variation of MPs and their quantification relative to zooplankton, demersal fish species contamination following the same sampling design. The density of MPs in the water column determines their bioavailability. Interest in studies on MPs distribution in relation to spatial and temporal variation of environmental factors and fauna are increasing in quantity and quality. If the ecological strategies presented in this study were replicated in other estuary, comparisons could be made in order to describe how ecosystems work. Standard protocols for sampling, extraction, enumeration and classification of MPs and others pollutant ingested by fishes have been developed and are presented here to encourage comparisons. Standardized and comparable sampling designs and laboratory procedures are an important strategy in order to devise and transfer managerial solutions among different sites and comparisons along time when studying the same environment.
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Background Stunted growth and development is a serious global public health problem. A limited number of field measures exist that can be used to evaluate stunting and its underlying biologic mechanisms. Purpose To assess bone age using tablet-based US in young children living in a rural community in Ecuador, where stunting is prevalent, and to evaluate the associations between bone age, anthropometry, and diet. Materials and Methods From June through August 2017, tablet-based US was used to assess bone age in young children within their homes in rural Cotopaxi, Ecuador. Bone age z scores (BAZs) were assigned using the standards of Greulich and Pyle. Anthropometric data were collected using international protocols; z scores were generated from World Health Organization Child Growth Standards. Groups were compared using the Student t test. Univariate analyses and generalized linear regression modeling were applied to test the association between bone age and anthropometry, adjusting for covariates including age, sex, dietary intake, and morbidities. Results A total of 128 children (mean age, 33.9 months ± 1.8 [standard deviation]; 59 girls, 69 boys) were evaluated. Mean BAZ was -1.20 ± 1.16. Mean BAZ was lower in children with stunted growth (-1.42 ± 1.18) than in children without stunted growth (-0.98 ± 1.10, P = .04). In adjusted analysis, BAZ was associated with the following variables: height-for-age z score (ß coefficient, 0.26; 95% confidence interval [CI]: 0.05, 0.46; P = .01), female sex (ß coefficient, 0.51; 95% CI: 0.15, 0.88; P = .006), number of times eggs were consumed in the previous 24 hours (ß coefficient, 0.22; 95% CI: 0.05, 0.38; P = .009), number of times savory or salty snacks were consumed in the previous 24 hours (ß coefficient, 0.42; 95% CI: 0.15, 0.68; P = .002), and ownership of pig livestock, which was a binary variable (ß coefficient, -0.46; 95% CI: -0.82, -0.09; P = .01). Conclusion Bone age determined using tablet-based US was lower in children who had stunted growth and was associated with diet in a cohort of children living in rural Ecuador. © RSNA, 2020 See also the editorial by Dillman and Ayyala in this issue.
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Antropometría/métodos , Huesos/diagnóstico por imagen , Trastornos del Crecimiento/diagnóstico por imagen , Estado Nutricional , Población Rural/estadística & datos numéricos , Ultrasonografía/métodos , Preescolar , Ecuador , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
One of the most recognized anthropogenic impacts in marine environments is solid waste pollution, especially plastic, which can be ingested by fish, thus interfering with their health. In this context, the aim of this study is to describe the ingestion of plastic fragments and to identify the possible effect of this contamination in the condition factor of Genidens genidens in the Laguna Estuarine System. The stomach contents of 92 G. genidens (26 juveniles and 66 adults) were analyzed. The Index of Relative Importance was performed to identify the contribution of each prey item. Condition factor (CF) was used to analyze the effect of plastic ingestion on the fish's body condition (by comparing individuals in the same ontogenetic phase). For the juveniles, eight items were observed, the most important of which were Penaeidae, followed by Portunidae and plastic. For the adults, 12 items were observed, the most important of which were Penaeidae, Portunidae, Polychaeta, and plastic. The analysis of CF demonstrated higher values for individuals without plastic in the stomach, which indicated a better health condition. The CF of a fish may be affected by variations in the physiological condition, environmental stresses, and nutritional and biological variations, and could be used to compare the body condition or health of a fish species. The ingestion of plastic could significantly influence the worst body condition of the individuals that were analyzed in the present study. The plastic pollution in marine coastal waters is associated with the appropriate waste management levels.
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Bagres , Plásticos/análisis , Contaminantes Químicos del Agua/análisis , Animales , Brasil , Exposición Dietética/análisis , Ingestión de Alimentos , Monitoreo del Ambiente , Contenido Digestivo , Residuos Sólidos/análisisRESUMEN
Atlantic Bigeye (Priacanthus arenatus) is a demersal species from the Priacanthidae family with little literature relating to its biology and catch aspects. Due to this lack of research, the focus of this effort was to describe the feeding preferences of Atlantic Bigeye and to evaluate the influence of plastic debris derived from the local fisheries activities on its diet. The most important items were Corophiidae, Penaeidae, Actinopterygii, Isopoda, Cephalopoda, Policheta and plastic. Plastic was present in 49.17% of the stomachs analyzed. A total of 210 plastic fragments were found, and 63% were derived from fishing. Of those, 55% were derived from paint fragments from vessels and 8% from synthetic fibers (PA). The results suggest that plastic fragments found in stomachs are related to the species' natural diet and that this debris is locally deposited in the coastal environment. Fishing resources appear to have been affected by this local marine pollution.
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Explotaciones Pesqueras , Tracto Gastrointestinal/química , Perciformes , Plásticos/análisis , Residuos/análisis , Animales , Ingestión de Alimentos , Ecología , Contaminantes Químicos del Agua/análisisRESUMEN
Worldwide, the marine debris emissions have been provoking impacts in ecosystems, generating massive mortality of different species with commercial interest. In South America, we have a lack of studies to verify the marine debris composition in transitional environments such as adjacent regions of coastal jetties. These are hydraulic engineering constructions used to maintain the navigation channel access between the sea-estuarine interface and are also used by teleost fishes, crustaceans, and mollusks like artificial shelters (reefs), being excellent fishing grounds. Therefore, the present study was devoted to qualitatively evaluate the composition of marine debris in an internal jetty portion of a Laguna Estuarine System (LES) located in South America (Brazil). Six hundred freediving were conducted to collect marine debris in the study region. The in situ campaigns were performed in 2016 during all spring season (sand substrata) in four distinct zones with 26,400 m2 each one covering almost all adjacent jetty extension, to evaluate possible spatial changes in the marine debris composition. All material obtained was identified, measured, weighed, and ordered in eight groups, with six groups being related to the fishing activity and two groups related to the tourism/community in the study region. So, it was possible to observe possible relations between the marine debris distribution to artisanal and recreational local fishing. After 600 freediving sampling efforts, 2142 marine debris items were obtained, totaling close to 100 kg of solid waste removed from the inner portion of the coastal jetty. Notably, 1752 units (50 kg) of fishing leads were collected being this item the main marine debris residue found in the four sampled areas, corresponding to nearly 50% of the total weight of the collected waste. Ninety-eight percent of marine debris were derived from the local fishing activities, and just 2% were derived from tourism/community. Considering the total contribution related to fishing, 83% of the marine debris were composed by lead (sinkers) adopted by recreational and artisanal fishing. Notably, the catch activity in this region has a close influence over the marine debris composition. Reductions of marine debris emissions derived from the fishing activities have been a global challenge, once this problem is occurring in practically all marine and estuarine environments under the anthropic action. The presence of marine debris changes the local landscape and can provoke serious environmental problems, such as ghost fishing that affects a wide variability of marine mammals, birds, and fishes. Most of marine debris collected came from recreational and artisanal fishing, being the fishing leads the most prominent material, especially in sector 4. This fact is possibly related to the intense mullet fishing using cast nets, usual in this sample area. In the other sectors, there was a great predominance of grapnel fishing leads, widely adopted by recreational fishermen in open water environments. The "fingernails" present in these fishing leads ensure the sinking of the line for a specific location independently of possible flow oscillations of the tidal current and/or currents generated by winds. The massive quantity of fishing leads into the sectors is a dangerous fact. Notably, lead is a heavy, non-biodegradable, and extremely toxic metal that, due to the anthropogenic activities, has been increasing around the world. Future efforts in our study region should evaluate the seasonal marine debris composition to observe possible changes along the different seasons of the year. In this way, it would be possible to infer quantitatively the emission of marine debris derived from the fishing activity, assessing its impacts and enabling the adoption of environmental management strategies. This effort adopted a qualitative analysis, serving to show the current situation of this region that we now know to be vulnerable to the presence of marine debris derived from the fishing activity.
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Residuos Sólidos/análisis , Residuos/análisis , Animales , Aves , Brasil , Ecosistema , Explotaciones Pesqueras , Estaciones del AñoRESUMEN
HIV pre-exposure prophyalxis (PrEP) might lead individuals to view serodisclosure as unnecessary. We examined the prevalence of non-disclosure and lack of knowledge of partner status in a global cohort of men who have sex with men (MSM) and transgender women (TW) enrolled in the iPrEx Open Label Extension (OLE). We calculated prevalence ratios by fitting a logistic model and estimating predicted probabilities using marginal standardization. Prevalence of non-disclosure and lack of knowledge of partner status were highest in Thailand (73% and 74%, respectively) and lowest in the USA (23% and 37%, respectively). In adjusted analyses, PrEP use was not significantly associated with non-disclosure or lack of knowledge of partner status (p-values>0.05). We found that relationship characteristics were significantly associated with both outcomes. Non-disclosure was higher among casual (adjusted prevalence ratio [aPR] 1.54, [95% confidence interval 1.24-1.84]) and transactional sex partners (aPR 2.03, [1.44-2.62]), and among partners whom participants have known only minutes or hours before their first sexual encounter (aPR 1.62, [1.33-1.92]). Similarly, participants were less likely to know the HIV status of casual partners (aPR 1.50, [1.30-1.71]), transactional sex partners (aPR 1.62, [1.30-1.95]), and those they have known for only days or weeks (aPR 1.13, [0.99-1.27]) or minutes or hours (aPR 1.27, [1.11-1.42]). Our findings underscore the role of dyadic factors in influencing serodisclosure. Comprehensive risk reduction counseling provided in conjunction with PrEP that address relationship characteristics are needed to help patients navigate discussions around HIV status.
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Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición/estadística & datos numéricos , Autorrevelación , Adulto , Anciano , Femenino , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Parejas Sexuales , Sudáfrica , América del Sur , Tailandia , Personas Transgénero , Estados Unidos , Adulto JovenRESUMEN
AIM: Studies examining the association between mortality and anticholinergic burden in the geriatric population are conflicting and are absent in the Mexican American population. The present study aimed to determine whether higher anticholinergic burden increases mortality in a cohort representative of community-based older Mexican Americans in the USA. METHODS: This retrospective cohort database study used the Hispanic Established Populations for the Epidemiologic Study of the Elderly cohort. The primary outcome, mortality, was assessed beginning at the second interview in 1995 until the fifth interview in 2005. Medications were classified for anticholinergic burden according to the modified-Anticholinergic Drug Scale and were summed across all reported medications creating a measure of total anticholinergic burden. Anticholinergic burden was tested for association with mortality using survival analysis. RESULTS: The 1497 older adults reporting medication usage were included. Survival analysis showed a statistically significant (P < 0.05) relationship between anticholinergic burden and increased mortality. CONCLUSIONS: Anticholinergic burden is associated with increased mortality in Southwestern Mexican American older adults who report taking prescription or non prescription medications. These findings suggest that anticholinergic burden might be a risk factor for mortality in this selected population, with additional studies required to further define the risk. Geriatr Gerontol Int 2017; 17: 1515-1521.
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Antagonistas Colinérgicos/uso terapéutico , Americanos Mexicanos , Factores de Edad , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores Socioeconómicos , Sudoeste de Estados Unidos , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
BACKGROUND: As pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine for the prevention of HIV infection is rolled out internationally, strategies to maintain effectiveness and to minimise adverse effects merit consideration. In this study, we aimed to assess reductions in renal function and predictors of renal toxicity in a large open-label study of PrEP. METHODS: As part of the iPrEx open-label extension (OLE) study, men who have sex with men or transgender women aged 18-70 years who were HIV negative and had participated in three previous PrEP trials from Brazil, Ecuador, Peru, South Africa, Thailand, and the USA were enrolled into an open-label PrEP study. There were no restrictions on current renal function for enrolment into iPrEx OLE, in which participants were given combination tablets of tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) and advised to take one tablet per day. At follow-up sessions every 12 weeks, participants' creatinine clearance on PrEP was estimated and in a subset of participants, hair samples were collected to measure tenofovir and emtricitabine concentrations (a measure of adherence and exposure) via liquid-chromatography-tandem-mass-spectrometry. Reductions in creatinine clearance from baseline were calculated and predictors of decline were identified by use of multivariate models. iPrEx is registered with ClinicalTrials.com, number NCT00458393. FINDINGS: Baseline characteristics were similar between all participants in iPrEx-OLE (1224 participants with 7475 person-visits) and those participating in the hair substudy (220 participants with 1114 person-visits). During a median of 72 weeks, the mean decline in creatinine clearance was -2·9% (95% CI -2·4 to -3·4; ptrend<0·0001), but declines were greater for those who started PrEP at older ages: participants aged 40-50 years at baseline had declines of -4·2% (95% CI -2·8 to -5·5) and participants older than 50 years at baseline had declines of -4·9% (-3·1 to -6·8). In multivariate models, age and baseline creatinine clearance less than 90 mL/min predicted declines in renal function. We identified a monotonic association between percentage decrease in creatinine clearance and the number of doses of tenofovir disoproxil fumarate and emtricitabine taken per week, as estimated by hair concentrations of tenofovir and emtricitabine (ptrend=0·008). INTERPRETATION: Our data suggest that the frequency of safety monitoring for PrEP might need to be different between age groups and that pharmacological measures can monitor for toxic effects as well as adherence. FUNDING: National Institutes of Health.
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Fármacos Anti-VIH/efectos adversos , Creatinina/sangre , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición , Adulto , Factores de Edad , Fármacos Anti-VIH/análisis , Fármacos Anti-VIH/uso terapéutico , Brasil/epidemiología , Estudios de Cohortes , Ecuador/epidemiología , Emtricitabina/efectos adversos , Emtricitabina/análisis , Emtricitabina/uso terapéutico , Femenino , Infecciones por VIH/virología , Cabello/química , Humanos , Pruebas de Función Renal , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Perú/epidemiología , Sudáfrica , Tenofovir/efectos adversos , Tenofovir/análisis , Tenofovir/uso terapéutico , Tailandia/epidemiologíaRESUMEN
OBJECTIVE: To determine the contemporary etiology, burden, and short-term outcomes of seizures in neonates monitored with continuous video-electroencephalogram (cEEG). STUDY DESIGN: We prospectively collected data from 426 consecutive neonates (56% male, 88% term) ≤44 weeks' postmenstrual age with clinically suspected seizures and/or electrographic seizures. Subjects were assessed between January 2013 and April 2015 at 7 US tertiary care pediatric centers following the guidelines of the American Clinical Neurophysiology Society for cEEG for at-risk neonates. Seizure etiology, burden, management, and outcome were determined by chart review by the use of a case report form designed at study onset. RESULTS: The most common seizure etiologies were hypoxic-ischemic encephalopathy (38%), ischemic stroke (18%), and intracranial hemorrhage (11%). Seizure burden was high, with 59% having ≥7 electrographic seizures and 16% having status epilepticus; 52% received ≥2 antiseizure medications. During the neonatal admission, 17% died; 49% of survivors had abnormal neurologic examination at hospital discharge. In an adjusted analysis, high seizure burden was a significant risk factor for mortality, length of hospital stay, and abnormal neurological examination at discharge. CONCLUSIONS: In this large contemporary profile of consecutively enrolled newborns with seizures treated at centers that use cEEG per the guidelines of the American Clinical Neurophysiology Society, about one-half had high seizure burden, received ≥2 antiseizure medications, and/or died or had abnormal examination at discharge. Greater seizure burden was associated with increased morbidity and mortality. These findings underscore the importance of accurate determination of neonatal seizure frequency and etiology and a potential for improved outcome if seizure burden is reduced.