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OBJECTIVES: Stroke is the second most common cause of death and a major cause of disability. Besides the physical consequences, depressive symptoms are frequent in the aftermath after stroke. Every year, approximately 15 million stroke survivors worldwide are at risk of developing post-stroke depression. In this study we describe the natural course of depressive symptoms in stroke patients over a long-period of time post stroke and identify associated determinants. MATERIALS AND METHODS: From the Second Manifestations of ARTerial disease-Memory, depression and aging (SMART-Medea) study, an observational prospective cohort study, we selected patients with cerebrovascular disease, and used the biannually collected data of the Patient Health Questionnaire-9 for depressive symptoms. A score of ≥10 indicated the presence of depressive symptoms. A multinomial logistic regression analysis was used to identify prognostic determinants for courses of depressive symptoms after stroke. RESULTS: During a mean follow-up time of 7.9 years, 62% of the 172 participants was never depressed, 19% had a single episode and 19% had recurrent depressive symptoms. Physical function was associated with increased risk for single episode and recurrent depressive symptoms (OR=1.06 [1.01-1.11]). OR's for social, mental and (vascular) comorbidities variables were not significant. Participants' physical function was only measured at baseline. Several relevant variables were not present in this dataset, including information about clinical events during follow-up. CONCLUSION: Nearly 40% of the participants are confronted with depressive symptoms on the long-term. Physical function plays a substantial part for stroke survivors in the development of these symptoms.
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Depresión , Accidente Cerebrovascular , Sobrevivientes , Depresión/epidemiología , Estudios de Seguimiento , Humanos , Países Bajos/epidemiología , Estudios Prospectivos , Accidente Cerebrovascular/psicología , Accidente Cerebrovascular/terapia , Sobrevivientes/psicologíaRESUMEN
BACKGROUND: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously. OBJECTIVES: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV. METHODS: We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m2) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV. RESULTS: One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n=61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p<0.001). Neonatal outcomes were favourable. No significant differences in COVID-19 risk factors, disease severity, and maternal/neonatal outcome were noted for PLHIV v. those without HIV. CONCLUSIONS: In this cohort of high-risk pregnant women, the impact of COVID-19 was severe, significantly increasing maternal mortality risk compared with baseline rates. Virally suppressed HIV infection was not associated with worse COVID-19 outcomes in pregnancy.
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COVID-19/complicaciones , Infecciones por VIH/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo , Adulto , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Mortalidad Materna , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Embarazo de Alto Riesgo , Estudios Prospectivos , SudáfricaRESUMEN
BACKGROUND: Contamination of the hospital environment contributes to neonatal bacterial colonization and infection. Cleaning of hospital surfaces and equipment is seldom audited in resource-limited settings. METHODS: A quasi-experimental study was conducted to assess the impact of a multimodal cleaning intervention for surfaces and equipment in a 30-bed neonatal ward. The intervention included cleaning audits with feedback, cleaning checklists, in-room cleaning wipes and training of staff and mothers in cleaning methods. Cleaning adequacy was evaluated for 100 items (58 surfaces, 42 equipment) using quantitative bacterial surface cultures, adenosine triphosphate bioluminescence assays and fluorescent ultraviolet markers, performed at baseline (P1, October 2019), early intervention (P2, November 2019) and late intervention (P3, February 2020). RESULTS: Environmental swabs (55/300; 18.3%) yielded growth of 78 potential neonatal pathogens with Enterococci, S. marcescens, K. pneumoniae, S. aureus and A. baumannii predominating. Highest aerobic colony counts were noted from moist surfaces such as sinks, milk kitchen surfaces, humidifiers and suction tubing. The proportion of surfaces and equipment exhibiting no bacterial growth increased between phases (P1 = 49%, P2 = 66%, P3 = 69%; p = 0.007). The proportion of surfaces and equipment meeting the ATP "cleanliness" threshold (< 200 relative light units) increased over time (P1 = 40%, P2 = 54%, P3 = 65%; p = 0.002), as did the UV marker removal rate (P1 = 23%, P2 = 71%, P3 = 74%; p < 0.001). CONCLUSION: Routine environmental cleaning of this neonatal ward was sub-optimal at baseline but improved significantly following a multimodal cleaning intervention. Involving mothers and nursing staff was key to achieving improved environmental and equipment cleaning in this resource-limited neonatal unit.
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Infección Hospitalaria/prevención & control , Desinfección/métodos , Control de Infecciones/métodos , Bacterias/aislamiento & purificación , Lista de Verificación , Auditoría Clínica , Contaminación de Equipos/prevención & control , Hospitales Públicos , Hospitales de Enseñanza , Humanos , Recién Nacido , Madres , Personal de Hospital , SudáfricaRESUMEN
The South African National Department of Health published updated guidelines in 2019 for the prevention of mother-to-child transmission of communicable diseases. The proposed management of a neonate born to a mother with tuberculosis (TB) was included, and recommended referral of all symptomatic TB-exposed neonates to hospital for TB evaluation. However, no standard approach exists for evaluating hospitalised, symptomatic TB-exposed neonates, including preterm and low-birthweight (LBW) neonates born to mothers with TB. We use a clinical case report to illustrate a suggested approach to hospital-based evaluation of TB-exposed neonates, including preterm and LBW neonates. Guidance for the interpretation of different TB screening investigations in this population is also provided.
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Guías como Asunto , Tuberculosis/transmisión , Antituberculosos/uso terapéutico , Femenino , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Masculino , Sudáfrica/epidemiología , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiologíaRESUMEN
Despite a substantial decline in childhood mortality rates in South Africa (SA), progress in neonatal mortality reduction has been much slower. Severe bacterial infections remain a leading cause of neonatal morbidity and a direct cause of 13.1% of neonatal deaths among babies >1 kg. The incidence of hospital-acquired infections, antimicrobial resistance and outbreaks of infections in SA neonatal units is substantial, and is possibly higher than the currently available estimates. The SA Neonatal Sepsis Task Force was launched in Port Elizabeth, SA, on 13 September 2019 to provide technical advice and guidance on surveillance for neonatal sepsis, infection prevention, case management, antimicrobial stewardship and containment of neonatal unit outbreaks.
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Comités Consultivos , Programas de Optimización del Uso de los Antimicrobianos , Unidades de Cuidado Intensivo Neonatal , Sepsis Neonatal/epidemiología , Sepsis Neonatal/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Brotes de Enfermedades , Farmacorresistencia Microbiana , Humanos , Recién Nacido , Control de Infecciones , Vigilancia de la Población , Sudáfrica/epidemiologíaRESUMEN
The present study focuses on the investigation of the oxidized cell-free DNA (cfDNA) properties in several experimental models, including cultured cerebellum cells, peripheral blood lymphocytes (PBL), plasma, and hippocampus under an acute and chronic unpredictable stress model in rats. Firstly, our study shows that Spectrum Green fluorescence-labeled oxidized cfDNA fragments were transferred into the cytoplasm of 80% of the cerebellum culture cells; meanwhile, the nonoxidized cfDNA fragments do not pass into the cells. Oxidized cfDNA stimulates the antioxidant mechanisms and induction of transcription factor NRF2 expression, followed by an activation of NRF2 signaling pathway genes-rise of Nrf2 and Hmox1 gene expression and consequently NRF2 protein synthesis. Secondly, we showed that stress increases plasma cfDNA concentration in rats corresponding with the duration of the stress exposure. At the same time, our study did not reveal any significant changes of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) level in PBL of rats under acute or chronic stress, probably due to the significantly increased Nrf2 expression, that we found in such conditions. 8-oxodG is one of the most reliable markers of DNA oxidation. We also found an increased level of 8-oxodG in the hippocampal homogenates and hippocampal dentate gyrus in rats subjected to acute and chronic stress. Taken together, our data shows that oxidized cfDNA may play a significant role in systemic and neuronal physiological mechanisms of stress and adaptation.
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Antioxidantes/metabolismo , Ácidos Nucleicos Libres de Células/metabolismo , Estrés Oxidativo , 8-Hidroxi-2'-Desoxicoguanosina/análisis , Animales , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/química , Células Cultivadas , Cerebelo/citología , Cerebelo/metabolismo , Citoplasma/metabolismo , Regulación de la Expresión Génica , Hemo Oxigenasa (Desciclizante)/genética , Hemo Oxigenasa (Desciclizante)/metabolismo , Hipocampo/metabolismo , Linfocitos/metabolismo , Masculino , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Ratas Wistar , Transducción de SeñalRESUMEN
A recent fatal case of confirmed nosocomial tuberculosis (TB) transmission to a neonate in a kangaroo mother care (KMC) unit highlighted the infection risk to hospitalised neonates in South Africa, a high-burden TB setting. The index case was a 9-week-old infant who presented to another hospital's intensive care unit with severe respiratory distress shortly after discharge from the KMC unit. Contact tracing identified that the infant had been exposed to a postpartum woman with undiagnosed pulmonary TB while in the KMC unit. Molecular testing confirmed nosocomial transmission between the index case and the presumed source case in the KMC unit. We describe the subsequent process of tracing other TB-exposed infants and mothers, the difficulty in confirming TB infection/disease in pregnancy, and the provision of isoniazid preventive therapy in this cohort. We discuss the practical implementation of TB screening approaches in maternity and neonatal wards in high-burden TB settings.
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Infección Hospitalaria/transmisión , Complicaciones Infecciosas del Embarazo/diagnóstico , Tuberculosis Pulmonar/transmisión , Trazado de Contacto , Infección Hospitalaria/diagnóstico , Resultado Fatal , Femenino , Humanos , Lactante , Método Madre-Canguro , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Embarazo , Radiografía Torácica , Tuberculosis Pulmonar/diagnósticoRESUMEN
Data for six electric vehicle WOT interior sound measurements and eight enhanced sound signatures are presented. The measurement of electric vehicle interior sound signature data and the enhancement of these stimuli are documented in this data article. The procedures and equipment that were used to record the data, as well as the transposition, harmony and order addition, frequency filtering and modulation enhancement techniques that were applied to these stimuli are explained in detail. The transient frequency content of the 12 sound stimuli is presented in acoustic spectrograms along with the audio files in.mp3 format.
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BACKGROUND: A countrywide epidemic of Listeria monocytogenes (LM) in South Africa began in the first quarter of 2017, rapidly becoming the world's largest LM outbreak to date. METHODS: We describe the clinical course of neonates with culture-confirmed LM infection admitted to a tertiary neonatal unit at Tygerberg Hospital, Cape Town (1 January 2017 - 31 January 2018). Current epidemic LM cases were compared with a historical cohort of sporadic neonatal LM cases at our institution (2006 - 2016). The global literature on epidemic neonatal LM outbreaks (1 January 1978 - 31 December 2017) was reviewed. RESULTS: Twelve neonates (median gestational age 35 weeks, median birth weight 2 020 g) were treated for confirmed LM bacteraemia in 2017/18, presenting at a median age of 0.5 days. In 5 cases, neurolisteriosis was suspected. Three neonates died (25.0%) v. 8/13 neonatal deaths (61.6%) in the sporadic listeriosis cohort (2006 - 2016) (p=0.075). The institution's neonatal LM infection incidence increased significantly in 2017 from a historical rate of 0.17/1 000 live births to 1.4/1 000 (p<0.001). During the current LM epidemic, the crude neonatal fatality rate exceeded the average calculated global epidemic neonatal LM mortality (3/12 (25.0%) v. 50/290 (17.2%); p=0.448). Possible factors contributing to the high mortality rate in this epidemic LM neonatal cohort may include more virulent disease associated with sequence type 6 and the predominance of early-onset disease. CONCLUSIONS: Epidemic neonatal listeriosis at Tygerberg Hospital was associated with a predominance of bacteraemic, early-onset disease. Listeriosis-associated mortality rates were higher than previously published, but lower than the rate in a historical institutional cohort.
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Bacteriemia/epidemiología , Infecciones Bacterianas del Sistema Nervioso Central/epidemiología , Epidemias , Enfermedades del Recién Nacido/epidemiología , Listeriosis/epidemiología , Bacteriemia/mortalidad , Peso al Nacer , Infecciones Bacterianas del Sistema Nervioso Central/mortalidad , Femenino , Edad Gestacional , Humanos , Incidencia , Recién Nacido , Enfermedades del Recién Nacido/mortalidad , Recien Nacido Prematuro , Listeriosis/mortalidad , Masculino , Sudáfrica/epidemiología , Centros de Atención TerciariaRESUMEN
During ice navigation, blade measurements of ice-induced moments on ship propellers, are challenged by the harsh operating environment. To overcome this problem, shaft line measurements are performed inboard, and the required propeller loads are subsequently estimated using a dynamic model and the solution of an inverse problem. The inverse problem is mathematically ill-posed and requires the determination of the ice-induced moment on the propeller blades from shaft line measurements. Full-scale torsional response data is presented as calculated from indirect strain measurements on the shaft line of a polar supply and research vessel. The vessel operated on a 68-day voyage between Cape Town and Antarctica and spent almost 11 days in sea ice with observed concentrations above 90% and a maximum thickness of 3â¯m. Data for five ice-induced load cases are presented, including the shaft torque from indirect measurements and the estimated ice-induced moment, which is obtained by solving an ill-posed inverse problem. The ice-induced moments on the propeller are obtained by approximating the drive-train as a viscously damped, elastic lumped mass model. The ice-induced moment is then determined through existing approaches to solving the ill-conditioned inverse problem. The lumped mass model is presented along with algorithms to solve the inverse problem, including truncated singular value decomposition, truncated generalized singular value decomposition and Tikhonov׳s method. The resulting time series data for the inversely calculated ice-induced moments is published to provide industry with load cases for ice-going propulsion design.
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The history of the growth of continental crust is uncertain, and several different models that involve a gradual, decelerating, or stepwise process have been proposed1-4. Even more uncertain is the timing and the secular trend of the emergence of most landmasses above the sea (subaerial landmasses), with estimates ranging from about one billion to three billion years ago5-7. The area of emerged crust influences global climate feedbacks and the supply of nutrients to the oceans 8 , and therefore connects Earth's crustal evolution to surface environmental conditions9-11. Here we use the triple-oxygen-isotope composition of shales from all continents, spanning 3.7 billion years, to provide constraints on the emergence of continents over time. Our measurements show a stepwise total decrease of 0.08 per mille in the average triple-oxygen-isotope value of shales across the Archaean-Proterozoic boundary. We suggest that our data are best explained by a shift in the nature of water-rock interactions, from near-coastal in the Archaean era to predominantly continental in the Proterozoic, accompanied by a decrease in average surface temperatures. We propose that this shift may have coincided with the onset of a modern hydrological cycle owing to the rapid emergence of continental crust with near-modern average elevation and aerial extent roughly 2.5 billion years ago.
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Planeta Tierra , Sedimentos Geológicos/análisis , Sedimentos Geológicos/química , Ciclo Hidrológico , Agua/química , Historia Antigua , Minerales/análisis , Minerales/química , Isótopos de Oxígeno/análisis , Agua de Mar/química , TemperaturaRESUMEN
A polar supply and research vessel is pre-disposed to wave slamming which has caused complaints among crew and researchers regarding interference with sleep, equipment use and research activities. The present work undertook to survey passenger claims of sleep interference, disturbed motor tasks and equipment damage as a result of wave slamming during normal operations of this vessel. The hypothesis was investigated that whole-body vibration metrics from ISO 2631-1 are potentially suitable for the prediction of human slamming complaints. Full-scale acceleration measurements were performed and wave slamming events were subsequently identified from the human weighted acceleration time histories. A daily diary survey was also conducted to gather the human response. The vibration caused by wave slamming was found to be strongly correlated with sleep disturbances and activity interference. Sleep and equipment use were found to be the most affected parameters by slamming. Daily vibration dose values were determined by accumulating the vibration as a result of slamming over 24 h periods. This metric accounted for increased magnitudes and frequency of slamming incidents and proved to be the best metric to represent human responses to slamming vibration. The greatest percentage of activities affected by slamming related to sleep regardless of daily cumulative VDV magnitude. More than 50% of the recorded responses related to sleep when the daily cumulative VDV ranged between 8.0 m/s1.75-10.0 m/s1.75. The peak vertical vibration levels recorded on the vessel reach magnitudes which are associated with sleep disturbance in environments where acoustic noise is present.
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Enfermedades Profesionales/etiología , Exposición Profesional/análisis , Navíos , Trastornos del Sueño-Vigilia/etiología , Vibración/efectos adversos , Movimientos del Agua , Aceleración , Adulto , Humanos , Medicina Naval , SueñoRESUMEN
BACKGROUND: The rate of central-line-associated bloodstream infection (CLABSI) in South African (SA) public sector neonatal intensive care units (NICUs) is unknown. Tygerberg Children's Hospital (TCH), Cape Town, introduced a neonatal CLABSI surveillance and prevention programme in August 2012. OBJECTIVES: To describe CLABSI events and identify risk factors for development of CLABSI in a resource-limited NICU. METHODS: A retrospective case-control study was conducted using prospectively collected NICU CLABSI events matched to four randomly selected controls, sampled from the NICU registry between 9 August 2012 and 31 July 2014. Clinical data and laboratory records were reviewed to identify possible risk factors, using stepwise forward logistic regression analysis. RESULTS: A total of 706 central lines were inserted in 530 neonates during the study period. Nineteen CLABSI events were identified, with a CLABSI rate of 5.9/1 000 line days. CLABSI patients were of lower gestational age (28 v. 34 weeks; p=0.003), lower median birth weight (1 170 g v. 1 975 g; p=0.014), had longer catheter dwell times (>4 days) (odds ratio (OR) 5.1 (95% confidence interval (CI) 1.0 - 25.4); p=0.04) and were more likely to have had surgery during their NICU stay (OR 3.5 (95% CI 1.26 - 10); p=0.01). Significant risk factors for CLABSI were length of stay >30 days (OR 20.7 (95% CI 2.1 - 203.2); p=0.009) and central-line insertion in the operating theatre (OR 8.1 (95% CI 1.2 - 54.7); p=0.03). Gram-negative pathogens predominated (12/22; 54%), with most isolates (10/12; 83%) exhibiting multidrug resistance. CONCLUSION: The TCH NICU CLABSI rate is similar to that reported from resource-limited settings, but exceeds that of high-income countries. Prolonged NICU stay and central-line insertion in the operating theatre were important risk factors for CLABSI development. Intensified neonatal staff training regarding CLABSI maintenance bundle elements and hand hygiene are key to reducing CLABSI rates.
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BACKGROUND: Hospitalized neonates are vulnerable to infection, with pathogen exposures occurring in utero, intrapartum, and postnatally. African neonatal units are at high risk of outbreaks owing to overcrowding, understaffing, and shared equipment. METHODS: Neonatal outbreaks attended by the paediatric infectious diseases and infection prevention (IP) teams at Tygerberg Children's Hospital, Cape Town (May 1, 2008 to April 30, 2016) are described, pathogens, outbreak size, mortality, source, and outbreak control measures. Neonatal outbreaks reported from Africa (January 1, 1996 to January 1, 2016) were reviewed to contextualize the authors' experience within the published literature from the region. RESULTS: Thirteen outbreaks affecting 148 babies (11 deaths; 7% mortality) over an 8-year period were documented, with pathogens including rotavirus, influenza virus, measles virus, and multidrug-resistant bacteria (Serratia marcescens, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci). Although the infection source was seldom identified, most outbreaks were associated with breaches in IP practices. Stringent transmission-based precautions, staff/parent education, and changes to clinical practices contained the outbreaks. From the African neonatal literature, 20 outbreaks affecting 524 babies (177 deaths; 34% mortality) were identified; 50% of outbreaks were caused by extended-spectrum ß-lactamase-producing Klebsiella pneumoniae. CONCLUSIONS: Outbreaks in hospitalized African neonates are frequent but under-reported, with high mortality and a predominance of Gram-negative bacteria. Breaches in IP practice are commonly implicated, with the outbreak source confirmed in less than 50% of cases. Programmes to improve IP practice and address antimicrobial resistance in African neonatal units are urgently required.
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Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Control de Infecciones , África/epidemiología , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Sudáfrica/epidemiologíaRESUMEN
Background. The rate of central-line-associated bloodstream infection (CLABSI) in South African (SA) public sector neonatal intensive care units (NICUs) is unknown. Tygerberg Children's Hospital (TCH), Cape Town, introduced a neonatal CLABSI surveillance and prevention programme in August 2012.Objectives. To describe CLABSI events and identify risk factors for development of CLABSI in a resource-limited NICU.Methods. A retrospective case-control study was conducted using prospectively collected NICU CLABSI events matched to four randomly selected controls, sampled from the NICU registry between 9 August 2012 and 31 July 2014. Clinical data and laboratory records were reviewed to identify possible risk factors, using stepwise forward logistic regression analysis.Results. A total of 706 central lines were inserted in 530 neonates during the study period. Nineteen CLABSI events were identified, with a CLABSI rate of 5.9/1 000 line days. CLABSI patients were of lower gestational age (28 v. 34 weeks; p=0.003), lower median birth weight (1 170 g v. 1 975 g; p=0.014), had longer catheter dwell times (>4 days) (odds ratio (OR) 5.1 (95% confidence interval (CI) 1.0 - 25.4); p=0.04) and were more likely to have had surgery during their NICU stay (OR 3.5 (95% CI 1.26 - 10); p=0.01). Significant risk factors for CLABSI were length of stay >30 days (OR 20.7 (95% CI 2.1 - 203.2); p=0.009) and central-line insertion in the operating theatre (OR 8.1 (95% CI 1.2 - 54.7); p=0.03). Gram-negative pathogens predominated (12/22; 54%), with most isolates (10/12; 83%) exhibiting multidrug resistance. Conclusion. The TCH NICU CLABSI rate is similar to that reported from resource-limited settings, but exceeds that of high-income countries. Prolonged NICU stay and central-line insertion in the operating theatre were important risk factors for CLABSI development. Intensified neonatal staff training regarding CLABSI maintenance bundle elements and hand hygiene are key to reducing CLABSI rates
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Sangre/microbiología , Estudios de Casos y Controles , Unidades de Cuidado Intensivo Neonatal , Sepsis Neonatal , SudáfricaRESUMEN
SETTING: To assess the revised World Health Organization-recommended dose of 10-20 mg/kg rifampicin (RMP), we studied the steady state pharmacokinetics of RMP in South African children who received standard treatment for drug-susceptible tuberculosis (TB). OBJECTIVE: To determine the formulation effect on the pharmacokinetics of RMP. DESIGN: RMP plasma concentrations were characterised in 146 children (median age 1.4 years, range 0.2-10.2). The morning dose on the day of the pharmacokinetic evaluation was administered as one of two RMP single-drug oral suspensions. RESULTS: While one formulation achieved 2 h concentrations in the range of those observed in adults (median 6.54 mg/l, interquartile range [IQR] 4.47-8.84), the other attained a median bioavailability of only 25% of this, with a median 2 h concentration of 1.59 mg/l (IQR 0.89-2.38). CONCLUSION: RMP is a key drug for the treatment of TB. It is critical that the quality of RMP suspensions used to treat childhood TB is ensured.
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Antibióticos Antituberculosos/farmacocinética , Aprobación de Drogas , Concesión de Licencias , Rifampin/farmacocinética , Tuberculosis/tratamiento farmacológico , Administración Oral , Antibióticos Antituberculosos/administración & dosificación , Antibióticos Antituberculosos/química , Antibióticos Antituberculosos/normas , Disponibilidad Biológica , Niño , Preescolar , Composición de Medicamentos , Monitoreo de Drogas , Femenino , Humanos , Lactante , Concesión de Licencias/normas , Masculino , Soluciones Farmacéuticas , Garantía de la Calidad de Atención de Salud , Control de Calidad , Rifampin/administración & dosificación , Rifampin/química , Rifampin/normas , Sudáfrica , Tuberculosis/sangre , Tuberculosis/diagnósticoRESUMEN
There are limited pharmacokinetic data for use of the first-line antituberculosis drugs during infancy (<12 months of age), when drug disposition may differ. Intensive pharmacokinetic sampling was performed in infants routinely receiving antituberculosis treatment, including rifampin, isoniazid, pyrazinamide, and ethambutol, using World Health Organization-recommended doses. Regulatory-approved single-drug formulations, including two rifampin suspensions, were used on the sampling day. Assays were conducted using liquid chromatography-mass spectrometry; pharmacokinetic parameters were generated using noncompartmental analysis. Thirty-nine infants were studied; 14 (36%) had culture-confirmed tuberculosis. Fifteen (38%) were premature (<37 weeks gestation); 5 (13%) were HIV infected. The mean corrected age and weight were 6.6 months and 6.45 kg, respectively. The mean maximum plasma concentrations (Cmax) for rifampin, isoniazid, pyrazinamide, and ethambutol were 2.9, 7.9, 41.9, and 1.3 µg/ml, respectively (current recommended adult target concentrations: 8 to 24, 3 to 6, 20 to 50, and 2 to 6 µg/ml, respectively), and the mean areas under the concentration-time curves from 0 to 8 h (AUC0-8) were 12.1, 24.7, 239.4, and 5.1 µg · h/ml, respectively. After adjusting for age and weight, rifampin exposures for the two formulations used differed inCmax(geometric mean ratio [GMR],2.55; 95% confidence interval [CI], 1.47 to 4.41;P= 0.001) and AUC0-8(GMR, 2.52; 95% CI, 1.34 to 4.73;P= 0.005). HIV status was associated with lower pyrazinamideCmax(GMR, 0.85; 95% CI, 0.75 to 0.96;P= 0.013) and AUC0-8(GMR, 0.79; 95% CI, 0.69 to 0.90;P< 0.001) values. No other important differences were observed due to age, weight, prematurity, ethnicity, or gender. In summary, isoniazid and pyrazinamide concentrations in infants compared well with proposed adult target concentrations; ethambutol concentrations were lower but similar to previously reported pediatric studies. The low rifampin exposures require further investigation. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637558.).
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Antibacterianos/farmacocinética , Etambutol/farmacocinética , Isoniazida/farmacocinética , Mycobacterium tuberculosis/efectos de los fármacos , Pirazinamida/farmacocinética , Rifampin/farmacocinética , Tuberculosis Pulmonar/tratamiento farmacológico , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Área Bajo la Curva , Coinfección , Cálculo de Dosificación de Drogas , Etambutol/sangre , Etambutol/uso terapéutico , Femenino , VIH/efectos de los fármacos , VIH/crecimiento & desarrollo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Lactante , Recién Nacido , Isoniazida/sangre , Isoniazida/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/crecimiento & desarrollo , Guías de Práctica Clínica como Asunto , Pirazinamida/sangre , Pirazinamida/uso terapéutico , Rifampin/sangre , Rifampin/uso terapéutico , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/microbiologíaRESUMEN
Increasingly, postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly; but it's etiology remains unclear. Here we examine changes in cytokine levels during both the pre-operative and postoperative period, comparing them with long term variation in cognitive test scores. Forty-one patients aged 65 and older undergoing major surgery with general anesthesia were recruited after written consent in this IRB approved study. Thirty went on to complete this prospective, non-interven-tional and non-randomized study. Plasma levels of cytokines Il-6, Il-8, Il-10, and TNF were determined using ELISA with MILLIPLEX Multi-Analyte Profiling (Billerica, MA). All subjects had neurocognitive tests pre-operatively and 6 months post-surgery, including Paragraph Recall Immediate and Delayed, Digit Span Forward (DSF) and Backward (DSB), and Trail Making A and B. Spearman's Rho and repeated measure rank analysis were used to examine the dependence of z score changes in cognitive tests (baseline versus 6 months) as a function of 3 cytokine time points (presurgical, post anesthesia care unit (PACU), and post-operative day one (POD1)). A greater increase in PACU inflammatory burden correlated with a greater decline in performance on the DSB (IL6, IL8; r>-0.560; p<= 0.008). DSF changes correlated slightly better with pre-surgical cytokines, declining more with higher cytokines (IL6, r= -0.551, p=0.002; IL8, -0.468, 0.009). TNF, examining all 3 values, changed only slightly postoperatively, but still correlated with a decline in DSB (p=0.014). Thus, cognitive performance, over 6 months post surgery, declines with elevated perioperative inflammation. Specific cytokines at specific perioperative times may impact specific cognitive functions, serving as diagnostics as well as contributing causation.
RESUMEN
The effect of temperature on the growth kinetics and proteolytic activity of Chryseobacterium joostei and Chryseobacterium bovis was determined during this study. The results were compared with the activities of Pseudomonas fluorescens, which is regarded to be a major food spoilage psychrotolerant microorganism. For the growth studies, cultures were incubated in nutrient broth in a temperature gradient incubator (from 9 to 50 °C) and separately at 4 °C, and the optical density was measured at different time intervals. Growth temperature profiles for each organism were constructed. For determination of proteolytic activity, the cultures were incubated in fat-free ultra-high temperature processed milk in the temperature gradient incubator for 72 h (temperature range as above). Cell-free extracts were used to determine the proteolytic activity using the azocasein method. Results of the growth studies showed that C. joostei had the ability to grow over a wider temperature range than C. bovis and P. fluorescens without being affected by changes in the temperature. For the proteolytic activity, C. joostei had significantly (p < 0.001) higher activity per milligram of protein at 15.5 °C, followed by C. bovis and P. fluorescens. The results showed that C. joostei potentially has an even greater spoilage capacity in milk on the basis of growth rate and proteolytic activity than did P. fluorescens.
Asunto(s)
Chryseobacterium/crecimiento & desarrollo , Chryseobacterium/metabolismo , Leche/microbiología , Pseudomonas fluorescens/crecimiento & desarrollo , Pseudomonas fluorescens/metabolismo , Animales , Caseínas/metabolismo , Bovinos , Chryseobacterium/química , Cinética , Leche/metabolismo , Pseudomonas fluorescens/química , TemperaturaRESUMEN
Cortical bone is a visco-elastic material which implies that strain rate will affect its response. Although the Split-Hopkinson Pressure Bar is an accepted technique for determining the dynamic compressive properties of cortical bone it has been shown that the strain rate of compression does not remain constant throughout the duration of a classical experiment with a uniform striker. This raises concerns as to the measurement of smeared responses. This paper presents a shaped striker technique whereby the incident pulse can be shaped to attain a constant strain rate experiment for bovine bone. Shaped strikers offer benefits such as re-usability and increased test repeatability. A comparison of the stress-strain-strain rate responses attained through classical and constant strain rate experiments shows that the shape of the stress-strain curves from conventional experiments is adversely affected in the portion where the strain rate varies. The dynamic response corridors for the two tests are similar, however the ultimate properties are affected. It is concluded that the strain rate history should be presented with dynamic stress-strain responses since the instantaneous strain rate is a likely contributor to potential constitutive models.