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1.
Nephrol Dial Transplant ; 36(4): 657-665, 2021 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-31860096

RESUMEN

BACKGROUND AND OBJECTIVES: The Acute Kidney Outreach to Reduce Deterioration and Death trial was a large pilot study for a cluster-randomized trial of acute kidney injury (AKI) outreach. METHODS: An observational control (before) phase was conducted in two teaching hospitals (9 miles apart) and their respective catchment areas. In the intervention (after) phase, a working-hours AKI outreach service operated for the intervention hospital/area for 20 weeks, with the other site acting as a control. All AKI alerts in both hospital and community patients were screened for inclusion. Major exclusion criteria were patients who were at the end of life, unlikely to benefit from outreach, lacking mental capacity or already referred to the renal team. The intervention arm included a model of escalation of renal care to AKI patients, depending on AKI stage. The 30-day primary outcome was a combination of death, or deterioration, as shown by any need for dialysis or progression in AKI stage. A total of 1762 adult patients were recruited; 744 at the intervention site during the after phase. RESULTS: A median of 3.0 non-medication recommendations and 0.5 medication-related recommendations per patient were made by the outreach team a median of 15.7 h after the AKI alert. Relatively low rates of the primary outcomes of death within 30 days (11-15%) or requirement for dialysis (0.4-3.7%) were seen across all four groups. In an exploratory analysis, at the intervention hospital during the after phase, there was an odds ratio for the combined primary outcome of 0.73 (95% confidence interval 0.42-1.26; P = 0.26). CONCLUSIONS: An AKI outreach service can provide standardized specialist care to those with AKI across a healthcare economy. Trials assessing AKI outreach may benefit from focusing on those patients with 'mid-range' prognosis, where nephrological intervention could have the most impact.


Asunto(s)
Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/prevención & control , Diálisis Renal/mortalidad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Tasa de Supervivencia
3.
Diabet Med ; 35(8): 1005-1010, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30152588

RESUMEN

Optimal glycaemic control before and during pregnancy improves both maternal and fetal outcomes. This article summarizes the recently published guidelines on the management of glycaemic control in pregnant women with diabetes on obstetric wards and delivery units produced by the Joint British Diabetes Societies for Inpatient Care and available in full at www.diabetes.org.uk/joint-british-diabetes-society and https://abcd.care/joint-british-diabetes-societies-jbds-inpatient-care-group. Hyperglycaemia following steroid administration can be managed by variable rate intravenous insulin infusion (VRIII) or continuous subcutaneous insulin infusion (CSII) in women who are willing and able to safely self-manage insulin dose adjustment. All women with diabetes should have capillary blood glucose (CBG) measured hourly once they are in established labour. Those who are found to be higher than 7 mmol/l on two consecutive occasions should be started on VRIII. If general anaesthesia is used, CBG should be monitored every 30 min in the theatre. Both the VRIII and CSII rate should be reduced by at least 50% once the placenta is delivered. The insulin dose needed after delivery in insulin-treated Type 2 and Type 1 diabetes is usually 25% less than the doses needed at the end of first trimester. Additional snacks may be needed after delivery especially if breastfeeding. Stop all anti-diabetes medications after delivery in gestational diabetes. Continue to monitor CBG before and 1 h after meals for up to 24 h after delivery to pick up any pre-existing diabetes or new-onset diabetes in pregnancy. Women with Type 2 diabetes on oral treatment can continue to take metformin after birth.


Asunto(s)
Glucocorticoides/uso terapéutico , Hiperglucemia/terapia , Trabajo de Parto , Parto , Embarazo en Diabéticas/terapia , Atención Prenatal/métodos , Administración Intravenosa , Adulto , Parto Obstétrico/métodos , Parto Obstétrico/normas , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Femenino , Madurez de los Órganos Fetales/efectos de los fármacos , Humanos , Hiperglucemia/sangre , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Sistemas de Infusión de Insulina , Trabajo de Parto/efectos de los fármacos , Trabajo de Parto/fisiología , Parto/efectos de los fármacos , Parto/fisiología , Embarazo , Embarazo en Diabéticas/sangre
4.
Sensors (Basel) ; 19(1)2018 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-30577499

RESUMEN

Rotary-wing small unmanned aircraft systems (sUAS) are increasingly being used for sampling thermodynamic and chemical properties of the Earth's atmospheric boundary layer (ABL) because of their ability to measure at high spatial and temporal resolutions. Therefore, they have the potential to be used for long-term quasi-continuous monitoring of the ABL, which is critical for improving ABL parameterizations and improving numerical weather prediction (NWP) models through data assimilation. Before rotary-wing aircraft can be used for these purposes, however, their performance and the sensors used therein must be adequately characterized. In the present study, we describe recent calibration and validation procedures for thermodynamic sensors used on two rotary-wing aircraft: A DJI S-1000 and MD4-1000. These evaluations indicated a high level of confidence in the on-board measurements. We then used these measurements to characterize the spatiotemporal variability of near-surface (up to 300-m AGL) temperature and moisture fields as a component of two recent field campaigns: The Verification of the Origins of Rotation in Tornadoes Experiment in the Southeast U.S. (VORTEX-SE) in Alabama, and the Land Atmosphere Feedback Experiment (LAFE) in northern Oklahoma.

5.
Int J Biometeorol ; 57(1): 91-105, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22438053

RESUMEN

Respiratory morbidity (particularly COPD and asthma) can be influenced by short-term weather fluctuations that affect air quality and lung function. We developed a model to evaluate meteorological conditions associated with respiratory hospital admissions in the Shenandoah Valley of Virginia, USA. We generated ensembles of classification trees based on six years of respiratory-related hospital admissions (64,620 cases) and a suite of 83 potential environmental predictor variables. As our goal was to identify short-term weather linkages to high admission periods, the dependent variable was formulated as a binary classification of five-day moving average respiratory admission departures from the seasonal mean value. Accounting for seasonality removed the long-term apparent inverse relationship between temperature and admissions. We generated eight total models specific to the northern and southern portions of the valley for each season. All eight models demonstrate predictive skill (mean odds ratio = 3.635) when evaluated using a randomization procedure. The predictor variables selected by the ensembling algorithm vary across models, and both meteorological and air quality variables are included. In general, the models indicate complex linkages between respiratory health and environmental conditions that may be difficult to identify using more traditional approaches.


Asunto(s)
Hospitalización/estadística & datos numéricos , Modelos Teóricos , Enfermedades Respiratorias/epidemiología , Humanos , Enfermedades Respiratorias/prevención & control , Estaciones del Año , Virginia/epidemiología , Tiempo (Meteorología)
6.
Diabetologia ; 55(2): 282-93, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22080230

RESUMEN

AIMS/HYPOTHESIS: Although maternal hyperglycaemia is associated with increased risk of adverse pregnancy outcome, the mechanisms of postprandial hyperglycaemia during pregnancy are poorly understood. We aimed to describe glucose turnover in pregnant women with type 1 diabetes, according to stage of gestation (early vs late gestation). METHODS: The rates of systemic glucose appearance (R(a)) and glucose disposal (R(d)) were measured in ten pregnant women with type 1 diabetes during early (12-16 weeks) and late (28-32 weeks) gestation. Women ate standardised meals--a starch-rich 80 g carbohydrate dinner and a sugar-rich 60 g carbohydrate breakfast--and fasted between meals and overnight. Stable-label isotope tracers ([6,6-(2)H(2)]glucose and [U-(13)C]glucose) were used to determine R(a), R(d) and glucose bioavailability. Closed-loop insulin delivery maintained stable glycaemic conditions. RESULTS: There were no changes in fasting R(a) (10 ± 2 vs 11 ± 2 µmol kg(-1) min(-1); p = 0.32) or fasting R(d) (11 ± 2 vs 11 ± 1 µmol kg(-1) min(-1); p = 0.77) in early vs late gestation. There was increased hepatic insulin resistance (381 ± 237 vs 540 ± 242 µmol kg(-1) min(-1) × pmol/l; p = 0.04) and decreased peripheral insulin sensitivity (0.09 ± 0.04 vs 0.05 ± 0.02 µmol kg(-1) min(-1) per pmol/l dinner, 0.11 ± 0.05 vs 0.07 ± 0.03 µmol kg(-1) min(-1) per pmol/l breakfast; p = 0.002) in late gestation. It also took longer for insulin levels to reach maximal concentrations (49 [37-55] vs 71 [52-108] min; p = 0.004) with significantly delayed glucose disposal (108 [87-125] vs 135 [110-158] min; p = 0.005) in late gestation. CONCLUSIONS/INTERPRETATION: Postprandial glucose control is impaired by significantly slower glucose disposal in late gestation. Early prandial insulin dosing may help to accelerate glucose disposal and potentially ameliorate postprandial hyperglycaemia in late pregnancy. TRIAL REGISTRATION: ISRCTN 62568875 FUNDING: Diabetes UK Project Grant BDA 07/003551. H.R. Murphy is funded by a National Institute for Health Research (NIHR) research fellowship (PDF/08/01/036). Supported also by the Juvenile Diabetes Research Foundation (JDRF), Abbott Diabetes Care (Freestyle Navigator CGM and sensors free of charge), Medical Research Council Centre for Obesity and Related Metabolic Diseases and NIHR Cambridge Biomedical Research Centre.


Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Gestacional/fisiopatología , Hiperglucemia/fisiopatología , Complicaciones del Embarazo , Administración Oral , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Carbohidratos/química , Diabetes Mellitus Tipo 1/complicaciones , Ayuno , Femenino , Humanos , Resistencia a la Insulina , Periodo Posprandial , Embarazo , Resultado del Embarazo , Riesgo , Factores de Tiempo
7.
Clin Med (Lond) ; 12(4): 316-9, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22930873

RESUMEN

In an ageing population, patients are living longer with one or more chronic disease, and with acute illnesses increasingly extending outside the boundaries of a single medical specialty. Therefore, is it time for the general physician to take charge?


Asunto(s)
Médicos Generales , Cuerpo Médico de Hospitales/organización & administración , Rol del Médico , Comorbilidad , Continuidad de la Atención al Paciente , Necesidades y Demandas de Servicios de Salud , Servicios de Salud para Ancianos/organización & administración , Hospitalización , Humanos , Grupo de Atención al Paciente , Reino Unido
8.
Diabet Med ; 28(7): 845-8, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21395676

RESUMEN

AIMS: Maternal diabetes is a recognized risk factor for congenital malformation, perinatal morbidity and obesity in later childhood. The aim of this study is to assess the impact of maternal diabetes on cognitive function in offspring. METHODS: Participants were 6- to 12-year-old offspring of women with Type 1 diabetes. All women received their antenatal care and delivered at one university hospital. HbA(1c) was monitored monthly throughout pregnancy and cognitive function was assessed using the Wechsler Intelligence Scale for Children, version 4. RESULTS: We present results in 40 offspring. There was no difference in overall full-scale IQ compared with UK normative data. However, working memory was poorer than other parts of the Wechsler Intelligence Scale for Children version 4 test and significantly lower compared with UK normative data [8.4 (2.2) vs. 10.1 (3.2), P < 0.01]. We found no correlation between measurement of digit span or HbA(1c) at any stage during pregnancy (r = -0.225 to 0.002), gestational age at delivery (r = -0.178) or infant birthweight ratio (r = -0.176). There was no relationship between working memory score and maternal hypoglycaemia episodes or maternal duration of diabetes. Comparing infants born before (n = 9) or after 37 weeks' gestation, digit span was non-significantly lower [7.9 (1.8) vs. 8.6 (2.4)]. DISCUSSION: These results suggest offspring of women with Type 1 diabetes have normal overall cognitive function but poorer working memory. We have been unable to identify specific risk factors. Further larger studies are required to increase the understanding of this memory defect and identify any modifiable risk factors.


Asunto(s)
Cognición/fisiología , Diabetes Mellitus Tipo 1/fisiopatología , Hemoglobina Glucada/metabolismo , Embarazo en Diabéticas/fisiopatología , Niño , Diabetes Mellitus Tipo 1/genética , Femenino , Hemoglobina Glucada/genética , Humanos , Pruebas de Inteligencia , Masculino , Embarazo , Embarazo en Diabéticas/genética , Factores de Riesgo , Escalas de Wechsler
9.
Diabet Med ; 28(9): 1060-7, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21843303

RESUMEN

AIMS: To compare obstetric and perinatal outcomes in women with Type 1 and Type 2 diabetes and relate these to maternal risk factors. METHODS: Prospective cohort study of 682 consecutive diabetic pregnancies in East Anglia during 2006-2009. Relationships between congenital malformation, perinatal mortality and perinatal morbidity (large for gestational age, preterm delivery, neonatal care) with maternal age, parity, ethnicity, glycaemic control, obesity and social disadvantage were examined using bivariable and multivariate models. RESULTS: There were 408 (59.8%) Type 1 and 274 (40.2%) Type 2 diabetes pregnancies. Women with Type 2 diabetes were older (P < 0.001), heavier (P < 0.0001), more frequently multiparous (P < 0.001), more ethnically diverse (p < 0.0001) and more socially disadvantaged (P = 0.0004). Although women with Type 2 diabetes had shorter duration of diabetes (P < 0.0001) and better pre-conception glycaemic control [HbA(1c) 52 mmol/mol (6.9%) Type 2 diabetes vs. 63 mmol/l (7.9%) Type 1 diabetes; p < 0.0001), rates of congenital malformation and perinatal mortality were comparable. Women with Type 2 diabetes had fewer large-for-gestational-age infants (37.6 vs. 52.9%, P < 0.0008), fewer preterm deliveries (17.5 vs. 37.1%, P < 0.0001) and their offspring had fewer neonatal care admissions (29.8 vs. 43.2%, P = 0.001). Third trimester HbA(1c) (OR 1.35, 95% CI 1.09-1.67, P = 0.006) and social disadvantage (OR 0.80, 95% CI 0.67-0.98; P = 0.03) were risk factors for large for gestational age. CONCLUSIONS: Despite increased age, parity, obesity and social disadvantage, women with Type 2 diabetes had better glycaemic control, fewer large-for-gestational-age infants, fewer preterm deliveries and fewer neonatal care admissions. Better tools are needed to improve glycaemic control and reduce the rates of large for gestational age, particularly in Type 1 diabetes.


Asunto(s)
Anomalías Congénitas/epidemiología , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada/metabolismo , Obesidad/epidemiología , Embarazo en Diabéticas/epidemiología , Adulto , Estudios de Cohortes , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Recién Nacido , Edad Materna , Obesidad/complicaciones , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Factores de Riesgo , Factores Socioeconómicos , Adulto Joven
10.
Diabet Med ; 27(1): 92-100, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20121895

RESUMEN

AIMS: To explore the views of women who did not attend pre-pregnancy care (PPC), in particular their accounts of contraception, previous pregnancies and the influence of healthcare advice. METHODS: We conducted semi-structured interviews with 29 pregnant women (21 with Type 1 diabetes, eight with Type 2 diabetes) at three UK specialist diabetes antenatal clinics. Interviews explored women's journeys to becoming pregnant, including use of contraception, their views regarding diabetes and pregnancy and the factors which encouraged and discouraged them from attending PPC. RESULTS: All women had some understanding of the issues concerning diabetes during pregnancy, predominantly regarding the benefits of PPC (90%) and optimal glycaemic control (80%) and risks of malformation (48%) and macrosomia (35%). Most were not regularly using contraception (70%), having stopped deliberately (45%), become unintentionally less rigorous (28%) or experienced side effects/contraindications (14%). Knowledge concerning the risks of pregnancy (90%) and past pre-conception counselling (38%) did not encourage women to attend PPC, and neither did personal experience of miscarriage, malformation or stillbirth in women with previous poor pregnancy outcome (41%). Barriers included conceiving faster than anticipated (45%), fertility concerns (31%), negative experiences with health professionals (21%), desire for a 'normal' pregnancy (17%) and the logistics of attending (10%). CONCLUSIONS: More integrated diabetes and reproductive health/contraceptive advice, increased awareness of the potentially short time between stopping contraception and conception and more intensive support between pregnancies are required, particularly for women with previously poor outcomes. Research is also needed into how communication between health professionals and women with diabetes can be improved.


Asunto(s)
Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 2/psicología , Atención Preconceptiva/métodos , Embarazo en Diabéticas/psicología , Embarazo de Alto Riesgo/psicología , Atención Prenatal/métodos , Adulto , Actitud Frente a la Salud , Anticonceptivos , Consejo , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Entrevistas como Asunto , Embarazo , Embarazo en Diabéticas/epidemiología , Factores de Riesgo , Reino Unido/epidemiología
11.
Diabet Med ; 27(11): 1264-70, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20950384

RESUMEN

AIMS: We tested the hypothesis that diabetes during pregnancy leads to chromosomal DNA damage and telomere attrition in the feto placental unit and cord blood, and provides evidence for intrauterine programming towards a senescent phenotype in the offspring. METHODS: We obtained cord blood from pregnant women with pregestational Type 1 diabetes (n=26), Type 2 diabetes (n=20) or gestational diabetes (n=71), and control subjects without diabetes (n=45, n=76 and n=81, respectively) matched for maternal and gestational age. We measured cord blood mononuclear cell telomere length, telomerase activity (a reverse transcriptase that limits telomere attrition), and concentrations of insulin, high-sensitivity C-reactive protein (hs-CRP) and soluble intercellular adhesion molecule-1 (sICAM-1). RESULTS: We found no significant differences between groups in cord blood telomere length in any nucleated cell type, or in hs-CRP or sICAM-1 concentrations, but telomerase activity was higher in cord blood from Type 1 (P<0.05) and gestational diabetes pregnancies (P<0.05), but not in Type 2 diabetes pregnancies. There were no significant relationships between glycaemic control, cord blood telomere length, telomerase activity or inflammatory markers in any group. CONCLUSIONS: We found no difference in cord blood telomere length in pregnancies of women with diabetes compared with control subjects, but higher cord blood telomerase activity in Type 1 and gestational diabetes. This may reflect upregulated telomere reverse transcriptase in response to in utero oxidative DNA and telomere damage. These observations are relevant to the hypothesis that diabetes during pregnancy leads to in utero preprogramming towards senescence in the offspring.


Asunto(s)
Daño del ADN/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , Sangre Fetal , Embarazo en Diabéticas/genética , Telomerasa/metabolismo , Telómero/genética , Adulto , Biomarcadores/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Gestacional/sangre , Femenino , Humanos , Recién Nacido , Embarazo , Embarazo en Diabéticas/sangre
12.
Diabetologia ; 52(2): 226-34, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19034420

RESUMEN

AIMS/HYPOTHESIS: The offspring of mothers with pre-gestational type 1 diabetes (PGDM) may be at increased risk of glucose intolerance and cardiovascular disease in childhood. The underlying causes of these observations, and whether they persist into adulthood, are unknown. The aim of the present study was to test the hypothesis that fetal chromosomal telomere oxidative DNA damage resulting from maternal PGDM programmes the offspring towards a senescent phenotype that is detectable in young adulthood. METHODS: We studied 21 young adult offspring (age 16-23 years) with a maternal history of PGDM and 23 age- and weight-matched controls with no maternal history of diabetes. All participants underwent anthropometric assessments, a standard 75 g OGTT, measurement of peripheral blood mononuclear cell and skin fibroblast telomere length, fibroblast senescence, cell DNA damage (by determination of 8-oxoguanine levels using flow cytometry), plasma lipoprotein profiles (determined by nuclear magnetic resonance) and plasma levels of soluble adhesion molecules and inflammatory markers. RESULTS: The groups did not differ significantly with respect to anthropometric measures, glucose tolerance, fasting and 2 h plasma insulin levels during OGTT, estimated peripheral insulin resistance, peripheral blood mononuclear cell or fibroblast telomere length, DNA damage or senescence in vitro, plasma NMR lipoprotein profiles or levels of high-sensitivity C-reactive protein. Plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1; p < 0.05) and IL-6 (p = 0.08) were higher in the PGDM offspring. CONCLUSIONS/INTERPRETATION: Young adult offspring of mothers with PGDM do not differ in terms of glucose tolerance, DNA damage or telomere length from controls of the same weight and BMI. This does not preclude such abnormalities at an earlier age, but there is no evidence of telomere damage as a pre-programming mechanism in the young adults enrolled in this study.


Asunto(s)
Daño del ADN , Diabetes Mellitus Tipo 1/genética , Telómero/genética , Adolescente , Biopsia , Femenino , Fibroblastos/citología , Fibroblastos/fisiología , Humanos , Madres , Selección de Paciente , Embarazo , Fenómenos Fisiológicos de la Piel , Adulto Joven
15.
Ecol Evol ; 8(15): 7553-7562, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30151170

RESUMEN

A frequent assumption in ecology is that biotic interactions are more important than abiotic factors in determining lower elevational range limits (i.e., the "warm edge" of a species distribution). However, for species with narrow environmental tolerances, theory suggests the presence of a strong environmental gradient can lead to persistence, even in the presence of competition. The relative importance of biotic and abiotic factors is rarely considered together, although understanding when one exerts a dominant influence on controlling range limits may be crucial to predicting extinction risk under future climate conditions. We sampled multiple transects spanning the elevational range limit of Plethodon shenandoah and site and climate covariates were recorded. A two-species conditional occupancy model, accommodating heterogeneity in detection probability, was used to relate variation in occupancy with environmental and habitat conditions. Regional climate data were combined with datalogger observations to estimate the cloud base heights and to project future climate change impacts on cloud elevations across the survey area. By simultaneously accounting for species' interactions and habitat variables, we find that elevation, not competition, is strongly correlated with the lower elevation range boundary, which had been presumed to be restricted mainly as a result of competitive interactions with a congener. Because the lower elevational range limit is sensitive to climate variables, projected climate change across its high-elevation habitats will directly affect the species' distribution. Testing assumptions of factors that set species range limits should use models which accommodate detection biases.

16.
Clin Pharmacol Ther ; 81(2): 298-304, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17259955

RESUMEN

One of the most effective ways in which regulatory agencies communicate with sponsors and guide drug development is through the issuance of guidances or guidelines. These can be issued domestically in a given region such as the United States by the Food and Drug Administration (FDA) or internationally through the International Conference on Harmonization. Currently, there are over 400 final or draft guidances that can be found through the FDA website. The development of guidances proceeds through a process known as Good Guidance Practices, which is intended to assure that there is an appropriate level of meaningful public participation in the development of guidance. In the past 10 years, clinical pharmacology guidances covering important areas have been issued, including pharmacokinetic data in patients with renal and hepatic impairment, dose-response studies, and drug-drug interactions.


Asunto(s)
Ensayos Clínicos como Asunto/métodos , Interacciones Farmacológicas , Proyectos de Investigación/normas , Ensayos Clínicos como Asunto/normas , Ensayos Clínicos como Asunto/estadística & datos numéricos , Relación Dosis-Respuesta a Droga , Etiquetado de Medicamentos/métodos , Etiquetado de Medicamentos/normas , Guías como Asunto/normas , Humanos , Política Pública , Proyectos de Investigación/estadística & datos numéricos , Estados Unidos , United States Food and Drug Administration/normas
17.
J Clin Invest ; 51(10): 2746-56, 1972 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-4115707

RESUMEN

Since lithium has been shown to inhibit release of iodine from the thyroid, we have investigated its therapeutic potential in thyrotoxicosis. Eight detailed (131)I kinetic studies were performed on seven thyrotoxic women and data was analyzed using a computer program. Lithium at serum levels of about 1 mEq liter decreased the loss of (131)I from the thyroid, led to a fall in serum (131)I levels and diminished urinary (131)I excretion. Computer simulation of the lithium effect required, in every case, that lithium inhibit hormonal and nonhormonal thyroid iodine release. In five cases a second lithium effect was required for a satisfactory fit of the model soluton with observed data: namely, an inhibition of hormone disappearance from serum. NEITHER INHIBITION OF RELEASE NOR OF HORMONE DISAPPEARANCE SEEMED TO BE AFFECTED BY METHIMAZOLE (RELEASE: 52% decrease without methimazole, 60% with methimazole; hormone disappearance: approximately 60% decrease in both). When Li(+) was discontinued, recovery of the iodine release rate and hormone disappearance rate over the observed time span was variable, ranging from no recovery to rates that exceeded pre-Li(+) values. When Li(+) is used alone its effect on serum hormone levels is diminished due to continued accumulation of iodide by the thyroid. Thus, serum thyroxine-iodine levels fell 21-30% in 6-8 days in patients who did not receive methimazole and 15-67% in the methimazole-treated subjects. For prolonged therapy, therefore, a thiocarbamide drug must be used in conjunction with Li(+). The similarity of inhibition of iodine release from the thyroid produced by Li(+) and iodides is discussed.


Asunto(s)
Hipertiroidismo/tratamiento farmacológico , Litio/uso terapéutico , Adolescente , Adulto , Computadores , Femenino , Humanos , Yodo/sangre , Yodo/orina , Radioisótopos de Yodo , Cinética , Matemática , Metimazol/farmacología , Modelos Biológicos , Pruebas de Función de la Tiroides , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Tiroxina/sangre
18.
BMJ Open ; 7(12): e018747, 2017 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-29275347

RESUMEN

INTRODUCTION: The mortality associated with weekend admission to hospital (the 'weekend effect') has for many years been attributed to deficiencies in quality of hospital care, often assumed to be due to suboptimal senior medical staffing at weekends. This protocol describes a case note review to determine whether there are differences in care quality for emergency admissions (EAs) to hospital at weekends compared with weekdays, and whether the difference has reduced over time as health policies have changed to promote 7-day services. METHODS AND ANALYSIS: Cross-sectional two-epoch case record review of 20 acute hospital Trusts in England. Anonymised case records of 4000 EAs to hospital, 2000 at weekends and 2000 on weekdays, covering two epochs (financial years 2012-2013 and 2016-2017). Admissions will be randomly selected across the whole of each epoch from Trust electronic patient records. Following training, structured implicit case reviews will be conducted by consultants or senior registrars (senior residents) in acute medical specialities (60 case records per reviewer), and limited to the first 7 days following hospital admission. The co-primary outcomes are the weekend:weekday admission ratio of errors per case record, and a global assessment of care quality on a Likert scale. Error rates will be analysed using mixed effects logistic regression models, and care quality using ordinal regression methods. Secondary outcomes include error typology, error-related adverse events and any correlation between error rates and staffing. The data will also be used to inform a parallel health economics analysis. ETHICS AND DISSEMINATION: The project has received ethics approval from the South West Wales Research Ethics Committee (REC): reference 13/WA/0372. Informed consent is not required for accessing anonymised patient case records from which patient identifiers had been removed. The findings will be disseminated through peer-reviewed publications in high-quality journals and through local High-intensity Specialist-Led Acute Care (HiSLAC) leads at the 121 hospitals that make up the HiSLAC Collaborative.


Asunto(s)
Servicio de Urgencia en Hospital/normas , Mortalidad Hospitalaria , Admisión del Paciente/estadística & datos numéricos , Factores de Tiempo , Estudios Transversales , Inglaterra , Humanos , Modelos Logísticos , Programas Nacionales de Salud , Calidad de la Atención de Salud/organización & administración , Proyectos de Investigación , Estudios Retrospectivos
19.
Sci Rep ; 6: 28296, 2016 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-27329575

RESUMEN

We have investigated single electron spin transport in individual single crystal bcc Co30Fe70 nanoparticles using scanning tunnelling microscopy with a standard tungsten tip. Particles were deposited using a gas-aggregation nanoparticle source and individually addressed as asymmetric double tunnel junctions with both a vacuum and a MgO tunnel barrier. Spectroscopy measurements on the particles show a Coulomb staircase that is correlated with the measured particle size. Field emission tunnelling effects are incorporated into standard single electron theory to model the data. This formalism allows spin-dependent parameters to be determined even though the tip is not spin-polarised. The barrier spin polarisation is very high, in excess of 84%. By variation of the resistance, several orders of magnitude of the system timescale are probed, enabling us to determine the spin relaxation time on the island. It is found to be close to 10 µs, a value much longer than previously reported.

20.
BMJ Open ; 6(8): e012253, 2016 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-27543592

RESUMEN

INTRODUCTION: Acute kidney injury (AKI) contributes to morbidity and mortality, and its care is often suboptimal and/or delayed. The Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) study is a large pilot testing provision of early specialist advice, to improve outcomes for patients with AKI. METHODS AND ANALYSIS: This before and after study will test an Outreach service for adult patients with AKI, identified using the national algorithm. During the 2-month before phase, AKI outcomes (30-day mortality, need for dialysis or AKI stage deterioration) will be observed in the intervention and control hospitals and their respective community areas; no interventions will be delivered. Patients will receive good standard care. During the 5-month after phase, the intervention will be delivered to patients with AKI in the intervention hospital and its area. Patients with AKI in the control hospital and its area will continue to have good standard care only. Patients already on dialysis and at end of life will be excluded. The interventions will be initially delivered via a phone call, with or without a visit to the primary clinician, aiming at rapidly establishing the aetiology, correcting reversible causes and conducting further appropriate investigation. Surviving stage 3 patients will be followed-up in an AKI clinic. We will conduct qualitative research using focus group-based discussions with primary and secondary care clinicians during the early and late phases of the trial. This will help break down potential barriers and improve care delivery. ETHICS AND DISSEMINATION: Patients will be contacted about the study allowing them to 'opt out'. The work of an Outreach team, guided by AKI alerts and delivering timely advice to clinicians, may improve outcomes. If the results suggest that benefits are delivered by an AKI Outreach team, this study will lead to a full cluster randomised trial. TRIAL REGISTRATION NUMBER: NCT02398682: Pre-results.


Asunto(s)
Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/economía , Adolescente , Adulto , Anciano , Costos y Análisis de Costo , Progresión de la Enfermedad , Diagnóstico Precoz , Inglaterra , Femenino , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Atención Primaria de Salud/economía , Atención Primaria de Salud/estadística & datos numéricos , Pronóstico , Estudios Prospectivos , Adulto Joven
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