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1.
J Vasc Surg ; 71(4): 1358-1369, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32035776

RESUMEN

OBJECTIVE: Prior studies have evaluated the effects of statin and antiplatelet agent (APA) medications on patients with peripheral arterial disease. Although the benefits of statin and APA use are well-described, there is a paucity of research into the specific outcomes of patients who are not compliant or those who are unable to take the medication owing to intolerance. Here we examine the outcomes of patients intolerant to statin and APA and compare them with patients who are compliant or noncompliant with these therapies. METHODS: Patients treated from 2005 to 2018 in the Vascular Quality Initiative registry were included. Patients with missing data or deaths within 30 days of procedure were removed. Patients were considered noncompliant if they were previously prescribed a medication at discharge but were not taking it at 1-year follow-up or if the patient was reported to be noncompliant in the registry. Medication intolerance was defined if listed as "no, for medical reasons," and mortality data were ascertained using the Social Security Death Index, which is regularly cross-referenced to the Vascular Quality Initiative registry. RESULTS: We identified 105,628 patients who met our inclusion criteria. Statin intolerance was noted in 2.3% at discharge and 2.1% at the 1-year follow-up, with 0.7% listed as intolerant at all stages. Factors associated with increased risk of intolerance to statins included female gender (P = .001), discharge APA intolerance (P = .004), insurance status (non-U.S. insurance) (P < .001), discharge APA noncompliance (P = .019), and discharge angiotensin converting enzyme inhibitor noncompliance (P = .005). Patients who were compliant with statins showed a 91% survival at 5 years vs 87% survival in noncompliant patients and 87% in intolerant patients at 5 years (P < .001). Patients with statin intolerance have a similar survival curve as noncompliant patients across all registry cohorts. Noncompliance with statins was correlated with noncompliance with APA medications (R = 0.16, P < .001). Factors associated with increased risk of statin noncompliance included preoperative ambulatory status (requiring assistance) (P = .039), female sex (P < .001), peripheral vascular intervention (P < .001) or infrainguinal open bypass procedure surgery (P = .001), discharge status (to nursing home) (P = .006) and insurance (self-pay) (P < .001). CONCLUSIONS: Patients not taking statin and APA medications have a substantially decreased 5-year survival irrespective of the reason for not taking. Importantly, patients noted to be intolerant have a similar survival curve as noncompliant patients across all registry cohorts. Intolerant patients may benefit from attempts to alter statin dose, type (hydrophilic vs lipophilic), or from newer agents such as PCSK9 inhibitors.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/cirugía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Procedimientos Quirúrgicos Vasculares , Anciano , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Enfermedad Arterial Periférica/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Sistema de Registros , Estudios Retrospectivos , Tasa de Supervivencia
2.
Surgeon ; 16(4): 227-231, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29248360

RESUMEN

INTRODUCTION: 10-year study examining differences in total knee arthroplasty (TKA) functional outcomes and survivorship in patients operated on by consultant and trainee orthopaedic surgeons. METHOD: Data was prospectively collected from all elective TKAs performed at our three linked institutions. Patient demographics, surgeon grade, and length of hospital stay were recorded. Outcomes pre-operatively and at 1, 3, 5, 7 and 10 years included mortality, need for revision surgery and function as documented by the patients' Knee Society Score. RESULTS: 686 patients were included in the study. 450 (65.5%) patients were operated by consultant surgeons and 236 (34.4%) by trainees. On multivariate analysis no significant differences were observed between groups in length of hospital stay (p = 0.695), implant survival (p = 0.422), and function (p = 0.507) at 10 years. On Cox regression analysis no significant difference was observed in mortality (p = 0.209) at 10 years. 4 patients over this time period were lost to formal follow up. CONCLUSION: No significant difference was observed in the TKA outcomes between consultants and trainees 10 years post-operatively.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/educación , Artroplastia de Reemplazo de Rodilla/normas , Artropatías/cirugía , Articulación de la Rodilla/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Prótesis de la Rodilla , Persona de Mediana Edad , Resultado del Tratamiento
3.
Nat Chem Biol ; 11(6): 432-7, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25915199

RESUMEN

Protein arginine methyltransferase-5 (PRMT5) is reported to have a role in diverse cellular processes, including tumorigenesis, and its overexpression is observed in cell lines and primary patient samples derived from lymphomas, particularly mantle cell lymphoma (MCL). Here we describe the identification and characterization of a potent and selective inhibitor of PRMT5 with antiproliferative effects in both in vitro and in vivo models of MCL. EPZ015666 (GSK3235025) is an orally available inhibitor of PRMT5 enzymatic activity in biochemical assays with a half-maximal inhibitory concentration (IC50) of 22 nM and broad selectivity against a panel of other histone methyltransferases. Treatment of MCL cell lines with EPZ015666 led to inhibition of SmD3 methylation and cell death, with IC50 values in the nanomolar range. Oral dosing with EPZ015666 demonstrated dose-dependent antitumor activity in multiple MCL xenograft models. EPZ015666 represents a validated chemical probe for further study of PRMT5 biology and arginine methylation in cancer and other diseases.


Asunto(s)
Antineoplásicos/farmacología , Isoquinolinas/farmacología , Linfoma de Células del Manto/patología , Proteína-Arginina N-Metiltransferasas/antagonistas & inhibidores , Pirimidinas/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Humanos , Concentración 50 Inhibidora , Isoquinolinas/química , Isoquinolinas/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/enzimología , Masculino , Metilación , Ratones Endogámicos , Modelos Moleculares , Estructura Molecular , Unión Proteica , Pirimidinas/química , Pirimidinas/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Nucleares snRNP/metabolismo
4.
Psychol Med ; 46(6): 1331-41, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26867715

RESUMEN

BACKGROUND: Psychiatric disorders commonly emerge during the first year following traumatic brain injury (TBI). However, it is not clear whether these disorders soon remit or persist for long periods post-injury. This study aimed to examine, prospectively: (1) the frequency, (2) patterns of co-morbidity, (3) trajectory, and (4) risk factors for psychiatric disorders during the first 5 years following TBI. METHOD: Participants were 161 individuals (78.3% male) with moderate (31.2%) or severe (68.8%) TBI. Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV, administered soon after injury and 3, 6 and 12 months, and 2, 3, 4 and 5 years post-injury. Disorder frequencies and generalized estimating equations were used to identify temporal relationships and risk factors. RESULTS: In the first 5 years post-injury, 75.2% received a psychiatric diagnosis, commonly emerging within the first year (77.7%). Anxiety, mood and substance-use disorders were the most common diagnostic classes, often presenting co-morbidly. Many (56.5%) experienced a novel diagnostic class not present prior to injury. Disorder frequency ranged between 61.8 and 35.6% over time, decreasing by 27% [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.65-0.83] with each year post-injury. Anxiety disorders declined significantly over time (OR 0.73, 95% CI 0.63-0.84), whilst mood and substance-use disorder rates remained stable. The strongest predictors of post-injury disorder were pre-injury disorder (OR 2.44, 95% CI 1.41-4.25) and accident-related limb injury (OR 1.78, 95% CI 1.03-3.07). CONCLUSIONS: Findings suggest the first year post-injury is a critical period for the emergence of psychiatric disorders. Disorder frequency declines thereafter, with anxiety disorders showing greater resolution than mood and substance-use disorders.


Asunto(s)
Trastornos de Ansiedad/epidemiología , Lesiones Traumáticas del Encéfalo/psicología , Trastornos del Humor/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Anciano , Australia , Lesiones Traumáticas del Encéfalo/rehabilitación , Comorbilidad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Factores de Tiempo , Adulto Joven
6.
Langmuir ; 31(13): 3854-60, 2015 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-25781182

RESUMEN

Crystallization of liquids confined in disordered low-density nanoporous scaffolds is poorly understood. Here, we use relaxation calorimetry to study the liquid-solid phase transition of H2 in a series of silica and carbon (nanotube- and graphene-based) aerogels with porosities ≳94%. Results show that freezing temperatures of H2 inside all the aerogels studied are depressed but do not follow predictions of the Gibbs-Thomson theory based on average pore diameters measured by conventional gas sorption techniques. Instead, we find that, for each material family investigated, the depression of average freezing temperatures scales linearly with the ratio of the internal surface area (measured by gas sorption) and the total pore volume derived from the density of aerogel monoliths. The slope of such linear dependences is, however, different for silica and carbon aerogels, which we attribute to microporosity of carbons and the presence of macropores in silica aerogels. Our results have important implications for the analysis of pore size distributions of low-density nanoporous materials and for controlling crystallization of fuel layers in targets for thermonuclear fusion energy applications.

7.
Intern Med J ; 45(5): 537-45, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25583161

RESUMEN

BACKGROUND: High on-treatment platelet reactivity has been associated with poor outcomes following acute coronary syndromes (ACS). Both the loss of function CYP2C19*2 allele and the gain of function CYP2C19*17 allele along with a range of clinical characteristics have been associated with variation in the response to clopidogrel. AIM: The study aims to examine the frequency of CYP2C19 variants and understand the factors associated with on-treatment platelet reactivity in a New Zealand ACS population. METHODS: We prospectively enrolled 312 ACS patients. We collected clinical characteristics and measured on-treatment platelet reactivity using two validated point-of-care assays, VerifyNow and Multiplate. DNA was extracted and CYP2C19*2 and *17 alleles were identified using real-time polymerase chain reaction. RESULTS: CYP2C19*2 or CYP2C19*17 alleles were observed in 101 (32%) and 106 (34%) of patients, respectively, with significant differences in distribution by ethnicity. In Maori and Pacific Island patients, 47% (confidence interval (CI) 31-63%) had CYP2C19*2 and 11% (CI 4-19%) CYP2C19*17 compared with 26% (CI 19-32%) and 41% (CI 32-49%) in white people. Carriage of CYP2C19*2 alleles was associated with higher levels of platelet reactivity measured by either assay, but we observed no relationship between platelet reactivity and CYP2C19*17. In multivariate analysis diabetes, clopidogrel dose and CYP2C19*2 status were all significant independent predictors of platelet reactivity. CONCLUSIONS: Both CYP2C19*2 and *17 were common in a New Zealand ACS population, with CYP2C19*2 observed in almost half the Maori and Pacific Island patients. CYP2C19*2, diabetes and clopidogrel dose were independent contributors to on-treatment platelet reactivity.


Asunto(s)
Síndrome Coronario Agudo/genética , Plaquetas/patología , Citocromo P-450 CYP2C19/genética , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/epidemiología , Alelos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Pruebas de Función Plaquetaria , Prevalencia , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Índice de Severidad de la Enfermedad
8.
Neurobiol Dis ; 51: 82-92, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23069680

RESUMEN

We investigated two measures of neural integrity, T1-weighted volumetric measures and diffusion tensor imaging (DTI), and explored their combined potential to differentiate pre-diagnosis Huntington's disease (pre-HD) individuals from healthy controls. We applied quadratic discriminant analysis (QDA) to discriminate pre-HD individuals from controls and we utilised feature selection and dimension reduction to increase the robustness of the discrimination method. Thirty six symptomatic HD (symp-HD), 35 pre-HD, and 36 control individuals participated as part of the IMAGE-HD study and underwent T1-weighted MRI, and DTI using a Siemens 3 Tesla scanner. Volume and DTI measures [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for each group within five regions of interest (ROI; caudate, putamen, pallidum, accumbens and thalamus). QDA was then performed in a stepwise manner to differentiate pre-HD individuals from controls, based initially on unimodal analysis of motor or neurocognitive measures, or on volume, MD or FA measures from within the caudate, pallidum and putamen. We then tested for potential improvements to this model, by examining multi-modal MRI classifications (volume, FA and MD), and also included motor and neurocognitive measures, and additional brain regions (i.e., accumbens and thalamus). Volume, MD and FA differed across the three groups, with pre-HD characterised by significant volumetric reductions and increased FA within caudate, putamen and pallidum, relative to controls. The QDA results demonstrated that the differentiation of pre-HD from controls was highly accurate when both volumetric and diffusion data sets from basal ganglia (BG) regions were used. The highest discriminative accuracy however was achieved in a multi-modality approach and when including all available measures: motor and neurocognitive scores and multi-modal MRI measures from the BG, accumbens and thalamus. Our QDA findings provide evidence that combined multi-modal imaging measures can accurately classify individuals up to 15 years prior to onset when therapeutic intervention is likely to have maximal effects in slowing the trajectory of disease development.


Asunto(s)
Ganglios Basales/patología , Enfermedad de Huntington/patología , Interpretación de Imagen Asistida por Computador/métodos , Anisotropía , Imagen de Difusión por Resonancia Magnética , Análisis Discriminante , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
9.
Cytogenet Genome Res ; 139(4): 234-42, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23548580

RESUMEN

Despite extensive analyses on the centromere and its associated proteins, detailed studies of centromeric DNA structure have provided limited information about its topography in condensed chromatin. We have developed a method with correlative fluorescence light microscopy and atomic force microscopy that investigates the physical and structural organization of α-satellite DNA sequences in the context of its associated protein, CENP-B, on human metaphase chromosome topography. Comparison of centromeric DNA and protein distribution patterns in fixed homologous chromosomes indicates that CENP-B and α-satellite DNA are distributed distinctly from one another and relative to observed centromeric ridge topography. Our approach facilitates correlated studies of multiple chromatin components comprising higher-order structures of human metaphase chromosomes.


Asunto(s)
Proteína B del Centrómero/metabolismo , Centrómero/metabolismo , ADN Satélite/metabolismo , Línea Celular Tumoral , Centrómero/genética , Proteína B del Centrómero/genética , Cromatina/genética , Cromatina/metabolismo , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 17/metabolismo , Sondas de ADN/metabolismo , ADN Satélite/genética , Técnica del Anticuerpo Fluorescente , Humanos , Hibridación Fluorescente in Situ/métodos , Linfocitos/citología , Metafase , Microscopía de Fuerza Atómica , Fijación del Tejido/métodos
10.
J Antimicrob Chemother ; 68(7): 1505-9, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23524466

RESUMEN

OBJECTIVES: Vancomycin-resistant enterococci (VRE) can be associated with serious bacteraemia. The focus of this study was to characterize the molecular epidemiology of VRE from bacteraemia cases that were isolated from 1999 to 2009 as part of Canadian Nosocomial Infection Surveillance Program (CNISP) surveillance activities. METHODS: From 1999 to 2009, enterococci were collected from across Canada in accordance with the CNISP VRE surveillance protocol. MICs were determined using broth microdilution. PCR was used to identify vanA, B, C, D, E, G and L genes. Genetic relatedness was examined using multilocus sequence typing (MLST). RESULTS: A total of 128 cases of bacteraemia were reported to CNISP from 1999 to 2009. In 2007, a significant increase in bacteraemia rates was observed in western and central Canada. Eighty-one of the 128 bacteraemia isolates were received for further characterization and were identified as Enterococcus faecium. The majority of isolates were from western Canada (60.5%), followed by central (37.0%) and eastern (2.5%) Canada. Susceptibilities were as follows: daptomycin, linezolid, tigecycline and chloramphenicol, 100%; quinupristin/dalfopristin, 96.3%; high-level gentamicin, 71.6%; tetracycline, 50.6%; high-level streptomycin, 44.4%; rifampicin, 21.0%; nitrofurantoin, 11.1%; clindamycin, 8.6%; ciprofloxacin, levofloxacin and moxifloxacin, 1.2%; and ampicillin, 0.0%. vanA contributed to vancomycin resistance in 90.1% of isolates and vanB in 9.9%. A total of 17 sequence types (STs) were observed. Beginning in 2006 there was a shift in ST from ST16, ST17, ST154 and ST80 to ST18, ST412, ST203 and ST584. CONCLUSIONS: The increase in bacteraemia observed since 2007 in western and central Canada appears to coincide with the shift of MLST STs. All VRE isolates remained susceptible to daptomycin, linezolid, chloramphenicol and tigecycline.


Asunto(s)
Bacteriemia/epidemiología , Infección Hospitalaria/epidemiología , Enterococcus faecium/clasificación , Infecciones por Bacterias Grampositivas/epidemiología , Resistencia a la Vancomicina , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/microbiología , Canadá/epidemiología , Niño , Preescolar , Infección Hospitalaria/microbiología , ADN Bacteriano/genética , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/genética , Enterococcus faecium/aislamiento & purificación , Femenino , Genes Bacterianos , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Reacción en Cadena de la Polimerasa , Adulto Joven
11.
Clin Nutr ; 41(6): 1228-1235, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35504165

RESUMEN

BACKGROUND & AIMS: The aim of this study was to determine the effect of krill oil supplementation, on muscle function and size in healthy older adults. METHODS: Men and women, aged above 65 years, with a BMI less than 35kg/m2, who participated in less than 1h per week of structured self-reported exercise, were enrolled in the study (NCT04048096) between March 2018 and March 2020. Participants were randomised to either control or krill oil supplements (4g/day) for 6 months in this double blind randomised controlled trial. At baseline, 6 weeks and 6 months, knee extensor maximal torque was measured as the primary outcome of the study. Secondary outcomes measured were grip strength, vastus lateralis muscle thickness, short performance physical battery test, body fat, muscle mass, blood lipids, glucose, insulin, and C-Reactive Protein, neuromuscular (M-Wave, RMS and voluntary activation), and erythrocyte fatty acid composition. RESULTS: A total of 102 men and women were enrolled in the study. Ninety-four participants (krill group (26 women and 23 men) and placebo group (27 women and 18 men)) completed the study (mean (SD): age 71.2 (5.1) years and weight 71.8 (12.3) kg). Six months supplementation with krill oil resulted in, an increase in knee extensor maximal torque, grip strength and vastus lateralis muscle thickness, relative to control (p<0.05). The 6-month treatment effects were 9.3% (95%CI: 2.8, 15.8%), 10.9% (95%CI: 8.3, 13.6%) and 3.5% (95%CI: 2.1, 4.9%) respectively. Increases in erythrocyte fatty acid profile were seen with krill oil for EPA 214% (95%CI: 166, 262%), DHA 36% (95%CI: 24, 48%) and the omega-3 index 61% (95%CI: 49, 73%), relative to control (p < 0.05). Krill oil resulted in an increased, relative to control (p < 0.05), M-Wave of 17% (95%CI: 12.7, 38.1%) but there was no effect of krill oil on RMS, voluntary activation, or on any other secondary outcomes such as performance of the short performance physical battery test or quality of life. CONCLUSION: Krill oil supplementation for 6 months results in statistically and clinically significant increases in muscle function and size in healthy older adults. GOV IDENTIFIER: NCT04048096.


Asunto(s)
Euphausiacea , Enfermedades Musculares , Anciano , Animales , Suplementos Dietéticos , Método Doble Ciego , Ácidos Grasos/farmacología , Femenino , Humanos , Masculino , Músculo Esquelético , Calidad de Vida
12.
Nat Commun ; 13(1): 936, 2022 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-35177612

RESUMEN

Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Ceramidas/sangre , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/metabolismo , Ceramidas/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Masculino , Metabolómica , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos
13.
Hum Reprod ; 26(2): 369-75, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21127355

RESUMEN

BACKGROUND: First-line treatments for unexplained infertility traditionally include clomifene citrate (CC) or unstimulated intrauterine insemination (IUI). A recently published randomized controlled trial considered the effectiveness of CC and IUI in patients with unexplained infertility and found that neither treatment offered a superior live birth rate when compared with expectant management (EM). This paper reports the economic evaluation conducted alongside this trial in order to assess whether health care providers are gaining value for money in this clinical area. METHODS: Five hundred and eighty women across five Scottish hospitals were randomized to either EM, CC or IUI for 6 months. The primary outcome measure was live births. Resource-use data were collected during the trial and costs were calculated from a UK National Health Service (NHS) perspective. Incremental cost-effectiveness ratios were calculated, expressed as cost per live birth, in order to compare the cost-effectiveness of CC and IUI with that of EM to treat unexplained infertility. RESULTS: Live birth rates in the three randomized groups were: EM = 32/193 (17%), CC = 26/194 (13%) and IUI = 43/193 (22%). The mean (standard deviation) costs per treatment cycle were £0 for EM, £83 (£17) for CC and £98 (£31) for IUI. The mean treatment costs per patient for EM, CC and IUI were £12 (£117), £350 (£220) and £331 (£222), respectively. The cost per live birth for EM, CC and IUI was £72 (95% confidence interval £0-£206), £2611 (£1870-£4166) and £1487 (£1116-£2155), respectively. The incremental cost-effectiveness ratio for IUI versus EM was £5604 (-£12204 to £2227), with CC dominated by IUI. CONCLUSIONS: Despite being more expensive, existing treatments such as empirical CC and unstimulated IUI do not offer superior live birth rates compared with EM of unexplained infertility. They are unlikely to be a cost-effective use of limited NHS resources. The study's main limitation is that it did not consider the psychological effects on couples. ISRCT Number: 71762042.


Asunto(s)
Tasa de Natalidad , Clomifeno/uso terapéutico , Infertilidad/terapia , Clomifeno/economía , Análisis Costo-Beneficio , Femenino , Humanos , Infertilidad/tratamiento farmacológico , Infertilidad/economía , Inseminación , Masculino , Embarazo , Escocia , Espera Vigilante/economía
14.
Psychol Med ; 41(10): 2099-109, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21477420

RESUMEN

BACKGROUND: Psychiatric disorders are common following traumatic brain injury (TBI). However, few studies have examined the course of disorder development and the influence of pre-injury psychiatric history. The present study aimed to examine the frequency of, and association between, psychiatric disorders occurring pre- and post-injury, and to examine the post-injury course of disorders. METHOD: Participants were 102 adults (75.5% male) with predominantly moderate-severe TBI. Participants were initially assessed for pre-injury and current disorders, and reassessed at 3, 6 and 12 months post-injury using the Structured Clinical Interview for DSM-IV Disorders (SCID). RESULTS: Over half of the participants had a pre-injury psychiatric disorder; predominantly substance use, mood, and anxiety disorders. In the first year post-injury, 60.8% of participants had a psychiatric disorder, commonly anxiety and mood disorders. Post-injury disorders were associated with the presence of a pre-injury history (p<0.01), with 74.5% of participants with a pre-injury psychiatric history experiencing a post-injury disorder, which commonly presented at initial assessment or in the first 6 months. However, 45.8% of participants without a pre-injury history developed a novel post-injury disorder, which was less likely to emerge at the initial assessment and generally developed later in the year. CONCLUSIONS: Despite evidence that most post-injury psychiatric disorders represent the continuation of pre-existing disorders, a significant number of participants developed novel psychiatric disorders. This study demonstrates that the timing of onset may differ according to pre-injury history. There seem to be different trajectories for anxiety and depressive disorders. This research has important implications for identifying the time individuals are most at risk of psychiatric disorders post-injury.


Asunto(s)
Lesiones Encefálicas/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Lesiones Encefálicas/complicaciones , Femenino , Humanos , Entrevista Psicológica , Masculino , Trastornos Mentales/complicaciones , Trastornos Mentales/diagnóstico , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Adulto Joven
15.
J Endocrinol Invest ; 34(4): 296-9, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20585202

RESUMEN

Fifteen children and adolescents (4 male) with a median age of 5.4 yr (range 1.2 -13.6 yr) were entered into a screening protocol to identify lesions of von Hippel-Lindau (VHL) disease. Fourteen had an affected first-degree relative and one had a previous VHL lesion. Screening during the period of 2000 to 2008 followed published guidelines and consisted of measurement of urinary catecholamines, adrenal and renal imaging and ophthalmological and central nervous system examinations and imaging. Screening identified 8 VHL lesions in 6 asymptomatic patients with confirmed genetic mutations. Five patients had elevated urinary noradrenaline excretion and in each case the presence of a pheochromocytoma was identified on adrenal magnetic resonance imagin scan. In one patient a left-sided tumor was identified 1 yr after a right-sided tumor had been removed. In a sixth patient a retinal capillary hemangioma and a cerebellar hemangioblastoma were identified. Patient compliance with the screening protocol was variable reflecting its time-intensive nature. A formal screening programme for this at-risk population of pediatric patients, despite being intensive, can identify VHL lesions during a pre-morbid phase and may thus have a beneficial impact on prognosis in this serious disorder.


Asunto(s)
Tamizaje Masivo , Cooperación del Paciente , Enfermedad de von Hippel-Lindau/diagnóstico , Enfermedad de von Hippel-Lindau/patología , Adolescente , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/cirugía , Catecolaminas/orina , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/cirugía , Niño , Preescolar , Femenino , Hemangioma/diagnóstico , Hemangioma/genética , Hemangioma/patología , Hemangioma/cirugía , Humanos , Lactante , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/patología , Feocromocitoma/cirugía , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/genética , Neoplasias de la Retina/patología , Neoplasias de la Retina/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/cirugía
16.
Aust Vet J ; 99(1-2): 11-14, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33025586

RESUMEN

CASE REPORT: This case report describes the clinical signs and case management of a 1-year-old neutered male Siberian Husky that accidentally ingested 635 mg/kg of oral acetazolamide (a carbonic anhydrase inhibitor). The dog presented with severe tachypnoea due to the development of hyperchloraemic metabolic acidosis and associated hypokalaemia that persisted for 7 days. Clinical and biochemical changes resolved with intravenous and subsequent oral supplementation of sodium bicarbonate and potassium. Complete recovery occurred within 9 days of presentation. CONCLUSION: To the authors' knowledge, this is the first case that reports overdosage of an oral carbonic anhydrase inhibitor in a dog and subsequent recovery with adequate supplementation and supportive care.


Asunto(s)
Acidosis , Enfermedades de los Perros , Acetazolamida/uso terapéutico , Acidosis/inducido químicamente , Acidosis/veterinaria , Animales , Inhibidores de Anhidrasa Carbónica , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológico , Perros , Masculino , Potasio
17.
J Small Anim Pract ; 62(1): 19-27, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33107069

RESUMEN

INTRODUCTION: To report the clinical presentation, laboratory and imaging findings, treatment and outcome of abdominal cryptococcosis in dogs and cats in Australia. MATERIALS AND METHODS: Canine and feline cases from Australia were retrospectively identified (2000 to 2018) via laboratory and referral centre searches for abdominal cryptococcosis diagnosed by cytology (needle aspirates) or histopathology (biopsy or necropsy) of abdominal organs/tissues. Signalment, presenting complaints, clinical signs, laboratory findings, medical imaging, latex cryptococcal antigen agglutination test (LCAT) titres, treatment and outcome data was collected. RESULTS: Thirty-eight cases were included (35 dogs, three cats) in the study. Median age of presentation was 2 years for dogs and 6 years for cats. Common presenting complaints included vomiting (23/38), lethargy (19/38) and inappetence/anorexia (15/38). Abdominal ultrasound (25/38 cases) revealed mesenteric and intestinal lesions in most of the cases. On surgical exploration, seven cases had an intestinal lesion associated with an intussusception. Nineteen cases had a pre-treatment LCAT performed, with a median initial titre of 1:2048 (range 1:2 to 65,536). Twenty-four cases (23 dogs, one cat) received treatment, either medical, surgical or both. Median survival time for cases with combined medical and surgical treatment, surgical treatment alone or medical treatment alone was 730, 140 and 561 days, respectively. Eleven remain alive at the time of follow up. CLINICAL SIGNIFICANCE: Abdominal cryptococcosis although rare should be a considered as a diagnostic possibility in an especially young dog presenting with gastro-intestinal signs. Older dogs can also present with this condition and should not be euthanised based on imaging alone due to the likenesses with neoplasia. With appropriate treatment and monitoring many dogs may have a prolonged survival period and some may be cured.


Asunto(s)
Enfermedades de los Gatos , Criptococosis , Enfermedades de los Perros , Animales , Australia , Enfermedades de los Gatos/diagnóstico , Gatos , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Criptococosis/veterinaria , Enfermedades de los Perros/diagnóstico , Perros , Estudios Retrospectivos
18.
Transl Anim Sci ; 5(3): txab140, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34549168

RESUMEN

The objective of this experiment was to determine the dietary inclusion rate of camelina cake (CC) that would support the growth performance of growing-finishing pigs similar to that of a corn-soybean meal-based diet. Pigs (n = 192; BW = 35.2 kg; Duroc x (Yorkshire x Landrace)), balanced for sex and initial weight, were assigned to pens (8 pigs/pen) and pens were assigned randomly to one of four dietary treatments (6 pens/treatment). Treatments consisted of a non GMO corn-soybean meal control diet (CON), or CON containing 5% (5CC), 10% (10CC), or 15% (15CC) camelina cake. Feed disappearance on a pen basis and individual body weights of pigs were recorded every other week to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) on a pen basis. Prior to harvest, real-time ultrasonic measurements of back fat depth and loin eye area were collected on all live pigs. Pigs were harvested as a single group at about 23 weeks of age at a commercial abattoir. Data were analyzed using Proc Glimmix with dietary treatment as a fixed effect and pen serving as the experimental unit. Growth performance data collected over time were analyzed using repeated measures within the Proc Glimmix procedure. Overall, pigs fed CON exhibited similar ADG to those consuming 5CC and higher ADG than pigs consuming 10CC and 15CC diets (1.10 kg vs. 1.05 kg for 10CC and 1.02 kg for 15CC; P < 0.05 for both mean comparisons). Pigs fed CON consumed more feed than pigs fed any of the CC diets (ADFI = 2.66 kg for CON vs. 2.46 kg for 5CC, 2.46 kg for 10CC and 2.47 kg for 15CC; P < 0.05 for all). These differences resulted in heavier (P < 0.05) CON-fed pigs at marketing than 10CC or 15CC-fed pigs. There were no differences in any carcass traits analyzed. From these data, we conclude that feeding up to 5% CC in corn-soybean meal-based diets did not negatively influence growth performance, or carcass traits of growing-finishing pigs.

19.
J Anim Sci ; 99(3)2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33677551

RESUMEN

This study was conducted to evaluate whether cooled floor pads combined with chilled drinking water could alleviate negative impacts of heat stress on lactating sows. Thirty sows (Landrace × Yorkshire, Parity = 1 to 6) were housed in individual farrowing stalls in two rooms with temperatures being controlled at 29.4°C (0700-1900 hours) and 23.9°C (1900-0700 hours). Sows in one room (Cool), but not in the other room (Control) were provided cooled floor pads (21-22°C) and chilled drinking water (13-15°C). Behavior of sows (15 sows/treatment) was video recorded during farrowing, and days 1, 3, 7, 14, and 21 after farrowing. Videos were viewed continuously to register the birth time of each piglet, from which total farrowing duration and birth intervals were calculated. The number of drinking bouts and the duration of each drinking bout were registered for each sow through viewing videos continuously for 2 h (1530-1730 hours) each video-recording day. Postures (lying laterally, lying ventrally, sitting, and standing) were recorded by scanning video recordings at 5-min intervals for 24 h each video-recording day, and time budget for each posture was calculated. Rectal temperature and respiration rate were measured for all sows the day before and after farrowing, and then once weekly. Sow and litter performance was recorded. Data were analyzed using the Glimmix procedure of SAS. The cooling treatment did not affect sow behavior or litter performance. Sows in the Cool room had lower rectal temperature (P = 0.03) and lower respiration rate (P < 0.001), consumed more feed (P = 0.03), tended to have reduced weight loss (P = 0.07), and backfat loss (P = 0.07) during lactation than sows in the Control room. As lactation progressed, sows increased drinking frequency (P < 0.001) and time spent lying ventrally (P < 0.0001), standing (P < 0.001), and sitting (P < 0.0001), and decreased time spent lying laterally (P < 0.0001) in both Cool and Control rooms. While cooled floor pads combined with chilled drinking water did not affect sow behavior, they did alleviate heat stress partially, as indicated by decreased rectal temperature, respiration rate, weight, and backfat loss, and increased feed intake in lactating sows.


Asunto(s)
Agua Potable , Trastornos de Estrés por Calor , Enfermedades de los Porcinos , Animales , Femenino , Trastornos de Estrés por Calor/veterinaria , Respuesta al Choque Térmico , Lactancia , Paridad , Embarazo , Porcinos
20.
Trends Cell Biol ; 2(12): 353-7, 1992 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14731955

RESUMEN

Increasing evidence suggests that cell-cycle-regulated gene expression plays a crucial role in cell cycle control. In building yeast, as many as 250 genes (3-4% of all genes in this yeast) may be regulated in this way. One large group is expressed at the G1-S transition and includes cyclin genes, whose products control the p34(CDC28) protein kinase, as well as many genes essential for DNA synthesis. Two separate systems control the expression of these genes in the late G1 phase, but these systems have in common the SW16 protein, which may be a cell cycle stage-specific transcription factor.

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