RESUMEN
Background: Contralateral prophylactic mastectomy (cpm) in women with known unilateral breast cancer (bca) has been increasing despite the lack of supportive evidence. The purpose of the present study was to identify the determinants of cpm in women with unilateral bca. Methods: This qualitative descriptive study used semi-structured interviews informed by the Theoretical Domains Framework. We interviewed 74 key informants (surgical oncologists, plastic surgeons, medical oncologists, radiation oncologists, nurses, women with bca) across Canada. Interviews were analyzed using thematic analysis and an analysis for shared and discipline-specific beliefs. Results: In total, 58 factors influencing the use of cpm were identified: 26 factors shared by various health care professional groups, 15 discipline-specific factors (identified by a single health care professional group), and 17 factors shared by women with unilateral bca. Health care professionals identified more factors discouraging the use of cpm (n = 26) than encouraging its use (n = 15); women with bca identified more factors encouraging use of cpm (n = 12) than discouraging its use (n = 5). The factor most commonly identified by health care professionals that encouraged cpm was lack of awareness of existing evidence or guidelines for the appropriate use of cpm (n = 44, 75%). For women with bca, the factor most likely influencing their decision for cpm was wanting a better esthetic outcome (n = 14, 93%). Conclusions: Multiple factors discouraging and encouraging the use of cpm in unilateral bca were identified. Those factors identify potential individual, team, organization, and system targets for behaviour change interventions to reduce cpm.
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Neoplasias de la Mama/cirugía , Neoplasias Primarias Secundarias/prevención & control , Mastectomía Profiláctica/métodos , Adulto , Canadá , Toma de Decisiones Clínicas , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Investigación Cualitativa , Medición de RiesgoRESUMEN
BACKGROUND: Ketosis in dairy cattle has been shown to cause a high morbidity in the farm and substantial financial losses to dairy farmers. Ketosis symptoms, however, are difficult to identify, therefore, the amount of ketone bodies (mainly ß-hydroxybutyric acid, BHB) is used as an indicator of subclinical ketosis in cows. It has also been shown that milk BHB concentrations have a strong correlation with ketosis in dairy cattle. Mid-infrared spectroscopy (MIR) has recently became a fast, cheap and high-throughput method for analyzing milk components. The aim of this study was to perform a genome-wide association study (GWAS) on the MIR-predicted milk BHB to identify genomic regions, genes and pathways potentially affecting subclinical ketosis in North American Holstein dairy cattle. RESULTS: Several significant regions were identified associated with MIR-predicted milk BHB concentrations (indicator of subclinical ketosis) in the first lactation (SCK1) and second and later lactations (SCK2) in Holstein dairy cows. The strongest association was located on BTA6 for SCK1 and BTA14 on SCK2. Several SNPs on BTA6 were identified in regions and variants reported previously to be associated with susceptibility to ketosis and clinical mastitis in Jersey and Holstein dairy cattle, respectively. One highly significant SNP on BTA14 was found within the DGAT1 gene with known functions on fat metabolism and inflammatory response in dairy cattle. A region on BTA6 and three SNPs on BTA20 were found to overlap between SCK1 and SCK2. However, a novel region on BTA20 (55-63 Mb) for SCK2 was also identified, which was not reported in previous association studies. Enrichment analysis of the list of candidate genes within the identified regions for MIR-predicted milk BHB concentrations yielded molecular functions and biological processes that may be involved in the inflammatory response and lipid metabolism in dairy cattle. CONCLUSIONS: The results of this study confirmed several SNPs and genes identified in previous studies as associated with ketosis susceptibility and immune response, and also found a novel region that can be used for further analysis to identify causal variations and key regulatory genes that affect clinical/ subclinical ketosis.
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Ácido 3-Hidroxibutírico/metabolismo , Estudio de Asociación del Genoma Completo , Leche/metabolismo , Animales , Bovinos , Biología Computacional/métodos , Ontología de Genes , Genómica/métodos , Anotación de Secuencia MolecularRESUMEN
Background: Rates of contralateral prophylactic mastectomy (cpm) continue to rise internationally despite evidence-based guidance strongly discouraging its use in most women with unilateral breast cancer. The purpose of the present study was to develop and assess the feasibility of a knowledge translation tool [a patient decision aid (da)] designed to enhance evidence-informed shared decision-making about cpm. Methods: A consultation da was developed using the Ottawa Patient Decision Aid Development eTraining in consultation with clinicians and knowledge translation experts. The final da was then assessed for feasibility with health care professionals and patients across Canada. The assessment involved a survey completed online (health care professionals) or by telephone (patients). Survey data were analyzed using descriptive statistics for closed-ended questions and qualitative content analysis for open-ended questions. Results: The 51 participants who completed the survey included 39 health care professionals and 12 patients. The da was acceptable; 88% of participants viewed it as having the right amount of information or slightly more or less information than they would like. Almost all participants (98%) felt that the da would prepare patients to make better decisions. The aid was perceived to be usable, with 73% of participants stating that they would be willing to use or share the da. Conclusions: The cpm patient da developed for the present study was viewed by health care professionals and patients across Canada to be acceptable and usable during the clinical consultation. It holds promise as a knowledge translation tool to be used by clinicians in consultation with women who have unilateral breast cancer to enhance evidence-informed and shared decision-making with respect to undergoing cpm.
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Neoplasias de la Mama/cirugía , Técnicas de Apoyo para la Decisión , Mastectomía Profiláctica , Adulto , Anciano , Toma de Decisiones , Estudios de Factibilidad , Femenino , Personal de Salud , Humanos , Masculino , Persona de Mediana Edad , Ontario , Derivación y Consulta , Encuestas y CuestionariosRESUMEN
AIM: To undertake a preliminary assessment of the potential for computed tomography (CT) measurement of tumour heterogeneity to stratify risk of nodal metastasis in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Tumour heterogeneity in CT images from combined positron-emission tomography (PET)/CT examinations in 150 consecutive patients with NSCLC was assessed using CT texture analysis (CTTA). The short axis diameter of the largest mediastinal node was also measured. Forty-two patients without distant metastases subsequently had tumour nodal status confirmed at surgery (n=26) or endobronchial ultrasound (EBUS; n=16). CTTA parameters and largest nodal diameter were related to nodal status using the rank correlation and the risk ratio for each nodal stage (>N0, >N1, >N2) was compared between patients categorised as high and low risk by CTTA or nodal size. The most significant predictor of nodal status was related to overall survival using Kaplan-Meier analysis. RESULTS: N-stage was more significantly correlated with CTTA than nodal diameter (Rs = -0.39, p=0.011, Rs = -0.45, p=0.0025, Rs = -0.40, p=0.0091 for normalised standard deviation (SD), normalised entropy and kurtosis respectively; Rs = -0.39, p=0.042 for nodal diameter). The presence of two or more high-risk CTTA values was the greatest risk factor for mediastinal metastasis (risk ratio: 11.0, 95% confidence interval: 1.56-77.8, p=0.0014) and was associated with significantly poorer overall survival (p=0.016). CONCLUSION: CTTA in NSCLC is related to nodal status in patients without distant metastases and has the potential to inform selection of investigative strategies for the assessment of mediastinal malignancy.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X , Humanos , Estimación de Kaplan-Meier , Pulmón/diagnóstico por imagen , Pulmón/patología , Metástasis Linfática , Estudios Prospectivos , Reproducibilidad de los Resultados , RiesgoRESUMEN
BACKGROUND: Information pertaining to clinical presentation and outcome of neonatal New World camelids (NWC) is limited when compared to calves and foals. HYPOTHESIS: Values of variables at admission and subsequent treatment would predict survival in sick neonatal NWC. ANIMALS: Fifty-six client-owned sick neonatal NWC presented over a 10-year period to the Purdue University Veterinary Teaching Hospital. METHODS: A retrospective study was performed. Inclusion criteria were NWC less than 30 days of age with complete medical records that presented between 2000 and 2010. RESULTS: The median age at presentation was 1 day (range 1-20). The most common diagnoses were systemic inflammatory response syndrome (50%), congenital defects (41%), ophthalmic lesions (21%), sepsis (16%), and gastrointestinal diseases (16%). Sixty-six percent of NWC survived to discharge. Clinicopathologic findings on admission were variable and not specific for disorders. Factors associated with survival were absence of choanal atresia (P = .001, OR: 55.9 [2.5-1,232]), administration of llama plasma (P = .013, OR: 4.9 [1.4-17.7]), and antimicrobial treatment with trimethoprim-sulfamethoxazole (TMS) (P = .016, OR: 6.5 [1.3-32.2]). CONCLUSIONS AND CLINICAL IMPORTANCE: The use of antibiotics, particularly TMS, and llama plasma are recommended in sick neonatal NWC. Results from this study could contribute toward defining a NWC-specific sepsis scoring system.
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Animales Recién Nacidos , Camélidos del Nuevo Mundo , Anomalías Congénitas/veterinaria , Oftalmopatías/veterinaria , Sepsis/veterinaria , Síndrome de Respuesta Inflamatoria Sistémica/veterinaria , Animales , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/mortalidad , Anomalías Congénitas/patología , Anomalías Congénitas/terapia , Oftalmopatías/diagnóstico , Oftalmopatías/mortalidad , Oftalmopatías/patología , Oftalmopatías/terapia , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/mortalidad , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/terapia , Enfermedades Gastrointestinales/veterinaria , Masculino , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Sepsis/diagnóstico , Sepsis/mortalidad , Sepsis/patología , Sepsis/terapia , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/patologíaRESUMEN
BACKGROUND: Smoking is a risk factor for incident colorectal cancer (CRC); however, it is unclear about its influence on survival after CRC diagnosis. METHODS: A cohort of 706 CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and recurrence until April 2010. Smoking and other relevant data were collected by questionnaire after cancer diagnosis, using a referent period of '2 years before diagnosis' to capture pre-diagnosis information. Molecular analyses of microsatellite instability (MSI) status and BRAF V600E mutation status were performed in tumour tissue using standard techniques. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards regression, controlling for major prognostic factors. RESULTS: Compared with never smokers, all-cause mortality (overall survival, OS) was higher for current (HR: 1.78; 95% CI: 1.04-3.06), but not for former (HR: 1.06; 95% CI: 0.71-1.59) smokers. The associations of cigarette smoking with the study outcomes were higher among patients with ≥40 pack-years of smoking (OS: HR: 1.72; 95% CI: 1.03-2.85; disease-free survival (DFS: HR: 1.99; 95% CI: 1.25-3.19), those who smoked ≥30 cigarettes per day (DFS: HR: 1.80; 95% CI: 1.22-2.67), and those with microsatellite stable (MSS) or MSI-low tumours (OS: HR: 1.38; 95% CI: 1.04-1.82 and DFS: HR: 1.32; 95% CI: 1.01-1.72). Potential heterogeneity was noted for sex (DFS HR: 1.68 for men and 1.01 for women: P for heterogeneity=0.04), and age at diagnosis (OS: HR: 1.11 for patients aged <60 and 1.69 for patients aged ≥60: P for heterogeneity=0.03). CONCLUSIONS: Pre-diagnosis cigarette smoking is associated with worsened prognosis among patients with CRC.
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Neoplasias Colorrectales/mortalidad , Fumar/mortalidad , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Fenotipo , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Factores de Riesgo , Fumar/efectos adversos , Fumar/genética , Encuestas y CuestionariosRESUMEN
The association of the Kidd blood group system with hemolytic transfusion reactions and hemolytic disease of the newborn is well known. The Kidd antigens, which are localized to the HUT/UT-B urea transport protein, are found on red blood cells and the endothelial cells of the blood vessels of the medulla of the kidney. Recently it has been suggested that these antigens might play a role as minor histocompatibility antigens in renal transplantation. In the current case, the appearance of an anti-Jk(b) 10 years after renal transplantation associated with early renal allograft rejection further supports the potential importance of these antigens in renal transplantation and allograft rejection.
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Rechazo de Injerto/inmunología , Sistema del Grupo Sanguíneo de Kidd/inmunología , Trasplante de Riñón/inmunología , Proteínas de Transporte de Membrana/inmunología , Antígenos de Histocompatibilidad Menor/inmunología , Células Endoteliales/inmunología , Eritrocitos/inmunología , Rechazo de Injerto/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Lactante , Sistema del Grupo Sanguíneo de Kidd/genética , Proteínas de Transporte de Membrana/genética , Antígenos de Histocompatibilidad Menor/genética , Cooperación del Paciente , Trasplante Homólogo , Transportadores de UreaRESUMEN
BACKGROUND: We previously reported preliminary results of our phase I study of continuous daily sorafenib with bevacizumab every other week for solid tumours. Toxicity was moderate, leading to additional dose levels (DL) testing intermittent sorafenib dosing. METHODS: Seventeen patients with advanced solid tumours were treated on three additional DLs testing sorafenib days 1-5 per week. Dose level 4 was sorafenib 200 mg twice daily (b.i.d.) and bevacizumab 5 mg kg(-1). DL5 alternated between bevacizumab 10 mg kg(-1)-sorafenib 200 mg b.i.d. (A) and sorafenib 400 mg b.i.d. with bevacizumab 5 mg kg(-1) (B). Outcome and toxicity data from 19 epithelial ovarian cancer (EOC) patients from DL 1-5 were analysed. RESULTS: Fewer patients required sorafenib dose reduction with the intermittent schedule (41 vs 74% daily, P=0.01). Hand-foot skin reaction (HFSR) remained the primary cause of dose reduction (n=5). Partial responses (12%) or disease stabilisation > or =4 months (53%; median 6 (4-26)) occurred in most patients on the intermittent schedule. Partial response occurred in 47% EOC patients treated in pooled analysis of duration 4-37 months. CONCLUSION: Intermittent sorafenib dosing with bevacizumab has promising clinical activity and less sorafenib dose reduction and side effects, but does not ameliorate HFSR. We are conducting a phase II clinical trial with intermittent sorafenib and bevacizumab in patients with EOC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bencenosulfonatos/administración & dosificación , Bencenosulfonatos/efectos adversos , Bevacizumab , Femenino , Humanos , Dosis Máxima Tolerada , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piridinas/administración & dosificación , Piridinas/efectos adversos , SorafenibRESUMEN
BACKGROUND: Healthcare providers work increasingly under a variety of shift work systems to cover the continuous care required by patients. However, the effects of shift work on patient and provider outcomes in healthcare settings has not been systematically evaluated. OBJECTIVE: To identify and analyse the available evidence on the effect of shift length (8-h vs 12-h shifts) on quality of patient care and healthcare provider outcomes. METHODS: Systematic searching of eight online databases, key governmental/organisational websites and academic journals with ancestry search of relevant articles (limited to articles published in English and Spanish). RESULTS: Of 562 articles that were retrieved from 20 446 titles identified through database and manual searches, 27 satisfied the inclusion criteria, of which 15 were rejected because of low methodological quality. The 12 final studies included cross-sectional/survey (7), before-after (3) and prospective cohort (2) designs. The main primary outcomes evaluated were: (1) quality of patient care and (2) healthcare provider outcomes. The results were equivocal. With respect to the effect of shift length on quality of patient care, two studies found that errors and near errors were associated with working longer shifts, and another study reported decreased patient complications and length of stay with longer shifts. Specific healthcare provider outcomes such as health complaints, well-being, drug and alcohol consumption, stress and job satisfaction were mostly evaluated by single studies and therefore there was insufficient evidence from which to draw conclusions. CONCLUSIONS: Methodological quality of the studies generally was low and results equivocal with insufficient evidence to determine the effects of shift length on quality of patient care and healthcare provider outcomes. Clearly, robust well-designed studies are needed to examine the effect of shift length on patient and healthcare provider outcomes.
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Personal de Salud , Admisión y Programación de Personal , Calidad de la Atención de Salud , Humanos , Evaluación de Resultado en la Atención de Salud , Carga de TrabajoRESUMEN
BACKGROUND: Accurate and efficient developmental screening measures are critical for early identification of developmental problems; however, few reliable and valid tests are available in Korea as well as other countries outside the USA. The Ages and Stages Questionnaires (ASQ) was chosen for study with young children in Korea. METHODS: The ASQ was translated into Korean and necessary cross-cultural adaptations were made. The translated version was then distributed and completed by 3220 parents of young children between the ages of 4 months and 5 years. Reliability was studied including domain correlations, internal consistency, and performance of identification cut-off scores for the Korean population. Rasch analyses including tests of Differential Item Functioning, contrasting Korean and US samples were also performed. RESULTS: In general, internal consistency of the Korean ASQ was high, with overall correlations 0.75 for communication, 0.85 for gross motor, 0.74 for fine motor, 0.72 for problem solving, and 0.65 for personal-social. Validity, including concurrent validity, also had strong evidence. Mean scores of children on the Korean translation of the ASQ and the US normative sample were generally similar. Rasch analyses indicated the majority of items functioned similarly across the Korean sample. CONCLUSIONS: In general, the ASQ was translated with cultural appropriateness in mind and functioned as a valid and reliable parent-completed screening test to assist in early identification of young children with developmental delays. Further research is needed to confirm these results with a larger and more diverse Korean sample.
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Desarrollo Infantil , Comparación Transcultural , Discapacidades del Desarrollo/diagnóstico , Tamizaje Masivo/métodos , Psicometría/métodos , Encuestas y Cuestionarios/normas , Análisis de Varianza , Preescolar , Discapacidades del Desarrollo/psicología , Femenino , Humanos , Lactante , Corea (Geográfico) , Masculino , Padres , Psicometría/normas , Reproducibilidad de los Resultados , Estados UnidosRESUMEN
OBJECTIVES: Alternative response schemes for emergency calls are being set up by many UK ambulance services. The barriers to such developments from the perspective of ambulance service staff have not been formally investigated. The aims of this study are to identify attitudes and barriers to the development of alternative response schemes and ways of easing the transition as they are implemented. METHODS: South Yorkshire Ambulance Service crews and control room staff were interviewed, using South Yorkshire's paramedic practitioner (PP) scheme as a model of an alternative response scheme. RESULTS: 55 ambulance crew and 17 control staff were interviewed. Most (97%, n = 70) thought that the PP scheme was a good way of dealing with patients who call 999 but may not need urgent transport and hospital treatment. The perceived effect of the PP scheme on traditional ambulance service duties was equally divided between a third who thought there had been no effect, a third who perceived an improvement, and a third a deterioration. Recurrent difficulties with the scheme were found relating to the AMPDS methodology of ambulance dispatch, and ambulance service performance targets. CONCLUSIONS: Flexibility of AMPDS and dispatch targets will need to be reviewed to permit the successful implementation of alternative responses to 999 calls. Careful consideration needs to be given to communicating the aims and value of such schemes to all staff and ensuring a common understanding of, and commitment to, a shared vision. The effect of implementation on the remaining service function must be well planned.
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Ambulancias , Actitud del Personal de Salud , Servicio de Urgencia en Hospital/organización & administración , Técnicos Medios en Salud/educación , Servicio de Urgencia en Hospital/tendencias , Inglaterra , Accesibilidad a los Servicios de Salud/organización & administración , Necesidades y Demandas de Servicios de Salud/organización & administración , Necesidades y Demandas de Servicios de Salud/tendencias , Humanos , Derivación y ConsultaRESUMEN
AIM: To compare normative data of a Norwegian translation of the Ages and Stages Questionnaires with original US normative data. METHODS: Norwegian-born mothers randomly selected from the population register completed Norwegian translations of the Ages and Stages Questionnaires, a series of 19 age-specific child development screening questionnaires each made up of 30 items in five domains: Communication, Gross Motor, Fine Motor, Problem Solving, and Personal-Social. Domain score group differences with original US normative data on 10 age-specific questionnaires (for ages 4, 8, 12, 16, 20, 24, 30, 36, 48, and 60 mo) were investigated. The Norwegian data consisted of 1341 children, varying between 82 and 176 per age interval. RESULTS: On the whole, parents' reports of their children's development were very similar in the two data sets. Only five out of 50 mean comparisons revealed a mean difference either greater than a Cohen's d of 0.5 or greater than the smallest increment on a domain score. The variation in scores tended to be somewhat smaller in the Norwegian sample. CONCLUSION: It seems reasonable to expect that domain scores on the Ages and Stages Questionnaires may be interpreted in the same way in Norway and the United States, and these results may also generalize to other Western settings. These findings from a true random sample also increase the confidence in the original normative data.
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Desarrollo Infantil , Encuestas y Cuestionarios , Preescolar , Comparación Transcultural , Humanos , Lactante , Recién Nacido , Noruega , Estados UnidosRESUMEN
BACKGROUND: The developmental outcomes of children born after ICSI are still a matter of concern. The purpose of the present study was to investigate psychological outcomes for 5-year-old children born after ICSI and compare these with outcomes for children born after spontaneous conception (SC). METHODS: Three hundred singleton children born after ICSI in Belgium, Sweden and the USA were matched by maternal age, child age and gender. Outcome measures included the Wechsler Preschool and Primary scales of intelligence (WPPSI-R), Peabody Developmental Motor Scales, Parenting Stress Index and Child Behaviour Checklist. RESULTS: Regarding cognitive development, no significant differences were found on WPPSI-R verbal and performance scales between ICSI and SC children. However, some differences were noted on subtests of the Performance Scale. ICSI children more often obtained a score below 1 SD of the mean on the subtests: Object Assembly, Block Design and Mazes (all P<0.05). Significant differences by site (i.e. Belgium, Sweden and New York) were found on subtests related to parenting stress, child behaviour problems and motor development (all P<0.05). These findings can probably be explained by variables other than conception mode, such as cultural differences and selection bias. CONCLUSIONS: Although the finding that a higher proportion of ICSI children obtained scores below the cut-off on some of the visual-spatial subscales of the WPPSI-R warrants further investigation, ICSI does not appear to affect the psychological well-being or cognitive development at age 5.
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Psicología Infantil , Inyecciones de Esperma Intracitoplasmáticas , Peso al Nacer , Estudios de Casos y Controles , Conducta Infantil/psicología , Desarrollo Infantil , Preescolar , Cognición/fisiología , Escolaridad , Emociones , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Inteligencia , Masculino , Edad Materna , Madres , Actividad Motora , Valores de Referencia , Estrés PsicológicoRESUMEN
Early adequate cyclosporine exposure has been shown to predict low acute rejection. Recently basiliximab induction has been added to immunosuppressive regimens to further reduce rejection. The aim of this study was to determine the importance of achieving the early cyclosporine therapeutic threshold with basiliximab induction. A retrospective analysis of first cadaver and nonidentical living donor transplant recipients treated with or without basiliximab induction was performed. All patients (n = 170) received neoral, mycophenolate mofetil, and prednisone. The cyclosporine absorption profile was measured on day 3. Adequate cyclosporine exposure was defined as area under the curve (AUC) 0-4: >4400 microg x h/L at day 3. The primary outcome was acute rejection (AR) within the first 6 month. In the no basiliximab (control) group, AR occurred in 22% (17/78) of recipients and was strongly associated with low cyclosporine exposure on day 3. AR occurred in 39% (9/23) with cyclosporine AUC0-4 < 4400 microg x h/L compared with 15% (8/55) with AUC0-4 > 4400 microg x h/L (P =.016). In the basiliximab group, AR occurred in only 9% (8/92) of recipients and did not correlate with cyclosporine exposure. AR occurred in 8% (2/24) with cyclosporine AUC0-4 < 4400 microg x h/L compared with 9% (6/68) with AUC0-4 > 4400 microg x h/L (P =.94). Achieving cyclosporine therapeutic targets by day 3 may not be required when anti-IL2 induction is used.
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Anticuerpos Monoclonales/uso terapéutico , Ciclosporina/farmacocinética , Trasplante de Riñón/inmunología , Proteínas Recombinantes de Fusión , Anticuerpos Monoclonales/farmacocinética , Área Bajo la Curva , Basiliximab , Cadáver , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Donadores Vivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Donantes de TejidosRESUMEN
The purpose of this study was to determine which tacrolimus pharmacokinetic parameters best predicted efficacy in kidney transplantation. Blood tacrolimus levels at 0, 1, 2, 3, and 4 hours postdose were measured in 28 kidney transplants. All received tacrolimus-based triple-drug therapy with mychophenolate mofetil and prednisone. Associations between blood concentrations at each sampling time point and the area under the curve (AUC) 0-4 were measured by Pearson's correlation coefficients. Tacrolimus dosing was based on C0 not AUC. AUC and blood concentrations at each sampling time were retrospectively compared with C0 as predictor of acute rejection and nephrotoxicity. Although tacrolimus C0 correlated with AUC0-4 (r =.86), correlations were higher with C2 and C3 (r =.96 and r =.94, respectively). C0 levels were not significantly different in six patients with acute rejection and 23 patients without. There was a trend toward lower tacrolimus C3 in patients with AR than without AR (P =.06). C2 and C3 correlate better with AUC0-4 than C0. Early tacrolimus C3 levels may be a better than C0 as a predictor of efficacy.
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Inmunosupresores/farmacocinética , Trasplante de Riñón/fisiología , Tacrolimus/farmacocinética , Adulto , Área Bajo la Curva , Monitoreo de Drogas/métodos , Femenino , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/sangre , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Tacrolimus/sangre , Tacrolimus/uso terapéutico , Factores de TiempoRESUMEN
BACKGROUND: The Pediatric Spectrum of HIV Diseases (PSD) project has been collecting data on HIV-exposed children in Texas since 1989. These data have now been analyzed to describe mother-to-child transmission in Texas and to provide much needed information on the magnitude of the pediatric HIV epidemic in the state. METHODS: We examined trends in the numbers of perinatally exposed children and perinatally acquired cases of HIV in the Texas PSD cohort. We calculated transmission rates and relative risks for 656 children born from January, 1995, to July, 1998, that received all or part of the ACTG 076 regimen. RESULTS: Only a small proportion (38%) of pairs of an HIV-infected mother and her HIV-exposed child received the full AIDS Clinical Trial Group 076 (ACTG 076) regimen; only 73% of the mothers received at least some prenatal care. In recent years, however, the numbers of perinatally exposed children and perinatally acquired cases of HIV have decreased in Texas. Univariate analyses showed that a reduction in the vertical transmission of HIV was associated with receipt of a full ACTG 076 regimen, receipt of a partial ACTG 076 regimen and residence in Dallas County. CONCLUSIONS: Findings identify a gap in meeting the health care needs of pregnant HIV-infected women and suggest missed opportunities to prevent mother-to-child transmission of HIV. At the same time this study confirms progress in prevention efforts to reduce mother-to-child transmission of HIV in Texas.
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Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Fármacos Anti-VIH/uso terapéutico , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo , Atención Prenatal , Factores de Riesgo , Texas/epidemiología , Zidovudina/uso terapéuticoRESUMEN
BACKGROUND: Because HIV-infected and HIV-exposed children are at risk of acquiring infectious diseases, they should be immunized. METHODS: We abstracted charts at pediatric HIV clinics in Dallas and San Antonio, matched the children to birth certificates and assessed up-to-date immunization status. RESULTS: Of the 178 children, 108 (61%) were up to date for the diphtheria-tetanus-pertussis (DTP), polio, and measles-mumps-rubella (MMR) series. In multivariate analysis, predictors of delayed immunization included maternal high-risk sexual partners and infant antiretroviral therapy. CONCLUSION: In this population of children born to HIV-infected mothers, immunizations were up to date in 61%, a figure that exceeds or equals immunization levels for other Texas children. Texas falls short of the recommended goal of 90% immunization for children of HIV-infected mothers and healthy children.
Asunto(s)
Infecciones por VIH/inmunología , Vacunación/estadística & datos numéricos , Preescolar , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Femenino , Infecciones por VIH/transmisión , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Vacuna Antisarampión/administración & dosificación , Vacuna contra el Sarampión-Parotiditis-Rubéola , Vacuna contra la Parotiditis/administración & dosificación , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna contra la Rubéola/administración & dosificación , Factores Socioeconómicos , Texas , Vacunas Combinadas/administración & dosificaciónAsunto(s)
Maltrato a los Niños , Adolescente , Niño , Maltrato a los Niños/clasificación , Maltrato a los Niños/diagnóstico , Maltrato a los Niños/prevención & control , Abuso Sexual Infantil/diagnóstico , Abuso Sexual Infantil/prevención & control , Defensa del Niño , Conducta Infantil , Desarrollo Infantil , Preescolar , Traumatismos Craneocerebrales/diagnóstico , Registros Odontológicos , Odontólogos , Traumatismos Faciales/diagnóstico , Humanos , Lactante , Recién NacidoRESUMEN
BACKGROUND: Identification of a clonal proliferation of lymphocytes is central to the diagnosis of lymphoma compared with a reactive lymphoproliferation. We propose a novel diagnostic technique based on restriction fragment length polymorphism (RFLP) of amplified polymerase chain reaction (PCR) products of the T-cell receptor -gamma (TCR-gamma) gene rearrangement to rapidly identify monoclonality in T-cell lymphomas and improve diagnosis of malignancy. MATERIALS AND METHODS: DNA from peripheral blood mononuclear cells (PBMCs) of 10 healthy volunteers and 7 T-cell lymphoma patients were isolated and the TCR-gamma was amplified with consensus primers for the different variable (V) and joining (J) segments. Restriction digests were done using BstN1 and the fragments separated via gel electrophoresis. Verification was by Southern analysis. RESULTS: Restriction digests of the 10 healthy controls show a characteristic nine-band digest pattern whereas the restriction digests of the 7 T-cell lymphomas each show altered banding patterns completely distinct from the normal nine-band pattern (Fisher exact test = 0.00005). Sensitivity assays demonstrate the test can detect clonal populations representing 2% of total. This method also enables identification of particular clonal populations. The entire procedure can be performed in one day, does not require radioactivity, and requires only small quantities of specimens. CONCLUSIONS: This RFLP-PCR-based diagnostic method for T-cell lymphomas is specific, sensitive, efficient, and reproducible, and enables the identification of clonally expanded populations of T lymphocytes. It offers the ability to identify particular clonal populations, as with Southern analysis, combined with the benefits of a PCR method.