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1.
N Z Vet J ; 72(4): 236-240, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38705579

RESUMEN

CASE HISTORY: A line of 25 cull cows were all found to have ulcerative lesions of the tongue at post-mortem inspection in a New Zealand slaughter plant. A further 9 of 10 cows inspected at the farm of origin had similar oral lesions. There were no other clinical signs or indicators of ill-health observed at ante-mortem inspection in the abattoir or on the farm. The cows had been fed baleage for 3 weeks prior to slaughter, made from pasture in paddocks heavily contaminated with yellow bristle grass (Setaria pumila). CLINICAL FINDINGS: There was extensive and deep transverse linear ulceration in the lingual fossa immediately rostral to the torus linguae. At histological examination, full-thickness ulceration of the stratified squamous epithelium was observed with a bed of disorganised collagenous tissue and extensive mixed inflammatory infiltrate extending into the sub-epithelial connective tissue and skeletal muscle. Barbed plant fragments were embedded in both the superficial and deeper areas of inflammation. Detailed examination of the baleage also found that yellow bristle grass seedheads were present. DIAGNOSIS: Based on the presence of barbed plant material in the tongue and yellow bristle grass seeds in the baleage, a diagnosis of ulcerative stomatitis associated with yellow bristle grass was made. CLINICAL RELEVANCE: Clinicians should be aware of the potential for hay or baleage contaminated with yellow bristle grass to cause oral lesions in cattle.


Asunto(s)
Enfermedades de los Bovinos , Animales , Bovinos , Nueva Zelanda/epidemiología , Femenino , Enfermedades de los Bovinos/patología , Enfermedades de los Bovinos/epidemiología , Estomatitis/veterinaria , Estomatitis/patología , Poaceae , Lengua/patología , Alimentación Animal/análisis
2.
J Surg Res ; 269: 119-128, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34551368

RESUMEN

INTRODUCTION: Abdominal aortic aneurysm (AAA) repair may be performed through open or endovascular approaches, but the factors influencing a patient's repair-type preference are not well characterized. Here we performed a qualitative analysis to better understand factors influencing patient preference within the Preference for Open Versus Endovascular Repair of AAA Trial. METHODS: Open-ended responses regarding primary (n = 21) and secondary (n = 47) factors influencing patient preference underwent qualitative analysis using the constant comparative method with iterative reviews. Codes were used to generate themes and themes grouped into categories, with each step conducted via consensus agreement between three researchers. Relative prevalence of themes were compared to ascertain trends in patient preference. RESULTS: Patient responses regarding both primary and secondary factors fell into four categories: Short-term concerns, long-term concerns, advice & experience, and other. Patients most frequently described short-term concerns (23) as their primary influence, with themes including post-op complications, hospitalization & recovery, and intraoperative concerns. Long-term concerns were more prevalent (20) as secondary factors, which included themes such as survival, and chronic management. The average age of patients voicing only long-term concerns as a primary factor was 11 years younger than those listing only short-term concerns. CONCLUSION: Short-term concerns relating to the procedure and recovery are more often the primary factor influencing patient preference, while long term concerns play a more secondary role. Long-term concerns are more often a primary factor in younger patients. Vascular surgeons should consider this information in shared decision making to reach an optimal outcome.


Asunto(s)
Aneurisma de la Aorta Abdominal , Prioridad del Paciente , Procedimientos de Cirugía Plástica , Humanos , Resultado del Tratamiento
3.
Ir Med J ; 115(8): 649, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36302298

RESUMEN

Aims Ireland has the highest vancomycin-resistant Enterococcus faecium (VRE) bloodstream infection prevalence in Europe. Two patterns of VRE carriage are recognised. European, with widespread community prevalence and North American, where carriage is predominantly nosocomial. It is unclear which pattern is dominant in Ireland. This uncertainty limits infection control measures. This study sought to explore this issue via a cross sectional point prevalence study. Methods Asymptomatic community volunteers, represented by patients undergoing elective outpatient colonoscopy testing, were opportunistically screened for VRE. Demographic and risk factor data were collected via a patient survey. Rectal swabs were collected before colonoscopy and VRE was identified using the VITEK MS system. Results 102 patients were cultured. A single patient tested positive, representing a prevalence rate of 0.98% (95% CI <0.01-5.8%). This patient demonstrated traditional risk factors, suggesting nosocomial rather than community acquisition. 94% (N=94) of patients had no knowledge of VRE, while 83% (N=83) had low levels of concern regarding hospital acquired infections. Conclusion There is a low incidence of VRE in the Irish community setting, in contrast to other European Countries, suggesting asymptomatic community colonization is not responsible for the high rates of VRE seen in Ireland. Wider screening or atypical infection control measures would not be supported by this data.


Asunto(s)
Infección Hospitalaria , Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Humanos , Prevalencia , Estudios Transversales , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Colonoscopía , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/epidemiología , Antibacterianos
4.
J Dairy Sci ; 104(1): 550-560, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33189290

RESUMEN

The goal of this study was to identify potential quantitative trait loci (QTL) for 27 production, fitness, and conformation traits of Guernsey cattle through genome-wide association (GWA) analyses, with extra emphasis on BTA19, where major QTL were observed for several traits. Animals' de-regressed predicted transmitting abilities (PTA) from the December 2018 traditional US evaluation were used as phenotypes. All of the Guernsey cattle included in the QTL analyses were predictor animals in the reference population, ranging from 1,077 to 1,685 animals for different traits. Single-trait GWA analyses were carried out by a mixed-model approach for all 27 traits using imputed high-density genotypes. A major QTL was detected on BTA19, influencing several milk production traits, conformation traits, and livability of Guernsey cattle, and the most significant SNP lie in the region of 26.2 to 28.3 Mb. The myosin heavy chain 10 (MYH10) gene residing within this region was found to be highly associated with milk production and body conformation traits of dairy cattle. After the initial GWA analyses, which suggested that many significant SNP are in linkage with one another, conditional analyses were used for fine mapping. The top significant SNP on BTA19 were fixed as covariables in the model, one at a time, until no more significant SNP were detected on BTA19. After this fine-mapping approach was applied, only 1 significant SNP was detected on BTA19 for most traits, but multiple, independent significant SNP were found for protein yield, dairy form, and stature. In addition, the haplotype that hosts the major QTL on BTA19 was traced to a US Guernsey born in 1954. The haplotype is common in the breed, indicating a long-term influence of this QTL on the US Guernsey population.


Asunto(s)
Constitución Corporal/genética , Bovinos/genética , Leche , Sitios de Carácter Cuantitativo , Animales , Bovinos/anatomía & histología , Bovinos/fisiología , Mapeo Cromosómico , Femenino , Ligamiento Genético , Estudio de Asociación del Genoma Completo/veterinaria , Genotipo , Haplotipos , Fenotipo
5.
Ir Med J ; 114(7): 406, 2021 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-34520641

RESUMEN

Aim Knowledge of latent tuberculosis infection (LTBI) screening and treatment practices are lacking in Ireland, where LTBI is not programmatically surveyed or managed. The aim of this research was to describe current clinical practice when screening and treating patients for LTBI in a tertiary referral centre in Ireland. Methods A 17-question survey relating to LTBI screening and management practices with both open-ended questions and close ended multiple-choice questions was created using SurveyMonkey. The survey target sample was healthcare workers in the tertiary centre who direct LTBI screening and treatment for patients at risk of TB disease in their respective departments. Results The response rate to the survey was 45% (21/47). Seventy-one percent (15/21) of those surveyed responded to the question "What barriers exist to screening patients for latent TB in your clinical practice?". Fifty-three percent (8/15) said that they found it difficult to access LTBI testing and 27% (4/15) cited accessing the interferon-gamma release assay (IGRA) result as a barrier. Forty-three percent (9/21) responded that there was not a clear referral pathway for patients that they would like specialist input on when diagnosing and managing patients with LTBI. Conclusion Access to LTBI testing, LTBI test results, TB specialist services and the use of rifamycin-based regimens should be improved in this tertiary centre. Consideration should be given to developing a national LTBI education programme for healthcare professionals and updating national LTBI treatment guidelines.


Asunto(s)
Tuberculosis Latente , Humanos , Ensayos de Liberación de Interferón gamma , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Tamizaje Masivo , Encuestas y Cuestionarios , Centros de Atención Terciaria
6.
J Dairy Sci ; 103(3): 2477-2486, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31954583

RESUMEN

Genomic selection is an important tool to introduce feed efficiency into dairy cattle breeding. The goals of the current research are to estimate genomic breeding values of residual feed intake (RFI) and to assess the prediction reliability for RFI in the US Holstein population. The RFI data were collected from 4,823 lactations of 3,947 Holstein cows in 9 research herds in the United States, and were pre-adjusted to remove phenotypic correlations with milk energy, metabolic body weight, body weight change, and for several environmental effects. In the current analyses, genomic predicted transmitting abilities of milk energy and of body weight composite were included into the RFI model to further remove the genetic correlations that remained between RFI and these energy sinks. In the first part of the analyses, a national genomic evaluation for RFI was conducted for all the Holsteins in the national database using a standard multi-step genomic evaluation method and 60,671 SNP list. In the second part of the study, a single-step genomic prediction method was applied to estimate genomic breeding values of RFI for all cows with phenotypes, 5,252 elite young bulls, 4,029 young heifers, as well as their ancestors in the pedigree, using a high-density genotype chip. Theoretical prediction reliabilities were calculated for all the studied animals in the single-step genomic prediction by direct inversion of the mixed model equations. In the results, breeding values were estimated for 1.6 million genotyped Holsteins and 60 million ungenotyped Holsteins, The genomic predicted transmitting ability correlations between RFI and other traits in the index (e.g., fertility) are generally low, indicating minor correlated responses on other index traits when selecting for RFI. Genomic prediction reliabilities for RFI averaged 34% for all phenotyped animals and 13% for all 1.6 million genotyped animals. Including genomic information increased the prediction reliabilities for RFI compared with using only pedigree information. All bulls had low reliabilities, and averaged to only 16% for the top 100 net merit progeny-tested bulls. Analyses using single-step genomic prediction and high-density genotypes gave similar results to those obtained from the national evaluation. The average theoretical reliability for RFI was 18% among the elite young bulls under 5 yr old, being lower in the younger generations of elite bulls compared with older bulls. To conclude, the size of the reference population and its relationship to the predicted population remain as the limiting factors in the genomic prediction for RFI. Continued collection of feed intake data is necessary so that reliabilities can be maintained due to close relationships of phenotyped animals with breeding stock. Considering the currently low prediction reliability and high cost of data collection, focusing RFI data collection on relatives of elite bulls that will have the greatest genetic contribution to the next generation will give more gains and profit.


Asunto(s)
Cruzamiento , Bovinos/fisiología , Ingestión de Alimentos , Animales , Peso Corporal/genética , Bovinos/genética , Femenino , Genoma , Lactancia , Masculino , Leche/metabolismo , Linaje , Fenotipo , Reproducibilidad de los Resultados
7.
J Intellect Disabil Res ; 64(5): 368-380, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32215976

RESUMEN

BACKGROUND: Depression and anxiety are amongst the most prevalent mental health disorders in the older population with intellectual disability (ID). There is a paucity of research that pertains to associative biopsychosocial factors for depression and anxiety in this population. The aim of this study is to determine the biopsychosocial factors associated with depression and anxiety in a population of older adults with ID in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. Depressive symptoms were assessed using the Glasgow Depression Scale for people with a Learning Disability. Anxiety symptoms were measured using the Glasgow Anxiety Scale for people with a Learning Disability. The cross-sectional associations of depression and anxiety with biopsychosocial parameters were measured using a variety of self-report and proxy-completed questionnaires. RESULTS: For the study population, 9.97% met the criteria for depression, and 15.12% met the criteria for an anxiety disorder. Participants meeting criteria for depression were more likely to be taking regular mood stabiliser medications and to exhibit aggressive challenging behaviour. Participants meeting criteria for anxiety were more likely to have sleep difficulties and report loneliness. Participants meeting criteria for either/both depression and anxiety were more likely to report loneliness. CONCLUSIONS: This study identified both treatable and modifiable, as well as unmodifiable, biopsychosocial factors associated with depression and/or anxiety in older adults with ID. A longitudinal study follow-up will further develop our knowledge on the causality and direction of associated biopsychosocial factors with depression and anxiety in older adults with ID and better inform management strategies, prevention policies and funding of services.


Asunto(s)
Envejecimiento , Ansiedad , Depresión , Discapacidad Intelectual , Anciano , Envejecimiento/fisiología , Envejecimiento/psicología , Ansiedad/epidemiología , Ansiedad/fisiopatología , Ansiedad/psicología , Comorbilidad , Estudios Transversales , Depresión/epidemiología , Depresión/fisiopatología , Depresión/psicología , Femenino , Humanos , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/fisiopatología , Discapacidad Intelectual/psicología , Irlanda , Estudios Longitudinales , Masculino , Persona de Mediana Edad
8.
J Dairy Sci ; 102(4): 3216-3229, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30772032

RESUMEN

Whole-genome sequencing studies can identify causative mutations for subsequent use in genomic evaluations. Speed and accuracy of sequence alignment can be improved by accounting for known variant locations during alignment instead of calling the variants after alignment as in previous programs. The new programs Findmap and Findvar were compared with alignment using Burrows-Wheeler alignment (BWA) or SNAP and variant identification using Genome Analysis ToolKit (GATK) or SAMtools. Findmap stores the reference map and any known variant locations while aligning reads and counting reference and alternate alleles for each DNA source. Findmap also outputs potential new single nucleotide variant, insertion, and deletion alleles. Findvar separates likely true variants from read errors and outputs genotype probabilities. Strategies were tested using cattle, human, and a completely random reference map and simulated or actual data. Most tests simulated 10 bulls, each with 10× simulated sequence reads containing 39 million variants from the 1000 Bull Genomes Project. With 10 processors, clock times for processing 100× data were 105 h for BWA, 25 h for GATK, and 11 h for SAMtools but only about 4 h for SNAP, 3 h for Findmap, and 1 h for Findvar. Alignment programs required about the same total memory; BWA used 46 GB (4.6 GB/processor), whereas >10 processors can share the same memory in SNAP and Findmap, which used 40 and 46 GB, respectively. Findmap correctly mapped 92.9% of reads (compared with 92.6% from SNAP and 90.5% from BWA) and had high accuracy of calling alleles for known variants. For new variants, Findvar found 99.8% of single nucleotide variants, 79% of insertions, and 67% of deletions; GATK found 99.4, 95, and 90%, respectively; and SAMtools found 99.8, 12, and 16%, respectively. False positives (as percentages of true variants) were 11% of single nucleotide variants, 0.4% of insertions, and 0.3% of deletions from Findvar; 12, 8.4, and 2.9%, respectively, from GATK; and 37, 1.3, and 0.4%, respectively, from SAMtools. Advantages of Findmap and Findvar are fast processing, precise alignment, more useful data summaries, more compact output, and fewer steps. Calling known variants during alignment allows more efficient and accurate sequence-based genotyping.


Asunto(s)
Bovinos/genética , Variación Genética , Alineación de Secuencia , Secuenciación Completa del Genoma , Algoritmos , Alelos , Animales , Simulación por Computador , ADN , Genoma Humano , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Programas Informáticos
9.
J Intellect Disabil Res ; 63(5): 454-465, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30697858

RESUMEN

BACKGROUND: Exposures to life events are associated with emotional, psychological and behavioural problems in those with intellectual disability (ID). Older adults with ID may experience different life events given differences in living circumstances, cognitive decline, greater dependency on others and less autonomy. This study examines the relationship of life events and mental ill health in an older ID population in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. The frequency of life events was assessed using a 20-item checklist, and the level of stress experienced was assessed using a three-point Likert scale measuring the burden of the life event. The associations of life events with factors associated with mental ill health were measured using a variety of self-report and proxy completed questionnaires. RESULTS: For the study population, 88.1% had been exposed to at least one life event in the preceding 12 months and 64.5% to two or more life events. Frequency and burden of life events were significantly higher in individuals living in institutional settings and in individuals with any current psychiatric condition, increased depressive and anxiety symptoms, challenging behaviour and reported poorer self-rated mental and physical health. More life events were significantly associated with new psychiatric diagnoses as well as initiation and increased dosage of mood stabilising, hypnotic and sedative medications. CONCLUSIONS: Life events are significantly associated with mental ill health in the older ID population. Service providers must focus on limiting the exposure to these events and, in situations where they cannot be avoided, should support and manage individuals compassionately and effectively, prioritising their mental and physical well-being.


Asunto(s)
Envejecimiento , Ansiedad/epidemiología , Depresión/epidemiología , Estado de Salud , Discapacidad Intelectual/epidemiología , Trastornos Mentales/epidemiología , Problema de Conducta , Estrés Psicológico/epidemiología , Adulto , Anciano , Comorbilidad , Femenino , Humanos , Irlanda/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad
10.
J Dairy Sci ; 101(10): 9089-9107, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30031583

RESUMEN

Experimental designs that exploit family information can provide substantial predictive power in quantitative trait nucleotide discovery projects. Concordance between quantitative trait locus genotype as determined by the a posteriori granddaughter design and marker genotype was determined for 30 trait-by-chromosomal segment effects segregating in the US Holstein population with probabilities of <10-20 to accept the null hypotheses of no segregating gene affecting the trait within the chromosomal segment. Genotypes for 83 grandsires and 17,217 sons were determined by either complete sequence or imputation for 3,148,506 polymorphisms across the entire genome; 471 Holstein bulls had a complete genome sequence, including 64 of the grandsires. Complete concordance was obtained only for stature on chromosome 14 and daughter pregnancy rate on chromosome 18. For each quantitative trait locus, effects of the 30 polymorphisms with highest concordance scores for the analyzed trait were computed by stepwise regression for predicted transmitting abilities of 26,750 bulls with progeny test and imputed genotypes. Effects for stature on chromosome 11, daughter pregnancy rate on chromosome 18, and protein percentage on chromosome 20 met 3 criteria: complete or almost complete concordance, nominal significance of the polymorphism effect after correction for all other polymorphisms, and marker coefficient of determination >40% of total multiple-regression coefficient of determination for the 30 polymorphisms with highest concordance. An intronic variant marker on chromosome 5 at 93,945,738 bp explained 7% of variance for fat percentage and 74% of total multiple-marker regression variance but was concordant for only 24 of 30 families. The missense polymorphism Phe279Tyr in GHR at 31,909,478 bp on chromosome 20 was confirmed as the causative mutation for fat and protein concentration. For effect on fat percentage on chromosome 14, 12 additional missense polymorphisms were found that had almost complete concordance with the suggested causative polymorphism (missense mutation Ala232Glu in DGAT1). The only polymorphism found likely to improve predictive power for genomic evaluation of dairy cattle was on chromosome 15; that polymorphism had a frequency of 0.45 for the allele with economically positive effects on all production traits.


Asunto(s)
Bovinos/genética , Mapeo Cromosómico , Sitios de Carácter Cuantitativo , Animales , Femenino , Genotipo , Masculino , Leche , Nucleótidos , Fenotipo , Polimorfismo de Nucleótido Simple , Embarazo , Índice de Embarazo
11.
Pflugers Arch ; 469(10): 1257-1265, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28550471

RESUMEN

Pulmonary oxygen uptake ([Formula: see text]) slowly increases during exercise above the anaerobic threshold, and this increase is called the slow component of [Formula: see text]. The mechanism of the increase in [Formula: see text] is assumed to be due to increasing energy cost associated with increasingly inefficient muscle contraction. We hypothesized that the increase in [Formula: see text] would be accompanied by a constant or increasing rate of accumulation of blood lactate, indicating sustained anaerobic metabolism while [Formula: see text] increased. Ten male subjects performed cycle ergometry for 3, 6, and 9 min at a power output representing 60% of the difference between lactate threshold and maximal [Formula: see text] while [Formula: see text] and blood lactate accumulation were measured. Blood lactate accumulation decreased over time, providing the energy equivalent of (mean ± SD) 1586 ± 265, 855 ± 287, and 431 ± 392 ml of [Formula: see text] during 0-3, 3-6, and 6-9 min of exercise, respectively. As duration progressed, [Formula: see text] supplied 86.3 ± 2.0, 93.6 ± 1.9, and 96.8 ± 2.9% of total energy from 0 to 3, 3 to 6, and 6 to 9 min, respectively, while anaerobic contribution decreased. There was no change in total energy cost after 3 min, except that required by ventilatory muscles for the progressive increase in ventilation. The slow component of [Formula: see text] is accompanied by decreasing anaerobic energy contribution beyond 3 min during heavy exercise.


Asunto(s)
Metabolismo Energético/fisiología , Ejercicio Físico/fisiología , Ácido Láctico/sangre , Músculo Esquelético/metabolismo , Consumo de Oxígeno/fisiología , Oxígeno/sangre , Adulto , Umbral Anaerobio/fisiología , Humanos , Masculino , Contracción Muscular/fisiología
12.
Ann Oncol ; 27(9): 1712-8, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27287210

RESUMEN

BACKGROUND: ARCHER 1042, a randomized phase II trial, explored the impact of prophylactic treatment on select dermatologic adverse events of interest (SDAEI), diarrhea, and mucositis associated with dacomitinib, an oral irreversible pan-human epidermal growth factor receptor (HER) inhibitor, in development for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC treated with dacomitinib were enrolled in two cohorts. Cohort I patients were randomized 1:1 to receive oral doxycycline or placebo (4 weeks). Cohort II patients received oral VSL#3 probiotic plus topical alclometasone. Primary end points for Cohorts I and II were incidence of all grade and grade ≥2 SDAEI in the first 8 weeks of treatment and quality of life (QoL) assessed by the Skindex-16 survey. Additional primary end points for Cohort II were incidence of all grade and grade ≥2 diarrhea and mucositis in the first 8 weeks of treatment; QoL regarding diarrhea and mucositis incidence was assessed by the modified-Oral Mucositis Daily Questionnaire. RESULTS: Cohort I randomized 114 evaluable patients: 56 in the doxycycline arm, 58 in the placebo arm. Cohort II enrolled 59 evaluable patients. Doxycycline significantly reduced the incidence of grade ≥2 SDAEI by 50% (P = 0.016) compared with placebo. The incidence of all grade SDAEI was lower with doxycycline than with placebo but did not reach statistical significance. Doxycycline was associated with less deterioration in QoL compared with placebo. Alclometasone was associated with less deterioration in QoL compared with placebo but did not statistically significantly reduce the incidence of all grade or grade ≥2 SDAEI. VSL#3 did not reduce the incidence of all grade or grade ≥2 diarrhea and did not impact mucositis scores. CONCLUSIONS: Doxycycline was effective as a prophylactic treatment for dacomitinib-induced grade ≥2 SDAEI. Both doxycycline and alclometasone reduced the negative impact in patient-reported dermatologic AEs. The probiotic was not effective for preventing diarrhea or mucositis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Enfermedades Gastrointestinales/patología , Quinazolinonas/administración & dosificación , Enfermedades de la Piel/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Mutación , Calidad de Vida , Quinazolinonas/efectos adversos , Enfermedades de la Piel/inducido químicamente , Resultado del Tratamiento
13.
Ann Oncol ; 26(7): 1421-7, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25899785

RESUMEN

BACKGROUND: HER2 mutations and amplifications have been identified as oncogenic drivers in lung cancers. Dacomitinib, an irreversible inhibitor of HER2, EGFR (HER1), and HER4 tyrosine kinases, has demonstrated activity in cell-line models with HER2 exon 20 insertions or amplifications. Here, we studied dacomitinib in patients with HER2-mutant or amplified lung cancers. PATIENTS AND METHODS: As a prespecified cohort of a phase II study, we included patients with stage IIIB/IV lung cancers with HER2 mutations or amplification. We gave oral dacomitinib at 30-45 mg daily in 28-day cycles. End points included partial response rate, overall survival, and toxicity. RESULTS: We enrolled 30 patients with HER2-mutant (n = 26, all in exon 20 including 25 insertions and 1 missense mutation) or HER2-amplified lung cancers (n = 4). Three of 26 patients with tumors harboring HER2 exon 20 mutations [12%; 95% confidence interval (CI) 2% to 30%] had partial responses lasting 3+, 11, and 14 months. No partial responses occurred in four patients with tumors with HER2 amplifications. The median overall survival was 9 months from the start of dacomitinib (95% CI 7-21 months) for patients with HER2 mutations and ranged from 5 to 22 months with amplifications. Treatment-related toxicities included diarrhea (90%; grade 3/4: 20%/3%), dermatitis (73%; grade 3/4: 3%/0%), and fatigue (57%; grade 3/4: 3%/0%). One patient died on study likely due to an interaction of dacomitinib with mirtazapine. CONCLUSIONS: Dacomitinib produced objective responses in patients with lung cancers with specific HER2 exon 20 insertions. This observation validates HER2 exon 20 insertions as actionable targets and justifies further study of HER2-targeted agents in specific HER2-driven lung cancers. CLINICALTRIALSGOV: NCT00818441.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Amplificación de Genes , Mutación/genética , Quinazolinonas/uso terapéutico , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Administración Oral , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Esquema de Medicación , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia
14.
Eur J Neurol ; 22(11): 1488-91, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26333310

RESUMEN

BACKGROUND AND PURPOSE: Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. METHODS: This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age ≥ 55 years). RESULTS: Heritabilities for young-onset stroke and old-onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively. CONCLUSIONS: Our data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.


Asunto(s)
Isquemia Encefálica/genética , Predisposición Genética a la Enfermedad , Accidente Cerebrovascular/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Accidente Cerebrovascular/epidemiología , Población Blanca/genética
16.
Ir Med J ; 108(5): 134-6, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26062237

RESUMEN

Childhood Obesity poses a public health problem in Ireland. Complications associated include metabolic disease and cardiovascular disease risk. Our aim was to determine the prevalence of cardiovascular risk factors in a cohort of obese Irish children. Assessments were performed on obese children attending weight management clinic. Pedometers and self report physical activity questionnaires were administered to each participant to determine physical activity levels. Fifty-nine children (21 prepubertal and 38 pubertal/post-pubertal) were metabolically profiled. Mean ± SD of z scores for BMI, Waist Circumference and Body Fat % were +3.29 ± 0.48, +3.98 ± 0.73 and +2.75 ± 0.50 respectively. 43% (n = 9) prepubertal and 68% (n = 26) pubertal/postpubertal children had at least one other cardiovascular risk factor in addition to obesity. Increased moderate-vigorous physical activity levels correlated with reduced incidence of cardiovascular risk factors. There is a significant prevalence of cardiovascular risk factors among obese pre-pubertal children and pubertal/post-pubertal adolescents attending an Irish obesity clinic.


Asunto(s)
Glucemia/metabolismo , Enfermedades Cardiovasculares , HDL-Colesterol/sangre , Actividad Motora/fisiología , Obesidad , Triglicéridos/sangre , Adolescente , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Niño , Femenino , Humanos , Irlanda/epidemiología , Masculino , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/epidemiología , Obesidad/metabolismo , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios
17.
J Wound Care ; 23(10): 465-74, 476, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25296347

RESUMEN

OBJECTIVE: To evaluate how the different processing methods cryopreservation and dehydration affect the structural integrity and biological composition of key signalling molecules within amniotic membrane and umbilical cord tissues. METHOD: We directly compared cryopreserved amniotic membrane (AM) and umbilical cord (UC) tissues with dehydrated amniotic membrane/chorion (dHACM) tissue using biochemical and functional assays including histological and histochemical staining, BCA, agarose gel electrophoresis, western blot, ELISA, and proliferation and cell death assays. RESULTS: Cryopreservation retains the native architecture of the AM/UC extracellular matrix and maintains the quantity and activity of key biological signals present in fresh AM/UC, including high molecular weight hyaluronic acid, heavy chain-HA complex, and pentraxin 3. In contrast, dehydrated tissues were structurally compromised and almost completely lacked these crucial components. CONCLUSION: The results presented here indicate that cryopreservation better preserves the structural and biological signaling molecules of foetal tissues.


Asunto(s)
Amnios/citología , Corion/química , Corion/citología , Criopreservación , Desecación , Cordón Umbilical/citología , Amnios/química , Humanos , Cordón Umbilical/química
18.
Ir Med J ; 107(6): 171-3, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24988832

RESUMEN

The objective of this project was to analyse the current access to in-patient stroke services and MDT rehabilitation in an acute stroke centre and to compare these services to the recommended "National Clinical Guidelines and Recommendations for the Care of People with Stroke and TIA" (IHF 2010). A retrospective chart review was carried out, recording activity statistics of all patients admitted with acute stroke over a three-month period. 73 patients (male = 40, 54.8%) were included. Patients were discharged from the stroke service after a mean stay of 20.2 days (SD = 19.3). 76.7% (N = 56) of patients were admitted to the acute stroke unit (ASU). The mean length of time from admission to first assessment 3.4 days (SD. = 2.68), with an average of 138 minutes of treatment received per day across all disciplines. This is compared to the IHF's recommendation of patients being assessed within 24-48 hours of admission and receiving 180 minutes of treatment across all disciplines. As demands for stroke MDT services increase, it is important to recognise the benefits of increasing staff and resources to maintain and continue to improve standards of care.


Asunto(s)
Accesibilidad a los Servicios de Salud , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Rehabilitación de Accidente Cerebrovascular , Dietética/estadística & datos numéricos , Femenino , Humanos , Irlanda , Terapia del Lenguaje/estadística & datos numéricos , Tiempo de Internación , Masculino , Terapia Ocupacional/estadística & datos numéricos , Grupo de Atención al Paciente , Modalidades de Fisioterapia/estadística & datos numéricos , Estudios Retrospectivos , Logopedia/estadística & datos numéricos , Factores de Tiempo
19.
Br J Oral Maxillofac Surg ; 62(5): 391-395, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38777718

RESUMEN

The patient concerns inventory (PCI) allows patients to highlight the issues they would like to discuss at their outpatient consultation. It improves patient-clinician communication and has proven benefits. While the PCI is effective, patient experiences could be improved with better access to it and the ability to more easily and frequently express their concerns. This, of course, is in the context of ever-increasing healthcare challenges and limited resources. Use of conversational artificial intelligence (CAI) represents an opportunity to improve information flow between patients and professionals remote from the consultation. This paper highlights the potential for CAI to provide an 'always-on' platform, using natural language interface technology and based on the PCI, which patients can access via their mobile devices. We also discuss potential pitfalls and concerns, along with outlining a current clinical trial assessing, in the first instance, usability of this technology.


Asunto(s)
Inteligencia Artificial , Comunicación , Humanos , Relaciones Médico-Paciente
20.
Int J Obes (Lond) ; 37(11): 1510-3, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23439322

RESUMEN

Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7±7.3 kg m(-2)), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.


Asunto(s)
Antígenos CD/metabolismo , Células Dendríticas/inmunología , Inmunidad Innata/genética , Inmunoglobulinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Obesidad Mórbida/inmunología , Linfocitos T/inmunología , Adulto , Susceptibilidad a Enfermedades , Femenino , Citometría de Flujo , Anticuerpos contra la Hepatitis B/sangre , Vacunas contra Hepatitis B/inmunología , Humanos , Masculino , Obesidad Mórbida/complicaciones , Toxoide Tetánico/inmunología , Antígeno CD83
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