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1.
J Hosp Infect ; 146: 125-133, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38295904

RESUMEN

BACKGROUND: Surveillance is an acknowledged method to decrease nosocomial infections, such as surgical site infections (SSIs). Electronic healthcare records create the opportunity for automated surveillance. While approaches for different types of surgeries and indicators already exist, there are very few for obstetrics and gynaecology. AIM: To analyse the sensitivity and workload reduction of semi-automated surveillance in obstetrics and gynaecology. METHODS: In this retrospective, single-centre study at a 1438-bed tertiary care hospital in Germany, semi-automated SSI surveillance using the indicators 'antibiotic prescription', 'microbiological data' and 'administrative data' (diagnosis codes, readmission, post-hospitalization care) was compared with manual analysis and categorization of all patient files. Breast surgeries (BSs) conducted in 2018 and caesarean sections (CSs) that met the inclusion criteria between May 2013 and December 2019 were included. Indicators were analysed for sensitivity, number of analysed procedures needed to identify one case, and potential workload reduction in detecting SSIs in comparison with the control group. FINDINGS: The reference standard showed nine SSIs in 416 BSs (2.2%). Sensitivities for the indicators 'antibiotic prescription', 'diagnosis code', 'microbiological sample taken', and the combination 'diagnosis code or microbiological sample' were 100%, 88.9%, 66.7% and 100%, respectively. The reference standard showed 54 SSIs in 3438 CSs (1.6%). Sensitivities for the indicators 'collection of microbiological samples', 'diagnosis codes', 'readmission/post-hospitalization care', and the combination of all indicators were 38.9%, 27.8%, 85.2% and 94.4%, respectively. CONCLUSIONS: Semi-automated surveillance systems may reduce workload by maintaining high sensitivity depending on the type of surgery, local circumstances and thorough digitalization.


Asunto(s)
Infección Hospitalaria , Ginecología , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Control de Infecciones , Infección Hospitalaria/microbiología , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/diagnóstico , Antibacterianos/uso terapéutico
2.
Psychol Med ; : 1-9, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38284217

RESUMEN

BACKGROUND: Increased autocorrelation (AR) of system-specific measures has been suggested as a predictor for critical transitions in complex systems. Increased AR of mood scores has been reported to anticipate depressive episodes in major depressive disorder, while other studies found AR increases to be associated with depressive episodes themselves. Data on AR in patients with bipolar disorders (BD) is limited and inconclusive. METHODS: Patients with BD reported their current mood via daily e-diaries for 12 months. Current affective status (euthymic, prodromal, depressed, (hypo)manic) was assessed in 26 bi-weekly expert interviews. Exploratory analyses tested whether self-reported current mood and AR of the same item could differentiate between prodromal phases or affective episodes and euthymia. RESULTS: A total of 29 depressive and 20 (hypo)manic episodes were observed in 29 participants with BD. Self-reported current mood was significantly decreased during the two weeks prior to a depressive episode (early prodromal, late prodromal), but not changed prior to manic episodes. The AR was neither a significant predictor for the early or late prodromal phase of depression nor for the early prodromal phase of (hypo)mania. Decreased AR was found in the late prodromal phase of (hypo)mania. Increased AR was mainly found during depressive episodes. CONCLUSIONS: AR changes might not be better at predicting depressive episodes than simple self-report measures on current mood in patients with BD. Increased AR was mostly found during depressive episodes. Potentially, changes in AR might anticipate (hypo)manic episodes.

3.
Sci Rep ; 13(1): 18201, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37875557

RESUMEN

Monitoring the presence of commensal and pathogenic respiratory microorganisms is of critical global importance. However, community-based surveillance is difficult because nasopharyngeal swabs are uncomfortable and painful for a wide age range of participants. We designed a methodology for minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. Participants were invited to take part in an exit interview. Thirty-three families completed the study. Sampling using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Multi-niche self-sampling at home can be used by adults and children for longitudinal surveillance of respiratory microorganisms, providing key data for design of future studies.


Asunto(s)
Microbiota , Nariz , Adulto , Niño , Humanos , Preescolar , Encuestas y Cuestionarios , Manejo de Especímenes/métodos , Saliva
4.
Antimicrob Agents Chemother ; 66(4): e0173221, 2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35311524

RESUMEN

Botulism is a rare, life-threatening paralytic disease caused by botulinum neurotoxin (BoNT). Available treatments including an equine antitoxin and human immune globulin are given postexposure and challenging to produce and administer. NTM-1633 is an equimolar mixture of 3 human IgG monoclonal antibodies, E1, E2, and E3, targeting BoNT serotype E (BoNT/E). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1633. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy volunteers to receive a single intravenous dose of NTM-1633 (0.033, 0.165, or 0.330 mg/kg) or saline placebo. Safety monitoring included physical examinations, clinical laboratory studies, and vital signs. Blood sampling was performed at prespecified time points for PK and immunogenicity analyses. Twenty-four subjects received study product (18 NTM-1633; 6 placebo), and no deaths were reported. An unrelated serious adverse event was reported in a placebo subject. Adverse events in the NTM-1633 groups were generally mild and similar in frequency and severity to the placebo group, and no safety signal was identified. NTM-1633 has a favorable PK profile with a half-life >10 days for the 0.330 mg/kg dose and an approximately linear relationship with respect to maximum concentration and area under the concentration-time curve (AUC0→t). NTM-1633 also demonstrated low immunogenicity. NTM-1633 is well tolerated at the administered doses. The favorable safety, PK, and immunogenicity profile supports further development as a treatment for BoNT/E intoxication and postexposure prophylaxis.


Asunto(s)
Toxinas Botulínicas , Botulismo , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Método Doble Ciego , Caballos , Humanos , Inmunoglobulina G
5.
Antimicrob Agents Chemother ; 65(7): e0232920, 2021 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-33875433

RESUMEN

Botulism is a rare, life-threatening paralytic disease caused by Clostridium botulinum neurotoxin (BoNT). Available treatments, including an equine antitoxin and human immune globulin, are given postexposure and challenging to produce and administer. NTM-1632 is an equimolar mixture of 3 human IgG monoclonal antibodies, B1, B2, and B3, targeting BoNT serotype B (BoNT/B). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1632. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy volunteers to receive a single intravenous dose of NTM-1632 (0.033, 0.165, or 0.330 mg/kg) or saline placebo. Safety monitoring included physical examinations, clinical laboratory studies, and vital signs. Blood sampling was performed at prespecified time points for PK and immunogenicity analyses. Twenty-four subjects received study product (18 NTM-1632; 6 placebo), and no deaths or serious adverse events were reported. Adverse events in the NTM-1632 groups were generally mild and similar in frequency and severity to the placebo group, and no safety signal was identified. NTM-1632 has a favorable PK profile with a half-life of >20 days for the 0.330-mg/kg dose and an approximately linear relationship with respect to maximum concentration and area under the concentration-time curve (AUC0→t). NTM-1632 demonstrated low immunogenicity with only a few treatment-emergent antidrug antibody responses in the low and middle dosing groups and none at the highest dose. NTM-1632 is well tolerated at the administered doses. The favorable safety, PK, and immunogenicity profile of NTM-1632 supports further clinical development as a treatment for BoNT/B intoxication and postexposure prophylaxis. (This study has been registered at ClinicalTrials.gov under identifier NCT02779140.).


Asunto(s)
Anticuerpos Monoclonales , Botulismo , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Botulismo/tratamiento farmacológico , Método Doble Ciego , Voluntarios Sanos , Humanos , Inmunoglobulina G
6.
Biol Psychol ; 162: 108096, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33891995

RESUMEN

Recent trends in literature, along with the changes to the Diagnostic and Statistical Manual (DSM), make it imperative to study Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) together, in order to better understand potential aetiological commonalities between these highly comorbid disorders. The present study examines social cueing, a highly studied construct in ASD, and intra-subject variability (ISV), a potential endophenotype of ADHD, in four groups of typically developing (TD), ADHD, ASD- (ASD without ADHD), ASD+ (ASD with ADHD) participants (N = 85) aged 10-13 years. Results showed that social cueing is intact in the 'pure' ASD group when task expectations are clear. The ADHD group showed faster saccadic reaction times, no increased ISV and a pattern of viewing comparable to the TD group. However, the ASD + group showed a differences in processing style and ISV. A secondary analysis gives evidence of non-additive effects of the ASD and ADHD factors.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Trastorno del Espectro Autista/complicaciones , Señales (Psicología) , Endofenotipos , Humanos , Tiempo de Reacción
7.
Eur Child Adolesc Psychiatry ; 30(4): 549-562, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32314021

RESUMEN

Recent debates in the literature discuss commonalities between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) at multiple levels of putative causal networks. This debate requires systematic comparisons between these disorders that have been studied in isolation in the past, employing potential markers of each disorder to be investigated in tandem. The present study, choose superior local processing, typical to ASD, and increased Intra-Subject Variability (ISV), typical to ADHD, for a head-to-head comparison of the two disorders, while also considering the comorbid cases. It directly examined groups of participants aged 10-13 years with ADHD, ASD with (ASD+) or without (ASD-) comorbid ADHD and a typically developing (TD) group (total N = 85). A visual search task consisting of an array of paired words was designed. The participants needed to find the specific pair of words, where the first word in the pair was the cue word. This visual search task was selected to compare these groups on overall search performance and trial-to-trial variability of search performance (i.e., ISV). Additionally, scanpath analysis was also carried out using Recurrence Quantification Analysis (RQA) and the Multi-Match Model. Results show that only the ASD- group exhibited superior search performance; whereas, only the groups with ADHD symptoms showed increased ISV. These findings point towards a double dissociation between ASD and ADHD, and argue against an overlap between ASD and ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno del Espectro Autista/diagnóstico , Trastornos Disociativos/diagnóstico , Adolescente , Niño , Femenino , Humanos , Masculino
8.
PLoS One ; 15(6): e0224186, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32497045

RESUMEN

Recent discussions in the literature, along with the revision of the Diagnostic and Statistical Manual (DSM) (American Psychiatric Association 2013), suggest aetiological commonalities between the highly comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Addressing this discussion requires studying these disorders together by comparing constructs typical to each of them. In the present study, we investigate global processing, known to be difficult for participants with ASD, and Intra-Subject Variability (ISV), known to be consistently increased in participants with ADHD, in groups, aged 10-13 years, with ADHD (n = 25), ASD without comorbid ADHD (ASD-) (n = 13) and ASD with ADHD (ASD+) (n = 18) in comparison with a typically developing group (n = 22). A Copying task, typically requiring global processing and in this case particularly designed using equally complex stimuli to also measure ISV across trials, was selected. Oculomotor measures in this task proved to be particularly sensitive to group differences. While increased ISV was not observed in the present task in participants with ADHD, both ASD groups looked longer on the figure to be drawn, indicating that global processing takes longer in ASD. However, the ASD+ group fixated on the figure only between drawing movements, whereas the ASD- group did this throughout the drawing process. The present study provides evidence towards ASD and ADHD being separate, not-overlapping, disorders. Since the pure ASD- group was affected more by central coherence problems than the ASD+ group, it may suggest that neuropsychological constructs interact differently in different clinical groups and sub-groups.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno del Espectro Autista/fisiopatología , Movimiento , Desempeño Psicomotor , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno del Espectro Autista/diagnóstico , Niño , Femenino , Humanos , Masculino
9.
Med Mycol ; 58(6): 730-736, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31711221

RESUMEN

Coccidioidomycosis is an emerging infection in Washington State. The epidemiology of the disease in Washington is poorly understood at present; underrecognition and underreporting of coccidioidomycosis is suspected based on reports of only severe disease. We sought to characterize healthcare provider knowledge, attitudes, and practices regarding coccidioidomycosis awareness, diagnosis, and treatment in south-central Washington. We conducted a cross-sectional survey of actively practicing healthcare providers in four counties in south-central Washington, an area recently described as endemic for Coccidioides. Survey results were used to assess awareness of reporting requirements, confidence in ability to diagnose and treat, confidence that knowledge is current, calculated knowledge score, and consideration of risk in patient population. The majority of respondents were unaware of the reporting requirement for coccidioidomycosis in Washington and further unaware that the disease had been reported in the state. Less than a third of survey respondents reported confidence in their ability to diagnose coccidioidomycosis and confidence that their knowledge is current. The majority of respondents never or rarely consider a diagnosis of coccidioidomycosis, and <25% of respondents indicated a working knowledge of serologic tests for the infection. The average knowledge score for respondents was 65%. Previous education, training, or practice regarding coccidioidomycosis was the only identified predictor of confidence and consideration of risk. These data indicate the substantial need for education and training among healthcare providers in south-central Washington and support the concern that a small proportion of existing cases of coccidioidomycosis are reported to the health department.


Asunto(s)
Coccidioidomicosis/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/educación , Adulto , Anciano , Antifúngicos/uso terapéutico , Coccidioidomicosis/diagnóstico , Coccidioidomicosis/tratamiento farmacológico , Estudios Transversales , Femenino , Humanos , Internet , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Washingtón/epidemiología
10.
Nervenarzt ; 90(12): 1215-1220, 2019 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-31748866

RESUMEN

BACKGROUND: Reliable and valid diagnostics and treatment of bipolar disorders and affective episodes are subject to extensive, especially methodological limitations in the clinical practice. OBJECTIVE: The use of smartphones and mobile sensor technology for improvement in diagnostics and treatment of bipolar disorders. METHODS: Critical discussion of current research on the use of ambulatory monitoring and digital phenotyping with bipolar disorders. RESULTS: In many studies the observation periods were too short and the sensors applied were too inaccurate to enable reliable and valid detection of behavioral changes in the context of affective episodes. CONCLUSION: The clarification and operationalization of psychopathological constructs to allow for the measurement of objectively observable and ascertainable behavioral changes during depressive and (hypo)manic states are essential for the successful application of modern mobile technologies in the diagnostics and treatment of bipolar disorders.


Asunto(s)
Trastorno Bipolar , Monitoreo Ambulatorio , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/terapia , Humanos , Psiquiatría/tendencias , Teléfono Inteligente
11.
Vaccine ; 37(37): 5535-5543, 2019 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-31160101

RESUMEN

Recent studies have suggested that among those receiving seasonal influenza vaccine (SIV), reduced immunogenicity is observed in recently vaccinated (RV; within the past season or 2) persons when compared with those not recently vaccinated (NRV). We performed a meta-analysis to assess the effect of recent immunization with SIV on serum H5 hemagglutination inhibition (HAI) antibody responses after influenza A/H5N1 vaccination using data from a series of randomized controlled trials. The primary outcome was seroconversion measured by HAI assays following receipt of 2 doses of H5N1 vaccine. The geometric mean titer (GMT) of serum HAI antibody after vaccination was the secondary outcome. Analyses were performed using propensity score (PS) matching. The PS for each individual in the meta-analysis cohort was calculated using logistic regression and covariates included age, gender, race, antigen dose, adjuvant, statin use and vaccine manufacturer. 2015 subjects enrolled in 7 clinical trials were eligible for inclusion in the meta-analysis cohort; among these, 915 (45%) were RV. 901 RV subjects were matched (1:1) with replacement to a subject who was NRV. Subjects who received SIV within the previous season were significantly less likely to seroconvert following H5N1 vaccination (adjusted odds ratio 0.76; 95%CI 0.60-0.96; p = 0.024), and the GMT was 18% higher among NRV subjects (GM ratio of HAI antibody 1.18; 95%CI 1.04-1.33; p = 0.008). Further work is needed to better define the effects of, and mechanisms contributing to, reduced immune responses to H5N1 vaccine among RV subjects.


Asunto(s)
Anticuerpos Antivirales/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Estaciones del Año , Vacunación , Femenino , Humanos , Inmunogenicidad Vacunal , Masculino , Evaluación de Resultado en la Atención de Salud , Puntaje de Propensión
12.
Clin Genet ; 94(2): 246-251, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29652087

RESUMEN

ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra-axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335-associated microcephaly.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/genética , Microcefalia/genética , Degeneración Nerviosa/genética , Neurogénesis/genética , Proteínas Nucleares/genética , Alelos , Empalme Alternativo/genética , Ganglios Basales/patología , Encéfalo/metabolismo , Encéfalo/fisiopatología , Proteínas de Unión al ADN , Femenino , Homocigoto , Humanos , Lactante , Recién Nacido , Masculino , Microcefalia/epidemiología , Microcefalia/fisiopatología , Mutación , Degeneración Nerviosa/epidemiología , Degeneración Nerviosa/fisiopatología , Linaje , Polimorfismo de Nucleótido Simple/genética , Factores de Transcripción
13.
Mucosal Immunol ; 11(2): 486-495, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28853442

RESUMEN

Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4+ memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.


Asunto(s)
Vacuna BCG/inmunología , Pulmón/inmunología , Células TH1/fisiología , Tuberculosis/inmunología , Vacunación/métodos , Administración Oral , Adolescente , Adulto , Anticuerpos Antibacterianos/metabolismo , Antígenos CD4/metabolismo , Dinamarca , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Inmunidad Mucosa , Inmunoglobulina A Secretora/metabolismo , Inyecciones Intradérmicas , Interferón gamma/metabolismo , Pulmón/microbiología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Transcriptoma , Adulto Joven
14.
Community Dent Health ; 34(2): 102-106, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28573841

RESUMEN

OBJECTIVES: To assess the efficiency of service provision in the Community Dental Services and its determinants in the North-West of England. SETTING AND SAMPLE: 40 Community Dental Services sites operating across the North-West of England. BASIC RESEARCH DESIGN: A data envelopment analysis was undertaken of inputs (number of surgeries, hours worked by dental officers, therapists, hygienists and others) and outputs (treatments delivered, number of courses of treatment and patients seen) of the Community Dental Services to produce relative efficiency ratings by health authority. These were further analyzed in order to identify which inputs (determined within the Community Dental Services) or external factors outside the control of the Community Dental Services are associated with efficiency. MAIN OUTCOME MEASURE: Relative efficiency rankings in Community Dental Services production of dental healthcare. RESULTS: Using the quantity of treatments delivered as the measure of output, on average the Community Dental Services in England is operating at a relative efficiency of 85% (95% confidence interval 77%- 99%) compared to the best performing services. Average efficiency is lower when courses of treatment and unique patients seen are used as output measures, 82% and 68% respectively. Neither the input mix nor the patient case mix explained variations in the efficiency across Community Dental Services. CONCLUSIONS: Although large variations in performance exist across Community Dental Services, the data available was not able to explain these variations. A useful next step would be to undertake detailed case studies of several best and under-performing services to explore the factors that influence relative performance levels.


Asunto(s)
Servicios de Salud Comunitaria/organización & administración , Servicios de Salud Dental/organización & administración , Eficiencia Organizacional , Inglaterra , Humanos
15.
N Engl J Med ; 374(11): 1032-1043, 2016 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-26981933

RESUMEN

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells. METHODS: We used whole-exome sequencing and array-based comparative genomic hybridization to evaluate a subset of patients with CVID and low B-cell numbers. Mutant proteins were analyzed for DNA binding with the use of an electrophoretic mobility-shift assay (EMSA) and confocal microscopy. Flow cytometry was used to analyze peripheral-blood lymphocytes and bone marrow aspirates. RESULTS: Six different heterozygous mutations in IKZF1, the gene encoding the transcription factor IKAROS, were identified in 29 persons from six families. In two families, the mutation was a de novo event in the proband. All the mutations, four amino acid substitutions, an intragenic deletion, and a 4.7-Mb multigene deletion involved the DNA-binding domain of IKAROS. The proteins bearing missense mutations failed to bind target DNA sequences on EMSA and confocal microscopy; however, they did not inhibit the binding of wild-type IKAROS. Studies in family members showed progressive loss of B cells and serum immunoglobulins. Bone marrow aspirates in two patients had markedly decreased early B-cell precursors, but plasma cells were present. Acute lymphoblastic leukemia developed in 2 of the 29 patients. CONCLUSIONS: Heterozygous mutations in the transcription factor IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-cell numbers. (Funded by the National Institutes of Health and others.).


Asunto(s)
Linfocitos B , Inmunodeficiencia Variable Común/genética , Factor de Transcripción Ikaros/genética , Mutación , Adolescente , Adulto , Antígenos CD/análisis , Médula Ósea/inmunología , Examen de la Médula Ósea , Niño , Preescolar , Cromosomas Humanos Par 7 , Inmunodeficiencia Variable Común/inmunología , Exoma , Femenino , Heterocigoto , Humanos , Inmunoglobulina G/sangre , Recuento de Linfocitos , Masculino , Linaje , Análisis de Secuencia de ADN/métodos
16.
J Biol Inorg Chem ; 21(1): 5-12, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26841789

RESUMEN

Our appreciation of the scholarly ideas and thinking of Bob Williams is illustrated here by a few of the areas in which he inspired us. His journey to bring inorganic chemistry to life began with an early interest in analytical chemistry, rationalising the relative stabilities of metal coordination complexes (The Irving-Williams Series), and elucidating the organometallic redox chemistry of vitamin B12. He (and Vallee) recognised that metal ions are in energised (entatic) states in proteins and enzymes, which themselves are dynamic structures of rods and springs. He played a key role in helping Rosenberg to pave the road toward the clinic for the anticancer drug cisplatin. He believed that evolution is not just dependent on DNA, but also on the metallome. Organisms and the environment are one system: does DNA code directly for all the essential elements of life?


Asunto(s)
Química Inorgánica , Antineoplásicos/química , Antineoplásicos/farmacología , Historia del Siglo XX
17.
Epidemiol Infect ; 144(4): 768-71, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26330204

RESUMEN

Non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit antibody production by peripheral blood mononuclear cells; one consequence of this could be decreased effectiveness of vaccines in NSAID users. Because many older adults use low-dose aspirin for primary or secondary prevention of coronary events, any inhibitory effect of aspirin on vaccine immune response could reduce the benefits of vaccination programmes in older adults. We tested whether immune response to vaccination differed between users vs. non-users of low-dose aspirin, using data from four randomized trials of monovalent 2009 pandemic influenza A(H1N1) vaccine. Geometric mean haemagglutination inhibition antibody titres were not significantly lower in low-dose aspirin users compared to non-users. Our results provide reassurance that influenza vaccination effectiveness is probably not reduced in older adults taking chronic low-dose aspirin.


Asunto(s)
Antiinflamatorios no Esteroideos/inmunología , Aspirina/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/terapia , Anciano , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Anticuerpos Antivirales/sangre , Aspirina/administración & dosificación , Perros , Relación Dosis-Respuesta a Droga , Humanos , Persona de Mediana Edad
18.
Br Dent J ; 217(9): E17, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25377846

RESUMEN

OBJECTIVES: Key reforms in England and Japan have called for greater clinical leadership from general dental practitioners to deliver improvements in the quality of care for patients. In England, the reorganisation of the National Health Service has led to the development of Local Professional Networks to ensure services are clinically led, patient and outcome focused. In Japan, the rapidly changing demographics have led to calls for general dental practitioners to become more active in meeting the emerging population health challenges. Both require engagement at a strategic and a local level. However, little is known about what is meant by clinical leadership in dentistry or what training needs exist. The aim of this study was to develop and pilot a questionnaire to understand what general dental practitioners feel is important about clinical leadership and how they rate themselves. METHODS: A 61-item questionnaire was developed from the literature, an earlier qualitative study and refined through cognitive interviews. Questionnaires were distributed to general dental practitioners across the North West of England and Tokyo, using random sequence generation. For each item, the participant had to record whether they thought the statement was an important component of clinical leadership and how they rated themselves. Both were rated using a seven-point Likert scale. Data reduction was undertaken using principal component analysis to examine for factor loadings within the questionnaire. Differences in mean scores were also used to highlight substantive differences in how general dental practitioners rated the different components of leadership and how they rated themselves. RESULTS: The response rate for the pilot was low (22.9% and 7.5% for North West and Tokyo respectively). The items that were considered to be important in leadership reduced to two components in the North West (accounting for 62.1% of the total variance): 'How to lead' and 'How not to lead'. In Tokyo, 56.4% of the total variance was explained by three components: 'Demonstrating personal qualities', 'Working with others' and 'How not to lead'. When the self-rated items were reduced, three factors were found to be important in the North West: 'Working with others', 'Setting direction' and 'Managing services' (55.1% of the variance). 'Working with others', 'Demonstrating personal qualities', 'Pragmatism', 'Setting direction' and 'Improving services' were found to be important in Tokyo (52.8% of the variance). The questionnaire items relating to integrity, team-working and having a positive attitude during difficult times were rated highly by both groups. Items relating to providing vision for team, being assertive and having a positive attitude had the greatest mean difference, suggesting possible areas of training need. CONCLUSION: The nature of the pilot study and the poor response rate makes any conclusion difficult to infer. Among those that participated, leadership was understood to be more important at a practice level rather than at a strategic level. The questionnaire should be refined further based on the results of the pilot and the data reduction.


Asunto(s)
Servicios de Salud Dental/organización & administración , Odontólogos , Liderazgo , Inglaterra , Proyectos Piloto , Encuestas y Cuestionarios , Tokio
19.
Ultraschall Med ; 35(5): 451-8, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25014479

RESUMEN

PURPOSE: In controlled environments such as the operating room, bedside ultrasound (BUS) of the neck has shown high accuracy for distinguishing endotracheal (ETI) from esophageal intubations. We sought to determine the accuracy of BUS for endotracheal tube (ETT) position in the emergency department (ED) setting. MATERIALS AND METHODS: We assessed the utility of BUS in a single-center observational study in an ED setting. BUS was performed either simultaneously with ED intubation (S/ED), within < 3 minutes of ED intubation (A/ED), or in < 3 minutes of patient's ED arrival after pre-hospital intubation (A/EMS). Trained ED providers performed BUS; intubators were blinded to ultrasound findings. We used Cormack and Lehane categories (CL) to classify intubation attempts as "easy" (CL-I/II), "moderate" (CL-III) and "difficult" (CL-IV). Additional data included the diagnostic accuracy of the sonographer and intubator compared to the clinical outcome, anatomy identified by sonography and time to diagnosis. RESULTS: During a 10-month period, 89 subjects with 115 intubation attempts were included in the study, and 86 patients/101 attempts with complete data were used in the study (63-easy, 19-moderate, 19-difficult). The sonographers achieved 100 % accuracy with respect to determining the correct ETT position utilizing an anterior neck approach, while the intubators' accuracy in assessing correct tube location was 97 % compared to the clinical outcome. A blinded review of sonography findings confirmed all BUS anatomical findings. A sonographically empty esophagus was 100 % specific for endotracheal intubation, and a "double trachea sign" was 100 % sensitive and 91 % specific for esophageal intubation. The sonographic time to diagnosis was significantly faster than the intubator time to diagnosis ("easy" p < 0.001; n = 47; "moderate" p = 0.001; n = 15; "difficult" p < 0.001; n = 19); Wilcoxon test; A/EMS cases excluded). CONCLUSION: In this emergency setting, ultrasound determined ETT locations rapidly with 100 % accuracy and independently of the CL-category.


Asunto(s)
Servicio de Urgencia en Hospital , Intubación Intratraqueal/instrumentación , Cuello/diagnóstico por imagen , Sistemas de Atención de Punto , Tráquea/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Servicios Médicos de Urgencia , Esófago/diagnóstico por imagen , Femenino , Humanos , Intubación Intratraqueal/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resucitación , Método Simple Ciego , Estudios de Tiempo y Movimiento , Ultrasonografía , Heridas y Lesiones/diagnóstico por imagen , Heridas y Lesiones/terapia , Adulto Joven
20.
J Food Prot ; 77(6): 885-93, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24853509

RESUMEN

Poultry have been identified as one of the major sources of salmonellosis, with estimates ranging from 10 to 22% of total cases. Despite several advances in the industry and new performance standards, the incidence of salmonellosis in the population has not declined over the last 15 years. Salmonella is pervasive in a wide variety of foods, and thus, estimating its burden resulting from specific food categories has been challenging and plagued with uncertainty due to critical data gaps. The objective of this study was to conduct a year-long market survey (1,322 samples) to help bridge the data gaps on the contamination rates and levels of Salmonella on raw poultry by product type (i.e., breast, thighs, drums, wings, and split breast) and production method (conventional versus organic). The isolates recovered were serotyped and tested for antibiotic sensitivities. A PCR method was utilized for initial screening of samples after an overnight enrichment in tryptic soy broth. Three-tube most-probable-number (MPN) assays and anti-Salmonella immunomagnetic separation methods were utilized to determine the levels of Salmonella and aid with the recovery of Salmonella species, respectively. Eleven percent of the samples were positive for Salmonella. Significant differences in percent positive rates by product type included up to a 4-fold difference in percent positive rates between establishments, ranging from 7 to 31%. Of the samples positive for Salmonella species, 94% had <30 MPN/100 g. Production methods identified as organic or as not using antibiotics had significantly higher rates of recovery of Salmonella. On the other hand, all of the Salmonella isolates that were resistant to two or more antibiotics originated from conventional processing establishments where antibiotics were utilized. In addition, a significant proportion of isolates from conventionally processed products were serotypes clinically relevant to humans.


Asunto(s)
Antibacterianos/farmacología , Reservorios de Enfermedades/microbiología , Contaminación de Alimentos , Productos Avícolas/microbiología , Salmonella/aislamiento & purificación , Animales , Pollos , Contaminación de Alimentos/análisis , Contaminación de Alimentos/estadística & datos numéricos , Humanos , Incidencia , Pruebas de Sensibilidad Microbiana , Productos Avícolas/economía , Prevalencia , Salmonella/clasificación , Salmonella/efectos de los fármacos , Salmonella/genética , Intoxicación Alimentaria por Salmonella/prevención & control , Washingtón
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