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1.
Bioinformatics ; 39(3)2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36752514

RESUMEN

MOTIVATION: With the rapidly growing volume of knowledge and data in biomedical databases, improved methods for knowledge-graph-based computational reasoning are needed in order to answer translational questions. Previous efforts to solve such challenging computational reasoning problems have contributed tools and approaches, but progress has been hindered by the lack of an expressive analysis workflow language for translational reasoning and by the lack of a reasoning engine-supporting that language-that federates semantically integrated knowledge-bases. RESULTS: We introduce ARAX, a new reasoning system for translational biomedicine that provides a web browser user interface and an application programming interface (API). ARAX enables users to encode translational biomedical questions and to integrate knowledge across sources to answer the user's query and facilitate exploration of results. For ARAX, we developed new approaches to query planning, knowledge-gathering, reasoning and result ranking and dynamically integrate knowledge providers for answering biomedical questions. To illustrate ARAX's application and utility in specific disease contexts, we present several use-case examples. AVAILABILITY AND IMPLEMENTATION: The source code and technical documentation for building the ARAX server-side software and its built-in knowledge database are freely available online (https://github.com/RTXteam/RTX). We provide a hosted ARAX service with a web browser interface at arax.rtx.ai and a web API endpoint at arax.rtx.ai/api/arax/v1.3/ui/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Bases del Conocimiento , Programas Informáticos , Bases de Datos Factuales , Lenguaje , Navegador Web
2.
Phys Rev Lett ; 131(22): 222502, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38101341

RESUMEN

Collinear laser spectroscopy was performed on the isomer of the aluminium isotope ^{26m}Al. The measured isotope shift to ^{27}Al in the 3s^{2}3p ^{2}P_{3/2}^{○}→3s^{2}4s ^{2}S_{1/2} atomic transition enabled the first experimental determination of the nuclear charge radius of ^{26m}Al, resulting in R_{c}=3.130(15) fm. This differs by 4.5 standard deviations from the extrapolated value used to calculate the isospin-symmetry breaking corrections in the superallowed ß decay of ^{26m}Al. Its corrected Ft value, important for the estimation of V_{ud} in the Cabibbo-Kobayashi-Maskawa matrix, is thus shifted by 1 standard deviation to 3071.4(1.0) s.

3.
J Peripher Nerv Syst ; 28(3): 368-381, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37209301

RESUMEN

BACKGROUND/AIMS: Charcot-Marie-Tooth Disease type 1A (CMT1A), the most common inherited peripheral neuropathy, is characterized by progressive sensory loss and weakness, which results in impaired mobility. Increased understanding of the genetics and pathophysiology of CMT1A has led to development of potential therapeutic agents, necessitating clinical trial readiness. Wearable sensors may provide useful outcome measures for future trials. METHODS: Individuals with CMT1A and unaffected controls were recruited for this 12-month study. Participants wore sensors for in-clinic assessments and at-home, from which activity, gait, and balance metrics were derived. Mann-Whitney U tests were used to analyze group differences for activity, gait, and balance parameters. Test-retest reliability of gait and balance parameters and correlations of these parameters with clinical outcome assessments (COAs) were examined. RESULTS: Thirty individuals, 15 CMT1A, and 15 controls, participated. Gait and balance metrics demonstrated moderate to excellent reliability. CMT1A participants had longer step durations (p < .001), shorter step lengths (p = .03), slower gait speeds (p < .001), and greater postural sway (p < .001) than healthy controls. Moderate correlations were found between CMT-Functional Outcome Measure and step length (r = -0.59; p = .02), and gait speed (r = 0.64; p = .01); 11 out of 15 CMT1A participants demonstrated significant increases in stride duration between the first and last quarter of the 6-min walk test, suggesting fatigue. INTERPRETATION: In this initial study, gait and balance metrics derived from wearable sensors were reliable and associated with COAs in individuals with CMT1A. Larger longitudinal studies are needed to confirm our findings and evaluate sensitivity and utility of these disease-specific algorithms for clinical trial use.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Dispositivos Electrónicos Vestibles , Humanos , Marcha , Estudios Longitudinales , Reproducibilidad de los Resultados
4.
Nature ; 551(7679): 187-191, 2017 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-29088701

RESUMEN

Forest edges influence more than half of the world's forests and contribute to worldwide declines in biodiversity and ecosystem functions. However, predicting these declines is challenging in heterogeneous fragmented landscapes. Here we assembled a global dataset on species responses to fragmentation and developed a statistical approach for quantifying edge impacts in heterogeneous landscapes to quantify edge-determined changes in abundance of 1,673 vertebrate species. We show that the abundances of 85% of species are affected, either positively or negatively, by forest edges. Species that live in the centre of the forest (forest core), that were more likely to be listed as threatened by the International Union for Conservation of Nature (IUCN), reached peak abundances only at sites farther than 200-400 m from sharp high-contrast forest edges. Smaller-bodied amphibians, larger reptiles and medium-sized non-volant mammals experienced a larger reduction in suitable habitat than other forest-core species. Our results highlight the pervasive ability of forest edges to restructure ecological communities on a global scale.


Asunto(s)
Biodiversidad , Bosques , Anfibios/anatomía & histología , Animales , Aves/anatomía & histología , Tamaño Corporal , Mapeo Geográfico , Mamíferos/anatomía & histología , Dinámica Poblacional , Reptiles/anatomía & histología
5.
BMC Bioinformatics ; 23(1): 400, 2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36175836

RESUMEN

BACKGROUND: Biomedical translational science is increasingly using computational reasoning on repositories of structured knowledge (such as UMLS, SemMedDB, ChEMBL, Reactome, DrugBank, and SMPDB in order to facilitate discovery of new therapeutic targets and modalities. The NCATS Biomedical Data Translator project is working to federate autonomous reasoning agents and knowledge providers within a distributed system for answering translational questions. Within that project and the broader field, there is a need for a framework that can efficiently and reproducibly build an integrated, standards-compliant, and comprehensive biomedical knowledge graph that can be downloaded in standard serialized form or queried via a public application programming interface (API). RESULTS: To create a knowledge provider system within the Translator project, we have developed RTX-KG2, an open-source software system for building-and hosting a web API for querying-a biomedical knowledge graph that uses an Extract-Transform-Load approach to integrate 70 knowledge sources (including the aforementioned core six sources) into a knowledge graph with provenance information including (where available) citations. The semantic layer and schema for RTX-KG2 follow the standard Biolink model to maximize interoperability. RTX-KG2 is currently being used by multiple Translator reasoning agents, both in its downloadable form and via its SmartAPI-registered interface. Serializations of RTX-KG2 are available for download in both the pre-canonicalized form and in canonicalized form (in which synonyms are merged). The current canonicalized version (KG2.7.3) of RTX-KG2 contains 6.4M nodes and 39.3M edges with a hierarchy of 77 relationship types from Biolink. CONCLUSION: RTX-KG2 is the first knowledge graph that integrates UMLS, SemMedDB, ChEMBL, DrugBank, Reactome, SMPDB, and 64 additional knowledge sources within a knowledge graph that conforms to the Biolink standard for its semantic layer and schema. RTX-KG2 is publicly available for querying via its API at arax.rtx.ai/api/rtxkg2/v1.2/openapi.json . The code to build RTX-KG2 is publicly available at github:RTXteam/RTX-KG2 .


Asunto(s)
Conocimiento , Reconocimiento de Normas Patrones Automatizadas , Semántica , Programas Informáticos , Ciencia Traslacional Biomédica
6.
Subst Use Misuse ; 57(14): 2134-2141, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36315582

RESUMEN

Background: There has been a notable deficiency in the implementation of addiction science in clinical practice and many healthcare providers feel unprepared to treat patients with substance use disorders (SUD) following training. However, the perceptions of addiction medicine training by learners in health professions have not been fully investigated. This qualitative study explored perceptions of prior training in SUD care among early-career trainees enrolled in Addiction Medicine fellowships and electives in Vancouver, Canada. Methods: From April 2015 - August 2018, we interviewed 45 early-career physicians, social workers, nurses, and 17 medical students participating in training in addiction medicine. We coded transcripts inductively using qualitative data analysis software (NVivo 11.4.3). Results: Findings revealed six key themes related to early-career training in addiction medicine: (1) Insufficient time spent on addiction education, (2) A need for more structured addictions training, (3) Insufficient hands-on clinical training and skill development, (4) Lack of patient-centeredness and empathy in the training environment, (5) Insufficient implementation of evidence-based medicine, and (6) Prevailing stigmas toward addiction medicine. Conclusion: Early clinical training in addiction medicine appears insufficient and largely focused on symptoms, rather than etiology or evidence. Early career learners in health professions perceived benefit to expanding access to quality education and reported positive learning outcomes after completing structured training programs.


Asunto(s)
Medicina de las Adicciones , Estudiantes de Medicina , Trastornos Relacionados con Sustancias , Humanos , Canadá , Becas , Investigación Cualitativa , Trastornos Relacionados con Sustancias/terapia
7.
Comput Chem Eng ; 1532021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38235368

RESUMEN

Process design and optimization continue to provide computational challenges as the chemical engineering and process optimization communities seek to address more complex and larger scale applications. Software tools for digital design and flowsheet simulation are readily available for traditional chemical processing applications such as in commodity chemicals and hydrocarbon processing; however, tools for pharmaceutical manufacturing are much less well developed. This paper introduces, PharmaPy, a Python-based modelling platform for pharmaceutical manufacturing systems design and optimization. The versatility of the platform is demonstrated in simulation and optimization of both continuous and batch processes. The structure and features of a Python-based modeling platform, PharmaPy are presented. Illustrative examples are shown to highlight key features of the platform and framework.

8.
J Biomed Sci ; 27(1): 96, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33008372

RESUMEN

BACKGROUND: A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). METHODS: After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema). RESULTS: Our results showed a significant improvement in gas exchange [elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03)] in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin-eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control. CONCLUSIONS: These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.


Asunto(s)
Antagonistas de los Receptores de Endotelina/farmacología , Pulmón/efectos de los fármacos , Piridinas/farmacología , Pruebas de Función Respiratoria , Tetrazoles/farmacología , Vasodilatadores/farmacología , Animales , Modelos Animales de Enfermedad , Pulmón/fisiología , Perfusión , Oveja Doméstica , Donantes de Tejidos
9.
Am J Drug Alcohol Abuse ; 46(5): 625-631, 2020 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-32689810

RESUMEN

Background: With the emergence of illicitly-manufactured fentanyl, drug overdose deaths have risen in unprecedented numbers. In this context, there is an urgent need to characterize potential changes in drug use behaviors among people who use drugs (PWUD). Objective: To examine changes in drug use behaviors following the emergence of illicit fentanyl among people who use drugs (PWUD). Methods: Data for this cross-sectional analysis was derived from three prospective cohorts of PWUD between December 2016 and May 2017 in Vancouver, Canada. Multivariable logistic regression was used to determine factors associated with self-reported behavior changes (binary variable "yes" or "no") following the emergence of illicit fentanyl. Results: Among 999 participants [363 (36.3%) females], 388 (38.8%) reported some behavior change. The remaining 611 (61.2%) reported no change in behavior; 240 (39.3%) of these individuals had recently been exposed to fentanyl. In multivariable analyses, factors independently associated with behavior change included recent non-fatal overdose (Adjusted Odds Ratio [AOR] = 2.28), active injection drug use (AOR = 1.96), being on opioid agonist therapy (AOR = 1.80), and urine drug screen positive for fentanyl (AOR = 1.45), (all p < .05). Conclusion: The majority of PWUD in our sample did not change their drug use behavior despite a high prevalence of fentanyl exposure, indicating a need for targeted behavior change messaging and overdose prevention efforts such as naloxone and addiction treatment for this sub-population of PWUD. Further, the high fentanyl exposure observed in our sample suggests a need to address upstream structural factors shaping the overdose risk in addition to individual behavioral change.


Asunto(s)
Sobredosis de Droga/epidemiología , Consumidores de Drogas/estadística & datos numéricos , Fentanilo/efectos adversos , Drogas Ilícitas/efectos adversos , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Analgésicos Opioides/efectos adversos , Colombia Británica/epidemiología , Estudios Transversales , Consumidores de Drogas/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Naloxona/uso terapéutico , Prevalencia , Estudios Prospectivos , Abuso de Sustancias por Vía Intravenosa/epidemiología
10.
Colorectal Dis ; 21(12): 1372-1378, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31276286

RESUMEN

AIM: Sarcopenia, or a reduction of lean muscle mass, is associated with poorer outcomes in cancer patients. Few previous studies have examined this potentially correctable risk factor in patients with locally advanced rectal cancer. METHOD: Skeletal muscle mass index was measured retrospectively on initial staging CT scans of patients undergoing chemoradiation followed by radical resection for rectal cancer for the period 2007-2013. Patients were categorized as sarcopenic or nonsarcopenic and differences in terms of demographics, pre-, peri- and postoperative outcomes were examined. RESULTS: Forty-seven patients were included; their mean age was 59.3 (36-82) years and 61.7% were men. We considered that 55.2% of men and 44.4% of women were sarcopenic; the overall prevalence of sarcopenia was 51.1%. Age, preoperative haemoglobin and albumin were significantly related to sarcopenia. Body mass index (BMI) and obesity (BMI > 30 kg/m2 ) were not associated with sarcopenia. Blood transfusions were more frequent in sarcopenic patients (P = 0.001). Although readmissions and length of stay were not increased, overall postoperative complications were significantly higher in sarcopenic patients (P = 0.03). Neither BMI nor obesity was associated with postoperative complications. CONCLUSION: Sarcopenia was present in over 50% of patients with locally advanced rectal cancer at diagnosis. It was associated with a higher incidence of both blood transfusion and postoperative complications. BMI did not correlate with these negative outcomes. Sarcopenia may be a better predictor of surgical outcomes than BMI or obesity.


Asunto(s)
Obesidad/fisiopatología , Complicaciones Posoperatorias/mortalidad , Proctectomía/efectos adversos , Neoplasias del Recto/fisiopatología , Sarcopenia/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Quimioradioterapia/efectos adversos , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético , Obesidad/complicaciones , Complicaciones Posoperatorias/etiología , Prevalencia , Estudios Prospectivos , Neoplasias del Recto/complicaciones , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/complicaciones , Resultado del Tratamiento
11.
Transfus Med ; 29(4): 231-238, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30666733

RESUMEN

In this review, we explore how to assess potential harm related to neonatal transfusion practice. We consider different sources of information, including passive or active surveillance systems such as registries, observational studies, randomised trials and systematic reviews. Future research directions are discussed.


Asunto(s)
Transfusión de Eritrocitos , Sistema de Registros , Reacción a la Transfusión/prevención & control , Humanos , Recién Nacido , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo
12.
Transfus Med ; 29(1): 33-40, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29637650

RESUMEN

OBJECTIVES: To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. BACKGROUND: Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end-organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. METHODS: We describe the bottom-up, time-driven, activity-based costing methodology used to develop process maps to provide a step-by-step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. RESULTS: Thirty-one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. CONCLUSIONS: Detailed process maps using bottom-up, time-driven, activity-based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings.


Asunto(s)
Transfusión de Eritrocitos/economía , Talasemia beta/economía , Talasemia beta/terapia , Adulto , Costos y Análisis de Costo , Femenino , Humanos , Masculino
13.
Transfus Med ; 29(4): 221-230, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30729612

RESUMEN

The International Haemovigilance Network (IHN) defines haemovigilance as 'a set of surveillance procedures covering the whole transfusion chain (from the collection of blood and its components to the follow-up of recipients), intended to collect and assess information on unexpected or undesirable effects resulting from the therapeutic use of labile blood products, and to prevent their occurrence or recurrence'. IHN, the International Society of Blood Transfusion and World Health Organization work together to support both developing and established haemovigilance systems. Haemovigilance systems provide valuable data on a range of adverse events related to blood donation and clinical transfusion, from donor syncopal events to transfusion-transmitted infections, immunological complications and the impact of human errors. Harmonised definitions for most adverse reactions have been developed and validated internationally. Definitions of pulmonary complications are again under review. Haemovigilance data have resulted in changes in policy, products and practice, and can complement and inform clinical audit and research, leading to improved blood donor safety, optimised product use and better clinical outcomes after transfusion. However, more work is needed. Not all countries have haemovigilance systems in place. More robust data and careful analysis are required to improve the understanding of the causes, occurrence and clinical outcomes of these events. Wider dissemination of results will facilitate health policy development internationally, and implementation of haemovigilance recommendations will support further important progress in blood safety.


Asunto(s)
Donantes de Sangre , Seguridad de la Sangre , Transfusión Sanguínea , Reacción a la Transfusión/prevención & control , Humanos , Reacción a la Transfusión/epidemiología
14.
Hum Genet ; 137(9): 723-734, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30167848

RESUMEN

Rare variants are thought to contribute to the genetics of inflammatory bowel disease (IBD), which is more common amongst the Ashkenazi Jewish (AJ) population. A family-based approach using exome sequencing of AJ individuals with IBD was employed with a view to identify novel rare genetic variants for this disease. Exome sequencing was performed on 960 Jewish individuals including 513 from 199 multiplex families with up to eight cases. Rare, damaging variants in loci prioritized by linkage analysis and those shared by multiple affected individuals within the same family were identified. Independent evidence of association of each variant with disease was assessed. A number of candidate variants were identified, including in genes involved in the immune system. The ability to achieve statistical significance in independent case/control replication data was limited by power and was only achieved for variants in the well-established Crohn's disease gene, NOD2. This work demonstrates the challenges of identifying disease-associated rare damaging variants from exome data, even amongst a favorable cohort of familial cases from a genetic isolate. Further research of the prioritized rare candidate variants is required to confirm their association with the disease.


Asunto(s)
Predisposición Genética a la Enfermedad , Variación Genética , Enfermedades Inflamatorias del Intestino/genética , Judíos/genética , Proteína Adaptadora de Señalización NOD2/genética , Sistemas de Lectura Abierta , Estudios de Casos y Controles , Femenino , Ligamiento Genético , Humanos , Masculino , Linaje , Análisis de Secuencia de ADN/métodos
15.
Vox Sang ; 113(3): 275-282, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29392786

RESUMEN

BACKGROUND AND OBJECTIVES: The timing of blood administration in critically ill patients is first driven by patients' needs. This study aimed to define the epidemiology and significance of overnight transfusion in critically ill patients. MATERIALS AND METHODS: This is a post hoc analysis of a prospective multicentre observational study including 874 critically ill patients receiving red blood cells, platelets, fresh frozen plasma (FFP) or cryoprecipitate. Characteristics of patients receiving blood only during the day (8 am up until 8 pm) were compared to those receiving blood only overnight (8 pm up until 8 am). Characteristics of transfusion were compared, and factors independently associated with major bleeding were analysed. RESULTS: The 287 patients transfused during the day only had similar severity and mortality to the 258 receiving blood products overnight only. Although bleeding-related admission diagnoses were similar, major bleeding was the indication for transfusion in 12% of patients transfused in daytime only versus 30% of patients transfused at night only (P < 0·001). Similar total amount of blood products were transfused at day and night (2856 versus 2927); however, patients were more likely to receive FFP and cryoprecipitate at night compared with daytime. Overnight transfusion was independently associated with increased odds of major bleeding (odds ratio, 3·16, 95% confidence interval, 2·00-5·01). CONCLUSION: Transfusion occurs evenly across day and night in ICU; nonetheless, there are differences in type of blood products administered that reflect differences in indication. Critically ill patients were more likely to receive blood for major bleeding at night irrespective of admission diagnosis.


Asunto(s)
Transfusión Sanguínea/métodos , Ritmo Circadiano , Cuidados Críticos/métodos , Adulto , Anciano , Transfusión Sanguínea/normas , Cuidados Críticos/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad
16.
Transfus Med ; 28(2): 140-149, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29607593

RESUMEN

Massive transfusion or major haemorrhage protocols have been widely adopted in the treatment of critically bleeding patients. Following evidence that higher ratios of transfused plasma and platelets to red blood cells may offer survival benefits in military trauma patients, these ratios are now commonly incorporated into massive transfusion protocols. They more closely resemble the effects of whole blood transfusion, which in the second half of last century was largely replaced by individual blood component transfusion based on laboratory-guided indicators. However, high-quality evidence to guide transfusion support for critically bleeding patients across the range of bleeding contexts is lacking, including for both trauma and non-trauma patients. More data on major haemorrhage support and clinical outcomes are needed to inform guidelines and practice.


Asunto(s)
Transfusión de Componentes Sanguíneos/métodos , Hemorragia/terapia , Heridas y Lesiones/terapia , Transfusión de Componentes Sanguíneos/normas , Hemorragia/fisiopatología , Humanos , Guías de Práctica Clínica como Asunto , Heridas y Lesiones/fisiopatología
17.
HIV Med ; 18(8): 580-586, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28317290

RESUMEN

OBJECTIVES: HIV treatment-as-prevention campaigns emphasize early diagnosis and immediate access to care and antiretroviral therapy for HIV-positive individuals in order to increase levels of plasma HIV RNA viral load (VL) suppression. However, the possible role of harm reduction-based programmes in this objective has not yet been well evaluated. The objective of the study was to examine the relationship between being a client of the Dr. Peter Centre (DPC; an HIV/AIDS-focused adult integrated health programme) and VL suppression among highly active antiretroviral therapy (HAART)-exposed HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada. METHODS: Data were derived from the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) study, a study of a community-recruited cohort of HIV-positive PWUD. A marginal structural model using inverse probability of treatment weights was used to estimate the longitudinal relationship between being a DPC client and exhibiting a VL < 50 HIV-1 RNA copies/mL plasma. RESULTS: Between 2005 and 2014, 746 HAART-exposed participants were included in the study, of whom 269 (36.1%) reported being a DPC client at some time during the study period. A marginal structural model estimated a 1.54 greater odds of achieving VL suppression (95% confidence interval 1.20-1.99) among DPC clients. CONCLUSIONS: Our findings demonstrate that participating in an innovative HIV/AIDS-focused adult integrated health programme that provides a broad range of clinical, harm reduction, and support services may contribute to optimizing the benefits of HAART in terms of morbidity, mortality and viral transmission among PWUD, and as a result help to fulfill the goals of the treatment-as-prevention strategy.


Asunto(s)
Antirretrovirales/uso terapéutico , Prestación Integrada de Atención de Salud/estadística & datos numéricos , Infecciones por VIH/complicaciones , VIH-1/aislamiento & purificación , ARN Viral/sangre , Trastornos Relacionados con Sustancias/complicaciones , Carga Viral , Adulto , Canadá , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Plasma/virología , Estudios Prospectivos
18.
Vox Sang ; 112(3): 240-248, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28181262

RESUMEN

BACKGROUND AND OBJECTIVES: Critically bleeding patients requiring massive transfusion (MT) are clinically challenging, and limited data exist to support management decisions. This study describes patient characteristics, transfusion support and clinical outcomes from the Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR). MATERIALS AND METHODS: Retrospective, cohort study of all adult patients receiving MT (≥5 units red blood cells [RBC] in 4 h) at participating ANZ-MTR hospitals, 2011-2015. Mortality information was collected from the Australian National Death Index and NZ Ministry of Health. Associations between patient characteristics and outcomes were modelled using logistic regression. RESULTS: A total of 3560 MT cases were identified. For in-hospital deaths, cardiothoracic surgery was the most frequent bleeding context (24·5%) followed by trauma (18·3%). Age (OR = 1·03; 95% CI: 1·02-1·04), more comorbidities (OR = 1·14; 95% CI: 1·09-1·21), larger volume of RBC in first 24 h from MT onset (OR = 1·04; 95% CI: 1·02-1·06), higher platelet to RBC ratio at 4 h (OR = 2·76; 95% CI: 1·14-6·65) and higher activated partial thromboplastin time (OR = 1·02; 95% CI: 1·01-1·03) were associated with in-hospital mortality. CONCLUSION: Patients with more comorbidities, older age, traumatic or surgical bleeding or requiring more blood components had higher in-hospital mortality. These findings provide a basis to evaluate and monitor practice relating to optimal use of blood products, variation in transfusion practices and patient outcomes, and also enable benchmarking of hospital performance for management of MT in specific patient groups.


Asunto(s)
Transfusión Sanguínea , Hemorragia/mortalidad , Mortalidad Hospitalaria , Adulto , Factores de Edad , Anciano , Australia , Pérdida de Sangre Quirúrgica/mortalidad , Pérdida de Sangre Quirúrgica/prevención & control , Estudios de Cohortes , Comorbilidad , Transfusión de Eritrocitos , Femenino , Hemorragia/terapia , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nueva Zelanda , Oportunidad Relativa , Tiempo de Tromboplastina Parcial , Transfusión de Plaquetas , Sistema de Registros , Estudios Retrospectivos
19.
Transfus Med ; 27(2): 114-121, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27966239

RESUMEN

OBJECTIVES: To evaluate the use of routinely collected data to determine the cause(s) of critical bleeding in patients who receive massive transfusion (MT). BACKGROUND: Routinely collected data are increasingly being used to describe and evaluate transfusion practice. MATERIALS/METHODS: Chart reviews were undertaken on 10 randomly selected MT patients at 48 hospitals across Australia and New Zealand to determine the cause(s) of critical bleeding. Diagnosis-related group (DRG) and International Classification of Diseases (ICD) codes were extracted separately and used to assign each patient a cause of critical bleeding. These were compared against chart review using percentage agreement and kappa statistics. RESULTS: A total of 427 MT patients were included with complete ICD and DRG data for 427 (100%) and 396 (93%), respectively. Good overall agreement was found between chart review and ICD codes (78·3%; κ = 0·74, 95% CI 0·70-0·79) and only fair overall agreement with DRG (51%; κ = 0·45, 95% CI 0·40-0·50). Both ICD and DRG were sensitive and accurate for classifying obstetric haemorrhage patients (98% sensitivity and κ > 0·94). However, compared with the ICD algorithm, DRGs were less sensitive and accurate in classifying bleeding as a result of gastrointestinal haemorrhage (74% vs 8%; κ = 0·75 vs 0·1), trauma (92% vs 62%; κ = 0·78 vs 0·67), cardiac (80% vs 57%; κ = 0·79 vs 0·60) and vascular surgery (64% vs 56%; κ = 0·69 vs 0·65). CONCLUSION: Algorithms using ICD codes can determine the cause of critical bleeding in patients requiring MT with good to excellent agreement with clinical history. DRG are less suitable to determine critical bleeding causes.


Asunto(s)
Algoritmos , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Codificación Clínica , Hemorragia Gastrointestinal , Heridas y Lesiones , Adulto , Australia , Estudios Transversales , Femenino , Hemorragia Gastrointestinal/clasificación , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Nueva Zelanda , Procedimientos Quirúrgicos Vasculares/efectos adversos , Heridas y Lesiones/clasificación , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/terapia
20.
BMC Med Educ ; 17(1): 22, 2017 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-28114925

RESUMEN

BACKGROUND: Despite a large evidence-base upon which to base clinical practice, most health systems have not combined the training of healthcare providers in addiction medicine and research. As such, addiction care is often lacking, or not based on evidence or best practices. We undertook a qualitative study to assess the experiences of physicians who completed a clinician-scientist training programme in addiction medicine within a hospital setting. METHODS: We interviewed physicians from the St. Paul's Hospital Goldcorp Addiction Medicine Fellowship and learners from the hospital's academic Addiction Medicine Consult Team in Vancouver, Canada (N = 26). They included psychiatrists, internal medicine and family medicine physicians, faculty, mentors, medical students and residents. All received both addiction medicine and research training. Drawing on Kirkpatrick's model of evaluating training programmes, we analysed the interviews thematically using qualitative data analysis software (Nvivo 10). RESULTS: We identified five themes relating to learning experience that were influential: (i) attitude, (ii) knowledge, (iii) skill, (iv) behaviour and (v) patient outcome. The presence of a supportive learning environment, flexibility in time lines, highly structured rotations, and clear guidance regarding development of research products facilitated clinician-scientist training. Competing priorities, including clinical and family responsibilities, hindered training. CONCLUSIONS: Combined training in addiction medicine and research is feasible and acceptable for current doctors and physicians in training. However, there are important barriers to overcome and improved understanding of the experience of addiction physicians in the clinician-scientist track is required to improve curricula and research productivity.


Asunto(s)
Conducta Adictiva/terapia , Investigación Biomédica/educación , Neurociencia Cognitiva/educación , Educación Médica , Investigadores/educación , Estudiantes de Medicina , Trastornos Relacionados con Sustancias/terapia , Actitud del Personal de Salud , Canadá , Competencia Clínica/normas , Curriculum , Educación Médica/organización & administración , Evaluación Educacional , Becas/organización & administración , Becas/normas , Necesidades y Demandas de Servicios de Salud , Humanos , Mentores , Rol del Médico , Evaluación de Programas y Proyectos de Salud , Investigación Cualitativa , Especialización
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