Biomedical subjects

Kevin McDonald

Publications and source records attributed to Kevin McDonald.

7 recordsLinked to original sources

PubMed2005

Reliability of point-of-care testing for glucose measurement in critically ill adults.

BACKGROUND: Glycemic control is increasingly being recognized as a priority in the treatment of critically ill patients. Titration and monitoring of insulin infusions involve frequent blood glucose measurement to achieve target glucose ranges and prevent adverse events related to hypoglycemia. Therefore, it is imperative that bedside glucose testing methods be safe and accurate. OBJECTIVE: To determine the accuracy and clinical impact of three common methods of bedside point-of-care testing for glucose measurements in critically ill patients receiving insulin infusions. DESIGN: Prospective observational study. SETTING: A 21-bed mixed medical/surgical intensive care unit of a tertiary care teaching hospital. PATIENTS: Thirty consecutive critically ill patients who were vasopressor-dependent (n = 10), had significant peripheral edema (n = 10), or were admitted following major surgery (n = 10). MEASUREMENTS: Findings from three different methods of glucose measurement were compared with central laboratory measurements: (1) glucose meter analysis of capillary blood (fingerstick); (2) glucose meter analysis of arterial blood; and (3) blood gas/chemistry analysis of arterial blood. Patients were enrolled for a maximum of 3 days and had a maximum of nine sets of measurements determined during this time. RESULTS: Clinical agreement with the central laboratory was significantly better with arterial blood analysis (69.9% and 76.5% for glucose meter and blood gas/chemistry analysis, respectively) than with capillary blood analysis (56.8%; p = .039 and .001, respectively). During hypoglycemia, clinical agreement was only 26.3% with capillary blood analysis and 55.6% and 64.9% for glucose meter and blood gas/chemistry analysis of arterial blood (p = .010 and <.001, respectively). Glucose meter analysis of both arterial and capillary blood tended to provide higher glucose values, whereas blood gas/chemistry analysis of arterial blood tended to yield lower glucose values. CONCLUSIONS: The magnitude of the differences in the glucose values offered by the four different methods of glucose measurement led to frequent clinical disagreements regarding insulin dose titration in the context of an insulin infusion protocol for aggressive glucose control.

APACHE↗

PubMed2005

A pilot study of spatial patterns in referrals to a multicentre cancer genetics service.

OBJECTIVES: To analyse spatial and temporal patterns in patients referred to a cancer genetics service in order to monitor service utilization and accessibility. METHODS: Postcodes of patients during a 4-year period were used to examine spatial patterns using a Geographical Information System (GIS). Referral rates were compared visually and statistically to explore yearly variation for administrative areas in Wales. RESULTS: There has been a four-fold increase in actual referrals to the service over the period of study. The variance between unitary authority referral rates has decreased from the inception of the service from an almost ten-fold difference between lowest and highest in year 1 to less than a three-fold difference in year 4. CONCLUSIONS: This study shows the potential of GIS to highlight spatial variations in referral rates across Wales. Although the disparity in referral rates has decreased, trends in referral rates are not consistent. Ongoing research will examine those referral and referrer characteristics affecting uptake.

Feasibility Studies↗

PubMed2004

Analysing spatial trends in referral patterns to cancer genetics services: a preliminary investigation of regional variations in Wales.

This paper discusses spatial trends in referral patterns to a cancer genetics service. It presents a literature review outlining the paucity of existing research, a preliminary analysis at the Unitary Authority level in Wales and advances a programme of further research to be conducted at a more detailed spatial level. The preliminary analysis shows a weak negative relationship between referral rates from primary care and social deprivation by Unitary Authority (Spearman rank correlation coefficient, sigma = -0.38). There is also a weak positive relationship between average settlement size and referral rates (sigma = +0.28), which taken together may indicate that primary care practices in affluent urban areas are more likely to refer than those in poorer rural areas. Future research will be conducted at a finer spatial scale, and will take into account characteristics of primary care practices and the patients being referred, amongst other variables.

Humans↗

PubMed2004

Modeling guidelines for integration into clinical workflow.

The success of clinical decision-support systems requires that they are seamlessly integrated into clinical workflow. In the SAGE project, which aims to create the technological infra-structure for implementing computable clinical practice guide-lines in enterprise settings, we created a deployment-driven methodology for developing guideline knowledge bases. It involves (1) identification of usage scenarios of guideline-based care in clinical workflow, (2) distillation and disambiguation of guideline knowledge relevant to these usage scenarios, (3) formalization of data elements and vocabulary used in the guideline, and (4) encoding of usage scenarios and guideline knowledge using an executable guideline model. This methodology makes explicit the points in the care process where guideline-based decision aids are appropriate and the roles of clinicians for whom the guideline-based assistance is intended. We have evaluated the methodology by simulating the deployment of an immunization guideline in a real clinical information system and by reconstructing the workflow context of a deployed decision-support system for guideline-based care. We discuss the implication of deployment-driven guideline encoding for sharability of executable guidelines.

Decision Making, Computer-Assisted↗

PubMed2003

Public attitudes to human gene therapy: a pilot study in Wales.

OBJECTIVE: This study aimed to explore some factors influencing perceptions of human gene therapy. METHOD: A small qualitative study using two semi-structured interviews per participant (n = 22). The groups comprised (1) people with cystic fibrosis and members of their family (n = 9), and (2) students from a science evening class as well as lay members of the public selected from the practice list of a local general practitioner (n = 13). RESULTS: This pilot study demonstrates support for somatic gene therapy and ambivalence about germline gene therapy. A clear distinction is drawn between therapy and enhancement, with the majority opposing gene enhancement. CONCLUSIONS: Attitudes towards the acceptability of gene therapy are not necessarily determined by experience of, or exposure to, a genetic condition. More research is needed with the general public to determine what is perceived to be acceptable public policy in this field.

Adolescent↗

PubMed2002

Programmed death-1 targeting can promote allograft survival.

The recently identified CD28 homolog and costimulatory molecule programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2, which are homologs of B7, constitute an inhibitory regulatory pathway of potential therapeutic use in immune-mediated diseases. We examined the expression and functions of PD-1 and its ligands in experimental cardiac allograft rejection. In initial studies, we found that most normal tissues and cardiac isografts had minimal expression of PD-1, PD-L1, or PD-L2, but intragraft induction of all three molecules occurred during development of cardiac allograft rejection. Intragraft expression of all three genes was maintained despite therapy with cyclosporin A or rapamycin, but was prevented in the early posttransplant period by costimulation blockade using CD154 or anti-inducible costimulator mAb. We prepared PD-L1.Ig and PD-L2.Ig fusion proteins and showed that each bound to activated PD-1(+) T cells and inhibited T cell functions in vitro, thereby allowing us to test the effects of PD-1 targeting on allograft survival in vivo. Neither agent alone modulated allograft rejection in wild-type recipients. However, use of PD-L1.Ig administration in CD28(-/-) recipients, or in conjunction with immunosuppression in fully MHC-disparate combinations, markedly prolonged cardiac allograft survival, in some cases causing permanent engraftment, and was accompanied by reduced intragraft expression of IFN-gamma and IFN-gamma-induced chemokines. PD-L1.Ig use also prevented development of transplant arteriosclerosis post-CD154 mAb therapy. These data show that when combined with limited immunosuppression, or in the context of submaximal TCR or costimulatory signals, targeting of PD-1 can block allograft rejection and modulate T and B cell-dependent pathologic immune responses in vivo.

Animals↗

PubMed2002

Anti GPVI human antibodies neutralizing collagen-induced platelet aggregation isolated from a combinatorial phage display library.

Glycoprotein VI is a type I membrane protein identified as a key platelet receptor for collagen. In vitro binding of the GPVI receptor with collagen leads to activation and ultimately to aggregation of platelets. In vivo, GPVI-collagen interactions could cause formation of occlusive thrombi within vessels with damaged endothelial barriers. GPVI antagonists are therefore important therapeutics in patients suffering from collagen-mediated ischemic disorders such as myocardial infarction or stroke. Polyclonal antibodies to GPVI prepared from one patient serum have previously been described. However, only their monovalent Fab fragments, incapable of receptor crosslinking, were found to protect platelets from collagen-mediated aggregation. Here we describe GPVI-neutralizing human antibodies derived from a combinatorial phage display library of single-chain antibodies. By selecting phage on GPVI-expressing U937 cells, we isolated five specific antibodies - A4, A9, A10, C3 and C9. Of the set A10 and C3 specifically blocked GPVI binding to collagen-rich adventitial layers in aorta sections. The higher affinity antibody A10 inhibited binding of snake-venom convulxin to GPVI. It also specifically protected human platelets from collagen-induced aggregation in vitro. A10-bound platelets could still be activated by ADP or thrombin suggesting that this human scFv may represent an original anti-platelet agent for the treatment of collagen-mediated thrombotic diseases.

Animals↗