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Biomedical subjects

P McNair

Publications and source records attributed to P McNair.

At least 19 recordsLinked to original sources

User requirements specifications: a hierarchical structure covering strategical, tactical and operational requirements.

The present study is a long-term review and follow-up on conclusions and recommendations on the role and contents of a User Requirements Specification Document (URD) from a previous in-depth case study. The follow-up comprises a succession of investigations and two case studies to explore the role and contents of a URD within systems development and assessment, thereby gradually extending and refining the original recommendations. Finally, the recommended three-layered structure and approach for a URD were applied in full scale within a real-life project, in which the URD serves as the basis for a Call for Tender. The preparation was entirely user-driven with the aid of a consultant for four man months. The present paper outlines the essence of the approach and the outcome of applying the recommended structure, with numerous examples of the implications.

Clinical Laboratory Information Systems↗

Cutaneous metal sensitivity in patients with orthopaedic injuries.

BACKGROUND: Manufactures of orthopaedic fracture implants have turned to titanium in a pure form and an alloy during the past ten to fifteen years. Although primarily because of the biomechanical properties of this metal, concern for allergy to nickel and chromium ions in stainless steel was a factor in these decisions. OBJECTIVES: To document the incidence of baseline sensitivity to metal ions and the incidence of conversion to sensitivity to one of three ions in stainless steel in a population of trauma patients at a Level I trauma center. DESIGN: Prospective, consecutive patient series. SETTING: Level I trauma center. PATIENTS: Patients eighteen years of age and older with no history of metallic implants were recruited for this study between October 1995 and July 1997. Four hundred ninety-three patients had a Finn chamber device with chromium, nickel, and cobalt ions, which were read using a photographic scale on day three. Two hundred forty-two of these patients had placement of a second patch, at a mean interval of 187 days (range 45 to 589 days). INTERVENTION: Internal fixation of fracture or osteotomy with metal implant. MAIN OUTCOME MANAGEMENT: Cutaneous reactivity to metal ions. RESULTS: Prevalence of sensitivity to chromium was 0.2 percent, to nickel 1.3 percent, and to cobalt 1.8 percent. Rates for conversion from a negative to positive status were 2.7 percent for chromium, 3.8 percent for nickel, and 3.8 percent for cobalt. Rates for desensitization (i.e., converting from a positive to negative status) were 2.1 percent for nickel and 3.8 percent for cobalt. CONCLUSION: The prevalence of sensitivity to nickel, cobalt, and chromium is apparently low. Similarly, internal fixation devices composed of stainless steel appear to result in an equal incidence of conversion to metal ionic sensitivity and desensitization to metal ions. It is conceivable that cutaneous sensitivity is not representative of deep immune response.

Adult↗

Research needs and priorities in health informatics.

A Delphi study was accomplished on the topic "what is needed to implement the information society within healthcare? and which research topics should be given higher priority than other topics to achieve the desired evolution?", involving 29 international experts. The study comprised of four phases, (I) a brainstorming phase based on a open question; (II) an evaluation phase for mutual commenting; (III) a feedback phase allowing corrections/extensions; and (IV) a phase collecting the ratings of individual issues within a questionnaire synthesised from the previous phases. A total of 110 research items and 58 supplementary barriers were raised, divided into 14 topics grouped according to homogeneity. The emphasised research topics are business process re-engineering, the electronic patient record and connected inter-operating systems, (support for) evidence-based medicine and clinical guidelines, and education. Issues inherent to the healthcare domain often are the kernel of the research recommended. Similarly, methods and 'people'-issues are strongly emphasised among the research issues in general and among those for which the experts' joint opinion was rated as statistically significant. In contrast, only a minority of the research issues emphasised was related to technical issues.

Delphi Technique↗

Screening for preclinical type 1 diabetes in a discrete population with an apparent increased disease incidence.

Environmental agents are proposed to play a role in triggering or exacerbating pancreatic islet autoimmunity in people genetically predisposed to type 1 diabetes. However, with few exceptions, these agents remain enigmatic. Clues to environmental agents may be found by investigating population/geographic clusters or 'hotspots' of high disease incidence. We were alerted to a small community where the incidence of type 1 diabetes appeared to be five-fold higher than expected. Because type 1 diabetes is now recognized to have a subclinical phase during which anti-islet antibodies can be detected, we aimed to identify and characterize a reservoir of children with subclinical disease in this community. Venous blood samples were collected from 1906/2347 (81%) local school children during one week. Islet cell antibodies (ICAs) were detected in 122 (6.4%) children, 18 (0.9%) being high titer (> or = 20 Juvenile Diabetes Foundation units (JDFu)). On retest, 15 months later, the majority of low titer ICAs were undetectable, whereas high-titer ICAs persisted. The latter were found in two distinct age-related, ethnically similar groups. The younger group, aged 6-9 yr, had antibodies to insulin (IAAs), glutamic acid decarboxylase (GAD) and tyrosine phosphatase IA2 in addition to ICA, human leukocyte antigen (HLA) genes associated with susceptibility to type 1 diabetes, and lower first-phase insulin responses (FPIRs) to intravenous glucose. The older group, aged 13-16 yr, the age cohort of the index clinical cases, had few antibodies other than ICA, non-susceptibility HLA genes and normal FPIRs. During follow-up, three children, all from the younger group with multiple antibodies and FPIRs less than the first percentile, developed diabetes 4, 6 and 7 yr after screening. The finding of two age groups of subclinical disease suggests that if environmental agents triggered islet autoimmunity they did not act constantly on the community. Furthermore, the absence of multiple autoantibodies and/or HLA susceptibility genes in the older group, the source of index clinical cases, implies they are a residual subgroup with slow or absent progressive beta-cell destruction. This study illustrates that the natural history of type 1 diabetes may be elucidated by analyzing age-related subclinical disease in the general population.

Journal Article↗

User requirements in a system development & evaluation context.

The case study presented investigates how the interaction between users and developers changed when introducing a three level User Requirements Specification with a coarse granularity of the lowest (operational) requirements.

Clinical Laboratory Information Systems↗

Landing in netball: effects of taping and bracing the ankle.

OBJECTIVES: To investigate the effect of bracing and taping on selected electromyographic, kinematic, and kinetic variables when landing from a jump. METHODS: Fifteen netball players performed a jump, so as to land on their dominant limb on a force plate. Electromyographic activity was recorded from the gastrocnemius, tibialis anterior, and peroneus longus muscles. Subjects were also filmed and measures of rearfoot motion were derived. RESULTS: Significantly less electromyographic activity (p<0.007) was observed from the gastrocnemius and peroneus longus muscle groups when subjects were braced. No other significant electromyographical findings were observed. Peak vertical ground reaction force and time to peak for vertical ground reaction force were not affected by bracing and taping, nor were the rearfoot and Achilles tendon angles at foot strike. CONCLUSIONS: The effect of bracing and taping on the selected biomechanics variables associated with landing was specifically limited to a reduction in muscle action, particularly for the braced condition. Netball players can be confident that the biomechanics of their landing patterns will not be altered whether they choose to wear a brace or tape their ankle joints.

Adult↗

Research needs and priorities in health informatics--early results of a Delphi study.

A four-phased Delphi study has been performed on the topic of "research needs and priorities to implement the Information Society within Healthcare". This contribution presents the outcome of the first three phases. The biggest surprises are that 'Telemedicine' is relatively lower ranked than expected, and that 'Business Process Re-engineering' is the highest ranking topic, as judged from the number of issues and barriers raised by the expert panel.

Delphi Technique↗

The Melbourne Pre-Diabetes Study: prediction of type 1 diabetes mellitus using antibody and metabolic testing.

OBJECTIVES: To determine the utility of various autoantibodies in predicting progression to clinical diabetes in first-degree relatives of patients with type 1 diabetes mellitus. PARTICIPANTS: 3315 first-degree relatives of patients with type 1 diabetes (1161 parents, 1206 siblings and 948 offspring) recruited through diabetes clinics, private endocrinologists, Diabetes Australia and the Juvenile Diabetes Foundation. MAIN OUTCOME MEASURES: Prevalence of islet cell antibodies (ICA) levels > or = 20 JDFu, insulin autoantibodies (IAA) levels > 100 nU/mL, and antibodies to glutamic acid decarboxylase (GADAb) and tyrosine phosphatase IA2 (IA2Ab); change in beta cell function over time; and development of clinical diabetes. RESULTS: 2.6% of relatives had elevated ICA levels, 1.3% had elevated IAA levels and 0.3% had both. High ICA levels were significantly more frequent in siblings than in offspring or parents, and were more frequent in relatives younger than 20 years. GADAb were detected in 68% and IA2Ab in 57% of relatives with elevated ICA and/or IAA levels. Diabetes developed in 33 relatives (25 siblings, 2 offspring and 6 parents). Before diagnosis of clinical diabetes, high ICA levels were detected in 18 (58%), high IAA levels in 7 (23%), both in 5 (15%), and either in 19 (61%); GADAb were detected in 26 (84%), IA2Ab in 13 (42%), both in 11 (35%), and either in 28 (90%). First phase insulin release (FPIR) less than 50 mU/L was very strongly associated with progression to diabetes. In relatives with FPIR initially greater than 50 mU/L who eventually developed diabetes, there was a gradual and continuous reduction in FPIR over time before diagnosis. CONCLUSIONS: Type 1 diabetes can be diagnosed in the preclinical stage. The recently described antibodies to glutamic acid decarboxylase and tyrosine phosphatase IA2 appear superior to ICA as screening tools for the preclinical diagnosis of type 1 diabetes.

Adult↗

Diurnal rhythms of pro-inflammatory cytokines: regulation by plasma cortisol and therapeutic implications.

Clinical features of certain immuno-inflammatory disorders such as rheumatoid arthritis and asthma exhibit diurnal fluctuation, which could be related to diurnal rhythmicity of pro-inflammatory cytokine production. To investigate the latter, the authors performed measurements of lipopolysaccharide (LPS)-stimulated whole blood, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1) and IL-12 production in 13 healthy volunteers over 24 h. These cytokines exhibited distinct diurnal rhythms that peaked in the early morning and were inversely related to the rhythm of plasma cortisol. Elevation of plasma cortisol within the physiological range by administration of cortisone acetate, 25 mg at 21.00, markedly suppressed IFN-gamma, TNF-alpha, IL-1 and IL-12 production, but not the later early morning rise of endogenous plasma cortisol. Suppression of cytokine production was temporally dissociated from changes in numbers of circulating mononuclear cells. Regulation of pro-inflammatory cytokine production by plasma cortisol has potential therapeutic implications. In contrast to standard schedules, a small, late evening, dose of glucocorticoid to suppress the diurnal increase in pro-inflammatory cytokine production could alleviate early morning inflammatory symptoms and minimize side-effects.

Adult↗

Computer-aided test selection and result validation-opportunities and pitfalls.

Dynamic test scheduling is concerned with pre-analytical preprocessing of the individual samples within a clinical laboratory production by means of decision algorithms. The purpose of such scheduling is to provide maximal information with minimal data production (to avoid data pollution and/or to increase cost-efficiency). Our experience shows that there is a practical limit to the extent of exploitation of the principle of dynamic test scheduling, unless it is automated in one way or the other. This paper analyses some issues of concern related to the profession of clinical biochemistry, when implementing such dynamic test scheduling within a Laboratory Information System (and/or an advanced analytical workstation). The challenge is related to 1) generation of appropriately validated decision models, and 2) mastering consequences of analytical imprecision and bias.

Algorithms↗

Incidence of sporting injury in New Zealand youths aged 6-15 years.

OBJECTIVE: To document the incidence of injury in 6-15 year olds playing rugby union, rugby league, and netball, and to identify the common mechanisms, sites, severity, and time of injury. METHODS: Cross sectional data were collected by trained observers who watched 258 games of rugby union, netball, and rugby league over a four week period. The condition of the injured participants was monitored until recovery. RESULTS: In total, 5174 players were observed and an injury rate of 18 per 1000 player hours was calculated. Of all observed injuries, 29% required some form of medical treatment. A significant difference (p<0.05) in the distribution of injury over the four quarters of the games was recorded, most occurring in the first three quarters. In total, 81% of the injuries were classified as contact injuries, and these mainly occurred through direct contact with the opposition. Of all observed injuries, 27% were recurrent. CONCLUSIONS: The incidence of injury in rugby union, netball, and rugby league is low for children aged between 6 and 15 years relative to adult rates.

Adolescent↗

Lymphocytopenia in a hospital population--what does it signify?

BACKGROUND: Lymphocytopenia is a common finding in hospital patients especially since the advent of automated differential leukocyte counters. The causes and significance of lymphocytopenia are generally poorly understood. There has been no large-scale study of its significance for 25 years. The HIV epidemic, and the recently described idiopathic CD4+ T-lymphocytopenia have raised interest in this finding. AIMS: To describe the spectrum of lymphocytopenia in an adult teaching hospital and investigate its clinical significance. METHODS: Using the available computer facilities, patients with significant lymphocytopenia (< 0.6 x 10(9)/L) were identified over a 102 day period and diagnoses, operations and medication lists obtained. Where necessary, patient histories were examined to supplement the above information. If feasible, previous and subsequent lymphocyte counts were checked to establish if the lymphocytopenia were temporary or longstanding. RESULTS: One thousand and forty-two patients were identified, with a mean age of 59.6 years, of whom 563 were male, and 757 were inpatients. Thirty-six patients were pancytopenic. We checked previous and subsequent counts for 698 patients and found 45 patients who were consistently lymphocytopenic, some for more than ten years. Thirty-four patients with previously normal counts remained lymphocytopenic throughout follow up, while 457 had at least one subsequent lymphocyte count > 1 x 10(9)/L. We found only one patient who was suspected of having idiopathic CD4+ T-lymphocytopenia. Patients fell into several categories (with some overlap): bacterial/fungal sepsis (250), post-operative (228), corticosteroid therapy (definite 159, suspected 53, inhaled steroids alone 14), malignancy (174 definite, six probable), cytotoxic therapy and/or radiotherapy (90), trauma or haemorrhage (86), transplants (73-38 renal and 35 bone marrow), 'viral infections' (26) and HIV infection (13). Thirty-four patients died within the study period. CONCLUSIONS: Lymphocytopenia in hospital patients is most frequently reversible, and due to acute illness, notably sepsis and trauma (including surgery). Malignancy, with or without chemotherapy, and steroid use are also common causes, but HIV infection is a relatively uncommon cause in our hospital.

Adolescent↗

Within-centre evaluation of hypercalcaemia discriminant functions 5 years after their development.

Diagnostic hypercalcaemia discriminant functions, discriminating between clinically significant and non-significant hypercalcaemia, were tested 5 years after their development in order to evaluate the impact of time on their diagnostic capacity. Two populations, consisting of 257 and 129 patients with hypercalcaemia, were consecutively recorded, during six and three months respectively, 5 years apart under similar circumstances. The prevalence of hypercalcaemia was comparable in both populations, being 2.57 and 2.38% respectively (non-significant) (NS). The female/male ratio was 1.9 and 1.7 (NS). The discriminant functions correctly classified 81 and 80% of the women, respectively (NS) and respectively 75% and 64% of the men (NS) in the first and second recorded populations.

Adult↗

User requirements on the future laboratory information systems.

Today numerous information technology solutions exist for the clinical laboratory which operate either as stand-alone functionalities or with ad hoc integration solutions. The OpenLabs (A2028) AIM Project puts emphasis on the design and specification of a framework for the interoperability of existing systems and new advanced services, and consequently concentrates on the issue of integration. The purpose of the OpenLabs open architecture is to serve as a functional solution to this integration. A basic principle for this open architecture is that each of the advanced services shall be able to function individually or in any combination with an existing Laboratory Information System (LIS), and that it shall enable new modular functionalities to be incorporated in a 'plug-and-play' fashion. The synthesis of the main user needs and requirements implies that the future IT solutions: (a) must be highly flexible and maximally customizable--by the users themselves; (b) are based on the concept of open systems, both technically and functionally, which enables modular functionalities from different vendors to co-operate forming a global LIS functionality; (c) are future viable and able to incorporate already installed IT functionalities; (d) support management of failure prevention, of repair, of success, and of change. The establishment of an open architecture implies that a market will develop for modular, scaleable, and cost-effective LIS features without today's dependence on individual manufacturers and hardware/software platforms.

Clinical Laboratory Information Systems↗

Time course of platelet alpha granule release in acute myocardial infarction treated with streptokinase.

OBJECTIVE: To determine the time course of platelet alpha granule release in patients with acute myocardial infarction treated with streptokinase. DESIGN: A prospective study. SETTING: Coronary care unit. PATIENTS: Nine with myocardial infarction treated with both streptokinase and aspirin, and nine with acute chest pain but without myocardial infarction, who were treated with aspirin only. METHODS: All patients received 250 mg aspirin on admission and 150 mg once daily thereafter. All patients who fulfilled the indications for streptokinase received 1.5 megaunits, in a single infusion. After the initial medication, serial measurements of plasma beta thromboglobulin and plasma platelet factor 4 were performed at fixed intervals after the onset of chest pain. The primary endpoint sought was the peak value of beta thromboglobulin and platelet factor 4 in each individual. RESULTS: The median peak plasma beta thromboglobulin in the infarction group was substantially higher than in those without infarction, at 37 (range 12 to 210) v 15 (9 to 36) mg/litre, P < 0.01. The corresponding values for plasma platelet factor 4 were 4.6 (2.4 to 60.0) v 2.2 (< 2 to 8.5) mg/litre, P < 0.01. Increased values were seen only within the first 12 h after onset of chest pain, and after 12 h there was no difference between the patients with myocardial infarction and those without. Aspirin treatment did not abolish alpha granule release. CONCLUSIONS: In patients with acute myocardial infarction treated with streptokinase the content of the alpha granules is released within the first 12 h after the onset of chest pain. Aspirin apparently does not abolish this release.

Adult↗

Framework for quality assessment of knowledge.

One of the key issues in the development (and subsequent application) of medical knowledge-be it in terms of a KBS or otherwise-is the assessment of its quality. We present a framework for how to manage and make measurable the quality of the semantic as well as pragmatic aspects of the knowledge embedded in classification models during the development of such models.

Artificial Intelligence↗

Similar peptides from two beta cell autoantigens, proinsulin and glutamic acid decarboxylase, stimulate T cells of individuals at risk for insulin-dependent diabetes.

BACKGROUND: Insulin (1) and glutamic acid decarboxylase (GAD) (2) are both autoantigens in insulin-dependent diabetes mellitus (IDDM), but no molecular mechanism has been proposed for their association. We have identified a 13 amino acid peptide of proinsulin (amino acids 24-36) that bears marked similarity to a peptide of GAD65 (amino acids 506-518) (G. Rudy, unpublished). In order to test the hypothesis that this region of similarity is implicated in the pathogenesis of IDDM, we assayed T cell reactivity to these two peptides in subjects at risk for IDDM. MATERIALS AND METHODS: Subjects at risk for IDDM were islet cell antibody (ICA)-positive, first degree relatives of people with insulin-dependent diabetes. Peripheral blood mononuclear cells from 10 pairs of at-risk and HLA-DR matched control subjects were tested in an in vitro proliferation assay. RESULTS: Reactivity to both proinsulin and GAD peptides was significantly greater among at-risk subjects than controls (proinsulin; p < 0.008; GAD; p < 0.018). In contrast to reactivity to the GAD peptide, reactivity to the proinsulin peptide was almost entirely confined to the at-risk subjects. CONCLUSIONS: This is the first demonstration of T cell reactivity to a proinsulin-specific peptide. In addition, it is the first example of reactivity to a minimal peptide region shared between two human autoimmune disease-associated self antigens. Mimicry between these similar peptides may provide a molecular basis for the conjoint autoantigenicity of proinsulin and GAD in IDDM.

Adolescent↗