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Biomedical subjects

Andrew Wilson

Publications and source records attributed to Andrew Wilson.

At least 19 recordsLinked to original sources

CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure.

BACKGROUND: An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising. METHODS/DESIGN: The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18-65 years) with severe, but potentially reversible, respiratory failure (Murray score >/= 3.0 or hypercapnea with pH < 7.2) will be randomised for consideration of extracorporeal membrane oxygenation at Glenfield Hospital, Leicester or continuing conventional care in a centre providing a high standard of conventional treatment. The central randomisation service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables. Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial. 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance (2-sided test). Secondary outcomes include patient morbidity and health status at 6 months. DISCUSSION: Analysis will be based on intention to treat. A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments.

Adolescent↗

Parallel, high-throughput purification of recombinant antibodies for in vivo cell assays.

We describe a method for high-throughput, parallel purification of secreted proteins to analyse large numbers of protein samples in cell-based assays for the discovery of protein therapeutics. The procedure is generic and capable of 96 parallel purifications and compatible, in both yield and purity, with a wide assay range. By optimising expression and purification steps as well as using novel hardware, in particular a chromatography press capable to purify target proteins from viscous media, we exemplify the process for the generation of single-chain Fv antibody fragments (scFv) and the purification of full-length IgG. The described process can operate robustly with a throughput of over 2,000 samples per month.

Antibodies, Monoclonal↗

Adenotonsillectomy for obstructive sleep apnea in obese children: effects on respiratory parameters and clinical outcome.

OBJECTIVE: To assess the efficacy of adenotonsillar surgery on respiratory sleep parameters and avoiding continuous positive airway pressure (CPAP) treatment in morbidly obese children with obstructive sleep apnea syndrome (OSAS). DESIGN: Retrospective. SETTING: Tertiary referral institution. PATIENTS: Children aged 2 to 18 years, with a body mass index (BMI) at or higher than the 95th percentile (adjusted for age and sex), undergoing adenotonsillar surgery for OSAS. INTERVENTIONS: Adenotonsillectomy. MAIN OUTCOME MEASURES: Preoperative and postoperative respiratory disturbance index, oxygen saturation nadir, overall severity of OSAS (mild, moderate, or severe) and candidacy for CPAP treatment were assessed and compared. Variables such as age, severity of disease, adenotonsillar size, and BMI z scores were compared between responders and nonresponders to surgical treatment. RESULTS: A total of 19 patients with full preoperative and postoperative data for evaluation were identified. The median (SD) age was 78 months (53.3 months). The median (SD) BMI z score was 2.84 (0.94). Eighteen patients (95%) had OSAS preoperatively to warrant CPAP treatment. Surgery reduced the overall median (SD) respiratory disturbance index from 20.7 (24.5) to 7.3 (14.9) (P<.001) and improved the median (SD) oxygen saturation nadir from 77.5% (16.3%) to 88.5 (13.1%) (P<.01). A total of 7 patients (37%) were cured by surgery. Ten patients (53%) had postoperative disease of sufficient severity to require CPAP. Surgery obviated the need for further treatment in only 8 (44%) of the 18 patients with preoperative disease warranting CPAP. No differences were identified between responders and nonresponders to surgical treatment. CONCLUSIONS: Adenotonsillar surgery improves sleep respiratory parameters in morbidly obese children with OSAS. Most patients have residual OSAS requiring further treatment.

Adenoidectomy↗

Is real reform of the Medicare Benefits Schedule for psychiatrists in Australia economically, socially or professionally desirable?

OBJECTIVE: To propose alternative Medicare Benefits Schedule-based funding models for outpatient psychiatric services in Australia. METHOD: Development of alternative funding schedules for a variety of under-serviced populations. CONCLUSIONS: Consideration of alternative systems is necessary to address the restrictive work practices, inequity and poor distribution of the psychiatric workforce.

Attitude to Health↗

Blood pressure and hypertension for Australian Aboriginal and Torres Strait Islander people.

BACKGROUND: Reliable, large-scale, population-based data on blood pressure for Australian Aboriginal and Torres Strait Islander populations are limited. This present study aims to describe the blood pressure levels and to explore the clinical risk factors for hypertension among Australian Aboriginal and Torres Strait Islander peoples. DESIGN: A cross-sectional population survey was conducted in isolated communities in northern and central Australia. METHODS: Australian Aboriginal people (n = 1088) and Torres Strait Islanders (n = 606) aged 15 years and over were examined between 1993 and 1997. Blood pressure, body mass index, plasma glucose and urinary albumin-creatinine ratio were measured. The association of systolic, diastolic and pulse blood pressure to age was determined and independent associations of hypertension with other clinical variables were tested using logistic regression. Comparisons with results from other Australian data (including AusDiab) were made. RESULTS: Systolic blood pressure and pulse pressure increased in a linear manner with age but mean diastolic blood pressure leveled off at around 50 years and decreased thereafter, suggestive of arterial stiffening. The age-standardized prevalence of hypertension (blood pressure > or = 140/90 mmHg or medication) for subjects aged 25-54 years was 27%, compared with 9% in non-Indigenous Australians in the Northern Territory and Queensland (AusDiab Survey). Older age, male sex, higher body mass index, albumin-creatinine ratio and diabetes were independently associated with hypertension. CONCLUSIONS: Elevated blood pressure is a public health concern for indigenous people, which again highlights health differentials in Australia. Early detection and management of high blood pressure should be assigned a high priority in Indigenous communities.

Adolescent↗

Automated detection of lung nodules in CT scans: false-positive reduction with the radial-gradient index.

We present a number of approaches based on the radial gradient index (RGI) to achieve false-positive reduction in automated CT lung nodule detection. A database of 38 cases was used that contained a total of 82 lung nodules. For each CT section, a complementary image known as an "RGI map" was constructed to enhance regions of high circularity and thus improve the contrast between nodules and normal anatomy. Thresholds on three RGI parameters were varied to construct RGI filters that sensitively eliminated false-positive structures. In a consistency approach, RGI filtering eliminated 36% of the false-positive structures detected by the automated method without the loss of any true positives. Use of an RGI filter prior to a linear discriminant classifier yielded notable improvements in performance, with the false-positive rate at a sensitivity of 70% being reduced from 0.5 to 0.28 per section. Finally, the performance of the linear discriminant classifier was evaluated with RGI-based features. RGI-based features achieved a substantial improvement in overall performance, with a 94.8% reduction in the false-positive rate at a fixed sensitivity of 70%. These results demonstrate the potential role of RGI analysis in an automated lung nodule detection method.

Algorithms↗

The effect of interventions to alter the consultation length of family physicians: a systematic review.

BACKGROUND: Observational studies have shown differences in process and outcome between the consultations of primary care physicians whose average length of consultation differs, however, these differences may be due to self selection. AIM: To assess the effectiveness and cost effectiveness of interventions to alter primary care physicians' consultation length. DESIGN OF STUDY: Systematic review with narrative analysis. METHOD: Data sources included Medline, EMBASE, the Cochrane Controlled Trials Register and Effective Practice and Organisation of Care Group specialised register, the NHS National Research Register and author contacts. To be eligible, studies had to be controlled trials. They had to evaluate interventions to alter the consultation length of primary care physicians, and provide objectively measured process or outcome data. Data were extracted independently using agreed criteria and disagreements resolved by discussion. RESULTS: Six articles describing four trials were included. All took place in the UK and tested short term changes in the time allocated to each patient, and all had methodological weaknesses, particularly due to non random allocation of patients. Altering appointment length resulted in modest changes in average consultation length. There were no consistent differences in problem recognition, examination, prescribing, referral or investigation rates. There was some evidence that blood pressure was checked more frequently and smoking discussed more often when more time was available. None of the interventions were associated with differences in patient satisfaction. No trials examined cost effectiveness. CONCLUSIONS: Our findings do not provide sufficient evidence to support or resist a policy of altering consultation lengths of primary care physicians. Further trials are needed, focussing on health outcomes and cost effectiveness.

Appointments and Schedules↗

External fixation of pediatric femur fractures with cortical contact.

The cases of 40 pediatric femur fractures treated with external fixation were reviewed to determine whether stabilization with cortical contact resulted in clinical leg-length discrepancy (LLD). Mean follow-up was 29.4 months, mean age was 6.6 years (range, 2-10 years), 25 injuries were isolated, 100% of the fixators were applied with cortical contact, all fractures healed by a mean of 92 days, 72.5% were dynamized before removal, mean LLD was 0.24 cm short, and complications included 1 refracture (2.5%), early removal of 2 loose pins (1.25% of 160 pins), pin-tract infections in 21 patients (52.5%), and 1 LLD (2.5%) of more than 1.0 cm (5.0 cm short). External fixation with cortical contact was an effective treatment for pediatric femur fractures. It limited overgrowth and resulted in few refractures. Pin-tract infections were common.

Adolescent↗

Estradiol protects against alteration of protein kinase C(epsilon) in a binge model of ethanol dependence and withdrawal.

This study tested the hypothesis that a binge type of ethanol intake and ethanol withdrawal disturbs protein kinase C (PKC) homeostasis in a manner protected by 17beta-estradiol. Ovariectomized rats implanted with 17beta-estradiol or oil pellets received ethanol (7.5% weight/volume, 7 days) or control solution by a gavage method. The cerebelli were collected during ethanol exposure or ethanol withdrawal to assess the activity, protein levels, and cellular distribution of PKC(epsilon) and total PKC, using an ATP phosphorylation and immunoblot assays. While both ethanol exposure and ethanol withdrawal increased membrane protein levels and membrane translocation, only ethanol withdrawal enhanced activity of PKC(epsilon). Ethanol withdrawal not ethanol exposure increased the three parameters of total PKC. 17beta-Estradiol treatment prevented these changes in PKC profiles. These data suggest that an excessive episodic intake of ethanol followed by ethanol withdrawal disturbs PKC homeostasis and cellular distribution of PKC, in particular PKC(epsilon), in a manner that is protected by estrogen. PKC(epsilon) appears more vulnerable during ethanol withdrawal than during ethanol exposure.

Alcoholic Intoxication↗

Does increased use of private health care reduce the demand for NHS care? A prospective survey of general practice referrals.

BACKGROUND: The use of the private sector for health care is increasing, but it is unclear whether this will reduce demand on the NHS. The aim of this study was to examine the relationship between private and NHS outpatient referral rates accounting for their association with deprivation. METHODS: This is a prospective survey of general practitioner referrals to private and NHS consultant-led services between 1 January and 31 December 2001 from 10 general practices in the Trent Focus Collaborative Research Network, United Kingdom. Patient referrals were aggregated to give private and NHS referral rates for each electoral ward in each practice. RESULTS: Of 17,137 referrals, 90.4 percent (15,495) were to the NHS and 9.6 percent (1642) to the private sector. Private referral rates were lower in patients from the most deprived fifth of wards compared with the least deprived fifth (rate ratio 0.25, 95 percent CI 0.15 to 0.41, p < 0.001), whereas NHS referral rates were slightly higher in patients in the most deprived fifth of wards (rate ratio 1.18, 95 percent CI 0.98 to 1.42, p = 0.08) both after age standardisation and adjustment for practice. The NHS referral rate was significantly higher (rate ratio 1.40, 95 percent CI 1.15 to 1.71, p = 0.001) in wards with private referral rates in the top fifth compared with the bottom fifth after adjustment for deprivation and practice. CONCLUSIONS: Increased private health care activity does not reduce the demand for NHS care: NHS and private referral rates were positively associated with each other after adjusting for age, deprivation and practice.

Adolescent↗

A comparison of spirometry in general practice and a pulmonary function laboratory.

AIMS: : To compare the results of spirometry testing in primary care with those obtained at a pulmonary function laboratory and to explore whether differences were due to technique or equipment. METHODS: : Patients on the waiting list for spirometry in six participating practices had the test performed in their own practice and at the pulmonary function laboratory (PFL). RESULTS: : A total of 45 patients had spirometry performed at both locations. Practice nurses underestimated FEV(1) and FVC. The mean difference in FEV(1) was 0.109litres (6.69%, 95% CI 2.88, 9.51) compared with a bellows spirometer, and 0.07litres (6.2% 95% CI 0.89, 8.25) when the same type of spirometer was used. The mean difference in FVC was 0.413litres (15.0% 95% CI 9.3, 20.6) when compared with bellows, and 0.267litres (10.2% 95% CI 4.1, 16.2) when the same type of spirometer was used. All differences were statistically significant (p<0.05, paired t test). Agreement on categorization of COPD was moderate (Kappa 0.46) with practice nurses overestimating severity. Compared to PFL categorisation for the presence or absence of COPD using bellows spirometers, the sensitivity of practice nurse spirometry was 0.93 (95% CI: 0.76, 0.99) and specificity 0.65 (95% CI: 0.38, 0.86). CONCLUSION: : Spirometry results obtained by practice nurses were lower than those obtained in a PFL, leading to over-diagnosis of COPD severity.

Journal Article↗

Ensuring reliability in UK written tests of general practice: the MRCGP examination 1998-2003.

Reliability in written examinations is taken very seriously by examination boards and candidates alike. Within general education many factors influence reliability including variations between markers, within markers, within candidates and within teachers. Mechanisms designed to overcome, or at least minimize, the impact of such variables are detailed. Methods of establishing reliability are also explored in the context of a range of assessment situations. In written tests of general practice within the Membership of the Royal College of General Practitioner (MRCGP) examination considerable effort has put been put into achieving acceptable levels of reliability. Current mechanisms designed to ensure high reliability are described and related to the evolution of the written component of the examination. In addition to description of marker selection and training, question development including construct a detailed example of specific and generic marking schedules is provided. Examination results for the Written Paper of the MRCGP from 1998 to 2003 are reported including Cronbach's alpha coefficients and standard error of measurements, mean scores (and SD) and pass rates. In addition individual discrimination scores for each question in the October 2002 paper are shown. Consistent high reliability of the written component of the MRCGP examination provides valuable lessons in terms of selection, training and monitoring of markers as well as practical methods of moderating factors affecting candidate variability. The challenge for examination developers is to carry these important lessons forward into a modernized assessment structure of UK general practice.

Education, Medical, Graduate↗

Role of parvalbumin in estrogen protection from ethanol withdrawal syndrome.

BACKGROUND: Parvalbumin (PA) is a calcium-binding protein that has been implicated in protecting neurons from hyperexcitability by sequestering intracellular calcium. This study examined whether ethanol exposure and/or ethanol withdrawal (EW) alter the levels of PA in a manner that is protected by 17beta-estradiol (E2). METHODS: Ovariectomized rats implanted with E2 (EW/E2) or oil pellets (EW/Oil) received chronic ethanol (7.5% w/v, 5 weeks) or control dextrin (Dex/Oil and Dex/E2) diets. At 0 hr, 24 hr, and 2 weeks of EW, three brain areas (the cerebellum, hippocampus, and cortex) were prepared for immunoblotting and immunohistological assessment of PA. RESULTS: At 24 hr of EW, the EW/Oil group showed reduced levels of PA protein and PA-positive neurons in the cerebellum and hippocampus compared with the dextrin control and the EW/E2 groups. At 2 weeks of EW, the reduced levels of PA persisted in the cerebellum but recovered toward the control levels in the hippocampus. The cortex showed no change in PA levels in any of the treatment groups. When tested at 24 hr of EW, the magnitude of EW signs inversely correlated with the levels of PA in the cerebellum and hippocampus. Ethanol exposure itself did not affect PA levels. CONCLUSION: These data suggest that EW, rather than ethanol exposure, reduces PA levels in a manner that is brain region specific and that is protected by estrogen. Disturbed PA homeostasis is hypothesized to play a role in the hyperexcitability of EW signs.

Animals↗

Improved detection of obstructive events in childhood sleep apnoea with the use of the nasal cannula and the differentiated sum signal.

The efficacy of the nasobuccal thermistor (NT) was compared with the nasal pressure cannula (NC) and the calibrated, time-differentiated respiratory inductance plethysmography sum signal (DS) in the detection of obstructive events in children during polysomnography (PSG). The overnight PSG of 20 consecutive referrals were selected for analysis. Obstructive events were scored in each study three times by one operator using a blinded procedure whereby either the NT, the NC or the DS was visible. The standard PSG channels were also visible. SPSS software was used for statistical analysis. Twenty patients aged 5 weeks to 16 years were studied. Agreement in obstructive apnoea-hypopnoea index (OAHI) was highest between the NT and NC, and the NC and DS. The NC signal was significantly more likely to be uninterpretable than the NT (P = 0.02) and this did not correlate with age. Event detection by the NT was significantly improved by the addition of either the NC (P = 0.01) or the DS (P = 0.001), while the NC stood alone unless the DS was added (P = 0.02). There was no significant difference in OAHI by the NC versus the DS. The NC detected significantly more OA than the NT or the DS (P = 0.04), while the DS trended towards detecting more OH. There was no significant difference in OAHI between any combination pair. The nasal cannula and differentiated sum signal perform better as measures of paediatric airflow than the NT. To optimize the detection of obstructive events in children we recommend using at least one, if not both these methods in paediatric sleep laboratories.

Catheterization↗

Adapting the 'family wellbeing' empowerment program to the needs of remote indigenous school children.

OBJECTIVE: To adapt the Family Wellbeing empowerment program, which was initially designed to support adults to take greater control and responsibility for their decisions and lives, to the needs of Indigenous school children living in remote communities. METHOD: At the request of two schools in remote Indigenous communities in far north Queensland, a pilot personal development and empowerment program based on the adult Family Wellbeing principles was developed, conducted and evaluated in the schools. The main aims of the program were to build personal identity and to encourage students to recognise their future potential and be more aware of their place in the community and wider society. RESULTS: Participation in the program resulted in significant social and emotional growth for the students. Outcomes described by participating students and teachers included increased analytical and reflective skills, greater ability to think for oneself and set goals, less teasing and bullying in the school environment, and an enhanced sense of identity, friendship and 'social relatedness'. CONCLUSION: This pilot implementation of the Family Wellbeing Program adapted for schools demonstrated the program's potential to enhance Indigenous young people's personal growth and development. Challenges remain in increasing parental/ family involvement and ensuring the program's sustainability and transferability. The team has been working with relevant stakeholders to further develop and package the School-based Family Wellbeing program for Education Queensland's New Basics curriculum framework.

Child↗

A benefit-cost analysis of retrofitting diesel vehicles with particulate filters in the Mexico City metropolitan area.

In the Mexico City metropolitan area, poor air quality is a public health concern. Diesel vehicles contribute significantly to the emissions that are most harmful to health. Harmful diesel emissions can be reduced by retrofitting vehicles with one of several technologies, including diesel particulate filters. We quantified the social costs and benefits, including health benefits, of retrofitting diesel vehicles in Mexico City with catalyzed diesel particulate filters, actively regenerating diesel particulate filters, or diesel oxidation catalysts, either immediately or in 2010, when capital costs are expected to be lower. Retrofit with either type of diesel particulate filter or an oxidation catalyst is expected to provide net benefits to society beginning immediately and in 2010. At current prices, retrofit with an oxidation catalyst provides greatest net benefits. However, as capital costs decrease, retrofit with diesel particulate filters is expected to provide greater net benefits. In both scenarios, retrofit of older, dirtier vehicles that circulate only within the city provides greatest benefits, and retrofit with oxidation catalysts provides greater health benefits per dollar spent than retrofit with particulate filters. Uncertainty about the magnitude of net benefits of a retrofit program is significant. Results are most sensitive to values used to calculate benefits, such as the concentration-response coefficient, intake fraction (a measure of exposure), and the monetary value of health benefits.

Air Pollution↗

Death certification: issues from a pilot of the Shipman Inquiry's interim proposals.

This article investigates the issue of death certification in England and Wales. The Shipman Inquiry published interim proposals designed to make the system of death certification safer and more accurate. The proposed forms were piloted by doctors and relatives on a sample of deaths in one locality. They were then interviewed to assess the forms' feasibility and acceptability.

Death Certificates↗