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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 37 records · Page 2Linked to original sources
PubMed2006

Improving the management and referral of patients with transient ischaemic attacks: a change strategy for a health community.

PROBLEM: Rapid referral and management of patients with transient ischaemic attacks is a key component in the national strategy for stroke prevention. However, patients with transient ischaemic attacks are poorly identified and undertreated. DESIGN AND SETTING: Before and after evaluation of quality improvement programme with controlled comparison in three primary care trusts reflecting diverse populations and organisational structures in an urban district in the North of England. KEY MEASURES FOR IMPROVEMENT: The proportion of patients receiving antiplatelet drugs and safe driving advice on referral to a specialty clinic, and the numbers of referrals, adjusted for age, to the specialist clinic before and after the improvement programme. STRATEGIES FOR CHANGE: Interviews with patient and professionals to identify gaps and barriers to good practice; development of evidence based guidelines for the management of patients with transient ischaemic attacks; interactive multidisciplinary workshops for each primary care trust with feedback of individual audit results of referral practice; outreach visits to teams who were unable to attend the workshops; referral templates and desktop summaries to provide reminders of the guidelines to clinicians; incorporation of standards into professional contracts. EFFECTS OF CHANGE: A significant improvement occurred in identification and referral of patients with transient ischaemic attacks to specialist clinics, with a 41% increase in referrals from trained practices compared with control practices. There were also significant improvements in the early treatment and safety advice provided to patients before referral. LESSONS LEARNT: A strategic approach to effective quality improvement across a diverse health community is feasible and achievable. Careful planning with patient and professional involvement to develop a tailored and multifaceted quality improvement programme to implement evidence based practice can work in very different primary care settings. Key components of the effectiveness of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication, and use of established networks and opinion leaders.

Communication↗
PubMed2005

Proteasome inhibition with bortezomib (PS-341): a phase I study with pharmacodynamic end points using a day 1 and day 4 schedule in a 14-day cycle.

PURPOSE: We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained. PATIENTS AND METHODS: Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m2 on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. RESULTS: On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m2 dose levels, most commonly in patients receiving individual total doses > or = 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m2; 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non-small-cell lung cancer, and renal cell carcinoma. CONCLUSION: Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea.

Adult↗
PubMed2005

Annihilation dynamics of umbilical defects in nematic liquid crystals under applied electric fields.

Umbilical defects were induced in a nematic liquid crystal with negative dielectric anisotropy, confined to Hele-Shaw cells with homeotropic boundary conditions, and their annihilation dynamics were investigated experimentally. Dynamic scaling laws, previously proposed for Schlieren defects, were verified also for electric field induced umbilical defects while varying external parameters, such as electric field amplitude, frequency, Hele-Shaw cell gap, and temperature. In all cases, scaling relations of rho(t) proportional to t(-1) for the defect density and D proportional to (t(0) - t)(1/2) for the defect pair separation were obtained, independent of external field parameters. The experimental results give evidence of the universality of scaling relations for the annihilation of topological defects in liquid crystals, extended to umbilical defects and their annihilation dynamics under applied external fields.

Journal Article↗
PubMed2005

Rapid assessment and initial patient treatment team -- a way forward for emergency care.

As a consequence of the UK Department of Health drive to introduce the 4-h emergency care target acute trusts have attempted to initialize a myriad of programmes to improve the patients' experience in this sector. Changes to how patients are managed and the flow that they enter within the emergency care system have become a popular option. This paper seeks to explore the concept of the Rapid Assessment and Initial Patient Treatment team (RAPT) within the Accident and Emergency (A and E) environment. We intend to provide information for readers who may be considering introducing such teams. The paper will explore the initial practical difficulties that were encountered. We will explore associated benefits for the RAPT approach including improved teamwork, better communication with the family, avoiding unnecessary duplication of work and discuss the benefits of having a direct referral process in place for emergency patients.

Choice Behavior↗
PubMed2005

Do clinical trials improve quality of care? A comparison of clinical processes and outcomes in patients in a clinical trial and similar patients outside a trial where both groups are managed according to a strict protocol.

BACKGROUND: The conventional view that participants in randomised controlled trials sacrifice themselves for the good of future patients is challenged by increasing evidence to suggest that individual patients benefit from participation in trials. OBJECTIVE: To test the hypothesis that trial participants receive higher quality care and, as a consequence, have better outcomes than patients receiving guideline driven routine care. METHODS: Retrospective comparative study of 408 women with pre-eclampsia all managed according to a strict protocol. Trial participants were 86 women who participated in a multicentre randomised controlled trial of magnesium sulphate for the treatment of pre-eclampsia (Magpie Trial); 322 non-participants formed the control group. Indicators of the process of care and clinical outcomes were compared between the two groups. RESULTS: Trial participants were significantly more likely to have received daily blood tests (odds ratio (OR) 6.82, 95% CI 1.62 to 28.72) and had their respiration rate measured hourly (OR 3.42, 95% CI 1.69 to 6.92) than control patients. There were no significant differences in other markers of clinical process and no significant difference in clinical outcomes. CONCLUSION: This study shows minor differences in process markers and no difference in clinical outcomes between patients in a clinical trial and patients receiving protocol driven care. The benefits of improved clinical care that have previously been associated with being in a trial may be explained by the use of clear clinical protocols. In routine practice, patients may be well advised to insist on treatment as part of a protocol.

Clinical Protocols↗
PubMed2005

Evaluation of the implementation of the alert issued by the UK National Patient Safety Agency on the storage and handling of potassium chloride concentrate solution.

OBJECTIVES: To assess the effectiveness of the response of NHS hospital trusts to an alert issued by the National Patient Safety Agency designed to limit the availability of concentrated potassium chloride in hospitals in England and Wales, and to determine the nature of any unintended consequences. DESIGN: Multi-method study involving interviews and a physical inspection of clinical areas. SETTING: 207 clinical areas in 20 randomly selected acute NHS trusts in England and Wales between 31 October 2002 and 31 January 2003. PARTICIPANTS: Senior managers and ward based medical and nursing staff. MAIN OUTCOME MEASURES: Degree of staff awareness of and compliance with the requirements of the national alert, withdrawal of concentrated potassium chloride solutions from non-critical areas, provision of pre-diluted alternatives, storage and recording in accordance with controlled drug legislation. RESULTS: All trusts required that potassium chloride concentrate be stored in a separate locked cup-board from common injectable diluents (100% compliance). Unauthorized stocks of potassium chloride were found in five clinical areas not authorized by the trust (98% compliance). All trusts required documentation control of potassium chloride concentrate in clinical areas, but errors were recorded in 20 of the 207 clinical areas visited (90% compliance). Of those interviewed, 78% of nurses and 30% of junior doctors were aware of the alert. CONCLUSIONS: The NPSA alert was effective and resulted in rapid development and implementation of local policies to reduce the availability of concentrated potassium chloride solutions. The success is likely to be partly due to the nature of the proposed changes and it cannot be assumed that future alerts will be equally effective. Continued vigilance will be necessary to help sustain the changes.

Drug Storage↗
PubMed2004

Oral appliances for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea-hypopnoea is a syndrome characterised by recurrent episodes of partial or complete upper airway obstruction during sleep that are usually terminated by an arousal. Nasal continuous positive airway pressure is the primary treatment for obstructive sleep apnoea-hypopnoea, but many patients are unable or unwilling to comply with this treatment. Oral appliances are an alternative treatment for sleep apnoea. OBJECTIVES: The objective was to review the effects of oral appliance in the treatment of sleep apnoea in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Sleep Apnoea RCT Register. Searches were current as of June 2004. Reference lists of articles were also searched. SELECTION CRITERIA: Randomised trials comparing oral appliance with control or other treatments in adults with sleep apnoea. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two reviewers extracted data independently. Study authors were contacted for missing information. MAIN RESULTS: Thirteen trials involving 553 participants were included. All the studies had some shortcomings, such as small sample size, under-reporting of methods and data, and lack of blinding. Oral appliances versus control appliances (five studies): Oral appliances reduced daytime sleepiness in two crossover trials (WMD -1.81 [95%CI: -2.72, -0.90]), and improved apnoea-hypopnoea index (AHI) (-13.17 [-18.53 to -7.80] parallel group data - four studies). Oral appliances versus CPAP (seven studies): Oral appliances were less effective than continuous positive pressure in reducing apnoea-hypopnoea index (WMD 13 [95% CI: 7.63, 18.36], parallel studies - two trials; WMD 6.96 [4.82, 9.10] cross-over studies - six trials). However, no significant difference was observed on symptom scores. Nasal continuous positive pressure was more effective at improving minimum arterial oxygen saturation during sleep compared with oral appliance. In two small crossover studies, participants preferred oral appliance therapy to continuous positive airways pressure. Oral appliances versus surgery (one study): Symptoms of daytime sleepiness were initially lower with surgery, but this difference disappeared at 12 months. AHI did not differ significantly initially, but did so after 12 months in favour of OA. REVIEWERS' CONCLUSIONS: There is some evidence suggesting that oral appliance improves subjective sleepiness and sleep disordered breathing compared with a control. Nasal continuous positive airways pressure appears to be more effective in improving sleep disordered breathing than oral appliance. Until there is more definitive evidence on the effectiveness of oral appliances, it would appear to be appropriate to restrict oral appliance therapy to patients with sleep apnoea who are unwilling or unable to comply with continuous positive airways pressure therapy.

Adult↗
PubMed2004

Interactions of poly(amino acids) in aqueous solution with charged model surfaces--analysis by colloidal probe.

Biomolecules in a confined solution environment may be subject to electrostatic forces with a range up to 100 nm, while van der Waals interaction will account for shorter-range forces. The response of two model poly(amino acids)--poly-L-lysine and poly-L-glutamic acid--has been investigated for a silica/Si-oxide surface at pH 6. The model amino acids were adsorbed, or covalently coupled, to colloidal probes consisting of a microsphere attached to a force-sensing lever. The methodology was based on sensing interaction between the probe and a flat surface through carrying out force versus distance analysis with a scanning force microscope. The results were analyzed within the framework of the conventional DLVO theory. The outcomes illustrate both repulsive and attractive long-range interactions that will hinder, or promote, colloidal biospecies in solution entering the region of attractive short-range interactions at the physical interface. Large 'snap-on' distances were observed for some systems and have been ascribed to compression of the 'soft' functionalized layers. Those observations and measurements of adhesion provided insight into conformation of the adsorbed species and strength of attachment. The results have implications for the efficacy of methods and devices that seek to exploit the properties of micro/nano-fluidic systems.

Data Interpretation, Statistical↗
PubMed2004

Usefulness of Blalock-Taussig shunt Doppler flow velocity profiles in the assessment of pulmonary artery pressure and flow.

AIM: To assess the utility of continuous wave Doppler evaluation of velocity profiles across a Blalock-Taussig (BT) shunt in the evaluation of pulmonary artery pressure and pulmonary blood flow. METHODS AND RESULTS: Eleven children with complex congenital heart disease with a BT shunt as the sole source of pulmonary blood supply were studied prospectively (median age 5 (0.3-21) months). Doppler evaluations of shunt flow velocity profile and cardiac catheterization were carried out simultaneously. Pulmonary artery pressure and flow were estimated using the modified Bernoulli equation and velocity time integral of shunt flow. There was a positive correlation between (1) the Doppler estimates for mean pulmonary artery pressure, using the diastolic flow velocity, and the mean pulmonary venous wedge pressure ( r = 0.93, SEE = 1.0 mmHG; P<0.001 ) and (2) the Doppler derived and calculated pulmonary blood flow ( r = 0.9, SEE = 0.19 l/min; P<0.001). In contrast, the Doppler estimates for mean pulmonary artery pressure using the peak or mean Doppler gradients were poor. CONCLUSION: The diastolic BT shunt flow velocity can be used reliably to predict mean pulmonary artery pressure when a BT shunt is the sole source of pulmonary artery flow. There was agreement between Doppler predicted pulmonary blood flow and catheter based calculations. These findings may prove a useful tool for perioperative management.

Arteriovenous Shunt, Surgical↗
PubMed2004

Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study.

BACKGROUND: CDP870 is a PEGylated Fab' fragment of a humanized monoclonal antibody that neutralizes tumour necrosis factor-alpha. AIM: To evaluate the safety and efficacy of a single intravenous dose of CDP870 or placebo over a 12-week period in patients with moderate-to-severe Crohn's disease. METHODS: Ninety-two adult patients with Crohn's disease (Crohn's Disease Activity Index: 220-450 points) were randomized to receive CDP870 [1.25 (n = 2), 5 (n =26), 10 (n = 17) or 20 mg/kg (n = 23)] or placebo (n = 24). Crohn's Disease Activity Index scores were determined at weeks 0, 2, 4, 8 and 12. The primary end-point was the percentage of patients achieving clinical response [i.e. a decrease in Crohn's Disease Activity Index score > or = 100 points or remission (Crohn's Disease Activity Index score: < or =150 points)] at week 4 in the intent-to-treat population. RESULTS: The percentage of patients achieving the primary end-point was comparable across all treatment groups (56.0%, 60.0%, 58.8% and 47.8% for placebo, CDP870 5, 10 and 20 mg/kg, respectively). The remission rate at week 2 was 47.1% with CDP870 10 mg/kg vs. 16.0% for placebo (P = 0.041). All treatments were well-tolerated: adverse events, reported by 43 patients treated with CDP870 and 15 patients treated with placebo, were mainly mild-to-moderate in intensity. There were no infusion reactions. CONCLUSIONS: A single intravenous dose of CDP870 was well-tolerated by patients with Crohn's disease. While no statistically significant difference in clinical response rates between CDP870 and placebo was observed, clinical benefit in terms of remission was demonstrated.

Adolescent↗
PubMed2004

Day case management of sickle pain: 3 years experience in a UK sickle cell unit.

A day centre was established to determine whether an alternative approach to the management of uncomplicated sickle pain would improve the quality of care and reduce hospital admissions in patients with sickle cell disease. Since the centre opened there has been a 43% decrease in hospital admissions and 49% decrease in occupied bed days. In the third year, 84% of patients treated for severe sickle pain were managed without the need for hospital admission. A centre offering day case management of painful crisis reduced unnecessary hospital admissions for uncomplicated pain. This approach is safe and cost-effective.

Ambulatory Care↗
PubMed2004

Risk factors for venous thrombosis in medical inpatients: validation of a thrombosis risk score.

BACKGROUND/OBJECTIVES: The occurrence of and risk factors for venous thrombosis (VT) complicating hospital admission in unselected medical inpatients have not been widely studied. PATIENTS AND METHODS: In a 400-bed teaching hospital we identified all cases of VT complicating hospital admission between September 2000 and September 2002 using discharge codes and chart review. Controls were randomly selected adult inpatients frequency matched to cases for medical service. RESULTS: The incidence of VT complicating hospital admission was 7.6 per 1000 admissions. On average, VT was diagnosed on the fifth hospital day. The median age of the 65 cases and 123 controls was 68 years and 45% were men. Cases had a 4-fold higher death rate than controls [95% confidence interval (CI) 1.9, 8.8]. At admission, trauma within 3 months, leg edema, pneumonia, platelet count > 350 x 10(3) mm(-3) and certain cancers were associated with risk of VT. Age, body mass index, and acute myocardial infarction were not associated with VT risk. One of three published VT risk models was able to risk stratify patients and was associated with a 2.6-fold increased risk of VT (95% CI 1.3, 5.5). Use of VT prophylaxis did not differ in cases and controls; prophylaxis was used < 1/3 of hospital days in 52% of patients. CONCLUSIONS: VT was common among medical inpatients. Of the risk factors identified, elevated platelet count has not been previously reported. Only one of three published risk scores was associated with risk of inpatient VT. Future study should improve upon risk prediction models for in-hospital VT among medical patients.

Adolescent↗
PubMed2003

Effect of a novel 5-HT3 receptor agonist MKC-733 on upper gastrointestinal motility in humans.

BACKGROUND: Although 5-HT3 antagonists have been used to treat chemotherapy-induced emesis and diarrhoea-predominant irritable bowel syndrome, the effects of 5-HT3 agonists in humans are unknown. AIM: To determine the effect of MKC-733, a selective 5-HT3 receptor agonist, on upper gastrointestinal motility. METHODS: Oral MKC-733 (0.2, 1 and 4 mg) was compared with placebo in three randomized, double-blind, cross-over studies in healthy males. Antroduodenal manometry was recorded for 8 h during fasting and 3 h post-prandially (n = 12). Gastric emptying and small intestinal transit were determined by gamma-scintigraphy (n = 16). Gastric emptying, accommodation and antral motility were determined by echoplanar magnetic resonance imaging (n = 12). RESULTS: MKC-733 (4 mg) increased the number of migrating motor complexes recorded in the antrum and duodenum (P < 0.001), but had no effect on post-prandial motility. MKC-733 delayed scintigraphically assessed liquid gastric emptying (P = 0.005) and accelerated small intestinal transit (P = 0.038). Echoplanar magnetic resonance imaging confirmed the delayed gastric emptying (P < 0.001) and demonstrated a significant increase in cross-sectional area of the proximal stomach (P < 0.01). CONCLUSIONS: MKC-733 delays liquid gastric emptying in association with relaxation of the proximal stomach, stimulates fasting antroduodenal migrating motor complex activity and accelerates small intestinal transit.

Adolescent↗
PubMed2003

Comparative genome analysis of Campylobacter jejuni using whole genome DNA microarrays.

Whole genome DNA microarrays were constructed and used to investigate genomic diversity in 18 Campylobacter jejuni strains from diverse sources. New algorithms were developed that dynamically determine the boundary between the conserved and variable genes. Seven hypervariable plasticity regions (PR) were identified in the genome (PR1 to PR7) containing 136 genes (50%) of the variable gene pool. When comparisons were made with the sequenced strain NCTC11168, the number of absent or divergent genes ranged from 2.6% (40 genes) to 10.2% (163) and in total 16.3% (269) of the genes were variable. PR1 contains genes important in the utilisation of alternative electron acceptors for respiration and may confer a selective advantage to strains in restricted oxygen environments. PR2, 3 and 7 contain many outer membrane and periplasmic proteins and hypothetical proteins of unknown function that might be linked to phenotypic variation and adaptation to different ecological niches. PR4, 5 and 6 contain genes involved in the production and modification of antigenic surface structures.

Algorithms↗
PubMed2003

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy--a prospective, randomised, double-blind trial.

BACKGROUND: Peristomal infection can sometimes complicate percutaneous endoscopic gastrostomy (PEG) placement. Antibiotic prophylaxis has, in some studies, been shown to reduce the incidence. However, the use of prophylaxis varies widely, possibly because the design and findings of the studies have differed, making their relevance to clinical practice difficult to interpret. AIM: To determine the efficacy of antibiotics, either prophylaxis or concurrent antibiotics at the time of the procedure, in reducing peristomal infection after PEG insertion in the context of a study designed to reflect current practice. METHODS: One hundred and forty-one patients undergoing PEG placement were randomised to group one to receive either a single dose of 750 mg of intravenous cefuroxime (n=50) or placebo (n=51) 30 min before PEG insertion. Forty patients who, for various reasons, were already receiving antibiotics were allocated to group two. The peristomal site was evaluated on day 3, 5 and 7 following insertion. Erythema and exudate were scored on a scale from 0 to 4; induration was scored on a scale of 0-3. A maximum combined score of 8 or higher or the presence of pus was criteria for infection. The primary outcome measure was the occurrence of a peristomal wound infection at any time within one week of PEG insertion. RESULTS: Peristomal wound infection was significantly reduced in patients who received antibiotics either as a single dose of cefuroxime [one of 33 (3%)], or in those on antibiotics for prior indications [one of 36 (3%)], compared with placebo [six of 33 (18%)], P=0.04 and 0.03, respectively. CONCLUSION: Antibiotics, either prophylaxis or concurrent, reduce the incidence of peristomal wound infection after PEG placement.

Adult↗