Survival after resection for primary lung cancer.
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Humans↗
Biomedical subjects
M Utley
Publications and source records attributed to M Utley.
A prospective randomized controlled trial of suction versus non-suction to the under-water seal drains following lung resection.
OBJECTIVE: Practice varies as to whether or not suction is applied to under-water seal drains following lung surgery. We tested the null hypothesis that there is no difference with respect to air leak duration. METHODS: Patients undergoing thoracotomy or video assisted thoracoscopic surgery for lobectomy or wedge resection had either low-pressure suction or no suction applied to their underwater seal bottles postoperatively. Patients were allocated using minimization, a method of unbiased allocation ensuring balance between the arms of a trial with respect to known or suspected confounding factors. The trial was powered for duration of air leak. If an air leak persisted on the 7th post-operative day, the surgeon determined further management. Kaplan-Meier survival analysis of air leak duration and a log rank test were performed on an intention-to-treat basis, with observations censored at 144h (6 complete days). RESULTS: Of the 254 patients that entered the trial, data were available for analysis for 239 (123 no-suction and 116 suction). There was no significant difference in the cumulative persistence of air leaks between the two groups (P=0.62) and inspection of the Kaplan-Meier curves suggests that any difference is negligible. CONCLUSIONS: Applying suction to the underwater seal drains following lung surgery makes no difference in terms of air leak duration. In the light of this finding we have adopted a uniform policy of no suction being applied to the underwater seal, from the time of surgery, unless a specific clinical judgment is made to use it. The anticipated gains are that this will reduce work and cost and aid mobilization.
Adult↗
Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis.
OBJECTIVES: To compare the effects of combined hydrotherapy and land-based physiotherapy (combined) with land-based physiotherapy only (land) on cost, health-related quality of life (HRQoL) and outcome of disease in children with juvenile idiopathic arthritis (JIA). Also to determine the cost-effectiveness of combined hydrotherapy and land-based physiotherapy in JIA. DESIGN: A multicentre randomised controlled, partially blinded trial was designed with 100 patients in a control arm receiving land-based physiotherapy only (land group) and 100 patients in an intervention arm receiving a combination of hydrotherapy and land-based physiotherapy (combined group). SETTING: Three tertiary centres in the UK. PARTICIPANTS: Patients aged 4-19 years diagnosed more than 3 months with idiopathic arthritides, onset before their 16th birthday, stable on medication with at least one active joint. INTERVENTIONS: Patients in the combined and land groups received 16 1-hour treatment sessions over 2 weeks followed by local physiotherapy attendances for 2 months. MAIN OUTCOME MEASURES: Disease improvement defined as a decrease of > or =30% in any three of six core set variables without there being a 30% increase in more than one of the remaining three variables was used as the primary outcome measure and assessed at 2 months following completion of intervention. Health services resource use (in- and outpatient care, GP visits, drugs, interventions, and investigations) and productivity costs (parents' time away from paid work) were collected at 6 months follow-up. HRQoL was measured at baseline and 2 and 6 months following intervention using the EQ-5D, and quality-adjusted life-years (QALYs) were calculated. Secondary outcome measures at 2 and 6 months included cardiovascular fitness, pain, isometric muscle strength and patient satisfaction. RESULTS: Seventy-eight patients were recruited into the trial and received treatment. Two months after intervention 47% patients in the combined group and 61% patients in the land group had improved disease with 11 and 5% with worsened disease, respectively. The analysis showed no significant differences in mean costs and QALYs between the two groups. The combined group had slightly lower mean costs (-6.91 pounds Sterling) and lower mean QALYs (-0.0478, 95% confidence interval -0.11294 to 0.0163 based on 1000 bootstrap replications). All secondary measures demonstrated a mean improvement in both groups, with the combined group showing greater improvements in physical aspects of HRQoL and cardiovascular fitness. CONCLUSIONS: JIA is a disease in which a cure is not available. This research demonstrates a beneficial effect from both combined hydrotherapy and land-based physiotherapy treatment and land-based physiotherapy treatment alone in JIA without any exacerbation of disease, indicating that treatments are safe. The caveat to the results of the cost-effectiveness and clinical efficacy analysis is that the restricted sample size could have prevented a true difference being detected between the groups. Nevertheless, there appears to be no evidence to justify the costs of building pools or initiating new services specifically for use in this disease. However, this conclusion may not apply to patients with unremitting active disease who could not be entered into the trial because of specified exclusion criteria. For this group, hydrotherapy or combined treatment may still be the only physiotherapy option. Further research is suggested into: the investigation and development of appropriate and sensitive outcome measures for use in future hydrotherapy and physiotherapy trials of JIA; preliminary studies of methodologies in complex interventions such as physiotherapy and hydrotherapy to improve recruitment and ensure protocol is acceptable to patients and carers; hydrotherapy in the most common paediatric user group, children with neurological dysfunction, ensuring appropriate outcome measures are available and methodologies previously tried; patient satisfaction and compliance in land-based physiotherapy and hydrotherapy and European studies of hydrotherapy in rare disorders such as JIA.
Adolescent↗
A health impact assessment model for environmental changes attributable to development projects.
STUDY OBJECTIVE: European Union legislation requires large industrial and civil development projects to undergo environmental impact assessment. The study objective was to identify environmental health risk estimates for these developments from the epidemiological literature and to develop, and apply these within, a mathematical health impact assessment model. DESIGN AND RESULTS: In the UK, good practice guidelines have set out environmental issues to be considered in development projects, but little attention is given to direct health effects. Broad quantifiable risks were identified for four-air, chemicals, noise, and road traffic-of 14 standard environmental effects. A mathematical model was constructed that is based on people moving between different health states over their lifetime. Age related hazard functions are applied to cause specific measures of mortality and morbidity. A hypothetical example for a development creating air and chemical pollutants is given. CONCLUSIONS: A mathematical model applying epidemiological risks to an exposed population can provide quantification of environmental health effects. The approach may in future find application during project development, and by public health regulatory authorities for environmental health impact assessment.
Air Pollution↗
Opinions and experiences in general practice on osteoporosis prevention, diagnosis and management.
We determined to survey the general practice population regarding their attitudes to and knowledge of osteoporosis as a baseline prior to publication of national guidelines for the management of osteoporosis. All 2515 general practitioners registered in the 10 Health Authorities of the North Thames region, London, UK were surveyed by a postal questionnaire. Responses relating to epidemiology, public health and education on osteoporosis were analyzed. The overall response was 1153 (46%). General practitioners who responded were younger, predominantly female and in group practice. There is considerable awareness of the importance of preventing osteoporosis. General practitioners are active in identifying groups at risk, particularly those who are aged 40 years and older. A prevention strategy for osteoporosis is viewed as effective. However, two thirds of general practitioners remain unconvinced about the efficacy of drug therapy. Education on osteoporosis is considered inadequate. General practitioners would welcome further information on management issues and access to osteoporosis services. In conclusion, educational initiatives will be important both at undergraduate and postgraduate levels to increase awareness and knowledge of osteoporosis. General practitioners are aware of the public health impact of this condition and express a preference for educational material of direct relevance to the care of their patients. Therefore better cooperation between primary and secondary care should lead to ways of breaking down barriers to change in clinical practice and promoting fully integrated care of patients with osteoporosis.
Attitude of Health Personnel↗
Specific phospholipids enhance the activity of beta-lactam antibiotics against Pseudomonas aeruginosa.
Pseudomonas aeruginosa PAO1 became considerably more sensitive to the action of ampicillin when grown in the presence of certain phospholipids. Only phospholipids capable of forming lipid bilayers or micelles proved to be capable of enhancing ampicillin activity. Of the phospholipids tested, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphate, also called monopalmitoylphosphatidic acid (MPPA), was the best enhancer. In the absence of MPPA, the MIC and MBC of ampicillin for P. aeruginosa PAO1 were 1 and 2 g/L, respectively. In the presence of MPPA, the MIC and MBC were 20 and 40 mg/L, respectively. MPPA was shown to enhance ampicillin activity by binding both Ca(2+) and Mg(2+), suggesting that the mechanism of enhancement is similar to that previously reported for Ca(2+) and Mg(2+) chelators. Surprisingly, MPPA by itself slowed the growth of four mucoid multiply antibiotic-resistant strains of P. aeruginosa recently isolated from the sputum of cystic fibrosis patients, and enhanced their sensitivity to piperacillin. It also increased the sensitivity of two ceftazidime-resistant P. aeruginosa cystic fibrosis strains to ceftazidime.
Ampicillin↗
Potential bias in Kaplan-Meier survival analysis applied to rheumatology drug studies.
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Antirheumatic Agents↗
A functional cra gene is required for Salmonella enterica serovar typhimurium virulence in BALB/c mice.
A minitransposon mutant of Salmonella enterica serovar Typhimurium SR-11, SR-11 Fad(-), is unable to utilize gluconeogenic substrates as carbon sources and is avirulent and immunogenic when administered perorally to BALB/c mice (M. J. Utley et al., FEMS Microbiol. Lett., 163:129-134, 1998). Here, evidence is presented that the mutation in SR-11 Fad(-) that renders the strain avirulent is in the cra gene, which encodes the Cra protein, a regulator of central carbon metabolism.
Animals↗
Correlation analysis versus Bland-Altman analysis: comment on the article by Genant et al.
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Arthritis, Rheumatoid↗
Larsen scoring of digitized X-ray images.
OBJECTIVE: To determine how Larsen scores from digitized X-rays compare to those from film originals. METHODS: A hundred sets of radiographs of patients recruited with early rheumatoid arthritis (RA) were assessed using the Larsen scoring system. Digitized copies of these sets were then viewed on a computer screen and scored according to Larsen in a random order. The quality of the digitized image was also recorded. For each set of X-rays, the signed difference between the score from film and the score from the digitized images was calculated. RESULTS: A total of 95% of the digitized X-ray sets were scored successfully; 5% were not scored due to the images being unreadable. The mean difference between the two sets of scores was -1.2 (95% CI [-2.06, -0.37]). There was no trend in the difference with respect to the mean of the two scores (P>0.1). CONCLUSION: The Larsen scoring of digitized X-ray images has been validated.
Analog-Digital Conversion↗
A Salmonella typhimurium mutant unable to utilize fatty acids and citrate is avirulent and immunogenic in mice.
Salmonella typhimurium SR-11 is extremely virulent at a dose as low as 10(5) colony forming units (cfu) when administered perorally to BALB/c mice. Utilizing mini-transposon mutagenesis, a mutant of S. typhimurium SR-11 was isolated that was unable to utilize oleate and citrate as carbon sources. This mutant, designated S. typhimurium SR-11 Fad- (Fatty acid), was found to utilize sugars under cya/crp control as sole carbon sources, suggesting that the mutation is not in either of these genes. In addition, SR-11 Fad- utilized pyruvate and succinate, but was unable to utilize either acetate or isocitrate as sole carbon source. In contrast to SR-11, SR-11 Fad- was found to be avirulent, i.e. BALB/c mice were completely healthy after oral infection with 10(9) S. typhimurium SR-11 Fad- cells. Moreover, 21 days after SR-11 Fad- infection, BALB/c mice were found to be protected against an oral challenge with 10(9) cells of S. typhimurium SR-11.
Animals↗
The leuX-encoded tRNA5(Leu) but not the pathogenicity islands I and II influence the survival of the uropathogenic Escherichia coli strain 536 in CD-1 mouse bladder mucus in the stationary phase.
The uropathogenic Escherichia coli strain 536 carries two pathogenicity islands, each of which is associated with either of the tRNA genes selC or leuX, respectively. Growth competition in CD-1 mouse mucus between the wild-type strain E. coli 536, its leuX mutant 536 delta 102 and its mutant 536R3, lacking both pathogenicity islands but expressing a functional tRNA5(Leu), revealed a major impact of leuX on E. coli survival in bladder mucus. The impaired survival in CD-1 mouse mucus observed upon deletion of the leuX gene was abolished after complementation with the leuX gene. The survival of bacteria in bladder mucus was not influenced by the presence of pathogenicity islands I and II.
Animals↗
Isolation and characterization of an attenuated strain of Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader.
Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader, is a mouse pathogen and has a reported 50% lethal dose (LD50) of 1.05 x 10(7) CFU when given intranasally to C3H/HeJ mice (S.E. George, M.J. Kohan, M.I. Gilmour, M.S. Taylor, H.G. Brooks, J.P. Creason, and L.D. Claxton, Appl. Environ, Microbiol. 59:3585-3591, 1993). AC869 was serotyped as O6 when grown in CD-1 mouse cecal and lung mucus but could not be assigned an O serotype when grown in Luria broth (LB). After growth in mouse cecal mucus, a less virulent mutant, AC869-11, was isolated from AC869 by using bacteriophage E79, which adsorbs to the O side chain of lipopolysaccharide (LPS). AC869-11 produced significantly less O antigen on its LPS than AC869 when grown in mouse lung and cecal mucus. The mutant also produced half the amount of exoenzyme S and 16-fold less extracellular protease than AC869 and was more sensitive than its parent to a number of antibiotics when grown either in LB or in mouse lung mucus. AC869-11 had ninefold higher LD50 than AC869 in CD-1 mice when administered intranasally. AC869-11 was found in the lungs, small intestine, cecum, and large intestine in numbers at least 100-fold below AC869, 3 h after intranasal exposure of mice to a sublethal dose of the two strains. Moreover, AC869-11 induced a decreased pulmonary inflammatory response relative to AC869. In contrast to AC869, AC869-11 did not translocate to the mesenteric lymph nodes, liver, and spleen following a sublethal dose. Despite attenuation, AC869-11 grew as well as AC869 with 3,5-dichlorobenzoate as the sole carbon and energy source. However, although AC869-11 survived in 3,5-dichlorobenzoate-contaminated soil as well as AC869 for 1 week, it failed to survive as well thereafter. These results suggest the possibility that mutations that lead to pulmonary attenuation of P. aeruginosa in mice also lead to weakness in the environment, despite such mutants maintaining the ability to degrade toxic substances under laboratory conditions.
Animals↗
The Escherichia coli K-12 gntP gene allows E. coli F-18 to occupy a distinct nutritional niche in the streptomycin-treated mouse large intestine.
Escherichia coli F-18 is a human fecal isolate that makes type 1 fimbriae, encoded by the fim gene cluster, and is an excellent colonizer of the streptomycin-treated mouse intestine. E. coli F-18 fimA::tet, lacking type 1 fimbriae, was constructed by bacteriophage P1 transduction of the fim region of the E. coli K-12 strain ORN151, containing the tetracycline resistance gene from Tn10 inserted in the fimA gene, into E. coli F-18. E. coli F-18 fimA::tet was found to occupy a distinct niche in the streptomycin-treated mouse intestine when fed in small numbers (10(4) CFU) to mice, along with large numbers (10(10) CFU) of E. coli F-18, as defined by the ability of the E. coli F-18 fimA::tet strain to grow and colonize only 1 order of magnitude below E. coli F-18. The same effect was observed when mice already colonized with E. coli F-18 were fed small numbers of E. coli F-18 fimA::tet. Experiments which show that the E. coli K-12 gene responsible for this effect is not fim::tet but gntP, which maps immediately downstream of the fim gene cluster, are presented. gntP encodes a high-affinity gluconate permease, suggesting that the distinct niche in the mouse large intestine is defined by the presence of gluconate. The data presented here support the idea that small numbers of an ingested microorganism can colonize the intestine as long as it can utilize an available nutrient better than any of the other resident species can.
Animals↗
Identification of systems failures in successful paediatric cardiac surgery.
Patient safety will benefit from an approach to human error that examines systemic causes, rather than blames individuals. This study describes a direct observation methodology, based on a threat and error model, prospectively to identify types and sources of systems failures in paediatric cardiac surgery. Of substantive interest were the range, frequency and types of failures that could be identified and whether minor failures could accumulate to form more serious events, as has been the case in other industries. Check lists, notes and video recordings were employed to observe 24 successful operations. A total of 366 failures were recorded. Coordination and communication problems, equipment problems, a relaxed safety culture, patient-related problems and perfusion-related problems were most frequent, with a smaller number of skill, knowledge and decision-making failures. Longer and more risky operations were likely to generate a greater number of minor failures than shorter and lower risk operations, and in seven higher-risk cases frequently occurring minor failures accumulated to threaten the safety of the patient. Non-technical errors were more prevalent than technical errors and task threats were the most prevalent systemic source of error. Adverse events in surgery are likely to be associated with a number of recurring and prospectively identifiable errors. These may be co-incident and cumulative human errors predisposed by threats embedded in the system, rather than due to individual incompetence or negligence. Prospectively identifying and reducing these recurrent failures would lead to improved surgical standards and enhanced patient safety.
Adolescent↗