Assessment of generalisability in trials of health interventions: suggested framework and systematic review.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Biomedical subjects
J Hargreaves
Publications and source records attributed to J Hargreaves.
Myocarditis and myositis due to infection with Hepatozoon species in pine martens (Martes martes) in Scotland.
Postmortem examinations of four pine martens which had died as a result of road accidents in Scotland revealed focal, granulomatous lesions in the heart and skeletal muscles of three of them. An immunoperoxidase staining technique showed that the lesions were due to infection with Hepatozoon species. A PCR-based assay was used to confirm the presence of Hepatozoon DNA in the infected tissues. The nucleotide base sequence of the PCR products suggested that the infecting organism was probably a new species of Hepatozoon, most closely related to, but distinct from, Hepatozoon canis. The pine martens were in good physical condition and there was no indication that the infection was causing ill health.
Animals↗
Reviewing measures of outcome: reliability of data extraction.
RATIONALE, AIMS AND OBJECTIVES: Although there is wide acceptance of the necessary domains for the evaluation of measures of health outcome, there has been little development or evaluation of methods of data extraction, such as checklists. This study aimed to assess the inter-rater reliability of data extraction from published articles using a new electronic database developed for structured reviews of health outcome measures. METHODS: Domains considered important in the evaluation of measures of health outcome provided the foundation for a checklist for data extraction using a new electronic database. The database utilized Microsoft Access 2000 software (Microsoft Corporation, 2000). Following training, three independent reviewers extracted data from seven selected articles using the electronic database, and assessed article and measure quality against pre-defined criteria. Data extraction was compared for consistency and item content. Inter-reviewer agreement for categorical data was assessed by multiple kappa correlation. RESULTS: Analysis demonstrated strong agreement between reviewers for all aspects of data extraction. However, lack of clarity in published articles affected the ability to clearly identify measures of outcome. CONCLUSIONS: The high level of inter-reviewer agreement supports the use of multiple trained reviewers in data extraction for reviews of measures of outcome using the checklist and Access software described. The electronic database supports standardized data extraction from published articles, benefiting from the combination of data extraction and data entry in a single step. Adaptation of the database to support structured reviews of measures of outcome adopted in the evaluation of other health states is proposed.
Ankle Injuries↗
Multi-item outcome measures for lateral ligament injury of the ankle: a structured review.
OBJECTIVE: To identify and review evidence relating to the measurement properties of published multi-item outcome measures for the conservative management of lateral ligament injuries of the ankle. METHODS: Systematic literature searches were used to identify measures, which were then assessed against pre-defined criteria relating to development, item content, reliability, validity and responsiveness. RESULTS: Seven disease-specific measures of ankle status [Ankle Joint Functional Assessment Tool, Clinical Trauma Severity Score, Composite Inversion Injury Scale, Kaikkonen Functional Scale (KFS), Karlsson Ankle Function Score (KAFS), Olerud and Molander Ankle Score (OMAS), and the Point System] and two generic measures of health (McGill Pain Questionnaire, Sickness Impact Profile) met the review inclusion criteria. While all measures had been used in acute injuries, only two had also been applied during later stages of recovery (>6 months). The studies covered a comprehensive range of graded ligament injuries. Expert opinion dominated item generation for all measures. All measures lack evidence of test-retest or internal consistency reliability in patients with ankle sprain. Several measures were assessed for validity through comparison with other measures, but there was limited evidence of construct validity and no formal assessment of responsiveness for any measure. CONCLUSION: The disappointing lack of evidence for measurement properties suggests that any measure should be used with caution until appropriate evidence is provided. On the basis of limited evidence, the KFS offers the most promising approach to a combined clinician- and patient-assessment of ankle function, and the KAFS or OMAS if a patient-assessed evaluation of function is required.
Adult↗
Severe complications of hysterectomy: the VALUE study.
OBJECTIVES: To model the determinants of serious operative and post-operative complications of hysterectomy and their potential risk factors. DESIGN: A prospective cohort of women undergoing hysterectomies for benign indications in 1994/1995, with a six-week postsurgery follow up. POPULATION AND SETTING: A total of 37,512 women from 276 NHS and 145 private hospitals in England, Wales and Northern Ireland, originally recruited to compare the outcomes of endometrial destruction with those of hysterectomy. METHODS: Gynaecologists reported hysterectomies for non-malignant indications carried out during a 12-month period beginning in October 1994 and follow up data were obtained at outpatient follow up six weeks postsurgery. Odds ratios of severe complications by indication and method, adjusting for measured intrinsic risk factors, were calculated. MAIN OUTCOME MEASURES: Severe operative and post-operative complications. RESULTS: Severe operative complications occurred in 3%. The risk decreased with age and increased with greater parity and history of serious illness. Women with symptomatic fibroids (4.4%, 95% CI 3.9-4.9) experienced more complications than women with dysfunctional uterine bleeding (3.6%, 3.2-3.8), adjusted odds ratio (OR) = 1.3 (95% CI 1.1-1.6). Laparoscopic procedures (6.1%) doubled the risk of operative complications of abdominal hysterectomy (3.6%) (adjusted OR = 1.9, 1.5-2.5). Post-operative complications occurred in around 1% of women, with a slight decrease with increasing age, and the strongest risk factor was a history of operative complications. Relative to dysfunctional uterine bleeding (1.0%), a higher risk for fibroids (1.2%) persisted after adjustments (RR = 1.5, 1.1-2.0). Both vaginal (1.2%) and laparoscopic (1.7%) techniques had significantly higher adjusted risks than abdominal operations (0.9%), RR = 1.4 (1.0-1.9) and RR = 1.6 (1.0-2.7). There were no operative deaths; 14 women died within the six-week postsurgery (a crude mortality rate of 3.8/1000, 2.5-6.4). CONCLUSIONS: Hysterectomy is a common, routine surgery with comparatively rare serious complications. However, younger women, women with more vascular pelvis, who undergo hysterectomy, especially laparoscopically assisted vaginal surgery for symptomatic fibroids, are at most risk of experiencing severe complications both operatively and post-operatively. Therefore, a less invasive alternative treatment for symptomatic fibroids could particularly benefit this group of women, while less invasive treatments for dysfunctional uterine bleeding, such as various methods of endometrial ablations or resections, would need to meet the current low levels of clinical complications in order to replace hysterectomy.
Adolescent↗
The VALUE national hysterectomy study: description of the patients and their surgery.
OBJECTIVES: To describe hysterectomies practised in 1994 and 1995: the patients, their surgery and short term outcomes. DESIGN: One of two large cohorts, with prospective follow up, recruited to compare the outcomes of endometrial destruction with those of hysterectomy. SETTING: England, Wales and Northern Ireland. POPULATION: All women who had hysterectomies for non-malignant indications carried out during a 12-month period. METHODS: Gynaecologists in NHS and independent hospitals were asked to report cases. Follow up data were obtained at outpatient follow up approximately six weeks post-surgery. MAIN OUTCOME MEASURES: Indication for surgery, method of hysterectomy, ovarian status post-surgery, surgical complications. RESULTS: 37,298 cases were reported which is estimated to reflect about 45% of hysterectomies performed during the period studied. The median age was 45 years, and the most common indication for surgery was dysfunctional uterine bleeding (46%). Most hysterectomies were carried out by consultants (55%). The proportions of women having abdominal, vaginal or laparoscopically-assisted hysterectomy were 67%, 30% and 3%, respectively. Forty-three percent of women had no ovaries conserved after surgery. The median length of stay was five days. The overall operative complication rate was 3.5%, and highest for the laparoscopic techniques. The overall post-operative complication rate was 9%. One percent of these was regarded as severe, with the highest rate for severe in the laparoscopic group (2%). There were no operative deaths; 14 deaths were reported within the six-week post-operative period: a crude mortality rate soon after surgery of 0.38 per thousand (95% CI 0.25-0.64). CONCLUSIONS: This large study describes women who undergo hysterectomy in the UK, and presents results on early complications associated with the surgery. Operative complications occurred in one in 30 women, and post-operative complications in at least one in 10. Laparoscopic techniques tend to be associated with higher complication rates than other methods.
Adolescent↗
Delya's story: from expert to novice, a critique of Benner's concept of context in the development of expert nursing practice.
The concepts identified within Benner's Nineteen Eighty Four research 'From Novice to Expert' have been widely adopted within UK nursing education and development. This paper combines a narrative from a post-registration student with analysis of the literature as a case study for gaining greater understanding of Benner's work in practice. Delya's story both validates aspects of the concept of skill acquisition and challenges some of the interpretations of the model within professional education. The focus of the critique of Benner's work within the literature to date has been on a deconstruction of the concepts and semantics of her work. In presenting verbatim extracts from a case study this paper seeks to move the focus to nursing practice.
Decision Making↗
Gene information for fungal plant pathogens from expressed sequences.
Gaining information on global gene function in fungal plant pathogens through analysis of expressed sequences is a valuable step towards understanding the overall metabolism and biology underlying the pathogenic habit. Such large-scale gene-finding exercises are poised to provide many useful leads for discovering key events that contribute to the processes of infection and colonisation of host plants.
Expressed Sequence Tags↗
Bacterial contamination associated with electronic faucets: a new risk for healthcare facilities.
OBJECTIVE: To investigate the safety of the hospital water supply following a major flood. DESIGN: Surveillance was conducted of the hospital water supply as it entered the hospital and at randomly selected water faucets throughout the facility. SETTING: A newly constructed surgical critical-care unit in a 265-bed community hospital that had to be evacuated and was out of operation for 6 weeks following a major flood of the city. METHODS: Random water samples throughout the facility were analyzed for heterotrophic plate counts (HPCs), chlorine, and coliforms utilizing standard methods. RESULTS: Water samples entering the hospital met appropriate standards, indicating the city water distribution system was not contaminated. Of 169 faucets tested, 13 (22%) of 59 electronic faucets exceeded the HPC threshold, and 12 (11%) of 110 manual faucets exceeded the HPC threshold (P<.14). A comparison of two brands of electronic faucets with manual faucets and with each other revealed that the HPC threshold was exceeded by 11 (32%) of 34 brand A faucets as compared to 12 (11%) of 110 manual faucets (P<.006). The HPC threshold was exceeded by 2 (8%) of 25 brand B faucets compared to 12 (11%) of 110 manual faucets (P<.94). Contamination rates of brand A and brand B faucets differed significantly (P<.003). Similar testing 2 months after hyperchlorination of the water supply indicated that the HPC threshold was exceeded by 16 (52%) of 31 brand A faucets compared to 10 (9.%) of 110 manual faucets (P<.0000003) and by 2 (18%) of 25 brand B faucets compared to 10 (9%) of 110 manual faucets (P=1.0). CONCLUSIONS: A certain brand of electronic water faucet used in the hospital was associated with unacceptable levels of microbial growth in water and was a continuing source of bacteria potentially hazardous to patients.
Chlorine↗
A group of expressed cDNA sequences from the wheat fungal leaf blotch pathogen, Mycosphaerella graminicola (Septoria tritici).
A group of expressed sequence tags (ESTs) from the wheat fungal pathogen Mycosphaerella graminicola utilizing ammonium as a nitrogen source has been analyzed. Single pass sequences of complementary DNAs from 986 clones were determined. Contig analysis and sequence comparisons allowed 704 unique ESTs (unigenes) to be identified, of which 148 appeared as multiple copies. Searches of the nrdb95 protein database at EMBL using the BLAST2x algorithm revealed 407 (57.8%) sequences that generated high to moderate high scoring pairs with proteins of known and unknown function. The rest of the sequences (297) showed either weak or no similarities to database entries. Among the unigenes with assigned function, 26.7% were involved in primary metabolism and 17.9% were associated with protein and RNA metabolism. Fewer clones were ascribed roles in signal transduction (4.9%), transport and secretion (6.1%), cell structure (3.1%), and cell division (3.6%). Approximately 18.1% of the identities found were to hypothetical or unknown proteins mainly from the yeasts Saccharomyces cerevisiae and Schizosaccaromyces pombe. Comparison of the 297 sequences with no clear function to other fungal ESTs in the public domain revealed 12 sequences that had high to moderate similarity to Neurospora crassa, Emericella (Aspergillus) nidulans, or Magnaporthe grisea sequences.
Ascomycota↗
Extensive transmission of Mycobacterium tuberculosis from a child.
BACKGROUND AND METHODS: Young children rarely transmit tuberculosis. In July 1998, infectious tuberculosis was identified in a nine-year-old boy in North Dakota who was screened because extrapulmonary tuberculosis had been diagnosed in his female guardian. The child, who had come from the Republic of the Marshall Islands in 1996, had bilateral cavitary tuberculosis. Because he was the only known possible source for his female guardian's tuberculosis, an investigation of the child's contacts was undertaken. We identified family, school, day-care, and other social contacts and notified these people of their exposure. We asked the contacts to complete a questionnaire and performed tuberculin skin tests. RESULTS: Of the 276 contacts of the child whom we tested, 56 (20 percent) had a positive tuberculin skin test (induration of at least 10 mm), including 3 of the child's 4 household members, 16 of his 24 classroom contacts, 10 of 32 school-bus riders, and 9 of 61 day-care contacts. A total of 118 persons received preventive therapy, including 56 young children who were prescribed preventive therapy until skin tests performed at least 12 weeks after exposure were negative. The one additional case identified was in the twin brother of the nine-year-old patient. The twin was not considered infectious on the basis of a sputum smear that was negative on microscopical examination. CONCLUSIONS: This investigation showed that a young child can transmit Mycobacterium tuberculosis to a large number of contacts. Children with tuberculosis, especially cavitary or laryngeal tuberculosis, should be considered potentially infectious, and screening of their contacts for infection with M. tuberculosis or active tuberculosis may be required.
Adult↗
'Levels' of attainment in nursing practice: reality or illusion?
In earlier research based on an analysis of course documentation, it had been found that there was little consensus among nurse educators concerning the parameters which distinguish levels of practice skills, particularly those which differentiate diploma and degree qualifications in the United Kingdom. This result was confirmed and strengthened in the current study. Lecturers in nursing, when presented with a sorting task using 40 statements derived from course documentation selected from the earlier study, were unable to distinguish statements describing diploma level from those describing degree level practice. Possible reasons for the difficulty are discussed. It is concluded that the attempt to represent practice skill in a hierarchy of assessment for degree or diploma qualifications is premature since the parameters of practice remain unreliably specified.
Achievement↗
Isolation and heterologous expression of a gene encoding 4-hydroxyphenylpyruvate dioxygenase from the wheat leaf-spot pathogen, Mycosphaerella graminicola.
We describe the isolation and sequence of a gene encoding 4-hydroxyphenylpyruvate dioxygenase (HPPD) (EC 1.13.11.27)) from the wheat leaf-spot fungal pathogen Mycosphaerella graminicola (Septoria tritici), that directs the synthesis of 2,5-dihydroxyphenylacetate (homogentisic acid, HGA). The sequence of the deduced peptide showed homology to HPPDs from other organisms; the greatest identity was to a T-cell reactive protein, also identified as HPPD, from the human fungal pathogen Coccidioides immitis. As observed for HPPD from other sources, expression of the M. graminicola HPPD gene in Escherichia coli cells could be detected by the gradual development of a brown pigment in cultures as a result of the spontaneous oxidation and polymerisation of HGA. Pigment development in these cultures was prevented by the HPPD inhibitor sulcotrione.
4-Hydroxyphenylpyruvate Dioxygenase↗
A single amino-acid substitution in the iron-sulphur protein subunit of succinate dehydrogenase determines resistance to carboxin in Mycosphaerella graminicola.
A gene encoding the iron-sulphur protein (Ip) subunit of succinate dehydrogenase (Sdh, EC 1.3.99.1) from Mycosphaerella graminicola (Septoria tritici) has been cloned andsequenced. The deduced amino-acid sequence exhibited a high degree of homology to Ip subunits of Sdh from other organisms; three cysteine-rich clusters associated with the iron-sulphur centres involved in electron transport were particularly conserved. Expression studies using a synthetic green fluorescent protein (SGFP) expression vector demonstrated that the cloned DNA also contained a functional promoter region and confirmed that the deduced initiation codon could act as a translational start site. Mutants resistant to the fungicide carboxin (Cbx), a known inhibitor of Sdh, were found to contain a single amino-acid substitution in the third cysteine-rich domain of the Ip protein. These mutations resulted in the conversion of a highly conserved His residue, located in a region of the protein associated with the [3Fe-4 S] high-potential non-heme iron sulphur-redox (S3) centre, to either Tyr or Leu. AnIp gene containing the His -> Tyr mutation was constructed and shown to confer Cbx resistance following co-transformation into the Cbx-sensitive wild-type strain. This confirmed that the mutation identified by sequence analysis was responsible for determining Cbx resistance.
Alleles↗
Phosphate diabetes in patients with chronic fatigue syndrome.
Phosphate depletion is associated with neuromuscular dysfunction due to changes in mitochondrial respiration that result in a defect of intracellular oxidative metabolism. Phosphate diabetes causes phosphate depletion due to abnormal renal re-absorption of phosphate be the proximal renal tubule. Most of the symptoms presented by patients with phosphate diabetes such as myalgia, fatigue and mild depression, are also common in patients with chronic fatigue syndrome, but this differential diagnosis has not been considered. We investigated the possible association between chronic fatigue syndrome and phosphate diabetes in 87 patients who fulfilled the criteria for chronic fatigue syndrome. Control subjects were 37 volunteers, who explicitly denied fatigue and chronic illness on a screening questionnaire. Re-absorption of phosphate by the proximal renal tubule, phosphate clearance and renal threshold phosphate concentration were the main outcome measures in both groups. Of the 87 patients with chronic fatigue syndrome, nine also fulfilled the diagnostic criteria for phosphate diabetes. In conclusion, we report a previously undefined relationship between chronic fatigue syndrome and phosphate diabetes. Phosphate diabetes should be considered in differential diagnosis with chronic fatigue syndrome; further studies are needed to investigate the incidence of phosphate diabetes in patients with chronic fatigue syndrome and the possible beneficial effect of vitamin D and oral phosphate supplements.
Adult↗
Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome.
The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p = 0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.
Adult↗
Using patients: exploring the ethical dimension of reflective practice in nurse education.
Within nurse education there is a growing interest in the use of reflective practice as a vehicle for professional development. Additionally, clinically reflective practice is seen as an ideal way of improving performance and patient care. In this paper it will be argued that whilst this development is potentially valuable to both professionals and clients, there are major ethical issues which need to be addressed. The "how to' literature appears to focus predominately on the practitioners subjective description and interpretation of events. It is usual for these events to include details of clients: but not usual for clients to be aware that information about them is being used in this way. Within a deontological ethical framework the use of people as means rather than ends is considered to be morally wrong. However, clients have probably always been used by professionals to some extent: Things such as case conferences and clinical trials are legitimated by the intention to improve training and practice, and are regulated by various professional codes and committees. It would appear, however, that reflective practice is quantitatively and qualitatively different from the above, and thus may cross a moral boundary. Reflective practice is not simply re-examining someone's case: it involves personal interpretation and judgement. The reflector may be recording incidents, verbally or in written form, which would not otherwise be recorded, and may be controversial. This raises questions about the nature and ownership of knowledge, and the responsibilities of people who have such knowledge. Systematic and continued reflection may be akin to action research and, as such, considerations of rigour, authenticity and informed consent need to be addressed. Thus whilst reflective practice may prove to be a good thing, it cannot be seen in isolation from wider ethical concerns.
Education, Nursing↗