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Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 55 records · Page 3Linked to original sources

Can health care quality indicators be transferred between countries?

OBJECTIVE: To evaluate the transferability of primary care quality indicators by comparing indicators for common clinical problems developed using the same method in the UK and the USA. METHOD: Quality indicators developed in the USA for a range of common conditions using the RAND-UCLA appropriateness method were applied to 19 common primary care conditions in the UK. The US indicators for the selected conditions were used as a starting point, but the literature reviews were updated and panels of UK primary care practitioners were convened to develop quality indicators applicable to British general practice. RESULTS: Of 174 indicators covering 18 conditions in the US set for which a direct comparison could be made, 98 (56.3%) had indicators in the UK set which were exactly or nearly equivalent. Some of the differences may have related to differences in the process of developing the indicators, but many appeared to relate to differences in clinical practice or norms of professional behaviour in the two countries. There was a small but non-significant relationship between the strength of evidence for an indicator and the probability of it appearing in both sets of indicators. CONCLUSION: There are considerable benefits in using work from other settings in developing measures of quality of care. However, indicators cannot simply be transferred directly between countries without an intermediate process to allow for variation in professional culture or clinical practice.

Cross-Cultural Comparison↗

Quality indicators for primary care mental health services.

OBJECTIVES: To identify a generic set of face valid quality indicators for primary care mental health services which reflect a multi-stakeholder perspective and can be used for facilitating quality improvement. DESIGN: Modified two-round postal Delphi questionnaire. SETTING: Geographical spread across Great Britain. PARTICIPANTS: One hundred and fifteen panellists representing 11 different stakeholder groups within primary care mental health services (clinical psychologist, health and social care commissioner, community psychiatric nurse, counsellor, general practitioner, practice nurse/district nurse/health visitor, psychiatrist, social worker, carer, patient and voluntary organisations). MAIN OUTCOME MEASURES: Face validity (median rating of 8 or 9 on a nine point scale with agreement by all panels) for assessing quality of care. RESULTS: A maximum of 334 indicators were rated by panels in the second round; 26% were rated valid by all panels. These indicators were categorised into 21 aspects of care, 11 relating to general practices and 10 relating to health authorities or primary care groups/trusts. There was variation in the total number of indicators rated valid across the different panels. Overall, GPs rated the lowest number of indicators as valid (41%, n=138) and carers rated the highest number valid (91%, n=304). CONCLUSIONS: The quality indicators represent consensus among key stakeholder groups in defining quality of care within primary care mental health services. These indicators could provide a guide for primary care organisations embarking on quality improvement initiatives in mental health care when addressing national targets and standards relating to primary care set out in the National Service Framework for Mental Health for England. Although many of the indicators relate to parochial issues in UK service delivery, the methodology used in the development of the indicators could be applied in other settings to produce locally relevant indicators.

Attitude of Health Personnel↗

Team structure, team climate and the quality of care in primary care: an observational study.

OBJECTIVES: To determine whether practice structure (for example, list size, number of staff) predicts team processes and whether practice structure and team process in turn predict team outcomes DESIGN: Observational study using postal questionnaires and medical note audit. Team process was assessed through a measure of "climate" which examines shared perceptions of organisational policies, practices, and procedures. SETTING: Primary care. SUBJECTS: Members of the primary health care team from 42 practices. MAIN OUTCOME MEASURES: Objective measures of quality of chronic disease management, patients' evaluations of practices, teams' self-reported ratings of effectiveness, and innovation. RESULTS: Team climate was better in singlehanded practices than in partnerships. Practices with longer booking intervals provided superior chronic disease management. Higher team climate scores were associated with superior clinical care in diabetes, more positive patient evaluations of practice and self-reported innovation and effectiveness. CONCLUSIONS: Although the conclusions are preliminary because of the limited sample size, the study suggests that there are important relationships between team structure, process, and outcome that may be of relevance to quality improvement initiatives in primary care. Possible causal mechanisms that might underlie these associations remain to be determined.

Angina Pectoris↗

Cancer chemoprevention drug targets.

Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Chemoprevention can either prevent DNA damage that initiates the neoplastic transformation process or reverses the progression of pre-invasive lesions. Epidemiological observations, experimental evidence from animal carcinogenesis models, knock-out models, cancer cell lines and clinical trials have shown the efficacy of this approach. Recent advances in our understanding of carcinogenesis have led to the synthesis of new drugs that target specific receptors. Non-steroidal anti-inflammatory drugs target the prostaglandin pathway. The identification of the role of cyclooxygenase-2 in epithelial carcinogenesis led to the synthesis of selective cyclooxygenase-2 inhibitors (Celecoxib). Celecoxib was subsequently approved for the prevention of colon polyps in familial adenomatous polyposis after the completion of a randomized clinical trial. The large chemoprevention clinical trial with the selective estrogen receptor modulator, tamoxifen, showed the benefit of tamoxifen in the prevention of breast cancer in high-risk women. Retinoids and rexinoids target the retinoid receptors and have a role in chemoprevention of aerodigestive, hepatic and cervical neoplasia. Selenium, an inhibitor of the glutathione peroxidase system, is being tested in the chemoprevention of prostate cancer and lung cancer. The different isoforms of vitamin E (tocopherols) may be chemopreventive. Recent evidence indicates that gamma-tocopherol may be a more powerful chemopreventive than the alpha-tocopherol. The review details the rationale, experimental and clinical evidence and the drug targets of the chemopreventive agents that are currently in various phases of clinical development.

Animals↗

Characterization of normal and polycystic ovaries using three-dimensional power Doppler ultrasonography.

PURPOSE: To evaluate the characteristics of polycystic compared to normal ovaries using three-dimensional (3-D) power Doppler ultrasonography. METHODS: We recruited 42 volunteers, all of whom were commencing IVF treatment. Each patient was examined in the cycle preceeding the start of drug therapy during the late follicular phase. If eight or more subcapsular follicles of 2-8 mm in diameter in one two-dimensional (2-D) plane were detected in either of the ovaries, the patient was categorized as having polycystic ovaries (PCO); otherwise the ovaries were considered normal. The parameters examined were volume of the ovary, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and mean greyness (MG). In addition, the ovary was arbitrarily divided into cortex and stroma, and thereafter volume, VI, FI, VFI, and MG were calculated for these two regions. RESULTS: Twenty-eight women had normal ovaries and 14 had PCO. The comparison between normal and PCO showed that as a group the PCO were larger, without any differences in VI, Fl, VFI, or MG. In patients with PCO, the right ovary was larger than the left one. In patients with normal ovaries, Fl was higher on the left side. Division into cortex and stroma revealed that there were no differences in cortical or stromal VI, FI, VFI, or MG between normal and PCO on either side. CONCLUSIONS: The ovaries defined as polycystic were larger than normal ovaries, but there was no difference in the echogenicity of the stroma between polycystic and normal ovaries. We were also unable to demonstrate that the polycystic ovarian stroma was more vascularized than the stroma in the normal ovaries.

Adult↗

Relevance of thiopurine methyltransferase activity in inflammatory bowel disease patients maintained on low-dose azathioprine.

BACKGROUND: It is well-recognized that patients with low thiopurine methyltransferase activity are more susceptible to the development of bone marrow suppression side-effects. AIM: To study the impact of thiopurine methyltransferase activity on the clinical course of inflammatory bowel disease patients treated with low-dose azathioprine (< 2 mg/kg). METHODS: We measured the thiopurine methyltransferase activity of blood samples from 113 inflammatory bowel disease patients who were taking azathiopurine, had discontinued azathioprine because of side-effects, or had never taken azathioprine. The thiopurine methyltransferase activity was compared with that of 17 healthy controls. Relapse rates and time to first relapse were compared in inflammatory bowel disease patients and stratified according to their thiopurine methyltransferase activity. RESULTS: Patients who became neutropenic had a significantly lower mean thiopurine methyltransferase activity than that of patients who developed other side-effects (analysis of variance, P < 0.05). Survival curves were constructed (time to first relapse) for patients treated with low-dose azathioprine for thiopurine methyltransferase activities of < 20 and > 20 nmol/mL red blood cells/h. There was a significantly lower number of relapses in inflammatory bowel disease patients with lower thiopurine methyltransferase levels (P < 0.05). CONCLUSIONS: The mean thiopurine methyltransferase activity was significantly lower in patients on a low dose of azathioprine in remission compared with those who relapsed. The thiopurine methyltransferase activity was significantly lower in patients who discontinued azathioprine due to neutropenia than in those who discontinued due to other side-effects.

Adolescent↗

Evaluation of an information booklet for patients considering participation in phase I clinical trials in cancer.

Phase I trials in cancer patients, although essential, are a difficult field of clinical research. A particularly challenging area for all members of the clinical research team is that concerned with information-giving and informed consent leading to patient participation in the trial. An information booklet for patients was written in an attempt to address some of those issues, with the overall aim of improving the informed consent process and influencing patient decision-making. Questions covered in the booklet include: What is a phase I trial? Who can take part? Are there any side-effects or risks involved? What if I say no? The booklet was given to patients prior to consent. On the first day of receiving treatment they were given a questionnaire to evaluate the usefulness and acceptability of the booklet. The results showed the booklet to be generally well accepted by patients and the majority of them perceived the content and volume of information to be appropriate. The booklet did support patient decision-making and the evaluation showed that the optimal time for patients to receive it was prior to the signing of a consent form. Minor amendments have been made to the booklet, which is now given routinely to all patients at the cancer centre who are considering participation in a phase I trial, and is a valuable addition to the informed consent process.

Clinical Trials, Phase I as Topic↗

Risk factors for developing renal stones in inflammatory bowel disease.

OBJECTIVE: To correlate renal calculi and other clinical factors with urinary biochemical analytes in patients with inflammatory bowel disease, and to investigate the relative importance of hyperoxaluria (associated with fat malabsorption) or reduced stone inhibitors in the development of calculi in these patients. PATIENTS, SUBJECTS AND METHODS: Samples were obtained from 25 patients with Crohn's disease (CD), 15 with ulcerative colitis (UC) and 17 normal subjects (controls). Evidence for the presence of renal calculi was obtained from plain films, ultrasonography or intravenous urography. Urine oxalate and citrate were analysed using commercial enzymatic assays; magnesium was measured using atomic absorption and other analytes assayed using standard methods on automated analysers. RESULTS: Renal calculi were found in two patients with CD and in none with UC. Hyperoxaluria was present in 36% of patients with CD but was absent in those with UC. Analysis of covariance showed an association between low urinary citrate/creatinine ratio and renal stones (P=0.02), and between a combined urinary citrate and magnesium deficit relative to calcium, as expressed in the CMC index ((citratexmagnesium)/calcium), and renal stones (P=0.017). Changes in urinary calcium, oxalate, urate, magnesium or the calcium oxalate index were not associated with the presence of stones. There was no independent relationship between any clinical factor and the presence of stones. CONCLUSION: Lower urinary concentrations of magnesium and citrate (stone inhibitors), relative to calcium (stone promoter; the CMC index) may be more important in lithogenesis in inflammatory bowel disease than is hyperoxaluria. In patients with a functioning colon, a low CMC index may predict likely stone-formers; this requires a prospective evaluation. Avoiding low urinary levels of magnesium and citrate may aid in preventing and treating renal calculi.

Acute-Phase Proteins↗

The human ductus venosus between 13 and 17 weeks of gestation: histological and morphometric studies.

BACKGROUND: Doppler studies of the ductus venosus are increasingly being integrated in the assessment of fetal well-being. Establishing the precise morphology and structure of the ductus venosus would provide a better understanding of Doppler findings during fetal adaptation. There is conflicting evidence from previous studies about the structure of the ductus venosus, especially with regard to the presence of a sphincter at the ductus venosus inlet. The aim of this study was to examine the morphology and histological structure of the ductus venosus wall and surrounding tissues at 13-17 weeks' gestation. DESIGN: This was a prospective study on 28 fetuses obtained from medical termination of pregnancies between 13 and 17 weeks' gestation. Scanning electron microscopy and histological and immunohistochemical studies were carried out on ductus venosus sections obtained from different spatial planes. RESULTS: The inlet of the ductus venosus contained a shelf which was rich in elastin, but devoid of any evidence of a smooth muscle sphincter. The isthmus of the ductus venosus above the inlet was narrowed, giving the lumen of the vessel an hourglass appearance. The endothelial surface of the ductus venosus, above the level of the inlet, showed longitudinal corrugations along its entire length. Longitudinally arranged elastin fibers were also seen along the length of the ductus venosus. A single layer of longitudinally arranged smooth muscle cells was present along the entire length of the ductus venosus, with occasional individual nerve cells visible in this layer. CONCLUSIONS: The presence of an elastin-rich shelf and a narrow ductus venosus inlet orifice may act to accelerate flow from the portal sinus into a high-velocity system in the ductus venosus. The abundant elastin fibers in the adventitia of the ductus venosus may help antegrade wave propagation by elastic recoil. This study clearly demonstrates the lack of an anatomical smooth muscle sphincter at the ductus venosus inlet. However, the combination of endothelial corrugations and innervated smooth muscle support the hypothesis that the ductus venosus is an actively regulated vessel with the capacity to rapidly change diameter along its entire length in response to certain stimuli.

Endothelium, Vascular↗

Three-dimensional sonographic and power Doppler characterization of ovaries in late follicular phase.

OBJECTIVE: To determine ovarian blood flow characteristics using three-dimensional power Doppler ultrasound. METHODS: We examined 30 patients (30 cycles) prior to the start of their in vitro fertilization treatment in the late follicular phase using three-dimensional power Doppler ultrasound. The volume, vascularization index, flow index, vascularization flow index, mean grayness and the presence of the dominant follicle were determined for each ovary separately. RESULTS: The dominant follicle could be detected in 24 out of 30 cycles (80.0%). The volume of the dominant ovary was 9.9 (standard deviation, 4.0) cm3 and the volume of the non-dominant ovary 6.8 (standard deviation, 2.8) cm3 (P < 0.001). Mean grayness in the dominant ovary was 43.3 (standard deviation, 5.0) and in the non-dominant 47.2 (standard deviation, 4.0) (P < 0.001), but no other differences could be observed between dominant and non-dominant ovaries. The shell with a diameter of 2 mm surrounding the dominant follicle had a higher vascularization index (mean, 9.0; standard deviation, 5.9) and vascularization flow index (mean, 4.2; standard deviation, 2.8) than the whole dominant ovary (mean, 5.5; standard deviation, 2.5 and mean, 2.5; standard deviation, 1.3, respectively) (P = 0.003 and 0.002, respectively). In the cycles without a dominant follicle (n = 6), flow index (mean, 50.0; standard deviation, 5.9) and vascularization flow index (mean, 7.3; standard deviation, 6.2) on the left side were higher than on the right side (mean, 40.2; standard deviation, 3.1; mean, 1.5; standard deviation, 1.4; P-values 0.013 and 0.046, respectively). CONCLUSION: In the dominant ovary, the volume was higher and mean grayness lower than in the non-dominant ovary. The vascularization index in the shell surrounding the dominant follicle was higher than the average vascularization index in the whole dominant ovary. In addition, there were differences in the vascularization and flow indices between right and left ovaries, which may be related to the anatomical difference in the venous drainage between right and left ovaries.

Female↗

Elastin distribution in the myometrial and vascular smooth muscle of the human uterus.

Magnetic resonance imaging and transvaginal ultrasonography in women of reproductive age suggest that the myometrium consists of inner and outer layers. It was hypothesized that these structural and functional differences in the myometrium might be associated with a variation in elastin distribution. Fifty-one hysterectomy specimens representing all phases of the normal menstrual cycle were studied by immunocytochemistry, orcein staining and image analysis. Elastin was present within the outer myometrial smooth muscle, but was less widely distributed in the inner smooth muscle. Immunoreactivity and staining were observed in the myometrial arteries and arterioles and within the basal portions of endometrial arterioles. Elastin was also present in perivascular tissue, particularly near the large vessels. More extravascular (i.e. perivascular and smooth muscle) elastin was present in the outer myometrium in all cases, although no distinct layering was observed. Semi-quantitative analysis of the elastin distribution in 11 full thickness specimens demonstrated a decreasing gradient from outer to inner myometrium rather than distinct layering. Contrary to previous reports, these data suggest that the external region of the myometrium is more elastic than the inner region and that elastin is found throughout the arteriolar tree of the human uterus.

Elastin↗

Production of avirulent mutants of Mycobacterium bovis with vaccine properties by the use of illegitimate recombination and screening of stationary-phase cultures.

A better tuberculosis vaccine is urgently required to control the continuing epidemic. Molecular techniques are now available to produce a better live vaccine than BCG by producing avirulent strains of the Mycobacterium tuberculosis complex with known gene deletions. In this study, 1000 illegitimate recombinants of Mycobacterium bovis were produced by illegitimate recombination with fragments of mycobacterial DNA containing a kanamycin resistance gene. Eight recombinant strains were selected on the basis of their inability to grow when stationary-phase cultures were inoculated into minimal medium. Five of these recombinants were found to be avirulent when inoculated into guinea pigs. Two of the avirulent recombinants produced vaccine efficacy comparable to BCG against an aerosol challenge in guinea pigs with M. bovis. One of these recombinants had an inactivated glnA2 gene encoding a putative glutamine synthetase. Transcriptional analysis showed that inactivation of glnA2 did not affect expression of the downstream glnE gene. The other recombinant had a block of 12 genes deleted, including the sigma factor gene sigG. Two avirulent recombinants with an inactivated pckA gene, encoding phosphoenolpyruvate carboxykinase which catalyses the first step of gluconeogenesis, induced poor protection against tuberculosis. It is clear that live avirulent strains of the M. tuberculosis complex vary widely in their ability as vaccines to protect against tuberculosis. Improved models may be required to more clearly determine the difference in protective effect between BCG and potential new tuberculosis vaccines.

Animals↗

A prospective, observational study of a chest pain observation unit in a British hospital.

OBJECTIVES: To establish a chest pain observation unit, monitor its performance in terms of appropriate discharge after assessment, and estimate the cost per patient. METHODS: Prospective, observational, cohort study of patients attending a large, city, teaching hospital accident and emergency department between 1 March 1999 and 29 February 2000 with acute undifferentiated chest pain. Patients were managed on a chest pain observation unit, entailing two to six hours of observation, serial electrocardiograph recording, cardiac enzyme measurement, and, where appropriate, exercise stress test. Patients were discharged home if all tests were negative and admitted to hospital if tests were positive or equivocal. The following outcomes were measured-proportion of participants discharged after assessment; clinical status three days after discharge; cardiac events and procedures during the following six months; and cost of assessment and admission. RESULTS: Twenty three participants (4.3%) had a final diagnosis of myocardial infarction. All were detected and admitted to hospital. A total of 461 patients (86.3%) were discharged after assessment, 357 (66.9%) avoided hospital admission entirely. At review three days later these patients had no new ECG changes and only one raised troponin T measurement. In the six months after assessment, three cardiac deaths, two myocardial infarctions, and two revascularisation procedures were recorded among those discharged. The mean cost of assessment and hospital admission was 221 pound per patient, or 323 pound if subsequent interventional cardiology costs were included. CONCLUSIONS: The chest pain observation unit is a practical alternative to routine care for acute chest pain in the United Kingdom. Negative assessment effectively rules out immediate, serious morbidity, but not longer term morbidity and mortality. Costs seem to be similar to routine care.

Angina Pectoris↗

Improving the effectiveness of routine prenatal screening for major congenital heart defects.

OBJECTIVE: To evaluate the effectiveness of adding outlet views to the four chamber view in routine prenatal ultrasound screening for major congenital heart defects (CHD) as performed by trained sonographers, and to compare the procedure with current practice. DESIGN AND SETTING: Prospective observational study at a London teaching hospital. PARTICIPANTS AND METHODS: 9277 women booked at a single institution (80% had first trimester nuchal translucency measurement) due to have routine fetal cardiac screening using the four chamber and outflow tract views at > 18 weeks of gestation. MAIN OUTCOME MEASURE: Identification of major CHD in chromosomally normal and abnormal pregnancies antenatally or postnatally. RESULTS: There were 40 abnormalities (4.3/1000), of which 30 were chromosomally normal (3.3/1000). The overall antenatal detection rate was 75% (95% confidence interval (CI) 59% to 87%) and 70% (95% CI 51% to 85%) for euploid pregnancies. Abnormal cardiac views accounted for 70% of all prenatal diagnoses, 30% of which were made at < or = 18 weeks. The sensitivity of cardiac views during the first scan at > 18 weeks was 52%. Of all patients undergoing nuchal translucency screening, 34 had major CHD, nine with increased nuchal translucency (26.5%). Factors influencing the results of this screening programme were training and audit of operators, adequate equipment for antenatal examination, ease of access, and low threshold for referral to specialised fetal echocardiography. CONCLUSION: Adding ventricular outlet views to the four chamber assessment of the heart at routine fetal anomaly scans at > 18 weeks is the most effective technique to detect CHD prenatally. The success of such a programme depends on an infrastructure committed to continuous in house training of obstetric ultrasonographers coupled with feedback from specialised fetal cardiologists, as well as adequate resource allocation to obstetric hospitals involved with antenatal screening.

Adolescent↗

Isolation and characterisation of rhabdovirus from wild common bream Abramis brama, roach Rutilus rutilus, farmed brown trout Salmo trutta and rainbow trout Oncorhynchus mykiss in Northern Ireland.

Rhabdovirus was isolated from wild common bream Abramis brama during a disease outbreak with high mortality in Northern Ireland during May 1998. Rhabdovirus was also isolated at the same time from healthy farmed rainbow Oncorhynchus mykiss and brown trout Salmo trutta on the same stretch of river and 11 mo later from healthy wild bream and roach Rutilus rutilus in the same river system. Experimental intra-peritoneal infection of bream and mirror carp Cyprinus carpio var specularis with 2 of these isolates produced low mortality rates of < or = 12%. Serological testing of these isolates by virus neutralisation indicated that they were antigenically closely related to pike fry rhabdovirus (PFRV) but not to spring viraemia of carp virus (SVCV), while testing by enzyme-linked immunosorbent assay indicated them to be antigenically different from both. Comparison of nucleotide sequence data of a 550 base pair segment of the viral glycoprotein generated by reverse transcription-polymerase chain reaction indicated a high (> or = 96.6%) degree of similarity between these isolates and a previous Northern Ireland isolate made in 1984, a 1997 isolate from bream in the Republic of Ireland and an earlier Dutch isolate from roach. In contrast, similarity between these isolates and PFRV was < 82.4%, indicating that these viruses belong to 2 distinct genogroups, while similarity to SVCV was even lower (< 67.4%).

Amino Acid Sequence↗