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D Campbell

Publications and source records attributed to D Campbell.

At least 19 recordsLinked to original sources

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Adolescent↗

Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study.

BACKGROUND: There is a need to understand what affects the success of in-vitro fertilisation (IVF) and the rate of resulting twin births so that pregnancy rates can be improved and multiple gestations avoided. Our aim was to assess the role of B vitamins and genetics. METHODS: We did a prospective cohort study of 602 women undergoing fertility treatment. We assessed intake of folate and vitamin B12 with a questionnaire and measured their plasma and red-blood-cell concentrations by radioimmunoassay. We measured five B-vitamin-related gene variants in women who received treatment and in 932 women who conceived naturally. FINDINGS: The likelihood of a twin birth after IVF rose with increased concentrations of plasma folate (1.52, 1.01-2.28; p=0.032) and red-cell folate (1.28, 1.00-1.65; p=0.039). There was no association between folate and vitamin B12 levels and likelihood of a successful pregnancy. Women homozygous for the 1298 CC variant of methylenetetrahydro-folate reductase (MTHFR), rather than the AA variant, were less likely to produce a livebirth after IVF (0.24, 0.08-0.71; p=0.003) or to have had a previous pregnancy (0.42, 0.21-0.81; p=0.008). INTERPRETATION: Our findings suggest that MTHFR genotype is linked to a woman's potential to produce healthy embryos (possibly through interaction with genes related to DNA methylation). In women likely to have a successful IVF pregnancy, high folate status increases the likelihood of twin birth after multiple embryo transfer. Proposals to fortify the UK diet with folic acid could lead to an increase in the number of twins born after IVF.

Chorionic Gonadotropin↗

Cautionary tales in the interpretation of systematic reviews of therapy trials.

This is the second in a series of articles emphasizing the cautions in the interpretation of health-care studies. Systematic reviews are presented as comprehensive, unbiased summaries of evidence and are often referred to by clinicians, guideline developers and health policy-makers. Their strengths and limitations, and how their results can be subject to bias and misinterpretation, are discussed.

Humans↗

Clinical practice guidelines: barriers to durability after effective early implementation.

BACKGROUND: Clinical practice guidelines in general (General-CPG) may reduce variation in clinician performance and improve patient outcomes. Short-term evaluation is now routine, but demonstration of early successful implementation does not necessarily ensure longer-term effectiveness. AIM: To assess adherence to chronic obstructive pulmonary disease (COPD)-CPG recommendations at the Royal Melbourne Hospital (RMH), 2 years after successful implementation. To identify barriers to sustained success of General-CPG. METHODS: A multi-faceted evaluation was performed to document: (i) current adherence to COPD management recommendations (medical record audit); (ii) awareness of attitudes towards and barriers for the use of COPD-CPG and General-CPG (staff survey, focus groups and key informant interviews) and (iii) access to and quality of available General-CPG (internet review and random sample General-CPG evaluation. RESULTS: Adherence to COPD-CPG recommendations was highly variable. Adherence was higher in the Emergency Department than the general wards and for specific therapeutic recommendations. It was lower for non-pharmacological therapy and for recommendations relating to processes of care. Most health professionals were in favour of General-CPG. Barriers to use of General-CPG were in keeping with previous literature reports. Organizational issues including high levels of staff turnover and lack of integration of General-CPG into hospital quality frameworks were highlighted as major barriers. Hospital intranet access and presentation of General-CPG identified lack of consistency in terminology and presentation. CONCLUSION: Short-term effectiveness of COPD-CPG implementation did not ensure sustained success. Departmental organizational behaviours and organizational system barriers are major factors influencing durability.

Aged↗

Readmission patterns in patients with chronic obstructive pulmonary disease, chronic heart failure and diabetes mellitus: an administrative dataset analysis.

Comprehensive disease management programmes for chronic disease aim to improve patient outcomes and reduce health-care utilization. Readmission rates are often used as an outcome measure of effectiveness. This study aimed to document readmission rates, and risk for early and late readmission, for patients discharged from the Royal Melbourne Hospital with a disease diagnosis of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) or diabetes mellitus compared to those with other general medical conditions. Eighty five (8.6%) of patients were readmitted within 28 days and 183 (20.8%) were readmitted between 29 and 180 days. No risk factors for early readmission were identified. Patients with a primary disease diagnosis of CHF and COPD are at increased risk of late readmissions (29-180 days).

Adult↗

Primary mode of delivery and subsequent pregnancy.

OBJECTIVE: To investigate the relationship between primary mode of delivery and subsequent pregnancy and to compare the findings with a previous study conducted on an earlier cohort from the same population. DESIGN: Population cohort. SETTING: Aberdeen City, Scotland. POPULATION: Women who delivered their first singleton child in Aberdeen Maternity Hospital between 1980 and 1997. METHODS: Population-based data relating to the index and next pregnancy event, if any, were obtained from the Aberdeen Maternity Neonatal Databank. Subsequent pregnancy was compared across the three modes of delivery groups using log rank tests and Cox proportional hazards regression models. MAIN OUTCOME MEASURE: First subsequent pregnancy following index delivery. RESULTS: Women who delivered by caesarean section (CS) were less likely to have a subsequent pregnancy compared with those who had a spontaneous vaginal delivery (SVD), hazard ratio = 0.91 (95% CI 0.87, 0.95). This confirmed the findings of a previous study conducted on an earlier cohort of the same population. The median time to next pregnancy following CS was 36.3 months, 31.8 months following instrumental vaginal delivery (IVD) and 30.4 months following SVD. In contrast to the earlier study where women who had an instrumental delivery were found to be an intermediate group, we found no difference in subsequent pregnancy following IVD compared with SVD, HR = 1.0 (95% CI 0.96, 1.03). CONCLUSIONS: Following an initial delivery by CS, fewer women went on to have another pregnancy compared with SVD. The incidence of subsequent pregnancy is similar following instrumental and SVD.

Adult↗

Screening for lung cancer.

BACKGROUND: While population based screening for lung cancer has not been adopted by most countries, it is not clear whether sputum examinations, chest radiography or newer methods such as computed tomography are effective in reducing mortality from lung cancer. OBJECTIVES: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality. SEARCH STRATEGY: Electronic databases (the Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE and EMBASE; 1966 to July 2000) ), bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest. DATA COLLECTION AND ANALYSIS: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effects model, but for other outcomes the fixed effect model was used. MAIN RESULTS: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT. REVIEWER'S CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

Adult↗

Parameters associated with persistent airflow obstruction in chronic severe asthma.

The significance of severe airflow obstruction in severe asthma is unclear. The current study determined whether severe airflow obstruction is related to inflammatory or structural changes in the airways. Patients with severe asthma from a tertiary referral clinic were divided into two groups according to their postbronchodilator forced expiratory volume in one second (FEV1): severe persistent airflow limitation (FEV1 <50% predicted; group S; n=37) and no obstruction (FEV1 >80% pred; group N; n=29). Smoking history, atopic status, lung function tests, exhaled NO, blood eosinophil count, quality of life scores using St George's Respiratory Questionnaire and high resolution computed tomography (HRCT) of the lungs were assessed. Patients from group S were older and had longer disease duration. There was no difference in smoking history, atopic status, hospital admissions, quality of life scores and amount of treatment with inhaled or oral corticosteroids. Exhaled NO and peripheral blood eosinophils were higher in group S (21.0 +/- 2.4 versus 12.8 +/- 2.3 ppb; 0.41 +/- 0.06 versus 0.15 +/- 0.03 x 10(9) cells x L(-1) respectively). HRCT scores for bronchial wall thickening and dilatation were higher in group S with no differences in air trapping. Peripheral blood eosinophilia and bronchial wall thickening on HRCT scan were the only parameters significantly and independently associated with persistent airflow obstruction. Patients with severe asthma and irreversible airflow obstruction had longer disease duration, a greater inflammatory process and more high resolution computed tomography airway abnormalities suggestive of airway remodelling, despite being on similar treatments and experiencing equivalent impairment in quality of life.

Administration, Inhalation↗

Metastatic pulmonary ameloblastoma. An unusual case.

We present a patient who had a large metastatic pulmonary ameloblastoma resected 25 years after removal of an apparently benign primary ameloblastoma of the jaw. It highlights three areas: problems with the histopathological diagnosis of pulmonary metastases using fine needle aspiration; a noted radiological improvement after a 5-year course of oral cyclophosphamide, in keeping with occasional patients who have responded to chemotherapy; and the technical difficulties of resection of a large pulmonary metastasis, particularly when it is adherent to the mediastinum.

Ameloblastoma↗

Is Doppler ultrasound sufficient as the sole investigation before carotid endarterectomy?

BACKGROUND AND AIMS: Doppler ultrasound (DU) of the extracranial carotid arteries has been advocated as the sole imaging modality in carotid endarterectomy (CE) candidates. However this approach fails to identify patients with potentially significant intracranial disease, at high risk of stroke and death. Therefore, many stroke clinicians recommend angiography after screening DU. We aimed to identify the proportion of cases referred for CE in whom the identification of intracranial disease could have altered management. METHODS: Two neuroradiologists, blinded to the clinical history, reviewed the films of 111 CE candidates, predominantly of Caucasian background, who had undergone carotid angiography after screening DU. Intracranial stenoses >50% luminal diameter, incidental aneurysms and non-atherosclerotic lesions were documented. Demographic and epidemiological data were collected. RESULTS: Of the 111 patients, 87 had >50% extracranial stenoses although two thirds were asymptomatic. Intracranial stenotic lesions were recorded in 29% of patients. Over half of these were tandem lesions, distal to an extracranial stenosis. Aneurysms were found in 4.5% of patients. CONCLUSIONS: DU alone would have failed to detect significant intracranial disease in nearly a third of cases. These patients are at high risk of stroke. The identification of this group allows more aggressive stroke prevention therapy.

Carotid Arteries↗

A cohort study of reproductive risk factors, weight and weight change and the development of diabetes mellitus.

AIMS: Reproductive factors (parity, miscarriages, terminations), oral contraceptive use, hormone replacement therapy, body weight at first pregnancy and weight gain following pregnancy may be associated with a long-term risk of diabetes. The aim of this study is to investigate the independent risks of reproductive factors and body weight for diabetes in later life. METHODS: This is a retrospective cohort study of 1257 parous women who had a first pregnancy between 1951 and 1970. Reproductive history, weight and height were measured at the time of first pregnancy, then assessed by questionnaire in 1997 for all women. A clinical examination and an analysis of blood samples were undertaken for 992 women. The main outcome was incidence of diabetes based on medical history, medication and random glucose measurement. RESULTS: Sixty of the 1257 (4.8%) women developed diabetes. Body mass index at index pregnancy and after 28-48 years follow-up were both significantly associated with risk of diabetes, this increased with greater weight gain. There was a non-significant increased risk of diabetes associated with stillbirths and miscarriages after age and BMI adjustment. CONCLUSIONS: In parous women, higher BMI at index pregnancy, weight gain during follow-up and BMI in later life strongly predict diabetes risk.

Abortion, Induced↗

Transvaginal power Doppler ultrasound in pelvic congestion.

PURPOSE: Pelvic congestion is diagnosed by transuterine venography, an invasive procedure requiring sedation and irradiation. Ultrasound may be an alternative but is hindered by slow flow within pelvic veins. In an attempt to counter this, we investigated the possible role of transvaginal power Doppler ultrasound. MATERIAL AND METHODS: 42 women with a clinical suspicion of pelvic congestion underwent transvaginal ultrasound. Adnexal veins were examined and a congestion score established. Planimetric measurements of adnexal vessels were obtained using power Doppler ultrasound, and uterine and ovarian morphology noted. All women then underwent transuterine venography and agreement with the ultrasound congestion score and morphologic features was determined. RESULTS: There was a trend towards weak positive correlation between ultrasound and venography congestion scores (r = 0.29, p = 0.06). However, agreement between scores was poor on an individual basis (95% limits of agreement, -3.9 to +2.7). Planimetric power Doppler assessments of adnexal vascularity were unrelated to venographic congestion. Instead, there was correlation between the number and diameter of ovarian follicles and venographic congestion: women with congestion tended to have significantly more (0.04) and smaller follicles (p = 0.001). CONCLUSION: There was poor individual agreement between ultrasound and venographic estimates of congestion. However, there was a direct relationship between venographic congestion score and ovarian morphology.

Adnexa Uteri↗