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Biomedical subjects

T Clark

Publications and source records attributed to T Clark.

At least 19 recordsLinked to original sources

Palliative radiotherapy improves pain and reduces functional interference in patients with painful bone metastases: a quality assurance study.

AIMS: To characterise the effect of palliative radiotherapy treatment outcomes as evaluated by the Brief Pain Inventory within a radiotherapy clinic, as a quality assurance initiative. MATERIALS AND METHODS: Tumour and treatment parameters of patients with painful bone metastases treated through a dedicated bone pain radiotherapy clinic have been prospectively recorded since 2002. One hundred and nine ambulatory patients provided pre- and post-treatment pain assessments at 4-6 weeks after palliative radiotherapy. The self-administered Brief Pain Inventory questionnaire was completed by patients during their visits. Changes in pain and seven-item functional interference scores were analysed. RESULTS: Most of the patients had prostate (n=42) or breast (n=42) cancer. The mean Karnofsky performance score was 70 before palliative radiation therapy. Sixty-eight per cent of patients were treated with a single fraction (6-8 Gy) and 25% received 20 Gy/five fractions. The overall response (reduction in worst pain by > or = 2/10) was 72%. Sixty-one per cent of patients had stable or reduced consumption of opioid analgesics. A significant reduction for all seven functional interference items was seen after treatment, the greatest improvement being general activity (-2.4/10). There was significant correlation between pain reduction and improvement in functional interference. CONCLUSION: This quality assurance initiative showed that palliative radiotherapy reduced both pain and its interference on function among ambulatory patients with symptomatic bone metastases. The reduction in pain was correlated with reductions in functional interference. Clinical trials of palliative radiotherapy should provide data that allow an evaluation of various domains of chronic pain.

Adult↗

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis.

We attempted to replicate the findings of two recent meta-analyses that personality inventory moderates the association between the serotonin transporter gene and anxiety-related traits. A total of 24 studies contributed to the meta-analysis, of which three reported genotype frequencies that deviated from Hardy-Weinberg (HW) equilibrium. We found some support for the view that results depend on the type of questionnaire used, although in a direction opposite to that previously reported. Contrasts between the S/S and L/L groups were significant for TCI/TPQ harm avoidance studies (P=0.0024) but not NEO neuroticism (P=0.9757). When studies not in HW equilibrium were excluded the TCI/TPQ result for the S/S genotype still exceeded our 5% threshold, although with reduced significance (P=0.0082), and the NEO result remained nonsignificant (P=0.9109). While we cannot rule out an association between the 5HTT gene and anxiety-related traits, particularly for TCI/TPQ harm avoidance, our findings do indicate that the effect, if present, is small. Our results emphasise the importance of complete ascertainment of studies and the identification of relevant sources of heterogeneity.

Adolescent↗

Motor vehicle driver injury and marital status: a cohort study with prospective and retrospective driver injuries.

OBJECTIVE: To investigate the association of marital status with risk of motor vehicle driver injury. DESIGN: A cohort study with prospective and retrospective outcomes. SETTING: New Zealand. PARTICIPANTS: A total of 10,525 adults (a volunteer sample of a multi-industry workforce, n = 8008; and a random sample of urban electoral rolls, n = 2517). EXPOSURE VARIABLE: Self reported marital status, assessed from a questionnaire administered in 1992-93 (baseline). MAIN OUTCOME MEASURE: Motor vehicle driver injury resulting in admission of the driver to hospital and/or the driver's death, during the period 1988-98; hospitalisation and mortality data were obtained by record linkage to national health databases. RESULTS: During 108 741 person-years of follow up, 139 driver injury cases occurred (85 before baseline, 54 after). After adjustment for age, sex, and study cohort, never married participants had twice the risk of driver injury (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.35 to 3.16) as married participants (HR 1.00). The relative risk for never married participants was slightly higher (HR 2.29), though less precise (95% CI 1.39 to 3.76), after further adjustment for alcohol intake, driving exposure, area of residence, body mass index, and occupational status. CONCLUSIONS: After taking age, sex, and other variables into account, never married people had a substantially higher risk of driver injury than married people. While requiring corroboration, these findings imply that it may be appropriate for driver injury countermeasures to be targeted to never married people.

Accidents, Traffic↗

Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB.

SETTING: Zomba Central Hospital, Malawi. OBJECTIVES: To determine the outcome of all adult patients who were registered for tuberculosis (TB) treatment 7 years previously according to initial human immunodeficiency virus (HIV) status and type of TB. DESIGN: A retrospective cohort study of adult patients registered for TB treatment between July and December 1995. Follow-up at patients' homes was performed at the end of treatment, at 32 months and at 84 months (7 years) from the time of TB registration. FINDINGS: Eight hundred and twenty-seven TB patients were registered: 793 had concordant HIV test results, of whom 612 (77%) were HIV-positive. At 7 years, 136 (17%) patients were alive, 539 (65%) had died and 152 (18%) were lost to follow-up. The death rate for all TB patients was 23.7 per 100 person-years of observation. HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.2, 95% confidence interval [95%CI] 1.7-2.8). Death rates in smear-negative pulmonary TB patients (HR 2.1, 95%CI 1.7-2.6) and in patients with extra-pulmonary TB (HR 1.7, 95% CI 1.3-2.0) were higher than in patients with smear-positive PTB. CONCLUSIONS: There was a high mortality rate in TB patients during and after anti-tuberculosis treatment. Adjunctive treatments to reduce death rates are urgently needed.

Adult↗

Motor vehicle driver injury and socioeconomic status: a cohort study with prospective and retrospective driver injuries.

STUDY OBJECTIVE: To investigate the association between motor vehicle driver injury and socioeconomic status. DESIGN: Cohort study with prospective and retrospective outcomes. SETTING: New Zealand. PARTICIPANTS: 10 525 adults (volunteer sample of a multi-industry workforce, n=8008; and a random sample of urban electoral rolls, n=2517). OUTCOME MEASURE: Motor vehicle driver injury resulting in admission of the driver to hospital or the driver's death, or both, during the period 1988-98; hospitalisation and mortality data were obtained by record linkage to national health databases. MAIN RESULTS: After adjustment for age and sex, driver injury risk was inversely associated with both occupational status (p for linear trend <0.0001) and educational level (p for linear trend =0.007). Participants in the lowest approximate quartile of occupational status were four times as likely (HR 4.17, 95% CI 2.31 to 7.55) to have experienced a driver injury during follow up as participants in the highest approximate quartile. Participants who had been to secondary school for less than two years were twice as likely (HR 2.26, 95% CI 1.34 to 3.81) to have experienced a driver injury as those who had been to university or polytechnic. There was little evidence that driver injury risk was associated with neighbourhood income (p for linear trend =0.12) CONCLUSIONS: Occupational status and educational level seem to be important determinants of driver injury risk. Driver injury countermeasures should be targeted to people in low status occupations, as well as to people with comparatively little formal education.

Accidents, Traffic↗

The pattern of gene expression in human CD34(+) stem/progenitor cells.

We have analyzed the pattern of gene expression in human primary CD34(+) stem/progenitor cells. We identified 42,399 unique serial analysis of gene expression (SAGE) tags among 106,021 SAGE tags collected from 2.5 x 10(6) CD34(+) cells purified from bone marrow. Of these unique SAGE tags, 21,546 matched known expressed sequences, including 3,687 known genes, and 20,854 were novel without a match. The SAGE tags that matched known sequences tended to be at higher levels, whereas the novel SAGE tags tended to be at lower levels. By using the generation of longer sequences from SAGE tags for gene identification (GLGI) method, we identified the correct gene for 385 of 440 high-copy SAGE tags that matched multiple genes and we generated 198 novel 3' expressed sequence tags from 138 high-copy novel SAGE tags. We observed that many different SAGE tags were derived from the same genes, reflecting the high heterogeneity of the 3' untranslated region in the expressed genes. We compared the quantitative relationship for genes known to be important in hematopoiesis. The qualitative identification and quantitative measure for each known gene, expressed sequence tag, and novel SAGE tag provide a base for studying normal gene expression in hematopoietic stem/progenitor cells and for studying abnormal gene expression in hematopoietic diseases.

3' Untranslated Regions↗

The pattern of gene expression in human CD15+ myeloid progenitor cells.

We performed a genome-wide analysis of gene expression in primary human CD15(+) myeloid progenitor cells. By using the serial analysis of gene expression (SAGE) technique, we obtained quantitative information for the expression of 37,519 unique SAGE-tag sequences. Of these unique tags, (i) 25% were detected at high and intermediate levels, whereas 75% were present as single copies, (ii) 53% of the tags matched known expressed sequences, 34% of which were matched to more than one known expressed sequence, and (iii) 47% of the tags had no matches and represent potentially novel genes. The correct genes were confirmed by application of the generation of longer cDNA fragments from SAGE tags for gene identification (GLGI) technique for high-copy tags with multiple matches. A set of genes known to be important in myeloid differentiation were expressed at various levels and used different spliced forms. This study provides a normal baseline for comparison of gene expression in myeloid diseases. The strategy of using SAGE and GLGI techniques in this study has broad applications to the genome-wide identification of expressed genes.

Biomarkers↗

The pattern of gene expression in mouse Gr-1(+) myeloid progenitor cells.

To understand the pattern of gene expression in mouse myeloid progenitor cells, we carried out a genome-wide analysis of gene expression in mouse bone marrow Gr-1(+) cells using SAGE and GLGI techniques. We identified 22,033 unique SAGE tags with quantitative information from 73,869 collected SAGE tags. Among these unique tags, 64% match known sequences, including many genes important for myeloid differentiation, and 36% have no matches to known sequences and are likely to represent novel genes. We compared the expression of mouse Gr-1(+) and human CD15(+) myeloid progenitor cells and showed that the pattern of gene expression of these two cell populations had some similarities. We also compared the expression of mouse Gr-1(+) myeloid progenitor cells with that of mouse brain tissue and found a highly tissue-specific manner of gene expression in these two samples. Our data provide a basis for studying altered gene expression in myeloid disorders using mouse models.

Animals↗

Physician-patient communication about over-the-counter medications.

The purpose of this study was to describe physician-patient communication about over-the-counter medications using a data set comprised of audio-tapes and transcripts of 414 primary care medical visits. The data set was collected during 1995 at the family practice and general medicine clinics at the University of New Mexico Health Sciences Center. Twenty-seven resident physicians and 414 of their adult patients participated. Fifty-seven percent of patients reported using one or more OTC medications during the past month. Analgesics, cold or allergy products, and antacids were the most commonly used OTC medications. White patients were significantly more likely to have reported using an analgesic in the past month than non-white patients. Female, white, and younger patients were more likely to have reported using a cold or allergy product in the past month than male, non-white, and older patients. Approximately 58% of patients discussed OTC medications with their physicians. Older patients and female patients as well as patients who reported using an antacid in the past month were significantly more likely to have discussed OTC medications with their physicians. Physicians asked questions about OTC medications during only 37% of encounters. Patients asked questions about OTC medications during 11% of encounters. Patient ethnicity did not influence physician or patient question-asking and information-giving about OTC medications. Male physicians were more likely to state information and ask questions about OTC medications than female physicians. Patients were more likely to ask male physicians questions about OTC medications. Physicians were more likely to state OTC information to and ask OTC questions of female and older patients. Physicians were more likely to ask less educated patients questions about OTC medications. Less educated patients were more likely to ask physicians questions about OTC medications. Despite the fact that more than half of all patients reported using OTC medications, physicians asked questions about OTC use during only approximately one-third of encounters. Of patients who reported using an OTC medication in the past month, 58% did not tell their physicians, yet only 14% of patients believed that it was not important for the physician to know about their OTC use. Physician-patient communication about OTC medications should be encouraged so that the patient becomes a collaborative partner in medication management.

Adolescent↗

Random errors in the measurement of 10 cardiovascular risk factors.

Random errors in the measurement of 10 commonly investigated cardiovascular risk factors (systolic and diastolic blood pressure, blood cholesterol, blood glucose, pulse rate, body mass index (BMI), cigarette consumption, passive smoking, alcohol intake and physical exercise) were assessed in a general population cohort (n = 2517) and a workforce cohort (n = 8008). Random errors were estimated from regression dilution ratios (lower ratios imply greater random error, and a ratio of one implies no random error). All of the risk factors, except for BMI (which had regression dilution ratios of 0.93 and 0.98 in the two cohorts), were measured with substantial levels of random error. Particularly low regression dilution ratios were observed for physical exercise (0.28 and 0.39) and pulse rate (0.47 and 0.56). For each of these risk factors, with the possible exception of BMI, associations with long-term average values could be importantly biased toward the null unless appropriate corrections are made.

Bias↗

Ethnicity and physician-older patient communication about alternative therapies.

OBJECTIVES: The purpose of this study was to describe ethnic differences in physician-patient communication about alternative therapies, using a data set comprised of audiotapes and transcripts of primary care medical visits. METHODS: The data set was collected during 1995 at the family practice and general medicine clinics at the University of New Mexico Health Sciences Center, Albuquerque, NM. Twenty-seven (27) resident physicians and 205 of their Hispanic and non-Hispanic white patients age 50 and over participated. RESULTS: Almost 18 percent of patients reported using one or more alternative therapies during the preceding month. Herbal medicine was the most widely used therapy. Eighty-three percent (83%) of patients who reported using an alternative therapy in the previous month did not tell their physicians. Physicians asked one or more questions about alternative therapies during only 3.4% of encounters. Only 2% of patients asked their physicians one or more questions about alternative therapies. There were no ethnic differences in physician-older patient communication about alternative therapies. DISCUSSION: Physician-patient communication could be improved to enhance physician understanding of the spectrum of interventions patients pursue to improve their health.

Adult↗

Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials.

OBJECTIVES: To obtain reliable estimates of the effects of neuraxial blockade with epidural or spinal anaesthesia on postoperative morbidity and mortality. DESIGN: Systematic review of all trials with randomisation to intraoperative neuraxial blockade or not. STUDIES: 141 trials including 9559 patients for which data were available before 1 January 1997. Trials were eligible irrespective of their primary aims, concomitant use of general anaesthesia, publication status, or language. Trials were identified by extensive search methods, and substantial amounts of data were obtained or confirmed by correspondence with trialists. MAIN OUTCOME MEASURES: All cause mortality, deep vein thrombosis, pulmonary embolism, myocardial infarction, transfusion requirements, pneumonia, other infections, respiratory depression, and renal failure. RESULTS: Overall mortality was reduced by about a third in patients allocated to neuraxial blockade (103 deaths/4871 patients versus 144/4688 patients, odds ratio=0.70, 95% confidence interval 0.54 to 0.90, P=0. 006). Neuraxial blockade reduced the odds of deep vein thrombosis by 44%, pulmonary embolism by 55%, transfusion requirements by 50%, pneumonia by 39%, and respiratory depression by 59% (all P<0.001). There were also reductions in myocardial infarction and renal failure. Although there was limited power to assess subgroup effects, the proportional reductions in mortality did not clearly differ by surgical group, type of blockade (epidural or spinal), or in those trials in which neuraxial blockade was combined with general anaesthesia compared with trials in which neuraxial blockade was used alone. CONCLUSIONS: Neuraxial blockade reduces postoperative mortality and other serious complications. The size of some of these benefits remains uncertain, and further research is required to determine whether these effects are due solely to benefits of neuraxial blockade or partly to avoidance of general anaesthesia. Nevertheless, these findings support more widespread use of neuraxial blockade.

Anesthesia, Epidural↗

Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril.

OBJECTIVES: The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease. BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis. METHODS: Six hundred seventeen patients were randomized in equal proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography. RESULTS: Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p<0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04). CONCLUSIONS: The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗

QM/NN QSPR models with error estimation: vapor pressure and logP

QSPR models for logP and vapor pressures of organic compounds based on neural net interpretation of descriptors derived from quantum mechanical (semiempirical MO; AM1) calculations are presented. The models are cross-validated by dividing the compound set into several equal portions and training several individual multilayer feedforward neural nets (trained by the back-propagation of errors algorithm), each with a different portion as test set. The results of these nets are combined to give a mean predicted property value and a standard deviation. The performance of two models, for logP and the vapor pressure at room temperature, is analyzed, and the reliability of the predictions is tested.

Journal Article↗

Serial fetal lung volume measurement using three-dimensional ultrasound.

OBJECTIVE: To establish reference intervals for fetal lung growth. DESIGN: Longitudinal observational study. SUBJECTS: Fifty-eight women with initially uncomplicated singleton pregnancies were recruited from the antenatal population of a teaching hospital. Four women were excluded from the final analysis because of complications arising in their pregnancy. METHODS: Each subject was serially scanned at monthly intervals. At each visit lung volume was measured using an ultrasound-based computerized three-dimensional imaging system. Multilevel models were used to determine conditional and unconditional reference intervals. RESULTS: Reference intervals for fetal lung growth were derived. Fetal lung volume increases in a non-linear way with gestation. CONCLUSIONS: Our computerized system has the capacity to be used in conjunction with any standard two-dimensional ultrasound scanner in order to measure volume. Lung volume measurement may be useful in predicting pulmonary hypoplasia.

Adult↗

A systematic survey of 13 randomized trials of non-steroidal anti-inflammatory drugs for the prevention of heterotopic bone formation after major hip surgery.

We performed a systematic survey of randomized trials to determine the effects of perioperative NSAIDs on the occurrence of heterotopic bone formation, gastrointestinal side-effects and long-term clinical outcomes after major hip surgery. 13 trials involving 4,129 individuals were identified. Overall, in 12 small trials of medium-to-high-dose regimens, there was a 57% reduction (95% confidence interval 51%-63%) in the risk of heterotopic bone formation. The results of one large trial of low-dose aspirin differed markedly (2% reduction (95% CI 12% reduction to 15% increase)). The NSAID regimens studied had no definite effect on gastrointestinal complications, and data about the effects of NSAIDs on pain and function were too few, and too incompletely reported, to draw conclusions about their effects on these outcomes. Routine prophylaxis against heterotopic bone formation with NSAIDs may be a useful adjuvant therapy for patients undergoing major hip surgery, but the overall balance of risks and benefits requires assessment in a large-scale randomized trial.

Anti-Inflammatory Agents, Non-Steroidal↗