Clinical Trial Service Unit

About: Clinical Trial Service Unit is a based out in . It is known for research contribution in the topics: Population & Stroke. The organization has 428 authors who have published 1387 publications receiving 181920 citations.

Estimating cardiac exposure from breast cancer radiotherapy in clinical practice.

Abstract: Purpose To assess the value of maximum heart distance (MHD) in predicting the dose and biologically effective dose (BED) to the heart and the left anterior descending (LAD) coronary artery for left-tangential breast or chest wall irradiation. Methods and Materials A total of 50 consecutive breast cancer patients given adjuvant left-tangential irradiation at a large U.K. radiotherapy center during 2006 were selected. For each patient, the following were derived using three-dimensional computed tomography (CT) planning: (1) mean dose and BED to the heart, (2) mean dose and BED to the LAD coronary artery, (3) MHD, (4) position of the CT slice showing the maximum area of the irradiated heart relative to the mid-plane slice, and (5) sternal and contralateral breast thickness (measures of body fat). Results A strong linear correlation was found between the MHD and the mean heart dose. For every 1-cm increase in MHD, the mean heart dose increased by 2.9% on average (95% confidence interval 2.5–3.3). A strong linear-quadratic relationship was seen between the MHD and the mean heart BED. The mean LAD coronary artery dose and BED were also correlated with the MHD but the associations were weaker. These relationships were not affected by body fat. The mid-plane CT slice did not give a reliable assessment of cardiac irradiation. Conclusion The MHD is a reliable predictor of the mean heart dose and BED and gives an approximate estimate of the mean LAD coronary artery dose and BED. Doses predicted by the MHD could help assess the risk of radiation-induced cardiac toxicity where individual CT-based cardiac dosimetry is not possible.

Reverse Causality in Cardiovascular Epidemiological Research: More Common Than Imagined?

Abstract: Article, see p 2357 It is now well established that observational studies seeking evidence that a risk factor causes a disease are susceptible to various biases. Among the most important are residual confounding, whereby unmeasured or imprecisely measured confounders prevent causal inferences being drawn from associations between any 2 parameters, and reverse causality. Although the former is typically acknowledged in reports of such studies, the latter concept appears to be less well understood and, therefore, is more often overlooked as a potential explanation for apparent, often unexpected, associations between risk factors and adverse outcomes. With the potential for reverse causality in mind, Ravindrarajah and colleagues1 in this issue of Circulation , sought to determine whether the association of lower systolic blood pressure (SBP) values with higher mortality in observational studies in the elderly (>75–80 years of age) could be afflicted by this same phenomenon. They did so because recent trial data, in particular the SPRINT study (Systolic Blood Pressure Intervention Trial),2 demonstrated that lowering SBP to a target of 75 years of age, findings in almost complete contrast with such observational data. To test their hypotheses, the authors analyzed data from the Clinical Practice Research Datalink, a primary care cohort collected in the United Kingdom that, importantly, includes serial measurements of many risk factors. Using this resource, they not only addressed the association between SBP and mortality, but they did so according to (1) frailty category and (2) antihypertensive treatment. They also asked whether SBP levels declined before death and, if so, how did this decline compare with the pattern of SBP in those who survived, and whether these patterns differed in those on or off blood pressure–lowering treatments. The researchers were able to confirm that …

Amplification of AML1 in acute lymphoblastic leukemia is associated with a poor outcome

Abstract: A total of 28 children and nine adults with relapsed T-ALL were analyzed for the configuration of their T-cell receptor (TCR) and TAL1 genes at diagnosis and relapse to evaluate their stability throughout the disease course. A total of 150 clonal TCR and TAL1 gene rearrangements were identified in the 37 patients at diagnosis. In 65% of cases all rearrangements and in 27% of cases most rearrangements found at diagnosis were preserved at relapse. Two children with unusually late T-ALL recurrences displayed completely different TCR gene rearrangement sequences between diagnosis and relapse. This indicates that a proportion of very late T-ALL recurrences might represent second T-ALL. Specifically, 88% of clonal rearrangements identified at diagnosis in truly relapsed T-ALL were preserved at relapse. This is significantly higher as compared to previously studied precursor-B-ALL (~70%). Thus, from biological point of view, immunogenotype of T-ALL is more stable as compared with precursor-B-ALL. The overall stability of TCR gene rearrangements was higher in adult T-ALL (97%) than in childhood T-ALL (86%). Based on the stability of TCR gene rearrangements, we propose a strategy for PCR target selection (TCRD+TAL1 TCRB TCRG), which probably allows reliable minimal residual disease detection in all T-ALL patients.

Verbal autopsy of 80,000 adult deaths in Tamilnadu, South India

Abstract: Registration of the fact of death is almost complete in the city of Chennai and not so in the rural Villupuram district in Tamilnadu, India. The cause of death is often inadequately recorded on the death certificate in developing countries like India. A special verbal autopsy (VA) study of 48 000 adult (aged ≥ 25 yrs) deaths in the city of Chennai (urban) during 1995–97 and 32 000 in rural Villupuram during 1997–98 was conducted to arrive at the probable underlying cause of death to estimate cause specific mortality. A ten day training on writing verbal autopsy (VA) report for adult deaths was given to non-medical graduates with at least 15 years of formal education. They interviewed surviving spouse/close associates of the deceased to write a verbal autopsy report in local language (Tamil) on the complaints, symptoms, signs, duration and treatment details of illness prior to death. Each report was reviewed centrally by two physicians independently. Random re-interviewing of 5% of the VA reports was done to check the reliability and reproducibility of the VA report. The validity of VA diagnosis was assessed only for cancer deaths. Verbal autopsy reduced the proportion of deaths attributed to unspecified and unknown causes from 54% to 23% (p < 0.0001) in urban and from 41% to 26% (p < 0.0001) in rural areas in Tamilnadu for adult deaths (≥ 25). The sensitivity of VA to identify cancer was 95% in the age group 25–69. A ten day training programme to write verbal autopsy report with adequate feed back sessions and random sampling of 5% of the verbal autopsy reports for re-interview worked very well in Tamilnadu, to arrive at the probable underlying cause of death reliably for deaths in early adult life or middle age (25–69 years) and less reliably for older ages (70+). Thus VA is practicable for deaths in early adult life or middle age and is of more limited value in old age.