Background
Systematic reviews are increasingly informing policies in tuberculosis (TB) care and control. They may also be a source of questions for future research. As part of the process of developing the International Roadmap for TB Research, we did a systematic review of published systematic reviews on TB, to identify research priorities that are most frequently suggested in reviews.Methodology/Principal Findings
We searched EMBASE, MEDLINE, Web of Science, and the Cochrane Library for systematic reviews and meta-analyses on any aspect of TB published between 2005 and 2010. One reviewer extracted data and a second reviewer independently extracted data from a random subset of included studies. In total, 137 systematic reviews, with 141 research questions, were included in this review. We used the UK Health Research Classification System (HRCS) to help us classify the research questions and priorities. The three most common research topics were in the area of detection, screening and diagnosis of TB (32.6%), development and evaluation of treatments and therapeutic interventions (23.4%), and TB aetiology and risk factors (19.9%). The research priorities determined were mainly focused on the discovery and evaluation of bacteriological TB tests and drug-resistant TB tests and immunological tests. Other important topics of future research were genetic susceptibility linked to TB and disease determinants attributed to HIV/TB. Evaluation of drug treatments for TB, drug-resistant TB and HIV/TB were also frequently proposed research topics.Conclusions
Systematic reviews are a good source of key research priorities. Findings from our survey have informed the development of the International Roadmap for TB Research by the TB Research Movement. 相似文献Aim
The aim of this research is to establish if variation exists in the dose delivered for head and neck (HN) localisation computed tomography (CT) imaging in radiation therapy (RT); to propose a national diagnostic reference levels (DRLs) for this procedure and to make a comparison between the national DRL and a DRL of a European sample.Background
CT has become an indispensable tool in radiotherapy (RT) treatment planning. It is a requirement of legislation in many countries that doses of ionising radiation for medical exposures be kept ‘As Low As Reasonably Achievable’. There are currently no dose guidelines for RT localisation CT of the HN.Materials and methods
All RT departments in Ireland and a sample of European departments were surveyed. Dose data on CT dose length product (DLP); dose index volume (CTDIvol); current time product; tube voltage and scan length was acquired for ten average-sized HN patients from each department. DRLs were proposed for DLP and CTDIvol using the rounded 75th percentile of the distribution of the means.Results
42% of Irish departments and one European department completed the survey. Significant variation was found in the mean DLP, CTDIvol and scan lengths across the Irish departments. The proposed Irish DRL is 882?mGy?cm and 21?mGy and the European department DRL is 816?mGy?cm and 21?mGy, for DLP and CTDIvol, respectively.Conclusions
Variation exists in doses used for HN RT localisation CT. DRLs have been proposed for comparison purposes with the aim of dose optimisation. 相似文献With respect to the issue of re-introducing ruminant protein into the feed-chain, our opinion is that sustaining an absolute ban on feeding ruminant protein to ruminants is essential. In particular, the spread and impact of non-classical forms of scrapie and BSE in ruminants is not fully understood and the risks cannot be estimated. Atypical prion agents will probably continue to represent the dominant form of prion diseases in the near future in Europe. Atypical L-type BSE has clear zoonotic potential, as demonstrated in experimental models. Similarly, there are now data indicating that the atypical scrapie agent can cross various species barriers. More epidemiological data from large cohorts are necessary to reach any conclusion on the impact of its transmissibility on public health. Re-evaluations of safety precautions may become necessary depending on the outcome of these studies.
Intensified searching for molecular determinants of the species barrier is recommended, since this barrier is key for important policy areas and risk assessment. Understanding the structural basis for strains and the basis for adaptation of a strain to a new host will require continued fundamental research, also needed to understand mechanisms of prion transmission, replication and how they cause nervous system dysfunction and death. Early detection of prion infection, ideally at a preclinical stage, also remains crucial for development of effective treatment strategies. 相似文献
Background
Patients exposed to low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction may be at increased risk of cancer.Methods
Using an administrative database, we selected a cohort of patients who had an acute myocardial infarction between April 1996 and March 2006 and no history of cancer. We documented all cardiac imaging and therapeutic procedures involving low-dose ionizing radiation. The primary outcome was risk of cancer. Statistical analyses were performed using a time-dependent Cox model adjusted for age, sex and exposure to low-dose ionizing radiation from noncardiac imaging to account for work-up of cancer.Results
Of the 82 861 patients included in the cohort, 77% underwent at least one cardiac imaging or therapeutic procedure involving low-dose ionizing radiation in the first year after acute myocardial infarction. The cumulative exposure to radiation from cardiac procedures was 5.3 milliSieverts (mSv) per patient-year, of which 84% occurred during the first year after acute myocardial infarction. A total of 12 020 incident cancers were diagnosed during the follow-up period. There was a dose-dependent relation between exposure to radiation from cardiac procedures and subsequent risk of cancer. For every 10 mSv of low-dose ionizing radiation, there was a 3% increase in the risk of age- and sex-adjusted cancer over a mean follow-up period of five years (hazard ratio 1.003 per milliSievert, 95% confidence interval 1.002–1.004).Interpretation
Exposure to low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction is associated with an increased risk of cancer.Studies involving atomic bomb survivors have documented an increased incidence of malignant neoplasm related to the radiation exposure.1–4 Survivors who were farther from the epicentre of the blast had a lower incidence of cancer, whereas those who were closer had a higher incidence.5 Similar risk estimates have been reported among workers in nuclear plants.6 However, little is known about the relation between exposure to low-dose ionizing radiation from medical procedures and the risk of cancer.In the past six decades since the atomic bomb explosions, most individuals worldwide have had minimal exposure to ionizing radiation. However, the recent increase in the use of medical imaging and therapeutic procedures involving low-dose ionizing radiation has led to a growing concern that individual patients may be at increased risk of cancer.7–12 Whereas strict regulatory control is placed on occupational exposure at work sites, no such control exists among patients who are exposed to such radiation.13–16It is not only the frequency of these procedures that is increasing. Newer types of imaging procedures are using higher doses of low-dose ionizing radiation than those used with more traditional procedures.8,11 Among patients being evaluated for coronary artery disease, for example, coronary computed tomography is increasingly being used. This test may be used in addition to other tests such as nuclear scans, coronary angiography and percutaneous coronary intervention, each of which exposes the patient to low-dose ionizing radiation.12,17–21 Imaging procedures provide information that can be used to predict the prognosis of patients with coronary artery disease. Since such predictions do not necessarily translate into better clinical outcomes,8,12 the prognostic value obtained from imaging procedures using low-dose ionizing radiation needs to be balanced against the potential for risk.Authors of several studies have estimated that the risk of cancer is not negligible among patients exposed to low-dose ionizing radiation.22–27 To our knowledge, none of these studies directly linked cumulative exposure and cancer risk. We examined a cohort of patients who had acute myocardial infarction and measured the association between low-dose ionizing radiation from cardiac imaging and therapeutic procedures and the risk of cancer. 相似文献Introduction
The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII), which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than acute exposures of atomic bomb survivors. This correction is known as the dose and dose rate effectiveness factor for the life span study of atomic bomb survivors (DDREFLSS). It was calculated by applying a linear-quadratic dose response model to data from Japanese atomic bomb survivors and a limited number of animal studies.Methods and Results
We argue that the linear-quadratic model does not provide appropriate support to estimate the risk of contemporary exposures. In this work, we re-estimated DDREFLSS using 15 animal studies that were not included in BEIR VII’s original analysis. Acute exposure data led to a DDREFLSS estimate from 0.9 to 3.0. By contrast, data that included both acute and protracted exposures led to a DDREFLSS estimate from 4.8 to infinity. These two estimates are significantly different, violating the assumptions of the linear-quadratic model, which predicts that DDREFLSS values calculated in either way should be the same.Conclusions
Therefore, we propose that future estimates of the risk of protracted exposures should be based on direct comparisons of data from acute and protracted exposures, rather than from extrapolations from a linear-quadratic model. The risk of low dose exposures may be extrapolated from these protracted estimates, though we encourage ongoing debate as to whether this is the most valid approach. We also encourage efforts to enlarge the datasets used to estimate the risk of protracted exposures by including both human and animal data, carcinogenesis outcomes, a wider range of exposures, and by making more radiobiology data publicly accessible. We believe that these steps will contribute to better estimates of the risks of contemporary radiation exposures. 相似文献Background/Aim
Targeted radiotherapy of liver malignancies has found to be effective in selected patients. A key limiting factor of these therapies is the relatively low tolerance of the liver parenchyma to radiation. We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI).Methods and Materials
Patients with liver metastases from colorectal carcinoma who were scheduled for local ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy) were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks (treatment) or no medication (control). Focal RILI at follow-up was assessed using functional hepatobiliary magnetic resonance imaging (MRI). A minimal threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly exposed to, was quantified by merging MRI and dosimetry data.Results
Results from an intended interim-analysis made a premature termination necessary. Twenty-two patients were included in the per-protocol analysis. Minimal mean hepatic threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly higher in the study treatment-group compared with the control (19.1 Gy versus 14.6 Gy, p = 0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed in 45.5% of patients in the treatment versus 90.9% of the control group. No significant differences between the groups were observed at the 12-week follow-up.Conclusions
The post-therapeutic application of PTX, UDCA and low-dose LMWH significantly reduced the extent and incidence fRILI at 6 weeks after radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after cessation of PTX, UDCA and LMWH during weeks 1–8) in the treatment group was comparable to the control group thus supporting the observation that the agents mitigated fRILI.Trial Registration
EU clinical trials register 2008-002985-70 ClinicalTrials.gov NCT01149304相似文献Aim
When investigating radiation accidents, it is very important to determine the exposition dose to the individuals. In the case of exposures over 1 Gy, clinicians may expect deterministic effects arising the following weeks and months, in these cases dose estimation will help physicians in the planning of therapy. Nevertheless, for doses below 1 Gy, biodosimetry data are important due to the risk of developing late stochastic effects. Finally, some accidental overexposures are lack of physical measurements and the only way of quantifying dose is by biological dosimetry.Background
The analysis of chromosomal aberrations by different techniques is the most developed method of quantifying dose to individuals exposed to ionising radiations.1,2 Furthermore, the analysis of dicentric chromosomes observed in metaphases from peripheral lymphocytes is the routine technique used in case of acute exposures to assess radiation doses.Materials and methods
Solid stain of chromosomes is used to determine dicentric yields for dose estimation. Fluorescence in situ hybridization (FISH) for translocations analysis is used when delayed sampling or suspected chronically irradiation dose assessment. Recommendations in technical considerations are based mainly in the IAEA Technical Report No. 405.2Results
Experience in biological dosimetry at Gregorio Marañón General Hospital is described, including own calibration curves used for dose estimation, background studies and real cases of overexposition.Conclusion
Dose assessment by biological dosimeters requires a large previous standardization work and a continuous update. Individual dose assessment involves high qualification professionals and its long time consuming, therefore requires specific Centres. For large mass casualties cooperation among specialized Institutions is needed. 相似文献![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)