Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Keeping the ICRP recommendations fit for purpose.

The International Commission on Radiological Protection (ICRP) has embarked on a review and revision of the system of Radiological Protection that will update the 2007 general recommendations in ICRPPublication 103. This is the beginning of a process that will take several years, involving open and transparent engagement with organisations and individuals around the world. While the system is robust and has performed well, it must adapt to address changes in science and society to remain fit for purpose. The aim of this paper is to encourage discussions on which areas of the system might gain the greatest benefit from review, and to initiate collaborative efforts. Increased clarity and consistency are high priorities. The better the system is understood, the more effectively it can be applied, resulting in improved protection and increased harmonisation. Many areas are identified for potential review including: classification of effects, with particular focus on tissue reactions; reformulation of detriment, potentially including non-cancer diseases; re-evaluation of the relationship between detriment and effective dose, and the possibility of defining detriments for males and females of different ages; individual variation in the response to radiation exposure; heritable effects; and effects and risks in non-human biota and ecosystems. Some of the basic concepts are also being considered, including the framework for bringing together protection of people and the environment, incremental improvements to the fundamental principles of justification and optimisation, a broader approach to protection of individuals, and clarification of the exposure situations introduced in 2007. In addition, ICRP is considering identifying where explicit incorporation of the ethical basis of the system would be beneficial, how to better reflect the importance of communications and stakeholder involvement, and further advice on education and training. ICRP invites responses on these and other areas relating to the review of the System of Radiological Protection.

The identification of sulfide oxidation as a potential metabolism driving primary production on late Noachian Mars.

The transition of the martian climate from the wet Noachian era to the dry Hesperian (4.1-3.0 Gya) likely resulted in saline surface waters that were rich in sulfur species. Terrestrial analogue environments that possess a similar chemistry to these proposed waters can be used to develop an understanding of the diversity of microorganisms that could have persisted on Mars under such conditions. Here, we report on the chemistry and microbial community of the highly reducing sediment of Colour Peak springs, a sulfidic and saline spring system located within the Canadian High Arctic. DNA and cDNA 16S rRNA gene profiling demonstrated that the microbial community was dominated by sulfur oxidising bacteria, suggesting that primary production in the sediment was driven by chemolithoautotrophic sulfur oxidation. It is possible that the sulfur oxidising bacteria also supported the persistence of the additional taxa. Gibbs energy values calculated for the brines, based on the chemistry of Gale crater, suggested that the oxidation of reduced sulfur species was an energetically viable metabolism for life on early Mars.

The International Atomic Energy Agency action plan on radiation protection of patients and staff in interventional procedures: Achieving change in practice.

INTRODUCTION: The International Atomic Energy Agency (IAEA) organized the 3rd international conference on radiation protection (RP) of patients in December 2017. This paper presents the conclusions on the interventional procedures (IP) session. MATERIAL AND METHODS: The IAEA conference was conducted as a series of plenary sessions followed by various thematic sessions. "Radiation protection of patients and staff in interventional procedures" session keynote speakers presented information on: 1) Risk management of skin injuries, 2) Occupational radiation risks and 3) RP for paediatric patients. Then, a summary of the session-related papers was presented by a rapporteur, followed by an open question-and-answer discussion. RESULTS: Sixty-seven percent (67%) of papers came from Europe. Forty-four percent (44%) were patient studies, 44% were occupational and 12% were combined studies. Occupational studies were mostly on eye lens dosimetry. The rest were on scattered radiation measurements and dose tracking. The majority of patient studies related to patient exposure with only one study on paediatric patients. Automatic patient dose reporting is considered as a first step for dose optimization. Despite efforts, paediatric IP radiation dose data are still scarce. The keynote speakers outlined recent achievements but also challenges in the field. Forecasting technology, task-specific targeted education from educators familiar with the clinical situation, more accurate estimation of lens doses and improved identification of high-risk professional groups are some of the areas they focused on. CONCLUSIONS: Manufacturers play an important role in making patients safer. Low dose technologies are still expensive and manufacturers should make these affordable in less resourced countries. Automatic patient dose reporting and real-time skin dose map are important for dose optimization. Clinical audit and better QA processes together with more studies on the impact of lens opacities in clinical practice and on paediatric patients are needed.

Nailfold capillary morphology in exfoliation syndrome.

PurposeThe purpose of the study was to investigate nailfold microvascular morphology in exfoliation syndrome with or without glaucoma (XFS/XFG) compared with primary open-angle glaucoma (POAG) and control subjects using nailfold capillary videomicroscopy.Patients and methodsWe used a JH-1004 capillaroscope to perform nailfold capillary videomicroscopy on the fourth and fifth digit of the non-dominant hand. We enrolled 56 XFS/XFG patients, 87 POAG patients, and 75 control subjects. Masked observers graded the videos for hemorrhages, avascular zones ≥200 microns (µm), and degree of microvascular tortuosity on a four-point subjective scale. Multivariable odds ratios, 95% confidence intervals and P-for trends for assessing the relation between morphological changes and POAG or XFS/XFG were obtained from logistic regression analyses. We also assessed this relation with XFS/XFG compared with POAG in multivariable models.ResultsAfter adjusting for multiple covariates, nailfold hemorrhages, avascular zones ≥200 µm, and higher degree of vascular tortuosity were more common in XFS/XFG vs controls (P-for trend ≤0.0001) and in POAG vs controls (P-for trend ≤0.01). For each 100 capillaries, the number of hemorrhages was similar (P-for trend=0.91) between XFS/XFG and POAG patients; however, there were more avascular zones per 100 capillaries with borderline significance (P-for trend=0.04) in the XFS/XFG group. XFS/XFG patients had more tortuosity than POAG patients; specifically, having a tortuosity score ≥1.5 was associated with a 4.4-fold increased odds of XFS/XFG (95% confidence interval: 1.5-13.3) relative to a tortuosity score <1.0 (P-for trend=0.005).ConclusionA high degree of nailfold capillary tortuosity is a distinct non-ocular feature associated with XFS/XFG compared with either POAG or controls.

The future of ICRP: towards a centenary and beyond.

The International Commission on Radiological Protection (ICRP) has been in existence for 87 y, since its establishment in 1928. It remains a leading authority in radiological protection, and its role is to provide recommendations and guidance on all aspects of protection against ionising radiation. The published recommendations of ICRP form the basis of radiation safety standards worldwide. Modernisation of the organisation in recent years has led to new initiatives and changes. These have included writing a strategic plan and code of ethics for the first time. Elections for committee membership have been through open nominations, a process which will shortly be repeated for the membership in the next term, commencing on 1 July 2017. Biennial symposia started in 2011, and the success of the first two symposia has secured this venture as a regular part of the ICRP calendar. ICRP has also revised its method of working with other organisations by establishing 'special liaison organisation' status. This has improved collaboration with the ever-expanding number of organisations working in radiological protection, with whom it is important that ICRP has essential links. ICRP is also looking to review its legal basis and governing documents in the future, in order to ensure that best practices are being followed as ICRP evolves. In addition, the strategic plan will be reviewed and updated regularly. Other ways of working with organisations will be considered to further strengthen engagement with the wider radiological protection community. ICRP aims to make its publications available at low or no cost, and to produce both a plain language overview of the system of radiological protection and a summary of the recommendations. These activities will require additional financial resources, and ICRP has embarked on a fundraising campaign to support such efforts. ICRP can be proud of its history of maintaining its independence and preserving the wide respect earned over many years. Despite long traditions, ICRP has evolved and will continue to do so to perform as a more modern organisation as it heads towards a centenary and beyond.

ICRP: past, present, and future.

The International Commission on Radiological Protection (ICRP) is a premier international organisation for the protection of workers, patients, and the public against ionising radiation. It was established in 1928 to advance, for the public benefit, the science of radiological protection, with its work in the early years focusing mainly on occupational exposure in medicine. The name 'International Commission on Radiological Protection' was adopted in 1950 to reflect the wider and more diverse areas of work that were being undertaken. ICRP has published 13 sets of general recommendations and these form the basis of radiation safety standards worldwide. ICRP consists of the Main Commission and five standing committees. There are 84 official members of the Main Commission and Committees 1-5, but more than 200 members who work with ICRP through its task groups. ICRP has developed a strategic plan for 2011-2017 and has made progress with some of its initiatives. These include establishing close liaison with other radiological protection organisations, responding to the needs and concerns of the radiological protection community, and identifying areas of work that require scrutiny of science and practice to produce relevant recommendations. This strategy means that ICRP will continue to be a leader in radiological protection for many years to come.

Endovascular aneurysm repair (EVAR) follow-up imaging: the assessment and treatment of common postoperative complications.

Endovascular abdominal aortic aneurysm repair (EVAR) is a well-established procedure, which has long-term mortality rates similar to that of open repair. It has the additional benefit of being less invasive, making it the favoured method of treating abdominal aortic aneurysms in elderly and high-risk patients with multiple co-morbidities. The main disadvantage of EVAR is the higher rate of re-intervention, due to device-related complications, including endoleaks, limb occlusion, stent migration, kinking, and infection. As a result lifelong surveillance is required. In order to avoid missing these complications, intricate knowledge of stent graft design, good-quality diagnostic ultrasound skills, multiplanar reformatting of CT images, and reproducible investigations are important. Most of these complications can be treated via an endovascular approach using cuff extensions, uncovered stents, coils, and liquid embolic agents. Open surgery is reserved for complex complications, where an endovascular approach is not feasible.

ICRP PUBLICATION 120: Radiological protection in cardiology.

Cardiac nuclear medicine, cardiac computed tomography (CT), interventional cardiology procedures, and electrophysiology procedures are increasing in number and account for an important share of patient radiation exposure in medicine. Complex percutaneous coronary interventions and cardiac electrophysiology procedures are associated with high radiation doses. These procedures can result in patient skin doses that are high enough to cause radiation injury and an increased risk of cancer. Treatment of congenital heart disease in children is of particular concern. Additionally, staff(1) in cardiac catheterisation laboratories may receive high doses of radiation if radiological protection tools are not used properly. The Commission provided recommendations for radiological protection during fluoroscopically guided interventions in Publication 85, for radiological protection in CT in Publications 87 and 102, and for training in radiological protection in Publication 113 (ICRP, 2000b,c, 2007a, 2009). This report is focused specifically on cardiology, and brings together information relevant to cardiology from the Commission's published documents. There is emphasis on those imaging procedures and interventions specific to cardiology. The material and recommendations in the current document have been updated to reflect the most recent recommendations of the Commission. This report provides guidance to assist the cardiologist with justification procedures and optimisation of protection in cardiac CT studies, cardiac nuclear medicine studies, and fluoroscopically guided cardiac interventions. It includes discussions of the biological effects of radiation, principles of radiological protection, protection of staff during fluoroscopically guided interventions, radiological protection training, and establishment of a quality assurance programme for cardiac imaging and intervention. As tissue injury, principally skin injury, is a risk for fluoroscopically guided interventions, particular attention is devoted to clinical examples of radiation-related skin injuries from cardiac interventions, methods to reduce patient radiation dose, training recommendations, and quality assurance programmes for interventional fluoroscopy.

Prospective audit of cross-sectional imaging and radiation exposure in general surgical patients.

INTRODUCTION: Most patients admitted with an acute surgical problem undergo some imaging during their in-patient stay. As computed tomography (CT) scanning becomes more readily available, it is becoming the mainstay of assessment. Recent studies have commented on the potential adverse effects of early cross-sectional imaging. This audit aimed to determine the use of early cross-sectional imaging and associated radiation dose in an acute surgical cohort. PATIENTS AND METHODS: Data from 500 acute surgical patients were prospectively collected over a 3-month period. CT scans were undertaken, the effect on subsequent diagnostic and management decisions and the potential associated risks were evaluated. RESULTS: Almost 40% of subjects underwent CT scanning. Of these, 20% did not alter management and could be deemed unnecessary. The radiation exposure equated to an age- and gender-specific risk of fatal cancer induction between 1 in 1675 and 1 in 7130. CONCLUSIONS: Early-cross sectional imaging provides a valuable diagnostic adjunct. Decisions to expose patients to potentially hazardous radiation need to acknowledge the anticipated benefits versus risks.

Cuban healthcare providers in Venezuela: a case study.

Approximately 31,000 Cuban healthcare providers reside in Venezuela as part of an initiative to increase Venezuelans' access to health care. The concept began in 1999 as part of the new constitution, and has grown steadily to include 6000 clinics, health promotion and prevention programmes, an integrated healthcare system, and a vision to train and deploy community public health physicians selected from and trained within the neighbourhood. In the case study described herein, physician-patient consultations increased from 3.5 million to 17 million, and the numbers of primary care physicians, nurses and dentists increased dramatically. Furthermore, in Caracas, there has been a 30% reduction in the use of emergency rooms at public hospitals. Estimates are provided for preventive services and potential lives saved. As health care is a politically-laden issue in many countries, all approaches to reducing healthcare disparities are worth analysing for their potential contributions to population health improvement.

An emergency EVAR service reduces mortality in ruptured abdominal aortic aneurysms.

OBJECTIVES: The aim of this study was to compare all in-hospital mortality for ruptured abdominal aortic aneurysms (rAAAs) before and after the establishment of an emergency EVAR (eEVAR) service. DESIGN AND METHODS: An eEVAR service was established in January 2006, since when all patients presenting with rAAAs have been considered for endovascular repair. Data for all rAAAs presenting between January 2006 and December 2007 was prospectively collected (Group 1). This patient group was compared to those presenting with rAAA between January 2003 and December 2005 when eEVAR was not offered at our institution (Group 2). These records had also been collected prospectively and submitted to the National Vascular Database (NVD). RESULTS: A total of 50 rAAAs (17 eEVAR, 29 open repairs, 4 palliated) presented after the introduction of eEVAR (Group 1) and 71 in the historical Group 2 of which 54 underwent open repair and 17 were palliated. The total in-hospital mortality was significantly lower in Group 1 20% (eEVAR (n=1), 6%: Open (n=5), 17%: palliated (n=4), 100%) when compared to Group 2 54% (Open (n=21), 39%: palliated (n=17), 100%) (p=0.000001). Furthermore similar significant differences were seen in 30-day operative mortalities between the two groups 13% in Group 1 versus 39% in Group 2 (p=0.0003). In addition the proportion of patients who were palliated has significantly decreased (8% Group 1 versus 24% Group 2, p=0.01). CONCLUSIONS: The establishment of an eEVAR service has significantly reduced in-hospital mortality for patients presenting with ruptured abdominal aortic aneurysms.

Imaging appearances and endovascular management of uncommon pseudoaneurysms.

Pseudoaneurysms are uncommon and their aetiology is varied. They occur in numerous anatomical locations and present with a multitude of clinical presentations sometimes life-threatening. This review describes the causes, sites, and presentations of uncommon pseudoaneurysms, as well as illustrating their diagnostic appearances and endovascular management.

Endovascular stenting of large popliteal artery aneurysm is feasible!

INTRODUCTION: Endovascular stenting has been successfully employed in management of aortic aneurysms; however, its utility in managing popliteal aneurysms remains questionable. This is because of the non-availability of long term data about graft patency rates. CASE PRESENTATION: We report a case of large popliteal artery aneurysm stenting in a patient with significant co-morbidities and high risk for open surgical repair. He underwent successful endovascular stenting of a popliteal artery aneurysm measuring 6.4x9.7 cm extending for approximately 11.0 cm in length with Hemobahn grafts. The graft was patent at 12 months of follow up with complete exclusion of the aneurysm. CONCLUSIONS: Popliteal stents can be successfully used in treating large popliteal artery aneurysms in patients unfit for open repair.

Radiation exposure during endovascular aneurysm repair.

BACKGROUND: Endovascular stent-grafting is an established option for the repair of abdominal aortic aneurysm (AAA) that can involve prolonged manipulation under radiological control. The aim was to determine the average radiation exposure sustained during endovascular aneurysm repair (EVAR) and the first year of postoperative surveillance. METHODS: Prospective radiation dose data were recorded and used to calculate dose area product (DAP) values for 96 patients undergoing EVAR. The DAP data were then used to determine the entrance skin dose (ESD), an indicator of potential skin damage, and the effective dose, an indicator of long-term cancer risk, for each patient. RESULTS: The median ESD during EVAR was 0.85 (interquartile range 0.51-3.74) Gy. The threshold for possible radiation-induced skin damage of 2 Gy was exceeded in 29 per cent of procedures. The effective dose of radiation in the first year following EVAR was 79 mSv. CONCLUSION: Radiation doses administered during EVAR were higher than previously thought, with a potential risk of radiation-induced skin damage and later malignancy.

Internal iliac artery branch graft for common iliac artery aneurysm following previous open abdominal aortic aneurysm repair.

To demonstrate the use of a commercially available branch stent graft system, designed to preserve the internal iliac artery (IIA) in common iliac artery (CIA) aneurysms (CIAA) in two patients, who had undergone previous abdominal aortic aneurysm (AAA) surgery.

The clearance kinetics of autologous RhD-positive erythrocytes coated ex vivo with novel recombinant and monoclonal anti-D antibodies.

Anti-D is given routinely to pregnant RhD-negative women to prevent haemolytic disease of the fetus and newborn. To overcome the potential drawbacks associated with plasma-derived products, monoclonal and recombinant forms of anti-D have been developed. The ability of two such antibodies, BRAD-3/5 monoclonal anti-D IgG (MAD) and rBRAD-3/5 recombinant anti-D IgG (RAD), to clear RhD-positive erythrocytes from the circulation was compared using a dual radiolabelling technique. Six RhD-positive males received autologous erythrocytes radiolabelled with (99m)Tc and (51)Cr and coated ex vivo with MAD and RAD. Blood samples were collected up to 1 h following intravenous injection, and percentage dose of radioactivity in the samples determined. Three different levels of coating were used on three separate occasions. No significant differences between MAD and RAD were observed in the initial clearance rate constant at any dose level. The log[activity]-time clearance plots were curved, showing a reduction in the clearance rate constant with time. This reduction was more marked for RAD than for MAD. The results support a dynamic model for the clearance of antibody-coated erythrocytes that may have wider relevance for the therapeutic use of antibodies.

Scope of radiological protection control measures.

In this report, the Commission recommends approaches to national authorities for their definition of the scope of radiological protection control measures through regulations, by using its principles of justification and optimisation. The report provides advice for deciding the radiation exposure situations that should be covered by the relevant regulations because their regulatory control can be justified, and, conversely, those that may be considered for exclusion from the regulations because their regulatory control is deemed to be unamenable and unjustified. It also provides advice on the situations resulting from regulated circumstances but which may be considered by regulators for exemption from complying with specific requirements because the application of these requirements is unwarranted and exemption is the optimum option. Thus, the report describes exclusion criteria for defining the scope of radiological protection regulations, exemption criteria for planned exposure situations, and the application of these concepts in emergency exposure situations and in existing exposure situations. The report also addresses specific exposure situations such as exposure to low-energy or low-intensity adventitious radiation, cosmic radiation, naturally occurring radioactive materials, radon, commodities, and low-level radioactive waste. The quantitative criteria in the report are intended only as generic suggestions to regulators for defining the regulatory scope, in the understanding that the definitive boundaries for establishing the situations that can be or need to be regulated will depend on national approaches.

Hepatitis B virus (HBV) DNA screening of blood donations in minipools with the COBAS AmpliScreen HBV test.

BACKGROUND: The risk of hepatitis B virus (HBV) transmission by blood transfusion (estimated at 1 in 63,000-1 in 205,000 units in the United States) exceeds that of hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Reduction of window-period HBV transmissions through detection of HBV DNA-positive units by minipool nucleic acid testing (MP NAT) would be expected to decrease this risk. STUDY DESIGN AND METHODS: A large multicenter study of the COBAS AmpliScreen HBV test (Roche Molecular Systems) was conducted on minipools of 24 blood donation specimens. The yield of HBV DNA-positive, hepatitis B surface antigen (HBsAg)-negative window-period donations was determined relative to current and newly licensed HBsAg assays. Donors with selected HBV DNA, HBsAg, and anti-hepatitis B core antigen (HBc) results were further evaluated. RESULTS: The detection rate of window-period units was 1 in 352,451 (95% confidence interval, 1 in 2,941,176-1 in 97,561). Assay specificity was high (99.9964%). HBV DNA was detected in 84 percent of HBsAg-positive, anti-HBc-positive donations by MP NAT and in 94 percent when individual-donation (ID) NAT was added. HBV DNA was detected in 0.03 percent of HBsAg-negative, anti-HBc-positive donations by MP NAT and in 0.41 percent when ID NAT was added. CONCLUSIONS: Implementation of HBV MP NAT will provide an increment in safety relative to HBV serologic screening, similar to that for HCV and in excess of that for HIV. Our data indicate that the implementation of HBV MP NAT would likely interdict 39 HBV window-period units and prevent 56 cases of transfusion-transmitted HBV infection annually. The current data indicate that HBV MP NAT should not lead to discontinuation of anti-HBc testing but that discontinuation of HBsAg testing with retention of anti-HBc testing may be possible.