Out-of-field organ doses and associated risk of cancer development following radiation therapy with photons

Innovations in cancer treatment have contributed to the improved survival rate of these patients. Radiotherapy is one of the main options for cancer management nowadays. High doses of ionizing radiation are usually delivered to the tumor site with high energy photon beams. However, the therapeutic radiation exposure may lead to second cancer induction. Moreover, the introduction of intensity-modulated radiation therapy over the last decades has increased the radiation dose to out-of-field organs compared to that from conventional irradiation. The increased organ doses might result in elevated probabilities for developing secondary malignancies to critical organs outside the treatment volume. The organ-specific dosimetry is considered necessary for the theoretical second cancer risk assessment and the proper analysis of data derived from epidemiological reports. This study reviews the methods employed for the measurement and calculation of out-of-field organ doses from exposure to photons and/or neutrons. The strengths and weaknesses of these dosimetric approaches are described in detail. This is followed by a review of the epidemiological data associated with out-of-field cancer risks. Previously published theoretical cancer risk estimates for adult and pediatric patients undergoing radiotherapy with conventional and advanced techniques are presented. The methodology for the theoretical prediction of the probability of carcinogenesis to out-of-field sites and the limitations of this approach are discussed. The article also focuses on the factors affecting the magnitude of the probability for developing radiotherapy-induced malignancies. The restriction of out-of-field doses and risks through the use of different types of shielding equipment is presented.     

A Review of the International Atomic Energy Agency (IAEA) International Standards for Tissue Banks

The IAEA International Standards for Tissue Banks published in 2003 were based on the Standards then currently in use in the USA and the European Union, among others, and reflect the best practices associated with the operation of a tissue bank. They cover legal, ethical and regulatory controls as well as requirements and procedures from donor selection and tissue retrieval to processing and distribution of finished tissue for clinical use. The application of these standards allows tissue banks to operate with the current good tissue practice, thereby providing grafts of high quality that satisfy the national and international demand for safe and biologically useful grafts. The objective of this article is to review the IAEA Standards and recommend new topics that could improve the current version.     

Patient-Reported Outcome (PRO) Assessment in Clinical Trials: A Systematic Review of Guidance for Trial Protocol Writers

Background

Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers.

Methods and Findings

We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency.

Conclusions

PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care.     

Towards Harmonisation of Critical Laboratory Result Management - Review of the Literature and Survey of Australasian Practices

Timely release and communication of critical test results may have significant impact on medical decisions and subsequent patient outcomes. Laboratories therefore have an important responsibility and contribution to patient safety. Certification, accreditation and regulatory bodies also require that laboratories follow procedures to ensure patient safety, but there is limited guidance on best practices. In Australasia, no specific requirements exist in this area and critical result reporting practices have been demonstrated to be heterogeneous worldwide.Recognising the need for agreed standards and critical limits, the AACB started a quality initiative to harmonise critical result management throughout Australasia. The first step toward harmonisation is to understand current laboratory practices. Fifty eight Australasian laboratories responded to a survey and 36 laboratories shared their critical limits. Findings from this survey are compared to international practices reviewed in various surveys conducted elsewhere. For the successful operation of a critical result management system, critical tests and critical limits must be defined in collaboration with clinicians. Reporting procedures must include how critical results are identified; who can report and who can receive critical results; what is an acceptable timeframe within which results must be delivered or, if reporting fails, what escalation procedures should follow; what communication channels or systems should be used; what should be recorded and how; and how critical result procedures should be maintained and evaluated to assess impact on outcomes.In this paper we review the literature of current standards and recommendations for critical result management. Key elements of critical result reporting are discussed in view of the findings of various national surveys on existing laboratory practices, including data from our own survey in Australasia. Best practice recommendations are made that laboratories are expected to follow in order to provide high quality and safe service to patients.     

Echocardiography practice, training and accreditation in the intensive care: document for the World Interactive Network Focused on Critical Ultrasound (WINFOCUS)

Echocardiography is increasingly used in the management of the critically ill patient as a non-invasive diagnostic and monitoring tool. Whilst in few countries specialized national training schemes for intensive care unit (ICU) echocardiography have been developed, specific guidelines for ICU physicians wishing to incorporate echocardiography into their clinical practice are lacking. Further, existing echocardiography accreditation does not reflect the requirements of the ICU practitioner. The WINFOCUS (World Interactive Network Focused On Critical UltraSound) ECHO-ICU Group drew up a document aimed at providing guidance to individual physicians, trainers and the relevant societies of the requirements for the development of skills in echocardiography in the ICU setting. The document is based on recommendations published by the Royal College of Radiologists, British Society of Echocardiography, European Association of Echocardiography and American Society of Echocardiography, together with international input from established practitioners of ICU echocardiography. The recommendations contained in this document are concerned with theoretical basis of ultrasonography, the practical aspects of building an ICU-based echocardiography service as well as the key components of standard adult TTE and TEE studies to be performed on the ICU. Specific issues regarding echocardiography in different ICU clinical scenarios are then described. Obtaining competence in ICU echocardiography may be achieved in different ways – either through completion of an appropriate fellowship/training scheme, or, where not available, via a staged approach designed to train the practitioner to a level at which they can achieve accreditation. Here, peri-resuscitation focused echocardiography represents the entry level – obtainable through established courses followed by mentored practice. Next, a competence-based modular training programme is proposed: theoretical elements delivered through blended-learning and practical elements acquired in parallel through proctored practice. These all linked with existing national/international echocardiography courses. When completed, it is anticipated that the practitioner will have performed the prerequisite number of studies, and achieved the competency to undertake accreditation (leading to Level 2 competence) via a recognized National or European examination and provide the appropriate required evidence of competency (logbook). Thus, even where appropriate fellowships are not available, with support from the relevant echocardiography bodies, training and subsequently accreditation in ICU echocardiography becomes achievable within the existing framework of current critical care and cardiological practice, and is adaptable to each countrie's needs.     

Evolution of Point-of-Care Testing in Australia

Currently no mandatory standards or guidelines exist for Point-of-Care Testing (PoCT) in Australia. In 2001, a report on the role and value of ‘near patient testing’ in general practice outlined work that was required to assist the Australian Government to decide how to manage PoCT. Phillips Fox reported that adoption of mandatory accreditation requirements was not justified by the level of risk associated with PoCT.If implemented appropriately, PoCT could be useful with frontline management of chronic disease, relieving stress on general practice and expanding the reach of pathology.Interim PoCT standards in general practice were developed by a Quality Use of Pathology committee, and formed an accreditation framework for the PoCT in General Practice Trial. This trial concluded that PoCT has a role in supporting the primary healthcare team to manage chronic disease patients.While results of the trial are still being considered, the potential impact of funding PoCT in general practice is being treated as part of the wider review of pathology funding currently taking place in Australia.Although Australia has local models from which to draw experience, it has yet to decide the quality framework it would adopt if it was to roll out PoCT in general practice. The quality framework that Australia adopts for PoCT must achieve high quality pathology results that enhance clinical care.     

Benefit Sharing in a Global Context: Working Towards Solutions for Implementation

Due to the state of globalized clinical research, questions have been raised as to what, if any, benefits those who contribute to research should receive. One model for compensating research participants is “benefit sharing,” and the basic premise is that, as a matter of justice, those who contribute to scientific research should share in its benefits. While incorporated into several international documents for over two decades, benefit sharing has only been sparsely implemented. This analysis begins by addressing the concept of benefit sharing, its historical development, and how it has been applied in the context of virus sharing for influenza research. The second portion of this analysis presents recommendations for ensuring benefit sharing. These recommendations are threefold: 1) an emphasis on social pressure, 2) the revision of international documents as means to ensure benefit sharing, and 3) greater collaboration between sponsor IRB and host country IRB. Because clinical research is a globalized industry, a global model will be proposed in the second that focuses on collaboration between the sponsor and host country. This collaboration is vital in order to ensure that proper forms of benefit sharing are accomplished as a matter of justice.     

The use of out-of-plane high Z patient shielding for fetal dose reduction in computed tomography: Literature review and comparison with Monte-Carlo calculations of an alternative optimisation technique

When performing CT examinations on pregnant patients, great effort should be dedicated towards optimising the exposure of the mother and the conceptus. For this purpose, many radiology departments use high-Z garments to be wrapped around the patient's lower abdomen for out-of-plane organ shielding to protect the fetus. To assess their current protection efficiency, we performed a literature review and compared the efficiencies mentioned in the literature to Monte-Carlo calculations of CT protocols for which the overall scan length was reduced. We found 11 relevant articles, all of them reporting uterus exposure due to CT imaging performed for exclusion of pulmonary embolism, one of the leading causes of peripartum deaths in western countries. Uterus doses ranged between 60 and 660 µGy per examination, and relative dose reductions to the uterus due to high-Z garments were between 20 and 56%. Calculations showed that reducing the scan length by one to three centimetres could potentially reduce uterus dose up to 24% for chest imaging, and even 47% for upper abdominal imaging. These dose reductions were in the order of those achieved by high-Z garments. However, using the latter may negatively influence the diagnostic image quality and even interfere with the automatic exposure control system thus increasing patient dose if positioned in the primary beam, for example in the overranging length in helical acquisition. We conclude that efforts should be concentrated on positioning the patient correctly in the gantry and optimising protocol parameters, rather than using high-Z garments for out-of-plane uterus shielding.     

A review on photoneutrons characteristics in radiation therapy with high-energy photon beams

In radiation therapy with high-energy photon beams (E > 10 MeV) neutrons are generated mainly in linacs head thorough (γ,n) interactions of photons with nuclei of high atomic number materials that constitute the linac head and the beam collimation system. These neutrons affect the shielding requirements in radiation therapy rooms and also increase the out-of-field radiation dose of patients undergoing radiation therapy with high-energy photon beams. In the current review, the authors describe the factors influencing the neutron production for different medical linacs based on the performed measurements and Monte Carlo studies in the literature.     

Health System Barriers to Access and Use of Magnesium Sulfate for Women with Severe Pre-Eclampsia and Eclampsia in Pakistan: Evidence for Policy and Practice

Severe pre-eclampsia and eclampsia are rare but serious complications of pregnancy that threaten the lives of mothers during childbirth. Evidence supports the use of magnesium sulfate (MgSO4) as the first line treatment option for severe pre-eclampsia and eclampsia. Eclampsia is the third major cause of maternal mortality in Pakistan. As in many other Low- and Middle-Income Countries (LMIC), it is suspected that MgSO4 is critically under-utilized in the country. There is however a lack of information on context-specific health system barriers that prevent optimal use of this life-saving medicine in Pakistan. Combining quantitative and qualitative methods, namely policy document review, key informant interviews, focus group discussions and direct observation at health facility, we explored context-specific health system barriers and enablers that affect access and use of MgSO4 for severe pre-eclampsia and eclampsia in Pakistan. Our study finds that while international recommendations on MgSO4 have been adequately translated in national policies in Pakistan, the gap remains in implementation of national policies into practice. Barriers to access to and effective use of MgSO4 occur at health facility level where the medicine was not available and health staff was reluctant to use it. Low price of the medicine and the small market related to its narrow indications acted as disincentives for effective marketing. Results of our survey were further discussed in a multi-stakeholder round-table meeting and an action plan for increasing access to this life-saving medicine was identified.     

Legal challenges posed by the use of antimicrobials in food animal production

This review article provides a general analysis of the legal challenges presented by antimicrobial use in food animal production and the emerging public health responses to such use. The article stresses the importance of national and international law to the public health strategies and the interdependence between national and international law. The article argues that antimicrobial use in food animal production poses a challenge to the development of global health jurisprudence.     

Partnerships for better mental health worldwide: WPA recommendations on best practices in working with service users and family carers

WPA President M. Maj established the Task Force on Best Practice in Working with Service Users and Carers in 2008, chaired by H. Herrman. The Task Force had the remit to create recommendations for the international mental health community on how to develop successful partnership working. The work began with a review of literature on service user and carer involvement and partnership. This set out a range of considerations for good practice, including choice of appropriate terminology, clarifying the partnership process and identifying and reducing barriers to partnership working. Based on the literature review and on the shared knowledge in the Task Force, a set of ten recommendations for good practice was developed. These recommendations were the basis for a worldwide consultation of stakeholders with expertise as service users, families and carers, and the WPA Board and Council. The results showed a strong consensus across the international mental health community on the ten recommendations, with the strongest agreement coming from service users and carers. This general consensus gives a basis for Task Force plans to seek support for activities to promote shared work worldwide to identify best practice examples and create a resource to assist others to begin successful collaboration.     

Pharmacological and Host Considerations in the Selection of Dose and Duration of Azole Therapy for Adult Patients

Azole antifungals are used to treat a myriad of fungal infections in diverse patient populations. As a result, it becomes clear that use of one size fits all azole dosing regimens is illogical. Three general variable categories are essential to consider when developing an approach the management of fungal infections with the azoles. These categories are the pharmacological, microbiological, and host. In the clinical setting information regarding microbiological variables if often lacking; however, host and pharmacological data are abundant. Unfortunately, these available data are not always used to construct individualized dosing strategies. In this review, host and pharmacological factors that can influence azole activity will be presented. Additionally, recommendations will be provided to help the clinician optimize azole dosing regimens based on these variables.     

Overprescription of cholera vaccine to travellers by general practitioners.

A questionnaire describing five hypothetical patients intending to travel to different countries was sent to 113 general practitioners, who were asked to state which patients they would recommend cholera vaccination to. The response rate was 80%. The general practitioners'' recommendations were compared with those of the Liverpool School of Tropical Medicine. Sixty three of 86 respondents recommended cholera vaccination when it would probably have been unnecessary. A review of common sources of information on cholera vaccination showed that general practitioners are given confusing or inappropriate advice. General practitioners should be educated about when cholera vaccination is necessary; alternatively, the vaccine should be available only through special centres.     

Breaking new ground: challenging existing asthma guidelines

Background

While we have international guidelines and various national guidelines for asthma diagnosis and management, asthma remains poorly controlled in many children and adults. In this paper we review the limitations of current asthma guidelines and describe important issues and remaining questions regarding asthma guidelines for use, particularly in primary care.

Discussion

Clinical practice guidelines based on evidence from randomized controlled trials are considered the most rigorous and accurate. Current evidence-based guidelines are written predominantly from the perspective of the patient with a clear-cut asthma diagnosis, however, and tend not to consider the heterogeneity of asthma or to accommodate individual patient variations in response to treatment or their needs, differences in practice settings, or local differences in availability and cost of therapies. The results of randomized controlled trials, which are designed to establish efficacy of treatment under ideal conditions, may not apply to 'real-world' clinical practice, where patients are unselected, monitoring is less frequent, and effectiveness – the benefit of treatment in routine clinical practice – is the most relevant outcome. Moreover, most guidelines see asthma in isolation rather than considering other factors that may impact on asthma and response to asthma therapy, particularly age, allergic rhinitis, cigarette smoking, adherence, and genetic factors. When these links are recognized, guidelines rarely provide practical recommendations for treatment in these scenarios. Finally, there is some evidence that general practitioners are not convinced of the applicability of asthma guidelines to their practice settings, especially when those writing the guidelines principally work in specialist practice.

Conclusion

Developing country-specific guidelines or, ideally, local guidelines could provide more practical solutions for asthma care and could account for regional factors that influence patient choice and adherence to therapy. Pragmatic clinical trials and well-designed observational trials are needed in addition to randomized controlled trials to assess real-world effectiveness of therapies, and such evidence needs also to be considered by guideline writers. Finally, practical tools to facilitate the diagnosis and assessment of asthma and factors responsible for poor control, such as associated allergic rhinitis, limited adherence, and smoking behavior, are needed to supplement treatment information provided in clinical practice guidelines for asthma.

     

A multicenter dosimetry study to evaluate the imaging dose from Elekta XVI and Varian OBI kV-CBCT systems to cardiovascular implantable electronic devices (CIEDs)

The increasing use of daily CBCT in radiotherapy has raised concerns about the additional dose delivered to the patient, and it can also become a concern issue for those patients with cardiovascular implantable electronic devices (CIEDs) (Pacemaker [PM] and Implantable Cardioverter Defibrillator [ICD]). Although guidelines highly recommend that the cumulative dose received by CIEDs should be kept as low as possible, and a safe threshold based on patient risk classification needs to be respected, this additional imaging dose is not usually considered. Four centers with different dosimetry systems and different CBCT imaging protocols participated in this multicenter study to investigate the imaging dose to the CIEDs from Elekta XVI and Varian OBI kV-CBCT systems. It was found that although imaging doses received by CIEDs outside the CBCT field are negligible, special attention should be paid to this value when CIEDs are inside the field because the daily use of CBCT can sometimes contribute considerably to the total dose received by a CIED.     

One hundred years ago : Fashion and medicine

Objective: To determine which attributes of clinical practice guidelines influence the use of guidelines in decision making in clinical practice. Design: Observational study relating the use of 47 different recommendations from 10 national clinical guidelines to 12 different attributes of clinical guidelines—for example, evidence based, controversial, concrete. Setting: General practice in the Netherlands. Subjects: 61 general practitioners who made 12 880 decisions in their contacts with patients. Main outcome measures: Compliance of decisions with clinical guidelines according to the attribute of the guideline. Results: Recommendations were followed in, on average, 61% (7915/12 880) of the decisions. Controversial recommendations were followed in 35% (886/2497) of decisions and non-controversial recommendations in 68% (7029/10 383) of decisions. Vague and non-specific recommendations were followed in 36% (826/2280) of decisions and clear recommendations in 67% (7089/10 600) of decisions. Recommendations that demanded a change in existing practice routines were followed in 44% (1278/2912) of decisions and those that did not in 67% (6637/9968) of decisions. Evidence based recommendations were used more than recommendations for practice that were not based on research evidence (71% (2745/3841) v 57% (5170/9039)). Conclusions: People and organisations setting evidence based clinical practice guidelines should take into account some of the other important attributes of effective recommendations for clinical practice.

Key messages

• Specific attributes of clinical practice guidelines determine whether they are used in practice
• Evidence based recommendations are better followed in practice than recommendations not based on scientific evidence
• Precise definitions of recommended performance improve the use of guidelines
• Testing the feasibility and acceptance of clinical guidelines among the target group is important for effective implementation
• People setting evidence based guidelines need to understand the attributes of effective guidelines