Impact of solitary pulmonary nodule size on qualitative and quantitative assessment using 18F-fluorodeoxyglucose PET/CT: the SPUTNIK trial.

PURPOSE: To compare qualitative and semi-quantitative PET/CT criteria, and the impact of nodule size on the diagnosis of solitary pulmonary nodules in a prospective multicentre trial. METHODS: Patients with an SPN on CT ≥ 8 and ≤ 30 mm were recruited to the SPUTNIK trial at 16 sites accredited by the UK PET Core Lab. Qualitative assessment used a five-point ordinal PET-grade compared to the mediastinal blood pool, and a combined PET/CT grade using the CT features. Semi-quantitative measures included SUVmax of the nodule, and as an uptake ratio to the mediastinal blood pool (SURBLOOD) or liver (SURLIVER). The endpoints were diagnosis of lung cancer via biopsy/histology or completion of 2-year follow-up. Impact of nodule size was analysed by comparison between nodule size tertiles. RESULTS: Three hundred fifty-five participants completed PET/CT and 2-year follow-up, with 59% (209/355) malignant nodules. The AUCs of the three techniques were SUVmax 0.87 (95% CI 0.83;0.91); SURBLOOD 0.87 (95% CI 0.83; 0.91, p = 0.30 versus SUVmax); and SURLIVER 0.87 (95% CI 0.83; 0.91, p = 0.09 vs. SUVmax). The AUCs for all techniques remained stable across size tertiles (p > 0.1 for difference), although the optimal diagnostic threshold varied by size. For nodules < 12 mm, an SUVmax of 1.75 or visual uptake equal to the mediastinum yielded the highest accuracy. For nodules > 16 mm, an SUVmax ≥ 3.6 or visual PET uptake greater than the mediastinum was the most accurate. CONCLUSION: In this multicentre trial, SUVmax was the most accurate technique for the diagnosis of solitary pulmonary nodules. Diagnostic thresholds should be altered according to nodule size. TRIAL REGISTRATION: ISRCTN - ISRCTN30784948. ClinicalTrials.gov - NCT02013063.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. METHODS AND ANALYSIS: The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. ETHICS AND DISSEMINATION: Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30784948; Pre-results.

Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography.

Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular support of tumours through analysis of temporal changes in attenuation in blood vessels and tissues during a rapid series of images acquired with intravenous administration of iodinated contrast material. Commercial software for DCE-CT analysis allows pixel-by-pixel calculation of a range of validated physiological parameters and depiction as parametric maps. Clinical studies support the use of DCE-CT parameters as surrogates for physiological and molecular processes underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of drug action in early phase trials for the treatment of a range of cancers. DCE-CT can be appended to current imaging assessments of tumour response with the benefits of wide availability and low cost. This paper sets out guidelines for the use of DCE-CT in assessing tumour vascular support that were developed using a Delphi process. Recommendations encompass CT system requirements and quality assurance, radiation dosimetry, patient preparation, administration of contrast material, CT acquisition parameters, terminology and units, data processing and reporting. DCE-CT has reached technical maturity for use in therapeutic trials in oncology. The development of these consensus guidelines may promote broader application of DCE-CT for the evaluation of tumour vascularity. Key Points • DCE-CT can robustly assess tumour vascular support • DCE-CT has reached technical maturity for use in therapeutic trials in oncology • This paper presents consensus guidelines for using DCE-CT in assessing tumour vascularity.

Can imaging help improve the survival of cancer patients?

Survival, quality-adjusted survival and mortality are important and related measures of outcome in cancer care. The impact of imaging on these outcomes can be ascertained from observational and modelling studies, frequently performed to evaluate cost-effectiveness. Examples where incorporation of imaging into cancer care can be shown to improve survival include breast cancer screening, characterization of solitary pulmonary nodules, staging of non-small cell lung cancer, treatment response assessment in Hodgkin lymphoma, postoperative surveillance of colorectal cancer and selective internal radiation therapy of colorectal liver metastases. Modelling suggests the greatest opportunities for improvements in survival through imaging detection of cancer may lie in the investigation of mildly symptomatic patients. For applications where the improvements in survival are more modest, use of imaging frequently has additional demonstrable benefits including reductions in health care expenditure.

Microscopy detection of rectal gonorrhoea in asymptomatic men.

This audit aimed to determine the usefulness of microscopy to detect presumptive rectal gonorrhoea (GC) infection in asymptomatic men. We retrospectively audited more than 400 male patients attending a London genitourinary medicine clinic from January 2005 to March 2007 who tested rectal culture positive for Neisseria gonorrhoeae and compared this with the microscopy detection rate. In total, 123/423 (29%) of culture positive samples were microscopy positive. Of those that tested microscopy negative (300/423), 64 (21%) were symptomatic and 236 (79%) asymptomatic. In addition, a time and motion study examined 81 rectal slides over a two-week period to identify microscopy reading time required to make a presumptive diagnosis of GC. Three slides were positive, resulting in six hours and 45 minutes to detect one positive sample. Given the low sensitivity for rectal microscopy coupled with the length of time required to obtain a presumptive positive rectal GC result, we believe rectal microscopy is no longer a cost-effective tool screening for asymptomatic men, and this report supports the BASHH guideline that it is not recommended in the management of asymptomatic rectal infection.

Antiretroviral treatment roll-out in a resource-constrained setting: capitalizing on nursing resources in Botswana.

PROBLEM: As programmes to deliver antiretroviral therapy (ART) are implemented in resource-constrained settings, the problem becomes not how these programmes are going to be financed but who will be responsible for delivering and sustaining them. APPROACH: Physician-led models of HIV treatment and care that have evolved in industrialized countries are not replicable in settings with a high prevalence of HIV infection and limited access to medical staff. Therefore, models of care need to make better use of available human resources. LOCAL SETTING: Using Botswana as an example, we discuss how nurses are underutilized in long-term clinical management of patients requiring ART. RELEVANT CHANGES: We argue that for ART-delivery programmes to be sustainable, nurses will need to provide a level of clinical care for patients receiving this therapy, including prescribing ART and managing common adverse effects. LESSONS LEARNED: Practicalities involved in scaling up nurse-led models of ART delivery include overcoming political and professional barriers, identifying educational requirements, agreeing on the limitations of nursing practice, developing clear referral pathways between medical and nursing personnel, and developing mechanisms to monitor and supervise practice. Operational research is required to demonstrate that such models are safe, effective and sustainable.

Quantifying emerging drugs for very rare conditions.

BACKGROUND: EU legislation is encouraging pharmaceutical companies to develop drugs for rare conditions, but their often high cost, and potential for long-term administration has led to debate about their affordability and cost-effectiveness. AIM: To investigate how many drugs are in development for very rare conditions. METHODS: We defined very rare conditions as having a prevalence of <1:50,000, and identified pharmaceuticals in phase II, phase III trials or pre-registration for these conditions using commercial databases. RESULTS: We identified 42 very rare conditions with at least one drug in late-stage clinical development, with a total of 113 drugs in development (17 for at least two indications). Sixteen drugs were pre-registration, 29 were in phase III development, 65 were in phase II development, one drug was both pre-registration and phase II for different indications and two drugs were in both phase II and phase III trials for different indications. DISCUSSION: Not all the drugs in development will reach the market, but it is likely that a significant number will do so. Affordability and methods to assess cost-effectiveness will need debate and clear national policy for decision-makers to follow.

Nurse prescribing in low-resource settings: professional considerations.

AIM: This paper reviews the professional issues relating to nurse prescribing in low-resource countries. BACKGROUND: In order to meet community healthcare need, nurses in low-resource settings often perform roles such as prescribing medication, for which they may not have had adequate training, often in the absence of supervision, legislation and regulation. In general, however, there is a paucity of published evidence relating to nurse prescribing in low-resource settings. Several studies have demonstrated improved health and social outcomes resulting from nurse-prescribing interventions. Alternatively, other studies have shown unsatisfactory nurse-prescribing patterns, such as overuse of antibiotics and poor adherence to national treatment guidelines. There are several examples of how nurse prescribing in low-resource countries has been recognized and addressed at national level; these are discussed in detail. However, given that it is widely acknowledged how crucial nurses are for the delivery of health care in regions where there are no medical personnel, international policy and guidance relating to this issue is only just beginning to acknowledge and address the relevant issues. CONCLUSION: Where there is a need for nurses to extend their role in the ordering of medicines and other treatments, the responsibilities, training, rights and roles of these nurses need to be clearly defined and recognized at all levels of the health service. There is a need for rigorous evaluations incorporating health, social and economic outcomes of nurse-prescribing interventions, in addition to close monitoring of legislative and regulatory changes related to nursing roles.

Use of a corporate needs assessment to define the information requirements of an arthritis resource centre in Birmingham: comparison of patients' and professionals' views.

OBJECTIVES: Education and information are important components of the management of chronic disease, though provision of these in the routine clinic setting may be suboptimal. We carried out a corporate needs assessment, both to evaluate stakeholders' perceived usefulness of potential facilities that could be offered by a community-based arthritis resource centre in Birmingham and to compare the views of patients with rheumatological conditions and health professionals. METHODS: Rheumatology patients (n = 201 responders/309 contacted) and health professionals (n = 232/430) were asked to complete a questionnaire to assess both current rheumatology service provision and perceived needs for further information that could be offered within the proposed resource centre. Views of patients and professionals were compared using odds ratios. Logistic regression analysis determined patient characteristics associated with perceived usefulness of various information types. RESULTS: The overall response rate was 58%. Most patients were currently receiving medication but only 38% received written information on arthritis. Over 80% of responders felt that more information would be useful, particularly information in written leaflets. Compared with professionals, patients gave higher value to certain types of medical, non-medical, support and skills information, particularly individual information from trained volunteers, and specific information on benefits, diet and alternative therapy, and symptom management. Non-Caucasian patients gave higher value to the provision of material in different languages and the availability of multilingual volunteer staff. CONCLUSION: Rheumatology patients and professionals identified a relative lack of information for patients. There was wide interest in the provision of more information, with value placed on the provision of material in different languages, at an educational resource centre. This work has been used to develop the facilities currently offered at the Birmingham Arthritis Resource Centre. Further research is needed to investigate the effectiveness of the provision of good quality information to patients with arthritis.

Cancer imaging: is it cost-effective?

With expenditure on imaging patients with cancer set to increase in line with rising cancer prevalence, there is a need to demonstrate the cost-effectiveness of advanced cancer imaging techniques. Cost-effectiveness studies aim to quantify the cost of providing a service relative to the amount of desirable outcome gained, such as improvements in patient survival. Yet, the impact of imaging on the survival of patients with cancer is small compared to the impact of treatment and is therefore hard to measure directly. Hence, techniques such as decision-tree analysis, that model the impact of imaging on survival, are increasingly used for cost-effectiveness evaluations. Using such techniques, imaging strategies that utilise computed tomography, magnetic resonance imaging and positron emission tomography have been shown to be more cost-effective than non-imaging approaches for the management of certain cancers including lung, prostate and lymphoma. There is stronger evidence to support the cost-effectiveness of advanced cancer imaging for diagnosis, staging and monitoring therapy than for screening. The results of cost-effectiveness evaluations are not directly transferable between countries or tumour types and hence more studies are needed. As many of the techniques developed to assess the evidence base for therapeutic modalities are not readily applicable to diagnostic tests, cancer imaging specialists need to define the methods for health technology assessment that are most appropriate to their speciality.

Solitary pulmonary nodules: impact of quantitative contrast-enhanced CT on the cost-effectiveness of FDG-PET.

AIM: To determine the impact of quantitative contrast-enhanced computed tomography (QECT) on the cost-effectiveness of diagnostic strategies for the assessment of solitary pulmonary nodules (SPNs). MATERIALS AND METHODS: Four diagnostic strategies were evaluated using decision tree analysis: conventional CT alone; conventional CT followed by QECT; conventional CT followed positron emission tomography (PET); and conventional CT followed by QECT and PET (QECT+PET). The average cost per patient, accuracy of management and incremental cost:accuracy ratio (ICAR) were determined for each strategy. Although baseline assumptions reflected the Australian setting, sensitivity analysis was used to extrapolate the results to the UK. RESULTS: At the baseline prevalence of malignancy (54%) and cost of PET relative to surgery (16%), the QECT strategy incurs the least cost (5560 dollars/patient) but the QECT+PET strategy is the most cost-effective (ICAR 12,059 dollars/patient). At reported levels of disease prevalence (68.5%) and cost of PET relative to surgery (29.9%) in the UK, the QECT strategy is the most cost-effective. CONCLUSION: QECT offers a cost-effective approach to evaluation of SPNs. Whether QECT is used alone or in combination with PET will depend upon local availability and regional values for prior probability of malignancy within SPNs and the cost of PET relative to surgery.

Perfusion CT for the assessment of tumour vascularity: which protocol?

Perfusion CT is a technique that can be readily incorporated into the existing CT protocols that continue to provide the mainstay for anatomical imaging in oncology to provide an in vivo marker of tumour angiogenesis. By capturing physiological information reflecting the tumour vasculature, perfusion CT can be useful for diagnosis, risk-stratification and therapeutic monitoring. However, a wide range of perfusion CT techniques have evolved and the various commercial implementations advocate different acquisition protocols and processing methods. Acquisition choices include first pass studies or delayed imaging, temporal resolution versus image noise, and single location sequences or multiple spiral acquisitions. Data processing may be semi-quantitative or, using either compartmental analysis or deconvolution, produce results that are quantified in absolute physiological terms such as perfusion, blood volume and permeability. This article discusses the advantages and disadvantages of the more common CT perfusion protocols and offers proposals that could allow for easier comparison between studies employing different techniques.

The historical role and education of nurses for the care and management of sexually transmitted infections in the United Kingdom: 1 role.

Nurses have been involved in the management of sexually transmitted infections (STIs) well before the era of Florence Nightingale. Their role has varied from that of the technician, almoner, counsellor, and doctor's assistant, to one in which they are able to provide first line management of STIs in nurse led clinics. However, changes to the role of the nurse have not been entirely through choice. It appears that nurses have often been called upon in times of crisis and need-their role often evolving only through demand for services and personnel. Barriers to developing the role of the nurse continue to exist as we move into the 21st century. From Lock hospitals to specialised genitourinary medicine clinics, this historical review looks at how the role of the nurse has evolved over the past 150 years and suggests how past lessons can help enhance the contribution nurses will make to the future of STI management and control.

Solitary pulmonary nodules: accuracy and cost-effectiveness of sodium iodide FDG-PET using Australian data.

This study uses Australian data to confirm the accuracy of dedicated sodium iodide (NaI) fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in evaluating indeterminate solitary pulmonary nodules (SPNs) and to determine the conditions under which PET could play a cost-effective role in this evaluation. Ninety-two patients from two Australian hospitals in different states underwent FDG-PET for evaluation of an SPN. Observed values for prior probability of malignancy and diagnostic accuracy of PET were applied to previously published decision tree models using published Australian health care costs. The accuracy of FDG-PET was 93% with a sensitivity of 92% and a specificity of 95%. The prior probability of malignancy (0.54), PET sensitivity and PET specificity indicated cost savings per patient of up to EUR 455 (Adollars 774) based on a PET cost of EUR 706 (Adollars 1,200). PET would remain cost-effective for levels of prior probability up to 0.8-0.9 and a PET cost of EUR 736-1,161 (Adollars 1,252-Adollars 1,974). It is concluded that NaI PET is accurate, cost saving and cost-effective for the characterisation of indeterminate pulmonary nodules in Australia. Comparison with previous reports from the United States confirms that FDG-PET can remain cost-effective despite population differences in medical costs, disease prevalence and PET diagnostic performance.

An approach to demonstrating cost-effectiveness of diagnostic imaging modalities in Australia illustrated by positron emission tomography.

The aim of this study was to develop a framework in which the cost-effectiveness of new imaging technologies could be evaluated using data from other countries, while assessing the impact that any differences between the study populations and Australia may have upon the results. Publications reporting the cost-effectiveness or therapeutic impact of positron emission tomography (PET) were re-worked using Australian cost structures. PET was assigned a cost of $950. The effects of potential differences between the populations studied and the Australian population were evaluated by applying sensitivity analysis to those publications that describe decision tree methodology. The parameters included in the sensitivity analysis were disease prevalence and specificity of PET. The Australian cost savings per patient examined by PET were $505.50-$912.41 for investigation of solitary pulmonary nodules, $34.65-$360.03 for lung cancer staging, $550.08 for axillary staging of breast cancer, $230.75-$2301.27 for assessment of recurrent colorectal cancer and $300.24-$2069.65 for assessment of myocardial viability. Significant differences in disease prevalence and PET specificity could occur while the cost-effectiveness of PET was preserved. Decision tree sensitivity analysis can demonstrate the cost-effectiveness of diagnostic imaging modalities in Australia and provides indications that PET is cost-effective for a range of clinical indications.

A community-based occupational enrichment program for captive chimpanzees.

The authors describe a cost-effective program for providing chimpanzee enrichment that at the same time educates the local community about the care of these animals in research.

Sexual health seeking behaviours of young people in the Gambia.

In the Gambia, sexually transmitted infections (STIs) and their complications are a major health problem and although the prevalence of HIV-1 in the Gambia is currently low, it is increasing. Relatively little is known about the sexual health treatment-seeking behaviours of young people in West Africa. This information is vital to target resources appropriately. To investigate this concept, twelve single-sex focus group discussions (FGDs), within three rural villages, elicited the views, opinions, attitudes and experiences of 49 young men (mean age 17.4 years; range 15-21) and 48 young women (mean age 18.2 years; range 15-25). The participants talked openly about sexual activity within their peer communities. Six major themes were identified from the FGDs: (1) groups perceived to be at risk of acquiring STIs; (2) STI transmission and classification; (3) treatment-seeking behaviours; (4) barriers to treatment; (5) consequences of non-treatment; and (6) problem resolution strategies. The study concludes that whilst there may be barriers to improving sexual and reproductive health, young people in rural West Africa have enthusiasm for and commitment to finding solutions to the problems that local communities face.