Is it safe to use visible blue light-emitting diode phototherapy for neonatal jaundice in infants who are also treated with amiodarone?

Amiodarone is a useful treatment for neonatal cardiac arrhythmias. A minority of neonates with arrhythmias treated with amiodarone may also develop neonatal jaundice. Phototherapy is recommended to treat neonatal jaundice. However, amiodarone is known to cause skin reactions when patients are exposed to light. Therefore phototherapy may not be administered due to concerns about this interaction. Exchange transfusions are used as an alternative to phototherapy to avoid the interaction. However, exchange transfusions are associated with serious complications such as the transmission of bloodborne disease, seizures and haemodynamic instability. We report a literature review and outcome of a premature infant treated with amiodarone and visible blue light-emitting diode (LED) phototherapy. Phototherapy was used for 54 hours and no skin reactions were observed. This is because visible blue LED phototherapy lamps emit predominantly visible light. Therefore exposure to ultraviolet light that is known to cause amiodarone phototoxicity is minimised.

Understanding health and care expenditure by setting - who matters to whom?

OBJECTIVE: To assess service use and associated expenditure across a range of care settings in one local authority in London, United Kingdom. METHODS: An analysis of linked electronic health and council records of adults living in the borough of Barking and Dagenham, east London, for the financial year 2016/17. Unit costs were applied to individual service use to provide expenditure at an individual and population level for five settings of care. Population and expenditure volumes were compared for 32 possible combinations of service use. RESULTS: The total expenditure for the cohort (114,393 residents) for 2016/17 was £180.1 million. Almost half (47%) of total expenditure was incurred by community care, social care and mental health services, with hospital care and primary care incurring, respectively, 35% (£63.3 m) and 18% (£32.6 m). The two most common combinations in terms of total population volume and expenditure were primary and hospital care, and primary, hospital and community care. Primary care was present in all combinations. Mental health service use accounted for just over a tenth of all expenditure in the borough, but using mental health services substantially increased mean expenditure per patient. CONCLUSIONS: A whole system perspective across all settings of care improves understanding of service user patterns. Setting-level analysis remains important, particularly for mental health users.

Liver resection surgery compared with thermal ablation in high surgical risk patients with colorectal liver metastases: the LAVA international RCT.

BACKGROUND: Although surgical resection has been considered the only curative option for colorectal liver metastases, thermal ablation has recently been suggested as an alternative curative treatment. There have been no adequately powered trials comparing surgery with thermal ablation. OBJECTIVES: Main objective - to compare the clinical effectiveness and cost-effectiveness of thermal ablation versus liver resection surgery in high surgical risk patients who would be eligible for liver resection. Pilot study objectives - to assess the feasibility of recruitment (through qualitative study), to assess the quality of ablations and liver resection surgery to determine acceptable standards for the main trial and to centrally review the reporting of computed tomography scan findings relating to ablation and outcomes and recurrence rate in both arms. DESIGN: A prospective, international (UK and the Netherlands), multicentre, open, pragmatic, parallel-group, randomised controlled non-inferiority trial with a 1-year internal pilot study. SETTING: Tertiary liver, pancreatic and gallbladder (hepatopancreatobiliary) centres in the UK and the Netherlands. PARTICIPANTS: Adults with a specialist multidisciplinary team diagnosis of colorectal liver metastases who are at high surgical risk because of their age, comorbidities or tumour burden and who would be suitable for liver resection or thermal ablation. INTERVENTIONS: Thermal ablation conducted as per local policy (but centres were encouraged to recruit within Cardiovascular and Interventional Radiological Society of Europe guidelines) versus surgical liver resection performed as per centre protocol. MAIN OUTCOME MEASURES: Pilot study - patients' and clinicians' acceptability of the trial to assist in optimisation of recruitment. Primary outcome - disease-free survival at 2 years post randomisation. Secondary outcomes - overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, and disease-free survival measured from end of intervention. It was planned that 5-year survival data would be documented through record linkage. Randomisation was performed by minimisation incorporating a random element, and this was a non-blinded study. RESULTS: In the pilot study over 1 year, a total of 366 patients with colorectal liver metastases were screened and 59 were considered eligible. Only nine participants were randomised. The trial was stopped early and none of the planned statistical analyses was performed. The key issues inhibiting recruitment included fewer than anticipated patients eligible for both treatments, misconceptions about the eligibility criteria for the trial, surgeons' preference for one of the treatments ('lack of clinical equipoise' among some of the surgeons in the centre) with unconscious bias towards surgery, patients' preference for one of the treatments, and lack of dedicated research nurses for the trial. CONCLUSIONS: Recruitment feasibility was not demonstrated during the pilot stage of the trial; therefore, the trial closed early. In future, comparisons involving two very different treatments may benefit from an initial feasibility study or a longer period of internal pilot study to resolve these difficulties. Sufficient time should be allowed to set up arrangements through National Institute for Health Research (NIHR) Research Networks. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52040363. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 21. See the NIHR Journals Library website for further project information.

In about 50% of people with bowel cancer, cancer spreads to the liver (colorectal liver metastases) within 5 years of detection and treatment. Liver resection (i.e. surgical removal of a portion of the liver) is the standard treatment in people below 70 years of age who are otherwise well, provided that the liver cancer is confined to a limited part of the liver. Such patients are considered 'low-risk' patients. Older patients and those with major medical problems or extensive cancers are considered 'high-risk' patients, as they are at a higher risk of developing complications following liver resection. Thermal ablation destroys the liver cancers using a needle that heats the cancer deposits until they are destroyed. There is significant uncertainty as to whether or not ablation can offer equivalent survival compared with surgery for 'high-risk' patients. We planned and conducted a randomised controlled trial comparing ablation with surgery to resolve this uncertainty. In this trial, some patients received ablation and others received surgery. The treatment was allocated at random with neither patients nor the study organisers choosing the treatment. The trial had an internal pilot (i.e. a smaller version of the full trial to resolve any 'teething problems' and ensure that a sufficient number of participants can be included in the full trial). Only nine patients were recruited in the 1-year internal pilot, compared with the anticipated recruitment of 45 patients. Therefore, the trial closed early as a result of poor recruitment, and the uncertainty about the best treatment for high-risk patients with colorectal liver metastases continues. The main reasons for the poor recruitment included fewer than anticipated eligible participants, clinicians' unconscious bias towards surgery, and patients' preference for one treatment or the other. In the future, comparisons involving two very different treatments may benefit from a feasibility study or a longer period of pilot study to resolve any difficulties.

Holistic process development to mitigate proteolysis of a subunit rotavirus vaccine candidate produced in Pichia pastoris by means of an acid pH pulse during fed-batch fermentation.

To meet the challenges of global health, vaccine design and development must be reconsidered to achieve cost of goods as low as 15¢ per dose. A new recombinant protein-based rotavirus vaccine candidate derived from non-replicative viral subunits fused to a P2 tetanus toxoid CD4(+) T cell epitope is currently under clinical development. We have sought to simplify the existing manufacturing process to meet these aims. To this end, we have taken a holistic process development approach to reduce process complexity and costs while producing a product with the required characteristics. We have changed expression system from Escherichia coli to Pichia pastoris, to produce a secreted product, thereby reducing the number of purification steps. However, the presence of proteases poses challenges to product quality. To understand the effect of fermentation parameters on product quality small-scale fermentations were carried out. Media pH and fermentation duration had the greatest impact on the proportion of full-length product. A novel acidic pH pulse strategy was used to minimize proteolysis, and this combined with an early harvest time significantly increased the proportion of full-length material (60-75%). An improved downstream process using a combination of CIEX and AIEX to further reduce proteases, resulted in maintaining product quality (95% yield).

Mixed methods evaluation of a hospital group model using an embedded research approach: study protocol.

INTRODUCTION: Hospital group models represent an organisational form that aims to bring together multiple provider organisations with a central headquarters and unified leadership responsible for locally managed operating units, standardised systems and a value-set shared across the group. These models seek to improve outcomes by reducing unwarranted variations in care provision and reducing costs through economies of scale. There is limited evidence on the impact and processes of implementing these models, so this study aims to evaluate one case study of a hospital group model. METHODS AND ANALYSIS: We will conduct a formative, mixed-methods evaluation using an embedded research approach to analyse the implementation of the model and its impact on outcomes and costs. We will carry out a multisited ethnography to analyse the programme theory for model design and implementation, the barriers and facilitators in the implementation; and wider contextual issues that influence implementation using semi-structured interviews (n=80), non-participant observations (n=80 hours), 'shadowing' (n=20 hours) and documentary analysis. We will also carry out an economic evaluation composed of a cost-consequence analysis and a return on investment analysis to evaluate the costs of creating and running the model and balance these against the potential cost-savings. ETHICS AND DISSEMINATION: The study protocol was reviewed by the local R&D Office and University College London Ethics Committee and classified as a service evaluation, not requiring approval by a research ethics committee. We will follow guidelines for informed consent, confidentiality and information governance, and address issues of critical distance prevalent in embedded research. Findings will be shared at regular time points to inform the implementation of the model. The evaluation will also generate: an evaluation framework to evaluate future changes; recommendations for meaningful baseline data and measuring improvement; identification of implementation costs and potential cost-savings; and lessons for the National Health Service on implementing these models.

The effect of a change in co-payment on prescription drug demand in a National Health System: The case of 15 drug families by price elasticity of demand.

OBJECTIVES: To test the heterogeneity of the effect of a change in pharmaceutical cost-sharing by therapeutic groups in a Spanish region. METHODS: Data: random sample (provided by the Canary Islands Health Service) of 40,471 people covered by the Spanish National Health System (SNHS) in the Canary Islands. The database includes individualised monthly-dispensed medications (prescribed by the SNHS) from one year before (August 2011) to one year after (June 2013) the Royal Decree Law 16/2012 (RDL 16/2012). Sample: two intervention groups (low-income pensioners and middle-income working population) and one control group (low-income working population). Empirical model: quasi-experimental difference-in-differences design to study the change in consumption (measured in number of monthly Defined Daily Dose (DDDs) per individual) among 13 therapeutic groups. The policy break indicator (three-level categorical variable) tested the existence of stockpiling between the reform's announcement and its implementation. We ran 16 linear regression models (general, by therapeutic groups and by comorbidities) that considered whether the exclusion of some drugs from public provision impacted on consumption more than the co-payment increase. RESULTS: General: Reduction (-13.04) in consumption after the reform's implementation, which was fully compensated by a previous increase (16.60 i.e., stockpiling) among low-income pensioners. The middle-income working population maintained its trend of increasing consumption. Therapeutic groups: Reductions in consumption after the reform's implementation among low-income pensioners in 7 of the 13 groups, which were fully compensated for by a previous increase (i.e., stockpiling) in 4 groups and partially compensated for in the remaining 3. The analysis without the excluded medicines provided fewer negative coefficients. Comorbidities: Reduction in consumption that was only slightly compensated for by a previous increase (i.e., stockpiling). CONCLUSIONS: The negative impact of cost-sharing produced, among low-income pensioners, a risk of loss of adherence to treatments, which could deteriorate the health status of individuals, especially among pensioners within the most inelastic therapeutic groups (associated with chronic diseases) and patients with comorbidities (also, associated with chronic diseases). Notwithstanding the above, this risk was more related to the exclusion of some drugs from provision than to the cost-sharing increase.

Cost-Effectiveness Analysis of a National Newborn Screening Program for Biotinidase Deficiency.

BACKGROUND AND OBJECTIVES: There are conflicting views as to whether testing for biotinidase deficiency (BD) ought to be incorporated into universal newborn screening (NBS) programs. The aim of this study was to evaluate the cost-effectiveness of adding BD to the panel of conditions currently screened under the national NBS program in Spain. METHODS: We used information from the regional NBS program for BD that has been in place in the Spanish region of Galicia since 1987. These data, along with other sources, were used to develop a cost-effectiveness decision model that compared lifetime costs and health outcomes of a national birth cohort of newborns with and without an early detection program. The analysis took the perspective of the Spanish National Health Service. Effectiveness was measured in terms of quality-adjusted life years (QALYs). We undertook extensive sensitivity analyses around the main model assumptions, including a probabilistic sensitivity analysis. RESULTS: In the base case analysis, NBS for BD led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of $24,677. Lower costs per QALY gained were found when conservative assumptions were relaxed, yielding cost savings in some scenarios. The probability that BD screening was cost-effective was estimated to be >70% in the base case at a standard threshold value. CONCLUSIONS: This study indicates that NBS for BD is likely to be a cost-effective use of resources.

Effect of feeding strategies on weaning weight and milk production of Holstein × Zebu calves in dual purpose milk production systems.

The objective of this study was to evaluate the effect of five feeding strategies on calf weaning weight, and cow milk production and composition in Brazilian Holstein × Zebu cows. A total of 60 cows and their calves were allocated to each of five treatments. Cows in treatments 1, 2 and 3 were milked for 270 days and cows in treatments 4 and 5 were milked for 180 days. Calves in treatment 1 (CON) were not supplemented with concentrate whereas calves from treatment 2 (CLPN) received 1 kg of concentrate daily from 90 to 270 days of age and calves from treatment 3 received 1 kg of concentrated from 180 to 270 days of age. Calves in treatment 4 (CCPS) were supplemented with 1 kg of concentrate from 90 to 180 days of age and calves in treatment 5 (CLPS) were supplemented with 1 kg of concentrate from 90 to 270 days of age. Calves from the CLPS treatment had greater milk and protein intakes (P < 0.05) and greater growth rate than calves from the other treatments. Our results indicate that the traditional system of feeding calves with no concentrate results in a weight gain of 600 g/day. The CLPS treatment produced calves with the highest live weight and growth rate. The nutritional strategy with restricted supply of milk for the calves with concomitantly short-term concentrate supplementation does not improve performance of calves but did increase feed costs.

Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials.

BACKGROUND: Agitation in dementia is common, persistent and distressing and can lead to care breakdown. Medication is often ineffective and harmful. AIMS: To systematically review randomised controlled trial evidence regarding non-pharmacological interventions. Method We reviewed 33 studies fitting predetermined criteria, assessed their validity and calculated standardised effect sizes (SES). RESULTS: Person-centred care, communication skills training and adapted dementia care mapping decreased symptomatic and severe agitation in care homes immediately (SES range 0.3-1.8) and for up to 6 months afterwards (SES range 0.2-2.2). Activities and music therapy by protocol (SES range 0.5-0.6) decreased overall agitation and sensory intervention decreased clinically significant agitation immediately. Aromatherapy and light therapy did not demonstrate efficacy. CONCLUSIONS: There are evidence-based strategies for care homes. Future interventions should focus on consistent and long-term implementation through staff training. Further research is needed for people living in their own homes.

A systematic review of the clinical effectiveness and cost-effectiveness of sensory, psychological and behavioural interventions for managing agitation in older adults with dementia.

BACKGROUND: Agitation is common, persistent and distressing in dementia and is linked with care breakdown. Psychotropic medication is often ineffective or harmful, but the evidence regarding non-pharmacological interventions is unclear. OBJECTIVES: We systematically reviewed and synthesised the evidence for clinical effectiveness and cost-effectiveness of non-pharmacological interventions for reducing agitation in dementia, considering dementia severity, the setting, the person with whom the intervention is implemented, whether the effects are immediate or longer term, and cost-effectiveness. DATA SOURCES: We searched twice using relevant search terms (9 August 2011 and 12 June 2012) in Web of Knowledge (incorporating MEDLINE); EMBASE; British Nursing Index; the Health Technology Assessment programme database; PsycINFO; NHS Evidence; System for Information on Grey Literature; The Stationery Office Official Documents website; The Stationery National Technical Information Service; Cumulative Index to Nursing and Allied Health Literature; and The Cochrane Library. We also searched Cochrane reviews of interventions for behaviour in dementia, included papers' references, and contacted authors about 'missed' studies. We included quantitative studies, evaluating non-pharmacological interventions for agitation in dementia, in all settings. REVIEW METHOD: We rated quality, prioritising higher-quality studies. We separated results by intervention type and agitation level. As we were unable to meta-analyse results except for light therapy, we present a qualitative evidence synthesis. In addition, we calculated standardised effect sizes (SESs) with available data, to compare heterogeneous interventions. In the health economic analysis, we reviewed economic studies, calculated the cost of effective interventions from the effectiveness review, calculated the incremental cost per unit improvement in agitation, used data from a cohort study to evaluate the relationship between health and social care costs and health-related quality of life (DEMQOL-Proxy-U scores) and developed a new cost-effectiveness model. RESULTS: We included 160 out of 1916 papers screened. Supervised person-centred care, communication skills (SES = -1.8 to -0.3) or modified dementia care mapping (DCM) with implementing plans (SES = -1.4 to -0.6) were all efficacious at reducing clinically significant agitation in care home residents, both immediately and up to 6 months afterwards. In care home residents, during interventions but not at follow-up, activities (SES = -0.8 to -0.6) and music therapy (SES = -0.8 to -0.5) by protocol reduced mean levels of agitation; sensory intervention (SES = -1.3 to -0.6) reduced mean and clinically significant symptoms. Advantages were not demonstrated with 'therapeutic touch' or individualised activity. Aromatherapy and light therapy did not show clinical effectiveness. Training family carers in behavioural or cognitive interventions did not decrease severe agitation. The few studies reporting activities of daily living or quality-of-life outcomes found no improvement, even when agitation had improved. We identified two health economic studies. Costs of interventions which significantly impacted on agitation were activities, £80-696; music therapy, £13-27; sensory interventions, £3-527; and training paid caregivers in person-centred care or communication skills with or without behavioural management training and DCM, £31-339. Among the 11 interventions that were evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the incremental cost per unit reduction in CMAI score ranged from £162 to £3480 for activities, £4 for music therapy, £24 to £143 for sensory interventions, and £6 to £62 for training paid caregivers in person-centred care or communication skills with or without behavioural management training and DCM. Health and social care costs ranged from around £7000 over 3 months in people without clinically significant agitation symptoms to around £15,000 at the most severe agitation levels. There is some evidence that DEMQOL-Proxy-U scores decline with Neuropsychiatric Inventory agitation scores. A multicomponent intervention in participants with mild to moderate dementia had a positive monetary net benefit and a 82.2% probability of being cost-effective at a maximum willingness to pay for a quality-adjusted life-year of £20,000 and a 83.18% probability at a value of £30,000. LIMITATIONS: Although there were some high-quality studies, there were only 33 reasonably sized (> 45 participants) randomised controlled trials, and lack of evidence means that we cannot comment on many interventions' effectiveness. There were no hospital studies and few studies in people's homes. More health economic data are needed. CONCLUSIONS: Person-centred care, communication skills and DCM (all with supervision), sensory therapy activities, and structured music therapies reduce agitation in care-home dementia residents. Future interventions should change care home culture through staff training and permanently implement evidence-based treatments and evaluate health economics. There is a need for further work on interventions for agitation in people with dementia living in their own homes. PROTOCOL REGISTRATION: The study was registered as PROSPERO no. CRD42011001370. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The benefits and harms of providing parents with weight feedback as part of the national child measurement programme: a prospective cohort study.

BACKGROUND: Small-scale evaluations suggest that the provision of feedback to parents about their child's weight status may improve recognition of overweight, but the effects on lifestyle behaviour are unclear and there are concerns that informing parents that their child is overweight may have harmful effects. The aims of this study were to describe the benefits and harms of providing weight feedback to parents as part of a national school-based weight-screening programme in England. METHODS: We conducted a pre-post survey of 1,844 parents of children aged 4-5 and 10-11 years who received weight feedback as part of the 2010-2011 National Child Measurement Programme. Questionnaires assessed general knowledge about the health risks associated with child overweight, parental recognition of overweight and the associated health risks in their child, child lifestyle behaviour, child self-esteem and weight-related teasing, parental experience of the feedback, and parental help-seeking behaviour. Differences in the pre-post proportions of parents reporting each outcome were assessed using a McNemar's test. RESULTS: General knowledge about child overweight as a health issue was high at baseline and increased further after weight feedback. After feedback, the proportion of parents that correctly recognised their child was overweight increased from 21.9% to 37.7%, and more than a third of parents of overweight children sought further information regarding their child's weight. However, parent-reported changes in lifestyle behaviours among children were minimal, and limited to increases in physical activity in the obese children only. There was some suggestion that weight feedback had a greater impact upon changing parental recognition of the health risks associated with child overweight in non-white ethnic groups. CONCLUSIONS: In this population-based sample of parents of children participating in the National Child Measurement Programme, provision of weight feedback increased recognition of child overweight and encouraged some parents to seek help, without causing obvious unfavourable effects. The impact of weight feedback on behaviour change was limited; suggesting that further work is needed to identify ways to more effectively communicate health information to parents and to identify what information and support may encourage parents in making and maintaining lifestyle changes for their child.

Monitoring real-time enzymatic hydrolysis of Distillers Dried Grains with Solubles (DDGS) by dielectric spectroscopy following hydrothermal pre-treatment by steam explosion.

Dielectric spectroscopy (DS) has been used to monitor the simultaneous saccharification and fermentation of lignocellulosic biomass by measuring its dielectric state. However, it is unknown whether following steam explosion (SE) pre-treatment, lignocellulose would still maintain a dielectric state, and, if maintained, whether the dissipation during enzymatic hydrolysis could be monitored. Distillers Dried Grains with Solubles (DDGS), pre-treated by SE, was found to have a capacitance (C = 580 kHz) of approximately 24 pF cm(-1). Following addition of full-strength cellulolytic cocktail A (CC-A; R(2) = 0.97) and 1/3 strength cocktail B (CC-B; R(2) = 0.96), a natural logarithmic decay in capacitance was determined. Furthermore, the DS biomass probes quantified the initial linear rate of dissipation in capacitance during hydrolysis. The rate of CC-B was 34% that of CC-A. These data extend scope and utility of DS biomass probes for monitoring the enzymatic hydrolysis of SE-pre-treated lignocellulosic substrates in real-time.

Effect of parity on lymphocytes in peripheral blood and colostrum of healthy Holstein dairy cows.

Investigation of the bovine systemic and mammary gland immune cells at calving might provide crucial information about the susceptibility of the mammary gland to infection. This study investigated the leukocyte population and cytokine mRNA levels in peripheral blood mononuclear cells (PBMCs) and colostrum mononuclear cells (CCs) obtained from healthy cows soon after calving. Fifty dairy cows that did not show clinical diseases were divided into 4 groups on the basis of parity: heifer (group 1, n = 10), 2nd calving (group 2, n = 11), 3rd calving (group 3, n = 14), and more than 3rd calving (group 4, n = 15). In the peripheral blood the numbers of CD3(+)TcR1-N12(+), CD3(+), CD4(+), and major histocompatibility complex class II(+)CD14(-) lymphocytes were significantly higher in group 1 than in group 4, whereas in the colostrum the percentages of CD4(+) and CD4(+)CD26(+) lymphocytes and the CD4(+)/CD8(+) ratio were significantly lower in group 1 than in group 4. There were no significant differences in the cytokine mRNA levels of PBMCs among the 4 groups; however, in the CCs the ratio of interferon gamma to interleukin 4 was significantly lower in group 1 than in group 3. These results suggest that the cellular immune function of PBMCs is lower, whereas mammary gland immune cells are more active, in cows with higher parity compared with heifers at calving.

Cost effectiveness analysis of minimally invasive internal thoracic artery bypass versus percutaneous revascularisation for isolated lesions of the left anterior descending artery.

OBJECTIVE: To compare the cost effectiveness of percutaneous transluminal coronary artery stenting with minimally invasive internal thoracic artery bypass for isolated lesions of the left anterior descending artery. DESIGN: Cost effectiveness analysis. DATA SOURCES: Embase, Medline, Cochrane, Google Scholar, and Health Technology Assessment databases (1966-2005), and reference sources for utility values and economical variables. METHODS: Decision analytical modelling and Markov simulation were used to model medium and long term costs, quality of life, and cost effectiveness after either intervention using data from referenced sources. Probabilistic sensitivity and alternative analyses were used to investigate the effect of uncertainty about the value of model variables and model structure. RESULTS: Stenting was the dominant strategy in the first two years, being both more effective and less costly than bypass surgery. In the third year bypass surgery still remained more expensive but became marginally more effective. As the incremental cost effectiveness was 1,108,130.40 pounds sterling (1 682,146.00 euros; $2,179,194) per quality adjusted life year (QALY), the additional effectiveness could not be said to justify the additional cost at this stage. By five years, however, the incremental cost effectiveness ratio of 28,042.95 pounds sterling per QALY began to compare favourably with other interventions. At 10 years the additional effectiveness of 0.132 QALYs (range -0.166 to 0.430) probably justified the additional cost of 829.02 pounds sterling (range 205.56 pounds sterling to 1452.48 pounds sterling), with an incremental cost effectiveness of 6274.02 pounds sterling per QALY. Sensitivity and alternative analysis showed the results were sensitive to the time horizon and stent type. CONCLUSIONS: Minimally invasive left internal thoracic artery bypass may be a more cost effective medium and long term alternative to percutaneous transluminal coronary artery stenting.

Dynamic dose-feedback prostate brachytherapy in patients with large prostates and/or planned transurethral surgery before implantation.

OBJECTIVE: To compare the quality of permanent prostate brachytherapy (PPB) implants, dosimetric outcomes and urinary morbidity between patients with large (>50 mL) and those with smaller prostates, treated with a dynamic dose-feedback technique as monotherapy for localized prostate cancer. PATIENTS AND METHODS: The series included patients with pre-existing bladder outlet obstruction managed with planned transurethral resection or incision of the prostate; 155 consecutive men had PPB implants as monotherapy for localized prostate cancer using a dynamic dose-feedback approach. Dosimetric variables assessed included the implant volume, the minimum dose to 90% of the prostate (D90), and the volumes of prostate receiving 100% and 150% of the prescribed dose as a percentage of the total volume (V100 and V150), during and after implantation. Urinary morbidity was recorded in terms of acute urinary retention (AUR), the need for surgical intervention after implantation and the American Urologic Association (AUA) symptom score at baseline, 1.5, 3, 6, 9, 12 and 18 months. RESULTS: In all, 38 patients had prostate volumes of >or=50 mL; prostate volume had no influence on any dosimetric variable assessed. Two patients with large prostates (>or=50 mL) had AUR and required delayed surgery. Three patients with small prostates (<50 mL) had transient retention; the differences were not statistically significant (Fisher's exact test). AUA symptom scores peaked at 6 weeks and returned to baseline within a year; there were no statistically significant differences between the groups. Eight patients had planned transurethral surgery at >or=4 months before implantation; they all had D90s of >130 Gy and had no incontinence. CONCLUSION: Using the dynamic feedback technique, there was no adverse dosimetric and urinary morbidity in men having PPB and with prostates of >50 mL. Likewise, there were no impediments, e.g. pubic arch interference, which precluded a favourable dosimetric implant in men with a large prostate. Large prostates should not be a contraindication to PPB and require no hormonal cytoreduction. Patients with obstructive lower urinary tract symptoms can be managed with planned transurethral prostatic surgery before implantation, without compromising implant quality or morbidity.