Identifying core components of a radiotherapy comfort intervention package using nominal group technique.

INTRODUCTION: A comfortable treatment position in radiotherapy may promote patient stability and improve outcomes such as accuracy. The aim of this study was to identify, prioritise and determine the feasibility of delivery of intervention components as part of a radiotherapy comfort intervention package. METHODS: Prior research, consisting of a systematic review and qualitative interviews with patient and therapeutic radiographers, was triangulated and 15 intervention components developed. An online nominal group technique consensus meeting with 7 patients who received radiotherapy exceeding 10 min for one of three anatomical cancer sites and 3 therapeutic radiographers (TRs) participated. Four activities were undertaken: 1) discussion of comfort intervention components; 2) initial vote; 3) prioritisation of intervention components; and 4) discussion of feasibility in radiotherapy and were analysed using established quantitative and qualitative methods. RESULTS: One intervention component was added from initial discussions to the 15 pre-determined components being discussed. 11 components were recommended as 'accepted' (n = 5) or 'accepted with caution' (n = 6) to proceed to development. The highest scoring intervention components were 'Compassionate & empathetic communication training for TRs' and 'Tailored information, e.g., TRs provide the required information only as part of preparation for treatment'. Anther that followed closely was 'Adjustments & supports provided for arms or legs during treatment by TRs'. Those 'accepted with caution' included 'Soft pads/mattress under the body to alleviate body discomfort managed by TRs'. Qualitative analysis highlighted concerns over the radiation environment and emphasised the importance of resources such as equipment, training, and time. CONCLUSION: The recommended comfort interventions have potential to improve patient comfort during radiotherapy and should be considered to incorporate into positioning and immobilisation guidelines. However, specific intervention strategies to address these components will need to be developed and robustly evaluated. IMPLICATIONS FOR PRACTICE: Comfort interventions might help patients relax and stay still during treatment, which could improve treatment accuracy and efficacy. Introducing these comfort interventions in practice have potential to lead to a more positive patient experience and improved overall quality of care during radiotherapy.

Repeatability of plantar pressure assessment during barefoot walking in people with stroke.

PURPOSE: Stroke-related changes in foot structure and function affect balance and mobility and quantifying foot function following stroke could offer clinically useful information to inform rehabilitation. The aim of this work was to explore the feasibility of undertaking plantar pressure assessment during barefoot walking in people with stroke, and evaluate the repeatability of the assessment protocol and regional footprint analysis as a measure of dynamic foot characteristics. MATERIALS & METHODS: Plantar pressure analysis was undertaken using a pressure platform (Tekscan HR Mat) on two test sessions, approximately two weeks apart (mean = 15.64 ± 11.64 days). Peak plantar pressure (kPa) and contact area (cm2) for foot regions were extracted and repeatability analysis undertaken. Descriptive evaluation of field notes and experiences of the participants was undertaken to inform the feasibility of the data collection protocol. RESULTS: Twenty-one participants (61.8 ± 9.2 years; 11 male, 10 female; 8 right-sided, 13 left-sided stroke) were recruited and 18 returned for retesting. Full data capture was achieved from 14 participants. Peak pressure and contact area demonstrated moderate to good repeatability for at the toes (ICC 0.76 and 0.58 respectively) and good to excellent repeatability for the other foot regions (ICC ≥ 0.82). CONCLUSION: The protocol adopted in this study was feasible and yielded good to excellent repeatability for the foot regions, except the toes. The challenges with data collection in our study cohort could help inform future studies adopting similar protocols. This work also has relevance for use of pressure technology in clinical practice for assessing and monitoring foot function following stroke.

A systematic review of effectiveness of interventions applicable to radiotherapy that are administered to improve patient comfort, increase patient compliance, and reduce patient distress or anxiety.

OBJECTIVES: The aim of this review was to search existing literature to identify comfort interventions that can be used to assist an adult patient to undergo complex radiotherapy requiring positional stability for periods greater than 10 min. The objectives of this review were to; 1) identify comfort interventions used for clinical procedures that involve sustained inactivity similar to radiotherapy; 2) define characteristics of comfort interventions for future practice; and 3) determine the effectiveness of identified comfort interventions. The Preferred Reporting Items for Systematic Reviews and meta-analyses statement and the Template-for-Intervention-Description-and Replication guide were used. KEY FINDINGS: The literature search was performed using PICO criteria with five databases (AMED, CINAHL EMBASE, MEDLINE, PsycINFO) identifying 5269 titles. After screening, 46 randomised controlled trials met the inclusion criteria. Thirteen interventions were reported and were grouped into four categories: Audio-visual, Psychological, Physical, and Other interventions (education/information and aromatherapy). The majority of aromatherapy, one audio-visual and one educational intervention were judged to be clinically significant for improving patient comfort based on anxiety outcome measures (effect size ≥ 0.4, mean change is greater than the Minimal-Important-Difference and low-risk-of-bias). Medium to large effect sizes were reported in many interventions where differences did not exceed the Minimal-Important-Difference for the measure. These interventions were deemed worthy of further investigation. CONCLUSION: Several interventions were identified that may improve comfort during radiotherapy assisting patients to sustain and endure the same position over time. This is crucial for the continual growth of complex radiotherapy requiring a need for comfort to ensure stability for targeted treatment. IMPLICATIONS FOR PRACTICE: Further investigation of comfort interventions is warranted, including tailoring interventions to patient choice and determining if multiple interventions can be used concurrently to improve effectiveness.

Enhanced natural killer cell activity is found in exposed uninfected recipients of hepatitis C-contaminated blood.

A minority of injecting drug users, termed exposed uninfected, are resistant to hepatitis C (HCV) infection despite repeated low-dose exposures. We identify for the first time a cohort of blood recipients who remained uninfected despite large-dose exposure to HCV-contaminated blood and characterize immune factors that may confer protection. Of 1340 blood recipients from the English Look Back database who were transfused HCV-contaminated blood, we identified 8 who remained uninfected. In these 8 exposed uninfecteds, we characterized their natural killer (NK) cell populations and HCV-specific T-cell responses. Findings were compared with 10 spontaneous resolvers of HCV infection, 10 patients with chronic HCV infection and 10 healthy controls. Exposed uninfecteds had significantly greater numbers of NK cells with the activating receptor NKp30+ on CD56bright and CD56dim subsets compared with other groups (P < .05). Following interleukin-2 activation, NK cells of exposed uninfecteds had enhanced cytotoxicity that positively correlated with NKp30 expression (P = .02). Differences in NKp80 and KIR2DL3 expression were also observed. HCV-specific T-cell responses were observed in some exposed uninfecteds but of low amplitude. Exposure without infection following transfusion of HCV-contaminated blood is a very rare phenomenon and suggests a high level of resistance to infection. Enhanced NK cell activation and killing, with weak HCV-specific T-cell responses, were observed many years after exposure in uninfected recipients and may contribute to protection from HCV acquisition, although additional protective factors are being sought in this important cohort.

Identifying biomechanical gait parameters in adolescent boys with haemophilia using principal component analysis.

INTRODUCTION: Improvements in the medical management for those with haemophilia have resulted in improved clinical outcomes. However, current treatment regimens do not alleviate all joint haemarthroses with the potential for long-term joint deterioration remaining. The evaluation of functional activities such as gait, using standardized tools to monitor children with haemophilia is emerging. AIM: This study explored differences in sagittal plane biomechanics of walking in adolescent boys aged 11-18 years with haemophilia and an age-matched group of typically developing boys. METHODS: A motion capture system and 2 force platforms were used to collect sagittal plane kinematic, kinetic and temporal spatial data during level walking. Principal component analysis (PCA) was applied to kinematic and kinetic waveform variables. Group differences in temporal spatial and principal component scores for each kinematic and kinetic variable were evaluated using independent t tests. RESULTS: Significant alterations (P < .05) in temporal spatial and kinetic parameters were found in adolescent boys with haemophilia. Compared with typically developing adolescent boys, boys with haemophilia walked with reduced stance phase duration and altered pattern of external ankle joint moments during push off and the beginning of swing. CONCLUSION: The use of PCA rather than predetermined discriminatory variables provided additional insight into biomechanical alterations in adolescent boys with haemophilia, with adaptations occurring during terminal double support and early swing, affecting the ankle joint. This finding might be a key biomechanical marker that could be used to evaluate the joint function and the progression of early haemophilic arthropathy.

Exploration of potential mechanisms of hepatitis C virus resistance in exposed uninfected intravenous drug users.

A rare outcome following exposure to hepatitis C virus (HCV) is a lack of observable infection as clinically measured by HCV RNA- or HCV-recognizing antibodies. The population who exhibit this trait is termed exposed uninfected (EU). Increasing evidence has refined characterization of these individuals, distinct from those who become infected but spontaneously clear HCV. Study of the EU population is highly pertinent for the discovery of antiviral mechanisms of resistance that can reveal antiviral therapeutic strategies. This review provides an overview of similarities and differences of the EU population relative to spontaneous resolvers and the majority whom develop chronic HCV infection, and focusses on possible mechanisms of resistance including innate and adaptive immunity, genetics and lipid interactions.

Anti-envelope antibody responses in individuals at high risk of hepatitis C virus who resist infection.

Injection drug users uninfected by hepatitis C virus (HCV) despite likely repeated exposure through high-risk behaviour are well documented. Factors preventing infection in these individuals are incompletely understood. Here, we looked for anti-HCV-envelope antibody responses in a cohort of repeatedly exposed but uninfected subjects. Forty-two hepatitis C diagnostic antibody- and RNA-negative injection drug users at high risk of exposure were studied and findings compared to healthy controls and cases with chronic HCV infection. Purified IgGs from sera were tested by ELISA for binding to genotype 1a and 3a envelope glycoproteins E1E2 with further testing for IgG and IgM reactivity against soluble E2. Virus-neutralizing activity was assessed using an HCV pseudoparticle system. Uninfected subjects demonstrated significantly greater IgG and IgM reactivities to envelope glycoproteins than healthy controls with IgG from 6 individuals additionally showing significant neutralization. This study is the first to describe humoral immunological responses targeting the HCV envelope, important for viral neutralization, in exposed uninfected individuals. A subset of these cases also had evidence of viral neutralization via anti-envelope antibodies. In addition to confirming viral exposure, the presence of specific anti-envelope antibodies may be a factor that helps these individuals resist HCV infection.

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection.

A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment-naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution of HCV (HCV-Ab+ and HCV-RNA-) and 10 healthy unexposed controls. EU subjects had strikingly higher levels of both IL-6 (on average more than 100-fold, P = 0.001) and IL-8 (on average more than 10-fold, P < 0.001) than the comparison groups. Additionally higher levels of tumour necrosis factor-alpha (TNF-α; on average up to threefold, P = 0.02) were seen in EU individuals. The levels of interferon-alpha (IFN-α) were upregulated in all HCV exposed groups in comparison to healthy controls (P = 0.013). Adaptive immune cytokine levels were no different between the groups. Cytokine profiling demonstrated raised levels of pro-inflammatory innate immune cytokines and chemokines in EU IDU, in particular interleukin-6 and interleukin-8. These findings suggest innate immune activation may be the key to prevention of infection in this cohort.

Does physiotherapy treatment improve the self-reported pain levels and quality of life of women with vulvodynia? A pilot study.

The study investigated whether a 3-month period of physiotherapy treatment improved the pain levels and quality of life of women with vulvodynia. A quasi-experimental method was used, comprising a within-subjects, pre-test/post-test design in which subjects acted as their own controls. A convenience sample of 14 subjects was recruited from referrals to women's health physiotherapy between May and August 2004. The McGill Pain Questionnaire and Short Form 36 (version 2) were used to assess changes in self-reported pain levels and quality of life, respectively. Subjects completed questionnaires on recruitment to the study, 3 months later (immediately prior to commencing physiotherapy treatment), and after 3 months of treatment. The study investigated whether changes in pain levels and quality of life observed during the 3-month intervention phase differed from those observed during the 3-month control phase. The pain levels of study subjects reduced during the treatment period relative to the control period, and improvements were also observed in some aspects of quality of life. These results indicate that physiotherapy may offer some benefit in the treatment of vulvodynia. However, none of the findings reached statistical significance due to the small sample size. This study supports the view that physiotherapy provides pain relief for women with vulvodynia. Larger, randomised controlled trials are required to confirm the effectiveness of the treatment.

Surveillance of cirrhosis for hepatocellular carcinoma: a cost-utility analysis.

Using a decision-analytic model, we evaluated the effectiveness and cost-effectiveness of surveillance for hepatocellular carcinoma (HCC) in individuals with cirrhosis. Separate cohorts with cirrhosis due to alcoholic liver disease, hepatitis B and hepatitis C were simulated. Results were also combined to approximate a mixed aetiology population. Comparisons were made between a variety of surveillance algorithms using alpha-foetoprotein (AFP) assay and/or ultrasound at 6- and 12-monthly intervals. Parameter estimates were obtained from comprehensive literature reviews. Uncertainty was explored using one-way and probabilistic sensitivity analyses. In the mixed aetiology cohort, 6-monthly AFP+ultrasound was predicted to be the most effective strategy. The model estimates that, compared with no surveillance, this strategy may triple the number of people with operable tumours at diagnosis and almost halve the number of people who die from HCC. The cheapest strategy employed triage with annual AFP (incremental cost-effectiveness ratio (ICER): 20,700 pounds per quality-adjusted life-year (QALY) gained). At a willingness-to-pay threshold of 30,000 pounds per QALY the most cost-effective strategy used triage with 6-monthly AFP (ICER: 27,600 pounds per QALY gained). The addition of ultrasound to this strategy increased the ICER to 60,100 pounds per QALY gained. Surveillance appears most cost-effective in individuals with hepatitis B-related cirrhosis, potentially due to younger age at diagnosis of cirrhosis. Our results suggest that, in a UK NHS context, surveillance of individuals with cirrhosis for HCC should be considered effective and cost-effective. The economic efficiency of different surveillance strategies is predicted to vary markedly according to cirrhosis aetiology.

Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection.

Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposed-uninfected individuals and 105 healthy controls. Overall, the C allele was found in 27.6% of exposed-uninfected cases compared with 16.7% of healthy controls [chi(2) = 6.3, P = 0.02, odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.2]. CC genotype was found in 10.5% of exposed-uninfected cases compared with 0.9% controls (chi(2) = 9.3, P = 0.01, OR = 12, 95% CI = 1.5-100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed-uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection.

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis.

OBJECTIVES: To evaluate the effectiveness, cost-effectiveness and cost-utility of surveillance of patients with cirrhosis [alcoholic liver disease (ALD)-, hepatitis B (HBV)- and C virus (HCV)-related], using periodic serum alpha-fetoprotein (AFP) testing and/or liver ultrasound examination, to detect hepatocellular carcinoma (HCC), followed by treatment with liver transplantation or resection, where appropriate. DATA SOURCES: Electronic databases were searched up to March 2006. REVIEW METHODS: A systematic review was carried out using standard methodological guidelines. A computerised decision-analytic model was then developed to compare various surveillance strategies. RESULTS: No studies were identified that met the criteria of the systematic review. Based on the assumptions used in the model, the most effective surveillance strategy uses a combination of AFP testing and ultrasound at 6-monthly intervals. Compared with no surveillance, this strategy is estimated to more than triple the number of people with operable HCC tumours at time of diagnosis, and almost halves the number of deaths from HCC. On all effectiveness measures and at both testing frequencies, AFP- and ultrasound-led surveillance strategies are very similar. This may be because test sensitivity was varied according to tumour size, which means that AFP testing is capable of identifying many more small tumours than ultrasound. The best available evidence suggests that AFP tests will detect approximately six times as many small tumours as ultrasound. Increasing the frequency of either test to 6-monthly intervals is more effective than performing combined testing on an annual basis. The undiscounted lifetime cost of the surveillance strategies, including all care and treatment costs, ranges from 40,300 pounds (annual AFP triage) to 42,900 pounds (6-monthly AFP and ultrasound). The equivalent discounted costs are 28,400 pounds and 30,400 pounds. Only a small proportion of these total costs results from the cost of the screening tests. However, screening test costs, and the cost of liver transplants and caring for people post-transplant, accounted for most of the incremental cost differences between alternative surveillance strategies. The results suggest that different surveillance strategies may provide the best value for money in patient groups of different cirrhosis aetiologies. The surveillance of people with HBV-related cirrhosis for HCC provides the best value for money, while surveillance in people with ALD-related cirrhosis provides the poorest value for money. In people with HBV-related cirrhosis, at an assumed maximum willingness to pay (WTP) for a quality-adjusted life-year (QALY) of 30,000 pounds, both the deterministic and probabilistic cost-utility analyses suggest the optimal surveillance strategy would be 6-monthly surveillance with the combination of AFP testing and ultrasound. In contrast, for those with ALD-related cirrhosis, annual screening with AFP as a triage test is the only surveillance strategy that is likely to be considered cost-effective at this WTP. The probabilistic analysis implies that the estimated benefits of a 6-monthly AFP triage strategy will only be worth the cost in those with ALD when society's WTP for a QALY exceeds around 40,000 pounds. For people with HCV-related cirrhosis, the model suggests that the most cost-effective surveillance strategy at a WTP threshold of 30,000 pounds/QALY would be surveillance with a 6-monthly AFP triage strategy. CONCLUSIONS: In a mixed-aetiology cohort, the most effective surveillance strategy is to screen each patient with AFP assay and ultrasound imaging on a 6-monthly basis. However, when costs are taken into account it is doubtful whether ultrasound should be routinely offered to those with blood AFP of less than 20 ng/ml, unless policy-makers are prepared to pay over 60,000 pounds per QALY for the benefits achieved. Furthermore, the cost-effectiveness of surveillance for HCC varies considerably depending on the aetiology of cirrhosis; it is much more likely to be cost-effective in those with HBV-related cirrhosis, and much less likely to be cost-effective in those with ALD-related cirrhosis. Further development of the model would help to enable refinement of an optimal screening strategy. Research into the use of contrast-enhanced ultrasound technology for HCC detection would also be valuable, as would research into the epidemiology and natural history of ALD-related cirrhosis. Studies are also needed to investigate the influence of cirrhosis aetiology on tumour AFP expression.

The cost-effectiveness of testing for hepatitis C in former injecting drug users.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of testing for hepatitis C (HCV) among former injecting drug users (IDUs). DATA SOURCES: Electronic databases 1996-October 2004. Trent Regional Database Study. Routine UK mortality data. REVIEW METHODS: A decision analytic model was developed to investigate the impact of case-finding and treatment on progression of HCV disease in a hypothetical cohort of 1000 people. This was compared with a cohort in whom no systematic case-finding is implemented but spontaneous presentation for testing is allowed to occur. A group of epidemiological and clinical experts informed the structure of the model, which has three main components: (1) testing and diagnosis, (2) treatment, and (3) long-term consequences of infection. A fourth component, case-finding strategies, examines the potential impact of case-finding in three settings: prisons, general practice and drug services. RESULTS: Case-finding for HCV is likely to prevent, for 1000 people approached, three cases of decompensated cirrhosis, three deaths due to HCV and one case of hepatocellular cancer (at 30 years). Twenty-five additional people are likely to undergo combination therapy as a result of initial case-finding. One liver transplant is likely to be prevented for 10,000 people included in case-finding. Case-finding is likely to cost, in the general case, around pounds sterling 760,000 more than a policy of not case-finding. The total cost of either strategy is high and driven predominantly by the cost of treatment with combination therapy (the costs of long-term consequences are heavily discounted owing to the duration of the model). Systematically offering testing to 1000 people would cost around pounds sterling 70,000. In terms of life-years gained, case-finding is likely to result in an additional life-year gained for an investment of pounds sterling 20,084. Taking impacts on quality of life into account gives an estimate for the cost-utility of case-finding as pounds sterling 16,514 per QALY. The probabilistic sensitivity analysis shows that, if NHS policy makers view pounds sterling 30,000 per QALY as an acceptable return on investment, there is a 74% probability that case-finding for HCV would be considered cost-effective. At pounds sterling 20,000 per QALY, the probability that case-finding would be considered cost-effective is 64%. In all analyses, the probability of case-finding being considered cost-effective at a level of pounds sterling 30,000 per QALY was high. Case-finding in drug services is likely to be the most expensive, owing to the high prevalence of cases in the tested population. Correspondingly, benefits are highest for this strategy and cost-effectiveness is similar, in average terms, to the general case. Case-finding in general practice by offering testing to the whole population aged 30-54 years is, paradoxically, estimated to be the least expensive option as only a small number of people accept the offer of testing and HCV prevalence in this group is much higher than would be expected from the general population. Two approaches to case-finding in prison were considered, based on the results of studies in Dartmoor and the Isle of Wight prisons. These differed substantially in the prevalence of cases identified in the tested populations. The analysis based on data from Dartmoor prison had the least favourable average cost-effectiveness of the strategies considered (pounds sterling 20,000 per QALY). Subgroup analyses based on duration of infection show that case-finding is likely to be most cost-effective in people whose infection is more long-standing and who are consequently at greater risk of progression. In people who were infected more than 20 years previously, case-finding yields benefits at around pounds sterling 15,000 per QALY. Treatment effectiveness was modelled using estimates from randomised controlled trials and lower rates of viral response may be seen in practice. However, estimates of cost-effectiveness remained below pounds sterling 30,000 for all levels of treatment effectiveness above 58% of those shown in the relevant trials. The value of information analysis, based on assumptions that 10,000 people might be eligible for case-finding and that programmes would run for 15 years, suggests that the maximum value of further research into case-finding is in excess of pounds sterling 19 million. Partial expected value of perfect information (EVPI) analysis shows that the utility estimates used in the model eclipse all other factors in terms of importance to parameter uncertainty. This is not surprising, since the point estimates for differences in utility between states and across the arms of the model are small. CONCLUSIONS: Case-finding for hepatitis C is likely to be considered cost-effective by NHS commissioners. Although there remains considerable uncertainty, it appears unlikely that cost-effectiveness would exceed the levels considered acceptable. Further improvements in the effectiveness of treatments to slow or halt disease progression are likely to improve the cost-effectiveness of case-finding. Case-finding is likely to be most cost-effective if targeted at people whose HCV disease is probably more advanced. Further empirical work is required to specify, in practice, different approaches to case-finding in appropriate settings and to evaluate their effectiveness and cost-effectiveness directly.

Low intensity strength training for ambulatory stroke patients.

PURPOSE: To investigate feasibility and effectiveness of an individually-directed, group strength-training programme on knee muscle strength after stroke. METHOD: Ten volunteers (62 +/- 11 years, mean +/- SD), 6 - 12 months after first-ever unilateral stroke, walking independently with or without aids were recruited. Using an A1-B-A2 design, 3 sets of baseline measures were taken at 2 weekly intervals; volunteers then attended twice weekly sessions of low intensity progressive strengthening exercises and were assessed after each series of 8 sessions to a maximum of 24 sessions; post training, measures were repeated after 4 - 6 weeks. Measures included isometric and concentric knee extensor muscle strength and 10 m walking velocity. RESULTS: Strength of knee extensor muscles was improved after training (ANOVA, p < 0.05). On cessation of training, isometric strength increased by 58 +/- 19% and concentric strength at 30 degrees /s by 51 +/- 14%; walking velocity quickened from 0.47 +/- 0.06 m x s-1 to 0.57 +/- 0.08 m x s-1 (t = -3.31, p < 0.01). These gains were maintained 4 - 6 weeks after completion of training. CONCLUSIONS: These findings support the use of low intensity strength training after stroke and confirm published evidence. It was feasible for one therapist to deliver the training programmes for 4 - 6 participants at a time; an important feature when resources are limited.

Reactivation of latent hepatitis B virus infection with HIV-related immunosuppression.

The effect of HIV-related immunosuppression and antiretroviral therapy on the reactivation of latent hepatitis B virus (HBV) infection is unclear. We report four patients with advanced HIV-related immunosuppression and abnormal liver function tests who had evidence of HBV reactivation. Reclearance of hepatitis B occurred in two cases with HIV treatment regimens not containing lamivudine, suggesting that improved immune function may be responsible. In three cases, HBV reactivation was recognized during investigation for abnormal liver function initially attributed to drug toxicity. The possibility of HBV reactivation must be considered in the differential diagnosis of abnormal liver function in cases with advanced HIV.