Cost-effectiveness analysis of chronic hepatitis C treatment in the prison population in Spain.

OBJECTIVES: To evaluate the cost-effectiveness of direct-acting antiviral (DAAs) treatment versus non-treatment in prisoners awaiting treatment for chronic hepatitis C (CHC) and to analyse the clinical and economic impact of the treatment on liver complications and mortality. MATERIAL AND METHOD: A lifetime Markov model was developed to simulate treatment and disease progression from an estimated cohort of 4,408 CHC prisoners treated with DAAs over 2 years (50% of patient each year) versus no treatment. In the treated cohort, a sustained viral response of 95% was associated. Patient characteristics, transition probabilities, utilities and costs (pharmacological and healthcare states) were obtained from published literature. The model estimated healthcare costs and benefits, incremental cost-utility ratio (ICUR) based on total costs and the quality-adjusted life year (QALY) and avoided clinical events. A National Healthcare System perspective was adopted with a 3% annual discount rate for both costs and health outcomes. Sensitivity analyses were performed to assess uncertainty. RESULTS: In the DDA treated cohort, the model estimated a decrease of 92% of decompensated cirrhosis and 83% of hepatocellular carcinoma, 88% liver-related mortality cases were reduced, 132 liver transplants were avoided. The treatment achieved an additional 5.0/QALYs (21.2 vs. 16.2) with an incremental cost of €3,473 (€24,088 vs. €20,615) per patient with an ICUR of €690 per QALY gained. DISCUSSION: Considering the willingness-to-pay threshold used in Spain (€22,000-30,000/QALY), DAAs treatment for prisoners with CHC is a highly cost-effective strategy, reduces infection transmission, increases survival and reduces complications due to liver disease, as well as the cost associated with its management.

Is the universal population Hepatitis C virus screening a cost-effective strategy? A systematic review of the economic evidence.

OBJECTIVE: Efficient strategies are needed in order to achieve the objective of the WHO of eradicating Hepatitis C virus (HCV). Hepatitis C infection can be eliminated by a combination of direct acting antiviral (DAA). The problem is that many individuals remain undiagnosed. The objective is to conduct a systematic review of the evidence on economic evaluations that analyze the screening of HCV followed by treatment with DAAs. METHODS: Eleven databases were performed in a 2015-2018-systematic review. Inclusion criteria were economic evaluations that included incremental cost-effectiveness ratio (ICER) in terms of cost per life year gained or quality-adjusted life year. RESULTS: A total of 843 references were screened. Sixteen papers/posters meet the inclusion criteria. Ten of them included a general population screening. Other populations included were baby-boomer, people who inject drugs, prisoners or immigrants. Comparator was "standard of care", other high-risk populations or no-screening. Most of the studies are based on Markov model simulations and they mostly adopted a healthcare payer´s perspective. ICER for general population screening plus treatment versus high-risk populations or versus routinely performed screening showed to be below the accepted willingness to pay thresholds in most studies and therefore screening plus DAAs strategy is highly cost-effective. CONCLUSIONS: This systematic review shows that screening programmes followed by DAAs treatment is cost-effective not only for high risk population but for general population too. Because today HCV can be easily cured and its long-term consequences avoided, a universal HCV screening plus DAAs therapies should be the recommended strategy to achieve the WHO objectives for HCV eradication by 2030.

Assessment of Alimentación Normal con Ajuste de Insulina (ANAIS), a Spanish version of the DAFNE programme, in people with Type 1 diabetes: a randomized controlled parallel trial.

AIM: To evaluate the effects of Alimentación Normal con Ajuste de Insulina (ANAIS), a group-based, therapeutic education programme for Type 1 diabetes based on a flexible insulin regimen adjusted to the individual's food intake. METHODS: Participants with Type 1 diabetes and HbA1c levels of 53-86 mmol/mol (7-10%) were recruited from outpatient clinics at a tertiary care centre. They were randomized (using opaque, sealed envelopes, with a 2:1 treatment allocation ratio) to attend the training course immediately (immediate ANAIS; intervention group) or a year later (delayed ANAIS; control group). The main outcome was HbA1c level at 1 year. Secondary outcomes included lipid levels, weight, hypoglycaemic events, insulin dose, treatment satisfaction, self-perceived dietary freedom, quality of life and participant-defined goals. RESULTS: A total of 48 participants were assigned to the intervention group and 32 to the control group. Twelve months after completing the training, adjusted HbA1c was not significantly different in the intervention group [64 ± 1.3 vs 68 ± 1.6 mmol/mol (8.0 ±0.1% vs 8.4 ±0.1%); P=0.081]. Treatment satisfaction was significantly higher in the intervention group, but no differences were found in hypoglycaemic events, weight, insulin dose or changes in dietary freedom. At 1 year after the intervention, 72% of the participants (vs 33% in the control group; P=0.046) reported exceeding their expectations regarding achievement of their main personal goal. CONCLUSION: Promoting dietary freedom and empowering people with Type 1 diabetes through structured education programmes, such as ANAIS, improves treatment satisfaction and self-defined goals. No significant improvement in HbA1c level was achieved.

Efficacy and Cost of Trap-Bait Combinations for Capturing Rhynchophorus palmarum L. (Coleoptera: Curculionidae) in Ornamental Palm Polycultures.

Ornamental palms are an economically important component of international trade yet have recently experienced yield losses in Mexico due to red ring and bud rot diseases, which are spread by Rhynchophorus palmarum L. Considering that massive capture is a common strategy to control this pest and the cost of commercial traps and baits could be inaccessible for small farmers, an inexpensive trap-bait combination is desired. In this study, 16 trap-bait combinations for capturing R. palmarum were assessed in ornamental palm polycultures over the course of 1 year. An expensive yellow bucket trap combined with aggregation pheromone + insecticide + banana was compared with inexpensive, handmade trap-bait combinations. A total of 4712 weevils were collected in all traps, of which 52.7% were male and 47.3% female. The efficacy of the handmade trap made from a colorless polyethylene bottle and baited with banana + pineapple + sugarcane + sugarcane molasses was similar to that of the yellow bucket trap baited with aggregation pheromone + insecticide + banana. These two trap-bait combinations remained effective even when the R. palmarum population significantly decreased during the dry, warm season. The affordable handmade trap baited with food attractants and without insecticides was highly efficient in capturing R. palmarum and therefore represents an effective tool for monitoring weevil populations. As ornamental crops have recently gained greater economic importance in the studied region, the use of a novel and cheap trap-bait combination could offer great benefits to producers and form part of the integrated management of R. palmarum.

Cost-effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis.

To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings.

Monitoring ocular hypertension, how much and how often? A cost-effectiveness perspective.

OBJECTIVE: To assess the efficiency of alternative monitoring services for people with ocular hypertension (OHT), a glaucoma risk factor. DESIGN: Discrete event simulation model comparing five alternative care pathways: treatment at OHT diagnosis with minimal monitoring; biennial monitoring (primary and secondary care) with treatment if baseline predicted 5-year glaucoma risk is ≥6%; monitoring and treatment aligned to National Institute for Health and Care Excellence (NICE) glaucoma guidance (conservative and intensive). SETTING: UK health services perspective. PARTICIPANTS: Simulated cohort of 10 000 adults with OHT (mean intraocular pressure (IOP) 24.9 mm Hg (SD 2.4). MAIN OUTCOME MEASURES: Costs, glaucoma detected, quality-adjusted life years (QALYs). RESULTS: Treating at diagnosis was the least costly and least effective in avoiding glaucoma and progression. Intensive monitoring following NICE guidance was the most costly and effective. However, considering a wider cost-utility perspective, biennial monitoring was less costly and provided more QALYs than NICE pathways, but was unlikely to be cost-effective compared with treating at diagnosis (£86 717 per additional QALY gained). The findings were robust to risk thresholds for initiating monitoring but were sensitive to treatment threshold, National Health Service costs and treatment adherence. CONCLUSIONS: For confirmed OHT, glaucoma monitoring more frequently than every 2 years is unlikely to be efficient. Primary treatment and minimal monitoring (assessing treatment responsiveness (IOP)) could be considered; however, further data to refine glaucoma risk prediction models and value patient preferences for treatment are needed. Consideration to innovative and affordable service redesign focused on treatment responsiveness rather than more glaucoma testing is recommended.

Laboratory Animal Legislation in Latin America.

A review of existing legislation covering laboratory animals in Latin America is presented. The region presents a spectrum of economic development, political stability, and cultural diversity. With the exception of a few nations, there is a lack of regulations as well as minimal enforcement of existing laws pertaining to laboratory animals. Brazil, Mexico, and Uruguay stand out as the only nations in this region with specific legislation regulating laboratory animal care and use; the history and current status of regulations in these three nations is reviewed.

Economic evaluation of nurse-led intensive care follow-up programmes compared with standard care: the PRaCTICaL trial.

OBJECTIVE: Following intensive care discharge, many patients suffer severe physical and psychological morbidity and a continuing high use of health services. Follow-up programmes have been proposed to improve the outcomes for these patients. We tested the hypothesis that nurse-led intensive care follow-up programmes are cost-effective. METHODS: A pragmatic, multicentre, randomised controlled trial of nurse-led intensive care unit follow-up programmes versus standard care. A cost-utility analysis was conducted after 12 months' follow-up to compare the two interventions. Costs were assessed from the perspective of the UK NHS and outcomes were measured in quality-adjusted life years (QALYs) based upon responses to the EQ-5D administered at baseline, 6 and 12 months. RESULTS: A total of 286 patients were recruited to the trial. Total mean cost was £ 5,789 for standard care and £ 7,577 for the discharge clinic. The adjusted difference in means was £ 2,435 [95 % confidence interval (CI) -297 to 5,566]. Mean QALYs were 0.58 for standard care and 0.60 for the discharge clinic. The adjusted mean difference was -0.003 (95 % CI -0.066 to 0.060). If society were willing to pay £ 20,000 per QALY then there would be a 93 % chance that standard care would be considered most efficient. CONCLUSIONS: A nurse-led intensive care unit (ICU) follow-up programme showed no evidence of being cost-effective at 12 months. Further work should focus on evidence-based development of discharge clinic services and current ICU follow-up programmes should review their practice in light of these results.

A cost-effective method for estimating di(2-ethylhexyl)phthalate in coastal sediments.

This study describes the development of a new method for the analysis of di(2-ethylhexyl)phthalate (DEHP) using 0.1-0.3 g of sediment sample, based on matrix solid phase dispersion (MSPD) using C18 as dispersant phase (0.4 g) and acetonitrile-water as eluting solvent (3.4 mL 1:3.25, v/v). No evaporation step is required. 3 mL of extracts were processed on-line by in-tube solid phase microextraction (IT-SPME) coupled to capillary liquid chromatography (CapLC) and diode array detector (DAD). A short analytical column Zorbax SB C18 (35×0.5 mm, 5 µm) provided suitable results. FTIR-ATR was employed for characterizing sediment samples and MSPD procedure. The total analysis time was less than 20 min (MSPD takes about 10 min). The utility of the described approach has been tested by analyzing several real samples. No matrix effect was found. Achieved precision was less than 10% for DEHP estimation. Detection limits in samples were 270 and 90 µg/kg for 0.1 and 0.3 g of taken sediment, respectively.

Long-term outcome of the Cloward procedure for single-level cervical degenerative spondylosis. Clinical and radiological assessment after a 22-year mean follow-up.

PURPOSE: To evaluate the long-term outcomes of the classical Cloward procedure in single-level cervical spondylosis. METHODS: A retrospective study of 28 patients who were affected by cervical degenerative spondylosis at C4-C7 segments and treated by the Cloward technique at a single level from 1985-1995 was conducted. The average follow-up period was 22 years (range, 17-27 years). Preoperative clinical complaints were recorded and compared to the current clinical status. Preoperative, 3-6 months postoperative and a current radiographic study were analysed by evaluating the segmental and global sagittal alignment of the cervical spine as well as the occurrence of adjacent disc degeneration. RESULTS: The most frequently operated segment was C5-C6 (57.1 %), followed by C6-C7 (32.1 %) and C4-C5 (7.1 %). Pain relief and symptom recovery experienced 3-6 months following the surgery was maintained at the most recent follow-up in 85 % of patients. Adjacent disc degeneration was detected in a total of 17 cases (60.7 %). Overall, a group of 14 cases (50 %) had increased lordosis at C2-C7 at the most recent follow-up, with a mean gain of 1.5º Cobb. According to Odom's criteria, 17 patients (60.8 %) presented with excellent clinical outcome, 6 (21.4 %) presented with good outcome, 5 had a (17.8 %) fair outcome, and none had a poor outcome. CONCLUSIONS: The Cloward technique provided excellent long-term clinical outcome in the treatment of single-level cervical degenerative spondylosis. There were no major alterations of the cervical sagittal balance, and the development of adjacent segment disease (ASD) was not specifically associated with the previous surgery.

Surveillance for ocular hypertension: an evidence synthesis and economic evaluation.

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways. DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model. SETTING: Primary and secondary care. PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences). INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community. MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs). RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence. LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates. CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment. FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

The clinical effectiveness and cost-effectiveness of different surveillance mammography regimens after the treatment for primary breast cancer: systematic reviews registry database analyses and economic evaluation.

BACKGROUND: Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. OBJECTIVES: To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. METHODS: A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost-utility of differing surveillance regimens. RESULTS: The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring >20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was <10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. LIMITATIONS: Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. CONCLUSIONS: Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell's palsy: the BELLS study.

OBJECTIVE: To determine whether oral prednisolone or aciclovir, used separately or in combination, early in the course of Bell's palsy, improves the chances of recovery at 3 and 9 months. DESIGN: A 2 x 2 factorial randomised double-blind trial. Patients were randomly assigned to treatment by an automated telephone service using a permuted block randomisation technique with block sizes of four or eight, and no stratification. SETTING: Mainland Scotland, with referrals mainly from general practice to 17 hospital trial sites. PARTICIPANTS: Adults (aged 16 years or older) with unilateral facial nerve weakness of no identifiable cause presenting to primary care, the emergency department or NHS24 within 72 hours of symptom onset. INTERVENTIONS: Patients were randomised to receive active preparations or placebo for 10 days: (1) prednisolone (50 mg per day, 2 x 25-mg capsules) and aciclovir (2000 mg per day, 5 x 400-mg capsules); (2) prednisolone and placebo (lactose, indistinguishable); (3) aciclovir and placebo; and (4) placebo and placebo. OUTCOME MEASURES: The primary outcome was recovery of facial function assessed by the House-Brackmann scale. Secondary outcomes included health status, pain, self-perceived appearance and cost-effectiveness. RESULTS: Final outcomes were available for 496 patients, balanced for gender; mean age 44 years; initial facial paralysis moderate to severe. One half of patients initiated treatment within 24 hours of onset of symptoms, one-third within 24-48 hours and the remainder within 48-72 hours. Of the completed patients, 357 had recovered by 3 months and 80 at 9 months, leaving 59 with a residual deficit. There were significant differences in complete recovery at 3 months between the prednisolone comparison groups (83.0% for prednisolone, 63.6% for no prednisolone, a difference of + 19.4%; 95% confidence interval (CI): + 11.7% to + 27.1%, p < 0.001). The number needed to treat (NNT) in order to achieve one additional complete recovery was 6 (95% CI: 4 to 9). There was no significant difference between the aciclovir comparison groups (71.2% for aciclovir and 75.7% for no aciclovir). Nine-month assessments of patients recovered were 94.4% for prednisolone compared with 81.6% for no prednisolone, a difference of + 12.8% (95% CI: + 7.2% to + 18.4%, p < 0.001); the NNT was 8 (95% CI: 6 to 14). Proportions recovered at 9 months were 85.4% for aciclovir and 90.8% for no aciclovir, a difference of -5.3%. There was no significant prednisolone-aciclovir interaction at 3 months or at 9 months. Outcome differences by individual treatment (the four-arm model) showed significant differences. At 3 months the recovery rate was 86.3% in the prednisolone treatment group, 79.7% in the aciclovir-prednisolone group, 64.7% in the placebo group and 62.5% in the aciclovir group. At 9 months the recovery rates were respectively 96.1%, 92.7%, 85.3% and 78.1%. The increase in recovery rate conferred by the addition of prednisolone (both for prednisolone over placebo and for aciclovir-prednisolone over aciclovir) is highly statistically significant (p < 0.001). There were no significant differences in secondary measures apart from Health Utilities Index Mark 3 (HUI3) at 9 months in those treated with prednisolone. CONCLUSIONS: This study provided robust evidence to support the early use of oral prednisolone in Bell's palsy as an effective treatment which may be considered cost-effective. Treatment with aciclovir, either alone or with steroids, had no effect on outcome.

The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial.

OBJECTIVES: To test the hypothesis that nurse led follow-up programmes are effective and cost effective in improving quality of life after discharge from intensive care. DESIGN: A pragmatic, non-blinded, multicentre, randomised controlled trial. SETTING: Three UK hospitals (two teaching hospitals and one district general hospital). PARTICIPANTS: 286 patients aged >or=18 years were recruited after discharge from intensive care between September 2006 and October 2007. INTERVENTION: Nurse led intensive care follow-up programmes versus standard care. Main outcome measure(s) Health related quality of life (measured with the SF-36 questionnaire) at 12 months after randomisation. A cost effectiveness analysis was also performed. RESULTS: 286 patients were recruited and 192 completed one year follow-up. At 12 months, there was no evidence of a difference in the SF-36 physical component score (mean 42.0 (SD 10.6) v 40.8 (SD 11.9), effect size 1.1 (95% CI -1.9 to 4.2), P=0.46) or the SF-36 mental component score (effect size 0.4 (-3.0 to 3.7), P=0.83). There were no statistically significant differences in secondary outcomes or subgroup analyses. Follow-up programmes were significantly more costly than standard care and are unlikely to be considered cost effective. CONCLUSIONS: A nurse led intensive care follow-up programme showed no evidence of being effective or cost effective in improving patients' quality of life in the year after discharge from intensive care. Further work should focus on the roles of early physical rehabilitation, delirium, cognitive dysfunction, and relatives in recovery from critical illness. Intensive care units should review their follow-up programmes in light of these results. TRIAL REGISTRATION: ISRCTN 24294750.

Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal.

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of romiplostim for the treatment of adults with chronic immune or idiopathic thrombocytopenic purpura (ITP) based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from two relatively high-quality randomised controlled trials (RCTs). The ERG found no evidence that any important data were missed or that data extraction was inaccurate. In both RCTs more patients in the romiplostim than in the placebo group achieved a durable platelet response [non-splenectomised patients: romiplostim 25/41 (61%), placebo 1/21 (5%), odds ratio (OR) 24.45, 95% confidence interval (CI) 3.34 to 179.18; splenectomised patients: romiplostim 16/42 (38%), placebo 0/21 (0%), OR 8.5 (95% CI 1.15 to 372)] and an overall platelet response [non-splenectomised patients: romiplostim 36/41 (88%), placebo 3/21 (14%), OR 34.74, 95% CI 7.77 to 155.38; splenectomised patients: romiplostim 33/42 (79%), placebo 0/21 (0%), OR 16.6 (95% CI 2.37 to 706]. The difference in mean period with a platelet response was 13.9 weeks (95% CI 10.5 to 17.4) in favour of romiplostim in the RCT of non-splectomised patients and 12.1 weeks (95% CI 8.7 to 15.6) in favour of romiplostim in the RCT of splectomised patients. The manufacturer's economic model evaluated the cost-effectiveness of romiplostim compared with standard care. The ERG had concerns about the way the decision problem was addressed in the economic model and about the non-adjustment of findings for confounding factors. In non-splenectomised patients, using romiplostim as a first option treatment, the base-case incremental cost-effectiveness ratio (ICER) was 14,840 pounds per quality-adjusted life-year (QALY). In splenectomised patients the ICER was 14,655 pounds per QALY. Additional sensitivity analyses performed by the ERG identified two issues of importance: whether individuals entered the model on watch and rescue or on active therapy in the comparator arm (ICER 21,674 pounds per QALY for non-splenectomised patients, 29,771 pounds per QALY for splenectomised patients); whether it was assumed that any unused medicine would be wasted. Combining all of the separate sensitivity analyses, and assuming that watch and rescue was not the first-line treatment, increased the ICERs further (non-splenectomised 37,290 pounds per QALY; splenectomised 131,017 pounds per QALY). In conclusion, the manufacturer's submission and additional work conducted by the ERG suggest that romiplostim has short-term efficacy for the treatment of ITP, but there is no robust evidence on long-term effectiveness or cost-effectiveness of romiplostim compared with relevant comparators.

Systematic review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of oesophageal Doppler monitoring (ODM) compared with conventional clinical assessment and other methods of monitoring cardiovascular function. DATA SOURCES: Electronic databases and relevant websites from 1990 to May 2007 were searched. REVIEW METHODS: This review was based on a systematic review conducted by the US Agency for Healthcare Research and Quality (AHRQ), supplemented by evidence from any additional studies identified. Comparator interventions for effectiveness were standard care, pulmonary artery catheters (PACs), pulse contour analysis monitoring and lithium or thermodilution cardiac monitoring. Data were extracted on mortality, length of stay overall and in critical care, complications and quality of life. The economic assessment evaluated strategies involving ODM compared with standard care, PACs, pulse contour analysis monitoring and lithium or thermodilution cardiac monitoring. RESULTS: The AHRQ report contained eight RCTs and was judged to be of high quality overall. Four comparisons were reported: ODM plus central venous pressure (CVP) monitoring plus conventional assessment vs CVP monitoring plus conventional assessment during surgery; ODM plus conventional assessment vs CVP monitoring plus conventional assessment during surgery; ODM plus conventional assessment vs conventional assessment during surgery; and ODM plus CVP monitoring plus conventional assessment vs CVP monitoring plus conventional assessment postoperatively. Five studies compared ODM plus CVP monitoring plus conventional assessment with CVP monitoring plus conventional assessment during surgery. There were fewer deaths [Peto odds ratio (OR) 0.13, 95% CI 0.02-0.96], fewer major complications (Peto OR 0.12, 95% CI 0.04-0.31), fewer total complications (fixed-effects OR 0.43, 95% CI 0.26-0.71) and shorter length of stay (pooled estimate not presented, 95% CI -2.21 to -0.57) in the ODM group. The results of the meta-analysis of mortality should be treated with caution owing to the low number of events and low overall number of patients in the combined totals. Three studies compared ODM plus conventional assessment with conventional assessment during surgery. There was no evidence of a difference in mortality (fixed-effects OR 0.81, 95% CI 0.23-2.77). Length of hospital stay was shorter in all three studies in the ODM group. Two studies compared ODM plus CVP monitoring plus conventional assessment vs CVP monitoring plus conventional assessment in critically ill patients. The patient groups were quite different (cardiac surgery and major trauma) and neither study, nor a meta-analysis, showed a statistically significant difference in mortality (fixed-effects OR 0.84, 95% CI 0.41-1.70). Fewer patients in the ODM group experienced complications (OR 0.49, 95% CI 0.30-0.81) and both studies reported a statistically significant shorter median length of hospital stay in that group. No economic evaluations that met the inclusion criteria were identified from the existing literature so a series of balance sheets was constructed. The results show that ODM strategies are likely to be cost-effective. CONCLUSIONS: More formal economic evaluation would allow better use of the available data. All identified studies were conducted in unconscious patients. However, further research is needed to evaluate new ODM probes that may be tolerated by awake patients. Given the paucity of the existing economic evidence base, any further primary research should include an economic evaluation or should provide data suitable for use in an economic model.

Economic evaluation of early administration of prednisolone and/or aciclovir for the treatment of Bell's palsy.

OBJECTIVES: Bell's palsy (BP), which causes facial paralysis, affects 11-40 people per 100 000 per annum in the UK. Its cause is unknown but as many as 30% of patients have continuing facial disfigurement, psychological difficulties and occasionally facial pain. We present an randomised controlled trial (RCT)-based economic evaluation of the early administration of steroids (prednisolone) and/or antivirals (acyclovir) compared to placebo, for treatment of BP. METHODS: The RCT was not powered to detect differences in the cost-effectiveness; therefore, we adopted a decision analytic model approach as a way of gaining precision in our cost-effectiveness comparisons [e.g. prednisolone only (PO) versus acyclovir only versus prednisolone and acyclovir versus placebo, prednisolone versus no prednisolone (NP) and acyclovir versus no acyclovir]. We assumed that trial interventions affect the probability of being cured/not cured but their consequences are independent of the initial therapy. We used the percentage of individuals with a complete recovery (based on House-Brackmann grade = 1) at 9 months and Quality Adjusted Life Years (e.g. derived on responses to the Health Utilities Index III) as measures of effectiveness. Other parameter estimates were obtained from trial data. RESULTS: PO dominated-i.e. was less costly and more effective-all other therapy strategies in the four arms model [77% probability of cost-effective (CE)]. Moreover, Prednisolone dominated NP (77% probability of being CE at 30 000 UK pounds threshold) while no acyclovir dominated aciclovir (85% chance of CE), in the two arms models, respectively. CONCLUSIONS: Treatment of BP with prednisolone is likely to be considered CE while treatment with acyclovir is highly unlikely to be considered CE. Further data on costs and utilities would be useful to confirm findings.

New micromethod combining miniaturized matrix solid-phase dispersion and in-tube in-valve solid-phase microextraction for estimating polycyclic aromatic hydrocarbons in bivalves.

Miniaturized matrix solid-phase dispersion (MSPD) was developed for the extraction of common polycyclic aromatic hydrocarbons (PAHs) from bivalve samples (100mg, dry weight). Additional clean-up and analyte enrichment was accomplished by in-tube solid-phase microextraction (SPME). For this purpose the extracts collected after MSPD were diluted with water and injected into a capillary column coated with the extractive phase. This capillary column was connected to the analytical column by means of a switching valve. Separation and quantification of the PAHs were carried out using a monolithic LC column and fluorescence detection. Since the in-tube SPME device allowed the processing of large volumes of the extracts (2.0 mL) excellent sensitivity was achieved, thus making solvent evaporation operations unnecessary. The overall recoveries ranged from 10% to 28% for the studied compounds. The relative standard deviation (RSD) ranged from 2% to 10% for intra-day variation (n=3), and the limits of detection (LODs) were < or =0.6 ng/g (dry weight). The proposed procedure was very simple and rapid (total analysis time was approximately 20 min), and the consumption of organic solvents and extractive phases was drastically reduced. The reliability of the proposed MSPD/in-tube SPME method was tested by analysing several bivalves (mussels and tellins) as well as a standard reference material (SRM).

Systematic review of economic evaluations of laparoscopic surgery for colorectal cancer.

OBJECTIVE: Colorectal cancer is one of the most common cancers and the standard surgical treatment for this cancer is open resection (OS), but laparoscopic surgery (LS) may be an alternative treatment. In 2000, a Health Technology Assessment (HTA) review found little evidence on costs and cost-effectiveness in comparing the two methods. The evidence base has since expanded and this study systematically reviews the economic evaluations on the subject published since 2000. METHOD: Systematic review of studies reporting costs and outcomes of LS vs OS for colorectal cancer. National Health Service Economic Evaluation Database (NHS EED) methods for abstract writing were followed. Studies were summarized and incremental cost-effectiveness ratios (ICER) for common outcomes were calculated. RESULTS: Five studies met the inclusion criteria. LS generally had higher healthcare costs. Most studies reported longer operational time and shorter length of stay and similar long-term outcomes with LS vs OS. Only one outcome, complications, was common across all studies but results lacked consistency (e.g. in two studies, OS was less costly but more effective; in another study, LS was less costly but more effective; and in the further two studies, LS could potentially be cost effective depending on the decision-makers' willingness to pay for the health gain). CONCLUSION: The evidence on cost-effectiveness is not consistent. LS was generally more costly than OS. However, the effectiveness data used in individual economic evaluation were imprecise and unreliable when compared with data from systematic reviews of effectiveness. Nevertheless, short-term benefits of LS (e.g. shorter recovery) may make LS appear less costly when productivity gains are considered.