Pencil beam scanning proton therapy for mediastinal lymphomas in deep inspiration breath-hold: a retrospective assessment of plan robustness.

PURPOSE/BACKGROUND: The aim of this study was to evaluate pencil beam scanning (PBS) proton therapy (PT) in deep inspiration breath-hold (DIBH) for mediastinal lymphoma patients, by retrospectively evaluating plan robustness to the clinical target volume (CTV) and organs at risk (OARs) on repeated CT images acquired throughout treatment.  Methods: Sixteen mediastinal lymphoma patients treated with PBS-PT in DIBH were included. Treatment plans (TPs) were robustly optimized on the CTV (7 mm/4.5%). Repeated verification CTs (vCT) were acquired during the treatment course, resulting in 52 images for the entire patient cohort. The CTV and OARs were transferred from the planning CT to the vCTs with deformable image registration and the TPs were recalculated on the vCTs. Target coverage and OAR doses at the vCTs were compared to the nominal plan. Deviation in lung volume was also calculated. RESULTS: The TPs demonstrated high robust target coverage throughout treatment with D98%,CTV deviations within 2% for 14 patients and above the desired requirement of 95% for 49/52 vCTs. However, two patients did not achieve a robust dose to CTV due to poor DIBH reproducibility, with D98%,CTV at 78 and 93% respectively, and replanning was performed for one patient. Adequate OAR sparing was achieved for all patients. Total lung volume variation was below 10% for 39/52 vCTs. CONCLUSION: PBS PT in DIBH is generally a robust technique for treatment of mediastinal lymphomas. However, closely monitoring the DIBH-reproducibility during treatment is important to avoid underdosing CTV and achieve sufficient dose-sparing of the OARs.

Cost-Effectiveness of Risk Score-Stratified Hepatocellular Carcinoma Screening in Patients with Cirrhosis.

OBJECTIVES: Hepatocellular carcinoma (HCC) surveillance with biannual ultrasound is currently recommended for all patients with cirrhosis. However, clinical implementation of this "one-size-fits-all" approach is challenging as evidenced by its low application rate. We aimed to evaluate the cost-effectiveness of risk-stratified HCC surveillance strategies in patients with cirrhosis. METHODS: A Markov decision-analytic modeling was performed to simulate a cohort of 50-year-old subjects with compensated cirrhosis. Risk-stratified HCC surveillance strategies was implemented, in which patients were stratified into high-, intermediate-, or low-risk groups by HCC risk biomarker-based scores and assigned to surveillance modalities tailored to HCC risk (2 non-risk-stratified and 14 risk-stratified strategies) and compared with non-stratified biannual ultrasound. RESULTS: Quality-adjusted life expectancy gains for biannual ultrasound in all patients and risk-stratified strategies compared with no surveillance were 1.3 and 0.9-2.1 years, respectively. Compared with the current standard of biannual ultrasound in all cirrhosis patients, risk-stratified strategies applying magnetic resonance imaging (MRI) and/or ultrasound only in high- and intermediate-risk patients, without screening in low-risk patients, were cost-effective. Abbreviated MRI (AMRI) for high- and intermediate-risk patients had the lowest incremental cost-effectiveness ratio (ICER) of $2,100 per quality-adjusted life year gained. AMRI in intermediate- and high-risk patients had ICERs <$3,000 across a wide range of HCC incidences. CONCLUSIONS: Risk-stratified HCC surveillance strategies targeting high- and intermediate-risk patients with cirrhosis are cost-effective and outperform the currently recommended non-stratified biannual ultrasound in all patients with cirrhosis.

Cost-effectiveness of novel regimens for the treatment of hepatitis C virus.

BACKGROUND: New regimens for hepatitis C virus (HCV) have shorter treatment durations and increased rates of sustained virologic response compared with existing therapies but are extremely expensive. OBJECTIVE: To evaluate the cost-effectiveness of these treatments under different assumptions about their price and efficacy. DESIGN: Discrete-event simulation. DATA SOURCES: Published literature. TARGET POPULATION: Treatment-naive patients infected with chronic HCV genotype 1, 2, or 3. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Usual care (boceprevir-ribavirin-pegylated interferon [PEG]) was compared with sofosbuvir-ribavirin-PEG and 3 PEG-free regimens: sofosbuvir-simeprevir, sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir. For genotypes 2 and 3, usual care (ribavirin-PEG) was compared with sofosbuvir-ribavirin, sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir-ribavirin (genotype 3 only). OUTCOME MEASURES: Discounted costs (in 2014 U.S. dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Assuming sofosbuvir, simeprevir, daclatasvir, and ledipasvir cost $7000, $5500, $5500, and $875 per week, respectively, sofosbuvir-ledipasvir was cost-effective for genotype 1 and cost $12 825 more per QALY than usual care. For genotype 2, sofosbuvir-ribavirin and sofosbuvir-daclatasvir cost $110 000 and $691 000 per QALY, respectively. For genotype 3, sofosbuvir-ledipasvir-ribavirin cost $73 000 per QALY, sofosbuvir-ribavirin was more costly and less effective than usual care, and sofosbuvir-daclatasvir cost more than $396 000 per QALY at assumed prices. RESULTS OF SENSITIVITY ANALYSIS: Sofosbuvir-ledipasvir was the optimal strategy in most simulations for genotype 1 and would be cost-saving if sofosbuvir cost less than $5500. For genotype 2, sofosbuvir-ribavirin-PEG would be cost-saving if sofosbuvir cost less than $2250 per week. For genotype 3, sofosbuvir-ledipasvir-ribavirin would be cost-saving if sofosbuvir cost less than $1500 per week. LIMITATION: Data are lacking on real-world effectiveness of new treatments and some prices. CONCLUSION: From a societal perspective, novel treatments for HCV are cost-effective compared with usual care for genotype 1 and probably genotype 3 but not for genotype 2. PRIMARY FUNDING SOURCE: CVS Health.

Cost-effective choices of marine fuels in a carbon-constrained world: results from a global energy model.

The regionalized Global Energy Transition model has been modified to include a more detailed shipping sector in order to assess what marine fuels and propulsion technologies might be cost-effective by 2050 when achieving an atmospheric CO2 concentration of 400 or 500 ppm by the year 2100. The robustness of the results was examined in a Monte Carlo analysis, varying uncertain parameters and technology options, including the amount of primary energy resources, the availability of carbon capture and storage (CCS) technologies, and costs of different technologies and fuels. The four main findings are (i) it is cost-effective to start the phase out of fuel oil from the shipping sector in the next decade; (ii) natural gas-based fuels (liquefied natural gas and methanol) are the most probable substitutes during the study period; (iii) availability of CCS, the CO2 target, the liquefied natural gas tank cost and potential oil resources affect marine fuel choices significantly; and (iv) biofuels rarely play a major role in the shipping sector, due to limited supply and competition for bioenergy from other energy sectors.

Client-centred self-care intervention after stroke: a feasibility study.

BACKGROUND: The aim of the study was to evaluate the effect of client-centred, self-care intervention (CCSCI) on (i) activities of daily living (ADL) and life satisfaction in persons with stroke, (ii) caregiver burden, use of informal care and home-help services, and (iii) the feasibility of the study design. DESIGN: Randomized controlled trial, a pilot study of an intervention group (IG) receiving CCSCI or a control group (CG) receiving ordinary training. SUBJECTS: Forty persons with stroke (IG n = 19, CG n = 21) were included: non-demented, able to follow instructions, dependent regarding self-care and referred for rehabilitation, and their significant others (IG n = 8, CG n = 8). METHOD: Data were collected at baseline and three months later using established instruments regarding ADL, life satisfaction, caregiver burden, and use of health services from medical records, the county register, and by interviews. RESULTS: There were no differences in ADL, life satisfaction, caregiver burden, or use of services at three months. Both groups improved significantly and clinically important improvements were achieved by 86% in IG and 63% in CG. CONCLUSION: The CCSCI appears promising for the recapturing of self-care after stroke and a large randomized controlled trial is warranted, in which the present design and methods with some modification will be feasible.

Cost effectiveness of alternative surveillance strategies for hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND & AIMS: The increasing incidence of hepatocellular carcinoma (HCC) in the United States has significant health and economic consequences. Ultrasound (US) surveillance is recommended for patients with cirrhosis because of their high risk of HCC and improving treatment outcomes for small tumors. We assessed the costs, clinical benefits, and cost effectiveness of US surveillance and alternative strategies for HCC in cirrhosis using a computer-based state transition model with parameters derived from available literature. METHODS: Our model compared a policy of no surveillance with 6 surveillance strategies in cirrhotic patients ages 50 years and older in the United States: (1) annual US, (2) semiannual US, (3) semiannual US with alpha-fetoprotein, (4) annual computed tomography (CT), (5) semiannual CT, and (6) annual magnetic resonance imaging. The number of screening tests needed to detect one small HCC, cost per treated HCC, lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios were calculated. RESULTS: Semiannual US surveillance for HCC in cirrhosis increased quality-adjusted life expectancy by 8.6 months on average, but extended it nearly 3.5 years in patients with small treated tumors. Semiannual US surveillance had an incremental cost-effectiveness ratio of $30,700 per quality-adjusted life year (QALY) gained, and was more cost effective than the alternative surveillance strategies using a threshold of $50,000 per QALY gained. The incremental cost-effectiveness ratios for the combined alpha-fetoprotein/US and annual CT strategies exceeded $50,000/QALY unless the sensitivity and specificity of US decreased to less than 65% and 60%, respectively. CONCLUSIONS: Semiannual US surveillance for HCC in cirrhotic patients improves clinical outcomes at a reasonable cost.

An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles.

To evaluate an atomic force microscopy (AFM) approach for effective density analysis of single spray dried carbohydrate particles in order to investigate the internal structure of the particles. In addition, the AFM method was compared to an established technique, that is gas pycnometry. Resonant frequency AFM analysis was employed for determination of the mass of individual particles of spray-dried lactose, mannitol, and a mixture of sucrose/dextran (4:1). The effective particle density was calculated using the diameter of the spherical particles obtained from light microscopy. The apparent particle density was further analyzed with gas pycnometry. It was observed by microscopy that particles appeared either "solid" or "hollow." A solid appearance applied to an effective particle density close to the true density of the material, whereas a density around 1 g/cm(3) corresponded to a hollow appearance. However, carbohydrates, which crystallized during spray drying, for example, mannitol appeared solid but the average effective particle density was 0.95 g/cm(3), indicating a continuous but porous structure. AFM measurements of effective particle density corroborate the suggestion of differences in particle structure caused by the varying propensity of carbohydrates to crystallize during spray drying, resulting in mainly either amorphous hollow or crystalline porous particles.

[Treatment of venous leg ulcers can be better and cheaper. Annual costs calculation based on an inquiry study]. / Venösa bensår kan behandlas både bättre och billigare. Beräkning av årliga kostnader baserad på en enkätstudie.

Weekly resource use data for local wound treatment was collected from a clinical survey (138 patients). Annual costs were calculated from the weekly resource usage multiplied by unit costs and published epidemiological prevalence data for Sweden. The average weekly cost was 101 euro, though it differed depending by ulcer size. The total direct annual cost of venous leg ulcers in Sweden could be estimated at 73 million euro (2002 prices, 1 euro = SEK 9.16) based on a point prevalence of 0.3 percent and 45 percent venous ulcers. Treatment of leg ulcers seems to have improved compared with previous reports, resulting in slightly decreased costs. Nevertheless, the costs are still substantial and the management of these patients requires large resources. A more structured management, more careful selection of dressing products and decreased frequency of dressing changes imply further improvements in wound healing and quality of life for patients and decreased costs for the health care system and for society.