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Background: Branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) presents a clinical conundrum. Rigorous long-term surveillance or surgical resection is recommended. The economic consequences of the management have not been fully investigated., Methods: A Markov decision model compared 4 strategies for low-risk BD-IPMN: I = upfront total pancreatectomy, II = upfront partial pancreatectomy, III = initial surveillance, IV = watchful waiting. Surveillance was based on the Swedish Guidelines for Pancreatic Cancer. Probabilities and costs were obtained from the participating unit and from the scientific literature. The incremental cost-effectiveness ratios (ICERs) were calculated and sensitivity analyses were performed by varying relevant parameters. Survival was reported in quality-adjusted life-years (QALYs)., Results: Strategy III was the most cost-effective strategy with an ICER of €31 682 compared to strategy IV. Strategy I was the most expensive but yielded the best QALY (9.32). Total number of years, annual risk of pancreatic cancer and annual risk of a low-risk BD-IPMN turning into a high-risk lesion had the greatest impact in the model., Conclusions: Initial surveillance seems to be the most cost-effective strategy in the management of low-risk asymptomatic BD-IPMN. However, the possibility of personalized approaches remains to be investigated., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: A review of existing economic models in major depressive disorder (MDD) highlighted the need for models with longer time horizons that also account for heterogeneity in treatment pathways between patients. A core discrete event simulation model was developed to estimate health and cost outcomes associated with alternative treatment strategies., Methods: This model simulated short- and long-term clinical events (partial response, remission, relapse, recovery, and recurrence), adverse events, and treatment changes (titration, switch, addition, and discontinuation) over up to 5 years. Several treatment pathways were defined on the basis of fictitious antidepressants with three levels of efficacy, tolerability, and price (low, medium, and high) from first line to third line. The model was populated with input data from the literature for the UK setting. Model outputs include time in different health states, quality-adjusted life-years (QALYs), and costs from National Health Service and societal perspectives. The codes are open source., Results: Predicted costs and QALYs from this model are within the range of results from previous economic evaluations. The largest cost components from the payer perspective were physician visits and hospitalizations. Key parameters driving the predicted costs and QALYs were utility values, effectiveness, and frequency of physician visits. Differences in QALYs and costs between two strategies with different effectiveness increased approximately twofold when the time horizon increased from 1 to 5 years., Conclusion: The discrete event simulation model can provide a more comprehensive evaluation of different therapeutic options in MDD, compared with existing Markov models, and can be used to compare a wide range of health care technologies in various groups of patients with MDD., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Introduction: The utility of rehabilitative ultrasound imaging (RUSI) for assessing trapezius muscle contractile characteristics was investigated by examining whether muscle thickness changes during contraction (CT) differed between people with and without mild shoulder pain., Methods: In 18 subjects with mild shoulder pain (aged 28±8 years) and 18 matched controls, trapezius muscle thickness change was measured in prone at rest at 0° and during isometric CTs at 90° and 120° of shoulder abduction. Images were taken at four sites using a real-time ultrasound scanner (7-MHz linear transducer, 40 mm footprint). Percentage change in muscle thickness from rest was calculated. Differences between painful and non-painful shoulders and participant groups were examined by analysis of variance (ANOVA) and t-tests., Results: There were no significant differences between groups or sides in trapezius muscle thickness change during CT. There was no significant difference in trapezius muscle resting thickness (RT) between painful and non-painful shoulders in the same subjects., Conclusion: Contractile ability of the trapezius muscle, assessed using RUSI was not impaired in subjects with mild shoulder pain during the test manoeuvres used. Further research is warranted involving patients with different severity of symptoms, using other test manoeuvres before RUSI can be advocated for assessing scapular muscle dysfunction., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Work related thumb pain (WRTP) is a major problem among manipulative physiotherapists. Therapists who maintain the thumb joints in an extended alignment during PA mobilisation experience less WRTP. The purposes of this study were to investigate what effect taping of the thumbs has on thumb alignment during mobilisation and to gain normative data on the mobilisation forces applied by student physiotherapists. Forty final year student physiotherapists participated and were asked to apply a grade III PA mobilisation onto the C7 vertebra of one of 32 asymptomatic models. Participants were then instructed to apply the same mobilisation onto a force measurement instrument, in both the tape and no tape conditions, while the alignment of their metacarpophalangeal (MCP) and interphalangeal (IP) joints was noted via video recorder. Thumb alignment improved in 72.5% of participants post taping, with significant increases in the number of MCP joints maintained in a neutral alignment (p < 0.05). The mean peak mobilisation force applied by the students was 70.9 N. Taping of the thumbs prior to PA mobilisation improved thumb alignment during mobilisation in this cohort of undergraduate students, thus potentially influencing one of the contributory factors to WRTP., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Recently taping techniques with the primary purpose of altering muscle activity have become a part of clinical physiotherapy practice. A firmly applied tape across the fibres of the vastus lateralis (VL) muscle has been proposed to decrease the VL muscle activity. The primary aim of this study was to assess the effects of an inhibitory muscle tape applied over the vastus lateralis (VL) muscle during stair climbing. Twenty five subjects without lower limb pathology were recruited. Normalised integrated EMG (IEMG) was analysed from VL, vastus medialis obliquus (VMO), biceps femoris (BF) and soleus muscles during stair climbing. The subjects were assessed during three conditions: no tape (untaped), (no tension) control tape and (tensioned tape) VL inhibitory taping application. There was a significant decrease (p<0.05) in the VL IEMG during the initial stance phase during both stair ascent and descent. The inhibition if the VL muscle occurred with both control and VL inhibitory tape applied. No significant differences (p>0.05) were noted in any of the other muscles assessed. The results demonstrated that there was a significant decrease in the IEMG of the VL both during stair ascent and descent with VL inhibitory tape and control tape applied in normal subjects.

Objective: Our aims were to estimate 1) the costs of hospital treatment and 2) the value of lost production due to early death associated with overweight and obese patients, and then to extrapolate the findings to national costs., Methods: We use regression models to analyze survival, expected number of days in hospital treatment for patients with different body mass index (BMI), and costs with data obtained from screening of 33,196 middle-aged subjects living in Malmö, Sweden, and collected during a 15-year follow-up period. We subsequently scale up costs to national aggregate level using the BMI prevalence data from the screening project to the national population., Results: The total excess hospital (somatic, psychiatric) care cost (Swedish krona or SEK) for the national health-care budget, excess as compared to normal weight patients for obese (BMI > 30) and overweight (25 < or = BMI < 30) was estimated to SEK2155 million per annum (269 million dollars, assuming 1 dollar = SEK8), or about 2.3% of total hospital care costs in Sweden. The corresponding indirect costs due to early death were estimated to SEK2935 million (367 million dollars). For males at age 55, the potential hospital costs saving, excluding costs of the intervention that could be gained by an intervention that successfully and safely could alter the weight of an obese individual to become normal weight, was estimated on average to SEK4434 (554 dollars) per annum., Conclusion: Hospital treatment costs are found to be higher for obese and overweight patients than for normal weight patients indicating potential cost savings especially on indirect costs by effective, safe and low cost weight-loss intervention.

Purpose: To determine whether published cost-effectiveness studies on inhaled corticosteroids (ICS) in asthma adhered to basic analytical standards as defined in health economic textbooks and in guidelines assessing and comparing efficacy and safety., Methods: Original cost-effectiveness studies published between 1990 and 2000 in general medical or economic journals were reviewed to assess the adherence to five fundamental methodological principles: (1) design of the study, (2) choice of perspective and corresponding costs, (3) choice of outcome measure, (4) marginal cost analysis, and (5) sensitivity analysis and discussion about external validity. For each principle, the studies were ranked as high, medium or low quality., Results: Most of the 18 studies included were ranked medium on the first two principles. The studies adhered to a higher degree to the remaining three principles. Only three studies were high ranked in all five principles. The number of principles fulfilled increased over time. Studies comparing pharmaceutical products from competing companies were typically short-term studies, designed for other purposes than health economic analyses, and, in general, did not use therapeutically equivalent dosing., Conclusions: Attention should be drawn to the study design, the weak correspondence between perspective and costs, and especially to the impact of bias in health economic results when comparing different doses of ICSs.

Objectives: The objective of this study was to develop a model capable of assessing the cost-effectiveness in Sweden of treating diabetic neuropathic lower extremity ulcers with becaplermin gel (Regranex) plus good wound care (GWC) relative to treating them with GWC alone., Methods: A Markov simulation model was developed that includes six health states: Uninfected Ulcer, Infected Ulcer, Gangrene, Healed Ulcer, Healed Ulcer-History of Amputation, and Deceased. To predict clinical outcomes, information was taken from a specially designed prospective 9-month follow-up study of 183 neuropathic patients in the US treated with GWC. Cost of treatment data were taken primarily from a study of a cohort of 314 patients in Sweden. The efficacy of becaplermin was assumed equal to that achieved in a pooled analysis of four randomized clinical trials. A model application provides expected clinical outcomes for a cohort of patients. Annual treatment costs per patient were estimated using treatment practice and unit prices from Sweden., Results: Due to a higher rate of healing and a shorter average healing time, treatment with becaplermin gel was predicted to increase the average number of months spent in the healed state over the first year following development of an ulcer by 24% relative to GWC alone. In addition, the corresponding number of amputations was 9% lower for the becaplermin-treated cohort. The average expected cost of $12,078 US for an individual treated with GWC alone declines to $11,708 US for one treated with becaplermin, in spite of $1262 becaplermin costs. Expenses related to topical treatment and inpatient care account for 83% of the resources conserved., Conclusions: Our results suggest that in Sweden treatment with becaplermin in conjunction with GWC consumes fewer resources and generates better outcomes than treatment with GWC alone for diabetic neuropathic ulcers. In light of the high and increasing incidence of such ulcers, the potential savings in costs and suffering may be important. Results are difficult to extrapolate internationally because they are strongly related to country-specific treatment practices and price levels.

Objective: A 1-year semi-Markov model was constructed to simulate the cost-effectiveness of atypical and typical antipsychotic treatments for schizophrenia., Methods: The core model comprised nine 6-week cycles and includes events such as survival, response, adverse events, and compliance. The nature, duration, intensity, and timing of adverse events were incorporated. Compliance was modeled as a function of health state, time, and adverse events. Three first-line treatments were considered (risperidone, olanzapine, and haloperidol oral) and the transition probabilities of switching between five different therapies (haloperidol oral, haloperidol depot, risperidone, olanzapine and clozapine) were included. Effectiveness was modeled based on a modified method of TWiST (time without symptoms and toxicity). The direct costs of utilization of medical resources are taken into account, including five different patient care settings, consultations, neuroleptic medication, laboratory tests, and treatment of side-effects., Results: This paper reports the methodology used to construct the model and the results obtained when it was applied to the treatment of patients with schizophrenia in the Belgian health care system., Conclusions: Over the study period, risperidone and olanzapine were more cost-effective than haloperidol and of the two major atypical drugs, risperidone was the more cost-effective.

It has been reported that the assembly of MHC class I molecules in mutagenized cell lines could be induced by specific binding peptides. We have now demonstrated that the defect in assembly between heavy and light chains of class I molecules naturally occurred in tumor cells of one spontaneous ovarian carcinoma detected by one-dimensional isoelectric focusing of immunoprecipitates with anti-monomorphic class I MAb (W6/32) and by immunostaining with free heavy chain and beta 2m-specific MAbs. In vitro treatment of the tumor cells with IFN-gamma induced the assembly and surface expression of majority class I molecules (A2.1, B7, B15, Cw6, Cw7 out of A2.1, A2*, B7, B15, Cw6, Cw7). Moreover, assembly of A2 and Cw6 was induced by exposure of the tumor cells to a HLA A2-binding peptide K62 derived from influenza A matrix protein. Autologous blood T lymphocytes were activated in mixed lymphocyte-tumor cell culture (MLTC) by the IFN-gamma-treated but not by the unmanipulated tumor cells. Although activated lymphocytes damaged both IFN-gamma-treated and untreated tumor cells, the alpha class I MAb (W6/32) efficiently inhibited the lysis of IFN-gamma-treated targets, but not the untreated targets. These results indicate that the defect of MHC class I assembly may result in the escape of tumor cells from immune response.

As previously reported in this journal, alveolitis may occur in asymptomatic individuals exposed to antigens known as causative agents in hypersensitivity pneumonitis. We found an alveolitis, probably of sarcoid origin, in an apparently healthy volunteer.

A method has been developed for the rapid isolation of alpha 1-antitrypsin and other thiol proteins from plasma by an automated chromatography system. The thiol-proteins are initially bound to matrix-linked activated thiol-compounds by an SH-SS interchange reaction. The mixed disulphides are then reduced in two steps and subfractionated by passage through Blue-Sepharose and AH-Sepharose columns. The rate of the interchange reactions varies with the microenvironment of the reacting thiols. alpha 1-Antitrypsin is recovered with 95% purity in 60% yield within two days from 1 l of plasma.

Serum IgE levels were studied in 25 bone marrow transplant recipients (in 12 patients twice weekly and in 13 patients, at random). A 2-748-fold increase in serum IgE was recorded in 20 of the 25 patients after transplantation, the highest IgE value observed being 8,000 kU/liter. The IgE elevation appeared concomitantly with acute graft-versus-host disease (GVHD) in 14 patients. Both events occurred on day 24 +/- 2 (mean +/- SE). When the acute GVHD was diagnosed, there was a significant increase in serum IgE as compared to the first posttransplantation value. In one patient in whom GVHD recurred, a second IgE peak was seen, and in another patient with flaring GVHD, IgE levels increased on several occasions. In 6 patients without clinical signs of GVHD, a rise in IgE occurred on day 35 +/- 12. One of these patients was grafted with marrow from her identical twin. The rise in IgE did not correlate with an elevated proportion of eosinophil granulocytes. In the majority of the patients, no correspondent increases in serum IgG, IgA, or IgM were seen during the period with increased IgE after transplantation.

A new intracytoplasmic immunofluorescence staining to detect and quantify human interferon-gamma (IFN-gamma)-producing cells by means of flow cytometry is described. Mononuclear leukocytes, stimulated in vitro to produce IFN-gamma, were fixed and made permeable to antibodies by sequential exposure to paraformaldehyde and the detergent n-octyl-glucoside. Cytoplasmic IFN-gamma was demonstrated by indirect immunofluorescence using IFN-gamma-specific mouse monoclonal antibodies. The staining exhibited a very characteristic morphology and was localized in the Golgi apparatus. An excellent agreement between the enumeration of cytoplasmic IFN-gamma-positive cells by immunofluorescence microscopy and flow cytometry was noted. However, the latter has the advantage of a standardized control, is less labor consuming and is observer independent.

The acute and chronic effects of three types of humic material were studied using Daphnia magna at pH 5, 6, and 7. At neutral pH humic material had no biological effect. At pH 6 and 5 maximum survival and population growth rate occurred at intermediate levels of humus material (10 mg C/L, 300 mg Pt/L). Lowest survival and population growth rate occurred at pH 5 in either the absence of humus material or at concentrations exceeding 10 mg C/L (300 mg Pt/L). A second order polynomial was used to fit the dose response curve at pH 5 for both Aldrich humic acid and a natural bog water. Aldrich had greater biological activity. It is suggested that the biological behavior of aquatic humus conforms to second order rate phenomena controlled by high levels of free metals ions at low humus concentrations and direct toxic action of the dissolved organics at low pH due to increased lipophilicity.

A method for the chemical modification of plastic surfaces permits covalent binding of proteins and we have used this method in the development of an efficient panning technique. Thus, human peripheral T lymphocytes coated with mouse monoclonal antibodies directed against the CD4 marker may be selectively and reproducibly removed from a lymphocyte population by a short incubation in modified plastic dishes coated with rabbit anti-mouse IgG antibody. Due to the higher protein binding capacity of the dishes the use of the IgG fraction of the coating antibody was sufficient for optimal and reproducible results. In contrast, control dishes with passively adsorbed antibody required an affinity-purified fraction and even then were less efficient.