Relationship of faecal calprotectin and long-term outcomes in Finnish patients with Crohn's disease: retrospective multi-centre chart review study.

Background and Aims: A retrospective non-interventional, multi-centre patient chart review study was conducted to investigate the association of faecal calprotectin (FC) 1 year (±2 months) after biological therapy initiation with composite event-free survival (CEFS) consisting of surgical procedures, corticosteroid initiation, treatment failure or dose increase in patients with Crohn's disease (CD). In addition, the correlations of FC and other tests of disease activity were assessed.Materials and methods: Data on Finnish CD patients initiating a biological therapy between 2010 and 2016, were collected. The association of FC and CEFS was analysed with Kaplan-Meier and Cox proportional hazard modelling. The correlations were tested with Pearson's test.Results: Biological therapy was initiated in 186 patients, of which 87 (46.8%) had FC results available at 1 year and 80 had follow-up exceeding 14 months. The characteristics of patients with and without FC results were similar. Patients with elevated FC (>250 µg/g) had a significantly increased risk of experiencing composite event (HR 3.4, 95% CI: 1.3-8.9; p = .013) when compared to patients with normal FC (FC ≤ 100). No such risk was observed in patients with intermediately increased FC level (100 µg/g < FC ≤ 250 µg/g) (HR 2.2 (95% CI: 0.8-6.2; p = .120). FC value had significant positive correlation with CRP, HBI and leukocyte values when measured at similar timepoints.Conclusions: Elevated level of FC approximately 1 year after the initiation of biological therapy was associated with an increased risk of either surgical procedures, corticosteroid initiation, treatment failure or dose increase (i.e. composite outcome) in patients with CD.

Spinach consumption ameliorates the gut microbiota and dislipaemia in rats with diet-induced non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of fat in liver cells, which causes serious health consequences. Animal and human studies suggest that the gut microbiota plays a role in the pathogenesis of NAFLD. Here, we investigated whether spinach consumption could ameliorate high-fat-diet-induced disturbances in certain intestinal bacterial groups and products derived from their metabolism, such as short-chain fatty acids (SCFAs) and microbial phenolic catabolites. Attention is also paid to blood lipids and glucose. In the study, a rat model of high-fat-diet-induced NAFLD was used. There were six experimental groups: NC (normal diet), NB (normal diet + 2.5% spinach), NA (normal diet + 5% spinach), HC (high-fat diet), HB (high-fat diet + 2.5% spinach) and HA (high-fat diet + 5% spinach). The rats consumed these diets for five weeks, and after that, they were sacrificed and plasma, urine, intestinal content, faeces and liver samples were taken. Biochemical parameters were analyzed in plasma, phenolic catabolites were quantified in the faeces, urine, plasma and liver by UPLC-ESI-MS/MS, and the analysis of the microbiota and SCFAs in the intestinal content was performed by qPCR and GLC. Consumption of a high-fat diet caused NAFLD and dislipaemia and altered the gut microbiota and the pattern of SCFAs and phenolic gut microbial catabolites. Supplementation with spinach partially ameliorated some alterations induced by the high-fat diet, in particular by increasing the Lactobacillus counts, reducing the fasting glucose and total and LDL-cholesterol and preventing excess liver cholesterol accumulation, thereby improving the values of the steatosis biomarkers.

A study of the prebiotic-like effects of tomato juice consumption in rats with diet-induced non-alcoholic fatty liver disease (NAFLD).

Gut microbiota may play a role in the pathogenesis of NAFLD. We investigated whether tomato juice consumption for 5 weeks could ameliorate high-fat diet-induced alterations in certain intestinal bacterial groups and products arising from their metabolism (short-chain fatty acids and microbial phenolic catabolites). For this, we used a rat model with NAFLD induced by a high-fat diet, involving four experimental groups: NA (standard diet and water), NL (standard diet and tomato juice), HA (high-fat diet and water) and HL (high-fat diet and tomato juice). The onset of NAFLD impacted the gut microbiota profile, reducing the abundance of Bifidobacterium and Lactobacillus and increasing that of Enterobacteriaceae. Also, reduced concentrations of propionate, butyrate and phenolic catabolites and an increased acetate to propionate (Ac : Pr) ratio were observed. Tomato juice intake partially ameliorated high-fat diet-induced disturbances, particularly by increasing Lactobacillus abundance and diminishing the Ac : Pr ratio, suggesting a potential improvement of the metabolic pattern of NAFLD.

Primary-care-based episodes of care and their costs in a three-month follow-up in Finland.

OBJECTIVE: To explore patient characteristics, resource use, and costs related to different episodes of care (EOC) in Finnish health care. DESIGN: Data were collected during a three-month prospective, non-randomized follow-up study (Effective Health Centre) using questionnaires and an electronic health record. SETTING: Three primary health care practices in Pirkanmaa, Finland. SUBJECTS: Altogether 622 patients were recruited during a one-week period. Inclusion criteria: the patient had a doctor's or nurse's appointment on the recruiting day and agreed to participate. Exclusion criteria: patients visiting a specialized health guidance clinic for pregnant women, children, and mothers. MAIN OUTCOME MEASURES: Patient characteristics, resource use, and costs based on the ICPC-2 EOC classification. RESULTS: On average, the patients had 1.22 EOCs during the three months. Patient characteristics and resource use differed between the EOC chapters. Chapter L, "Musculoskeletal", had the most episodes (17%). The most common (8%) single EOC was "upper respiratory infection". The mean cost of an episode (COE) was €389.56 (standard error 61.11) and the median COE was €165.00 (interquartile range €118.46-288.56) during the three-month follow-up. The most expensive chapter was K, "Circulatory", with a mean COE of €909.85. The most expensive single COE was in chapter K, €32 545.56. The most expensive 1% of the COEs summed up covered 36% of the total COEs. CONCLUSION: Patient characteristics, resource use, and costs differed between the ICPC-2 chapters, which could be taken into account in service planning and pricing. Future studies should incorporate more specific diagnoses, larger data sets, and longer follow-up times. Key points The most common episodes were under the ICPC-2 "Musculoskeletal" chapter, but the highest mean and single-episode costs were related to the "Circulatory" chapter. The mean (median) cost of episodes that started in primary care was €390 (€165) during the three-month follow-up. Patient characteristics, resource use, and costs differed significantly between the ICPC-2 chapters. The most expensive 1% of the episodes covered 36% of the total costs of all the episodes.

Efficacy of a multicomponent support programme for the caregivers of disabled persons: a randomised controlled study.

AIM: The goal of the present work was to measure the efficacy of a multicomponent programme designed to provide tailored support for the caregivers of disabled persons. SUBJECTS: A total of 135 caregivers-care receiver dyads were randomly divided into an intervention group (n = 66) and a control group (n = 69). One-third of the care receivers were demented, and two-thirds had other diseases. SETTING: Health centres (publicly funded primary health care systems) in 8 rural and urban communities in southeast Finland. INTERVENTION: The multicomponent support programme for the caregivers consisted of a 2-week rehabilitation period. The control group received standard care. OUTCOME MEASUREMENTS: Continuation of the caregiver and care receiver relationship, care receiver mortality at the 2-year follow-up as well as the health-related quality of life (15D scale) and Zung's depression scale of the caregiver at the 1-year follow-up were evaluated. RESULTS: At the 2-year follow-up, the caregiver-care receiver relationship was terminated for any reason in 11 cases (17%) in the intervention group, and in 25 cases (36%) in the control group. After adjusting, the primary outcome (i.e., termination of care giving for any reason) indicated statistical significance (p = 0.04) with a hazard rate of 1.83 (95% confidence interval 1.03-3.29). With a similar adjustment, the difference in mortality and placement to institutional care between the two groups demonstrated a trend towards statistical significance. The caregivers' health, as related to quality of life and depressive symptoms, remained unchanged in both groups at the 1-year follow-up. CONCLUSION: These results indicate that a tailored support programme for caregivers may help the caregiver to continue the caregiver-care receiver relationship and delay institutionalization.

Cost-effectiveness of adalimumab, etanercept, and tocilizumab as first-line treatments for moderate-to-severe rheumatoid arthritis.

OBJECTIVE: The aim of this study was to assess the cost-utility and value of reducing the uncertainty associated with the decision to use first-line biologic treatment (bDMARD) after the failure of one or more traditional drugs (tDMARD) in moderate-to-severe rheumatoid arthritis (msRA) in Finland. RESEARCH DESIGN AND METHODS: The treatment sequences were compared among 3000 hypothetical Finnish msRA patients using a probabilistic microsimulation model in a lifetime scenario. Adalimumab + methotrexate, etanercept + methotrexate, or tocilizumab + methotrexate were used as first biologics followed by rituximab + methotrexate and infliximab + methotrexate. Best supportive care (BSC), including tDMARDs, was assumed to be used after the exhaustion of the biologics. Methotrexate alone was added as a further comparator. Efficacy was based on ACR responses that were obtained from a mixed treatment comparison. The resources were valued with Finnish unit costs (year 2010) from the healthcare payer perspective. Additional analyses were carried out, including productivity losses. The Health Assessment Questionnaire (HAQ) values were mapped to the EQ-5D values using the tocilizumab trials; 3% annual discounting for costs and quality-adjusted life years (QALY) and extensive sensitivity analyses were completed. MAIN OUTCOME MEASURES: Incremental cost per QALY gained and multinomial expected value of perfect information (mEVPI). RESULTS: bDMARDs significantly increase the QALYs gained when compared to methotrexate alone. Tocilizumab + methotrexate was more cost-effective than adalimumab + methotrexate or etanercept + methotrexate in comparison with methotrexate alone, and adalimumab + methotrexate was dominated by etanercept + methotraxate. A QALY gained with retail-priced (wholesale-priced) tocilizumab + methotrexate costs €18,957 (€17,057) compared to methotrexate alone. According to the cost-effectiveness efficiency frontier and cost-effectiveness acceptability frontier (CEAF), tocilizumab + methotrexate should be considered before rituximab + methotrexate, infliximab + methotrexate, and BSC. Based on the CEAF, tocilizumab + methotrexate had a 60-93% probability of being cost-effective with €20,000 per QALY gained (mEVPI €230-2182). CONCLUSIONS: Tocilizumab + methotrexate is a potentially cost-effective bDMARD treatment for msRA, indicating a low value of additional research information with the international threshold values. LIMITATIONS: Efficacy based on an indirect comparison (certolizumab pegol, golimumab excluded), fixed treatment sequence after the exhaustion of first bDMARD, Swedish resource use data according to HAQ scores, and inpatient costs assumed to include surgery.

Health economic consequences of reducing salt intake and replacing saturated fat with polyunsaturated fat in the adult Finnish population: estimates based on the FINRISK and FINDIET studies.

BACKGROUND/OBJECTIVES: To predict the health economic consequences of modest reductions in the daily intake of salt (-1.0 g per day) and replacement of saturated fat (SFA, -1.0 energy percent (E%)) with polyunsaturated fat (PUFA, +1.0 E%) in the Finnish population aged 30-74 years. SUBJECTS/METHODS: A Markov model with dynamic population structure was constructed to present the natural history of cardiovascular diseases (CVDs) based on the most current information about the age- and sex-specific cardiovascular risk factors, dietary habits and nutrient intake. To predict the undiscounted future health economic consequences of the reduction of dietary salt and SFA, the model results were extrapolated for the years 2010-2030 by replacing the baseline population in the year 2007 with the extrapolated populations from the official Finnish statistics. Finnish costs (€2009, societal perspective) and EQ-5D utilities were obtained from published references. RESULTS: During the next 20 years, a population-wide intervention directed at salt intake and dietary fat quality could potentially lead to 8000-13,000 prevented CVD cases among the Finnish adults compared the situation in year 2007. In addition, the reduced incidence of CVDs could gain 26,000-45,000 quality-adjusted life years and save €150-225 million over the same time period. CONCLUSION: A modest reduction of salt and replacement of SFA with PUFA in food products can significantly reduce the burden of CVD in the adult Finnish population. This impact may be even larger in the near future due to the ageing of Finnish population.

Treatment of follicular non-Hodgkin's lymphoma with or without rituximab: cost-effectiveness and value of information based on a 5-year follow-up.

BACKGROUND: Rituximab induction together with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab maintenance (RCHOP-R) resulted to significant progression-free survival (PFS) benefit in comparison to RCHOP in the EORTC20981 trial of relapsed/refractory follicular non-Hodgkin's lymphoma (FL). However, the overall survival (OS) difference between RCHOP-R and RCHOP was insignificant. This study evaluated the cost-effectiveness of RCHOP, RCHOP-R, and CHOP in the treatment of relapsed/refractory FL. DESIGN: A lifetime Markov modeling based on the 5-year EORTC20981 survivals (Weibull regressions) was carried out from the public health care payer perspective. Finnish costs (drug, routine, adverse event, and relapse management) were employed. The main outcomes were incremental cost (€2008) per quality-adjusted life-year (QALY), progression-free year (PFY), and life-years gained (LYG). Analyses included cost-effectiveness acceptability frontier and multinomial expected value of perfect information (mEVPI). RESULTS: RCHOP-R resulted to OS (PFS) benefit compared with RCHOP and CHOP: 6 (10) and 17 (25) months, respectively. The incremental costs per QALY gained/LYG/PFY gained were €18 147/€16 380/€10 416 for RCHOP-R versus RCHOP (mEVPI €5196); €14 360/€13 041/€8976 for RCHOP-R versus CHOP (mEVPI €1986); and €12 123/€11 049/€8004 for RCHOP versus CHOP (mEVPI €1,240). RCHOP-R was the optimal option when the willingness to pay per QALY gained exceeded €18 399. CONCLUSION: RCHOP-R is a potentially cost-effective treatment option for the FL.

Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.

BACKGROUND: to assess the cost-effectiveness of trabectedin compared with end-stage treatment (EST) after failure with anthracycline and/or ifosfamide in metastatic soft tissue sarcoma (mSTS). DESIGN: analysis was carried out using a probabilistic Markov model with trabectedin → EST and EST arms, three health states (stable disease, progressive disease and death) and a lifetime perspective (3% annual discount rate). Finnish resources (drugs, mSTS, adverse events and travelling) and costs (year 2008) were used. Efficacy was based on an indirect comparison of the STS-201 and European Organisation for Research and Treatment of Cancer trials. QLQ-C30 scale scores were mapped to 15D, Short Form 6D and EuroQol 5D utilities. The outcome measures were the cost-effectiveness acceptability frontier, incremental cost per life year gained (LYG) and quality-adjusted life year (QALY) gained and the expected value of perfect information (EVPI). RESULTS: trabectedin → EST was associated with 14.0 (95% confidence interval 9.1-19.2) months longer survival, €36 778 higher costs (€32 816 using hospital price for trabectedin) and €31 590 (€28 192) incremental cost per LYG with an EVPI of €3008 (€3188) compared with EST. With a threshold of €50 000 per LYG, trabectedin → EST had 98.5% (98.2%) probability of being cost-effective. The incremental cost per QALY gained with trabectedin → EST was €42 633-47 735 (€37 992-42 819) compared with EST. The results were relatively insensitive to changes. CONCLUSION: trabectedin is a potentially cost-effective treatment of mSTS patients.

Economic evaluation comparing From Home To Operation same day admission and preoperative admission one day prior to the surgery process: a randomized, controlled trial of laparoscopic cholecystectomy.

OBJECTIVE: A novel preoperative procedure From Home To Operation (FHTO) seeks to combat increasing operation and infection rates. This is the first prospective randomized controlled trial (RCT) comparing the cost-effectiveness and cost-utility of FHTO and conventional ward procedures for standardized Laparoscopic Cholecystectomy (LC). RESEARCH DESIGN AND METHODS: During 12/2004-7/2005, 47 patients with symptomatic gallstones were randomized to receive LC in the FHTO (28 patients) or in a conventional manner (19 patients) in a Finnish hospital setting. The 15D quality of life tool was administered at the baseline and 1 month after. MAIN OUTCOME MEASURES: A stochastic approach over a month interval for hospital costs, length of postoperative stay, infection rate and Quality-Adjusted Life Years (QALY) was employed. RESULTS: Baseline group characteristics were similar. The mean health care costs with FHTO (1695 EUR) were significantly lower (p < 0.001) than in the conventional arm (2234 EUR). The number of patients discharged on the first postoperative day was 27 (96.4%) and 15 (78.9%) with two (7.1%) infections in the FHTO and four (21.1%) in the conventional arm. A difference in QALYs gained (0.0174; p = 0.030) favouring FHTO was observed. According to a cost-effectiveness acceptability curve, the probability of FHTO being cost-effective was 99%. The results were robust to probabilistic sensitivity analyses. CONCLUSIONS: FHTO can introduce substantial cost savings and have a positive impact on both clinical measures and quality of life. Studies with larger numbers of patients are needed to assess whether conventional ward procedure can be a source of infections, which can be avoided with FHTO. CLINICAL TRIAL REGISTRY: ICJME-qualified registry of the Hospital District of Helsinki and Uusimaa (number 217849).

Direct costs of warfarin treatment among patients with atrial fibrillation in a Finnish health care setting.

OBJECTIVE: The main objective was to estimate the mean direct costs of warfarin treatment for atrial fibrillation (AF) patients. Secondly, the costs of initiating warfarin treatment during a 60-day period and the impact of International Normalized Ratio (INR) and co-morbidities on costs were estimated. DESIGN AND DATA: The study was performed as a retrospective cohort study over a 12-month period in a Finnish communal health care setting. All AF patients aged 65 years or older (n = 250) with warfarin treatment were identified from the database of the health service district of an urban area. Patient specific information related to comorbidities, INR-control, complications and health care resource use were collected. Cost information was obtained from the Finnish national health care unit cost list. METHODS: The effect of treatment balance and other background variables on treatment costs were evaluated using ordinary least squares regression (OLS), log-transformed OLS and generalized linear model (GLM). The mean costs were calculated on the basis of the different models and bias corrected and accelerated (BCa) bootstrap confidence intervals (CIs) were calculated for the mean costs. RESULTS: The best fitting cost model was log-transformed OLS. The costs of warfarin treatment on the basis of the log-transformed model were 589.82 Euros (BCa 95% CI: 586.68-591.99) per patient compared to 616.00 Euros (BCa 95% CI: 579.98-652.96) obtained with the OLS-model. For the treatment initiation period, the mean costs were 263 Euros (BCa 95% CI: 218.90-314.71). Depending on the way that INR-control was defined, the mean costs were 95.27 Euros or 166.92 Euros higher for patients who were not in the defined INR-balance. CONCLUSIONS: The INR-control has a significant impact on the warfarin treatment costs. The choice of model influences the estimated mean costs. In addition, different models identify statistically significant effects between different background variables and costs.

Perceived role of fibre in a healthy diet among Finnish consumers.

OBJECTIVE: The aim was to study how Finnish consumers perceive the role of fibre in the diet, which foods are regarded as good sources of fibre and the relationship between the respondents' self-estimated fibre intake and their measured intake. METHODS: A semistructured interview was conducted with 125 volunteers, including a background information questionnaire and an easy-to-use self-administered paper-and-pencil form estimating fibre intake. RESULTS: According to the self-administered form about half of the respondents had adequate fibre intake. Among those who estimated their fibre intake as adequate/maybe adequate, only 61% belonged to the highest fibre intake group. Most of the respondents defined their diet as being healthy. The key elements for a healthy diet were 'vegetables', 'low in fat', 'fruit and berries' and 'variety'. Only 5% of the respondents mentioned fibre spontaneously here. However, fibre was considered important for health because of its effect on bowel function and general well-being. The recommended intake of fibre could not be described in nutritional terms, but respondents could identify relevant sources of fibre in the diet. CONCLUSION: Finnish consumers considered fibre important for health and could recognize the sources of fibre correctly although they did not mention it spontaneously as a part of a healthy diet.

Two-photon fluorescence excitation in detection of biomolecules.

Two-photon fluorescence excitation has been found to be a very powerful method for enhancing the sensitivity and resolution in far-field light microscopy. Two-photon fluorescence excitation also provides a substantially background-free detection on the single-molecule level. It allows direct monitoring of formation of labelled biomolecule complexes in solution. Two-photon excitation is created when, by focusing an intensive light source, the density of photons per unit volume and per unit time becomes high enough for two photons to be absorbed into the same chromophore. In this case, the absorbed energy is the sum of the energies of the two photons. In two-photon excitation, dye molecules are excited only when both photons are absorbed simultaneously. The probability of absorption of two photons is equal to the product of probability distributions of absorption of the single photons. The emission of two photons is thus a quadratic process with respect to illumination intensity. Thus in two-photon excitation, only the fluorescence that is formed in the clearly restricted three-dimensional vicinity of the focal point is excited. We have developed an assay concept that is able to distinguish optically between the signal emitted from a microparticle in the focal point of the laser beam, and the signal emitted from the surrounding free labelled reagent. Moreover, the free labels outside the focal volume do not contribute any significant signal. This means that the assay is separation-free. The method based on two-photon fluorescence excitation makes possible fast single-step and separation-free immunoassays, for example, for whole blood samples. Since the method allows a separation-free assay in very small volumes, the method is very useful for high-throughput screening assays. Consequently we believe that two-photon fluorescence excitation will make a remarkable impact as a research tool and a routine method in many fields of analysis.

A new microvolume technique for bioaffinity assays using two-photon excitation.

Bioaffinity binding assays such as the immunoassay are widely used in life science research. In an immunoassay, specific antibodies are used to bind target molecules in the sample, and quantification of the binding reaction reveals the amount of the target molecules. Here we present a method to measure bioaffinity assays using the two-photon excitation of fluorescence. In this method, microparticles are used as solid phase in binding the target molecules. The degree of binding is then quantified from individual microparticles by use of two photon excitation of fluorescence. We demonstrated the effectiveness of the method using the human alpha-fetoprotein (AFP) immunoassay, which is used to detect fetal disorders. The sensitivity and dynamic range we obtained with this assay indicate that this method can provide a cost-effective and simple way to measure various biomolecules in solution for research and clinical applications.