T Macioch

Stellate neurones innervating the rat heart express N, L and P/Q calcium channels

The aim of the study was to investigate the kinetic properties and identify the subtypes of Ca2+ currents in the cardiac postganglionic sympathetic neurones of rats. Neurones were labelled with a fluorescent tracer--Fast-Blue, injected into the pericardial cavity. Voltage-dependent Ca2+ currents were recorded from dispersed stellate ganglion cells that showed Fast Blue labelling. Only high threshold voltage-dependent Ca2+ currents were found in the somata of cardiac sympathetic neurones. Their maximum amplitude, mean cell capacitance and current density were respectively: 0.67 nA, 19.3 pF and 36.4 pA/pF (n = 21). The maximum Ca2+ conductance was 51.3 nS (n = 14). Half activation voltage equalled +11.0 mV and the slope factor for conductance 11.1 (n = 14). As tested with a 10 s pre-pulse, the Ca2+ current began to inactivate at -80 mV. Half inactivation voltage and slope factor for steady-state inactivation were -36.6 mV and 14.1 (n = 9), respectively. Saturating concentration of L channel blocker (nifedipine), N channel blocker (omega-conotoxin-GVIA), P/Q channel blocker (omega-Agatoxin-IVA) and N/P/Q channel blocker (omega-conotoxin-MVIIC) reduced the total Ca2+ current by 26.8% (n = 7), 57.1% (n = 12), 25.9% (n = 6) and 69.4% (n = 6), respectively. These results show that the somata of cardiac postganglionic cardiac sympathetic neurones contain significant populations of N, L and P/Q high threshold Ca2+ channels.

The indirect costs of cancer-related absenteeism in the workplace in Poland.

Objectives: The aim of this study was to evaluate cancer-related absenteeism costs in Poland. Methods: Data on sickness absences and disability were retrieved from the Department of Statistics of the Social Insurance Institution. The cost of lost productivity owing to premature death was estimated from data retrieved from the Polish National Cancer Registry. Absenteeism costs were estimated on the basis of the measure of gross value added per employee. Results: The costs of lost productivity owing to sick leave, disability, and premature death were estimated to be 1.572 billion EUR, 0.504 billion EUR, and 0.535 billion EUR, respectively, in 2009. Conclusions: The indirect costs of lost productivity owing to cancer-related sick leave, disability, and premature death have a substantial effect on the Polish economy. In 2009, they accounted for more than 0.8% of GDP.

Kinetic and pharmacological properties of Ca2+ currents in postganglionic sympathetic neurones projecting to muscular and cutaneous effectors

Voltage-gated Ca(2+) channels are expressed in neurones and greatly influence neuronal activity by activating Ca(2+)-dependent K(+) channels. The whole cell patch-clamp technique was used to compare the kinetic and pharmacological properties of voltage-dependent Ca(2+) currents in two groups of sympathetic neurones identified by the fluorescent tracer Fast Blue: putative muscular sympathetic neurones (MSN) and putative cutaneous sympathetic neurones (CSN). The tracer was injected into the muscular part of the diaphragm (to mark MSN) and into the skin of the ear (to mark CSN). The capacitance of MSN (23.0 pF) was larger than the capacitance of CSN (12.6 pF). The maximum current in MSN (1.3 nA) was also larger than in CSN (0.93 nA). However, the current density was larger in CSN (77. 3 pA/pF) than in MSN (57.7 pA/pF) and the current activation rate was faster in CSN (0.27 nA/ms) than in MSN (0.19 nA/ms). V(1/2) and slope factors of activation and inactivation were not significantly different for MSN and CSN. The majority of Ca(2+) current was available for activation in both categories of neurones at resting membrane potential. Ca(2+) currents in MSN and CSN were blocked by nifedipine (7.0 and 3.6%, respectively), omega-Agatoxin-IVA (23.0 and 25.6%, respectively) and omega-conotoxin-GVIA (67.0 and 65.1%, respectively). We found that CSN are twice as small, have higher Ca(2+) current density and their Ca(2+) activation rate is faster in comparison to MSN. Such properties may lead to faster rise of Ca(2+) concentration in the cytoplasm of the CSN comparing to MSN and more effectively dampen their activity due to more effective activation of Ca(2+)-dependent K(+) current. Both kinds of neurones express high proportion of N and P/Q Ca(2+) current.

Health related quality of life in patients with diabetic foot ulceration — translation and Polish adaptation of Diabetic Foot Ulcer Scale short form

ObjectivesDiabetic foot ulcer (DFU) is a common complication of diabetes and not only an important factor of mortality among patients with diabetes but also decreases the quality of life. The short form of Diabetic Foot Ulcer Scale (DFS-SF) provides comprehensive measurement of the impact of diabetic foot ulcers on patients’ health related quality of life (HRQoL). The purpose of this study was to translate DFS-SF into Polish and evaluate its psychometric performance in patients with diabetic foot ulcers.MethodsThe DFS-SF translation process was performed in line with Principles of Good Practice for the Translation and Cultural Adaptation Process for patient reported outcome measures (PROMs) developed by ISPOR TCA group. Assessment of the reliability and validity of Polish DFS-SF was performed in native Polish patients with current DFU.ResultsThe DFS-SF validation study involved 212 patients diagnosed with DFU, with 4.4 years of DFU duration on average. The average ulcer size was 5.5 sq. cm, and generally only one limb was affected. Men (72%) and type 2 diabetes patients (86%) prevailed, with 17.8 years representing the mean time since diagnosis. The mean population age was 62.5 years. The internal consistency of all scales of the Polish DFS-SF was high (Cronbach’s alpha ranged from 0.82 to 0.93). Item convergent and discriminant validity was satisfactory (median corrected item-scale correlation ranged from 0.61 to 0.81). The Polish DFS-SF demonstrated good construct validity when correlated with the SF-36v2 and showed better psychometric performance than SF-36v2.ConclusionsThe newly translated Polish DFS-SF may be used to assess the impact of DFU on HRQoL in Polish patients.

The Indirect Costs of Diabetic Foot Ulcers in Poland

Aim: The purpose of this study was to estimate the productivity loss and indirect costs associated with foot ulcers in patients with diabetic foot syndrome (DFS). An additional goal was to estimate the productivity loss and indirect costs in the population of informal caregivers of patients with DFS. Methods: Based on a prospective survey the effects of ulcers on patients’ professional activities were measured, and in addition, the disease-associated loss of productivity in the population of professionally active patients and caregivers was examined. Loss of productivity was measured using a modified WPAI questionnaire. The indirect costs of both absenteeism and presenteeism were estimated using the human capital approach. Results: Mean absenteeism was estimated at 32.63% of the nominal working time, whereas presenteeism was estimated at 23.48% of real working time. Among informal caregivers, mean absenteeism was estimated at 13.67% of the nominal working time, and presenteeism was estimated at 27.21% of real working time. Total annual indirect costs associated with productivity loss in the patient population amounted to EUR 170.8 million, including EUR 117.3 million in costs for sickness absences and EUR 53.5 million in presenteeism costs. Total annual indirect costs associated with productivity loss in the population of informal caregivers amounted to EUR 303.3 million, including EUR 80.8 million in costs for sickness absence and EUR 222.6 million in presenteeism costs. Conclusions: The indirect costs associated with foot ulcers in patients with DFS impose a substantial burden on the Polish economy.

PMC24 SELF-ASSESSED HEALTH STATUS IN POLAND: EQ-5D FINDINGS FROM POLISH VALUATION STUDY

PMC22 THE IMPACT OF COMORBIDITY BURDEN ANDAGE ON PREFERENCE-BASED HRQL INTHE UNITED STATES Sullivan PW, Ghushchyan VH University of Colorado Denver, Aurora, CO, USA OBJECTIVES: Gains in life expectancy have lead to aging populations with more chronic comorbidity. This study aims to examine the impact of age and comorbidity on EQ-5D index scores in a nationally representative sample of the U.S. METHODS: The pooled 2001 and 2003 Medical Expenditure Panel Survey (MEPS) was used. MEPS is a nationally representative survey of the U.S. civilian, noninstitutionalized population based on self-report which collects detailed information on sociodemographic characteristics, medical conditions and HRQL. The total number of chronic conditions for each individual was calculated based on ICD-9 codes. Spline regression was used to allow for nonlinear age effects: individuals were separated into 4 quartiles based on age: 18–31; 32–44; 45–58; and >58 years. Censored least absolute deviations (CLAD), Tobit and OLS methods were used to regress EQ-5D index scores on age and chronic comorbidity, controlling for income, gender, race, ethnicity, education, physical activity and smoking status. Interactions between age and chronic conditions were also explored. RESULTS: After controlling for chronic comorbidities and other confounders, age was not statistically significant except for those >58 years and the magnitude of this coefficient was very small (coefficient age >58 years = -0.0006). However, the coefficients for chronic comorbidities were highly statistically significant with large magnitudes for those with 2 chronic conditions (coefficient 2 chronic conditions = -0.16; coefficient 9 chronic conditions = -0.28). Having only one chronic condition was not statistically significant. The interaction between age and chronic comorbidity was significant, but the deleterious impact of their interaction was largely dominated by the existence and number of chronic conditions. CONCLUSIONS: Chronic conditions have a significant deleterious impact on EQ-5D index scores regardless of age. The negative impact of age on EQ-5D index scores may be due to the existence and degree of chronic comorbidity.

Direct healthcare costs and cost-effectiveness of acute coronary syndrome secondary prevention with ticagrelor compared to clopidogrel: economic evaluation from the public payer???s perspective in Poland based on the PLATO trial results

BACKGROUND Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist designed to reduce clinical thrombotic events in patients with acute coronary syndrome (ACS). Compared to clopidogrel, ticagrelor has been proven to significantly reduce the rate of death from vascular causes, myocardial infarction (MI), or stroke without an increase in the rate of overall major bleeding in patients who have an ACS with or without ST-segment elevation (STEMI and NSTEMI) or unstable angina (UA). AIM To evaluate the cost-effectiveness and healthcare costs associated with secondary prevention of ACS using ticagrelor or clopidogrel in patients after STEMI, NSTEMI and UA. METHODS An economic model based on results from the PLATO trial was used to evaluate the cost-effectiveness of one-year therapy with ticagrelor or clopidogrel. The structure of the model consisted of two parts, i.e. the decision tree with one-year PLATO results and the Markov model with lifelong estimations, which exceeded PLATO follow-up data. The model was adjusted to Polish settings with country-specific data on death rates in the general population and direct medical costs calculated from the public payers perspective. Costs were derived from the National Health Fund (NHF) and the Ministry of Health and presented in PLN 2013 values. Annual mean costs of second and subsequent years after stroke or MI were obtained from the literature. Uncertainty of assumed parameters was tested in scenarios and probabilistic sensitivity analyses. The adopted model allowed the estimation of an incremental cost-effectiveness ratio for life years gained (LYG) and an incremental cost-utility ratio for quality adjusted life years (QALY). RESULTS Total direct medical costs to the public payer at a one year horizon were 2,905 PLN higher with ticagrelor than with clopidogrel. However, mean healthcare costs at a one year horizon (excluding drug costs and concomitant drugs) were 690 PLN higher for patients treated with clopidogrel. In a lifetime horizon, results indicated that ticagrelor was the more cost-effective option compared to generic clopidogrel, with an incremental cost per LYG estimated at 21,566 PLN and an incremental costper QALY estimated at 24,965 PLN. CONCLUSIONS In a lifetime horizon, which should be used when comparing technologies with different impacts on mortality, cost-effectiveness evaluation resulted in more favourable economic outcomes for ticagrelor than for generic clopidogrel, with the cost per QALY well below the recommended willingness to pay threshold in Poland (24,965 PLN vs. 111,381 PLN).

PMC6 ASSESSING PRODUCTIVITY AND ACTIVITY IMPAIRMENT DUE TO ILLNESS IN POLAND

lack of an RCT makes formal technology assessment vs. alternative treatment (e.g., best supportive care [BSC]) challenging. In such instances, naïve indirect comparison based on historical controls is typically employed. We present a method for estimating outcomes for untreated patients when appropriate historical controls are not available, by using data from non-responders in an uncontrolled trial. METHODS: Ofatumumab was licensed for fl udarabineand alemtuzumab-refractory chronic lymphocytic leukaemia (FA-Ref CLL) based on results of an uncontrolled trial (Hx-CD20-406). To evaluate the cost-effectiveness of ofatumumab vs. BSC from the UK National Health Service perspective, a partitioned survival analysis model was developed. Progression free survival (PFS) and overall survival (OS) for ofatumumab were estimated by fi tting Weibull survival functions to failure time data for all FA-Ref patients in Hx-CD20-406. Following a literature search, no suitable historical control representing BSC could be identifi ed; therefore hazard ratios for PFS and OS for BSC vs. ofatumumab were estimated by fi tting Cox regression models to data for non-responders vs. all FA-Ref patients. Costs and utilities were taken from both published and unpublished sources. RESULTS: BSC patients (approximated by non-responders) were estimated to achieve 4.7 months PFS, 11.3 months OS, 0.50 QALYs, and expected lifetime costs of £4,876. Ofatumumab patients were estimated to reach 6.5 months PFS, 17.9 months OS, 0.77 QALYs, with expected lifetime costs of £43,828. CONCLUSIONS: The novel approach presented permits a practical alternative for estimating cost-effectiveness when neither an RCT nor appropriate historical control can be identifi ed. Further research should be conducted using established data sets to validate the methodology, and to address potential limitations, e.g. unobserved differences between treatment groups, and potential benefi ts of treatment in patients classifi ed as non-responders.

PSY22 COST OF OBESITY TREATMENT IN POLAND

treatment regimens. The impact of patient profile (defined in terms of historical and pre-ITI titre levels, age at ITI, age at diagnosis of inhibitors) and FVIII dosage regimen on success rates and duration of ITI were estimated via simulation and competing risk survival models using data from 113 patients enrolled in two large ITI registries. RESULTS: A typical patient initiating ITI with a FVIII dosage of 50–199 IU/Kg/day has an estimated 70% success rate. The median time to ITI completion was estimated at 15 months. The FVIII-related costs (discounted at 3%) were

PSY51 THE IMPACT OF OBESITY ON QUALITY OF LIFE IN POLISH POPULATION

1,101,250. The main cost driver was the FVIII dosage. For instance, ITI costs ranged from