Routine Measurement of Health-Related Quality of Life in Assessing Cost-Effectiveness in Secondary Health Care

Aims: The aims of this study were 1) to identify and describe health economic studies that have used quality-adjusted life years (QALYs) based on actual measurements of patients' health-related quality of life (HRQoL); 2) to test the feasibility of routine collection of health-related quality of life (HRQoL) data as an indicator of effectiveness of secondary health care; and 3) to establish and compare the cost-utility of three large-volume surgical procedures in a real-world setting in the Helsinki University Central Hospital, a large referral hospital providing secondary and tertiary health-care services for a population of approximately 1.4 million. Patients and methods: So as to identify studies that have used QALYs as an outcome measure, a systematic search of the literature was performed using the Medline, Embase, CINAHL, SCI and Cochrane Library electronic databases. Initial screening of the identified articles involved two reviewers independently reading the abstracts; the full-text articles were also evaluated independently by two reviewers, with a third reviewer used in cases where the two reviewers could not agree a consensus on which articles should be included. The feasibility of routinely evaluating the cost-effectiveness of secondary health care was tested by setting up a system for collecting HRQoL data on approximately 4 900 patients' HRQoL before and after operative treatments performed in the hospital. The HRQoL data used as an indicator of treatment effectiveness was combined with diagnostic and financial indicators routinely collected in the hospital. To compare the cost-effectiveness of three surgical interventions, 712 patients admitted for routine operative treatment completed the 15D HRQoL questionnaire before and also 3-12 months after the operation. QALYs were calculated using the obtained utility data and expected remaining life years of the patients. Direct hospital costs were obtained from the clinical patient administration database of the hospital and a cost-utility analysis was performed from the perspective of the provider of secondary health care services. Main results: The systematic review (Study I) showed that although QALYs gained are considered an important measure of the effectiveness of health care, the number of studies in which QALYs are based on actual measurements of patients' HRQoL is still fairly limited. Of the reviewed full-text articles, only 70 reported QALYs based on actual before after measurements using a valid HRQoL instrument. Collection of simple cost-effectiveness data in secondary health care is feasible and could easily be expanded and performed on a routine basis (Study II). It allows meaningful comparisons between various treatments and provides a means for allocating limited health care resources. The cost per QALY gained was 2 770 for cervical operations and 1 740 for lumbar operations. In cases where surgery was delayed the cost per QALY was doubled (Study III). The cost per QALY ranges between subgroups in cataract surgery (Study IV). The cost per QALY gained was 5 130 for patients having both eyes operated on and 8 210 for patients with only one eye operated on during the 6-month follow-up. In patients whose first eye had been operated on previous to the study period, the mean HRQoL deteriorated after surgery, thus precluding the establishment of the cost per QALY. In arthroplasty patients (Study V) the mean cost per QALY gained in a one-year period was 6 710 for primary hip replacement, 52 270 for revision hip replacement, and 14 000 for primary knee replacement. Conclusions: Although the importance of cost-utility analyses has during recent years been stressed, there are only a limited number of studies in which the evaluation is based on patients own assessment of the treatment effectiveness. Most of the cost-effectiveness and cost-utility analyses are based on modeling that employs expert opinion regarding the outcome of treatment, not on patient-derived assessments. Routine collection of effectiveness information from patients entering treatment in secondary health care turned out to be easy enough and did not, for instance, require additional personnel on the wards in which the study was executed. The mean patient response rate was more than 70 %, suggesting that patients were happy to participate and appreciated the fact that the hospital showed an interest in their well-being even after the actual treatment episode had ended. Spinal surgery leads to a statistically significant and clinically important improvement in HRQoL. The cost per QALY gained was reasonable, at less than half of that observed for instance for hip replacement surgery. However, prolonged waiting for an operation approximately doubled the cost per QALY gained from the surgical intervention. The mean utility gain following routine cataract surgery in a real world setting was relatively small and confined mostly to patients who had had both eyes operated on. The cost of cataract surgery per QALY gained was higher than previously reported and was associated with considerable degree of uncertainty. Hip and knee replacement both improve HRQoL. The cost per QALY gained from knee replacement is two-fold compared to hip replacement. Cost-utility results from the three studied specialties showed that there is great variation in the cost-utility of surgical interventions performed in a real-world setting even when only common, widely accepted interventions are considered. However, the cost per QALY of all the studied interventions, except for revision hip arthroplasty, was well below 50 000, this figure being sometimes cited in the literature as a threshold level for the cost-effectiveness of an intervention. Based on the present study it may be concluded that routine evaluation of the cost-utility of secondary health care is feasible and produces information essential for a rational and balanced allocation of scarce health care resources.

Quality Assessment of a Forest Inventory Based on Airborne Laser Scanning

In this study, a quality assessment method based on sampling of primary laser inventory units (microsegments) was analysed. The accuracy of a laser inventory carried out in Kuhmo was analysed as a case study. Field sample plots were measured on the sampled microsegments in the Kuhmo inventory area. Two main questions were considered. Did the ALS based inventory meet the accuracy requirements set for the provider and how should a reliable, cost-efficient and independent quality assessment be undertaken. The agreement between control measurement and ALS based inventory was analysed in four ways: 1) The root mean squared errors (RMSEs) and bias were calculated. 2) Scatter plots with 95% confidence intervals were plotted and the placing of identity lines was checked. 3) Bland-Altman plots were drawn so that the mean difference of attributes between the control method and ALS-method was calculated and plotted against average value of attributes. 4) The tolerance limits were defined and combined with Bland-Altman plots. The RMSE values were compared to a reference study from which the accuracy requirements had been set to the service provider. The accuracy requirements in Kuhmo were achieved, however comparison of RMSE values proved to be difficult. Field control measurements are costly and time-consuming, but they are considered to be robust. However, control measurements might include errors, which are difficult to take into account. Using the Bland-Altman plots none of the compared methods are considered to be completely exact, so this offers a fair way to interpret results of assessment. The tolerance limits to be set on order combined with Bland-Altman plots were suggested to be taken in practise. In addition, bias should be calculated for total area. Some other approaches for quality control were briefly examined. No method was found to fulfil all the required demands of statistical reliability, cost-efficiency, time efficiency, simplicity and speed of implementation. Some benefits and shortcomings of the studied methods were discussed.

Automatic Lameness Detection in a Milking Robot : Instrumentation, measurement software, algorithms for data analysis and a neural network model

The aim of this thesis is to develop a fully automatic lameness detection system that operates in a milking robot. The instrumentation, measurement software, algorithms for data analysis and a neural network model for lameness detection were developed. Automatic milking has become a common practice in dairy husbandry, and in the year 2006 about 4000 farms worldwide used over 6000 milking robots. There is a worldwide movement with the objective of fully automating every process from feeding to milking. Increase in automation is a consequence of increasing farm sizes, the demand for more efficient production and the growth of labour costs. As the level of automation increases, the time that the cattle keeper uses for monitoring animals often decreases. This has created a need for systems for automatically monitoring the health of farm animals. The popularity of milking robots also offers a new and unique possibility to monitor animals in a single confined space up to four times daily. Lameness is a crucial welfare issue in the modern dairy industry. Limb disorders cause serious welfare, health and economic problems especially in loose housing of cattle. Lameness causes losses in milk production and leads to early culling of animals. These costs could be reduced with early identification and treatment. At present, only a few methods for automatically detecting lameness have been developed, and the most common methods used for lameness detection and assessment are various visual locomotion scoring systems. The problem with locomotion scoring is that it needs experience to be conducted properly, it is labour intensive as an on-farm method and the results are subjective. A four balance system for measuring the leg load distribution of dairy cows during milking in order to detect lameness was developed and set up in the University of Helsinki Research farm Suitia. The leg weights of 73 cows were successfully recorded during almost 10,000 robotic milkings over a period of 5 months. The cows were locomotion scored weekly, and the lame cows were inspected clinically for hoof lesions. Unsuccessful measurements, caused by cows standing outside the balances, were removed from the data with a special algorithm, and the mean leg loads and the number of kicks during milking was calculated. In order to develop an expert system to automatically detect lameness cases, a model was needed. A probabilistic neural network (PNN) classifier model was chosen for the task. The data was divided in two parts and 5,074 measurements from 37 cows were used to train the model. The operation of the model was evaluated for its ability to detect lameness in the validating dataset, which had 4,868 measurements from 36 cows. The model was able to classify 96% of the measurements correctly as sound or lame cows, and 100% of the lameness cases in the validation data were identified. The number of measurements causing false alarms was 1.1%. The developed model has the potential to be used for on-farm decision support and can be used in a real-time lameness monitoring system.

Regio- and stereoselectivity of oxidative coupling reactions of phenols : Spirodienones as construction units in lignin

Dimeric phenolic compounds lignans and dilignols form in the so-called oxidative coupling reaction of phenols. Enzymes such as peroxidases and lac-cases catalyze the reaction using hydrogen peroxide or oxygen respectively as oxidant generating phenoxy radicals which couple together according to certain rules. In this thesis, the effects of the structures of starting materials mono-lignols and the effects of reaction conditions such as pH and solvent system on this coupling mechanism and on its regio- and stereoselectivity have been studied. After the primary coupling of two phenoxy radicals a very reactive quinone me-thide intermediate is formed. This intermediate reacts quickly with a suitable nucleophile which can be, for example, an intramolecular hydroxyl group or another nucleophile such as water, methanol, or a phenolic compound in the reaction system. This reaction is catalyzed by acids. After the nucleophilic addi-tion to the quinone methide, other hydrolytic reactions, rearrangements, and elimination reactions occur leading finally to stable dimeric structures called lignans or dilignols. Similar reactions occur also in the so-called lignification process when monolignol (or dilignol) reacts with the growing lignin polymer. New kinds of structures have been observed in this thesis. The dimeric com-pounds with so-called spirodienone structure have been observed to form both in the dehydrodimerization of methyl sinapate and in the beta-1-type cross-coupling reaction of two different monolignols. This beta-1-type dilignol with a spirodienone structure was the first synthetized and published dilignol model compound, and at present, it has been observed to exist as a fundamental construction unit in lignins. The enantioselectivity of the oxidative coupling reaction was also studied for obtaining enantiopure lignans and dilignols. A rather good enantioselectivity was obtained in the oxidative coupling reaction of two monolignols with chiral auxiliary substituents using peroxidase/H2O2 as an oxidation system. This observation was published as one of the first enantioselective oxidative coupling reaction of phenols. Pure enantiomers of lignans were also obtained by using chiral cryogenic chromatography as a chiral resolution technique. This technique was shown to be an alternative route to prepare enantiopure lignans or lignin model compounds in a preparative scale.

Do Measurement Errors in GDP Announcements Cause Output Fluctuations?

This thesis studies empirically whether measurement errors in aggregate production statistics affect sentiment and future output. Initial announcements of aggregate production are subject to measurement error, because many of the data required to compile the statistics are produced with a lag. This measurement error can be gauged as the difference between the latest revised statistic and its initial announcement. Assuming aggregate production statistics help forecast future aggregate production, these measurement errors are expected to affect macroeconomic forecasts. Assuming agents’ macroeconomic forecasts affect their production choices, these measurement errors should affect future output through sentiment. This thesis is primarily empirical, so the theoretical basis, strategic complementarity, is discussed quite briefly. However, it is a model in which higher aggregate production increases each agent’s incentive to produce. In this circumstance a statistical announcement which suggests aggregate production is high would increase each agent’s incentive to produce, thus resulting in higher aggregate production. In this way the existence of strategic complementarity provides the theoretical basis for output fluctuations caused by measurement mistakes in aggregate production statistics. Previous empirical studies suggest that measurement errors in gross national product affect future aggregate production in the United States. Additionally it has been demonstrated that measurement errors in the Index of Leading Indicators affect forecasts by professional economists as well as future industrial production in the United States. This thesis aims to verify the applicability of these findings to other countries, as well as study the link between measurement errors in gross domestic product and sentiment. This thesis explores the relationship between measurement errors in gross domestic production and sentiment and future output. Professional forecasts and consumer sentiment in the United States and Finland, as well as producer sentiment in Finland, are used as the measures of sentiment. Using statistical techniques it is found that measurement errors in gross domestic product affect forecasts and producer sentiment. The effect on consumer sentiment is ambiguous. The relationship between measurement errors and future output is explored using data from Finland, United States, United Kingdom, New Zealand and Sweden. It is found that measurement errors have affected aggregate production or investment in Finland, United States, United Kingdom and Sweden. Specifically, it was found that overly optimistic statistics announcements are associated with higher output and vice versa.

Cardiac function before and after treatment for various types of loading conditions and in myocardial restriction : A prospective study on pediatric patients with two- and three-dimensional echocardiography and measurement of serum natriuretic peptides

Background: The incidence of all forms of congenital heart defects is 0.75%. For patients with congenital heart defects, life-expectancy has improved with new treatment modalities. Structural heart defects may require surgical or catheter treatment which may be corrective or palliative. Even those with corrective therapy need regular follow-up due to residual lesions, late sequelae, and possible complications after interventions. Aims: The aim of this thesis was to evaluate cardiac function before and after treatment for volume overload of the right ventricle (RV) caused by atrial septal defect (ASD), volume overload of the left ventricle (LV) caused by patent ductus arteriosus (PDA), and pressure overload of the LV caused by coarctation of the aorta (CoA), and to evaluate cardiac function in patients with Mulibrey nanism. Methods: In Study I, of the 24 children with ASD, 7 underwent surgical correction and 17 percutaneous occlusion of ASD. Study II had 33 patients with PDA undergoing percutaneous occlusion. In Study III, 28 patients with CoA underwent either surgical correction or percutaneous balloon dilatation of CoA. Study IV comprised 26 children with Mulibrey nanism. A total of 76 healthy voluntary children were examined as a control group. In each study, controls were matched to patients. All patients and controls underwent clinical cardiovascular examinations, two-dimensional (2D) and three-dimensional (3D) echocardiographic examinations, and blood sampling for measurement of natriuretic peptides prior to the intervention and twice or three times thereafter. Control children were examined once by 2D and 3D echocardiography. M-mode echocardiography was performed from the parasternal long axis view directed by 2D echocardiography. The left atrium-to-aorta (LA/Ao) ratio was calculated as an index of LA size. The end-diastolic and end-systolic dimensions of LV as well as the end-diastolic thicknesses of the interventricular septum and LV posterior wall were measured. LV volumes, and the fractional shortening (FS) and ejection fraction (EF) as indices of contractility were then calculated, and the z scores of LV dimensions determined. Diastolic function of LV was estimated from the mitral inflow signal obtained by Doppler echocardiography. In three-dimensional echocardiography, time-volume curves were used to determine end-diastolic and end-systolic volumes, stroke volume, and EF. Diastolic and systolic function of LV was estimated from the calculated first derivatives of these curves. Results: (I): In all children with ASD, during the one-year follow-up, the z score of the RV end-diastolic diameter decreased and that of LV increased. However, dilatation of RV did not resolve entirely during the follow-up in either treatment group. In addition, the size of LV increased more slowly in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides in patients treated percutaneously increased during the first month after ASD closure and normalized thereafter, but in patients treated surgically, they remained higher than in controls. (II): In the PDA group, at baseline, the end-diastolic diameter of LV measured over 2SD in 5 of 33 patients. The median N-terminal pro-brain natriuretic peptide (proBNP) concentration before closure measured 72 ng/l in the control group and 141 ng/l in the PDA group (P = 0.001) and 6 months after closure measured 78.5 ng/l (P = NS). Patients differed from control subjects in indices of LV diastolic and systolic function at baseline, but by the end of follow-up, all these differences had disappeared. Even in the subgroup of patients with normal-sized LV at baseline, the LV end-diastolic volume decreased significantly during follow-up. (III): Before repair, the size and wall thickness of LV were higher in patients with CoA than in controls. Systolic blood pressure measured a median 123 mm Hg in patients before repair (P < 0.001) and 103 mm Hg one year thereafter, and 101 mm Hg in controls. The diameter of the coarctation segment measured a median 3.0 mm at baseline, and 7.9 at the 12-month (P = 0.006) follow-up. Thicknesses of the interventricular septum and posterior wall of the LV decreased after repair but increased to the initial level one year thereafter. The velocity time integrals of mitral inflow increased, but no changes were evident in LV dimensions or contractility. During follow-up, serum levels of natriuretic peptides decreased correlating with diastolic and systolic indices of LV function in 2D and 3D echocardiography. (IV): In 2D echocardiography, the interventricular septum and LV posterior wall were thicker, and velocity time integrals of mitral inflow shorter in patients with Mulibrey nanism than in controls. In 3D echocardiography, LV end-diastolic volume measured a median 51.9 (range 33.3 to 73.4) ml/m² in patients and 59.7 (range 37.6 to 87.6) ml/m² in controls (P = 0.040), and serum levels of ANPN and proBNP a median 0.54 (range 0.04 to 4.7) nmol/l and 289 (range 18 to 9170) ng/l, in patients and 0.28 (range 0.09 to 0.72) nmol/l (P < 0.001) and 54 (range 26 to 139) ng/l (P < 0.001) in controls. They correlated with several indices of diastolic LV function. Conclusions (I): During the one-year follow-up after the ASD closure, RV size decreased but did not normalize in all patients. The size of the LV normalized after ASD closure but the increase in LV size was slower in patients treated surgically than in those treated with the percutaneous technique. Serum levels of ANPN and proBNP were elevated prior to ASD closure but decreased thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically. (II): Changes in LV volume and function caused by PDA disappeared by 6 months after percutaneous closure. Even the children with normal-sized LV benefited from the procedure. (III): After repair of CoA, the RV size and the velocity time integrals of mitral inflow increased, and serum levels of natriuretic peptides decreased. Patients need close follow-up, despite cessation of LV pressure overload, since LV hypertrophy persisted even in normotensive patients with normal growth of the coarctation segment. (IV): In children with Mulibrey nanism, the LV wall was hypertrophied, with myocardial restriction and impairment of LV function. Significant correlations appeared between indices of LV function, size of the left atrium, and levels of natriuretic peptides, indicating that measurement of serum levels of natriuretic peptides can be used in the clinical follow-up of this patient group despite its dependence on loading conditions.

Gastric motility: Measurement, symptoms and therapy

Gastric motility disorders, including delayed gastric emptying (gastroparesis), impaired postprandial fundic relaxation, and gastric myoelectrical disorders, can occur in type 1 diabetes, chronic renal failure, and functional dyspepsia (FD). Symptoms like upper abdominal pain, early satiation, bloating, nausea and vomiting may be related to gastroparesis. Diabetic gastroparesis is related to autonomic neuropathy. Scintigraphy is the gold standard in measuring gastric emptying, but it is expensive, requires specific equipment, and exposes patients to radiation. It also gives information about the intragastric distribution of the test meal. The 13C-octanoic acid breath test (OBT) is an alternative, indirect method of measuring gastric emptying with a stable isotope. Electrogastrography (EGG) registers the slow wave originating in the pacemaker area of the stomach and regulating the peristaltic contractions of the antrum. This study compares these three methods of measuring gastric motility in patients with type 1 diabetes, functional dyspepsia, and chronic renal failure. Currently no effective drugs for treating gastric motility disorders are available. We studied the effect of nizatidine on gastric emptying, because in preliminary studies this drug has proven to have a prokinetic effect due to its cholinergic properties. Of the type 1 patients, 26% had delayed gastric emptying of solids as measured by scintigraphy. Abnormal intragastric distribution of the test meal occurred in 37% of the patients, indicating impaired fundic relaxation. The autonomic neuropathy score correlated positively with the gastric emptying rate of solids (P = 0.006), but HbA1C, plasma glucose levels, or abdominal symptoms were unrelated to gastric emptying or intragastric distribution of the test meal. Gastric emptying of both solids and liquids was normal in all FD patients but abnormal intragastric distribution occurred in 38% of the patients. Nizatidine improved symptom scores and quality of life in FD patients, but not significantly. Instead of enhancing, nizatidine slowed gastric emptying in FD patients (P < 0.05). No significant difference appeared in the frequency of the gastric slow waves measured by EGG in the patients and controls. The correlation between gastric half-emptying times of solids measured by scintigraphy and OBT was poor both in type 1 diabetes and FD patients. According to this study, dynamic dual-tracer scintigraphy is more accurate than OBT or EGG in measuring gastric emptying of solids. Additionally it provides information about gastric emptying of liquids and the intragastric distribution of the ingested test meal.

Measurement of $d\sigma/dy$ of Drell-Yan $e^+e^-$ pairs in the $Z$ Mass Region from $p\bar{p}$ Collisions at $\sqrt{s}=1.96$ TeV

We report on a CDF measurement of the total cross section and rapidity distribution, $d\sigma/dy$, for $q\bar{q}\to \gamma^{*}/Z\to e^{+}e^{-}$ events in the $Z$ boson mass region ($66M_{ee}

Measurement of Particle Production and Inclusive Differential Cross Sections in pbar{p} Collisions at sqrt{s}=1.96 TeV

We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.