Balancing between competition and regulation in healthcare markets.

Systems of managed competition naturally seek the middle ground between competition and regulation. This debate essay makes the case for adjusting the level of regulation according to the characteristics of the submarket in question. We first develop a theoretical framework that can be used to identify the services in which relatively free competition will be beneficial. The framework is grounded in the economic literature and consists of eight criteria. Targeted regulatory tools are then discussed that can be used to structure submarkets in which these criteria are not (fully) met. Applying this framework and targeted interventions, regulators gain the flexibility to react to potential market failures, without foregoing the benefits of managed competition where it works well. This analysis is highly relevant for countries in transition to managed competition. Regulators can identify potential failure in submarkets for medical services, and apply the necessary regulatory tools to prepare for a smooth transition.

The goal of risk equalization in regulated competitive health insurance markets.

Different opinions exist about the goal of risk equalization in regulated competitive health insurance markets. There seems to be consensus that an element of the goal of risk equalization is 'to remove the predictable over- and undercompensations of subgroups of insured' or, equivalently, 'to achieve a level playing field for each risk composition of an insurer's portfolio' or, equivalently, 'to remove the incentives for risk selection'. However, the role of efficiency appears to be a major issue: should efficiency also be an element of the goal of risk equalization, or should it be a restriction to the goal, or should efficiency not be an element of the goal or a restriction to the goal? If efficiency plays a role, a comprehensive analysis of the total effect of risk equalization on efficiency needs to be done. An improvement of the performance of a risk equalization scheme has both negative and positive effects on efficiency. Negative effects include the reduction in efficiency via cost- or utilization-based risk adjusters. Positive effects result from leveling the playing field and reducing the incentives for risk selection, which increase efficiency as the outcome of a competitive market. In practice many regulators and policy makers take efficiency into consideration by looking at the negative effects, but hardly at the positive effects. The definition of the goal of risk equalization has consequences for the design and evaluation of risk equalization schemes and for the equalization payments. We describe relevant potential goals, tradeoffs and possible solutions.

Preferences and choices for care and health insurance.

Legislation that came into effect in 2006 has dramatically altered the health insurance system in the Netherlands, placing greater emphasis on consumer choice and competition among insurers. The potential for such competition depends largely on consumer preferences for price and quality of service by insurers and quality of affiliated providers. This study provides initial evidence on the preferences of Dutch consumers and how they view trade-offs between various aspects of health insurance product design. A key feature of the analysis is that we compare the responses of high and low risk individuals, where risk is defined by the presence of a costly chronic condition. This contrast is critically important for understanding incentives facing insurers and for identifying potential unanticipated consequences of market competition. The results from our conjoint analysis suggest that not only high risk but also low risk individuals are willing to pay substantially more for insurance products that can be shown to provide better health outcomes. This suggests that insurance products that are more expensive and provide better quality of care may also attract low risk individuals. Therefore, development and dissemination of good, reliable and understandable health plan performance indicators may effectively reduce the problem of adverse selection.

Psychometric properties of the Dutch version of the Hospital-level Consumer Assessment of Health Plans Survey instrument.

OBJECTIVES: To assess the reliability and validity of a translated version of the American Hospital-level Consumer Assessment of Health Plans Survey (H-CAHPS) instrument for use in Dutch health care. DATA SOURCES/STUDY SETTING: Primary survey data from adults aged 18 years or more who were recently discharged from two multispecialty city hospitals in the Netherlands. STUDY DESIGN: We used forward and backward translation procedures and a panel of experts to adapt the 66-item pilot H-CAHPS into a 70-item Dutch instrument. Descriptive statistics and standard psychometric methods were then used to test the reliability and validity of the new instrument. DATA COLLECTION: From late November 2003 to early January 2004, the survey was administered by mail to 1,996 patients discharged within the previous 2 months. PRINCIPAL FINDINGS: Analyses supported the reliability and validity of the following 7-factor H-CAHPS structure for use in Dutch hospitals: on doctor's communication, nurses' communication, discharge information, communication about medication, pain control, physical environment of hospital, and nursing services. The internal consistency reliability of the scales ranged from 0.60 to 0.88. Items related to "family receiving help when on visit,""hospital staff introducing self," and "admission delays" did not improve the psychometric properties of the new instrument. CONCLUSIONS: These findings suggest that the H-CAHPS instrument is reliable and valid for use in the Dutch context. However, more research will be needed to support its equivalence to the United States version, and its use for between-hospital comparisons.

Genetic analysis.

The Mendelian analysis of genetic variation, available as induced mutants or as natural variation, requires a number of steps that are described in this chapter. These include the determination of the number of genes involved in the observed trait's variation, the determination of dominance relationships between alleles of the same locus, and epistatic interactions with related genetic variants. A new variant should be compared with previously identified genetic variants, which is most efficiently done by allelism tests in case of recessive mutants. In addition the locus should be localized on the genetic and physical map by linkage analysis. The mapping of mutant loci in Arabidopsis is facilitated by the genomic resources available in Arabidopsis and often consists of two steps, a crude and a fine mapping, the latter enabling the approximate location of a variant on the sequence map of Arabidopsis.

Linkage disequilibrium mapping of yield and yield stability in modern spring barley cultivars.

Associations between markers and complex quantitative traits were investigated in a collection of 146 modern two-row spring barley cultivars, representing the current commercial germ plasm in Europe. Using 236 AFLP markers, associations between markers were found for markers as far apart as 10 cM. Subsequently, for the 146 cultivars the complex traits mean yield, adaptability (Finlay-Wilkinson slope), and stability (deviations from regression) were estimated from the analysis of variety trial data. Regression of those traits on individual marker data disclosed marker-trait associations for mean yield and yield stability. Support for identified associations was obtained from association profiles, i.e., from plots of P-values against chromosome positions. In addition, many of the associated markers were located in regions where earlier QTL were found for yield and yield components. To study the oligogenic genetic base of the traits in more detail, multiple linear regression of the traits on markers was carried out, using stepwise selection. By this procedure, 18-20 markers that accounted for 40-58% of the variation were selected. Our results indicate that association mapping approaches can be a viable alternative to classical QTL approaches based on crosses between inbred lines, especially for complex traits with costly measurements.

Managed care in four managed competition OECD health systems.

Managed care emerged in the American health system in the 1980s as a way to manage suppliers' induced demand and to contain insurers' costs. While in Israel the health insurers have always been managed care organizations, owning health care facilities, employing medical personnel or contracting selectively with independent providers, European insurers have been much more passive, submitting themselves to collective agreements between insurers' and providers' associations, accompanied by extensive government regulation of prices, quantities, and budgets. With the 1990s reforms, and the introduction of risk-adjusted "managed competition", a growing pressure to allow the European insurers to manage their own care - including selective contracting with providers - has emerged, with varying speed of the introduction of policy changes across the individual countries. This paper compares experiences with managed care in Israel, The Netherlands, Germany and Switzerland since the 1990s. After a brief description of the health insurance markets in the four countries, we focus comparatively on the emergence of managed care in the markets for ambulatory care and inpatient market care. We conclude with an evaluation of the current situation and a discussion of selected health policy issues.

Peroxidase profiling reveals genetic linkage between peroxidase gene clusters and basal host and non-host resistance to rusts and mildew in barley.

BACKGROUND: Higher plants possess a large multigene family encoding secreted class III peroxidase (Prx) proteins. Peroxidases appear to be associated with plant disease resistance based on observations of induction during disease challenge and the presence or absence of isozymes in resistant vs susceptible varieties. Despite these associations, there is no evidence that allelic variation of peroxidases directly determines levels of disease resistance. METHODOLOGY/PRINCIPAL FINDINGS: The current study introduces a new strategy called Prx-Profiling. We showed that with this strategy a large number of peroxidase genes can be mapped on the barley genome. In order to obtain an estimate of the total number of Prx clusters we followed a re-sampling procedure, which indicated that the barley genome contains about 40 peroxidase gene clusters. We examined the association between the Prxs mapped and the QTLs for resistance of barley to homologous and heterologous rusts, and to the barley powdery mildew fungus. We report that 61% of the QTLs for partial resistance to P. hordei, 61% of the QTLs for resistance to B. graminis and 47% of the QTLs for non-host resistance to other Puccinia species co-localize with Prx based markers. CONCLUSIONS/SIGNIFICANCE: We conclude that Prx-Profiling was effective in finding the genetic location of Prx genes on the barley genome. The finding that QTLs for basal resistance to rusts and powdery mildew fungi tend to co-locate with Prx clusters provides a base for exploring the functional role of Prx-related genes in determining natural differences in levels of basal resistance.

Meiotic interference among MLH1 foci requires neither an intact axial element structure nor full synapsis.

During meiosis, homologous chromosomes (homologs) perform reciprocal exchanges (crossovers) at a high frequency. Crossovers display interference, i.e. their spacing is more even than would be expected if they were placed randomly along the chromosomes. Concomitantly with crossover formation, synaptonemal complexes (SCs) appear between homologs: each chromosome forms an axial structure, the axial element (AE); the AEs of homologs align, and numerous transverse filaments connect the AEs to form an SC. Both the AE and the SC have been implicated in the imposition of interference. We investigated whether intact AEs or SCs are required for crossover interference in the mouse, using a mutant lacking AE protein SYCP3, which displays structurally abnormal AEs and incomplete synapsis. We estimated the level of interference from the spacing of immunofluorescent MLH1 foci, which mark almost all crossover sites in the mouse, along the SCs. The levels of interference among MLH1 foci in wild-type and Sycp3(-/-) mice were comparable, implying that neither an intact AE structure nor full synapsis is required for wild-type levels of interference.

Two levels of interference in mouse meiotic recombination.

During meiosis, homologous chromosomes (homologs) undergo recombinational interactions, which can yield crossovers (COs) or noncrossovers. COs exhibit interference; they are more evenly spaced along the chromosomes than would be expected if they were placed randomly. The protein complexes involved in recombination can be visualized as immunofluorescent foci. We have analyzed the distribution of such foci along meiotic prophase chromosomes of the mouse to find out when interference is imposed and whether interference manifests itself at a constant level during meiosis. We observed strong interference among MLH1 foci, which mark CO positions in pachytene. Additionally, we detected substantial interference well before this point, in late zygotene, among MSH4 foci, and similarly, among replication protein A (RPA) foci. MSH4 foci and RPA foci both mark interhomolog recombinational interactions, most of which do not yield COs in the mouse. Furthermore, this zygotene interference did not depend on SYCP1, which is a transverse filament protein of mouse synaptonemal complexes. Interference is thus not specific to COs but may occur in other situations in which the spatial distribution of events has to be controlled. Differences between the distributions of MSH4/RPA foci and MLH1 foci along synaptonemal complexes might suggest that CO interference occurs in two successive steps.

Made in the USA: the import of American Consumer Assessment of Health Plan Surveys (CAHPS) into the Dutch social insurance system.

BACKGROUND: In the Netherlands, managed competition between health plans has been introduced. For Dutch health plans this implies that they need to collect data about their own performance and that of the care providers they contract. To that end, Consumer Assessment of Health Plan Surveys (CAHPS) instruments have recently been adopted by a large Dutch health plan. OBJECTIVES: This paper presents the results of a validation study of the Dutch version of the CAHPS Adult Commercial questionnaire. The questions addressed are as follows: Can this questionnaire be adapted for use in the context of the Dutch insurance system? and Can it generate valid information about the quality of health care and the performance of Dutch health plans? METHODS: The translated questionnaire has been mailed to a sample of 977 enrollees. The psychometric properties of the translated instrument have been studied, and the results have been compared with those of other Dutch and American studies. RESULTS: The net response rate was 51% (n = 500). In general, the questionnaires were filled out completely and consistently. Principal component analyses revealed a factor that can be labelled as patient-centredness in the primary process. It contains the domains that in the CAHPS literature are described as 'courteous/helpful staff' and 'doctors communicating well'. CONCLUSIONS: The translated version of the CAHPS Adult Commercial questionnaire is a promising tool for Dutch health plans. More research is needed on the external and the content validity of these questionnaires in the Dutch context.

SMOOTH: a statistical method for successful removal of genotyping errors from high-density genetic linkage data.

High-density genetic linkage maps can be used for purposes such as fine-scale targeted gene cloning and anchoring of physical maps. However, their construction is significantly complicated by even relatively small amounts of scoring errors. Currently available software is not able to solve the ordering ambiguities in marker clusters, which inhibits the application of high-density maps. A statistical method named SMOOTH was developed to remove genotyping errors from genetic linkage data during the mapping process. The program SMOOTH calculates the difference between the observed and predicted values of data points based on data points of neighbouring loci in a given marker order. Highly improbable data points are removed by the program in an iterative process with a mapping algorithm that recalculates the map after cleaning. SMOOTH has been tested with simulated data and experimental mapping data from potato. The simulations prove that this method is able to detect a high amount of scoring errors and demonstrates that the program enables mapping software to successfully construct a very accurate high-density map. In potato the application of the program resulted in a reliable placement of nearly 1,000 markers in one linkage group.

QTL analysis and QTL-based prediction of flowering phenology in recombinant inbred lines of barley.

Combining ecophysiological modelling and genetic mapping has increasingly received attention from researchers who wish to predict complex plant or crop traits under diverse environmental conditions. The potential for using this combined approach to predict flowering time of individual genotypes in a recombinant inbred line (RIL) population of spring barley (Hordeum vulgare L.) was examined. An ecophysiological phenology model predicts preflowering duration as affected by temperature and photoperiod, based on the following four input traits: f(o) (the minimum number of days to flowering at the optimum temperature and photoperiod), theta1 and theta2 (the development stages for the start and the end of the photoperiod-sensitive phase, respectively), and delta (the photoperiod sensitivity). The model-input trait values were obtained from a photoperiod-controlled greenhouse experiment. Assuming additivity of QTL effects, a multiple QTL model was fitted for the model-input traits using composite interval mapping. Four to seven QTL were identified for each trait. Each trait had at least one QTL specific to that trait alone. Other QTL were shared by two or all traits. Values of the model-input traits predicted for the RILs from the QTL model were fed back into the ecophysiological model. This QTL-based ecophysiological model was subsequently used to predict preflowering duration (d) for eight field trial environments. The model accounted for 72% of the observed variation among 94 RILs and 94% of the variation among the two parents across the eight environments, when observations in different environments were pooled. However, due to the low percentage (34-41%) of phenotypic variation accounted for by the identified QTL for three model-input traits (theta1, theta2 and delta), the QTL-based model accounted for somewhat less variation among the RILs than the model using original phenotypic input trait values. Nevertheless, days to flowering as predicted from the QTL-based ecophysiological model were highly correlated with days to flowering as predicted from QTL-models per environment for days to flowering per se. The ecophysiological phenology model was thus capable of extrapolating (QTL) information from one environment to another.

RECORD: a novel method for ordering loci on a genetic linkage map.

A new method, REcombination Counting and ORDering (RECORD) is presented for the ordering of loci on genetic linkage maps. The method minimizes the total number of recombination events. The search algorithm is a heuristic procedure, combining elements of branch-and-bound with local reshuffling. Since the criterion we propose does not require intensive calculations, the algorithm rapidly produces an optimal ordering as well as a series of near-optimal ones. The latter provides insight into the local certainty of ordering along the map. A simulation study was performed to compare the performance of RECORD and JoinMap. RECORD is much faster and less sensitive to missing observations and scoring errors, since the optimisation criterion is less dependent on the position of the erroneous markers. In particular, RECORD performs better in regions of the map with high marker density. The implications of high marker densities on linkage map construction are discussed.

Genetic and physiological architecture of early vigor in Aegilops tauschii, the D-genome donor of hexaploid wheat. A quantitative trait loci analysis.

Plant growth can be studied at different organizational levels, varying from cell, leaf, and shoot to the whole plant. The early growth of seedlings is important for the plant's establishment and its eventual success. Wheat (Triticum aestivum, genome AABBDD) seedlings exhibit a low early growth rate or early vigor. The germplasm of wheat is limited. Wild relatives constitute a source of genetic variation. We explored the physiological and genetic relationships among a range of early vigor traits in Aegilops tauschii, the D-genome donor. A genetic map was constructed with amplified fragment-length polymorphism and simple sequence repeat markers, and quantitative trait loci (QTL) analysis was performed on the F(4) population of recombinant inbred lines derived from a cross between contrasting accessions. The genetic map consisted of 10 linkage groups, which were assigned to the seven chromosomes and covered 68% of the D genome. QTL analysis revealed 87 mapped QTLs (log of the odds >2.65) in clusters, 3.1 QTLs per trait, explaining 32% of the phenotypic variance. Chromosomes 1D, 4D, and 7D harbored QTLs for relative growth rate, biomass allocation, specific leaf area, leaf area ratio, and unit leaf rate. Chromosome 2D covered QTLs for rate and duration of leaf elongation, cell production rate, and cell length. Chromosome 5D harbored QTLs for the total leaf mass and area and growth rate of the number of leaves and tillers. The results show that several physiological correlations between growth traits have a genetic basis. Genetic links between traits are not absolute, opening perspectives for identification of favorable alleles in A. tauschii to improve early vigor in wheat.

A genetic analysis of relative growth rate and underlying components in Hordeum spontaneum.

Species from productive and unproductive habitats differ inherently in their relative growth rate (RGR) and a wide range of correlated quantitative traits. We investigated the genetic basis of this trait complex, and specifically assessed whether it is under the control of just one or a few genes that can act as 'master switches' by simultaneously affecting a range of traits in the complex. To address this problem, we crossed two Hordeum spontaneum lines originating from two habitats that differ in productivity. The F3 offspring, in which parental alleles are present in different combinations due to recombination and segregation, was analysed for RGR and its underlying components (leaf area ratio, unit leaf rate, photosynthesis, respiration), as well as a number of other physiological and morphological parameters. For this intra-specific comparison, we found a complex of positively and negatively correlated traits, which was quite similar to what is generally observed across species. A quantitative trait loci (QTL) analysis showed three major and one minor QTL for RGR. Most other variables of the growth-trait complex showed fewer QTLs that were typically scattered over various locations on the genome. Thus, at least in H. spontaneum, we found no evidence for regulation of the trait complex by one or two master switches.