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We present international consensus recommendations for improving diagnosis, management and treatment access in multiple sclerosis (MS). Our vision is that these will be used widely among those committed to creating a better future for people with MS and their families.

Zusammenfassung.Das Ziel einer medizinischen Rehabilitation ist die Wiedereingliederung ins Erwerbsleben. Für die individuelle Therapieplanung ist eine fundierte Diagnostik notwendig. Studien weisen jedoch darauf hin, dass Kliniker nur rund 53 % der Schlüsselkriterien einer psychischen Störung erfragen. Das Ziel der vorliegenden Studie dient der Validierung der im Rahmen eines Anamnesegesprächs gestellten Diagnosen innerhalb von psychosomatischen Rehabilitationszentren anhand eines strukturierten Interviewleitfadens (SKID). Die randomisierte Stichprobe (N = 136) wurde aus dem Patientenpool der Rehabilitationszentren Oberharz und Bad Pyrmont der Deutschen Rentenversicherung Braunschweig Hannover erhoben. Jeder Patient wurde durch einen Therapeuten im Rahmen des Anamnesegesprächs und zudem anhand eines strukturierten Interviews diagnostiziert. Die Ergebnisse der vorliegenden Studie weisen darauf hin, dass sich die Diagnosevergaben auf der Basis eines strukturierten Interviews und einem Anamnesegespräch stark unterscheiden. Demnach stellt ein strukturiertes Interview eine Möglichkeit dar, zu validen Diagnose im Kontext der psychosomatischen Rehabilitation zu gelangen.

Angiotensin-II receptor blockers (ARBs) have been associated with preventing posttraumatic stress disorder (PTSD) symptom development and improving memory. However, the underlying neural mechanisms are poorly understood. This study investigated ARB effects on memory encoding and hippocampal functioning previously implicated in PTSD development.

Zusammenfassung.Die vorliegende Arbeit untersucht das Konzept des posttraumatischen Wachstums anhand einer Stichprobe von Menschen mit einer traumatisch bedingten Querschnittlähmung (N = 70). Neben dem Ausmaß an posttraumatischem Wachstum werden mit varianzanalytischen Verfahren der Zusammenhang zwischen posttraumatischem Wachstum und weiteren Einzelmerkmalen der Probanden (Alter, Geschlecht, Lähmungshöhe, seelische Belastung, Schwere der Erschütterung, Unterstützung durch Familie, Freunde und andere querschnittgelähmte Personen, in Anspruch genommene psychologische Hilfe) ermittelt. Posttraumatisches Wachstum wird mit der deutschen Version des Posttraumatic Growth Inventory (PTGI) und die seelische Belastung mit den Depression, Anxiety and Stress Scales (DASS) gemessen. Alle anderen Merkmale werden anhand von Einzelitems erhoben. 62,9 % der Teilnehmer gaben an, posttraumatisches Wachstum in einem Ausmaß mittlerer Stärke erlebt zu haben. Weitere Faktoren, die mit posttraumatischem Wachstum in Zusammenhang stehen, konnten nicht eindeutig identifiziert werden. Folgen für die praktische Anwendung und zukünftige Forschungsarbeiten werden diskutiert.

The seed and forage production of a diverse group of the perennial forage legume Cullen spp., collected in southern Australia, was assessed with the aim of discovering diversity for exploitation in future breeding programs. Eighty ecotypes were assessed at the Waite Institute in South Australia, using replicated, spaced-plant field trials, between 2008 and 2012. Seed production in collected ecotypes of Cullen (Expt 1) ranged from 0 to 485kgha-1 for windrowed seed yield and from 0 to 790kgha-1 for total seed yield, which included vacuum-harvested seed from pods that had fallen to the ground. Individual plants were selected for seed production from their original populations, and the seed and fodder production of their progeny was evaluated in a further field experiment (Expt 2). Moderate to high heritability estimates were recorded for seed production traits. Seed production in progeny families ranged from 0 to1 423kgha-1 and was highly correlated with the number of seeds per inflorescence (r=0.85) and forage yield (r=0.59). Edible biomass, measured using the Adelaide visual appraisal method, ranged from 50 to 906gdryweight (DW) plant-1 in parent ecotypes and from 404 to 1248gDWplant-1 in the selected family progenies. Disease infection with anthracnose (Colletotrichum trifolii) caused considerable damage to plants in Expt 1, resulting in the death of all plants of 10 ecotypes, and infection with Alfalfa mosaic virus in Expt 2 was linked to the death of 67 individuals. The results are discussed in relation to breeding C. australasicum for increased seed yield and disease resistance to overcome these deficiencies as barriers to commercial adoption.

Resilienz umschreibt die Tatsache, dass es Menschen trotz belastender Lebensumstände gelingt, ihr Leben erfolgreich zu meistern. Resilienzförderliche Faktoren werden nicht nur in der Person selbst, sondern auch im Umfeld gefunden. Verlässliche, optimistische Bezugspersonen und ressourcenorientierte Fachkräfte tragen dazu bei, dass Kinder und Familien Eigenschaften und Kompetenzen entwickeln, die trotz Krankheit oder Behinderung eine nach vorne gerichtete Entwicklung ermöglichen.

Phenotypic variability is well recognized in severe hemophilia A. A few studies, mainly in adults treated lifelong on demand, suggest that bleeding phenotype correlates with factor VIII gene (F8) mutation type. Because treatment regimens influence outcomes to a large extent, examining bleeding phenotype during the first years of life may be the most suitable way to define this variability. We set out to analyze the very early phenotypic expression of severe hemophilia A in 621 consecutively enrolled, well-characterized previously untreated patients and to correlate this with patients’ F8 mutation. Detailed information was collected on bleeds and treatment of the first 75 exposure days or until inhibitor development. F8 mutation type was known for 531 patients; 402 had null mutations and 129 had non-null mutations. Considering only patients who had not started prophylaxis or developed an inhibitor before select bleeding events, we found that patients with null mutations experienced their first bleed and first joint bleed at younger median ages than patients with non-null mutations (9.7 vs 10.9 months and 13.8 vs 16.1 months, respectively). We conclude that F8 mutation type accounts for only a small component of the significant phenotypic variability found among patients with severe hemophilia A.

DNA vaccines are potential tools for the induction of immune responses against both infectious disease and cancer. The dermal application of DNA vaccines is of particular interest since the epidermal and dermal layers of the skin are characterized by an abundance of antigen-presenting cells (APCs). The aim of our study was to compare tumor protection as obtained by two different methods of intradermal DNA delivery (gene gun and jet injector) in a well-established HER2/neu mouse tumor model. BALB/c mice were immunized twice with a HER2/neu-coding plasmid by gene gun or jet injector. Mice were then subcutaneously challenged with HER2/neu+syngeneic D2F2/E2 tumor cells. Protection against subsequent challenges with tumor cells as well as humoral and T-cell immune responses induced by the vaccine were monitored. Gene gun immunization was far superior to jet injector both in terms of tumor protection and induction of HER2/neu-specific immune responses. After gene gun immunization, 60% of the mice remained tumor-free until day 140 as compared with 25% after jet injector immunization. Furthermore, gene gun vaccination was able to induce both a strong TH1-polarized T-cell response with detectable cytotoxic T-lymphocyte (CTL) activity and a humoral immune response against HER2/neu, whereas the jet injector was not. Although the disadvantages that were associated with the use of the jet injector in our model may be overcome with methodological modifications and/or in larger animals, which exhibit a thicker skin and/or subcutaneous muscle tissue, we conclude that gene gun delivery constitutes the method of choice for intradermal DNA delivery in preclinical mouse models and possibly also for the clinical development of DNA-based vaccines.

Purpose To describe treatment patterns among patients with central or branch retinal vein occlusion (CRVO or BRVO) in France, Germany, and Italy, and to estimate retinal vein occlusion (RVO)-related direct medical costs.Methods We used a retrospective chart review to determine 18-month RVO-related resource utilization and calculate 12-month health care costs. Country-specific unit costs (€) were assigned to each resource from the perspective of the health care payer. Costs for France and Germany were based on 2005, and for Italy on 2007 values.Results Data from a total of 109 BRVO and 119 patients with CRVO were used in the analysis. Laser therapy was the most commonly used intervention in Germany, for both CRVO and patients with BRVO (95%-98% of treatments), while patients in France with either condition had triamcinolone injections most often (63%-67% of treatments). Injections were also administered frequently in Italy and were the most common treatment for CRVO (50%), whereas patients with BRVO used laser therapy most often (41%). Inpatient treatment was most common in Germany (42% of CRVO and 34% of patients with BRVO), and did not occur at all in Italy except for day admissions. Total costs were higher for patients with CRVO in all countries. Most costs in Italy and France were attributable to outpatient treatment. In Germany, hospitalization made up the largest proportion of costs (80%), although more patients used outpatient services.Conclusions Approaches to treating BRVO and CRVO vary across European countries. Development of agreed-upon guidelines would support consistency in patient care and reimbursement policy.

OBJECTIVE: To estimate the incremental costs to public payers for patients with ankylosing spondylitis (AS) of working age compared with reference subjects from the general population. METHODS: We investigated total costs for 3 years (2005–2007) in 116 outpatients under 66 years of age with AS attending rheumatological care in Malmö, Sweden. Mean (SD) age was 46 (11) years and mean (SD) disease duration was 24 (11) years. Two subjects per AS patient matched for age, sex, and residential area were selected from the Population Register to serve as a reference group. We retrieved data concerning sick leave, prescription drugs, and healthcare consumption from Swedish health-cost registers by the unique personal identification numbers. RESULTS: The mean total cost for the 3-year period 2005–2007 was US $37,095 (SD $30,091) for patients with AS, and $11,071 (SD $22,340) for the reference group. The mean indirect cost was $19,618 and $5905, respectively. Mean cost for healthcare was $8998 for the AS patients and $4187 for the reference subjects, and mean cost for drugs was $8479 and $979, respectively. The patients with AS treated with biological therapy constituted 80% of the total drug cost, but just 40% of the cost for disability pension. CONCLUSION: Patients with AS had 3-fold increase in costs compared to reference subjects from the general population, and the drug costs were almost 10 times as high. Production losses (indirect cost) represented more than half of total cost (53%).

The article presents a study which tested fungicides, insecticides, miticides, and a herbicide on predatory mites in vineyards. Researchers from Victoria, South Australia and New Zealand selected Euseius victoriensis and Galendromus occidentalis for laboratory tests. They assesses the mortality and fertility of predatory mites after application of chemical treatment. The toxicity of the chemicals are also tested in the laboratory and in the vineyard.

To investigate long-term resource consumption and clinical outcome of patients with early primary open-angle glaucoma or ocular hypertension treated with prostaglandins in clinical practice in France.

Die Behandlung von Patienten mit Migrationshintergrund gewinnt im Kontext psychosomatischer Rehabilitation zunehmend an Bedeutung. Dabei stellt die Gruppe der türkischstämmigen Personen die größte Migrantengruppe dar. Erste Befunde weisen den Faktor Migrationshintergrund als negativen Prädiktor des Behandlungserfolges aus, die spezifischen Hemm- und Förderfaktoren dieser Patientengruppe sind jedoch nur unzureichend untersucht. Der vorliegende Beitrag klärt anhand einer Stichprobe von 521 Patienten einer psychosomatischen Rehabilitationseinrichtung, ob sich deutsch- und türkischstämmige Patienten in Bezug auf Ausgangsvoraussetzungen sowie Behandlungserwartungen und -erfolg unterscheiden. Hierbei zeigt sich, dass die türkische Migrantengruppe nicht nur schlechtere Behandlungsergebnisse aufweist als die deutsche Kontrollgruppe, sondern sich auch in den Störungsbildern und nahezu allen Ausgangsbedingungen unterscheidet (z. B. bildungs- und erwerbsbezogenen Angaben, den Lebensformen und Rentenbestrebungen).

Die psychosomatische Rehabilitation von Migranten ist in vielen Fällen nicht erfolgreich. Neben der sprachlichen Barriere wird die sozialmedizinische Situation, die Somatisierungstendenz, aber auch der häufig zu späte Zeitpunkt der Behandlung zur Erklärung herangezogen, dass Migranten sich bei Aufnahme in eine psychosomatische Rehabilitationsklinik bereits in einem fortgeschrittenen Desintegrationsprozess befinden. Fragestellung und Methodik: Es wird untersucht, welche Vorhersagevalidität der Migrationshintergrund für die subjektive Prognose der Erwerbstätigkeit unter Berücksichtigung persönlicher und umweltbezogener Faktoren hat. 640 Rehabilitanden wurden zu Beginn der stationären Rehabilitation hinsichtlich ihrer Beschwerdebelastung, ihrer Arbeitsmotivation, zum Mobbingerleben und zur subjektiven Prognose der Erwerbstätigkeit befragt. Ergebnisse: 28.5 % der Rehabilitanden hatten einen Migrationshintergrund. Die subjektive Prognose der Erwerbstätigkeit war vom Ausmaß der Beschwerdebelastung und der Motivation, sich mit arbeitsbezogenen Problemen auseinanderzusetzen, abhängig. Gleichzeitig erhöhte die Unterschichtzugehörigkeit das Risiko einer negativen Prognose. Der Einfluss des Migrationshintergrundes dagegen hatte eine nachgeordnete Bedeutung. Diskussion: Zur Verbesserung der Rehabilitationsprognose müssen persönliche und Umweltfaktoren unabhängig vom Migrationsstatus im Rehabilitationsplan berücksichtigt werden. Ein kultursensibles und arbeitsplatzbezogenes Fallmanagement könnte die Versorgung von Migranten zielführend verbessern.

Purpose This study describes the treatment in ordinary clinical practice in Spain of patients with glaucoma with a two-drug combination therapy. The authors present the treatment outcome as end-of-period intraocular pressure (IOP) and the calculated direct medical costs over a 2-year period.Methods Data were extracted retrospectively from patient charts recording the use of all medical resources related to glaucoma. Costs were estimated using unit costs from public sources (2005). Descriptive cost analysis according to combination treatment at baseline was performed.Results The study included 216 patients from 21 centers. Around half of the patients were started on a β-blocker/prostaglandin analogue combination, while the rest received various other combinations containing either an α2-agonist or a carbonic anhydrase inhibitor. Across the seven groups considered, there was a statistically significant difference in the costs of the least and the two most costly groups, while the confidence intervals were overlapping in all other pairwise comparisons. The least costly drug combination was brimonidine/timolol. Assessing IOP at the end of follow-up, all the groups were equally effective (overlapping confidence intervals). In a multivariate regression analysis, the drug combination did not have an independent, significant impact on total direct medical costs, drug costs, or end-of-period IOP. Significant determinants of these variables were surgical interventions and one or more changes of drug combination during the follow-up.Conclusions Costs are determined by the response to treatment. Inadequate response triggers treatment changes and sometimes eventually surgical interventions, thereby increasing costs significantly.

The serine/threonine protein kinase Sgk1 (serum- and glucocorticoid-inducible kinase 1) is characterized by a short half-life and has been implicated in the control of a large variety of functions in different subcellular compartments and tissues. Here, we analysed the influence of the N-terminus of Sgk1 on protein turnover and subcellular localization. Using green fluorescent protein-tagged Sgk1 deletion variants, we identified amino acids 17–32 to function as an anchor for the OMM (outer mitochondrial membrane). Subcellular fractionation of mouse tissue revealed a predominant localization of Sgk1 to the mitochondrial fraction. A cytosolic orientation of the kinase at the OMM was determined by in vitro import of Sgk1 and protease protection assays. Pulse–chase experiments showed that half-life and subcellular localization of Sgk1 are inseparable and determined by identical amino acids. Our results provide evidence that Sgk1 is primarily localized to the OMM and shed new light on the role of Sgk1 in the control of cellular function.

The sheep grazing tolerance of a diverse range of lucerne germplasm (Medicago sativa subspp. sativa, falcata and caerulea) was investigated at Roseworthy in South Australia. Lucerne entries were established on a sandy loam soil in 1998 and managed with rotational grazing management for the first 12 months. Continuous grazing by sheep in the following year reduced the plant density of each entry as measured by plant frequency estimates by 2?98%. Lucerne was allowed to recover, then grazed continuously for another 12 months. There was great diversity in tolerance to sheep grazing among the entries tested, with final plant frequency ranging from 0?13% for highly winter-active entries, 7?23% (at least 7?23 plants/m2) for winter-active entries and 11?40% for winter dormant entries. A grazing tolerance index of commercial cultivars was determined by comparing their plant frequency decline under continuous grazing to that under rotational grazing in an adjacent experiment. Australian-bred highly winter-active cultivars displayed a greater level of tolerance than those developed overseas. The superior performance of several breeders' lines in the continuously grazed trial indicates there is further scope for improvement with selection and breeding.

To investigate the effect of different levels of visual field defect in glaucoma on utilities and to test if utilities could be assessed using a general questionnaire such as the EQ‐5D.

To estimate current costs and quality of life (utility) of patients treated with disease modifying drugs (DMDs) in the United States, and to investigate the effect of disease severity on costs and utility.

OBJECTIVE:. To estimate the cost-effectiveness of the treatment of ankylosing spondylitis (AS) with infliximab (Remicade®) in Canada over the long term, with both international and Canadian treatment regimens. METHODS: A previously published disease model based on functional capacity and disease activity was adapted to the Canadian setting. Current resource consumption from a cross-sectional bottom-up burden-of-illness study in 545 patients at different levels of severity of AS in 4 Canadian provinces was incorporated into the model. Cost-effectiveness estimates were based on a 3-month placebo-controlled clinical trial with 2-year open extension as well as a 4-year followup study of clinical practice in Canada. In the cost-effectiveness model, patients with insufficient response to treatment at 12 weeks (≥ 50% reduction in Bath Ankylosing Spondylitis Disease Activity Index) discontinue treatment. In view of the long disease duration, simulations over a 30-year timeframe were performed, incorporating disease progression from cohort studies and assumptions about treatment continuation beyond the clinical trial from the trial extension period. Results are presented in Canadian dollars, from the societal and healthcare payer perspectives, with both costs and effects discounted at 5%. RESULTS: Over a 30-year timeframe, with the assumption that patients' disease would remain stable while on treatment, the cost per quality-adjusted life-year (QALY) gained in the societal perspective is $37,491, using the treatment regimen in the clinical trial (5 mg/kg every 6 weeks). Using the dosing regimen of the Canadian study (75% at 3 mg/kg every 8 weeks, 15% at 3 mg/kg every 6 weeks, and 10% at 5 mg/kg every 8 weeks) the cost per QALY is $10,264. Assuming that patients on treatment progress at half the rate of untreated patients, the cost-effectiveness ratios are $45,121 and $13,883, respectively, while the most conservative assumption that progression is the same in both arms, the ratios are $54,137 and $18,712, respectively. The results are sensitive to the dosing regimen adopted, the discontinuation rate, and assumptions concerning disease progression while on treatment. CONCLUSION: Our results indicate that infliximab therapy for patients with active AS would be cost-effective (ranges $10,264–$54,137 per QALY) in a Canadian setting.

OBJECTIVE:. The use of biological agents in the treatment of ankylosing spondylitis (AS) has emphasized the need for information about the current burden of the disease to estimate the cost-effectiveness of these drugs. We investigated resource utilization and utility of patients with AS in Canada. METHODS: A cross-sectional retrospective observational study was performed in a cohort of 545 patients with AS in Alberta, Ontario, British Columbia, and Manitoba. Patients completed a questionnaire asking about their healthcare consumption, out of pocket expenses, work capacity, and need for informal care during the past 3 months. Patients' current functional status and disease activity level was assessed using the Bath AS functional and disease activity indexes (BASFI and BASDAI), and utility was determined using the EQ-5D 5-dimensional health status classification. Descriptive analysis was performed to estimate costs and utility for the sample and by level of disease severity. RESULTS: Patients' mean age was 49.6 years and the mean disease duration was 22.3 years; 64% were male, and 63% of patients in the sample were working. The mean BASDAI score was 4.3 and BASFI 3.6, although 13% of patients in the sample had a BASFI score ≥ 7. The mean annual cost per patient is estimated at Cdn $9,008 (SD $17,724), and direct healthcare represented 28.9% of these costs. Patients' out of pocket costs represented 33.1%, and lost work capacity accounted for 38%. Costs increased significantly with diminishing physical function and high disease activity, covering a range of $4,000 to $30,000 per patient and year. The estimated cost-increase per unit-increase in the BASFI score at values < 5 was around $1,000, and more than $5,000 at values > 7. The mean utility was 0.65 (SD 0.23). Utility was significantly correlated with age, sex, BASFI, and BASDAI, covering a range from 0.87 for patients with BASFI/BASDAI ≤ 2 to 0.20 for patients with BASFI/BASDAI ≥ 8. On average, utility decreased by 0.075 for each unit-increase in the BASFI. CONCLUSION: All types of costs accelerate steeply with increasing loss of function (BASFI) and disease activity (BASDAI) in patients with AS, while utility decreases significantly. Treatments that control disease activity and maintain patients' function are likely to offset the high cost and low quality of life of severe disease. Our findings provide information on the burden of AS and a baseline for assessing the cost-effectiveness of the new biological agents in this indication.

We have measured the rotational energy distribution of benzene molecules both evaporated and desorbed by an IR laser from a liquid microjet. Analysis of the 601 vibronic band of benzene has shown that the benzene molecules evaporating from the liquid microjet surface have a rotational temperature of 157 7 K. In contrast, the rotational temperature of benzene molecules desorbed from the liquid microjet by a 1.9 ?m laser pulse is 82 5 K. However, in both cases careful inspection of the spectral profiles shows that the experimental rotational distributions are non-Boltzmann, displaying an underpopulation of high rotational states and a relative overpopulation of the low rotational states. The non-equilibrium evaporation and desorption spectral profiles are consistent with a model that involves transfer of internal energy into translation upon liberation from the condensed phase.

Objective. When treatments with the potential to change the natural history of a disease are introduced, their longer-term effect on costs and quality of life (utility) has to be estimated using economic models. However, to remain useful tools, models must be updated when new information becomes available. Our earlier models in rheumatoid arthritis (RA) have been based on functional status, but it has recently been shown that disease activity might have an independent effect on utility. The objective of this study was to improve the model by incorporating the effect of a subjective measure of disease severity and activity (global VAS).Methods. A Markov model was constructed with five states according to functional status (HAQ), and each state was subdivided according to the VAS (<40 and >40). Disease development (transition probabilities between the states) was taken from a longitudinal cohort study of patients with early RA in Sweden. A recent population-based survey of 616 patients with RA provided data on costs and utilities. The model incorporates the full distribution of costs and utilities from the survey, and long-term projections are made using Monte Carlo simulation.Results. The global VAS had a highly significant effect on utilities independently of HAQ. For resource consumption, only HAQ was a significant predictor, with the exception of sick leave, which was correlated with the VAS but not with HAQ. Using the cohort distribution from the longitudinal study, expected mean costs per patient over 10 yr were 106 034 euros (s.d. 5091 euros) (1 euro = SEK 9.20) and the expected number of quality-adjusted life years (QALYs) was 5.08 (s.d. 0.09). Patients starting at HAQ <0.6 but with consistently high VAS scores would have expected costs of 102 830 euros and 4.96 QALYs, while patients with low VAS scores would have costs of 81 603 euros and 6.01 QALYs.Conclusion. Our new model incorporates for the first time the effect of a subjective measure of disease severity and activity on both costs and utility, making it a sensitive tool to estimate the cost-effectiveness of disease-modifying treatments. New data on resource consumption indicate a shift to higher direct costs, particularly in early disease, and lower indirect costs in more advanced disease. The large size of the data sets used in this model reduces the uncertainty and makes estimates very stable.

This paper is the fifth in a series describing trials evaluating native and introduced grasses at eight locations across temperate Australia. In these trials, 62 perennial grass lines were assessed for herbage production, survival and recruitment under low fertiliser conditions using spaced plants produced in glass houses and transplanted into the field. Sites were grouped into three different climatic zones: Eastern Australian permanent pasture, Eastern Australian mixed farming and Mediterranean zone. For each of these zones, superior lines were identified and their potential use in permanent pastures or mixed farming discussed.  Among the C3 grasses tested, several lines of Dactylis glomerata from France on the Mediterranean coast near the Spanish border and from north-west maritime France proved to be superior lines in all zones and were better than the standard comparator cv. Currie with regard to the attributes assessed. In general, the D. glomerata lines were superior to the C3 native species except with respect to survival and recruitment.  The C4 introduced standard comparator Eragrostis curvula cv. Consol was outstanding with regard to its herbage production and survival in all climatic zones, although its recruitment was generally low. Native C4 lines of Themeda australis and Paspalidium jubiflorum yielded well in all climatic zones, and even produced more herbage than Consol in one zone. Survival rates of T. australis and P. jubiflorum were also very high but recruitment was low under the conditions of the trial.  In mixed pastures C4 grasses may reduce fluctuations in feed supply as well as increase water use. As a consequence mixtures of superior C3 and C4 lines identified in this study are likely to be suitable for pastures on infertile soils and in zones subjected to continuous or periodic drought.  Further work on the behaviour of these superior lines under sward conditions in association with forage legumes and their responses to grazing is needed; however, for the promising native lines, sward trials are not possible until suitable technology for commercial seed production and broad acre establishment of these lines has been developed.

A total of 62 perennial grasses were evaluated for herbage production under low-fertiliser conditions at eight sites in the temperate zone of southern Australia from 1999 to 2001. A brief assessment of relative preference ranking by sheep was also made at the end of the experimental period. Four sites were in the high rainfall areas of south-east Australia, two in the drier mixed farming areas of western NSW, and two sites in Mediterranean southern Australia. Seven standard cultivars were included in the comparisons. Plants were grown from seed in glasshouses and transplanted to the field as spaced plants at 6?8 weeks age. Plants were harvested at irregular intervals by clipping to determine herbage production. Relative preference was determined by enclosing sheep in the experimental area at high stocking rates and estimating the amount of herbage grazed after 1, 3 and 5 days.  Herbage production data were analysed using a multi-environment trial approach in which the environments comprised all combinations of sites and sampling times over the 3-year period. Overall, 73.6% of the total genetic variation for herbage production was accounted for. Average seasonal comparisons revealed good herbage production from Eragrostis curvula cv. Consol in both winter and summer, but in spring, several Dactylis glomerata lines were the most productive. Consol was not generally preferred by sheep, while D. glomerata lines were. Apart from cv. Consol, C4 species, including Bothriochloa macra, Chloris truncata, Enteropogon acicularis and Dichanthium sericeum had low herbage production in winter and spring, and had low acceptability to grazing sheep. These particular grasses were also not highly ranked for production in summer, although other C4 lines, notably selections of Themeda australis, Paspalidium jubiflorum and P. constrictum were. Few native C3 grasses had superior herbage production, although selections of Elymus scaber, Austrodanthonia fulva and A. duttoniana showed good growth rates. When considering further evaluation, grasses with very high recruitment (e.g. A. caespitosa) may need to be included, and the acceptability of grasses to sheep should also be assessed.

This paper describes the experimental methodology, sites, seasonal conditions and germplasm used in the Australian Native and Low Input Grass Network (NLIGN). In 1998, eight sites were established across the temperate pastoral zone of southern Australia. These were located at Armidale, Binya, Sutton and Trangie in NSW; Springhurst in Victoria; Jericho in Tasmania; Flaxley in South Australie and Kendenup in Western Australia. A total of 62 lines were evaluated, of which, 29 were Australian native grasses and 33 were introduced. With differences in seed size among species and a lack of information on dormancy and germination characteristics of the native plants, seedlings were transplanted into the field on weed-mat as spaced plants. Lines were compared over a 3-year period from 1998 to 2001. Methods used for determination of forage production, persistence and palatability are described. Information detailing the original collection sites of the germplasm, a list of NLIGN sites where each genotype was evaluated, as well as a detailed description of sites and seasonal conditions is also presented.

Objectives. In the past, treatment options for ankylosing spondylitis (AS) have been limited, and the introduction of new treatments such as infliximab will have a noticeable impact on health-care budgets. The objective of this study was therefore to assess the current burden of the disease and estimate the cost-effectiveness of infliximab treatments.Methods. A cross-sectional retrospective observational study of resource consumption and utility related to disease severity was performed in patients who had participated in a population survey between 1992 and 1994 at the University of Bath and patients regularly followed at the Royal National Hospital for Rheumatic Diseases in Bath for up to 9 years. Mean costs and utility were estimated using a regression model including age, gender, disease duration, disease activity and functional status, and disease development was expressed as annual progression of functional disability. Cost-effectiveness of infliximab was modelled using a 3-month placebo-controlled clinical trial with open 1-yr extension in 70 patients, over a total time frame of 2 yr. In the model, costs and utility controlled for disease severity and age from the observational study were assigned to individual patients. The effect of long-term treatment was evaluated in a hypothetical model over 30 yr.Results. Fifty-seven per cent of patients answered the questionnaires. The mean age was 57 (s.d. 11.2) yr, 74% were male and mean disease duration was 30.2 (11.7) yr. Mean total costs were estimated at £6765 (s.d. £166). Indirect costs represented 57.9% and non-medical costs such as investments and informal care accounted for 16.5% of total costs. Mean utility was 0.67 (0.21). In the main model, mean costs for untreated patients are estimated at £25,128. For the infliximab group, mean costs (excluding treatment) are estimated at £17,240, a reduction of 31%. Thus, part of the treatment cost was offset by savings in other resources (£7888), leaving an incremental cost of £6214. Treatment increased the number of quality-adjusted live years (QALYs) by 0.175 QALYs, leading to a cost per QALY gained of £35,400 for the first year of treatment. When treatment is assumed to continue for the full 2 yr, the cost per QALY is £32,800. When infliximab infusions are given every 8 weeks instead of every 6 weeks, the cost per QALY is reduced to £17,300. In the long-term model, the cost per QALY is estimated at £9600.Conclusions. Non-medical costs and production losses dominate costs in AS, and economic evaluation must therefore adopt a societal perspective. The cost of treatment with infliximab is partly offset by reductions in the cost of the disease and patients’ quality of life is increased, leading to a cost per QALY gained in the vicinity of £30,000 to £40,000 in the short term, but potentially below £10,000 in the long term.

The study was carried out to compare the overall effectiveness and direct economic costs of vaginal hysterectomy (VH), endometrial ablation (EA) and thermo-coagulation (TC) for the treatment menorrhagia.

Objective. The cost per quality‐adjusted life‐year (QALY) of infliximab (Remicade®) treatment in rheumatoid arthritis (RA) was estimated on the basis of a clinical trial comparing infliximab plus methotrexate with methotrexate alone in 428 patients with advanced disease [Anti‐Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT)].Methods. The effect of infliximab on disease progression and related costs and utilities was estimated using two disease progression models based on epidemiological cohorts followed for up to 15 yr in Sweden and the UK. The clinical trial data were used directly in the model and extrapolated to 10 yr using a cohort from the epidemiological studies matched for gender, age, time since onset of RA and disease severity.Results. One to two years of treatment with infliximab treatment reduced direct and indirect resource consumption in both countries, thereby partly offsetting the treatment cost. In the base case, including both direct and indirect costs, the cost per QALY gained was SEK 32 000 (&euro;3440) in Sweden and GBP 21 600 (&euro;34 800) for 1 yr of treatment. The respective QALY gains were 0.248 and 0.298. With 2 yr of treatment, the costs per QALY gained were SEK 150 000 (&euro;16 100) and GBP 29 900 (&euro;48 200).Conclusions. Although 1–2 yr of treatment with infliximab will lead to savings in both direct and indirect costs, these will not offset the drug cost. However, the cost‐effectiveness ratios remain within the usual range for treatments to be recommended for use.

Vesicoureteral reflux is a risk factor for progressive renal damage associated with urinary tract infection. Mild to moderate reflux is routinely treated with long-term antibiotic prophylaxis to prevent recurrent infections and open surgical reimplantation for breakthrough infections despite antibiotic therapy. Endoscopic subureteral injection of implant material is a therapeutic alternative to long-term prophylaxis and open surgery but its widespread use in the United States has been prevented by the lack of a stable implant material. Dextranomer/hyaluronic acid copolymer has been shown to be a safe, effective and durable implant material and was recently approved in the United States. We estimate the effect on costs and cure rates of introducing endoscopic injection with dextranomer/hyaluronic acid copolymer as a treatment alternative in the United States.

Glaucoma has not received a great deal of attention from health economists in the past, partly due to the fact that no new treatments have been introduced for some time. Economic evaluation is generally performed for new technologies, to assess their cost-effectiveness compared with current treatments, to estimate the potential changes in the use of health care resources that their introduction may produce, and to make decisions about their reimbursement status and formulary inclusion. Economic studies in glaucoma have been largely limited to studies about cost, because a useful outcome measure has been lacking. Therapy aims at reducing intraocular pressure, but the data to estimate the absolute risk of vision loss due to high pressure have been lacking. Hence, it has been impossible to assess the benefit of treatments in terms of their ability to reduce blindness. However, as new out knowledge about these issues increases and more data become available, such studies become possible. This review illustrates the issues encountered when performing economic evaluation in glaucoma and reviews the current economic literature in the field.

Two simulation models were developed to analyze the cost-effectiveness of new treatments that affect the progression of rheumatoid arthritis (RA). We used data from 2 cohorts of patients with early RA who had been followed up since disease onset (up to 15 years). In the Swedish study, 183 patients were followed up for a mean of 11.3 years. In the UK study, 916 patients were followed up for a mean of 7.8 years. Disease progression over 10 years was modeled as annual transitions between disease states, defined by Health Assessment Questionnaire (HAQ) scores. A regression model was used to estimate transition probabilities conditional on age, sex, and time since onset of disease, in order to allow simulation of different patient cohorts. Costs and utilities associated with different HAQ levels were based on data from the cohort studies and cross-sectional surveys. Costs increase and quality of life decreases as RA progresses. In Sweden, total annual costs range from $4,900 to $33,000 per patient, compared with $4,900 to $14,600 in the UK. Cumulative costs over 10 years for patients starting in disease state 1 (HAQ &lt; 0.6) are $54,600 in Sweden and $26,600 in the UK. The cumulative numbers of quality-adjusted life-years (QALYs) are 5.5 and 5.6, respectively. Both costs and QALYs were discounted at 3%. The 2 models, which were based on different patient cohorts, reach a similar conclusion in terms of the effect of RA over 10 years. They appear to accurately capture disease progression and its effects and can therefore be useful in estimating the cost-effectiveness of new treatments in RA.

Objectives: Different cost-effectiveness analyses have been presented for interferon beta-1b (IFNB) in the treatment of secondary progressive multiple sclerosis (SPMS). All studies have used modeling techniques since any effect on progression of disability achieved during a clinical trial will last beyond the trial. Different approaches to extrapolation have been taken, but generally they have been based on disease progression and relapse rates in clinical trials. The problem with this approach is that the population in clinical trials is a selected group of patients, which has the potential to bias results. A better method for extrapolation is to use epidemiologic data. The objective of this study is to incorporate natural history data for MS into a previously presented cost-utility model and to compare the two methods of extrapolation. Methods: Clinical trial data were used to model disease progression during the first 3 years in the model. To extrapolate beyond the trial (10 years), data on progression of disability were available from a geographically based epidemiologic study of the natural history of MS in Canada. There were 568 patients who had converted to SPMS during the follow-up that were included in the data set. Mean costs and utilities for each Markov state were calculated from a population-based cross-sectional study in Sweden. Results: The extrapolation using clinical trial data appears to have underestimated the progression of disability in the long term and thus also the potential benefit of treatment. Using the epidemiologic data, the incremental cost per QALY is SEK 257,000 (US $25,700; US $1 = SEK 10; November 2000) when all costs (direct, informal care, and indirect) are included (discounted 3%). This compares to SEK 342,000 in the previous model. The lower cost-effectiveness ratio is mostly due to a larger QALY gain with treatment than in the previous model (0.217 compared with 0.162). Conclusion: Cost-effectiveness analysis in SPMS requires that the effect of treatment beyond clinical trials be included. The method of extrapolation clearly affects the results, and when available, epidemiologic data should be used. Using the longitudinal data from Canada, the cost-utility ratios for IFNB-1b in the treatment of SPMS appear well within the acceptable range.

Purpose To develop a method to estimate the cost per quality-adjusted life year (QALY) gained with cataract surgery using large patient registries. Setting Four centers in Sweden. Methods Five hundred patients scheduled for cataract extraction in 1 eye at 1 of 4 centers in Sweden during March 1999 were asked to complete the EQ-5D, a preference-based quality-of-life instrument, and the Catquest, a disease-specific disability measure, before surgery. Multiple regression analysis was used to study the correlation between utility and visual acuity and/or disability and utility and QALY gain through the intervention estimated. Results Visual acuity and Catquest scores were available for 484 patients. The mean age was 76.1 years; the mean logMAR visual acuity was 0.59 in the surgical eye and 0.26 in the other eye. The mean Catquest disability score was 13.79 and the mean utility, 0.74. Utilities correlated significantly with visual acuity and disability scores, and the correlations remained significant when both were included in a regression model, indicating that the 2 measure different concepts. The hypothetical cost per QALY gained (discounted at 3%) was estimated at 45 000 SKr (4500 US$) using the Swedish Cataract Registry. Conclusions The results indicate that visual acuity and visual disability significantly affect utilities controlled for age and ophthalmic comorbidity. It is thus possible to use data on visual acuity and disability in large registries to estimate the cost-effectiveness of cataract surgery and to compare the cost per QALY gained with other health care interventions.

Objectives: Interferon beta-1b has recently become available for the treatment of secondary progressive multiple sclerosis (SPMS). This study aims at estimating the cost-effectiveness of this new treatment that has been shown in a clinical trial to reduce the progression of the disease. Effectiveness is measured as the number of quality-adjusted life-years (QALYs) gained from the reduction in progression. Because the clinical trial period will only capture part of the treatment's effect in terms of QALYs gained, since benefits achieved during the trial will have an effect beyond it, the cost-effectiveness analysis involves modeling over the longer term using complementary data. Methods: A Markov model with states based on disability expressed by EDSS scores was used. Transition probabilities were calculated directly from clinical trial data for the first 3 years and then extrapolated to 10 years. Mean costs and utilities for each Markov state were calculated from a population-based cross-sectional study in Sweden. Results: The incremental cost per QALY is SEK 342,700 (US $39,250;US $1 =

The obligate biotrophic pathogen Plasmodiophora brassicae induces cataplastic galls in the roots of various species of the Brassicaceae. The ecotypes Ze-0, Tsu-0, and Ta-0 of Arabidopsis thaliana carry alleles of a dominant single gene (RPB1) for resistance against this pathogen. The pathotype-specific resistance reactions in the roots were accompanied by a hypersensitive response. Infected cells were surrounded by necrotic boundaries and thereby the pathogen growth was restricted. The pathogen could induce hyperplasia and hypertrophy to a slight extent and develop spores within mini-galls surrounded by the necrotic cells, if it was able to colonise meristematic tissue. Ecotype Ze-0 showed the highest level of resistance to P. brassicae isolate ‘e’ as indicated by the very limited number of infected cells, whereas the resistance of the ecotype Ta-0 was rated lower. The results are discussed in relation to the interaction of the pathogen with Brassica crops.

The expression of nitrilase in Arabidopsis during the development of the clubroot disease caused by the obligate biotroph Plasmodiophora brassicae was investigated. A time course study showed that only during the exponential growth phase of the clubs was nitrilase prominently enhanced in infected roots compared with controls. NIT1 and NIT2 are the nitrilase isoforms predominantly expressed in clubroot tissue, as shown by investigating promoter-beta-glucuronidase fusions of each. Two peaks of beta-glucuronidase activity were visible: an earlier peak (21 d post inoculation) consisting only of the expression of NIT1, and a second peak at about 32 d post inoculation, which predominantly consisted of NIT2 expression. Using a polyclonal antibody against nitrilase, it was shown that the protein was mainly found in infected cells containing sporulating plasmodia, whereas in cells of healthy roots and in uninfected cells of inoculated roots only a few immunosignals were detected. To determine which effect a missing nitrilase isoform might have on symptom development, the P. brassicae infection in a nitrilase mutant (nit1-3) of Arabidopsis was investigated. As a comparison, transgenic plants overexpressing NIT2 under the control of the cauliflower mosaic virus 35S promoter were studied. Root galls were smaller in nit1-3 plants compared with the wild type. The phenotype of smaller clubs in the mutant was correlated with a lower free indole-3-acetic acid content in the clubs compared with the wild type. Overexpression of nitrilase did not result in larger clubs compared with the wild type. The putative role of nitrilase and auxins during symptom development is discussed.

To develop a simulation model for analysis of the cost-effectiveness of treatments that affect the progression of rheumatoid arthritis (RA). The Markov model was developed on the basis of a Swedish cohort of 116 patients with early RA who were followed up for 5 years. The majority of patients had American College of Rheumatology (ACR) functional class II disease, and Markov states indicating disease severity were defined based on Health Assessment Questionnaire (HAQ) scores. Costs were calculated from data on resource utilization and patients' work capacity. Utilities (preference weights for health states) were assessed using the EQ-5D (EuroQol) questionnaire. Hypothetical treatment interventions were simulated to illustrate the model. The cohort distribution among the 6 Markov states clearly showed the progression of the disease over 5 years of followup. Costs increased with increasing severity of the Markov states, and total costs over 5 years were higher for patients who were in more severe Markov states at diagnosis. Utilities correlated well with the Markov states, and the EQ-5D was able to discriminate between patients with different HAQ scores within ACR functional class II. The Markov model was able to assess disease progression and costs in RA. The model can therefore be a useful tool in calculating the cost-effectiveness of different interventions aimed at changing the progression of the disease.

Oculo-facio-cardio-dental syndrome is a very rare condition. So far, only nine cases have been documented. We report on three additional female patients representing the same entity. The clinical findings were: congenital cataract, microphthalmia/microcornea, secondary glaucoma, vision impairment, ptosis, long narrow face, high nasal bridge, broad nasal tip with separated cartilages, long philtrum, cleft palate, atrial septal defect, ventricular septal defect, and skeletal anomalies. The following dental abnormalities were found: radiculomegaly, delayed dentition, oligodontia, root dilacerations (extension), and malocclusion. For the first time, fusion of teeth and hyperdontia of permanent upper teeth were seen. In addition, structural and morphological dental changes were noted. These findings expand the clinical spectrum of the syndrome. Am. J. Med. Genet. 82:429–435, 1999. © 1999 Wiley-Liss, Inc.