Biomedical subjects

C Bakker

Publications and source records attributed to C Bakker.

At least 19 recordsLinked to original sources

PubMed2003

Does resource availability, resource heterogeneity or species turnover mediate changes in plant species richness in grazed grasslands?

Grazing by large ungulates often increases plant species richness in grasslands of moderate to high productivity. In a mesic North American grassland with and without the presence of bison ( Bos bison), a native ungulate grazer, three non-exclusive hypotheses for increased plant species richness in grazed grasslands were evaluated: (1) bison grazing enhances levels of resource (light and N) availability, enabling species that depend on higher resource availability to co-occur; (2) spatial heterogeneity in resource availability is enhanced by bison, enabling coexistence of a greater number of plant species; (3) increased species turnover (i.e. increased species colonization and establishment) in grazed grassland is associated with enhanced plant species richness. We measured availability and spatial heterogeneity in light, water and N, and calculated species turnover from long-term data in grazed and ungrazed sites in a North American tallgrass prairie. Both regression and path analyses were performed to evaluate the potential of the three hypothesized mechanisms to explain observed patterns of plant species richness under field conditions. Experimental grazing by bison increased plant species richness by 25% over an 8-year period. Neither heterogeneity nor absolute levels of soil water or available N were related to patterns of species richness in grazed and ungrazed sites. However, high spatial heterogeneity in light and higher rates of species turnover were both strongly related to increases in plant species richness in grazed areas. This suggests that creation of a mosaic of patches with high and low biomass (the primary determinant of light availability in mesic grasslands) and promotion of a dynamic species pool are the most important mechanisms by which grazers affect species richness in high productivity grasslands.

Animals↗

PubMed2003

Sulfidogenic volatile fatty acid degradation in a baffled reactor.

The effect of staging the sludge bed on volatile fatty acid degradation by sulfidogenic reactors was evaluated in a baffled reactor. In a 5.4 l baffled reactor, containing three equal compartments, a volatile fatty acid (VFA) mixture (acetate:propionate:butyrate ratio 1:2:2 on COD basis; pH 8) was treated under mesophilic (30 degrees C) and sulfidogenic (COD:SO4(2-) ratio: 0.5) conditions for 38 days. At a specific sludge loading rate of 0.50 g COD.gVSS(-1) x d(-1), a COD and sulfate removal of 85% and 30%, respectively, was obtained. In the baffled reactor, staging of the sulfidogenic VFA degradation occurred. Propionate and butyrate were mainly degraded in the first compartment. Their degradation was incomplete, resulting in elevated acetate concentrations in compartment I. In the second and third compartment of the baffled reactor, a net degradation of acetate took place. Acetate was the sole substrate present in compartment III and residual acetate concentrations of about 200 mg/l were present in the effluent at a specific sludge loading of 0.50 g COD x gVSS(-1) x d(-1). Sludges with different maximum specific VFA and acetate degrading activities developed in the first and second compartment. These maximal specific activities were almost equal for sludge present in compartment II and III.

Acetates↗

PubMed2000

The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins.

Fragile X syndrome is caused by the absence of the fragile X mental-retardation protein (FMRP). FMRP and the fragile X-related proteins 1 and 2 (FXR1P and FXR2P) form a gene family with functional similarities, such as RNA binding, polyribosomal association and nucleocytoplasmic shuttling. In a previous study, we found that FMRP and FXR1P shuttle between cytoplasm and nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. The nuclear and nucleolar-targeting properties of these proteins were investigated further. Here, we show that FXR2P contains in its C-terminal part, a stretch of basic amino acids 'RPQRRNRSRRRRFR' that resemble the nucleolar-targeting signal (NoS) of the viral protein Rev. This particular sequence is also present within exon 15 of the FXR1 gene. This exon undergoes alternative splicing and is therefore only present in some of the FXR1P isoforms. We investigated the intracellular distribution of various FXR1P isoforms with (iso-e and iso-f) and without (iso-d) the potential NoS in transfected COS cells treated with the nuclear export inhibitor leptomycin-B. Both iso-e and iso-f showed a nucleolar localization, as observed for FXR2P; iso-d was detected in the nucleo-plasm outside the nucleoli. Further, when a labelled 16-residue synthetic peptide corresponding to the NoS of FXR1P was added to human fibroblast cultures a clear nucleolar signal was observed. Based on these data we argue that the intranuclear distribution of FXR2P and FXR1P isoforms is very likely to be mediated by a similar NoS localized in their C-terminal region. This domain is absent in some FXR1P isoforms as well as in all FMRP isoforms, suggesting functional differences for this family of proteins, possibly related to RNA metabolism in different tissues.

Amino Acid Sequence↗

PubMed2000

Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome.

PURPOSE: To evaluate their susceptibility to audiogenic seizures, five groups of knockout mice with various forms of fragile X genetic involvement [hemizygous males (n = 46), and homozygous (n = 38) and heterozygous females (n = 45), and their normal male (n = 45) and female (n = 52) littermates] were studied. METHODS: All mouse groups were tested at ages 17, 22, 35, and 45 days. Audiogenic seizure susceptibility was scored, and the analysis of variance was used for the evaluation of the effects of age and genetic condition on seizure severity score (SSS). RESULTS: All groups of knockout fragile X mice exhibited SSSs significantly higher than those observed in their wild-type littermates; among knockout mice, hemizygous males and homozygous females showed the highest SSSs. Hemizygous males showed higher SSSs with increasing age, from 17 to 45 days; homozygous females showed a peak at age 22 days, followed by a decrease; finally, heterozygous females had their highest SSSs at age 17 days. CONCLUSIONS: This study demonstrates that an increased susceptibility to audiogenic seizures is present in fragile X knockout mice at all the ages tested. These results support the validity of this animal model also for epilepsy and seizures in the human fragile X syndrome.

Acoustic Stimulation↗

PubMed1999

Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P.

The absence of fragile-X mental-retardation protein (FMRP) results in fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been described, FXR1P and FXR2P, which are both very similar in amino acid sequence to FMRP. Interaction between the three proteins as well as with themselves has been demonstrated. The FXR proteins are believed to play a role in RNA metabolism. To characterize a possible functional role of the interacting proteins the complex formation of the FXR proteins was studied in mammalian cells. Double immunofluorescence analysis in COS cells over-expressing either FMRP ISO12/FXR1P or FMRP ISO12/FXR2P confirmed heterotypic interactions. However, Western-blotting studies on cellular homogenates containing physiological amounts of the three proteins gave different indications. Gel-filtration experiments under physiological as well as EDTA conditions showed that the FXR proteins were in complexes of >600 kDa, as parts of messenger ribonuclear protein (mRNP) particles associated with polyribosomes. Salt treatment shifted FMRP, FXR1P and FXR2P into distinct intermediate complexes, with molecular masses between 200 and 300 kDa. Immunoprecipitations of FMRP as well as FXR1P from the dissociated complexes revealed that the vast majority of the FXR proteins do not form heteromeric complexes. Further analysis by [(35)S]methionine labelling in vivo followed by immunoprecipitation indicated that no proteins other than the FXR proteins were present in these complexes. These results suggest that the FXR proteins form homo-multimers preferentially under physiological conditions in mammalian cells, and might participate in mRNP particles with separate functions.

Animals↗

PubMed1999

Learning and memory in the FMR1 knockout mouse.

The fragile X [fra(X)] syndrome is manifested phenotypically as a developmental disability comprised mainly of moderate-to-severe mental retardation (MR). Deficits are especially evident in auditory and visual short-term memory. Recently, an FMR1 knockout mouse developed by the Dutch-Belgian Fragile X Consortium demonstrated significantly lower visual-spatial abilities than littermate controls. We wondered if these results were associated with learning per se or to performance deficits only. Thus, we examined learning and memory in male FMR1 knockout mice crossbred from Fvb and E129 strains, and in male Fvb control mice, using operant conditioning techniques. In Experiment 1, we demonstrated that two aged male FMR1 knockouts could acquire the necessary bar-press response to discriminate visual (L+) and auditory (N+) stimuli. In Experiment 2, we showed that three naive male knockouts and two naive male controls, all 12 weeks old, also learned to discriminate L+ and N+. A third component, a complex discrimination task, during which light and noise were presented concurrently without reinforcement (LN-) was added to each session. All knockouts acquired both L+ and N+ discriminative responses in fewer sessions and with higher discrimination ratios than either control. Moreover, all knockouts exhibited the typical response pattern associated with complex discrimination (LN-) tasks. However, neither control made the complex discrimination. Our findings were unexpected and raise issues concerning FMR1 mouse strains and their cognitive-behavioral testing.

Animals↗

PubMed1997

Persistent unconjugated hyperbilirubinemia after liver transplantation due to an abnormal bilirubin UDP-glucuronosyltransferase gene promoter sequence in the donor.

BACKGROUND/AIMS: Gilbert's syndrome is genetically characterized by an extra TA element in the TATAA-box of the promotor region upstream of the bilirubin UDP-glucuronosyltransferase (UGT1A) coding region (Bosma et al. N Engl J Med 1995; 333: 1171-5). Persistent unconjugated hyperbilirubinemia is occasionally observed in liver transplant recipients with an otherwise normal liver function. We postulate that these patients could have received a liver from a donor with the Gilbert's syndrome genotype. Therefore, we investigated the UGT1A-gene TATAA-box in DNA from liver graft donors of jaundiced and non-jaundiced recipients. METHODS: DNA was obtained from stored donor lymphocytes and the number of TA elements in the TATAA-box of the UGT1A-gene promotor region was analyzed by polymerase chain-reaction. RESULTS: We observed two liver transplant recipients with persistent unconjugated hyperbilirubinemia. They received liver grafts from donors who were homozygous for an abnormal A(TA)7TAA-box in the UGT1A-gene. Four of 10 non-jaundiced recipients received livers from donors who were homozygous for the normal A(TA)6TAA-box and six received livers from donors who were heterozygous with a normal A(TA)6TAA-box on one allele and a prolonged A(TA)7TAA-box on the other allele. CONCLUSIONS: This study shows that liver graft recipients with persistent unconjugated hyperbilirubinemia may have received a liver from a donor with an abnormal TATAA-box in the bilirubin UGT1A-gene promotor region.

Adult↗

PubMed1996

Influence of dietary calcium phosphate on the disposition of bilirubin in rats with unconjugated hyperbilirubinemia.

The aim of this study was to test a possible form of therapy that could be used in the management of unconjugated hyperbilirubinemia. We hypothesized that unconjugated bilirubin (UCB) can permeate the intestinal wall and can thus be secreted with the feces. We have previously observed that UCB binds to amorphous calcium phosphate in vitro. Orally ingested amorphous calcium phosphate may act as a trapping agent for bilirubin in the intestine, thereby preventing back-diffusion across the intestinal wall. In this study, we tested whether feeding calcium phosphate leads to enhanced excretion of unconjugated bilirubin in Gunn rats. When a purified control diet was substituted by a high calcium phosphate diet, a decrease in bilirubin levels of 30% to 50% in male Gunn rats and of 23% in female rats was observed. The fecal output of bilirubin was more than doubled in Gunn rats in the first 3 days after the normal diet had been replaced by the high calcium-phosphate diet. The biological half-life of 3 H-labeled bilirubin in blood was 89.8 +/- 17.2 hours in rats fed the purified control diet and 50.9 +/- 1.4 hours in rats fed the high calcium phosphate diet (P = .004). After 30 weeks, plasma bilirubin levels were still significantly lower in Gunn rats fed a high calcium phosphate diet. No differences were found in plasma concentrations of calcium, magnesium, phosphate, urea, and creatinine in both Gunn rats and Wistar rats on control or high calcium phosphate diets. This therapy might be useful in the management of Crigler-Najjar patients, for example, as an adjunct to phototherapy.

Animals↗

PubMed1995

The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome.

BACKGROUND: People with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. Hepatic glucuronidating activity, essential for efficient biliary excretion of bilirubin, is reduced to about 30 percent of normal. METHODS: We sequenced the coding and promoter regions of the gene for bilirubin UDP-glucuronosyltransferase 1 (bilirubin/uridine diphosphoglucuronate-glucuronosyltransferase 1)--the only enzyme that contributes substantially to bilirubin glucuronidation--in 10 unrelated patients with Gilbert's syndrome, 16 members of a kindred with a history of Crigler-Najjar syndrome type II, and 55 normal subjects. RESULTS: The coding region of the gene for the enzyme was normal in the 10 patients with Gilbert's syndrome. These patients were homozygous for two extra bases (TA) in the TATAA element of the 5' promoter region of the gene (A(TA)7TAA rather than the normal A(TA)6TAA). The presence of the longer TATAA element resulted in the reduced expression of a reporter gene, encoding firefly luciferase, in a human hepatoma cell line. The frequency of the abnormal allele was 40 percent among the normal subjects. The 3 men in the control group who were homozygous for the longer TATAA element had significantly higher serum bilirubin levels than the other 52 normal subjects (P = 0.009). Among the kindred with a history of Crigler-Najjar syndrome type II, only the six heterozygous carriers who had a longer TATAA element on the structurally normal allele had mild hyperbilirubinemia, characteristic of Gilbert's syndrome. CONCLUSIONS: Reduced expression of bilirubin UDP-glucuronosyltransferase 1 due to an abnormality in the promoter region of the gene for this enzyme appears to be necessary for Gilbert's syndrome but not sufficient for the complete manifestation of the syndrome.

Adolescent↗

PubMed1995

Impaired hepatocanalicular organic anion transport in endotoxemic rats.

To investigate the mechanism of sepsis-associated hyperbilirubinemia we have studied hepatocanalicular transport of organic anions in a rat model of endotoxemia. Rats were injected intravenously with lipopolysaccharides (LPS), and at different times after injection, canalicular transport of 2,4-dinitrophenyl-S-glutathione (GS-DNP), as a model organic anion, was measured in perfused livers and isolated hepatocytes. In isolated liver perfusion experiments the initial biliary GS-DNP secretion rate was found to be significantly decreased 18 h after injection with 2 mg/kg LPS. In isolated hepatocytes from these rats, GS-DNP efflux rate was also significantly decreased (193.0 +/- 67 and 448.3 +/- 53 nmol.min-1.g dry wt-1 in endotoxemic and normal hepatocytes, respectively). Inhibition of GS-DNP effluxin isolated endotoxemic hepatocytes was dose dependent and reached a maximum with 0.25 mg/kg LPS. Inhibition was maximal at 12 h after LPS injection. Transport activity gradually returned to normal in 4-5 days after endotoxemia was induced. Dexamethasone pretreatment partially reversed the inhibition of GS-DNP transport in isolated endotoxemic hepatocytes. The phorbol ester phorbol 12-myristate 13-acetate increased GS-DNP efflux by 73 +/- 16 and 24 +/- 8% in endotoxemic and control hepatocytes, respectively, but could not restore the transport activity of endotoxemic hepatocytes to control levels. These results show that canalicular organic anion transport is decreased in the endotoxemic liver; this may play a role in the frequently observed hyperbilirubinemia during sepsis.

Alkaloids↗

PubMed1995

Patient utilities in fibromyalgia and the association with other outcome measures.

OBJECTIVE: To compare in patients with fibromyalgia (FM) utilities derived by rating scale and standard gamble methods; to gain insight into construct validity by relating utility values to other outcome measures; to assess the sensitivity to change of utilities. METHODS: A total of 73 patients with FM were randomized into one of 3 groups: low impact fitness training, biofeedback, or controls. At baseline and after 6 mo the Maastricht Utility Measurement Questionnaire was applied. By means of both the rating scale and standard gamble method patients were asked to value their own health status. Construct validity of patient utility measurements was evaluated by Spearman correlation and multiple regression of baseline values with pain, stiffness, patient's global assessment, Sickness Impact Profile (SIP), modified Health Assessment Questionnaire and Arthritis Impact Measurement Scale (AIMS). Sensitivity to change was assessed against changes in these outcomes. RESULTS: Rating scale utilities correlated significantly (p < 0.05) with patient's global assessment (rs = 0.53), pain (rs = -0.47), SIP (rs = -0.43), and with 9 of 11 dimensions of the AIMS (rs ranging from 0.23 to 0.62). Standard gamble utilities correlated significantly with mobility, pain, and arthritis impact of the AIMS scale (rs from 0.22 to 0.36) and with pain by visual analog scale (rs = -0.24) and patient's global assessment (rs = 0.32). Multiple regression analysis showed that patient's global assessment explained 41% (rating scale) and 10% (standard gamble) of total variance in baseline utilities. Also, 16% of the variance in change in rating scale utility values was explained by changes in patient's global assessment. In contrast, variance of changes in standard gamble utility values was not explained significantly by changes in other disease outcomes. CONCLUSION: Rating scale utilities correlated more strongly with disease outcome measures than standard gamble utilities. Also, construct validity for the rating scale was better than for the standard gamble. In FM, utility measurement is sensitive to the method chosen to elicit patient priorities.

Adolescent↗

PubMed1995

Problem elicitation to assess patient priorities in ankylosing spondylitis and fibromyalgia.

OBJECTIVE: To elicit patient priorities as outcome measures in ankylosing spondylitis (AS) and fibromyalgia (FM); to relate these measures to other outcomes; to assess construct validity and sensitivity to change of the problem elicitation technique (PET) questionnaire. METHODS: One hundred thirty-four patients with AS were randomly allocated to weekly sessions of group physical therapy or daily exercises at home, whereas 73 patients with FM were randomized into one of 3 groups (low impact fitness, biofeedback, controls). The PET questionnaire was applied by trained interviewers at baseline and at 6 (FM) and 9 (AS) month followup. A PET score was calculated at each assessment. Construct validity of the PET was assessed by correlation and multiple regression of baseline values with other disease outcomes (pain, stiffness, patient's global assessment, Sickness Impact Profile (SIP), Health Assessment Questionnaire (HAQ), Arthritis Impact Measurement Scale (AIMS), patient utilities). Sensitivity to change of PET was assessed against changes in these outcomes and by comparing the efficiency of the PET with other outcomes. RESULTS: Patients with FM identified more problems (mean 6.8) than patients with AS (mean 4.4). Moreover, more patients with AS than with FM were unable to identify any problem at baseline (10% compared to 1%). The PET score improved from 14.9 to 11.3 (p = 0.0001) in patients with AS but did not change from 21.8 to 21.1 (p = 0.24) in patients with FM. Construct validity testing of the PET score showed statistically significant (p < 0.05) correlations with AIMS, utilities, SIP, HAQ, pain, stiffness, and patient's global health in both groups of patients (r varying from 0.22 to 0.66). By multiple regression pain explained 29% of the variance in PET scores among patients with AS. In FM patient global assessment accounted for 39% of total variance of PET scores, whereas pain explained another 15%. Changes in PET scores correlated significantly (p < 0.05) with changes in AIMS, utilities, pain, stiffness, and patient global health in both AS and FM (r varying from 0.22 to 0.51). Some 6% of the variance in changes in PET scores was explained by changes in pain in patients with AS and 35% by changes in pain and subjective health in patients with FM. Assessment of sensitivity to change revealed that efficiency of the PET score was 0.6 in patients with AS and 0.09 in those with FM. Compared to other outcomes this was reasonable in patients with AS but low in those with FM. CONCLUSION: Obtaining patient priorities was generally feasible. In both groups of patients construct validity of the PET questionnaire was satisfactory. The PET was much more sensitive to change in patients with AS than in patients with FM.

Adolescent↗

PubMed1995

Health related utility measurement: an introduction.

Utility measures of health related quality of life are preference values that patients attach to their overall health status. In clinical trials, utility measures summarize both positive and negative effects of an intervention into one value between 0 (equal to death) and 1 (equal to perfect health). These measures allow for comparison of patient outcomes of different diseases, and for comparison between various health care interventions. There are 2 different approaches to utility measurement. The first is to classify patients into categories based on their responses to questions about their functional status, as for instance the Quality of Well-Being Questionnaire and the European Quality of Life Measure (EUROQOL). The 2nd approach is to ask patients to assign a single rating to their overall health by means of rating scale, standard gamble, time tradeoff, or willingness to pay. The Quality Adjusted Life Year (QALY) outcome measure includes both effects in terms of quality of quantity of life. Utilities are used as weights to adjust life years for the quality of life in order to calculate QALY. Both QALY and utilities are useful in decision making regarding appropriate procedures for groups of patients.

Disability Evaluation↗

PubMed1994

Conservation of CGG region in FMR1 gene in mammals.

Only two of the fragile sites found in humans (FRAXA and FRAXE) have been associated with a clinical phenotype. In mentally retarded individuals with cytogenetic expression of FRAXA a CGG repeat in the FMR1 gene is amplified. Fragile sites are found in many animals species. We have analyzed the FRAXA region containing the CGG repeat in several different species by PCR amplification. In most mammals this region could be amplified; the number of copies of the repeat is deduced.

Animals↗

PubMed1994

Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man.

Crigler-Najjar syndrome type I (CN-I) is caused by an inherited absence of UDP-glucuronosyltransferase activity toward bilirubin (B-UGT), resulting in severe non-hemolytic unconjugated hyperbilirubinemia. Based on the expression of cDNAs in COS cells, two UGT isoforms in human liver, B-UGT1 and B-UGT2, have been reported to catalyze bilirubin glucuronidation. These isoforms, which are derived from a single gene, ugt1, have identical carboxyl-terminal domains that are encoded by four consecutive exons shared by both isoforms. A critical lesion in any of these common exons should inactivate both B-UGT isoforms, giving rise to CN-I. The amino-terminal domains of the B-UGT isoforms are unique, each being encoded by a different 5' exon. If both B-UGT isoforms contribute significantly to bilirubin glucuronidation, a mutation in one of these unique 5' exons should affect a single isoform, while the other isoforms should provide residual B-UGT activity. However, in two patients with CN-I, we found a mutation only in the unique exon of B-UGT1, the other exons being normal. To clarify this apparent paradox, we expressed the cDNA for each B-UGT isoform in COS cells and determined the specific B-UGT activity. These studies show that only B-UGT1 has quantitatively significant catalytic activity. Furthermore, we show that the mutation in B-UGT1 observed in each of the two CN-I patients inactivates B-UGT1. Together, the results indicate that B-UGT1 is the only physiologically relevant isoform in bilirubin glucuronidation.

Animals↗

PubMed1994

Patient utilities in ankylosing spondylitis and the association with other outcome measures.

OBJECTIVE: To compare in patients with ankylosing spondylitis (AS) utilities derived by rating scale and standard gamble method, to relate these values to other outcome measures, and to assess the sensitivity to change of utilities relative to changes in other outcomes. METHODS: Patients with AS were randomly allocated to either weekly sessions of supervised group physical therapy for a period of 9 months or daily exercises at home. Analysis was restricted to the 59 patients who completed the Maastricht Utility Measurement Questionnaire (MUMQ) at baseline and after 9 months' followup and who were seen by the same interviewer. Reliability was assessed by intraclass correlation coefficient and change scores for marker states of disease. Construct validity was evaluated by correlation and multiple regression of baseline values with a variety of disease outcomes (pain and stiffness, patient's and physician's global assessment, Sickness Impact Profile, Health Assessment Questionnaire for the Spondyloarthropathies, Arthritis Impact Measurement Scale, functional, articular, and enthesis indices and spinal mobility measures). Sensitivity to change was assessed against changes in these outcome measures at followup. RESULTS: The test-retest intraclass correlation coefficients for patient utilities were 0.95 (rating scale) and 0.79 (standard gamble), and for the marker state of mild disease 0.70 (rating scale) and 0.77 (standard gamble). A multiple regression analysis with the baseline rating scale or standard gamble utilities as dependent variable showed that patient's global assessment explained 59 and 11% of the total variance respectively. By multiple regression analysis 10% of the variance of change in rating scale utilities was explained by changes of patient's global assessment. In contrast, variance in change in standard gamble utilities was not explained by changes in other disease outcomes. CONCLUSION: Findings obtained by rating scale and standard gamble differ considerably. Standard gamble utilities seem to address different aspects of health status than do rating scale utilities and more traditional outcomes. Utility measurement is sensitive to the method chosen to elicit patient well being.

Adult↗

PubMed1994

Cost effectiveness of group physical therapy compared to individualized therapy for ankylosing spondylitis. A randomized controlled trial.

OBJECTIVE: Cost effectiveness analysis is helpful in setting priorities for funding of health care programs. We studied the cost effectiveness of supervised group physical therapy compared to unsupervised exercises at home in patients with ankylosing spondylitis (AS). METHODS: A total of 144 patients with AS (modified New York criteria; mean age: 43 years) were randomized to unsupervised daily individualized exercises at home for 9 months or the same plus supervised group physical therapy (3 h weekly). At baseline and after 9 months we measured spinal mobility (thoracolumbar flexion and extension), fitness (maximum work capacity by ergometry), and patient's global assessment of change as measured on a visual analog scale. We used a questionnaire at baseline and a diary during the trial to measure AS related direct medical costs, such as doctor visits, paramedical treatment, medication and hospitalization. RESULTS: The mean effects of group therapy and home exercises were, respectively, +0.9 cm (16%) and +0.5 cm (9%) for mobility, +7 watts (4%) and -2 watts (-1%) for fitness, and +1.7 (34%) and +0.3 (6%) for global health. These 3 differences were significant (p < 0.01 for mobility, p = 0.05 for fitness and p < 0.01 for global health). During the trial total medical costs decreased by an average of US $379 (44%) for group therapy, and by $257 (35%)/patient/year for the "home" group. Additional costs of group therapy were estimated at $531/patient/year ($177 for accommodation, $256 for therapist and $98 for materials). After the study 75% of the patients wanted to continue group physical therapy and were willing to pay for it. CONCLUSION: Compared to therapy at home, additional benefits of group therapy cost $531/year, but reduced direct medical costs by $122/year. Hence, the beneficial effects of group therapy cost $409/patient with AS/year.

Adult↗

PubMed1994

Feasibility of utility assessment by rating scale and standard gamble in patients with ankylosing spondylitis or fibromyalgia.

OBJECTIVE: To assess the feasibility of utility measurement in patients with ankylosing spondylitis (AS) or fibromyalgia (FMS). Patient derived utilities provide overall estimates of the impact of a disease on patient well being. METHODS: The Maastricht Utility Measurement Questionnaire was applied cross sectionally to 57 patients with AS and 86 outpatients with FMS. By means of rating scale and standard gamble techniques, patients were asked to value their own health state. RESULTS: All 143 patients completed the interview. Patients with AS valued their personal health state on the rating scale (0-100) considerably higher than patients with FMS (AS: 69 and FMS: 54). Standard gamble utility values (0-1), however, were about the same at a higher level (AS: 0.86 and FMS: 0.83). Four weeks test-retest reliability was examined in 15 patients with FMS. The intraclass correlation coefficient of the utility score for the patient's own health state was 0.56 for the rating scale and 0.66 for the standard gamble technique. CONCLUSION: Feasibility of the Maastricht Utility Measurement Questionnaire was generally satisfactory in both patient groups. Utility values obtained by rating scale and standard gamble technique differed considerably. Our data support the view that utility measurement is sensitive to the method chosen to elicit patient well being.

Activities of Daily Living↗