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In vivo deamination of cytosine-containing cyclobutane pyrimidine dimers in E. coli: a feasible part of UV-mutagenesis.

We have estimated in vivo deamination rates for cytosines in cyclobutane pyrimidine dimers (CPD or PyPy) in UV-irradiated E. coli deficient in uracil DNA glycosylase. The protocol consisted of UV-irradiation, holding in buffer to allow for deamination of cytosines in CPDs and photoreversal (PR) to establish uracils where cytosines in CPD deaminated. The deamination rate at TC photoproducts targeting glutamine tRNA suppressor mutations was estimated from the increase in the mutation frequency after PR (MF(PR)) that developed as UV-irradiated cells were held before PR. Evidence suggested that an earlier study with this protocol under-estimated the deamination rate at sites producing the same mutations in an E. coli B/r strain. With a K12 strain, where the targeting apparently is principally by CPD and not (6-4) photoproducts, a larger rate of k = 0.0091 min(-1) at 42 degrees C resulted. The dark assay for MF also increased significantly with time for deamination consistent with a model for efficient mutation by translesion synthesis at uracil-containing CPD. In addition, we used a strain constructed by Cupples and Miller in which beta-galactosidase was inactive because -GGG- was at codon 461 and would revert to Lac(+) only when replaced by -GAG- or -GAA- for glutamate. CC photoproducts at this target site in the opposite DNA strand could reveal effects of first and second deaminations in the same CPD. MF(PR) for Lac(+) mutations increased and then decreased as a function of deamination time (at six temperatures 36-48 degrees C). Fitting an approximate model equation that distinguished two different deamination rates to these data suggested a first deamination producing Lac(+) at a rate about eight-fold less than a second deamination restoring the Lac(-) phenotype. We conclude that deamination, changing a cytosine-containing CPD to a uracil-containing CPD, could be an integral part of UV-induced C-to-T mutations.

Cytosine↗

Altered composition and DNA binding activity of the AP-1 transcription factor during the ageing of human fibroblasts.

We have investigated the expression of AP-1 transcription factor proteins during the in-vitro ageing of human fibroblasts. The numbers of these cells that are in the cell cycle gradually decreases up to 45 cumulative population doublings (cPD), thereafter the decline is steeper, until almost all cells enter a post-mitotic state by 60 cPD. We observed that a 34 kd junB species began to replace the 44 kd junB species after 41 cPD. This was followed, after 44 cPD, by a loss of fra1 and both junD species. After 49 cPD there was a gradual decline in the levels of fos and jun proteins, but disproportionately, so that the fos/jun protein ratio also declined. Although fos and jun proteins were still clearly present at 60 cPD, utilisation of the AP-1 DNA consensus sequence could not be demonstrated after 54 cPD. These data indicate that significant changes occur in the composition of the AP-1 transcription factor during ageing, but also that alterations in its DNA binding activity may involve other factors.

Cell Line↗

Cluster C personality disorder impedes alleviation of symptoms in major depression.

BACKGROUND: We investigated whether cluster C personality disorder (CPD) is associated with recovery from depression. METHODS: The study design was observational. Diagnoses of major depression (MD) and CPD were confirmed by means of the Structured Clinical Interview for DSM-III-R (SCID-I, -II). Changes in symptom scales in 52 patients with MD and CPD were compared with changes in 65 patients with MD alone over a 6-month follow-up period. RESULTS: On the Hamilton Depression Rating Scale and Beck Depression Inventory (BDI) scales, recovery of patients with MD and comorbid CPD was inferior to recovery of patients with MD alone. Findings were similar in relation to several other symptom scales. Of those with MD alone 54% had recovered from their depression, but only 16% of those with CPD and MD (BDI score <10 on follow-up). Logistic regression analysis revealed an independent association between lack of recovery and presence of CPD (OR 7.5, 95% CI 2.6-22.2). LIMITATIONS: Study design was observational. CONCLUSION: The presence of CPD hinders alleviation of depressive symptoms in major depression.

Adult↗

Mechanism of novel vitamin K analog induced growth inhibition in human hepatoma cell line.

BACKGROUND/AIMS: To understand the mechanisms of liver regeneration or hepatoma apoptosis, it is important to estimate the turning point of the signal transduction by growth factor receptor. Since 2-(2-hydroxyethylsulfaryl) 3-methyl-1,4-naphthoquinone or CPD 5 has been shown to mediate the phosphorylation of epidermal growth factor (EGF) receptor in Hep3B hepatoma cells, the differences between EGF and CPD 5-mediated signal transduction were studied. METHODS: DNA content was measured by Hoechst fluorescent assay. Phosphorylated proteins were described with Western blots or two-dimensional electrophoresis. RESULTS: CPD 5-induced EGFR phosphorylation was functional to stimulate Ras pathway. However, CPD 5-mediated extracellular signal-regulated kinase (ERK) phosphorylation was not antagonized by inhibition of upstream activation with PD153035. CPD 5 inhibited ERK dephosphorylation in cell lysate, suggesting that ERK phosphorylation by CPD 5 was depending on kinase activity and phosphatase inhibition. Two-dimensional electrophoresis showed extra phospho ERK spot, which was indicated to have close association with CPD 5-induced growth inhibition, since U0126 antagonized growth inhibition and appearance of this spot. CONCLUSIONS: The turning point of EGFR pathway was proved to have close association with the expressed level of phosphorylated ERK. ERK phosphorylation was suggested to play a critical role in growth factor-induced signal transduction.

Antineoplastic Agents↗

Photoinactivation of vesicular stomatitis virus by a photodynamic agent, chlorophyll derivatives from silkworm excreta.

The efficacy of chlorophyll derivatives from silkworm excreta (CpD) in photodynamic antimicrobial chemotherapy (PACT) was studied. An enveloped animal virus, vesicular stomatitis virus (VSV), was used as a target organism. For CpD mediated PACT, the viruses in suspensions were treated with various doses of CpD (15-60 microg/ml) and visible red light was fixed at 120 mJ/cm(2). The antiviral effect of the CpD-PACT was measured 1 h after light irradiation by the extent of suppression of plaque forming units (pfu). In cultures inoculated with PACT-treated VSV, suppression of pfu was prominent and the results were demonstrated in a dose-dependent manner. In assays of RT-PCR, a single dose of 30 microg/ml CpD and light caused complete inhibition of viral RNA synthesis in the host cells, which agreed with the complete loss of plaque forming activity observed in pfu assays. An in vitro transcription assay for viral RNA using [3H]UTP and gel electrophoresis for the level of M protein was conducted. A gradual decrease in viral RNA transcription and an immediate decrease in M protein levels were observed in cells inoculated with the CpD-PACT-treated virus. These results demonstrated that CpD is a potential photodynamic antiviral agent, which causes inactivation of the matrix protein as well as transcription mechanisms involved in VSV replication.

Animals↗

Rat tibial osteoblasts III: propagation in vitro is accompanied by enhancement of osteoblast phenotype.

Postproliferative confluent cultures of primary rat tibial osteoblasts (ROB), cultured in medium supplemented with ascorbic acid and beta-glycerophosphate (AS-bGP, differentiation medium) express, in sequence, specific bone markers which identify a succession of maturation stages, and eventually form mineralized noduli. We report an investigation on the effect of extensive proliferation in vitro in unsupplemented medium on the osteogenic potential of mass cultures of ROB. The growth rates of the populations, derived from two independent primary cultures, was constant throughout 110 cumulative population doublings (CPD) in culture. Propagated cells maintained features similar to osteoblasts in primary cultures with respect to serum and anchorage dependence for growth and to the chemokinetic effect on endothelial cells exerted by their conditioned media (CM). Propagated populations, set at confluence in differentiation medium, were tested for the expression of early [alkaline phosphatase (AP)] and late [osteocalcin (OC); bone sialoprotein (BSP); 45Ca incorporation and mineralization] osteogenic markers. We observed an increase, parallel to the increase in CPD, in both the level of maximal expression of AP (enzyme/microgram cellular DNA) and in the frequency of nodules, reaching five- to sixfold (at 78 CPD) and eightfold (at 60 CPD), respectively, the levels of primary cultures. AP expression (enzyme and mRNA) persisted during mineralization and 45Ca incorporation. The time required by propagated cultures for the formation of nodules decreased with increase of CPD, and was reduced to less than one third at 87 CDP. Nodules became mineralized over a similar lapse of time as in primary cultures and were positive by histochemistry for BSP and OC. We also obtained osteogenic clones from two independent cultures after 72 CPD. 90% of these showed an osteoblast phenotype, expressing AP and forming nodules positive for OC and BSP, which mineralized. Timing of formation and frequency of nodules/plated cells in clones was similar to that found in propagated cultures of equivalent CPD. In summary, propagated ROB populations and derived clones showed enhanced osteoblast phenotype, possibly due to an increase in osteogenic cells and enrichment of proliferating mature osteoblasts, consequent to extended propagation in culture.

Alkaline Phosphatase↗

pH dependence and structural interpretation of the reactions of Coprinus cinereus peroxidase with hydrogen peroxide, ferulic acid, and 2,2'-azinobis.

Steady-state and transient-state analysis of Coprinus cinereus peroxidase, CIP (identical to Arthromyces ramosus peroxidase), was used to characterize the kinetics of the three fundamental steps in heme peroxidase catalysis: compound I (cpd I) formation, cpd I reduction, and compound II (cpd II) reduction. The rate constant k1 for cpd I formation determined by transient-state analysis is (9.9 +/- 0.6) x 10(6) M-1 s-1. The k1 determined by steady-state analysis is (8.8 +/- 0.6) x 10(6) M-1 s-1 in the presence of ferulic acid and (6.7 +/- 0.2) x 10(6) M-1 s-1 in the presence of ABTS. The value of k1 is constant from pH 6 to 11. However, at low pH the value of k1 decreases, corresponding to titration of an enzyme group with a pKa of 5.0. Titration of this group is also detected from cyanide-binding kinetics. Furthermore, titration of this group is linked with marked spectroscopic changes unique to CIP. We ascribe these changes to protonation of proximal His183. A very low pKa is proposed for distal His55 in the resting state of CIP. The rate constants, k2 for cpd I and k3 for cpd II reduction, are very large for both ferulic acid and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS). For ferulic acid, transient-state kinetic analysis shows that the values of k2 and k3 are identical at pH 5-6, and the ratio k2/k3 increases to 10 at pH 10. The similar magnitude of k2 and k3 is unusual for a peroxidase. Both k2 and k3 decrease with increasing pH, and both are influenced by two ionizations: one with a pKa value near 7, assumed to reflect the protonation of His55; and the other with pKa of 9.0 +/- 0.7 for k2 and 8.8 +/- 0.4 for k3, perhaps reflecting the phenol-linked deprotonation of ferulic acid. Steady-state analysis at pH 7.0 gave k2k3/(k2 + k3) = (2.2 +/- 0.1) x 10(7) M-1 s-1 for ferulic acid, and (2.0 +/- 0.7) x 10(7) M-1 s-1 for ABTS and revealed a unimolecular step with ku = 1500 s-1, ascribed to slow ABTS radical product release. From transient-state results at pH 7, the values of k2 and k3 were found to be identical also for ABTS. A mechanism for cpd I and II reduction involving distal histidine and arginine is proposed.

Benzothiazoles↗

Photonic switching of photoinduced electron transfer in a dihydropyrene-porphyrin-fullerene molecular triad.

Photonic control of photoinduced electron transfer has been demonstrated in a dimethyldihydropyrene (DHP) porphyrin (P) fullerene (C(60)) molecular triad. In the DHP-P-C(60) form of the triad, excitation of the porphyrin moiety is followed by photoinduced electron transfer to give a DHP-P(*)(+)-C(60)(*)(-) charge-separated state, which evolves by a charge shift reaction to DHP(*)(+)-P-C(60)(*)(-). This final state has a lifetime of 2 micros and is formed in an overall yield of 94%. Visible (>or=300 nm) irradiation of the triad leads to photoisomerization of the DHP moiety to the cyclophanediene (CPD). Excitation of the porphyrin moiety of CPD-P-C(60) produces a short-lived (<10 ns) CPD-P(*)(+)-C(60)(*)(-) state, but charge shift to the CPD moiety does not occur, due to the relatively high oxidation potential of the CPD group. Long-lived charge separation is not observed. Irradiation of CPD-P-C(60) with UV (254 nm) light converts the triad back to the DHP form. Thermal interconversion of the DHP and CPD forms is very slow, photochemical cycling is facile, and in the absence of oxygen, many cycles may be performed without substantial degradation. Thus, light is used to switch long-lived photoinduced charge separation on or off. The principles demonstrated by the triad may be useful for the design of molecule-based optoelectronic systems.

Journal Article↗

Structural requirements for a successful chronic peritoneal dialysis program.

Recently, there has been a decline in chronic peritoneal dialysis (CPD) utilization in several countries. And, in these countries, the percent of patients with end-sage renal disease maintained on CPD is less than nephrologists think is appropriate. The reasons for these problems are uncertain, but it is likely that difficulties with the structural organization of CPD facilities play a contributory role. This paper discusses the structural requirements for a successful CPD program, focusing attention on the following domains: (1) adequate chronic kidney disease education, (2) provision and support of physician training in the principles and practice of CPD, (3) adequate size and organization of CPD centers, (4) development of appropriate support systems within the CPD facility, and (5) development of appropriate continuous quality improvement programs to monitor a variety of domains, including adequacy of dialysis, peritonitis rates, catheter infections and problems, psychosocial status of patients, etc.

Hemodialysis Units, Hospital↗

Stability of blood coagulation factors and inhibitors in blood drawn into half-strength citrate anticoagulant.

Drawing of blood into a citrate-phosphate-dextrose (CPD) solution with a reduced citrate concentration has been shown to improve the maintenance of coagulation factor VIII (F VIII) in plasma and to give possibilities to improve erythrocyte preservation. We studied the quality of plasma obtained from whole blood drawn under continuous mixing into CPD in which the citrate concentration was reduced by 50% (0.5CPD). The blood was stored at room temperature for 8 h before component preparation. We confirmed improved stability of F VIII by 0.5CPD. We found no clinically significant changes in inhibitors to the coagulation and kallikrein systems, and no signs of activation of these systems, during the 8-hour holding time. In control blood drawn into CPD, F VIII and coagulation factor IX decreased by 0.09 IU/ml (8%) and 0.07 U/ml (7%), respectively, otherwise we found no significant differences between 0.5CPD plasma and CPD plasma.

Anticoagulants↗

Platelet glycolysis in platelet storage. IV. The effect of supplemental glucose and adenine.

Platelet concentrates were prepared from blood collected in CPD, CPD-A1, and CPD-A3. CPD-A1 contains 1.25 times as much glucose as does CPD, and sufficient adenine to provide a final concentration of 0.25 mM; CPD-A3 contains twice as much glucose as does CPD, and sufficient adenine to provide a final concentration of 0.5 mM. The consumption of glucose and the production of lactate and pyruvate in the platelet concentrates during room temperature storage was not influenced by glucose or adenine concentration. There was no difference in the rates of fall of the pH of platelets collected in the three preservatives. However, the number of contaminating white blood cells had a significant effect on these parameters. It is suggested that minimizing the number of contaminating white blood cells in platelet preparations may prove to be an important factor in platelet preservation.

Adenine↗

An analysis of dialysis training in the United States and Canada.

BACKGROUND: Because the prevalence of end-stage renal disease (ESRD) has progressively increased in both the United States and Canada, patients with ESRD are likely to constitute progressively larger proportions of nephrology practices. METHODS: We mailed a questionnaire to US and Canadian nephrology program directors to determine methods used in dialysis training; 53% of US and 73% of Canadian programs responded. RESULTS: Training programs in the United States enrolled a larger median number of fellows and had a lower median faculty-fellow ratio compared with programs in Canada. However, the availability of faculty in providing training in the care of patients undergoing maintenance hemodialysis (MHD) or chronic peritoneal dialysis (CPD) was similar in both countries. There were wide variations in availability of patients in both the United States and Canada. US training programs offered trainees significantly lower numbers of MHD and CPD patients; 29% of US training programs had less than five CPD patients per fellow. Similarly, there were wide variations in the amount of time trainees spent providing care to MHD and CPD patients; in 14% of US training programs, fellows spent less than 5% of their time receiving training for patients undergoing CPD. Only a small proportion of training programs had faculty resources or ensured training for fellows in the placement of percutaneous tunneled venous hemodialysis catheters or peritoneal dialysis catheters. CONCLUSIONS: To conclude, there are wide variations in dialysis training in both the United States and Canada. This survey raises concerns that many US training programs either do not have an appropriate number of CPD patients or do not allocate appropriate time to ensure the preparedness of fellows in providing independent care for patients with ESRD undergoing CPD.

Canada↗

Crystal structure of cryptochrome 3 from Arabidopsis thaliana and its implications for photolyase activity.

Cryptochromes use near-UV/blue light to regulate a variety of growth and adaptive process. Recent biochemical studies demonstrate that the Cryptochrome-Drosophila, Arabidopsis, Synechocystis, Human (Cry-DASH) subfamily of cryptochromes have photolyase activity exclusively for single-stranded cyclobutane pyrimidine dimer (CPD)-containing DNA substrate [Selby C, Sancar A (2006) Proc Natl Acad Sci USA 103:17696-17700]. The crystal structure of cryptochrome 3 from Arabidopsis thaliana (At-Cry3), a member of the Cry-DASH proteins, at 2.1 A resolution, reveals that both the light-harvesting cofactor 5,10-methenyl-tetrahydrofolyl-polyglutamate (MTHF) and the catalytic cofactor flavin adenine dinucleotide (FAD) are noncovalently bound to the protein. The residues responsible for binding of MTHF in At-Cry3 are not conserved in Escherichia coli photolyase but are strongly conserved in the Cry-DASH subfamily of cryptochromes. The distance and orientation between MTHF and flavin adenine dinucleotide in At-Cry3 is similar to that of E. coli photolyase, in conjunction with the presence of electron transfer chain, suggesting the conservation of redox activity in At-Cry3. Two amino acid substitutions and the penetration of three charged side chains into the CPD-binding cavity in At-Cry3 alter the hydrophobic environment that is accommodating the hydrophobic sugar ring and thymine base moieties in class I CPD photolyases. These changes most likely make CPD binding less energetically favorable and, hence, insufficient to compete with pairing and stacking interactions between the CPD and the duplex DNA substrate. Thus, Cry-DASH subfamily proteins may be unable to stabilize CPD flipped out from the duplex DNA substrate but may be able to preserve the DNA repair activity toward single-stranded CPD-containing DNA substrate.

Amino Acid Sequence↗

Mutational analysis of a function of xeroderma pigmentosum group A (XPA) protein in strand-specific DNA repair.

To analyze the function of the xeroderma pigmentosum group A (XPA) protein in strand-specific DNA repair, we examined repair of UV-induced cyclobutane pyrimidine dimer (CPD) in transcribed and non-transcribed strands of the dihydrofolate reductase gene of xeroderma pigmentosum group A (XP-A) cell line (XP12ROSV) which was transfected with various types of mutant XPA cDNA. The transfectant overexpressing mutant XPA with a defect in the interaction with either ERCC1, replication protein A (RPA), or general transcription factor TFIIH, showed more or less decreased repair of CPD in each strand in parallel, while in the transfectant overexpressing R207G (Arg207to Gly) mutant XPA derived from XP129, a UV-resistant XP12ROSV revertant, the rate of CPD repair was almost normal in each strand. We also examined the dose responses of the XPA protein on CPD repair in each strand by the modulation of the expression levels of wild-type or R207G mutant XPA using an inducible expression system, LacSwitchtrade mark promoter. There were good correlations between the rate of CPD repair in each strand and the amount of XPA protein produced in these Lac cells. Our results indicate that the XPA protein is equally important for the CPD repair in both transcribed and non-transcribed strands and that the R207G mutation found in XP129 may not be responsible for a selective defect in CPD repair in the non-transcribed strand in XP129.

Cell Line↗

Ultraviolet-B sensitivities in Japanese lowland rice cultivars: cyclobutane pyrimidine dimer photolyase activity and gene mutation.

There is a cultivar difference in the response to ultraviolet-B (UVB: 280-320 nm) in rice (Oryza sativa L.). Among Japanese lowland rice cultivars, Sasanishiki, a leading Japanese rice cultivar, is resistant to the damaging effects of UVB while Norin 1, a close relative, is less resistant. We found previously that Norin 1 was deficient in cyclobutane pyrimidine dimer (CPD) photorepair ability and suggested that the UVB sensitivity in rice depends largely on CPD photorepair ability. In order to verify that suggestion, we examined the correlation between UVB sensitivity and CPD photolyase activity in 17 rice cultivars of progenitors and relatives in breeding of UV-resistant Sasanishiki and UV-sensitive Norin 1. The amino acid at position 126 of the deduced amino acid sequence of CPD photolyase in cultivars including such as Norin 1 was found to be arginine, the CPD photolyase activities of which were lower. The amino acid at that position in cultivars including such as Sasanishiki was glutamine. Furthermore, cultivars more resistant to UVB were found to exhibit higher photolyase activities than less resistant cultivars. These results emphasize that single amino acid alteration from glutamine to arginine leads to a deficit of CPD photolyase activity and that CPD photolyase activity is one of the main factors determining UVB sensitivity in rice.

Amino Acid Sequence↗

Accommodation and the third spatial harmonic.

PURPOSE: Mathews and Kruger recently reported that accommodative tracking of sine wave grating targets is best between 1 and 7 cpd. Their study suggests that the spatial third harmonic might not enhance the accommodative response if the fundamental is higher than roughly 2 cpd. This study tested the effect of adding the third harmonic with targets that included 1, 3, and 5 cpd fundamental sine wave gratings, compound gratings with the third harmonic of each of these fundamentals added in either peaks-add or peaks-subtract phase, as well as each third harmonic presented alone at one-third of the contrast of the fundamental gratings. METHODS: Accommodation was monitored continuously with a dynamic infrared optometer while the subject viewed the gratings in a Badal stimulus system. Dioptric vergence changed sinusoidally over a 2.00 or 0.50 D range at 0.2 Hz. A Fast Fourier Transform extracted the amplitude and phase of each response at the temporal frequency of the stimulus. RESULTS AND CONCLUSIONS: The third harmonic enhanced the accommodative response only when the fundamental was 1 cpd. This was true at both amplitudes of target motion. This contradicts models that suggest that high spatial frequencies are used to refine the accommodative response. Second, the responses to the peaks-add and peaks-subtract phase conditions were essentially the same for each fundamental. This suggests that the effect of harmonics cannot be described by any simple linear relationship between the increased luminance gradient of the grating target and the accommodative response. Third, the accommodative response to gratings with a 5 cpd fundamental were smaller than the responses to gratings with the 3 cpd fundamental. This contradicts the gradient hypothesis of accommodative control inasmuch as the luminance gradient is steeper in the gratings with the 5 cpd fundamental. Alternatively, it seems that harmonics will enhance an accommodative response regardless of phase if they are effective accommodative stimuli on their own.

Accommodation, Ocular↗

Medical professionalism and continuing professional development for medical specialists.

The present paper briefly describes a growing trend in continuing professional development (CPD) for medical practitioners, examines some recent published contributions related to professionalism in medicine and describes the theoretical platform of a CPD framework based on medical professionalism that has been developed for use in a variety of medical specialties. The work arises from a project funded by The Commonwealth Department of Health and Ageing and conducted by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists on behalf of the Committee of Presidents of Medical Colleges. Overall, the aim of the project was to design and develop a framework that can be considered 'best practice' in the field of medical specialist CPD, and which could be applicable to a wide variety of medical specialties and practice environments. The project was informed by available literature in areas such as the ways in which medical practitioners learn and the effectiveness of CPD, as well as consultations with a variety of stakeholders in the health-care field, including medical boards, medical defence organisations, health complaints organisations, specialist medical colleges and practising specialists. Overwhelmingly, the primary purpose of specialists participating in ongoing CPD was, according to the project consultations conducted, the maintenance, development and improvement of skills that enable consumers of healthcare to be confident of the level of care that they receive. Coupled with the need to recognise CPD as contributing to the wider context of professional practice, the resulting framework is underpinned by a theoretical platform based on the concept of medical professionalism. It is this theoretical platform, which articulates the nature of and responsibilities associated with the practice of specialist medicine, that enables a CPD framework to be constructed that can accommodate a wide range of specialist disciplines and practice settings, while also framing ongoing education expectations from the viewpoint of a range of stakeholders, rather than a single perspective; that of practitioners themselves.

Australia↗

Comparative performance data for critical access hospitals.

CONTEXT: Among small rural hospitals, there is a growing recognition of the need to measure and report on the use of resources and the safety and quality of the services provided. Dashboards, clinical value compasses, and balanced scorecards are approaches to performance measurement that have been adopted by many health care organizations. However, there exists very little comparative performance data specific for critical access hospitals. PURPOSE: To identify how comparative performance data for critical access hospitals (CPD-CAH) might facilitate performance and quality improvement, to assess the potential benefits and drawbacks of such data, and to identify some of the critical issues in the development and implementation of CPD-CAH. METHODS: Assessment of discussions by participants at a rural hospital performance improvement summit and authors' analyses. FINDINGS: CPD-CAH potentially could improve quality of care and patient outcomes, provide comparative data and benchmarks, inform policy development, facilitate collaboration, and enhance community relations. However, CPD-CAH could also impose an unaffordable cost, produce poor information, require complex coordination, induce a negative public reaction, and result in perverse hospital behavior. Development and implementation of CPD-CAH would require including stakeholders' assessment of its desirability and feasibility, setting objectives, establishing guiding principles, developing a method, collecting and analyzing data, and disseminating results. CONCLUSIONS: CPD-CAH could significantly advance CAH performance and quality improvement. However, development and implementation would be a complicated exercise requiring academic expertise and practitioner consultation. The potential value of CPD-CAH should be carefully weighed against its potential cost.

Benchmarking↗