Intensive care in a general hospital: demographics, utilization and outcomes.

INTRODUCTION: Intensive care units (ICU) in Irish academic centres are known to fare as well as their international counterparts. Our aim in this study was to characterise the role and outcomes of an ICU in a smaller Irish hospital and to compare these to international best practice. METHODS: We reviewed admissions of patients to the ICU of St. Luke's Hospital, Kilkenny. Patient demographics, indications for admission, and outcomes were all recorded and analysed. Sequential organ failure assessment (SOFA) scores were calculated. RESULTS: Forty-three patients were included in our study, 33 (76.7 %) of which were emergency admissions. Median length of stay was 2 days. The observed mortality rate in our cohort was 20.9 %. The median SOFA score in patients admitted was 7. Higher median SOFA scores on admission were predictive of mortality. The ICU occupancy rate during the duration of our study was 98 %, with only 15 (35.7 %) of admissions to ICU occurring within core working hours. CONCLUSION: Critical care can be provided safely and in line with current best practice in smaller Irish hospitals. There is a cohort of patients for whom care may be best provided in a tertiary centre, how best to provide for these patients will likely be achieved by early identification (e.g. with SOFA score). Bed capacity issues remain problematic.

"Bending the cost curve" in gastroenterology.

INTRODUCTION: Increasing attention is being focused on reigning in escalating costs of healthcare, i.e. trying to 'bend the cost curve'. In gastroenterology (GI), inpatient hospital care represents a major component of overall costs. This study aimed to characterize the trend in cost of care for GI-related hospitalizations in recent years and to identify the most costly diagnostic groups. METHODS: All hospital inpatients admitted between January 2008 and December 2009 with a primary diagnosis of one of the six most common GI-related Diagnosis Related Groups (DRGs) in this hospital system were identified; all DRGs contained at least 40 patients during the study period. Patient Level Costing (PLC) was used to express the total cost of hospital care for each patient; PLC comprised a weighted daily bed cost plus cost of all medical services provided (e.g., radiology, pathology tests) calculated according to an activity-based costing approach; cost of medications were excluded. All costs were discounted to 2009 values. Mean length of stay (LOS) was also calculated for each DRG. RESULTS: Over 2 years, 470 patients were admitted with one of the six most common GI DRGs. Mean cost of care increased from 2008 to 2009 for all six DRGs with the steepest increases seen in 'GI hemorrhage (non-complex)' (31 % increase) and 'Cirrhosis/Alcoholic hepatitis (non-complex)' (45 % increase). No differences in readmission rates were observed over time. There was a strong correlation between year-to-year change in costs and change in mean LOS, r = 0.93. CONCLUSION: The cost of GI-related inpatient care appears to be increasing in recent years with the steepest increases observed in non-complex GI hemorrhage and non-complex Cirrhosis/Alcoholic hepatitis. Efforts to control the increasing costs should focus on these diagnostic categories.

Does the cost of care differ for patients with fee-for-service vs. capitation of payment? A case-control study in gastroenterology.

INTRODUCTION: There is growing evidence to demonstrate overuse of medical resources in fee for service (FFS) payment models (in which physicians are reimbursed according to volume of care provided) compared to capitation payment models (in which physicians receive a fixed salary regardless of level of care provided). In this medical centre, patients with and without insurance are admitted through the same access point (emergency room) and cared for by the same physicians. Therefore, apart from insurance status, all other variables influencing delivery of care are similar for both patient groups. However, physician reimbursement differs for both groups: FFS for patients with private insurance (i.e. the admitting physician's reimbursement escalates progressively with each day that the patient spends in hospital) and base salary irrespective of care provided for patients with universal insurance (capitation payment model). All admitting physicians are aware of the patient's insurance status and the duration of hospitalization is at the discretion of the admitting physician. This study aimed to compare cost of care of patients with and without insurance admitted to a teaching hospital with a primary gastroenterology or hepatology (GIH) diagnosis. METHODS: All hospital inpatients admitted between January 2008 and December 2009 with a primary GI-related diagnosis related group (DRG) were identified. Patients were classified as uninsured (state-funded) or privately insured. Only DRGs with at least five patients in both the insured and uninsured patient groups were analyzed to ensure a precise estimate of inpatient costs. Patient level costing (PLC) was used to express the total cost of hospital care for each patient; PLC comprised a weighted daily bed cost plus cost of all medical services provided (e.g. radiology, pathology tests) calculated according to an activity-based costing approach, cost of medications were excluded. An overall mean cost of care per patient was calculated for both groups. All costs were discounted to 2009 values. RESULTS: In total, 630 patients were admitted with one of 11 GIH DRGs, 181 (29 %) with private insurance. Pooled mean cost of care was higher for uninsured (6,781 euros/patient) compared to insured patients (6,128 euros/patient). Apart from patients with 'non-cirrhotic non-alcoholic liver disease (non-complex)' in whom mean cost was higher for insured patients, there were no significant differences in mean cost of care nor mean patient age for insured and uninsured groups for any other diagnoses. CONCLUSION: Inpatient hospital costs were equivalent for patients with and without private health insurance when care was provided in a single hospital. Provision of care for all patients in a common hospital setting regardless of health insurance status may reduce disparities in healthcare utilization.

Randomized controlled trial of feedback on cost of hospital care among gastroenterology inpatients.

INTRODUCTION: Spending on hospital inpatients comprises a major proportion of healthcare costs. This study assessed the impact of systematic feedback to gastroenterologists on the cost of care provided to inpatients on a gastrointestinal/hepatology (GIH) hospital service. METHODS: Patients with a GIH diagnosis were randomly assigned to be cared for by one of two hospital services. Over 3 months, teams were randomized to receive feedback (GIH A) or no feedback (GIH B, control group); feedback consisted of an email sent twice weekly to all physicians on the GIH A service detailing the length of stay (LOS) and real-time cost of care accrued by each inpatient. RESULTS: Over 3 months, care was provided to 56 (GIH A) and 47 (GIH B) inpatients with a GIH illness. Patient complexity level was similar for both services as demonstrated by mean relative value: 1.11 (GIH A) vs. 1.27 (GIH B), p=0.2. Weighted LOS and weighted cost of care values were calculated to adjust for the respective RV of each patient. Mean weighted LOS (10.8 [GIH A] vs. 13.8 days/pt [GIH B], p=0.02) and mean weighted cost of care (9,904 [GIH A] vs. 12,654 euros/pt [GIH B], p=0.02) were significantly lower in the feedback group. Subsequent hospital readmission rates did not differ among both groups. CONCLUSION: Systematic feedback on cost of care was associated with lower healthcare costs without compromising quality. Incorporating a running total of patient costs into computer software used to order patient tests may represent one approach to controlling healthcare expenses.

Specialty-specific admission: a cost-effective intervention?

INTRODUCTION: Cost effectiveness of healthcare has become an important component in its delivery. Current practices need to be assessed and measured for variations that may lead to financial savings. Speciality specific admission is known not only to lead improved clinical outcomes but also to lead important cost reductions. METHODS: All patients admitted to an Irish teaching hospital via the emergency department over a 2-year period with a gastroenterology (GI) related illness were included in this analysis.GI illness was classified using the Disease related grouping (DRG) system. Mean length of stay (LOS) and patient level costing (PLC) were calculated. Differences between DRGs with respect to speciality (i.e. specialist vs. non-specialist) were calculated for the five commonest DRGs. RESULTS: Significant variations in LOS and PLC were demonstrated in the DRGs. Mean LOS varied with increasing complexity, from 3.2 days for non-complex GI haemorrhage to 14.4 days for complex alcohol related cirrhosis as expected. A substantial difference in LOS within DRG groups was demonstrated by large standard deviations in the mean (up to 8.1 days in some groups) and was independent of complexity of cases. PLC also varied widely in both complex and non-complex cases with standard deviations of up to 17,342 noted. Specialty-specific admission was associated with shorter LOS for most GI admissions. CONCLUSION: Significant disparity exists for both LOS and PLC for most GI diagnoses. Specialty-specific admissions are associated with reduced LOS. Specialty-specific admission would appear to be cost-effective which may also lead to improved clinical outcomes.

Developmental and TGF-beta-mediated regulation of Ank mRNA expression in cartilage and bone.

OBJECTIVES: Ank encodes a transmembrane protein that is involved in pyrophosphate (PPi) transport and mutations in the Ank gene have been associated with pathological mineralization in cartilage and bone. To understand how Ank works in normal skeletal development it is also important to know which cells within the developing skeleton express Ank. To this end, we examined the expression pattern of Ank mRNA during mouse embryonic development as well as in mouse hind limb joints with emphasis on the period when articular cartilage forms. Since it was previously shown that TGF-beta regulates PPi transport in cells in culture, we also tested the hypothesis that TGF-beta regulates Ank expression. METHODS: The localization of Ank mRNA was determined by radioactive in situ hybridization in E15.5 and E17.5 mouse embryos as well as in 1 and 3 week post-natal mice. Ank expression was compared to that of other cartilage markers. In situ hybridization and semi-quantitative RT-PCR were used to determine the effects of TGF-beta on Ank expression in metatarsal organ cultures. RESULTS: Ank expression was detected at high levels at sites of both endochondral and intramembranous bone development. In endochondral bones, expression was detected in a subset of hypertrophic cells at ossification centers. Expression was also detected in osteogenic/chondrogenic cells of the perichondrium/periosteum lining the metaphysis, an area associated with the formation and extension of the bone collar. High levels of expression were also detected in non-mineralized tissues of the skeletal system including tendons and the superficial layer of the articular cartilage. Treatment with TGF-beta resulted in an approximately four-fold induction of Ank mRNA in prehypertrophic chondrocytes and perichondrium of metatarsal cultures. CONCLUSIONS: The expression pattern of Ank suggests an important role both in inhibiting and regulating mineralization in the developing skeletal system. In addition, TGF-beta1 is able to mediate Ank mRNA expression in chondrocytes suggesting a possible role for TGF-beta and Ank in the regulation of normal mineralization.

Cloning and expression of cDNA for human poly(ADP-ribose) polymerase.

cDNAs encoding poly(ADP-ribose) polymerase from a human hepatoma lambda gt11 cDNA library were isolated by immunological screening. One insert of 1.3 kilobases (kb) consistently hybridized on RNA gel blots to an mRNA species of 3.6-3.7 kb, which is consistent with the size of RNA necessary to code for the polymerase protein (116 kDa). This insert was subsequently used in both in vitro hybrid selection and hybrid-arrested translation studies. An mRNA species from HeLa cells of 3.6-3.7 kb was selected that was translated into a 116-kDa protein, which was selectively immunoprecipitated with anti-poly (ADP-ribose) polymerase. To confirm that the 1.3-kb insert from lambda gt11 encodes for poly(ADP-ribose) polymerase, the insert was used to screen a 3- to 4-kb subset of a transformed human fibroblast cDNA library in the Okayama-Berg vector. One of these vectors [pcD-p(ADPR)P; 3.6 kb] was tested in transient transfection experiments in COS cells. This cDNA insert contained the complete coding sequence for polymerase as indicated by the following criteria: A 3-fold increase in in vitro activity was noted in extracts from transfected cells compared to mock or pSV2-CAT transfected cells. A 6-fold increase in polymerase activity in pcD-p(ADPR)P transfected cell extracts compared to controls was observed by "activity gel" analysis on gels of electrophoretically separated proteins at 116 kDa. A 10- to 15-fold increase in newly synthesized polymerase was detected by immunoprecipitation of labeled transfected cell extracts. Using pcD-p(ADPR)P as probe, it was observed that the level of poly(ADP-ribose) polymerase mRNA was elevated at 5 and 7 hr of S phase of the HeLa cell cycle, but was unaltered when artificial DNA strand breaks are introduced in HeLa cells by alkylating agents.

Interferon action: RNA cleavage pattern of a (2'-5')oligoadenylate--dependent endonuclease.

One of the mediators of interferon action is a latent endoribonuclease (ribonuclease L) that is activated by (2'-5')oligoadenylates. Among the homopolymers of the four common ribonucleotides, activated ribonuclease L degrades at an appreciable rate only polyuridylic acid. In two natural RNA's tested the most frequent ribonuclease L cleavages occur after UA, UG, and UU (A, adenine; U, uracil; and G, guanine) and much less frequent cleavages after CA and AC (C, cytosine).

Mouse interferons: production by Ehrlich ascites tumour cells infected with Newcastle disease virus and its enhancement by theophylline.

Conditions are described for the production of 0.3 to 0.7 NIH mouse reference standard units of interferon per cell from Ehrlich ascites tumour cells cultured as monolayers and induced by infection with Newcastle disease virus (NDV). Inclusion of theophylline (6 mM) in the medium increased the interferon yield three to four times. Cells infected with NDV started to lyse at about 15 p.i., but infected, theophylline-treated cells lysed only 24 p.i. Several other methylxanthines (e.g. theobromine, caffeine and isobutylmethylxanthine) when tested a concentrations similar to that of theophylline, did not boost interferon production. Dibutyryl cyclic AMP (10(-10) to 10(-2)M) did not substitute for theophylline in increasing interferon production, and, if used together with theophylline, did not cause further enhancement.

Large scale production of mouse interferons from monolayers of Ehrlich ascites tumour cells.

Conditions are described for the large scale production of mouse interferons from Ehrlich ascites tumour cells cultured as monolayers in roller bottles. With the procedure reported here, we have used 50 to 65 600 cm(2) roller bottles to produce routinely 2 X 10(9) to 3 X 10(9) International units of crude mouse interferon/week with a specific activity of 1 X 10(6) to 1.5 X 10(6) units/mg protein.

Double-stranded RNA and the enzymology of interferon action.

Extracts from interferon-treated, not virus-infected Ehrlich ascites tumor cells differ in various biochemical characteristics from extracts of control cells. We studied three enzymes whose level is enhanced in cells upon treatment with IF and which are causing some of the differences. (2'-5')(A)n synthetase, an enzyme converting ATP into a series of (2'-5') linked oligoadenylates ((2'-5')(An)) in the presence of dsRNA was purified to homogeneity and characterized. The second enzyme, RNase L, a latent endonuclease, which can be activated by (2'-5')(A)n to cleave single-stranded RNAs, was purified several hundredfold. The activation of this enzyme is reversible and is lost upon removal of (2'-5')(A)n. The activation is not accompanied by a large change in shape of conformation of the enzyme. The third enzyme is a protein kinase which if activated by dsRNA can phosphorylate the peptide chain initiation factor eIF-2 and a protein designated P1 of 67,000 daltons. This enzyme was purified several thousandfold. The most highly purified preparation consists of three proteins with P1 as the most abundant component.

Interferon, double-stranded RNA, and RNA degradation: activation of an endonuclease by (2'-5')An.

Among the mediators of interferon action are one enzyme that is activated by double-stranded RNA to convert ATP to (2'-5')An and a second enzyme, an endonuclease, that is activated by (2'-5')An to cleave single-stranded RNA. The binding of (2'-5')An to the endonuclease (partially purified from mouse Ehrlich ascites tumor cells) is revealed by its retention on nitrocellulose filters. This can serve as the basis for an assay of the enzyme. Activation of the enzyme is reversible and is lost upon removal of (2'-5')An:gel filtration of activated endonuclease on Sephacryl S-200 results in an inactive enzyme. The enzyme can be activated again, however, by addition of (2'-5')An. The elution volume of the nonactivated endonuclease from Sephadex G-200 indicates that its molecular weight is 185,000, unusually large for a nuclease. The elution volume of the maximally activated endonuclease from Sephadex G-200 equilibrated with (2'-5')An is not detectably different from that of enzyme that had not been previously activated that was passed through Sephadex G-200 not equilibrated with (2'-5')An. This indicates that the activation does not result in a large change in the size or conformation of the enzyme.

Structural characteristics of interferons from mouse Ehrlich ascites tumor cells.

An improved procedure for the isolation of interferons produced by mouse Ehrlich ascites tumor cells infected with Newcastle disease virus provides interferons of three size classes (33,000, 26,000, and 20,000 daltons) with specific activities between 2 and 3 x 10(9) units/mg of protein and a yield of 11 to 20%. The tryptic peptide maps of the two larger species are very similar; that of the smallest species is different, at least in part. The amino acid compositions of the three species are very close. Their NH2-terminal amino acids are identical and so are the amino acids released by carboxypeptidase A treatment. These data are consistent with the possibility that the differences in size between the three species may be due, at least in part, to unequal glycosylation.

Interferon action: two distinct pathways for inhibition of protein synthesis by double-stranded RNA.

Double-stranded RNA inhibits protein synthesis in at least two ways. It activates a protein kinase that blocks peptide chain initiation by phosphorylating the peptide chain initiation factor eIF-2 and also activates an endonuclease that inactivates different mRNAs at different rates. The protein kinase and the endonuclease have been partially purified from interferon-treated Ehrlich ascites tumor cells. The 2',5'-oligoadenylates [pppA(2'p5'A)n], found found earlier to be mediators in the activation of the endonuclease by double-stranded RNA, are not mediators in the activation of the protein kinase by double-stranded RNA.

Purification of interferon from mouse Ehrlich ascites tumor cells.

Interferon production was induced in mouse Ehrlich ascites tumor cells by infection with Newcastle disease virus. The interferon produced was purified by precipitation with ammonium sulfate, chromatography on carboxymethyl-Sephadex, treatment with blue dextran and polyethylene glycol, gel filtration on Bio-Gel P-60 and Bio-Gel P-200, chromatography on phosphocellulose, isoelectric focusing, and chromatography on octyl-Sepharose. The specific activity of the product was 1.6 x 10(9) NIH mouse interferon reference standard units/mg of protein. Electrophoresis in polyacrylamide gels in the presence of sodium dodecyl sulfate indicated that the apparent molecular weight of the interferon-active material ranged from 25,000 to 35,000. As revealed by staining the gels with Coomassie brilliant blue, the interferon activity co-migrated with the major, broad protein band. Minor, stainable bands of proteins were free of interferon activity and their apparent molecular weight was smaller than 12,000.