Identifying potentially ineffective care in a community hospital

OBJECTIVES: To develop a formula to predict mortality for intensive care unit patients between day 5 in an intensive care unit and 100 days after hospital discharge from a community hospital. DESIGN: Retrospective 1-yr derivation study with validation on a subsequent year's intensive care unit population. SETTING: An 850-bed, not-for-profit community hospital with three adult intensive care units, including medical-surgical, cardiac-medical, and cardiac-surgical units. PATIENTS: The development patient set included 4045 consecutive adult admissions to the intensive care unit between July 1995 and June 1996. The validation sample consisted of 4084 admissions between July 1996 and June 1997. RESULTS: During the first year, 100-day posthospital discharge mortality was predicted by the combination Acute Physiology and Chronic Health Evaluation (APACHE) III predicted mortality on day 5 of >0.92 or the product of day 1 and day 5 APACHE predicted mortality of >0.40, with an increase in the APACHE predicted mortality from day 1 to day 5 of >0.10. Specificity in the development cohort was 0.99, sensitivity was 0.30, and positive predictive value was 0.95. The second-year validation study demonstrated a specificity, sensitivity, and positive predictive value of 0.98, 0.29, and 0.91, respectively, when applying the model to the validation sample. CONCLUSIONS: By using readily available APACHE III data, we were able to identify patients at high risk of dying between intensive care unit day 5 and 100 days after discharge. Although the low sensitivity limits the number of patients for whom death at 100 days is predicted, the high specificity and positive predictive value suggests this information may provide useful information for families and physicians. If these formulas can be validated in diverse institutional settings, decisions regarding short- and long-term outcomes may be improved by using objective survival predictions from two time points.     

Reversion and maintenance of sinus rhythm in patients with permanent atrial fibrillation by internal cardioversion followed by biatrial pacing

Patients in atrialfibrillation (AF) who fail external cardioversion are usually regarded as in permanent AF. Internal cardioversion may revert many such patients into sinus rhythm (SR) but the majority relapse rapidly into AF. We investigated whether internal cardioversion followed by biatrial pacing is an effective to restore and subsequently maintain SR in patients with permanent AF. Patients in permanent AF underwent internal cardioversion that was followed by biatrial temporary pacing for 48 hours. Those who remained in SR received a permanent biatrial pacemaker programmed to a rate responsive mode with a lower rate 90 beats/min. Primary end point of the study included maintenance in SR 3 months after internal cardioversion. Sixteen patients (14 men, 57 +/- 11 years) were cardioverted. The median duration of AF was 24 months (quartiles, Q1 = 8.5 and Q3 = 102) and mean left atrium diameter was 48 +/- 04 mm. A permanent biatrial pacemaker was implanted in 11 patients. At a mean fallow-up of 15 months (range 4 to 24), 8 patients remained in SR for more than 3 months. AF was eliminated in 5 patients, while in two a second internal cardioversion on amiodarone was required. Antiarrhythmic therapy was used in half of our population and did not predict the long-term maintenance of SR. Following internal cardioversion with continuous biatrial pacing, 50% of patients with permanent AF were maintained for prolonged periods in SR. This is a new modality of treatment of permanent AF directed to the maintenance of SR that provides a further therapeutic option in end-stage AF.     

A 12-month,multicenter, prospective,open-label trial of radiographic analysis of disease progression in osteoarthritis of the knee or hip in patients receiving celecoxib

BACKGROUND: Studies have suggested that nonspecific nonsteroidal anti-inflammatory drugs may inhibit matrix biosynthesis by articular cartilage, thereby accelerating the progression of osteoarthritis (OA). OBJECTIVE: The objective of this analysis was to determine whether 1-year treatment with the cyclooxygenase-2-specific inhibitor celecoxib at up to twice the recommended and maximally effective dose for OA had any deleterious effects on OA progression by assessing radiographic changes in knee or hip joint morphology in patients with OA. METHODS: In a 12-month, multicenter, prospective, open-label trial, patients with OA of the knee or hip or rheumatoid arthritis received celecoxib at doses ranging from that recommended for the treatment of OA (200 mg/d) to twice the recommended daily dosage (400 mg/d). Available radiographs showing baseline and end-of-treatment status were analyzed using semiquantitative measures of index joint morphology in patients with mild to moderate OA. The morphologic scores were then subjected to mean change and shift-table analysis to determine the extent and rate of disease progression. RESULTS: A total of 2,327 patients (796 with OA of the knee, 1,531 with OA of the hip) were included. A subset of 344 patients (160 with OA of the knee, 184 with OA of the hip) had radiographs from both before and after 12 months' celecoxib treatment. One hundred forty-seven and 158 pairs of knee and hip radiographs, respectively, were available for analysis. These revealed that, with the exception of significant hip joint-space narrowing (P = 0.029), no evidence of disease progression with long-term celecoxib treatment could be detected. The observed increase in hip joint-space narrowing was small (0.14 units/y) (95% CI, 0.08-0.20), was observed prior to celecoxib exposure (by mean change or shift-table analysis), and was not dose related. CONCLUSION: These results are consistent with the hypothesis that long-term therapy with celecoxib does not accelerate progression of OA of the knee or hip.     

Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons

Long-term potentiation (LTP) in wide dynamic range (WDR) neurons in the dorsal horn has been suggested to contribute to central sensitization and the development of chronic pain. Indirect experimental evidence indicates an involvement of substance P (SP), in this respect. The aim of the present study was to monitor the extracellular level of substance P-like immunoreactivity (SP-LI) in the dorsal horn of the rat during and after induction of LTP in WDR neurons in vivo. Electrophysiological recordings of single (WDR) neurons were performed in parallel with microdialysis in the dorsal horn under urethane-anaesthesia. The amount of SP-LI in the microdialysate was determined by radioimmunoassay. As previously shown, high frequency conditioning stimulation of the sciatic nerve induced an increased firing response of WDR neurons. An increased response to C-fibre stimulation, but not A-fibre stimulation, could be determined. A significant increase of the extracellular level of SP-LI in the dorsal horn was detected during, but not after, induction of LTP. These data suggest that SP may be involved in the induction of LTP by high frequency stimulation. However, the maintenance of spinal LTP following high frequency peripheral nerve stimulation does not seem to depend on an increased release of SP.     

Social capital, local community participation and the construction of pakistani identities in England: implications for health inequalities policies

Emphasis has been placed on the importance of the participation of socially excluded groups in local initiatives to reduce health inequalities in England, in `partnerships' with government. We examine potential obstacles to such participation through a case study of factors shaping local participation by residents of a deprived multi-ethnic area who describe themselves as Pakistani. We draw on three-hour interviews with 26 men and women, aged 15-67 years. Assuming that a sense of common identification is a precondition for participation in local community networks, we examine how the construction of Pakistani identities, within conditions of material and symbolic social exclusion, constrains the likelihood of widespread, representative local participation by Pakistani people in our local area of interest. No matter how significant a category such as `Pakistani' might be in statistical analyses of health inequalities, an epidemiological category of this nature cannot simply be `mapped' onto policy recommendations.     

HLA tetramer-based artificial antigen-presenting cells for stimulation of CD4+ T cells

Current evidence suggests that immunotherapy for cancer or infectious diseases will require the activation of CD4(+) T cells in addition to the activation of cytotoxic CD8(+) T cells. To complement and overcome some of the limitations of dendritic-cell-based vaccines and ex vivo expansion of human T cells, we sought to engineer artificial antigen-presenting cells (aAPCs) for the stimulation of antigen-specific human CD4(+) T cells. We have designed a variety of aAPCs using magnetic beads as a scaffold on which to coat HLA-peptide tetrameric complexes along with costimulatory molecules such as anti-CD28. Here, we tested various forms of conjugation of the tetramers onto beads, characterized the relative concentration of antigen available on the surface of the beads, and evaluated the ability of different types of beads to promote activation of antigen-specific CD4(+) T cells. We find that an indirect coating of HLA-peptide tetramers on beads via an anti-Class II antibody provides specific stimulation of antigen-specific CD4(+) T cells.