Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.     

Quality of life after acoustic neuroma surgery

OBJECTIVE: To assess how surgery affected the quality of life of patients with acoustic neuromas and to investigate possible predictors of the functional outcome following surgery. STUDY DESIGN: A questionnaire based on the Glasgow Benefit Inventory was completed by patients randomly selected following acoustic neuroma surgery. SETTING: Skull base surgery unit of a university teaching hospital (tertiary referral center). PATIENTS: Fifty-three patients with acoustic tumors (follow-up, 1 to 3 y). RESULTS: With regard to overall quality of life, nine patients (17.4%) reported that it became better, 28 patients (53.8%) worse, and 15 patients (28.8%) that it remained the same. Four patients (7.8%) became better off financially, 15 patients (29.4%) worse, and 32 (62.8%) remained unchanged. Forty-one patients (78.8%) did not change their occupation, and 11 (21.2%) had to change their occupation, mainly because of the adverse effects of the operation. With regard to the age at operation, older patients were found to have better overall quality of life. Moreover, younger patients had worse postoperative financial status and they were more likely to change their occupation after the operation. The tumor size did not significantly affect the overall postoperative quality, but it did affect the postoperative financial status (patients with larger tumors were more likely to have worse postoperative financial status). CONCLUSION: Acoustic neuroma surgery has a significant impact on patients' overall quality of life. Surgeons proposing to operate on small tumors should not assume that the impact on patients' life will be necessarily less than that following the removal of larger tumors. All patients, especially in the younger age group, should be prepared and thoroughly informed about the consequences of the operation on their quality of life.     

Immunogenicity of Plasmodium falciparum circumsporozoite protein multiple antigen peptide vaccine formulated with different adjuvants

Only low antibody levels were obtained from vaccinating human volunteers with single-chain peptide from the Plasmodium falciparum circumsporozoite protein (PfCSP). This resulted in modest protection against sporozoite challenge. In addition, HLA restriction limits the probability of synthesis of a vaccine effective for a diverse population. We report immunization studies with a multiple antigen peptide (MAP) system consisting of multiple copies of a B-cell epitope from the central repeat region of the PfCSP in combination with a universal T-cell epitope, the P2P30 portion of tetanus toxin. This MAP4(NANP)6P2P30 vaccine was highly immunogenic in four different strains of mice when used with various safe and nontoxic adjuvants. When this MAP vaccine was encapsulated in liposomes with lipid A and adsorbed to aluminium hydroxide and given three times at 4-week intervals, the resultant antibody prevented 100% of sporozoites from invading and developing into liver stage infection. This high degree of immunogenicity of MAP4(NANP)6P2P30 vaccine formulated in liposomes, lipid A and aluminum hydroxide provides the foundation for consideration of human trials with this formulation.     

A novel role of ImmE7 in the autoregulatory expression of the ColE7 operon and identification of possible RNase active sites in the crystal structure of dimeric ImmE7

Site-specific cleavage of mRNA has been identified in vivo for the polycistronic colicin E7 operon (ColE7), which occurs between G and A nucleotides located at the Asp52 codon (GAT) of the immunity gene (ceiE7). In vitro, this specific cleavage occurs only in the presence of the ceiE7 gene product (ImmE7). The crystal structure of dimeric ImmE7 has been determined at 1.8 A resolution by X-ray crystallographic analysis. We found that several residues located at the interface of dimeric ImmE7 bear surprising resemblance to the active sites of some RNases. These results suggest that dimeric ImmE7 may possess a novel RNase activity that cleaves its own mRNA at a specific site and thus autoregulates translational expression of the downstream celE7 gene as well as degradation of the upstream ceaE7 mRNA.     

Estimated benefits of glycemic control in microvascular complications in type 2 diabetes

BACKGROUND: The benefits of intensive glycemic control in patients with type 2 diabetes are not well quantified. It is therefore not clear which patients will benefit most from aggressive glycemic control. OBJECTIVE: To evaluate the efficacy of glycemic control in type 2 diabetes. DESIGN: Markov decision model. PATIENTS: Diabetic patients at a health maintenance organization. MAIN OUTCOME MEASURES: Risks for developing blindness and end-stage renal disease; number of patients and patient-years needed to treat to prevent complications. RESULTS: For a patient in whom diabetes developed before 50 years of age, reducing hemoglobin A1c levels from 9% to 7% results in an estimated 2.3-percentage point decrease (from 2.6% to 0.3%) in lifetime risk for blindness due to retinopathy. The same change in a patient with diabetes onset at 65 years of age would be expected to decrease the risk for blindness by 0.5 percentage points (from 0.5% to < 0.1%). However, the Markov model predicts substantially greater benefit when moving from poor to moderate glycemic control than when moving from moderate to almost-normal glycemic control. Targeting less than 20% of the patients at one health maintenance organization for intensified therapy may prevent more than 80% of the preventable patient-time spent blind. The risks for end-stage renal disease and the risk reduction provided by improved glycemic control are lower than those for blindness. CONCLUSIONS: This probability model, based on extrapolation from the experience with type 1 diabetes, suggests that patients with early onset of type 2 diabetes will accrue substantial benefit from almost-normal glycemic control. In patients with later onset, moderate glycemic control prevents most end-stage complications caused by microvascular disease. These results have important implications for informing patients and allocating health care resources.     

The effect of ischemic preconditioning on the recovery of skeletal muscle following tourniquet ischemia

It has been well documented that ischemic preconditioning limits ischemic-reperfusion injury in cardiac muscle, but the ability of ischemic preconditioning to limit skeletal muscle injury is less clear. Previous reports have emphasized the beneficial effects of ischemic preconditioning on skeletal muscle structure and capillary perfusion but have not evaluated muscle function. We investigated the morphologic and functional consequences of ischemic preconditioning, followed by a 2-hour period of tourniquet ischemia on muscles in the rat hindlimb. The 2-hour ischemia was imposed without preconditioning, or was preceded by three brief (10 minutes on/10 minutes off) preischemic conditioning intervals. We compared muscle morphology, isometric contractile function, and muscle fatigue properties in predominantly fast-twitch, tibialis anterior muscles 3 (n = 8) and 7 (n = 8) days after ischemia-reperfusion. Two hours of ischemia, followed by reperfusion, results in a 20 percent reduction of muscle mass (p < 0.05) and a 33 percent reduction in tetanic tension (p < 0.05) when compared with controls (n = 8) at 3 days. The same protocol, when preceded by ischemic preconditioning, results in similar decreases in muscle mass and contractile function. Neuromuscular transmission was also impaired in both ischemic groups 7 days after ischemia. Nerve-evoked maximum tetanic tension was 69 percent of the tension produced by direct muscle stimulation in the ischemia group and 65 percent of direct tension in the ischemic preconditioning/ischemia group. In summary, ischemic preconditioning, using the same protocol reported to be effective in limiting infarct size in porcine muscle, had no significant benefit in limiting injury or improving recovery in the ischemic rat tibialis anterior. The value of ischemic preconditioning in reducing imposed ischemic-reperfusion-induced functional deficits in skeletal muscle remains to be demonstrated.