Immunogenicity of the hepatitis A vaccine 20 years after infant immunization.

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.

Incidence of diabetes mellitus in a population-based cohort of persons with chronic hepatitis B virus infection.

To investigate the effect of hepatitis B virus (HBV) infection on the development of diabetes mellitus (DM), we compared DM incidence and characteristics of Alaska Native persons with and without HBV infection. From 1990 to 2010, there were 52 incident DM cases among 1309 persons with infection vs 4557 DM cases among 85 698 persons without infection (log-rank test, P = 0.20). Compared to infected persons without DM, those with DM were significantly older (57.0 vs 47.4 years, P < 0.001) and had higher body mass index (34.5 vs 28.4 kg/m(2) , P < 0.001). Genotype, immune active disease and the presence of cirrhosis were not associated with DM. In this population-based cohort with over 20 years of follow-up, there was no effect of HBV infection on DM development.

Clinical significance of elevated alpha-fetoprotein in Alaskan Native patients with chronic hepatitis C.

The clinical significance of elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C virus (HCV) infection is not well defined. We analysed data from a population-based cohort of patients with HCV infection to assess the prevalence of elevated serum AFP, to determine its association with clinical and virologic parameters and with clinical outcomes. We defined a slightly elevated serum AFP level as 8 to <15 and a high-AFP level as > or =15 microg/L. Among 541 HCV-RNA-positive persons, 61 (11%) had a slightly elevated or high AFP at the time of consent. AFP > or =8 microg/L was associated with the older age, aspartate aminotransferase/alanine aminotransferase ratio >1, and higher alkaline phosphatase levels, but not with heavy alcohol use, IV drug use, genotype, viral load or duration of HCV infection. Among 192 persons with an AFP at liver biopsy, 17% had an AFP > or =8 microg/L. The sensitivity/specificity of an AFP level > or =8 in detecting Ishak 3-6 fibrosis was 39%/95%. Among 372 persons with a minimum of four AFP measurements over 6 years, 5% had persistently elevated AFP >8 microg/L, 19% had both elevated and normal AFP measurements, and 76% had persistently normal AFP. Elevated AFP at consent was associated with hepatocellular carcinoma (HCC) and end-stage liver disease. Over 6 years of follow-up, persistently elevated AFP was associated with the development of HCC; no person with AFP persistently <8 microg/mL developed HCC. Serial AFP measurements appear to be useful in identifying persons with advanced fibrosis and help to determine who needs periodic screening with liver ultrasound to detect HCC.

Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patients.

Liver biopsy is the primary method of assessing liver injury in hepatitis C patients. FIBROSpect II (FS), a diagnostic panel of three extracellular matrix remodelling markers, may be useful as a noninvasive alternative to this procedure. The purpose of this study was to correlate FS results with liver fibrosis scores to determine if this test is sufficiently accurate to be a viable alternative to liver biopsy. A total of 142 serum specimens were evaluated for fibrosis with FS and were compared with Knodell and Ishak fibrosis scores. FS reports an index score ranging from 0.1 to 1.0, which corresponds to the probability of progressive liver fibrosis. Using a FS index cut-off of 0.42, 50 of 54 patients with Ishak 3-6 were classified as having advanced fibrosis (METAVIR F2-F4) and 58 of 88 patients with Ishak 0-2 as having no/mild fibrosis (METAVIR F0-F1), resulting in a sensitivity of 93%, specificity of 66%, and an overall test accuracy of 76%. With a 38% prevalence of advanced fibrosis, the negative predictive value was 94% and positive predictive value was 63%. A biopsy length of > or = 2 cm was associated with higher concordance between FS results and liver fibrosis scores (P = 0.01). FS was clinically useful in ruling out advanced fibrosis in hepatitis C by identifying patients with mild disease in whom treatment could be deferred. The limitation of this test is its decreased sensitivity and specificity in the middle of the test's reporting range between scores of 0.42 and 0.80.

Brief report on the effect of providing single versus assorted brand name condoms to hospital patients: a descriptive study.

OBJECTIVES: This study examined condom acquisition by persons in a hospital setting when single versus assorted brand name condoms were provided. METHODS: Condom receptacles were placed in exam rooms of two clinics. During Phase 1, a single brand name was provided; for Phase 2, assorted brand names were added. Number of condoms taken was recorded for each phase. RESULTS: For one clinic there was nearly a two-fold increase in number of condoms taken (Phase 1 to Phase 2); for the second clinic there was negligible difference in number of condoms taken. CONCLUSIONS: The provision of assorted brand name condoms, over a single brand name, can serve to increase condom acquisition. Locations of condoms and target population characteristics are related factors.

Evolution of abstracts presented at the annual scientific meetings of academic emergency medicine.

There has been a general trend in medicine towards greater sophistication in research design. In order to assess this trend in emergency medicine we compared the characteristics of abstracts presented at the 1974, 1983, 1989, and 1997 annual scientific meetings of academic emergency medicine. All 870 abstracts were reviewed by 1 of 3 investigators who determined research design attributes using a standardized classification scheme that has good interrater reliability. Over the last 25 years the following trends were noted: more surveys (0% v1% v3% v8%, P = 0.002), more randomized studies (0% v10% v12% v15%, P = 0.05), and more blinded studies (0% v7% v5% v11%, P = 0.01). Tests of statistical significance were reported with increasing frequency (8% v26% v59% v69%, P < 0.001) as were power calculations (0% v0% v1% v3%, P = 0.02). During the study period there were also increases in the median number of authors, proportion of foreign lead authors, and the proportion of studies involving human subjects. These results reflect considerable improvement in the degree of research design sophistication reported in selected abstracts of academic emergency medicine over the study period. Further strategies to assure continued enhancement of emergency medicine research should be explored.

How well do patients obtain short-term follow-up after discharge from the emergency department?

STUDY OBJECTIVE: We sought to determine the follow-up rate of discharged emergency department patients who were instructed to obtain reevaluation within 48 hours at our ED, a clinic, or a private physician's office and to determine the reasons why patients do not obtain short-term follow-up when instructed. METHODS: Emergency physicians prospectively enrolled a convenience sample of patients discharged from a university hospital ED who were believed to be at risk for clinical deterioration. Patients were instructed to obtain reevaluation within 48 hours at a public clinic, private physician's office, or our ED (without charge). A telephone interview was conducted after 48 hours had elapsed. RESULTS: Three hundred twenty-five patients were enrolled, 300 were included in data analysis, and 203 (67.7%) of these obtained follow-up as instructed. Those referred to the ED had a higher follow-up rate (105/127 [82.7%]) than those referred to clinics (59/99 [59.6%]) or private physicians (39/74 [52.7%]). Inability to obtain an appointment was cited by 34.3% of those who did not obtain follow-up care as instructed. CONCLUSION: Many patients discharged from the ED who were believed to be at risk for clinical deterioration did not obtain medical follow-up within 48 hours when so instructed. Free ED follow-up resulted in a better rate of short-term follow-up than that for clinics and private physicians and may be especially useful if a patient's ability to obtain follow-up is uncertain or if timely reevaluation is particularly imperative.

Evolution of abstracts presented at the annual scientific meetings of academic emergency medicine.

There has been a general trend in medicine toward greater sophistication in research design. To assess this trend in emergency medicine, we compared the characteristics of abstracts presented at the 1974, 1983, 1989, and 1997 annual scientific meetings of Academic Emergency Medicine. All 870 abstracts were reviewed by 1 of 3 investigators who determined research design attributes using a standardized classification scheme that has good interrater reliability. Over the last 25 years, the following trends were noted: more surveys (0% v1% v3% v8%, P=.002), more randomized studies (0% v10% v12% v15%, P=.05), and more blinded studies (0% v7% v5% v11%, P=.01). Tests of statistical significance were reported with increasing frequency (8% v26% v59% v 69%, P < .001), as were power calculations (0% v0% v1% v3%, P=.02). During the study period, there were also increases in the median number of authors, proportion of foreign lead authors, and the proportion of studies involving human subjects. These results reflect considerable improvement in the degree of research design sophistication reported in selected abstracts of academic emergency medicine over the study period. Further strategies to assure continued enhancement of emergency medicine research should be explored.

Alterations in hepatic gluconeogenesis, prostanoid, and intracellular calcium during sepsis.

OBJECTIVE: The metabolic alterations observed during sepsis may be associated with changes in local concentrations of intracellular calcium (Ca2+) and prostanoid synthesis in the liver. The authors studied hepatocyte intracellular Ca2+ and the release of glucose and prostanoid in an in-vivo murine liver perfusion model. METHODS: Sepsis was induced in anesthetized, fasted rats by cecal ligation and puncture (CLP, n = 42). Hepatic glucose release was studied in control (n = 10) and CLP (n = 10) groups using a non-recirculating liver perfusion model with and without lactate as gluconeogenic substrate. Hepatocyte intracellular Ca2+ (n = 11) was measured using the selective indicator Fura-2 under basal and epinephrine (10(-5) M) stimulated conditions. 6-Keto-prostaglandin F1alpha (6-Keto) and thromboxane B2 (TxB2) were determined from liver perfusate by radioimmunassay (n = 11). Data were analyzed using t-tests and repeated-measures ANOVA. RESULTS: Plasma glucose was significantly lower in CLP groups compared with controls (74.9+/-6.6 vs 115.7+/-4.6 mg/dL, p < 0.05). Plasma lactate was significantly higher in CLP vs controls (3.7+/-0.4 vs 1.4+/-0.1 mM, p < 0.05). Glucose release in isolated perfused livers was significantly lower in CLP vs controls (8.5 vs 16+/-1.2 microM/g/hr, p < 0.001). With the addition of lactate + pyruvate to the perfusate, glucose output in CLP livers was significantly lower following 5 (9.9+/-0.7 vs 17.7+/-1.1 microM/g/hr, p < 0.05) and 10 (11.9+/-1.2 vs 20.6+/-1.3 microM/g/hr, p < 0.001) minutes of perfusion. The basal level of intracellular calcium ([Ca2+]i) in CLP rats (460.1+/-91.6 nM) was significantly higher than in control rats (196.3+/-35.5 nM) (p < 0.05). A significant increase (p < 0.05) in [Ca2+]i occurred after the addition of epinephrine in hepatocytes in control (196.3+/-35.5 vs 331.8+/-41.4 nM) but not CLP (460.1+/-91.6 vs 489.4+/-105 nM) rats. 6-Keto was significantly lower in CLP compared with controls at 30 minutes (25.7+/-3.9 vs 33.4+/-5.5 pg/mL, p < 0.05), whereas TxB2 was not significantly altered (52.1+/-34.7 vs 87.5+/-43.2 pg/mL). CONCLUSION: These results demonstrate that CLP sepsis is associated with an increase in hepatocyte intracellular free Ca2+ concentration along with attenuation of hormone-mediated Ca2+ mobilization and hepatic gluconeogenesis.

Thermal characteristics of neutralization therapy and water dilution for strong acid ingestion: an in-vivo canine model.

OBJECTIVE: To determine whether in-vivo neutralization therapy for acid ingestions will superimpose a thermal injury upon tissue already damaged by acid. METHODS: An in-vivo canine model was used with repeated measures of tissue and luminal temperatures. All dogs were placed under halothane general anesthesia. The stomach was exteriorized and temperature probes were placed in the lumen and mucosa. 25 mL of 0.5 N HCl (25 degrees C) was placed in the gastric lumen followed 5 minutes later by 75 mL of either 8% NaHCO3 neutralization (25 degrees C, n = 10) or water dilution (25 degrees C, n = 10). Temperature measurements were recorded at specified intervals for 5 minutes post HCl acid exposure and for 30 minutes post treatment. Temperature profiles were analyzed by repeated-measures ANOVA. Post-treatment changes were evaluated using signed-rank tests. RESULTS: In both treatment groups, treatment resulted in significant decreases in initial mucosa and intraluminal temperatures. Both the mucosa and intraluminal temperatures decreased immediately after treatment with HCO3 by an average of 1.6 degrees C (p = 0.05). In the water dilution treatment group, both temperatures decreased by 1.1 degrees C (p = 0.05). Ensuing post-treatment temperatures increased but did not reach baseline temperatures at any time up to 30 minutes post treatment. CONCLUSIONS: In the in-vivo setting, there is no evidence of hazardous temperature elevation when a weak alkali or dilution therapy is used to neutralize strong acid-induced injury. Contraindication of this form of emergency treatment should not be based on the preconceived idea that a resultant exothermic reaction will cause a superimposed thermal injury. Further clinical study is needed to determine the clinical utility of this emergency therapeutic modality.

Choosing a managed care information system--what you need to know.

The new environment created by managed care has prompted providers to reconsider their information systems. An understanding of the market, the capabilities of various kinds of systems, and the needs of the organization can enable HIM professionals to aid their employers in making the right choices.

Low-frequency sonophoresis: pathologic and thermal effects in dogs.

OBJECTIVE: Low-frequency sonophoresis has recently been shown to significantly facilitate transdermal permeability of various substances (e.g., insulin) in animal models, thus eliminating the need to inject such agents. Prior to human trials, the authors studied the safety profile of low-frequency sonophoresis in dogs by evaluating microscopic and temperature changes in the skin after sonophoresis. METHODS: An evaluator-blinded canine study of sonophoresis using different energy intensities and probe diameters was performed. Low-frequency ultrasound was applied for 60 seconds to the clipped abdominal skin of 3 anesthetized adult mongrel dogs using a sonicator operating at a frequency of 20 KHz with a maximal energy output of 400 W. The sonicator was immersed in normal saline, and intensities of 4%, 10%, 20%, 30%, and 50% were applied during 600 msec of every second (pulsed mode). Three probes, 1-cm cylindrical, 5-cm cylindrical, and 10-cm disc-shaped, were evaluated. Each experimental condition was performed twice. Subcutaneous temperatures were measured by temperature probe before and after sonophoresis. At 30 minutes post-sonophoresis, full-thickness skin biopsies were taken for blinded histopathologic evaluation. RESULTS: Minimal urticarial reactions were noted with the 1-cm probe at intensities of < or = 20% and with the 5-cm probe at 4% intensity. With higher intensity, thermal injuries were observed grossly with erythema and vesicles. The microscopic correlates were papillary and dermal edema with neutrophils and telangiectasia. The conditions producing vesicles grossly had foci of epidermal necrosis, subepidermal vesicles, and degeneration of papillary dermal collagen. With still higher intensities, confluent epidermal necrosis became apparent. Use of the 10-cm probe did not result in any injury. CONCLUSIONS: Low-frequency ultrasound at low intensities appears safe for use to enhance the topical delivery of medications, producing only minimal urticarial reactions. Higher-intensity conditions resulted in second-degree burns, most likely attributable to localized heating.

Comparison of types of research articles published in emergency medicine and non-emergency medicine journals.

INTRODUCTION: As the specialty of emergency medicine (EM) matures, its journals should be publishing research of a quality similar to that which appears in other premier journals. OBJECTIVE: To compare the types of original research published in 4 EM vs 3 non-EM journals. METHODS: Retrospective review of all 1995 articles published in Academic Emergency Medicine, American Journal of Emergency Medicine, Annals of Emergency Medicine, Journal of Emergency Medicine, Annals of Internal Medicine, JAMA, and New England Journal of Medicine. Research articles were classified as longitudinal vs cross-sectional, prospective vs retrospective, and interventional vs observational. Other characteristics noted were number of subjects, randomization, blinding, control, and power calculations. Journals were reviewed by 4 investigators who received specific training in research classification, adhering to previously reported criteria for retrospective reviews. Interobserver reliability was independently validated. RESULTS: The authors reviewed 3,524 articles, of which 874 (24.8%) were original research. Compared with research reported in non-EM journals, EM journals contained fewer longitudinal studies (40.5% vs 60.4%, p < 0.0001) and fewer prospective studies (70.8% vs 78.7%, p = 0.008). Fewer EM journals had studies that were blinded (13.7% vs 18.9%, p = 0.047) or controlled (36.3% vs 50.0%, p = 0.003). Studies reported in EM journals had fewer subjects (138 vs 300, p < 0.001). Research reports in EM journals were less likely to have been funded, even after adjustment for the differences in study designs (adjusted odds ratio 7.0, 95% CI 5.1-9.7). CONCLUSION: Significant differences in types of research published in EM and non-EN journals were identified.

Thermal effects of neutralization therapy and water dilution for acute alkali exposure in canines.

OBJECTIVE: To evaluate the change in temperature of the gastric mucosa and lumen contents when a weak acid or water is used to manage acute alkali exposure. METHODS: A prospective in-vivo canine model was used in a university-based animal laboratory setting. Eighteen adult canines weighing 20-25 kg were placed under a surgical plane of anesthesia and a laparotomy was performed. A gastrotomy was then made later ligation of the distal esophagus and proximal duodenum. Separate mucosa and lumen temperature probes were placed. Then 25 mL of room-temperature (24-26 degrees C) 50% sodium hydroxide (NaOH) was instilled in the gastric lumen. After 5 minutes, each canine was given treatment. Group 1 (n = 10) was treated with 75 mL of room-temperature orange juice. Group 2 (n = 8) was treated with 75 mL of room-temperature water. Continuous mucosa and lumen temperatures were observed and recorded at baseline and at specified intervals for 35 minutes after the alkali insult. Repeated-measures analysis of variance was used to evaluate the overall temperature profile. Signed-rank tests were used to compare the changes in temperature immediately following neutralization treatment. RESULTS: Significant temperature decreases of 1.1 degrees C and 2.1 degrees C were observed for both mucosa (p = 0.002) and lumen (p < 0.001) temperature, respectively, following neutralization therapy with room-temperature orange juice. In the group treated with room-temperature water, significant temperature decreases of 2.1 degrees C for mucosa (p = 0.01) and 2.4 degrees C for lumen (p = 0.01) were observed. Posttreatment temperatures did not exceed baseline for the entire observation period. CONCLUSION: Neutralization therapy with room-temperature orange juice or water dilution for acute gastric injuries by liquid alkali does not cause a rise in mucosal or intraluminal temperatures in an in-vivo canine model.

Renal gluconeogenesis and blood flow during endotoxic shock.

OBJECTIVES: To determine whether endotoxic shock decreases the renal gluconeogenic capacity and the renal artery blood flow. METHODS: An in-vivo, murine, nonrecirculating kidney perfusion model was studied in a trauma research laboratory. Each of 12 fasted, male Holtzman rats (shock n = 6, control n = 6) was injected with 1 mL of normal saline or endotoxin (20 mg/kg). Five hours after the injection, all the rats were anesthetized and blood samples were obtained for the determination of the plasma glucose. Right renal artery blood flow was measured by an ultrasonic small-animal flow meter. The kidney was then perfused via the renal artery with 37 degrees C, oxygenated, glucose-free Krebs-Henseleit solution in the presence of 100 mumol of phloridzin to inhibit the cellular uptake of glucose. Renal glucose production was determined by measuring glucose in both renal vein effluent and urine. After 30 minutes of equilibration, 5 mmol of lactate and 0.5 mmol of pyruvate were added to the perfusate as a gluconeogenic substrate. Renal vein and ureteral effluent samples were collected after 5, 10, and 15 minutes. RESULTS: The endotoxic shock group showed hypoglycemia (p < 0.05) as well as a decrease in renal artery blood flow (p < 0.05). Gluconeogenic stimulation was demonstrable in both the control and the endotoxic shock groups after 15 minutes of perfusion with substrate (p < 0.05). However, renal gluconeogenesis was significantly attenuated in the endotoxic shock group compared with the control. CONCLUSIONS: Renal glucose production in response to a gluconeogenic substrate is significantly attenuated during the hypoglycemic phase of endotoxic shock. Endotoxic shock also causes a significant decrease of renal artery blood flow.

In vivo tissue temperature comparison of cryotherapy with and without external compression.

STUDY OBJECTIVE: To compare the tissue-cooling efficiency of external cryotherapy with and without adjunctive compression. METHODS: We conducted an experimental repeated-measures study in which each of the 11 anesthetized subject dogs served as its own control. A chemical instant cold pack was applied to each subject's ventral thighs. One pack was held in position by gravity, and the other was compressed against the musculature with a tubular elastic wrap. Baseline and subsequent temperature measurements were taken every 10 minutes for 1 hour with the use of an IM temperature probe percutaneously inserted into each subject's hind legs. RESULTS: IM temperatures were not significantly different at baseline and were coldest at 20 minutes; they increased slowly thereafter. The recorded temperature was lower under the compressed cold pack (P = .003), and changes over time for both groups were also significant (P = .005). The instantaneous temperature difference at 10, 30, 40, 50, and 60 minutes was also significant. CONCLUSION: Externally applied instant cold packs in a dog model caused local tissue hypothermia that peaked by 20 minutes, persisted for at least 1 hour, and was significantly augmented by adjunctive compression. Further research is needed to evaluate the clinical efficacy and safety of these interventions in the management of acute soft-tissue injuries.

Effective treatment for acute alkali injury to the esophagus using weak-acid neutralization therapy: an ex-vivo study.

OBJECTIVE: 1) To evaluate whether neutralization therapy with weak acid is effective in reducing observed histopathologic esophageal tissue injury secondary to liquid alkali, 2) to quantify the temperature change of the neutralizing agent, and 3) to determine the effect of interval to therapy on injury severity. METHODS: Harvested Sprague-Dawley rat esophagi were catheterized and placed in an oxygenated saline bath (37 degrees C) for 60 minutes and then fixed in 10% formalin. Nine groups (n = 10) were perfused with 50% sodium hydroxide (NaOH). Six of the groups were treated by neutralization with cooled orange juice (OJ) or cola that was maintained between 2 degrees C and 4 degrees C. This was performed at 0, 5, or 30 minutes after injury. In addition, two positive control groups were exposed to OJ or cola at time 0 and were not exposed to strong alkali. A third control group was exposed to strong alkali but was not administered any subsequent treatment. The temperature of the neutralizing agent was recorded prior to instillation and after exiting the esophagus. Blinded pathologic scoring of 0 (no injury) to 3 (severe) was recorded performed for six histopathologic categories: epithelial cell viability, cornified epithelial cell differentiation, granular cell differentiation, epithelial cell nuclei, muscle cells, and muscle cell nuclei. Comparisons were made among treatment times using the Kruskal-Wallis test and linear trend analysis. RESULTS: For each histopathologic category and each treatment mode, the Kruskal-Wallis test showed significant differences between the groups (p < 0.002) over time. Trend analyses showed more severe injury with delayed neutralization therapy (p < 0.05) for each treatment mode and histopathologic category. CONCLUSION: Early neutralization therapy with OJ or cola reduces acute esophageal alkali injury. Additional in-vivo study is needed before neutralization therapy is adopted for clinical use.