Economic impact of respiratory syncytial virus-related illness in the US: an analysis of national databases

OBJECTIVE: To determine the impact of respiratory syncytial virus (RSV) infection on healthcare resource use and costs in the US from the third-party payer perspective. DESIGN: The study retrospectively analysed cross-sectional medical encounter data from three federally funded databases that comprise nationally representative samples of hospital inpatient stays, physician office visits and visits to hospital outpatient departments and emergency rooms. METHODS: Identification of RSV infection-related medical encounters was based on the occurrence of RSV-specific International Classification of Diseases (9th Edition)-Clinical Modification diagnosis codes (079.6, 466.11, 480.1) as principal discharge diagnoses or the assumption that 10-15% of all otitis media visits were due to RSV infection. Outpatient drug costs were estimated based on average wholesale price, and physician fees and test/procedure costs were estimated based on prevailing national fees. Inpatient costs were estimated from total billed charges using a cost-to-charge ratio of 0.53. RESULTS: In 2000, nearly 98% of RSV infection-related hospitalisations occurred in children <5 years old. There were approximately 86,000 hospitalisations, 1.7 million office visits, 402 000 emergency room visits and 236,000 hospital outpatient visits for children <5 years old that were attributable to RSV infection. Total annual direct medical costs for all RSV infection-related hospitalisations ($US394 million) and other medical encounters ($US258 million) for children <5 years old were estimated at $US652 million in 2000. Otitis media was a major cost driver for physician visits. RSV infection-related hospitalisations increased from 1993 to 2000, but average costs per hospitalisation were relatively stable. CONCLUSION: Treatment of RSV infection-related illness represents a significant healthcare burden in the US. The economic impact of ambulatory care for RSV infection-related illness could be as important as that for RSV infection-related hospitalisation.     

Increased antiviral activity of 1-O-hexadecyloxypropyl-[2-(14)C]cidofovir in MRC-5 human lung fibroblasts is explained by unique cellular uptake and metabolism

Recently, there has been renewed interest in finding orally active drugs against smallpox. Cidofovir (CDV) given by parenteral injection has been shown to protect against lethal poxvirus infection. We have been interested in the synthesis and evaluation of orally active derivatives of CDV. Previous studies showed that the CDV and cyclic cidofovir (cCDV) analogs 1-O-hexa-decyloxypropyl-CDV (HDP-CDV) and 1-O-hexadecyloxypropyl-cCDV (HDP-cCDV), show >100-fold increases in antiviral activity versus the unmodified nucleosides against cells infected with orthopoxviruses, cowpox, and vaccinia virus. In contrast to CDV, HDP-CDV is orally bioavailable and has been reported to be orally active in lethal cowpox virus infection in mice. To assess the metabolic basis for the increased antiviral activity of HDP-CDV in vitro, we studied the cellular uptake and anabolic metabolism of (14)C-labeled CDV, cCDV, and their alkoxyalkanol esters HDP-CDV and HDP-cCDV. HDP-CDV and HDP-cCDV were taken up rapidly by MRC-5 human lung fibroblasts in vitro, but uptake of CDV and cCDV was much slower. Analysis of cellular metabolites showed that levels of cidofovir diphosphate (CDV-DP), the active antiviral compound, were >100 times greater with HDP-CDV than levels observed with CDV. When cells were exposed to HDP-CDV, the intracellular half-life of CDV-DP was 10 days versus 2.7 days reported when cells are exposed to CDV. HDP-CDV seems to circumvent poor cellular uptake by rapid association with cellular membrane phospholipids, whereas CDV uptake proceeds via the slow process of fluid endocytosis.     

Outcomes of cytopathology studies presented at national pathology meetings

The purpose of this study was to determine what factors influence the final publication status of cytopathology studies presented at national meetings. Abstracts involving cytopathology material were obtained from the following journals: Modern Pathology (volume 11, 1998), Acta Cytologica (volume 42, 1998), and the American Journal of Clinical Pathology (volumes 109 and 110, 1998). Using the National Library of Medicine Website, each abstract was searched by author and topic to determine if the study was published as a peer-reviewed article. The following parameters were evaluated: meeting where the abstract was presented, type of institution where the research was based, type of material used in the study, and application of ancillary techniques used in the study. The subsequent published articles were evaluated for journal and time to publication. Out of 257 studies presented in 1998, 85 (33%) were published in peer-reviewed journals by May 2000. The majority of papers were published in Diagnostic Cytopathology (n = 21), Acta Cytologica (n = 15), and Cancer (n = 18). The mean time for publication was 12.8 mo. The highest percentage of published studies was presented at the United States and Canadian Academy of Pathology (USCAP) meeting (50% of presented abstracts), followed by American Society of Cytopathology (ASC) (28%) and American Society of Clinical Pathologists (ASCP) (17%) meetings. Ancillary techniques were applied in 40 of 85 (47%) published studies, 27 of 85 (32%) articles focused on morphology, and 18 of 85 (21%) papers covered other topics (e.g., quality assurance (QA), cost, and role of cytology). In nonpublished studies (n = 172), special techniques were the main focus in 40%, morphology in 25%, and other topics in 35% of abstracts. The great majority (97%) of published studies were from academic institutions. Gynecological and nongynecological material were roughly equally covered in published and nonpublished studies. Only a relatively small percentage of presented studies was finalized in the form of peer-reviewed articles. Type of material and application of ancillary techniques do not significantly influence the outcome.     

Phospholipase A(2)--derived neutral lipids from posthemorrhagic shock mesenteric lymph prime the neutrophil oxidative burst

BACKGROUND: Our previous work identified posthemorrhagic shock mesenteric lymph (PHSML) lipids as key elements in polymorphonuclear neutrophil (PMN)--provoked acute lung injury. We hypothesize that gut phospholipase A(2) (PLA(2)) is responsible for the generation of proinflammatory lipids in PHSML that primes circulating PMNs for enhanced oxidative burst. METHODS: Mesenteric lymph was collected from rats (n = 5) before (preshock), during the induction of hemorrhagic shock (mean arterial pressure, 40 mm Hg x 30 minutes), and at resuscitation (shed blood + 2x lactated Ringer's solution). PLA(2) inhibition (quinacrine, 10 mg/kg, intravenously) was given before shock was induced. Extracted lipids were separated by normal phase high-pressure liquid chromatography and resuspended in albumin. PMNs were exposed to a 5% vol:vol concentration of eluted lipids and activated with N-formyl-methionyl-leucyl-phenylalanine (1 micromol/L). Superoxide production was assessed by cytochrome C reduction. RESULTS: High-pressure liquid chromatography--extracted neutral lipids of lymph collected before hemorrhagic shock did not prime the PMN oxidase, whereas isolated neutral lipids of postshock lymph primed PMNs 2.6- +/- 0.32-fold above baseline (P <.05). PLA(2) inhibition returned PHSML neutral lipid priming to baseline levels. CONCLUSIONS: PLA(2) inhibition before hemorrhagic shock abrogates the neutrophil priming effects of PHSML through reduction of the accumulation of proinflammatory neutral lipids. Identification of these PLA(2)-dependent lipids provides a mechanistic link that may have therapeutic implications for postshock acute lung injury.     

Assessment of stool colour in community management of prolonged jaundice in infancy

Jaundice persisting beyond the first 2 wk of life is often regarded as an indication for investigation to exclude cholestatic liver disease. Most babies with prolonged jaundice have breast milk-related jaundice, which is a benign condition. Cholestatic liver disease is usually accompanied by pale stools and yellow or orange urine. A community programme was established to ascertain the incidence of prolonged jaundice and determine whether abnormal stool and urine colour could be used to assist primary care staff in referral decisions. Data were collected on normal stool and urine colour and used to devise a colour chart and information sheet for parents. Babies with prolonged jaundice were identified and referred for investigation. In all, 3661 babies were recruited into the study, of which 127 were jaundiced at 28 d of age. Of these, 125 were breastfed. The incidence of jaundice in breastfed babies at 28 d was 9.2% (95% CI 7.8%-11.0%) Abnormal liver function tests (LFTs) were common, but no baby had abnormal stool or urine colour and none was found to have liver disease. Jaundiced breastfed babies who are well are unlikely to have serious disease. Elevated LFTs are compatible with a diagnosis of breast milk-related jaundice. Prolonged jaundice in bottle-fed babies, and persistent pallor of stools or yellow/orange urine, are rare and merit immediate referral. Parents and professionals can be advised to report pale stools without generating a large number of unnecessary referrals. Further work is needed to determine whether a colour chart reduces the mean age of referral and treatment of infants with cholestatic liver disease.     

Vertebral-body collapse in focal and diffuse disease: patterns of pathologic processes

The radiographic patterns of vertebral-body collapse and/or endplate deformity were examined in 99 autopsy specimens of the thoracolumbar spine with benign and malignant disease. Angling of endplates was found to be highly predictive of underlying malignancy, whereas concavity was more suggestive of benign disease, for both individual vertebral bodies and intact spines (P less than .001). Diffuse-concave, diffuse-angled, and focal-angled patterns were more useful (P less than .001) than the focal-concave pattern (P = .07) in distinguishing between benign and malignant disease for superior endplates, whereas all were equally useful (P less than .025) in inferior endplates. Condition of the adjacent disks, location within the spine, and position of the apex of collapse were not predictive. Although these results and subsequent blinded testing suggest that reliable distinction between benign and malignant vertebral collapse is possible, extrapolation to clinical practice may be inappropriate because of population bias in the study and differences in radiographic quality between autopsy specimens and live subjects.     

Osteoarthritis of the facet joints: accuracy of oblique radiographic assessment

Sensitivity and specificity of lumbar spine radiography in the assessment of facet joint osteoarthritis were evaluated, with computed tomography (CT) as the standard. Two independent radiologists used a four-point scale to blindly grade facet joint osteoarthritis on oblique radiographs and transaxial CT scans obtained within an 8-month period in 50 consecutive patients with pain in the lower back. The L-3 to L-4, L-4 to L-5, and L-5 to S-1 facet joints were evaluated, and 68% appeared abnormal on CT scans, with 28% exhibiting moderate or severe disease. Interobserver agreement was high for conventional radiography (perfect agreement in 57% and agreement to within one grade in 39%) and still higher for CT (perfect in 63% and to within one grade in 35%). Receiver operating characteristic curve analysis indicated that oblique radiography was most accurate (55% sensitivity, 69% specificity) in distinguishing the presence from the absence of disease; in distinguishing absent or mild from moderate or severe disease, the specificity of oblique radiography was higher, at 94%, but its sensitivity was much lower, at 23%. Conventional radiography is a useful technique in screening for facet joint osteoarthritis but is insensitive compared with CT.     

Does the perception of downloading speed influence the evaluation of web-based lectures?

Medical schools put little emphasis upon education on public health, even though public health has played an important role in this century. One way to harness its benefit in order to improve global health in the 21st century is to globally share lectures on public health through the Internet. We have developed the Supercourse comprising of web-based learning modules on epidemiology in a standardized format with the size of each web page less than 10 kilobytes. A cross-sectional observational study was conducted to investigate the association of the perception of the access speed to Web-based lectures by teachers with their perception of lecture quality. There were 223 teachers who rated the lectures: 72% were from North America or Western Europe, 40% had taught epidemiology, and 14% reported that the speed of access was slow. Odds ratio of above-average rating among those who reported that the speed of access was fast relative to those who reported that the speed of access was slow was 4.25 (2.03-8.91; P = 0.001). The odds ratios were similar and significant after taking into account several other factors, including the variation of rating across lectures, region, and experiences in teaching epidemiology. The results indicate that the perception of the quality of Web-based lectures is related to the speed of access to a web page. The speed of access may be as important, if not more important, as the content itself. This suggests that, to share educational materials on the Web globally for teachers, one must consider not only the content, but also how people at local sites gain access to the Internet.     

Sternocostoclavicular hyperostosis: a review and report of 11 cases

Sternocostoclavicular hyperostosis is a benign ossifying diathesis of unknown etiology characterized by hyperostosis and soft-tissue ossification between the clavicles, anterior portion of the upper ribs, and manubrium, with variable hyperostosis or ankylosis in the spine and sacroiliac joints. Our cumulative experience with 11 cases is reported, with emphasis on radiographic features of the condition. Scintigraphic results in five patients and computed tomographic findings in one patient are presented. A review of the literature and our own material indicates that sternocostoclavicular hyperostosis may be more common than has been previously recognized.