Influenza virus-like particles as pandemic vaccines.

There is an urgent need to develop novel approaches for vaccination against emerging pathogenic avian influenza viruses as a priority for pandemic preparedness. Influenza virus-like particles (VLPs) have been suggested and developed as a new generation of non-egg-based cell culture-derived vaccine candidates against influenza infection. Influenza VLPs are formed by a self-assembly process incorporating structural proteins into budding particles composed of the hemagglutinin (HA), neuraminidase (NA) and M1 proteins, and may include additional influenza proteins such as M2. Animals vaccinated with VLPs were protected from morbidity and mortality resulting from lethal influenza infections. The protective mechanism of influenza VLP vaccines was similar to that of the currently licensed influenza vaccines inducing neutralizing antibodies and hemagglutination inhibition activities. Current studies demonstrate that influenza VLP approaches can be a promising alternative approach to developing a vaccine for pandemic influenza viruses. The first human clinical trial of a recombinant pandemic-like H5N1 influenza VLP vaccine was initiated in July 2007 (Bright et al., unpublished).

Neurological manifestations of avian influenza viruses in mammals.

The H5N1 viruses isolated from humans in Hong Kong directly infected both mice and ferrets without prior adaptation to either host. Two representative viruses, A/Hong Kong/483/97 (HK/483) and A/Hong Kong/486/97 (HK/486) were equally virulent in outbred ferrets but differed in their virulence in inbred mice. Both HK/483 and HK/486 replicated systemically in ferrets and showed neurologic manifestations. In contrast, intranasal infection of mice with HK/483, but not HK/486, resulted in viral spread to the brain, neurologic signs, and death. However, HK/486 was able to replicate in the brain and induce lethal disease following direct intracerebral inoculation.

Mechanisms of pathogenicity of influenza A (H5N1) viruses in mice.

Avian-like H5N1 influenza viruses isolated from humans in 1997 were shown to have two distinct pathogenic phenotypes in BALB/c mice, after intranasal inoculation and without prior adaptation to this host. To further understand the mechanisms of H5N1 pathogenicity, we investigated the consequences of the mute of viral inoculation on morbidity and mortality, viral replication in pulmonary and systemic organs, and lymphocyte depletion. This study demonstrates the importance of extrapulmonary spread and replication, particularly in the brain, for the lethality of H5N1 viruses.

Study design in the evaluation of breast cancer imaging technologies.

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge.

The ability of the C3d component of complement to enhance antibody responses and protective immunity to influenza virus challenges was evaluated using a DNA vaccine encoding a C3d fusion of the hemagglutinin (HA) from influenza virus. Plasmids were generated that encoded a transmembrane HA (tmHA), a secreted form of HA (sHA), or a sHA fused to three tandem copies of the murine homologue of the C3d (sHA-3C3d). Analysis of the titers, avidity maturation, and hemagglutinin-inhibition activity of raised antibody revealed that immunizations with sHA-3C3d DNA accelerated both the avidity maturation of antibody to HA and the appearance of hemagglutinin-inhibition activity. These accelerated antibody responses correlated to a more rapid appearance of protective immunity. They also correlated to complete protection from live virus challenge by a single vaccination at a dose ten times lower than the protective dose for non-C3d forms of HA.

Reported complications of silicone gel breast implants: an epidemiologic review.

PURPOSE: To review the range of local and systemic complications attributed to silicone breast implants and to evaluate the epidemiologic literature on these complications. DATA SOURCES: Epidemiologic studies of the potential risks of silicone breast implants identified by MEDLINE search and literature review. STUDY SELECTION: Epidemiologic studies with cohort, case-control, and cross-sectional designs. When epidemiologic studies were unavailable (as for estimates of local complications), case series were reviewed. DATA EXTRACTION: Epidemiologic studies evaluated for methodologic quality, including such characteristics as study design, sample size and selection, determination of silicone exposure and outcome variables, and duration of follow-up. DATA SYNTHESIS: The epidemiologic literature on the potential complications of silicone breast implants has concentrated primarily on connective tissue disorders and cancer. Estimated of the true incidence of local complications, such as rupture, capsular contracture, and breast pain, are unavailable. Studies of scleroderma and other defined connective tissue diseases suggest that implant recipients have no substantially increased risk for these disorders; however, the epidemiologic literature is insufficient to rule out an association between breast implants and connective tissue disease-like syndromes. Overall, the rate of breast cancer does not seem to be increased in women with silicone breast implants. However, the risk to women as they reach the postmenopausal years in not yet known. CONCLUSIONS: Information is insufficient to adequately advise women who currently have or are seeking to obtain breast implants about the overall risk of these devices. No epidemiologic study has indicated that the rate of well-defined connective tissue disease or breast cancer has greatly increased in women with silicone breast implants, but no studies have ruled out a moderately increased risk for these diseases. No studies have adequately addressed the crucial issue of local complications such as rupture and capsular contracture, although evidence increasingly points to a higher risk for rupture as implants age.

The prevalence of tympanostomy tubes in children in the United States, 1988.

Information from the 1988 National Health Interview Survey Medical Device Implant Supplement was used to obtain the first population estimates of the prevalence of implanted tympanostomy tubes, a common treatment for otitis media. The prevalence rate was estimated to be 13 per 1000 children aged younger than 18 years. Statistically significant differences in prevalence were found for sex (boys, 15/1000; girls, 10/1000), race (Whites, 15/1000; others, 4/1000), and activity level ("limited," 44/1000; others, 11/1000). Thirty percent of the tubes were replacements; infection was the reason for 75% of the original implants. The morbidity and costs associated with tympanostomy tubes are of public health importance.

The prevalence of internal orthopedic fixation devices in children in the United States, 1988.

This study provides the first estimated prevalence of implanted orthopedic fixation devices (e.g., pins or wires) among children in the United States, based on the Medical Device Implant Supplement to the 1988 National Health Interview Survey. The overall prevalence was 27 per 10,000 children younger than 18 years; prevalence was highest (59/10,000) among those aged 12 to 17 years. The lower extremities were the most frequent body site (43%) and injury was the leading specific reason for implantation (37%). Some (10%) were replacement implants.

National survey of self-reported breast implants: 1988 estimates.

This report provides the first population-based national estimates of the prevalence of adult women with breast implants in the U.S. These findings are based on the Medical Device Implant Supplement to the 1988 National Health Interview Survey. The overall prevalence was 33 implant recipients (95% confidence limits [CL]: 26 to 40) per 10,000 women. Almost three-fourths had two implants: prevalence peaked at 85 (59 to 100) per 10,000 for women aged 35 to 44 years. Implant prevalence was statistically significantly greater among women who were white, residents of the south and west, had higher family income, and had more education, who worked, or were slim. Among current implants, 87% were original. Complications were reported for 24% of the implants.

Racial differences in the prevalence of intraocular lens implants in the United States.

We generated population-based estimates of the prevalence of intraocular lens implants by using the 1988 Medical Device Implant Supplement to the National Health Interview Survey. This national survey of a probability sample of the civilian noninstitutionalized United States population comprised 47,485 households and 122,310 persons. To produce national projections, we used survey respondent-reported data based on 1,941 reported intraocular lenses in 1,337 persons. Projected to the United States population, an estimated 2.6 million people had a total of 3.8 million lens implants. The predominant reason for the implant was cataract. The intraocular lens replacement rate was 0.9%. The use of intraocular lens implants was statistically significantly different from the general population in persons with the following socioeconomic characteristics: age (65 years or older), race (white), gender (female), annual family income (less than $20,000, although more commonly at or above the poverty threshold), and education (less than high school). The prevalence rates per 1,000 persons according to age were as follows: 0.3 for persons 44 years old or younger, 9.9 for persons 45 to 64 years old, 33.3 for persons aged 65 to 69 years, 63.5 for persons aged 70 to 74 years, and 113.5 for persons 75 years old or older.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-blockers and depression. Evidence against an association.

OBJECTIVE: To evaluate the relationship between beta-blockers and depression. DESIGN: Case-control study. SETTING: New Jersey Medicaid recipients during July 1980 to December 1983. PARTICIPANTS: New depression case patients (N = 4302) were identified from Medicaid claims for depression markers (antidepressant drugs, in-hospital depression diagnosis, or electroconvulsive therapy). Control patients were randomly selected and matched on the basis of Medicaid enrollment on the case patients' date for first depression marker (index date), birth year, sex, race, and nursing home residency status. MAIN EXPOSURE MEASURE: beta-Blocker use as evidenced by prescription claims in the year before the index date. RESULTS: Case patients overall were more likely to have taken beta-blockers (simple, matched odds ratio [OR] of 1.45; 95% confidence interval [CI], 1.29 to 1.62). Controlling for confounders (benzodiazepine use, frequent outpatient visits, and frequent use of medications other than beta-blockers) resulted in a null effect (OR = 0.98; 95% CI, 0.87 to 1.12). The ORs were consistently lower for case patients with a depression diagnosis or electroconvulsive therapy than for cases with only antidepressant use as a marker. These results did not vary by age, sex, race, nursing home status, or use of other selected specific medications. CONCLUSIONS: Ongoing beta-blocker use was not causally related to markers of depression. The difference between this study and those it contradicts is that this one identified certain confounding variables that accounted for the apparent relationship.

The relationship of maternal race and insurance status to prenatal ultrasound use in a national population.

Data from the first group of respondents (N = 4,846) of the 1988 National Maternal and Infant Health Survey were analyzed. After controlling for potentially confounding factors, such as maternal age, in a multivariate analysis, no relationship could be demonstrated between insurance status or race and the probability of receiving a prenatal ultrasound examination.

How frequently are home pregnancy tests used? Results from the 1988 National Maternal and Infant Health Survey.

Many women use commercially available home pregnancy tests to determine their pregnancy status before seeking professional health care. Despite the increasing popularity of these products, no national estimates have been reported to date on their frequency of use. We analyzed available data from the 1988 National Maternal and Infant Health Survey to determine the frequency of use of home pregnancy tests during recent pregnancies of women of varying sociodemographic backgrounds. Approximately 33 percent (N = 4700) of the women surveyed used such a device. Use was most frequent among women who were white, married, over age 39 years, highly educated, or had a high family income. We conclude that home pregnancy testing appears to be a frequent procedure, especially among women of high socioeconomic background.

Histologic and mammographic specificity of risk factors for benign breast disease.

This study evaluates the effects of potential risk factors for benign breast disease (BBD) with special attention to the histologic and mammographic specificity of the effects. Cases were 172 women with BBD that underwent biopsy; controls were 134 women free of breast signs or symptoms. All cases and controls had undergone mammography. For all types of BBD combined, parity, use of oral contraceptives, and use of exogenous estrogen after menopause were strongly protective, whereas obesity and early menarche were weakly protective. Family history of breast cancer was virtually unrelated to BBD. The protective effect of parity was stronger for BBD with intralobular or extralobular fibrosis, and with mammographic homogeneous density or large nodular densities, than it was for BBD without these characteristics. Similar relations with the histologic and mammographic features were observed for obesity. These findings suggest that some risk factors for BBD have effects that are related to specific features of its morphology.

Medicaid data as a resource for epidemiologic studies: strengths and limitations.

Large claims databases from third-party insurance programs such as Medicaid have attracted the interest of epidemiologists because of their enormous size and apparent comprehensiveness. Over 20 million people are covered by the various state Medicaid programs and most states maintain detailed computerized records of all reimbursed health care encounters on a recipient-specific basis. For states covering medication costs, data on drug exposures are particularly complete and accurate. However, Medicaid claims data also have many limitations that can pose major methodological difficulties. Foremost among these is the uneven validity and completeness of the diagnoses appearing on claims. Likewise, the unique identification of specific program participants is not straightforward, although useful approaches can often be developed to track individuals over time. Consideration of the limitations as well as the possible strengths of claims-based data makes it possible to choose appropriate study hypotheses as well as to attempt solutions, where possible, to the biases of this methodology.