Regulatory initiatives and framework in the USA: interventional radiology.

Therapeutic procedures using interventional radiology equipment as the imaging tool are often the only available treatment for serious, life-threatening conditions. Many of these procedures require extended periods of radiation exposure often at one location on the patient. As a result, the US Food and Drug Administration (FDA) continues to receive reports of radiation-induced injuries to the skin in patients undergoing some of these therapeutic procedures. The regulatory scheme applicable to interventional radiology equipment in the US is described including federal, state and local aspects, and the impact of professional and non-governmental organisations. Current activities within the FDA and other organisations which have or will affect the use, maintenance and manufacture of interventional radiology equipment are also described.

Pretransplant varicella vaccination is cost-effective in pediatric renal transplantation.

Because of the severe complications that may result from varicella zoster virus (VZV) infection following renal transplantation (Tx), transplanted varicella-susceptible children exposed to varicella are typically given varicella zoster immunoglobulin (VZIG) as prophylaxis or are admitted and treated with parenteral acyclovir if VZIG prophylaxis fails. As both VZIG and hospitalization are costly, prevention of varicella infection by vaccination could potentially result in significant cost savings in addition to decreasing morbidity and mortality. To test this hypothesis, we developed a decision-analysis model to evaluate the cost-effectiveness of vaccinating patients with chronic renal failure (CRF) against varicella prior to renal transplant. Under baseline assumptions, vaccination for varicella pretransplant was a cost-effective strategy, with a cost of $211 per patient vaccinated compared with $1,828 per patient not vaccinated. The magnitude of cost savings from vaccination was sensitive to variations in the cost of varicella vaccine, the percentage of patients hospitalized for treatment with acyclovir, and the percentage of patients exposed to varicella infection. One- and two-way sensitivity analyses confirmed that vaccination was the dominant cost-effective strategy under all conditions examined. We conclude that vaccination for varicella pretransplant is cost-effective for patients with CRF, and that the magnitude of cost savings is sensitive to the cost of hospitalization, the percentage of patients exposed to varicella, and the cost of varicella vaccination. Pending results of ongoing studies of the safety and efficacy of VZV vaccine in children with CRF, we recommend that VZV vaccine be given to all children with CRF.

Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts.

CONTEXT: A growing proportion of young children in the United States participate in day care, and these children are considered to be at high risk for influenza infection. Whether vaccinating day care children reduces household transmission of influenza is not known. OBJECTIVE: To evaluate the effect of vaccinating day care children on reducing influenza-related morbidity among their household contacts. DESIGN: Single-blind, randomized controlled trial conducted during the 1996-1997 influenza season. SETTING: Ten day care centers for children of US Navy personnel in San Diego, Calif. PARTICIPANTS: A total of 149 day care attendees (aged 24-60 months) and their families were randomized; 127 children and their 328 household contacts received 2 vaccine doses and were included in the analysis. INTERVENTIONS: Inactivated influenza vaccine was administered to 60 children with 162 household contacts, and hepatitis A vaccine as a control was administered to 67 age-matched children with 166 household contacts. MAIN OUTCOME MEASURES: Information regarding febrile respiratory illnesses and related morbidity for household contacts of influenza-vaccinated vs control children (subgrouped by influenza-vaccinated and unvaccinated contacts), obtained by telephone interviews with parents every 2 weeks from November 1996 through April 1997. RESULTS: Influenza-unvaccinated household contacts (n = 120) of influenza-vaccinated day care children had 42% fewer febrile respiratory illnesses (P =.04) compared with unvaccinated household contacts of control children. Among school-aged household contacts (aged 5-17 years), there was an 80% reduction among contacts of vaccinated children (n = 28) vs contacts of unvaccinated children (n = 31) in febrile respiratory illnesses (P =.01), as well as reductions of more than 70% in school days missed (P =.02), reported earaches (P =.02), physician visits (P =.007), physician-prescribed antibiotics (P =.02), and adults who missed work to take care of ill children (P =.04). CONCLUSIONS: These results indicate that vaccinating day care children against influenza helps reduce influenza-related morbidity among their household contacts, particularly among school-aged contacts. Future studies should be conducted in civilian populations to assess the full effect of vaccinating day care children against influenza. JAMA. 2000;284:1677-1682.

Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness.

A randomized, blinded, pilot study of influenza vaccine administered to children attending day care centers was conducted during the 1996-1997 winter. Vaccine efficacy in preventing serologically proven influenza virus infection was 0.45 (95% confidence limit [CL]: -0.02, 0.69) for influenza B and 0.31 (95% CL: -0.95, 0.73) for influenza A(H3N2). For both influenza A(H3N2) and B, children without preexisting hemagglutination inhibition (HI) antibody to these antigens had lower antibody responses to vaccine, were less likely to develop a serological response, and were more likely to develop serological evidence of influenza infection. Although there were no reductions in respiratory or febrile respiratory illnesses among all vaccinated children, there was a trend for reductions in such illnesses among vaccinated children with preexisting HI antibodies to influenza A(H3N2) and B. Therefore, immunologic priming in young children may be important for vaccine response and for protection against infection. Larger studies are needed in other influenza seasons to assess vaccine efficacy and clinical effectiveness.

A block rotation in community pediatrics.

OBJECTIVES: To develop, implement, and evaluate a 1-month block rotation in community pediatrics. INTERVENTIONS: Faculty from University of California San Diego and Naval Medical Center San Diego developed a combined and integrated curriculum for second-year residents in community pediatrics. Resident activities included structured site visits to schools, day care centers, and community organizations that participate in child health promotion, advocacy, public health, and prevention activities. Resident school consultation and child advocacy projects were established and mentored during the block rotation. EVALUATION: Formative evaluation of the program by residents was used to shape the program design. Residents' self-perceived competence in eight areas of community pediatrics was measured with questionnaires administered before and after completion of the rotation. Resident involvement in school consultation and child advocacy projects was assessed in a cross-sectional survey. RESULTS: Twenty-three residents completed the rotation during the 1-year study period. Statistically significant improvements in self-perceived competence were noted in all eight areas of community pediatrics. Among residents who were at least 3 months beyond the rotation completion date, 55% (11/20) reported continued involvement with their school consultation or child advocacy project, and 25% (5/20) reported this involvement to be on a quarterly to monthly basis. CONCLUSIONS: Two institutions successfully implemented and integrated a block rotation in community pediatrics. Positive short-term improvements were noted in resident self-perceived competence in community pediatrics.

Radiation-induced skin injuries from fluoroscopy.

Since 1992, the U.S. Food and Drug Administration (FDA) has received reports of radiation-induced injuries to the skin in patients who had undergone fluoroscopically guided interventional procedures. The reports were investigated to determine the procedure- or equipment-related factors that may have contributed to the injury. The injuries ranged in severity from erythema to moist desquamation to tissue necrosis that required skin grafting. They occurred after a variety of interventional procedures that required extended periods of fluoroscopy compared with those of typical diagnostic procedures. Medical facilities and physicians should be aware of the magnitude of radiation doses to the skin that can result from the long exposure times required by complex interventional procedures. The FDA recommends several steps for reducing these injuries, including establishing protocols for each procedure, determining radiation dose rates for specific fluoroscopy systems and operating modes, and monitoring cumulative absorbed doses to areas of the skin.

Moraxella (Branhamella) catarrhalis bacteremia in children. A report of two patients and review of the literature.

We report two cases of Moraxella catarrhalis (M. catarrhalis) bacteremia in apparently healthy children. One patient had bilateral otitis media and the other had pharyngitis and sinusitis; both patients had uncomplicated clinical courses. A literature review revealed 22 reported cases of M. catarrhalis bacteremia in children, 14 (63%) of which occurred in patients who had no identified underlying condition. Eight (36%) cases were seen in children who were immunocompromised. Nine (40%) patients presented with either purpura, petechia, or a maculopapular rash. M. catarrhalis is well known as a respiratory pathogen, but it has not been recognized as a common cause of unsuspected bacteremia in children.

Multicenter trial of Towne strain attenuated virus vaccine in seronegative renal transplant recipients.

The Towne strain of attenuated CMV vaccine was compared with placebo in seronegative renal transplants who later received kidneys from seropositive donors. This was a double-blind, randomized, placebo-controlled trial conducted at 3 different institutions. The results were consistent with 2 prior studies, in that whereas mild CMV disease was only slightly and insignificantly reduced in vaccine recipients, severe disease was markedly reduced. In the current study, all 4 severe cases of CMV disease occurred in placebo recipients, for an incidence of 17%, versus 0% in vaccine recipients (P < 0.03). Thus, prior immunization rendered seronegative patients more resistant to the effects of CMV infection.

The Rhino-Probe nasal curette for detecting respiratory syncytial virus in children.

During two outbreaks of respiratory syncytial virus (RSV) infection, 68 children with acute respiratory illnesses were cultured for RSV using a Rhino-Probe (RP) nasal curette and either a nasopharyngeal (NP) swab or a nasal wash (NW). In the first outbreak isolations of RSV by the RP nasal curette and NP swab methods were compared. RSV was cultured from 25 of 42 (60%) subjects using the RP nasal curette and from 20 of 42 (48%) subjects using the NP swab. In the second outbreak the RP nasal curette and the NW collection techniques were compared. RSV was isolated from 15 of 26 (58%) children evaluated. RSV was cultured from 14 of 15 (93%) patients by RP and 13 of 15 (87%) when using NW. In the group of culture-positive subjects, the TESTPACK RSV rapid antigen test was positive in 10 of 15 (67%) using the RP and in 6 of 15 (40%) using the NW. Like the NP swab the RP nasal curette was simple, noninvasive and relatively inexpensive, yet it was as sensitive as the NW for detection of RSV.

Respiratory syncytial virus morbidity and mortality estimates in congenital heart disease patients: a recent experience.

OBJECTIVE: To determine recent morbidity and mortality rates from respiratory syncytial virus infection in a pediatric congenital heart disease population. DESIGN: Retrospective cohort study design. SETTING: The C. S. Mott Children's Hospital, University of Michigan Medical Center. PATIENTS: A total of 740 pediatric patients hospitalized at the University of Michigan Medical Center for symptomatic respiratory syncytial virus infection, of whom, 79 patients had clinically important congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We retrospectively examined the charts of 740 patients hospitalized at our children's hospital from July 1, 1983 to June 30, 1990 with symptomatic respiratory syncytial virus infection to assess morbidity and mortality outcomes. Seventy-nine patients had congenital heart disease and 40 of these patients had pulmonary hypertension. For the entire cohort and a subset of patients with community-acquired infection, those patients with congenital heart disease had longer durations of hospitalization and greater need for, and days of, both intensive care and mechanical ventilation than patients without congenital heart disease. Mortality risk for respiratory syncytial virus community-acquired infection was not different for congenital heart disease vs. noncongenital heart disease patients (0.0% vs. 0.2%; p = 1.00). When examining only patients with congenital heart disease, those patients with pulmonary hypertension had increased hospital days and greater intensive care and mechanical ventilation durations compared with patients without this diagnosis. The overall mortality rate was low and was equally low for congenital heart disease groups with or without pulmonary hypertension (2.5 vs. 2.6). For community-acquired illness, no mortality was found in either congenital heart disease group. When the cohort of congenital heart disease patients was divided into pre- and postribavirin administration eras, no differences in mean hospital duration, ICU days, and mechanical ventilation days were noted. Of the 79 congenital heart disease patients, only two died during their hospitalization in which respiratory syncytial virus infection occurred. Both patients had nosocomial-acquired respiratory syncytial virus and both were from the postribavirin administration cohort. One of these two patients had received antiviral therapy. Neither death was secondary to respiratory syncytial virus respiratory failure (based on pathologic examination). CONCLUSIONS: We conclude that respiratory syncytial virus mortality risk in pediatric patients with congenital heart disease is less than the risk reported a decade ago. Respiratory syncytial virus infection in congenital heart disease patients with pulmonary hypertension is associated with increased morbidity but not increased mortality rates. The markedly decreased respiratory syncytial virus mortality risk in patients with congenital heart disease currently experienced is likely secondary to improvements in intensive care management and advances in the surgical correction in this population rather than antiviral therapy.

A measles outbreak at university medical settings involving health care providers.

In 1985, a measles outbreak involved 14 students and non-student contacts in Michigan. Eight transmissions occurred at university medical facilities; five of these were likely airborne transmissions. Medical students and a medical resident were involved in the outbreak's propagation. Health care providers need to be immune to measles. Measles should be suspected in young adults with compatible illnesses; persons suspected to have measles should be placed in stringent respiratory isolation to preclude airborne transmission.

Serum isocitrate dehydrogenase activity in Reye's syndrome.

Serum levels of isocitrate dehydrogenase was determined in 12 Reye's syndrome patients and the enzyme levels were compared with serum ornithine carbamyl phosphate, glutamic oxaloacetic transaminase (aspartate aminotransferase), ammonia, and the stages of the disorder. Isocitrate dehydrogenase was elevated in 8 of the 12 patients and there was no direct correlation between elevated serum isocitrate dehydrogenase level and other clinical parameters.

Further evidence that stress hyperthermia is a fever.

Exposure of rats to an open-field results in a rapid rise in body temperature. Fifty-four percent of this rise in body temperature was blocked by intracerebroventricular administration of the antipyretic drug sodium salicylate. Intraperitoneal administration of indomethacin, a potent blocker of prostaglandin production, also attenuated the stress-induced hyperthermia to the same degree. Based on the data presented in this and an earlier study, we conclude that a major component of the rise in body temperature induced by psychological stress in rats is mediated by prostaglandins released by the central nervous system, and may therefore be a fever.

Intranasal interferon-alpha 2b for seasonal prophylaxis of respiratory infection.

Efficacy of intranasal recombinant alpha interferon (IFN-alpha 2b) was evaluated over a four-week period. The first 400 participants received either 1,500,000 IU of IFN-alpha 2b or placebo twice daily. Rhinovirus infections were prevented (protective efficacy, 76%). Parainfluenza infections were not prevented, but symptoms in associated episodes of disease were significantly reduced. The medication was generally well tolerated, but side effects were often observed. The most commonly reported symptom was blood-tinged mucus. A pilot study of IFN-alpha 2b or placebo administered on a once-daily dose schedule was also carried out in 150 participants. There was a suggestion of continued efficacy with reduced side effects. Overall, these findings would limit the use of IFN-alpha 2b on the twice-daily schedule to shorter time periods or to special situations in which the efficacy clearly outweighs side effects, and they encourage further examination of other dosage schedules.

A recommended approach to the evaluation of human rabies exposure in an acute-care hospital.

It is important to minimize the costs and risks associated with unnecessary prophylaxis of health care workers. We studied the process of providing rabies postexposure prophylaxis following the 24-day hospitalization of a rabies-infected patient. Of 209 persons who cared for the patient, only 12 (6%) reported high-risk contact, and treatment was recommended for them. Unnecessary prophylaxis was limited to 35 persons (18%) who did not report high-risk contacts but who requested treatment because of their uncertainty about the degree of exposure. These persons, however, spent significantly more time with the patient compared with persons who did not request treatment. Maintaining strict isolation precautions when rabies is being considered, educating employees about the risks of transmission in this setting, carefully documenting exposures, and adhering to the guidelines for postexposure prophylaxis may help reduce excessive prophylaxis of health care workers.