Harry Guess

Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination

Soon after the plasma-derived hepatitis B vaccine became available in the US, the Centers for Disease Control and the manufacturer received over 100 reports of vaccinated groups with unexpectedly low levels of vaccine-induced antibody. To confirm previous retrospective surveys relating these failures to buttock injection and to evaluate the effect of other host factors on vaccine-induced antibody responses, we conducted a clinical trial in healthy health-care workers. Participants were randomly assigned to one of three treatment groups: 1-Ar, 1-inch needle injection in the arm; 1-Bu, 1-inch needle injection in the buttock; 2-Bu, 2-inch needle injection in the buttock. All participants were administered vaccine according to the standard vaccine dosage schedule of 20 micrograms at 0, 1 and 6 months. Antibody response rates (antibody to hepatitis B surface antigen greater than or equal to 10 sample ratio units by radioimmunoassay) and geometric mean titres of antibody two months after the third vaccine dose were 93% and 1454 mIU ml-1 for group 1-Ar, 72% and 85 mIU ml-1 for group 1-Bu, and 83% and 387 mIU ml-1 for group 2-Bu. Seroconversion rates and titres of antibody in the three groups were significantly different from each other statistically. Increasing age, increasing total skinfold thickness and cigarette smoking were independently associated with lower antibody responses in persons receiving buttock injections but not in persons receiving arm injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors predisposing to seizures in seriously III infected patients receiving antibiotics: Experience with imipenem/cilastatin

Observations on 1,754 patients treated with imipenem/cilastatin in phase III dose-ranging studies in the United States were reviewed to determine risk factors for seizures. The patients were moderately to severely ill with numerous background disorders known to be associated with an increased risk of seizures. Fifty-two patients (3 percent) had seizures and in 16 (0.9 percent) of them the seizures were judged by the investigators to be possibly, probably, or definitely related to imipenem/cilastatin. An incidence of seizure of 2 to 3 percent was noted among patients treated with other antibiotics (usually including a beta-lactam in the regimen) at times when imipenem/cilastatin was not being given. The average time of onset of seizures for patients receiving imipenem/cilastatin was seven days after start of therapy. As with other beta-lactam antibiotics, central nervous system lesions and disorders including seizures and renal insufficiency were found to be strong risk factors for seizures. Imipenem/cilastatin dosages in excess of those currently recommended by the manufacturer, particularly in patients with renal insufficiency, were also associated with an increased risk of seizures. There was an association with Pseudomonas aeruginosa infection that remained statistically significant even after controlling for imipenem/cilastatin dosage as well as for the other factors indicated. A high background incidence of seizures in general in a group of severely ill patients makes it both difficult to assess the etiology of a seizure and important to consider the risk factors when choosing the appropriate dose of an antibiotic. Guidelines are presented for appropriate dosing of imipenem/cilastatin in relation to renal function, body weight, and infecting pathogen.

Postmarketing evaluation of the safety and effectiveness of varicella vaccine.

BACKGROUNDnThe Oka strain of live attenuated varicella virus was licensed for use in healthy children in the United States in March, 1995. We report a postmarketing evaluation of the short term safety of this vaccine within Kaiser Permanente.nnnMETHODSnAfter licensure varicella vaccination was introduced into the preventive care program of the Northern California Kaiser Permanente Medical Care Program. Potential adverse events after vaccination with varicella vaccine were identified from automated clinical databases of hospitalizations, emergency room visits and clinic visits. Deaths were identified from automated clinical databases at Kaiser as well as from the State death records for California. To evaluate safety, rates of diagnosis-specific events in the risk periods were compared with the rates of such diagnosis-specific events in two self control and one historical control period.nnnRESULTSnDuring the study period of April 1, 1995, to December 31, 1996, a total of 89753 adults and children received varicella vaccine. A total of 3200 relative risks were calculated, and of these 5 hospital diagnostic categories, 9 emergency visit diagnostic categories and 30 outpatient diagnostic categories demonstrated at least 1 relative risk with a P value of <0.05 in 1 or more age groups and in comparisons with 1 control period or more. The p value for these tests was not adjusted for multiple comparisons. Of these categories 14 demonstrated an increased risk either in more than 1 age group or against more than 1 comparison group. These categories included elective procedures, febrile seizure, febrile illness, well child, acute gastroenteritis, varicella, congenital anomaly, rule out sepsis, trauma, viral syndrome, apnea, back pain, congenital valvular heart disease and vision evaluation for glasses. Of these the outcomes of elective procedure, congenital anomaly, congenital valvular heart disease, well child and vision evaluation for glasses were judged not to have a biologically plausible association with vaccination. A second diagnostic grouping included febrile illness, viral illness, febrile seizure and rule out sepsis. In an analysis of these events which adjusted for the concomitant administration of M-M-R(II) vaccine, none of the associations was statistically associated with receipt of varicella vaccine. The diagnostic category of rule out sepsis still had a relative risk of 1.95 with P = 0.02. None of the children in the rule out sepsis category had positive bacteriologic cultures from any other normally sterile site. Because of the large number of gastroenteritis cases, we reviewed a random sample of 100 exposed and 100 unexposed cases. From this review no consistent time association or clustering of any of these events was seen in the exposed follow-up time interval. Only gastroenteritis and negative evaluations for sepsis were thought to be possibly associated with receipt of varicella vaccine. Although there was a statistically significant increased risk over the entire 30 day-period, there was no clustering of these events within the 30-day window.nnnCONCLUSIONnIn this study population of 89753 children and adults, the varicella vaccine (Oka strain, Merck) appeared to have a favorable safety profile. In addition rates of varicella-like rash and of breakthrough cases were both low and consistent with the rates observed in prelicensure studies.

Incidence and hospitalization rates of varicella and herpes zoster before varicella vaccine introduction : a baseline assessment of the shifting epidemiology of varicella disease

Background. A 15-year postmarketing evaluation of the impact of varicella vaccine on the age distribution of varicella disease is being conducted at Kaiser Permanente Medical Care Program, Northern California (KPMCP). We report on a baseline assessment of the age-specific incidence and hospitalization rates of varicella and herpes zoster that was conducted before vaccine introduction. Methods. To assess the annual incidence of varicella, a telephone survey was conducted in a random sample of ∼8000 youths 5 to 19 years of age. The annual incidence of hospitalizations for varicella and herpes zoster in 1994 was assessed with the use of the computerized database at KPMCP. Results. Varicella annual incidence was 10.3% in 5- to 9-year-olds, 1.9% in 10- to 14-year-olds and 1.2% in the 15- to 19-year age groups, respectively. Hospitalization rates among the entire KPMCP membership were 2.6 and 2.1 per 100 000 person years for varicella and zoster, respectively. Varicella incidence in the 15- to 19-year age group was higher among African-Americans than among Caucasians. Conclusions. Varicella rates were similar in the 5- to 9- and 10- to 14-year age groups to rates from other published studies conducted in 1972 to 1978, 1980 to 1988 and 1990 to 1992; however, the rate in 15- to 19-year-olds was 2 to 4 times higher than published rates in the same age category.

Epidemiology of bacterial meningitis among children in Brazil, 1997-1998

OBJECTIVEnTo document the incidence and the descriptive epidemiology of bacterial meningitis among individuals under age 20 in a geographically defined region in Brazil during the two-year period immediately preceding the introduction of Haemophilus influenzae type b (Hib) vaccines into the national immunization program of Brazil.nnnMETHODSnPopulation-based epidemiological study of all cases of bacterial meningitis reported among residents of Campinas, Brazil, under age 20 (n=316,570) during the period of 1997-98, using comprehensive surveillance records compiled by the Campinas Health Department from cases reported among hospital inpatients, outpatients, emergency room visits, death certificates, and autopsy reports.nnnRESULTSnThe incidence of bacterial meningitis (n=274) was 334.9, 115 and 43.5 cases/10(5) person-years (pys) for residents of Campinas under age 1, 5 and 20, respectively. All cases were hospitalized, with an average length of stay of 12 days. Documented prior antibiotic use was 4.0%. The case-fatality rate of bacterial meningitis in individuals under age 20 was 9% (24/274) with 75% of deaths occurring in children under the age of five. The incidence of Hib meningitis (n=26) was 62.8 and 17 cases/10(5) pys in children age <1 and <5, respectively.nnnCONCLUSIONSnThe incidence of Hib meningitis in children under the age of 5 in Campinas during 1997-98 was similar to that reported in the US, Western Europe, and Israel prior to widespread Hib vaccine use in those regions. This study provides a baseline for later studies to evaluate changes in the etiology and incidence of bacterial meningitis in children after introduction of routine Hib vaccination in Brazil.

Panel IV. Evaluation: The value and cost-effectiveness of drug utilization review programs*

Clinical Pharmacology and Therapeutics (1991) 50, 636–638; doi:10.1038/clpt.1991.199