Biomedical subjects

W Blackwelder

Publications and source records attributed to W Blackwelder.

7 recordsLinked to original sources

PubMed2001

Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception.

BACKGROUND: Studies have reported a temporal association between a first dose of rotavirus vaccine (Rotashield) and infant intussusception. We investigated the effect of Rotashield vaccination use on intussusception admissions in ten US states. METHODS: We analysed electronic databases containing 100% hospital discharge records for 1993-99 from ten US states, where an estimated 28% of the birth cohort had received Rotashield (based on manufacturer's net sales data). We examined records of infants admitted to hospital (<365 days old) with any mention of intussusception (International Classification of Diseases, ninth revision, clinical modification code 560.0). Excess admissions for intussusception during the period of Rotashield availability (October 1998 to June 1999) were estimated by direct comparison with the corresponding period of October 1997 to June 1998 (before Rotashield was available) and with adjustment for secular trends during 1993-98 by Poisson regression. FINDINGS: Hospital admission for intussusception among infants younger than 365 days of age during the Rotashield period compared with previously was 4% lower (10 cases) by direct comparison and 10% lower (27 cases) by trend comparison, corresponding to a negative population attributable risk. Among infants aged 45-210 days (target age range for a first Rotashield dose), we estimated an increase in intussusception admissions of 1% (one excess admission) by direct comparison and 4% (4.6 excess admissions) by trend comparison, corresponding to a population attributable risk range of one excess admission in 66000-302000. INTERPRETATION: We found no evidence of increased infant intussusception admissions during the period of Rotashield availability. The total intussusception admission risk attributable to Rotashield was substantially lower than previous estimates based on studies focusing on the immediate postvaccination weeks.

Case-Control Studies↗

PubMed2001

Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans.

Recent outbreaks of avian influenza in humans have demonstrated the need for vaccines for influenza viruses with pandemic potential. Recombinant hemagglutinins are an attractive option for such vaccines because they do not require handling potentially highly pathogenic influenza viruses for vaccine production. In order to evaluate the immunogenicity, optimum dosing and timing of administration of a recombinant baculovirus-expressed H5 HA (rH5) in humans, 147 healthy adults were assigned randomly to receive intramuscular rH5 as two doses of 25, 45 or 90 microg each, one dose of 90 microg followed by a dose of 10 microg, or two doses of placebo, at intervals between doses of 21, 28 or 42 days. All doses of rH5 were well tolerated. The rH5 vaccine was modestly immunogenic at high dose. Neutralizing antibody responses to a titer of 1:80 or greater were seen in 23% (14/60) of individuals after a single dose of 90 microg, and in 52% (15/29) after two doses of 90 microg. Varying intervals between doses from 21 to 42 days had no significant effect on antibody responses to vaccination. These results suggest that baculovirus-expressed H5 HA can induce functional antibody in individuals who have not had prior exposure to H5 viruses, but that further studies to improve the immunogenicity of the vaccine are needed.

Adult↗

PubMed2001

Importance of complement source in measuring meningococcal bactericidal titers.

Complement-mediated bactericidal antibodies in serum confer protection against meningococcal disease. The minimum protective titer is estimated to be between 1:4 and 1:8 when measured by the Goldschneider assay performed with human complement, the assay used in the 1960s to establish the correlation between bactericidal antibodies and protection. A more recently described bactericidal assay standardized by an international consortium uses rabbit complement, which is known to augment bactericidal titers. To define a protective titer measured by the standardized assay, we compared bactericidal titers against serogroup C strains measured by this assay to titers measured by the assay described by Goldschneider et al. A titer of > or =1:128 measured by the standardized assay was needed to predict with > or =80% certainty a positive titer of > or =1:4 as measured by the Goldschneider assay. However, the majority of samples with titers of 1:4 measured by the Goldschneider assay had titers of <1:128 when measured by the standardized assay. Therefore, by the results of the standardized assay such persons would be falsely categorized as being susceptible to disease. In conclusion, high bactericidal titers measured with the standardized assay performed with rabbit complement are predictive of protection, but no threshold titer is both sensitive and specific for predicting a positive titer measured by the Goldschneider assay using human complement. Up to 10% of the U.S. adult population lacks intrinsic bactericidal activity against serogroup C strains in serum and can serve as complement donors. Therefore, use of the Goldschneider assay or an equivalent assay performed with human complement is preferred over assays that use rabbit complement.

Adult↗

PubMed2000

Decreased bone mineral density during low dose glucocorticoid administration in a randomized, placebo controlled trial.

OBJECTIVE: While osteoporosis and bone fractures are clearly recognized side effects of high dose glucocorticoids, the effect of low dose glucocorticoids remains controversial. We investigated the effect of 3 months of low dose hydrocortisone on bone mineral density (BMD). METHODS: Subjects, 18 to 55 years old with chronic fatigue syndrome and no medical or psychiatric illness requiring medication, were randomized in a double blind, placebo controlled trial to receive oral hydrocortisone, 13 mg/m2 body surface area every morning and 3 mg/m2 every afternoon (25 to 35 mg/day, equivalent to about 7.5 mg prednisone/day) or placebo for 12 weeks. Before and after treatment BMD of the lumbar spine was measured by dual energy x-ray absorptiometry. RESULTS: We studied 23 subjects (19 women, 4 men). For the 11 hydrocortisone recipients there was a mean decrease in BMD: mean change from baseline of the lateral spine was -2.0% (95% CI -3.5 to -0.6. p = 0.03) and mean change of the anteroposterior spine was -0.8% (95% CI -1.5 to -0.1, p = 0.06). Corresponding changes for the 12 placebo recipients were +1.0% (95% CI -1.0 to 3.0, p = 0.34) and +0.2% (95% CI -1.4 to 1.5, p = 0.76). CONCLUSION: A 12 week course of low dose glucocorticoids given to ambulatory subjects with chronic fatigue syndrome was associated with a decrease in BMD of the lumbar spine. This decrease was statistically significant in lateral spine measurements and nearly so in anteroposterior spine measurements.

Adult↗

PubMed1995

A placebo-controlled trial of a pertussis-toxoid vaccine.

BACKGROUND: Although many whole-cell vaccines have been effective in preventing pertussis, these vaccines are difficult to standardize and can produce side effects. In Sweden, pertussis became endemic during the 1970s despite vaccination. Because of its limited efficacy, the Swedish-made whole-cell vaccine was withdrawn in 1979. METHODS: To evaluate the efficacy of an acellular vaccine consisting of pertussis toxin inactivated by hydrogen peroxide (pertussis toxoid), we conducted a randomized, double-blind, placebo-controlled trial in Sweden. Infants were vaccinated with either diphtheria and tetanus toxoids alone (DT toxoids, 1726 infants) or diphtheria, tetanus, and pertussis toxoids (DTP toxoids, 1724 infants) at 3, 5, and 12 months of age. RESULTS: There were no serious reactions. With the pertussis vaccine there were slightly more local reactions than with the DT toxoids alone, but the rates of postvaccination fever were the same. The main period of surveillance, which began 30 days after the third vaccination, continued for a median of 17.5 months. There were 312 cases of pertussis (72 in the DTP-toxoids group and 240 in the DT-toxoids group) that met the clinical criterion (paroxysmal cough lasting > or = 21 days) and laboratory criteria for pertussis as defined by the World Health Organization. The efficacy of this acellular vaccine was 71 percent (95 percent confidence interval, 63 to 78 percent). The recipients of DTP toxoids who had pertussis had cough of shorter duration than the recipients of DT toxoids, and fewer had whooping and vomiting. The vaccine efficacy after two doses was 55 percent (95 percent confidence interval, 12 to 78 percent), on the basis of 14 cases in the DTP-toxoids group and 31 in the DT-toxoids group that met the definition of the World Health Organization. CONCLUSIONS: A pharmacologically inert, acellular pertussis-toxoid vaccine that is easily standardized is safe and confers substantial protection against pertussis.

Diphtheria Toxoid↗

PubMed1987

Infection with the human immunodeficiency virus: clinical manifestations and their relationship to immune deficiency. A report from the Multicenter AIDS Cohort Study.

In 1984 a large prospective study of gay and bisexual men was begun to elucidate the natural history of the human immunodeficiency virus (HIV) infection. At two successive semiannual examinations, clinical or hematologic abnormalities were found up to 13 times more often among HIV-seropositive men (n = 1611) than HIV-seronegative men (n = 2646). More than 30% of the seropositive participants had persistent generalized lymphadenopathy, independent of T-helper lymphocyte (CD4) counts and most other signs and symptoms. Other clinical manifestations such as thrush, anemia, thrombocytopenia, neutropenia, fever, and fatigue occurred with only slightly reduced CD4 counts (400 to 700/mm3) and appeared to increase exponentially with progressively lower counts. A simple systematically derived clinical index using these manifestations identified more than 70% of the seropositive men with significant T-helper cell depletion. This kind of clinical index may be useful for assessing groups of HIV-infected persons, especially those whose T-lymphocyte numbers and function cannot be readily measured.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial.

CONTEXT: Chronic fatigue syndrome (CFS) is associated with a dysregulated hypothalamic-pituitary adrenal axis and hypocortisolemia. OBJECTIVE: To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS. DESIGN: A randomized, placebo-controlled, double-blind therapeutic trial, conducted between 1992 and 1996. SETTING: A single-center study in a tertiary care research institution. PATIENTS: A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications. INTERVENTION: Oral hydrocortisone, 13 mg/m2 of body surface area every morning and 3 mg/m2 every afternoon, or placebo, for approximately 12 weeks. MAIN OUTCOME MEASURES: A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment. Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment. Patients recorded adverse effects on a checklist. RESULTS: The number of patients showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients vs 20 (66.7%) of 30 hydrocortisone recipients (P =.31). Hydrocortisone recipients had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more points in Wellness score, and a higher average improvement in Wellness score on more days than did placebo recipients (P<.001). Statistical evidence of improvement was not seen with other self-rating scales. Although adverse symptoms reported by patients taking hydrocortisone were mild, suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group (P<.001). CONCLUSIONS: Although hydrocortisone treatment was associated with some improvement in symptoms of CFS, the degree of adrenal suppression precludes its practical use for CFS.

Adult↗