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E Miller

Publications and source records attributed to E Miller.

At least 73 records · Page 4Linked to original sources
PubMed2001

MMR and autism: further evidence against a causal association.

The hypothesis that MMR vaccines cause autism was first raised by reports of cases in which developmental regression occurred soon after MMR vaccination. A previous study found no evidence to support this hypothesis. It has recently been suggested that MMR vaccine might cause autism, but that the induction interval need not be short. The data from the earlier study were reanalysed to test this second hypothesis. Our results do not support this hypothesis, and provide further evidence against a causal association between MMR vaccination and autism.

Adolescent↗
PubMed2001

Comparison of antibody kinetics following meningococcal serogroup C conjugate vaccine between healthy adults previously vaccinated with meningococcal A/C polysaccharide vaccine and vaccine-naïve controls.

Few data are available on the kinetics of meningococcal serogroup C-specific antibody production following meningococcal serogroup C conjugate (MCC) vaccination, particularly in those who have received prior meningococcal A/C polysaccharide (MACP) vaccination(s). Laboratory staff who had previously received either one dose (n = 35), two doses (n = 18) of MACP vaccine or who were naïve to previous meningococcal vaccination (n = 42) were vaccinated with MCC. Bloods were taken pre-vaccination, on the subsequent 4 days and on days 10 and 28. Serogroup C serum bactericidal antibody (SBA), and anti-serogroup C-specific IgG, IgM and IgA were measured. There were no significant differences between the groups who had received either 2 or 1 prior dose(s) of MACP, therefore, these results were combined. Up to day 4 there was no evidence of a significant increase or decrease in the median levels of SBA, IgG, IgM or IgA in either the naïve or MACP groups, although about 20% of individuals did have 4-fold SBA rises by day 4. By day 10 there were large significant increases in the levels of SBA, IgG, IgM and IgA with respective fold increases from pre-vaccination levels of 4.6, 1.9, 1.2 and 2.1 in the MACP group and 270, 13.4, 4.8 and 33.8 in the naïve group. Further significant increases were seen between day 10 and 28 for SBA, IgG and IgM (naïve group only). By day 28, 4-fold SBA rises had occurred in 63.5% of the MACP group and 97.6% of the naïve group. The SBA GMT on day 28 significantly differed between the naïve and MACP groups with GMTs 2.8-fold higher in the naïve group (P = 0.021). In conclusion, no decline in serogroup C-specific antibody levels was demonstrated immediately post-MCC vaccination whilst these levels had risen significantly by day 10. Putative protective SBA titres (> or =8, 32 or 128) were observed by day 10 following MCC vaccination regardless of MACP history.

Adult↗
PubMed2001

Efficacy of meningococcal serogroup C conjugate vaccine in teenagers and toddlers in England.

The UK was the first country to use meningococcal serogroup C conjugate (MCC) vaccines, which were licensed on the basis of immunogenicity and safety data but without a formal efficacy study. Increased surveillance during the first 9 months since introduction has shown that short-term efficacy of the MCC vaccine in England was 97% (95% CI 77-99) for teenagers and 92% (65-98) for toddlers. These early results confirm the superiority of MCC over plain C polysaccharide vaccines, which are ineffective in young children.

Adolescent↗
PubMed2001

Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial.

BACKGROUND: Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control. METHODS: Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population. RESULTS: Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition. CONCLUSION: Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.

Adaptation, Psychological↗
PubMed2001

The seroepidemiology of measles in Western Europe.

The European Regional Office of WHO has targeted measles for elimination from the region in 2007. Large national, age and sex stratified serological surveys of measles antibody were conducted in seven Western European countries from 1994-8 as part of the European Seroepidemiology Network. Three patterns were observed in the country-specific measles seroprofiles, ranging from (very) low susceptibility (four countries) to high susceptibility (one country). Susceptibility levels amongst 2-4-year-olds ranged from 2.9 to 29.8%, in 5-9-year-olds from 2.5 to 25% and 10-19-year-olds from 2.1% to 13.9%. A country's susceptibility profile was highly associated with vaccine coverage for the first dose. First dose coverage ranged from 91 to 97.5% for low susceptibility countries, 75 to 85% for intermediate susceptibility countries and 55% for the high susceptibility country. Only the high susceptibility country still reports epidemic measles. In low susceptibility countries, which have achieved or are very close to measles elimination, the priority will be to maintain high MMR vaccine coverage in all geopolitical units for both vaccine doses. In moderate susceptibility countries there is still some endemic transmission, but also risk of outbreaks as pools of susceptibles accumulate. In the high susceptibility country the priority will be to increase infant vaccine coverage and reduce regional variation in coverage levels.

Adolescent↗
PubMed2001

Does oral polio vaccine cause intussusception in infants? Evidence from a sequence of three self-controlled cases series studies in the United Kingdom.

BACKGROUND: The use of live oral poliomyelitis vaccine (OPV) has led to the elimination of poliomyelitis disease in many countries since licensure in 1960. The discovery of an increased risk of an intestinal obstruction known as intussusception following live rotavirus vaccination raised questions about the possibility of a link between live OPV and intussusception. METHODS: Three self-controlled case-series studies were carried out. The first was exploratory and included 218 intussusception episodes from hospital admissions data linked to vaccination records in the Thames region. The two subsequent studies, which used further hospital admissions data and the General Practice Research Database (GPRD) included 107 and 198 episodes respectively and were used to test hypotheses generated in the first study. RESULTS: In the exploratory study risk periods of up to 6 weeks after each dose were examined. The only period with some evidence of an increased risk was the 14-27-day period after the third dose (relative incidence (RI) = 1.97, p = 0.011). The second hospital admissions study and the GPRD study showed no evidence of an increased relative incidence in any putative risk period and did not confirm the increased risk in the 14-27-day period after dose 3 with a combined RI of 1.03. CONCLUSIONS: The sequence of studies does not support the hypothesis that OPV causes intussusception. The increased RI in the first study may be explained as a chance finding due to the number of risk periods examined and highlights the need for caution when looking at many risk periods without an a priori hypothesis.

Chi-Square Distribution↗
PubMed2001

Serological basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: reevaluation of correlates of protection.

The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA). This may give higher titers than those obtained with human complement (hSBA), for which the "gold standard" correlate of protection for meningococcal C disease is a titer of > or =4. Comparison of rSBA and hSBA titers in sera from unvaccinated adults with an rSBA titer of > or =8 showed that for 93% (27 of 29) the titer was > or =4 by hSBA, confirming natural protection. Furthermore, sera from MCC vaccinees showed that an rSBA titer of <8 or > or =128 discriminated susceptibility and protection well (85% with rSBA titers of <8 had hSBA titers of <4, and 99% with rSBA titers of > or =128 had hSBA titers of > or =4). However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of > or =4. In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre- and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose with, if available, evidence of antibody avidity maturation or an hSBA titer of result > or =4. Applying these criteria to toddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single dose of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64. In addition, of those with titers of <128 post-MCC vaccination, 90% had titers of > or =128 after a 10-microg polysaccharide booster dose, compared with only 7% of unprimed age-matched toddlers given a full 50-microg dose. Furthermore, the increase in geometric mean avidity index pre- and postbooster was independent of post-primary MCC titer. These results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory.

Adolescent↗
PubMed2001

Evaluation of De-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: reactogenicity, immunogenicity, immunologic priming, and bactericidal activity against O-acetylated and De-O-acetylated serogroup C strains.

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc-) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc- MenC strains and OAc+ and OAc- polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of > or = 8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc- IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc- MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc- IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc- MenC strains in infancy.

Antibodies, Bacterial↗
PubMed2001

Genotypic variation in the Bordetella pertussis virulence factors pertactin and pertussis toxin in historical and recent clinical isolates in the United Kingdom.

The reemergence of pertussis has been reported in several countries despite high vaccination coverage. Studies in The Netherlands and Finland have investigated polymorphism in the genes coding for two important virulence factors of Bordetella pertussis, pertactin and pertussis toxin, and identified the emergence and subsequent dominance in circulating strains of pertactin and toxin variants not found in the whole-cell vaccine (WCV). The study described here investigated whether such variation had occurred in the United Kingdom, which presently has low levels of pertussis. Sequence analysis of the genes for pertactin (prnA) and the pertussis toxin S1 subunit (ptxA) among isolates of B. pertussis from 285 United Kingdom patients, from 1920 to 1999, revealed three prnA variants, prnA(1), prnA(2), and prnA(3), and two ptxA variants, ptxA(1) and ptxA(2), showing differences in nucleic acid sequence. The proportion of pertactin gene types not included in the United Kingdom WCV, i.e., prnA(2) and prnA(3), has increased in recent years and was found in 21 of 86 (24%) strains from the 1980s and 56 of 105 (53%) strains from the 1990s. To date, the presence of these nonvaccine prnA types has not been associated with a resurgence of pertussis in the United Kingdom. The distribution of prnA and ptxA types in The Netherlands, Finland, and the United Kingdom in the 1990s is distinct. The most striking difference in the United Kingdom isolates is that all 105 of the most recent circulating strains (from 1998 to 1999) are of a pertussis toxin type found in the United Kingdom WCV, i.e., ptxA(1).

Amino Acid Sequence↗
PubMed2001

Idiopathic thrombocytopenic purpura and MMR vaccine.

A CAUSAL ASSOCIATION BETWEEN MEASLES: mumps-rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post-immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences.

Female↗
PubMed2001

Vaccine trials.

This article reviews some of the issues involved in evaluating vaccines in humans. Vaccine trials are required for licensure and are essential for demonstrating a vaccine's safety and protective efficacy. The formal framework of phase I, II, and III trials is described, with particular emphasis on the choice of hypotheses, trial design, and biases that arise in the context of vaccine trials. However, some aspects of a vaccine's performance cannot be evaluated in clinical trials owing to their relatively small size. Thus, vaccine evaluation must continue after licensure, for example, to evaluate the vaccine with respect to rare reactions, duration of protection, and ecological effects. The article reviews some of the methods commonly used for post-licensure studies of vaccine efficacy and safety.

Clinical Trials as Topic↗
PubMed2001

Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes.

OBJECTIVE: To determine the efficacy of rosiglitazone compared with placebo in reducing hyperglycemia. RESEARCH DESIGN AND METHODS: After a 4-week placebo run-in period, 959 patients were randomized to placebo or rosiglitazone (total daily dose 4 or 8 mg) for 26 weeks. The primary measure of efficacy was change in the HbA1c concentration. RESULTS: Rosiglitazone produced dosage-dependent reductions in HbA1c of 0.8, 0.9, 1.1, and 1.5% in the 4 mg o.d., 2 mg b.i.d., 8 mg o.d., and 4 mg b.i.d. groups, respectively, compared with placebo. Clinically significant decreases from baseline in HbA1c were observed in drug-naive patients at all rosiglitazone doses and in patients previously treated with oral monotherapy at rosiglitazone 8 mg o.d. and 4 mg b.i.d. Clinically significant decreases from baseline in HbA1c were also observed with rosiglitazone 4 mg b.i.d. in patients previously treated with combination oral therapy. Approximately 33% of drug-naive patients treated with rosiglitazone achieved HbA1c < or =7% at study end. The proportions of patients with at least one adverse event were comparable among the rosiglitazone and placebo groups. There was no evidence of hepatotoxicity in any treatment group. There were statistically significant increases in weight and serum lipids in all rosiglitazone treatment groups compared with placebo. For LDL and HDL cholesterol, the observed increase appeared to be dose related. CONCLUSIONS: Rosiglitazone at total daily doses of 4 and 8 mg significantly improved glycemic control in patients with type 2 diabetes and was well tolerated.

Aged↗
PubMed2001

Nerve growth factor and neurotrophin-3 affect functional recovery following peripheral nerve injury differently.

PURPOSE: Many studies have investigated the roles of neurotrophic factors in nerve regeneration by examining either anatomical recovery (regenerated axon count) or functional recovery as measured by sensory and motor behavior. This longitudinal study examined the effects of NGF and NT3 on functional and anatomical recovery following transection of tbc sciatic nerve. METHODS: Alzet osmotic pumps were implanted to deliver a continuous supply of NGF, NT3 or buffer solution to the stumps of the transected sciatic nerve for the first 28 days following implantation. Rats were tested weekly to determine the extent of recovery of motor (footprint gait analysis) or nociceptive (warm water withdrawal), and mechanoreceptive (skin pinch) function. RESULTS: Neither NT3-, nor NGF-treatment significantly enhanced motor recovery as examined by gait analysis. At the end of 12 weeks of behavioral testing, there was no difference in motor recovery. In addition, the recovery of withdrawal response to warm water stimulus was delayed in NGF treated animals. After twelve weeks, nerves were removed for anatomical analysis. Regenerated sciatic nerves from NT3 treated animals had slightly more axons than control- or NGF-treated animals. CONCLUSION: This work shows that there were no long-lasting improvements of anatomical or functional recovery in NGF- or NT3-treated animals 12 weeks following sciatic nerve transection.

Animals↗
PubMed2000

Invasive pneumococcal disease in England and Wales: vaccination implications.

Knowledge of the epidemiology of invasive pneumococcal disease (IPD) will aid in planning the use of pneumococcal vaccines. A United Kingdom (UK)-based surveillance in England and Wales (1995-1997) of 11,528 individuals with IPD and a local enhanced surveillance in the Oxford (UK) area (1995-1999) have been analyzed. IPD has a high attack rate in children, with 37.1-48.1 cases per 100,000 infants <1 year old per year, and in older persons, with 21.2-36.2 cases per 100,000 persons >65 years old per year, for England, Wales, and Oxford. The 7-valent conjugate vaccine includes serotypes causing < or =79% of IPD in children <5 years old, but only 66% in adults >65 years old. The data also indicate that IPD varies by serotype, age, and country, emphasizing that the epidemiology of IPD is heterogeneous and requires continued surveillance.

Adolescent↗
PubMed2000

Reduced antibody response to revaccination with meningococcal serogroup A polysaccharide vaccine in adults.

Widespread use of meningococcal A and C polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to these polysaccharides. Immunological hyporesponsiveness to C polysaccharide has been clearly documented in infants, children and adults but only limited data from Gambian children are available for A polysaccharide. We investigated whether a second dose of MACP, given 6 months after an initial dose affected the immunological response as measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay (ELISA), to serogroup A meningococci in young adults (university students, n=36). Serogroup A SBA responses 1 month following the second dose of MACP (geometric mean titre (GMT) 103.6, 95% CI 45.6-235.1) were approximately one third of the levels observed 1 month post first dose (GMT 281.9, 95% CI 134.9-581.4). The serogroup A-specific IgG levels post second dose (GMC 21.2, 95% CI 15.3-29.4) were also significantly lower at an average of three-quarters the level post first dose (GMC 28.7, 95% CI 20.8-39.7). This confirms that revaccination with MACP vaccine, 6 months following the initial dose, results in a reduced immunological response to A polysaccharide in adults. Repeated vaccination with MACP vaccine may be ineffective and development and use of meningococcal serogroup A conjugate vaccines should be encouraged.

Adolescent↗
PubMed2000

Ability of 3 different meningococcal C conjugate vaccines to induce immunologic memory after a single dose in UK toddlers.

To test for immunologic memory after a single dose of meningococcal C conjugate (MCC) vaccine in toddlers, 226 children 12-18 months old were randomized to receive 1 of 3 MCC vaccines, with a C polysaccharide booster 6 months later. The protein conjugate was diphtheria mutant toxoid in 2 vaccines (MCC-CRM(197)) and was tetanus toxoid in the third (MCC-TT). One month after the MCC vaccines, 91%-100% of children had serum bactericidal antibody (SBA) titers > or =8, and 89%-100% had a > or =4-fold increase. Geometric mean titer (GMT) increased from <4 to 215 (95% confidence interval [CI], 166-279). MCC-TT induced higher SBA GMTs (P<.001) and higher proportions with SBA > or =8 (P=.02) than did the MCC-CRM(197) vaccines. By 6 months, GMTs had decreased to 55.1 (95% CI, 40-76), but IgG antibody avidity increased (P<.001). Induction of immunologic memory was confirmed by a GMT of 1977 (range, 1535-2547) after the polysaccharide booster and a further increase in avidity. This evidence justified the use of a single dose in a catch-up immunization program for children 1-18 years old.

Antibodies, Bacterial↗