Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn's Disease Regardless of Prior Biologic Exposure.

BACKGROUND & AIMS: Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849], U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease. Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status. METHODS: Patients were randomized to placebo or upadacitinib 45 mg (UPA45) for 12 weeks (induction). UPA45 clinical responders were enrolled in U-ENDURE and rerandomized to placebo, upadacitinib 15 mg, or upadacitinib 30 mg (UPA30) for 52 weeks. Assessments were by prior biologic failure. RESULTS: Of 1021 patients, 733 (71.8%) had prior biologic failure. Across outcomes and subgroups, upadacitinib-treated patients achieved higher rates vs placebo. During induction, upadacitinib had higher rates vs placebo for clinical remission based on stool frequency/abdominal pain score (without failure: 54.0% vs 28.3%; with failure: 42.2% vs 14.1%) and endoscopic response (without failure: 52.0% vs 16.2%; with failure: 35.7% vs 5.3%). In maintenance, the greatest treatment effect (upadacitinib vs placebo) was among patients with prior biologic failure treated with UPA30 (clinical remission without failure: 58.5% vs 32.7%; with failure: 42.5% vs 8.7%; endoscopic response without failure: 43.9% vs 17.9%; with failure: 38.9% vs 4.0%). Patients without vs with prior biologic failure had fewer adverse events. CONCLUSIONS: Upadacitinib led to higher absolutes rates of clinical and endoscopic outcomes in patients without vs with prior biologic failure. Patients treated with upadacitinib achieved greater rates of clinical and endoscopic improvements vs placebo, regardless of prior biologic exposure. CLINICALTRIALS: gov: NCT03345849, NCT03345836, NCT03345823.

Upadacitinib Reduces Crohn's Disease Symptoms Within the First Week of Induction Therapy.

BACKGROUND & AIMS: Upadacitinib (UPA), an oral Janus kinase inhibitor, is approved to treat moderately to severely active Crohn's disease (CD). Because symptomatic response is an important initial treatment goal for patients, we evaluated the rapidity of symptomatic improvement in patients with CD receiving UPA 45 mg once daily (UPA45) induction therapy. METHODS: This post hoc analysis included pooled data from 2 phase 3, multicenter, double-blind, 12-week induction trials (U-EXCEL and U-EXCEED) and 1 maintenance trial (U-ENDURE). Daily diary data for the first 15 days of UPA45 or placebo (PBO) treatment were used to analyze improvement in very soft/liquid stool frequency (SF) and abdominal pain score (APS). Clinical outcomes were evaluated at every study visit. RESULTS: Overall, 1021 patients (n = 674 UPA45; n = 347 PBO) were analyzed. UPA45 demonstrated greater efficacy vs PBO for SF <3 and APS ≤1, providing rapid relief by day 5 or 6, regardless of prior biologic exposure. Mean changes in SF and APS were greater with UPA45 beginning at week 2 (-2.0 and -0.5, respectively; P < .001) and were maintained through week 12 (-3.0 and -1.0, respectively; P < .001) vs PBO. The first achievement of daily SF/APS clinical remission occurred earlier with UPA45 (median, 13 d) vs PBO (median, 32 d), and patients treated with UPA45 showed improved rates of SF/APS clinical remission (21.1% UPA45 vs 8.9% PBO) and clinical response (58.8% UPA45 vs 37.9% PBO) starting at week 2 (both P ≤ .01). CONCLUSIONS: UPA45 provided rapid relief of clinical symptoms within the first week of treatment in patients with CD. CLINICALTRIALS: gov numbers: NCT03345849, NCT03345836, and NCT03345823.

Canadian Adalimumab Postmarketing Observational Epidemiological Study Assessing Effectiveness in Psoriatic Arthritis (COMPLETE-PsA): 12-month Results of Comparative Effectiveness of Adalimumab and nbDMARDs.

OBJECTIVE: COMPLETE-PsA was an observational study of biologic-naïve Canadian adults with active psoriatic arthritis (PsA) treated with adalimumab (ADA) or a nonbiologic disease-modifying antirheumatic drug (nbDMARD) regimen, after inadequate response/intolerance to a current nbDMARD treatment regimen. The aim of this analysis was to assess the 12-month effectiveness of ADA vs nbDMARDs. METHODS: Patients enrolled between March 2012 and November 2017 were included. The following clinical variables and patient-reported outcomes were collected/calculated per routine care: Disease Activity Index for Psoriatic Arthritis in 28 joints (DAPSA28), Disease Activity Score in 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein, physician global assessment (PGA), patient global assessment (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), 12-item Short Form Health Survey, enthesitis, dactylitis, body surface area (BSA), and time to achieving American College of Rheumatology (ACR) 50, ACR70, and modified minimal disease activity (mMDA). RESULTS: Two hundred and seventy-seven ADA-treated and 148 nbDMARD-treated patients were included. At baseline, ADA-treated patients were less likely to be employed, had longer morning stiffness, higher DAPSA28, DAS28, PGA, PtGA, pain, and HAQ-DI, and lower prevalence of dactylitis (all P < 0.05). ADA-treated patients showed lower baseline-adjusted DAPSA28 (16.5 vs 26.6), DAS28 (2.8 vs 3.9), PGA (25.3 vs 37.1), and ESR (10.4 vs 15.0 mm/h) after 3 months compared to nbDMARD-treated patients, with observed improvements maintained to month 12. Time to achievement of ACR50, ACR70, and mMDA was significantly shorter (P < 0.001) among ADA-treated patients, with the likelihood of having dactylitis (odds ratio [OR] 0.4, 95% CI 0.2-0.6) and BSA< 3% (OR 2.7, 95% CI 1.5-5.0) significantly lower and higher, respectively. Switching to another biologic was less likely in ADA-treated vs nbDMARD-treated patients (hazard ratio 0.3, 95% CI 0.2-0.5). CONCLUSION: In a real-world Canadian population of patients with PsA, ADA was more effective than nbDMARDs at reducing disease activity and the severity of skin involvement, and demonstrated higher retention. [ClinicalTrials.gov: NCT01559038].

Who knows more about immunization?: Survey of public health nurses and physicians.

OBJECTIVE: To report the findings of a knowledge survey of nurse and physician immunization providers. DESIGN: Cross-sectional postal survey assessing demographic characteristics and vaccine knowledge. SETTING: British Columbia (BC). PARTICIPANTS: Nurse and physician immunization providers in BC. MAIN OUTCOME MEASURES: Knowledge of vaccine-preventable diseases, vaccines in general, and vaccine administration and handling practices. RESULTS: Survey responses were received from 256 nurses and 292 physicians (response rates of 48.6% and 18.3%, respectively). Most nurses (98.4%) reported receiving immunization training outside of the academic setting compared with 55.6% of physicians. Overall, nurse immunizers scored significantly higher than physician immunizers on all 3 domains of immunization knowledge (83.7% vs 72.8%, respectively; P < .001). Physicians scored highest on the vaccine-preventable disease domain and least well on the general vaccine domain. Nurses with more experience as health care providers scored higher. Physicians scored higher if they were female, served patient populations predominantly younger than 5 years, or received immunization training outside of academic settings. CONCLUSION: In BC, nurse immunizers appear to have higher overall immunization knowledge than physicians and are more likely to receive immunization training when in practice. Physician immunizers might benefit most from further training on vaccines and vaccine administration and handling.

Community-based HIV and STI prevention in women working in indoor sex markets.

Community research into women's experiences in the indoor commercial sex industry illustrated an urgent need for sexually transmitted infection (STI) and HIV education, prevention, testing, and treatment and culturally appropriate services to support the sexual and reproductive health of commercial sex workers (CSWs). This work also revealed that a high number of immigrant--primarily Asian--women are involved in the indoor sex industry. In response, the authors developed a community-academic research partnership to design and implement a blended outreach research program to provide STI and HIV prevention interventions for indoor CSWs and their clients. This Community Health Worker Model HIV Prevention and Health Promotion Program incorporated health education, primary care referrals, STI testing using self-swab techniques, and a point-of-care HIV screening test. Here the authors report on program implementation, design, and the experiences of participants and team members and provide research and vaccination recommendations for future work in this area. This work work affirms that community-based service providers can be a key entry point for indoor CSWs to access health care and sexual health promotion and education and may be a solution to missed opportunities to provide culturally and contextually appropriate education and services to this population.

Hepatitis C infection among pregnant women in British Columbia: reported prevalence and critical appraisal of current prenatal screening methods.

BACKGROUND: Despite the fact that hepatitis C virus (HCV) is a relatively common infection in Canada, particularly in British Columbia (BC), there is a paucity of information on actual HCV prevalence in pregnant women. At present, pregnant women are only screened if they fit risk criteria, which may result in under-identification of HCV in this population. The purpose of this study was to determine the overall prevalence rate, age and geographic distribution of reported HCV infection among pregnant women in BC, and compare results to a previously conducted anonymous seroprevalence survey. METHODS: Reported HCV prevalence was determined through a confidential database linkage of all prenatal screening results at the Canadian Blood Services (CBS) with all HCV test results at the Provincial Laboratory, from May 2000 to Oct 2002. Data were stratified by age group and geographic location, and subsequently compared to an anonymous prenatal seroprevalence survey conducted in 1994. RESULTS: The overall HCV prevalence rate was 50.3/10,000 (95% CI 46.3-54.6), or 0.5% of the cohort. Prevalence was highest in the northern BC region (66.2/10,000, 95% CI 51.4-85.3) and lowest in the populous suburban region southwest of Vancouver (38.0/10,000, 95% CI 32.3-44.8). Of note, the rate of reported HCV among pregnant women was significantly lower than the anonymous seroprevalence rate: 50.3/10,000 vs. 91.3/10,000 (p < 0.0001). CONCLUSION: Rates of reported HCV among pregnant women were approximately 50% lower than the rates determined by the anonymous seroprevalence survey. Further research is needed to determine the relative merits of the current selective screening policy versus universal prenatal HCV screening in pregnancy.

Identifying attitudes, beliefs and reported practices of nurses and doctors as immunization providers.

AIM: This paper is a report of a study conducted to examine the attitudes, beliefs, behavioural intentions and self-reported behaviour of nurses and physicians relating to key immunization behaviours and compare the findings for nurses and physicians. BACKGROUND: Immunization is an important and effective public health intervention. Understanding immunization providers' attitudes and beliefs toward immunization has the potential to improve educational efforts and lead to behavioural change. METHOD: A postal survey was conducted with all immunization providers in British Columbia, Canada, in 2005. The survey elicited data on demographics, practice characteristics, attitudes, perceived social norms and perceived behavioural control related to key immunization behaviours. RESULTS: Responses were received from 344 nurses and 349 physicians. The response rate was 67% for nurses and 22% for physicians. More nurses than physicians thought that administering all recommended vaccines at one visit was important (89.2% vs. 63.2%P < 0.001); nurses felt more pressure from parents to administer all recommended vaccines (82.4% vs. 48.7%P < 0.001), and nurses were also more likely to intend to give all recommended vaccines at one visit (98.8% vs. 73.8%P < 0.001). Both nurses and physicians thought that their own receipt of influenza vaccine each year was important (88.9%, 87.1% respectively P = 0.65). CONCLUSION: The foundational work done to develop the survey tool can be used to modify it so that survey findings can be validated according to the Theory of Planned Behaviour. The results could inform the development of behavioural change interventions targeting the identified determinants of immunization provider behaviour.

One arm or two? Concurrent administration of meningococcal C conjugate and hepatitis B vaccines in pre-teens.

BACKGROUND: The purpose of this study was to: (a) compare rates of local reactions from meningococcal C conjugate (Neis Vac-C) and hepatitis B vaccines (Recombivax HB), and (b) compare local reactions when both injections were given in one arm versus one in each arm. METHODS: Schools were randomized to have grade six students receive both vaccines in one arm (One Arm Group), or one vaccine in each arm (Two Arm Group; MCC always given in left arm). Structured telephone interviews of parents were conducted, and respondents were asked about local and systemic reactions, interference with school or other activities, need for medical attention, and lost parental work time. FINDINGS: The Two Arm Group reported significantly more local redness >46 mm (6.5% vs. 0.5%, p < 0.001), moderate to severe tenderness (28% vs. 18%, p < 0.05), and drowsiness (14% vs. 7%, p < 0.05). When adjusted for sex, ethnicity, and town of residence, report of any tenderness was associated with town of residence only; moderate or severe tenderness was independently associated with the Two Arm Group (OR 1.4, 95% CI 1.1-1.85). There were no statistically significant differences between groups for interference with school attendance or other activities, need for medical attention, or lost parental work time. Among participants of the Two Arm Group (188 students), there was more redness (6% vs. 2%, p < 0.05) and tenderness (54% vs. 32%, p < 0.001) experienced with Neis Vac-C than with Recombivax HB, respectively. CONCLUSIONS: Injecting two vaccines in one arm did not cause more local reaction than one injection in each arm and remains an option for those who prefer it for logistical reasons, If vaccinating in two arms, Neis Vac-C should preferentially be given in the nondominant arm.

Parental intention to have daughters receive the human papillomavirus vaccine.

BACKGROUND: Concerns have been raised that parents may be reluctant to have their daughters receive the human papillomavirus (HPV) vaccine, because of a belief that doing so might be interpreted as condoning earlier and more frequent sexual activity. We determined intentions regarding vaccination among Canadian parents and factors that predicted parental intention to have their daughters vaccinated against HPV. METHODS: Parents of children 8-18 years of age, recruited from across Canada, were asked to respond to questions in the context of a grade 6, publicly funded, school-based HPV vaccine program. We performed backward logistic regression analysis to identify factors predictive of parents' intention to have their daughters vaccinated against HPV. RESULTS: Of the 1350 respondents with female children, more than 70% (73.8%; 95% confidence interval [CI] 71.5%-76.1%) intended to have their daughters undergo vaccination against HPV. In multivariable modelling, parents who had positive attitudes toward vaccines (odds ratio [OR] 9.9, 95% CI 4.7-21.1), those who were influenced by subjective norms (OR 9.2, 95% CI 6.6-12.9), those who felt that the vaccine had limited influence on sexual behaviour (OR 3.2, 95% CI 2.2-4.6) and those who thought someone they knew was likely to get cervical cancer (OR 1.5, 95% CI 1.1-2.1) were more likely to intend that their daughters receive the HPV vaccine. Parents who were older (v. younger) (OR 0.6, 95% CI 0.4-0.8) and those who resided in British Columbia or Yukon Territory (v. Atlantic Canada) (OR 0.5, 95% CI 0.3-0.9) were less likely to intend that their daughters receive the HPV vaccine. INTERPRETATION: Most of the parents surveyed intended that their daughters would receive vaccination against HPV. Overall attitudes toward vaccines in general and toward the HPV vaccine in particular constituted the most significant predictor of parental intention with regard to vaccination.

Clients of indoor commercial sex workers: heterogeneity in patronage patterns and implications for HIV and STI propagation through sexual networks.

OBJECTIVES: To determine whether "high-risk" clients occupied important sociometric positions in sexual networks of commercial sex workers and to estimate whether they were more likely to be HIV and STI infected. GOAL: To determine whether a classification of high-risk clients could be validated by network analysis. STUDY DESIGN: We used proxy data on clients collected from a cross-sectional survey of 49 indoor female sex workers. RESULTS: Two types of clients were categorized as high risk, including those who created sexual bridges between sex establishments and those who had sex with most or all the FSW at an establishment. High-risk clients were significantly more central and were more likely to be members of cohesive subgroups than were lower-risk clients. The few known HIV and STI infections were in high-risk clients. CONCLUSIONS: It is possible to identify theoretically high-risk commercial sex clients from the network perspective using simple data collection and categorization approaches.

Fertility intentions of women of reproductive age living with HIV in British Columbia, Canada.

BACKGROUND: We undertook a study to examine the fertility intentions and reproductive health issues of women living with HIV in a broad-based sample in British Columbia, Canada. METHODS: Between November 2003 and December 2004, we invited women with HIV at all HIV clinics and AIDS service organizations in the province of British Columbia, Canada, to complete the survey instrument 'Contraceptive Decisions of HIV-positive Women'. Logistic regression analysis was conducted to calculate adjusted odds ratios to identify factors that may be significant predictors of the intention of women living with HIV to have children. RESULTS: Of the 230 surveys completed, 182 women (79.1%) were of reproductive age (

Conducting HIV/AIDS research with indoor commercial sex workers: reaching a hidden population.

BACKGROUND: Although comprising up to 80% of the commercial sex industry in Canada, indoor female sex workers (FSW) are generally not represented in research because they are a hidden population and difficult to access. OBJECTIVES: This paper describes a community-academic partnership model that was established to gain access to, deliver outreach services to, and conduct community-based research with the indoor commercial sex industry in four cities in British Columbia. METHODS: The project employed an ongoing community consultation, peer-delivered approach to reaching this overlooked segment of the commercial sex industry. Peers (former and current FSW) were hired, trained, and supported as outreach workers and participated in the development, implementation, and evaluation of the project. Outreach teams visited sex establishments to deliver harm reduction materials and provide education, support, and referrals. The teams developed rapport with establishment managers and staff to facilitate research recruitment and data collection. The community team leader met with managers in targeted business to describe the study and elicit permission to recruit workers. The team leader conducted in-person interviews with consenting FSW. OBSERVATIONS: During the first 2 years of the project, more than 50 sex establishments were visited by outreach teams and 37 allowed repeat visits. Research interviews have been conducted with 49 FSW in seven establishments from four cities. CONCLUSIONS: Although the high cost in terms of time and resources must be recognized, this project represents a successful research and outreach model that permits access to the hidden commercial sex industry.

Solicited adverse events after influenza immunization among infants, toddlers, and their household contacts.

OBJECTIVES: We assessed adverse events, including oculorespiratory syndrome, following influenza immunization during the first year of a publicly-funded program for infants, toddlers and their household members in Canada. METHODS: Parents bringing infants and toddlers for influenza immunization to clinics in Quebec or British Columbia consented to structured telephone interview 5 to 10 days later. One adult provided information for all household members. Symptom experience commencing before and after immunization was assessed. Non-immunized persons also served as a comparison group for immunized household members. RESULTS: Sample included 690 immunized infants and toddlers and 1801 household members, 1374 immunized. Only fussiness, fever, decreased appetite, drowsiness, and nasal congestion/coryza were reported for >5% of infants/ toddlers within 72 hours of immunization, but only arm discomfort was reported among >5% of immunized household contacts. In multivariate analysis, muscle ache was the only systemic symptom reported more often by immunized household members compared to non-immunized persons. Oculorespiratory symptoms were infrequent and there was no difference between immunized and non-immunized household members in their report. Less than 1% of adults required time off work because of adverse events following influenza immunization in the household. Less than 2% of subjects experiencing an adverse event following influenza immunization were considered unlikely to be vaccinated again. CONCLUSION: Influenza vaccine is well-tolerated by infants, toddlers and their household members. Post-marketing observational designs are an expedient way to assess adverse events following influenza immunization. These methods should be established and rehearsed annually in preparation for a pandemic.

Use of Sno Strip filter-paper wicks for collection of genital-tract samples allows reproducible determination of human immunodeficiency virus type 1 (HIV-1) RNA viral load with a commercial HIV-1 viral load assay.

To assess the reproducibility of measurements of cervical and vaginal human immunodeficiency virus (HIV) viral load, 92 duplicate cervical and 88 duplicate vaginal samples were collected from 13 HIV-infected women using Sno Strip filter-paper wicks. RNA was eluted from the strips, extracted, and assayed using a modified protocol for the Roche Cobas Amplicor HIV-1 Monitor assay. Pearson's correlation coefficient (R), coefficient of determination (D), and Bland-Altman plots (BA) were used to compare paired log10-transformed viral loads. Analysis of duplicate same-site samples showed good reproducibility (cervix: R = 0.72, D = 52%, BA = 89% within range; vagina: R = 0.72, D = 51%, BA = 87% within range); paired cervix/vagina measurements showed moderate correlation only (R = 0.56; D = 31.3%). Standardized sample collection and simple modification of the Roche Cobas Amplicor HIV-1 Monitor assay allows reproducible measurement of genital viral load.

Needs, gaps and opportunities for infectious disease research in British Columbia: a perspective from population and public health.

BACKGROUND: A review of infectious disease research activity and capacity was performed in British Columbia and linked to a process for identifying needs, gaps and opportunities from a public health perspective. METHODS: The study was organized in three phases: an environmental scan to describe current research activity in BC; a consultation to identify needs, gaps and opportunities with those conducting research (key informants) and the end users of research results (stakeholders); and a prioritization of the research needs emerging from the consultation. RESULTS: Analysis and synthesis of the consultation data resulted in the identification of nine research themes, which were prioritized in the following order: efficacy and cost-benefit, disease patterns, emerging infectious disease, immunology and vaccines, disease-specific research, health promotion and communications, safe food and water, knowledge translation research and genomics. Six capacity-building themes were also identified: attraction and retention, education and training, collaboration and networks, funding, dissemination of findings, and public health input, surveillance, informatics and databases. INTERPRETATION: The findings were helpful in developing a multi-disciplinary, multi-level infectious disease research agenda linking researchers in universities, hospitals and public health institutions with practitioners and policy-makers in British Columbia's public health system. The approach is both feasible and important to undertake at the national level.

Adult tetanus, diphtheria and pertussis immunization: knowledge, beliefs, behavior and anticipated uptake.

BACKGROUND: Lifetime protection against pertussis has been adopted as a goal of immunization programs in Canada. To anticipate adult coverage with a combined product containing tetanus (T) and diphtheria (d) toxoids and acellular pertussis (aP) vaccine as a booster dose, we conducted a survey of households in British Columbia, Canada. METHODS: In a random telephone survey involving 800 adults, 25 years of age and older, we assessed current behaviors related to adult Td immunization and beliefs regarding pertussis vaccine under various scenarios relevant to adult decision-making. RESULTS: Forty-five percent of participants reported having received tetanus vaccine within the previous 10 years; this rate was lowest amongst elderly persons 65 years of age or more (28%). On multi-variate analysis, being up-to-date with tetanus immunization was independently associated with belief that an adult should be immunized against tetanus and perception that tetanus is life-threatening and inversely associated with being elderly. At baseline, 59% of respondents indicated willingness to receive pertussis immunization if provided free; this increased to 76% following sequential information about communicability and severity of pertussis illness and safety, efficacy and convenience of vaccine and up to 87% if accompanied by physician or nurse recommendation. Sixty-three percent of adults indicated they would receive the vaccine if required to pay $40.00 (Cdn) for it. CONCLUSIONS: Personal risk perception, public funding and physician recommendation are important to adults when considering tetanus and pertussis immunization. These factors may be relevant as immunization programs are expanded to include more adults generally.

Psychometric assessment of the Multidimensional Quality of Life Questionnaire for Persons with HIV/AIDS (MQOL-HIV) in a sample of HIV-infected women.

Since the late 1980s, several HIV-specific quality of life instruments have been developed; however, little testing has been done in terms of their validity and reliability for HIV-infected women. The purpose of this study was to test the content validity, concurrent validity, internal consistency, and test-retest reliability of the Multidimensional Quality of Life Questionnaire for Persons with HIV/AIDS (MQOL-HIV) in a sample of 85 HIV-infected women. The MQOL-HIV is a 40-item scale comprised of 10 dimensions. Most of the items and all of the domains were determined content valid but revision of some of the items and domains is recommended. Concurrent validity was measured between the MQOL-HIV and the MOS-HIV and ranged from 0.51-0.81 between similar domains. Of the 10 domains and the entire instrument, 7 had a Cronbach's alpha over 0.70 (range 0.43-0.92). Eight domains and the entire instrument achieved test-retest correlation coefficients over 0.70 (range 0.60-0.96). Although some revision may make the scale more content-valid for HIV-infected women, given due care in the interpretation of results, the MQOL-HIV can be used with female populations in its current form.

Injection-site reactions to booster doses of acellular pertussis vaccine: rate, severity, and anticipated impact.

BACKGROUND: Acellular pertussis (aP)-containing vaccines cause fewer adverse events than whole-cell versions for primary doses. Booster doses, however, may be followed by extensive injection-site reactions. This study compares the frequency, severity, and impact of local reactions among children receiving 5 consecutive doses of an aP combination vaccine (including inactivated polio virus, conjugated Haemophilus influenzae type b antigen, and diphtheria and tetanus toxoids) to children receiving a mixed series of whole-cell and aP combination vaccines. METHODS: Participants were parents or guardians of children 4 to 6 years old immunized at public health clinics across British Columbia, Canada. This included 398 children receiving the fifth consecutive dose of an aP combination vaccine and 402 receiving the fifth dose in a mixed series consisting of at least 1 prior dose of whole-cell pertussis combination vaccine with the remainder as aP combination vaccine. A cross-sectional telephone survey evaluated the extent of local reactions 48 to 96 hours after immunization by asking participants to compare the size of redness and swelling with familiar household items such as Oreo cookies or coins. Associated discomfort and impact on recreational activities, health care utilization, parental time off work, and attitudes toward immunization were also assessed. RESULTS: Children who received the fifth consecutive dose of an aP combination vaccine more often experienced redness (24%) or swelling (16%) the size of an Oreo cookie or larger (>or=46 mm) than children given a mixed series (10% and 9%, respectively) but less often experienced tenderness or limitation of movement at the injection site. Related health care utilization was low. There was no discernible effect on participation in recreational activities or parental attitudes toward vaccine; 90% would recommend the same vaccine to others with children of the same age. CONCLUSIONS: We conclude that injection-site reactions are more extensive after the fifth consecutive dose of an aP combination vaccine compared with the fifth dose in a mixed series of whole-cell and aP combination vaccines. These reactions are unlikely to affect parental acceptance of immunization recommendations or health care utilization.