Sources of viral respiratory infections in Canadian acute care hospital healthcare personnel.

BACKGROUND: Viral respiratory illnesses are common causes of outbreaks and can be fatal to some patients. AIM: To investigate the association between laboratory-confirmed viral respiratory infections and potential sources of exposure during the previous 7 days. METHODS: In this nested case-control analysis, healthcare personnel from nine Canadian hospitals who developed acute respiratory illnesses during the winters of 2010/11-2013/14 submitted swabs that were tested for viral pathogens. Associated illness diaries and the weekly diaries of non-ill participants provided information on contact with people displaying symptoms of acute respiratory illness in the previous week. Conditional logistic regression assessed the association between cases, who were matched by study week and site with controls with no respiratory symptoms. FINDINGS: There were 814 laboratory-confirmed viral respiratory illnesses. The adjusted odds ratio (aOR) of a viral illness was higher for healthcare personnel reporting exposures to ill household members [7.0, 95% confidence interval (CI) 5.4-9.1], co-workers (3.4, 95% CI 2.4-4.7) or other social contacts (5.1, 95% CI 3.6-7.1). Exposures to patients with respiratory illness were not associated with infection (aOR 0.9, 95% CI 0.7-1.2); however, healthcare personnel with direct patient contact did have higher odds (aOR 1.3, 95% CI 1.1-1.6). The aORs for exposure and for direct patient contact were similar for illnesses caused by influenza. CONCLUSION: Community and co-worker contacts are important sources of viral respiratory illness in healthcare personnel, while exposure to patients with recognized respiratory infections is not associated. The comparatively low risk associated with direct patient contact may reflect transmission related to asymptomatic patients or unrecognized infections.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial.

INTRODUCTION/HYPOTHESIS: Recruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014-2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study. METHODS: An online survey which included participants' prior experience with clinical trials, motivations to participate (including financial incentives), and demographic information was developed to examine the motivations of healthy participants in two phase 1 clinical vaccine trials conducted at the Canadian Center for Vaccinology in Halifax, Nova Scotia. Participants were invited via email to complete the online survey. Readability and clarity were assessed through pilot testing. RESULTS: A total of 49 (55.7%) of 88 participants of the two studies completed the survey (22 [55%] of 40 participants from the Ebola vaccine study and 27 [56.3%] of 48 from the adjuvanted influenza vaccine study). Motivations that were most frequently ranked among participants' top three in both trials were (1) wanting to contribute to the health of others, (2) wanting to participate in something important, (3) wanting to contribute to the advancement of science, and (4) wanting to receive an incentive such as money or a tablet. CONCLUSIONS/RECOMMENDATIONS: Although media attention and financial compensation were more often cited by Ebola vaccine trial participants as a reason to participate, both altruistic and self-interested factors were important motivations for participants in their decision to participate in a phase 1 vaccine clinical trial.

The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.

Do health care providers trust product monograph information regarding use of vaccines in pregnancy? A qualitative study.

BACKGROUND: Influenza immunization is recommended in pregnancy to prevent severe infections in pregnant women and newborns, yet vaccine uptake remains low. Studies suggest that cautionary language in vaccine product monographs regarding safety and use in pregnancy affects health care providers' perceptions of vaccine safety and how they counsel pregnant women. OBJECTIVE: To conduct a qualitative analysis of health care provider perceptions of the safety of inactivated influenza vaccines and their recommendations for use in pregnancy based on product monograph language statements. METHODS: Health care providers were recruited at two international health conferences and from teaching programs in Ethiopia, Ghana, Uganda, and Laos during September and October 2015. After reading the product monograph excerpts for three licensed inactivated influenza vaccines, participants completed a ten-item online survey with quantitative and qualitative components that captured perceptions of vaccine safety. RESULTS: Health care providers identified a lack of trust in manufacturers' and product monograph information. They perceived product monograph language as ambiguous and not "up-to-date" with current evidence. Health care providers wanted product monograph language that clearly conveyed evidence for the risks and benefits of the vaccine in an understandable manner. CONCLUSION: This study suggests that adopting best practices in the wording of product monographs would help to support evidence-based use of vaccines in pregnant women.

Knowledge, attitudes, beliefs, and behaviors of university students, faculty, and staff during a meningococcal serogroup B outbreak vaccination program.

OBJECTIVES: During an outbreak of invasive meningococcal B disease on a university campus, we explored the knowledge, attitudes, beliefs, and behaviors of members of the university community in relation to the disease, the vaccine, and the vaccination program. DESIGN: All students, faculty and staff were invited by email to participate in a 71-item online survey, which was administered after completion of the mass clinics for the first and second doses of a meningococcal B vaccination program. RESULTS: A total of 404 individuals responded to the survey; 75.7% were students. Knowledge about meningococcal disease and vaccine was generally high; more than 70% correct responses were received on each knowledge question except for one question about the different meningococcal serogroups. Gender (female) and higher knowledge scores were significantly associated with either being immunized or intending to be immunized (p<0.05). Positive attitudes about immunization, concern about meningococccal infection, a sense of community responsibility, and trust in public health advice also correlated with being vaccinated or intending to be vaccinated (p<0.05). CONCLUSIONS: A successful mass vaccination program in a Nova Scotia university was associated with high levels of knowledge, positive attitudes toward vaccination, and positive attitudes toward public health recommendations.

Impact of pharmacists as immunizers on vaccination rates: A systematic review and meta-analysis.

BACKGROUND: Underutilization of vaccination programs remains a significant public health concern. Pharmacists serve as educators, facilitators, and in some jurisdictions, as administrators of vaccines. Though pharmacists have been involved with immunizations in various ways for many years, there has yet to be a systematic review assessing the impact of pharmacists as immunizers in these three roles. OBJECTIVE: To complete a systematic review of the literature on the impact of pharmacists as educators, facilitators, and administrators of vaccines on immunization rates. METHODS: We identified 2825 articles searching the following databases from inception until October 2015: PubMed, EMBASE, Cochrane Libraries, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts, Google Scholar. Grey literature was identified through use of the Canadian Agency for Drugs and Technology in Health "Grey Matters" search tool. Content from relevant journals and references of included studies were also searched. Inclusion criteria were clinical or epidemiologic studies in which pharmacists were involved in the immunization process. Studies were excluded if no comparator was reported. Two reviewers independently completed data extraction and bias assessments using standardized forms. RESULTS: Thirty-six studies were included in the review, 22 assessed the role of pharmacists as educators and/or facilitators and 14 assessed their role as administrators of vaccines. All studies reviewed found an increase in vaccine coverage when pharmacists were involved in the immunization process, regardless of role (educator, facilitator, administrator) or vaccine administered (e.g., influenza, pneumococcal), when compared to vaccine provision by traditional providers without pharmacist involvement. Limitations of the results include the large number of non-randomized trials and the heterogeneity between study designs. CONCLUSIONS: Pharmacist involvement in immunization, whether as educators, facilitators, or administrators of vaccines, resulted in increased uptake of immunizations. PROSPERO Registration: CRD42013005067.

Rapid surveillance for health events following a mass meningococcal B vaccine program in a university setting: A Canadian Immunization Research Network study.

An outbreak of Neisseria meningitidis serotype B infection occurred at a small residential university; public health announced an organizational vaccination program with the 4-component Meningococcal B (4CMenB) vaccine (Bexsero(TM), Novartis/GlaxoSmithKline Inc.) several days later. Since there were limited published data on reactogenicity of 4CMenB in persons over 17years of age, this study sought to conduct rapid surveillance of health events in vaccinees and controls using an online survey. Vaccine uptake was 84.7% for dose 1 (2967/3500) and 70% (2456/3500) for dose 2; the survey response rates were 33.0% (987/2967) and 18.7% (459/2456) in dose 1 and dose 1 recipients respectively, and 12% in unvaccinated individuals (63/533). Most students were 20-29years of age (vaccinees, 64.0%; controls, 74.0). A new health problem or worsening of an existing health problem was reported by 30.0% and 30.3% of vaccine recipients after doses 1 and 2 respectively; and by 15.9% of controls. These health problems interfered with the ability to perform normal activities in most vaccinees reporting these events (74.7% post dose 1; 62.6% post dose 2), and in 60% of controls. The health problems led to a health care provider visit (including emergency room) in 12.8% and 14.4% of vaccinees post doses 1 and 2, respectively and in 40% of controls. The most common reactions in vaccinees were injection site reactions (20.6% post dose 1, 16.1% post dose 20 and non-specific systemic complaints (22.6% post dose 1, 17.6% post dose 2). No hospitalizations were reported. An online surveillance program during an emergency meningococcal B vaccine program was successfully implemented, and detected higher rates of health events in vaccinees compared to controls, and high rates of both vaccinees and controls seeking medical attention. The types of adverse events reported by young adult vaccinees were consistent with those previously.

Routine immunization of adults by pharmacists: Attitudes and beliefs of the Canadian public and health care providers.

Vaccine coverage among adults for recommended vaccines is generally low. In Canada and the US, pharmacists are increasingly becoming involved in the administration of vaccines to adults. This study measured the knowledge, attitudes, beliefs, and behaviors of Canadian adults and health care providers regarding pharmacists as immunizers. Geographically representative samples of Canadian adults (n = 4023) and health care providers (n = 1167) were surveyed, and 8 focus groups each were conducted nationwide with adults and health care providers. Provision of vaccines by pharmacists was supported by 64.6% of the public, 82.3% of pharmacists, 57.4% of nurses, and 38.9% of physicians; 45.7% of physicians opposed pharmacist-delivered vaccination. Pharmacists were considered a trusted source of vaccination information by 75.0% of the public, exceeding public health officials (68.3%) and exceeded only by doctors and nurses (89.2%). Public concerns about vaccination in pharmacies centered on safety (management of adverse events), record keeping (ensuring their family physician was informed), and cost (should be no more expensive than vaccination at public health or physicians' offices). Concerns about the logistics of vaccination delivery were expressed more frequently in regions where pharmacists were not yet immunizing than in jurisdictions with existing pharmacist vaccination programs. These results suggest that the expansion of pharmacists' scope of practice to include delivery of adult vaccinations is generally accepted by Canadian health care providers and the public. Acceptance of this expanded scope of pharmacist practice may contribute to improvements in vaccine coverage rates by improving vaccine accessibility.

The challenge of vaccinating adults: attitudes and beliefs of the Canadian public and healthcare providers.

OBJECTIVES: Vaccine coverage for recommended vaccines is low among adults. The objective of this study was to assess the knowledge, attitudes, beliefs and behaviours of adults and healthcare providers related to four vaccine-preventable diseases and vaccines (diphtheria-tetanus-pertussis, zoster, pneumococcus and influenza). DESIGN: We undertook a survey and focus groups of Canadian adults and healthcare providers (doctors, nurses, pharmacists). A total of 4023 adults completed the survey and 62 participated in the focus groups; 1167 providers completed the survey and 45 participated in the focus groups. RESULTS: Only 46.3% of adults thought they were up-to-date on their vaccines; 30% did not know. In contrast, 75.6% of providers reported being up-to-date. Only 57.5% of adults thought it was important to receive all recommended vaccines (compared to 87.1-91.5% of providers). Positive attitudes towards vaccines paralleled concern about the burden of illness and confidence in the vaccines, with providers being more aware of disease burden and confident in vaccine effectiveness than the public. Between 55.0% and 59.7% of adults reported willingness to be vaccinated if recommended by their healthcare provider. However, such recommendations were variable; while 77.4% of the public reported being offered and 52.8% reported being recommended the influenza vaccine by their provider, only 10.8% were offered and 5.6% recommended pertussis vaccine. Barriers and facilitators to improved vaccine coverage in adults, such as trust-mistrust of health authorities, pharmaceutical companies and national recommendations, autonomy versus the public good and logistical issues (such as insufficient time and lack of vaccination status tracking), were identified by both the public and providers. CONCLUSIONS: Despite guidelines for adult vaccination, there are substantial gaps in knowledge and attitudes and beliefs among both the public and healthcare providers that lead to low vaccine coverage. A systematic approach that involves education, elimination of barriers and establishing and improving infrastructure for adult immunisation is required.

Universal tetanus, diphtheria, acellular pertussis (Tdap) vaccination of adults: What the Canadian public knows and wants to know.

Tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in Canada but uptake is low. This study measured the knowledge, attitudes, beliefs, and behaviors of Canadian adults to identify potential barriers and facilitators to Tdap uptake. A survey was undertaken on a geographically representative sample of Canadian adults (n=4023) and 8 focus groups (62 participants) were conducted nationwide. The survey revealed that knowledge about pertussis and Tdap was low (38.3% correct answers). Only 36.0% of respondents reported being aware that all adults were recommended to receive Tdap and only 10.7% reported being immunized; 36.7% did not know whether they had received Tdap. Respondents who were aware of the immunization recommendations were twice as likely to be immunized (16.6% vs. 8.3%; p<0.001). Only 9.3% believed that their health care provider thought that Tdap was important for adults. The focus group data supported the survey results. Participants wanted information about pertussis and Tdap communicated through multiple modalities, but a recommendation by their family physician was most important to their decision to be immunized or not. This study demonstrates that current recommendations for universal adult vaccination with Tdap are not reaching the general public in Canada and an alternative strategy will be required to improve Tdap vaccine uptake.

Successful methodology for large-scale surveillance of severe events following influenza vaccination in Canada, 2011 and 2012.

In 2011 and 2012, a nationwide Canadian vaccine safety surveillance network rapidly collected safety data from healthcare workers (HCW) during the first weeks of the annual influenza vaccination campaign. This network provided the first available post-marketing safety data on seasonal influenza vaccines with information on background rates as a comparator. In 2012, these data were used to investigate a possible safety concern regarding a particular vaccine. An online questionnaire was provided to participating HCW two weeks before the annual influenza vaccination campaign for controls, and eight days after influenza vaccination for vaccinees. Control and vaccinees were requested to report health events occurring in the seven days prior to receiving the questionnaire. Control data were used to calculate background rates. HCW reporting a severe event were followed-up by telephone within 48 hours of the online report to validate the report and check on their health status. More than 22,000 vaccinated HCW were enrolled and surveyed over two seasons and > 90% reported no severe event following vaccination. Validated severe event rates were similar in vaccinated HCW and unvaccinated HCW (2.2% vs 2.3%; p < 0.70). The questionnaire was accurately completed for most reported symptoms, matched the validated report and was able to detect events of interest. Prior to the safety concern, the implicated vaccine was in use at one centre. Reassuring safety data were provided to public health authorities 48 hours after the vaccine was temporarily suspended. Data from this and similar networks can be used for rapid evaluation of vaccine safety and for safety assessment as required by the European Medicines Agency in 2015.

Universal tetanus, diphtheria, acellular pertussis (Tdap) vaccination of adults: What Canadian health care providers know and need to know.

The tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in both Canada and the United States. There are few data on the proportion of Canadian adults vaccinated with Tdap; however, anecdotal reports indicate that uptake is low. This study aimed to explore the knowledge, attitudes, beliefs, and behaviors of Canadian health care providers (HCPs) in an attempt to identify potential barriers and facilitators to Tdap uptake. HCPs were surveyed and a geographic and practice representative sample was obtained (N =1,167). In addition, 8 focus groups and 4 interviews were conducted nationwide. Results from the survey indicate that less than half (47.5%) of all respondents reported being immunized with Tdap themselves, while 58.5% routinely offer Tdap to their adult patients. Knowledge scores were relatively low (63.2% correct answers). The best predictor of following the adult Tdap immunization guidelines was awareness of and agreement with those recommendations. Respondents who were aware of the recommendations were more likely to think that Tdap is safe and effective, that their patients are at significant risk of getting pertussis, and to feel that they have sufficient information (p < 0.0001 for each statement). Focus group data supported the survey results and indicated that there are substantial gaps in knowledge of pertussis and Tdap among Canadian HCPs. Lack of public knowledge about adult immunization, lack of immunization registries, a costing differential between Td and Tdap, workload required to deliver the vaccine, and vaccine hesitancy were identified as barriers to compliance with the national recommendations for universal adult immunization, and suggestions were provided to better translate recommendations to front-line practitioners.

Impact of the Ottawa Influenza Decision Aid on healthcare personnel's influenza immunization decision: a randomized trial.

BACKGROUND: Influenza immunization for healthcare personnel reduces frequency and severity of nosocomial influenza outbreaks and influenza-associated morbidity and mortality among patients. The Ottawa Influenza Decision Aid (OIDA) was developed to assist undecided healthcare workers in deciding whether or not to be immunized. AIM: To assess the impact of the OIDA, and to ascertain whether its use would increase the level of confidence in healthcare workers' influenza immunization decision and positively affect their intent to be immunized. METHODS: Single-centre, single-blind, parallel-group, randomized controlled trial. FINDINGS: Eight per cent (151 of 1886) of the unimmunized healthcare personnel were randomized. Of 107 eligible respondents, 48 were in the Ottawa Influenza Decision Aid (OIDA) group and 59 in the control group. A statistically significant (P = 0.020) greater improvement in confidence in immunization decision was observed in the OIDA group compared with the control group. Whereas the odds of changing intent to be immunized from 'no/unsure' to 'yes' was 2.4 times greater in the OIDA group, this result did not reach statistical significance after adjusting for intent to be immunized at baseline. The post-OIDA intent to be immunized in the OIDA and control groups compared to the pre-OIDA intent to be immunized showed that the OIDA had a significant effect on reducing uncertainty (P = 0.035). CONCLUSIONS: Using an accessible, balanced, understandable format for all healthcare personnel about their influenza immunization decision appears to have an impact on both healthcare personnel's confidence in their immunization decision and in their intent to be immunized.

Kinetics of the antibody response to tetanus-diphtheria-acellular pertussis vaccine in women of childbearing age and postpartum women.

BACKGROUND: Because adolescents and adults act as a primary source of pertussis infection for infants, vaccination of mothers immediately postpartum is a potential strategy to reduce transmission (cocoon strategy). For this to be effective, high levels of antibodies must be achieved rapidly after vaccination. We sought to determine whether the antibody response to tetanus-diphtheria-acellular pertussis vaccine (Tdap) is sufficiently rapid to support the cocoon strategy. METHODS: Two sequential studies were performed. The first was a nonrandomized, open study of a 5-pertussis-component Tdap vaccine (tetanus toxoid, diphtheria toxoid, pertussis toxoid [PT], filamentous hemagglutinin [FHA], fimbriae types 2 and 3 [FIM], and pertactin [PRN]) given to women of childbearing age; the second was a randomized, open study of Tdap or no vaccine in postpartum women. Serum levels of immunoglobin (Ig) G and IgA against pertussis antigens, serum levels of IgG against diphtheria and tetanus, and breast milk levels of IgA against pertussis antigens were measured at various times after vaccination. RESULTS: In both studies, the antibody response was relatively rapid, with serum IgG and IgA levels beginning to increase noticeably by days 5-7 and approaching peak levels by day 14. Greater than 68% and 84.4% of IgG and IgA responders, respectively, achieved ≥ 90% of their maximum titer by day 14. The diphtheria and tetanus antibody kinetics followed a similar time course. Breast milk levels of IgA against PT, FHA, and FIM were first detectable at day 7, peaked by day 10, and then slowly decreased through day 28. Antibodies against PRN showed a similar response, although the peak occurred at day 14. There were no significant antibody responses in the control group. CONCLUSIONS: Although the antibody response to a dose of Tdap in healthy nonpregnant women of child-bearing age and postpartum women occurs by day 14 and is suggestive of an anamnestic immune response, it may not be sufficiently rapid to protect infants in the first weeks of life.

Oseltamivir pharmacokinetics in morbid obesity (OPTIMO trial).

BACKGROUND: Detailed pharmacokinetics to guide oseltamivir (Tamiflu®) dosing in morbidly obese patients is lacking. METHODS: The OPTIMO trial was a single-centre, non-randomized, open-label pharmacokinetic study of single-dose and steady-state oral oseltamivir phosphate and its carboxylate metabolite in healthy, morbidly obese [body mass index (BMI) >  40)] and healthy, non-obese (BMI  <  30) subjects. RESULTS: In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir oral clearance (CL/F) [840 (range 720-1640) L/h versus 580 (470-1800) L/h] was higher, the area under the curve from time zero to infinity (AUC(0-∞)) [89 (46-104) ng·h/mL versus 132 (42-160) ng·h/mL] was lower and the volume of distribution (V/F) [2320 (900-8210) L versus 1670 (700-7290) L] was unchanged. In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir carboxylate CL/F [22 (17-40) L/h versus 23 (12-33) L/h], AUC(0-∞) [3100 (1700-4100) ng·h/mL versus 3000 (2100-5900) ng·h/mL] and V/F [200 (130-370) L versus 260 (150-430) L] were similar. Similar results for oseltamivir and oseltamivir carboxylate CL/F, AUC0₋12 and V/F values were observed in the multiple-dose study. CONCLUSIONS: With single and multiple dosing, the systemic exposure to oseltamivir is decreased but that of oseltamivir carboxylate is largely unchanged. Based on these pharmacokinetic data, an oseltamivir dose adjustment for body weight would not be needed in morbidly obese individuals.

Intention of parents to have male children vaccinated with the human papillomavirus vaccine.

BACKGROUND: Although already approved for use in males in some jurisdictions, there is little information about parental attitudes toward having their sons receive the human papillomavirus (HPV) vaccine. The goal of this study was to ascertain parental intentions to vaccinate their sons with an HPV vaccine and to determine factors that predict this intention. METHODS: Parents of children aged 8-18 years were recruited from across Canada through random digit dialling. Participants were asked to respond to a series of questions in the context of a Grade 6 (age 11/12 years old), publicly funded school-based HPV vaccine programme, including their intention to vaccinate their sons with the HPV vaccine. Parents were also asked about a series of characteristics thought to predict intention to vaccinate as well as demographic characteristics. Backwards logistic regression was conducted to calculate adjusted odds ratios (AOR) to identify the factors that are predictive of parents' intention to vaccinate their son(s) against HPV. RESULTS: Of the 1381 respondents with male children, 67.8% (95% CI 65.3 to 70.3) intend to vaccinate their son(s) against HPV. Parents who had positive attitudes toward vaccines and the HPV vaccine in particular (AOR 41.5, 95% CI 9.5 to 181.7), parents who were influenced by subjective norms (AOR 7.8, 95% CI 5.8 to 10.5), parents who felt that the vaccine had limited influence on sexual behaviour (AOR 2.3, 95% CI 1.6 to 3.3) and parents who were aware of HPV (AOR 1.4, 95% CI 1.1 to 2.0) were significantly more likely to report an intention to vaccinate boys against HPV. In contrast, residence in British Columbia compared to Atlantic Canada (AOR 0.4, 95% CI 0.2 to 0.8) and higher education (AOR 0.7, 95% CI 0.5 to 0.9) were negatively associated with intention to vaccinate. Parents who reported an intention to vaccinate their daughters were also highly likely to report an intention to vaccinate their sons (kappa = 0.9, p<0.001). DISCUSSION: The majority of Canadian parents would intend to have their male children receive the HPV vaccine in the context of a publicly funded school-based immunisation programme. Overall attitudes toward vaccine, recommendations from health professionals and impact of the vaccine on sexual practices are important predictors of intention to have a male child receive the HPV vaccine.

Outbreak of sternal surgical site infections due to Pseudomonas aeruginosa traced to a scrub nurse with onychomycosis.

From 19 February 1999 through 31 October 1999, 16 (8.6%) of 185 patients who underwent median sternotomy developed infections with Pseudomonas aeruginosa. Seven patients had mediastinitis, 5 had deep sternal wound infection, 2 had superficial sternal wound infection, 1 had prosthetic valve endocarditis, and 1 had sepsis. Pulsed-field gel electrophoresis confirmed that all 13 isolates that were available for typing were the same strain. Cultures of hand specimens identified 1 nurse from whom the same strain of P. aeruginosa was repeatedly isolated; the nurse had been in contact with all 16 infected patients. Investigation revealed that the nurse had severe onycholysis and onychomycosis of the right thumbnail. Cultures of samples of this nail's subungual region and of multiple cosmetic products from the nurse's home yielded the identical P. aeruginosa strain. This outbreak of surgical site infections due to P. aeruginosa was caused by wound contamination from the thumbnail of this nurse, despite her appropriate use of latex surgical gloves.

Risk factors for anaerobic bloodstream infections in bone marrow transplant recipients.

The incidence of anaerobic bloodstream infections (BSI) in patients who underwent bone marrow transplantation (BMT) recently increased at our institution. A retrospective case-control study of patients undergoing BMT from January 1995 through December 1998 was performed to determine the microbiological characteristics, epidemiology, and outcome of anaerobic BSI and to identify independent risk factors for infection. Anaerobic BSI occurred in 23 patients, for a rate of 4 BSIs per 100 BMT procedures, and it accounted for 17% of all BSIs that occurred during the study period. Infection occurred at a mean (+/- standard deviation) of 7+/-4 days after BMT and 7+/-5 days after the onset of neutropenia. Fusobacterium nucleatum was the most frequently isolated pathogen (in 17 patients), followed by Leptotrichia buccalis (in 4), Clostridium septicum (in 1), and Clostridium tertium (in 1). Two case patients (9%) died. Severity of mucositis was an independent predictor of anaerobic BSI (odds ratio, 4.4; P=.01). Controlling mucositis is critical for the prevention of anaerobic BSI in this patient population.