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Introduction: Vaccination is considered to be the most practical and effective preventative measure against influenza. It is highly recommended for population subgroups most at risk of developing complications, including pregnant women. However, seasonal influenza vaccine uptake remains suboptimal among pregnant women, even in jurisdictions with universal vaccination. We summarized the evidence on the determinants of seasonal influenza vaccine uptake during pregnancy to better understand factors that influence vaccine uptake among pregnant women. Material and methods: We systematically searched MEDLINE, Embase and CINAHL from January 2000 to February 2020 for publications in English reporting on sociodemographic and/or health‐related determinants of seasonal influenza vaccine uptake during pregnancy. Two reviewers independently included studies. One reviewer extracted data and assessed study quality, and another reviewer checked extracted data and study quality assessments for errors. Disagreements were resolved through consensus, or a third reviewer. We meta‐analyzed using the inverse variance, random‐effects method, and reported the odds ratios (OR) and 95% confidence intervals (CI). Results: From 1663 retrieved citations, we included 36 studies. The following factors were associated with increased seasonal influenza vaccine uptake: Older age (20 studies: OR 1.13, 95% CI 1.07‐1.20), being nulliparous (13 studies: OR 1.26, 95% CI 1.15‐1.38), married (8 studies: OR 1.11, 95% CI 1.07‐1.15), employed (4 studies: OR 1.13, 95% CI 1.02‐1.24), a non‐smoker (8 studies: OR 1.25, 95% CI 1.04‐1.51) and having prenatal care (3 studies: OR 3.36, 95% CI 2.25‐5.02), a chronic condition (6 studies: OR 1.30, 95% CI 1.17‐1.44), been previously vaccinated (9 studies: OR 4.88, 95% CI 3.14‐7.57) and living in a rural area (9 studies: OR 1.09, 95% CI 1.05‐1.14). Compared with being black, being white was also associated with increased seasonal influenza vaccine uptake (11 studies: OR 1.30, 95% CI 1.20‐1.41). Conclusions: The evidence suggests that several sociodemographic and health‐related factors may determine seasonal influenza vaccination in pregnancy, and that parity, history of influenza vaccination, prenatal care and comorbidity status may be influential. [ABSTRACT FROM AUTHOR]

• A systematic review and meta -analysis of pertussis vaccine effectiveness. • Receipt of any pertussis vaccine provided short-term protection against disease. • Estimates varied widely and heterogeneity in pooled estimates was high. • Heterogeneity was partially due to factors which may be mitigated by study design. A comprehensive review of observational pertussis vaccine effectiveness (VE) studies is needed to update gaps from previous reviews. We conducted a systematic review of VE and duration of protection studies for the whole-cell (wP) and acellular (aP) pertussis vaccines and conducted a formal meta -analysis using random effects models. Evidence continues to suggest that receipt of any pertussis vaccine confers protection in the short-term against disease although this protection wanes rapidly for aP vaccine. We detected significant heterogeneity in pooled estimates due, in part, to factors such as bias and confounding which may be mitigated by study design. Our review of possible sources of heterogeneity may help interpretation of other VE studies and aid design decisions in future pertussis VE research. [ABSTRACT FROM AUTHOR]

Pertussis remains poorly controlled relative to other diseases targeted by childhood vaccination programs. We combined estimates from four population-based studies of pertussis vaccine effectiveness (VE) in three Canadian provinces using a meta -analytic approach to improve precision and explore regional variation in VE and durability of protection. Studies were conducted in Alberta, Manitoba, and Ontario over periods ranging from 1996 to 2015. Adjusted log odds ratios (OR; VE = 100*[1-OR]) of the effect of vaccination on pertussis risk were estimated by time since last vaccination in each study and pooled using DerSimonian and Laird random-effects models. We used the I2 statistic to estimate between-study heterogeneity and assessed methodological and clinical heterogeneity through subgroup analyses of study design and age. Data on 3,270 pertussis cases and 23,863 controls were available. Pertussis VE declined from 86% (95% CI 79%-90%, I2 = 81.5%) at < 1 year since last vaccination to 51% (11%-74%, I2 = 80.9%) by ≥ 8 years. Effect estimates were the most heterogeneous in the least and most elapsed time periods since last vaccine dose. This was attributable mostly to variation between provinces in the distribution of age groups and number of vaccine doses received within time periods, as well as study design and small numbers in the most elapsed time period. Interpretation : Consistent trends of decreasing pertussis VE with increasing time since last vaccination across three Canadian provinces indicate the need for immunization schedules and vaccine development to optimize protection for all individuals, especially for adolescents and young adults at greatest risk of infection. [ABSTRACT FROM AUTHOR]

• Comparison of vaccine uptake in 2 and 7 year-old children with and without epilepsy. • Vaccine coverage is similar between children with and without epilepsy. • Children diagnosed early have slightly lower vaccine coverage at age 2 years. Children with epilepsy are at increased risk of complications from vaccine-preventable infections, yet information on vaccine coverage in these children is scarce. We aimed to compare vaccine coverage among children with epilepsy to children without epilepsy. We conducted a retrospective cohort study including all 2005–2013 births in Manitoba and Ontario, Canada, creating two cohorts: 2-year-olds and 7-year-olds (followed to age 2 and 7 years). We split each cohort into epilepsy and non-epilepsy subcohorts. We assessed vaccination coverage based on provincial schedules and determined timeliness of MMR (measles, mumps, rubella) dose 1 (recommended at 12 months) and DTaP (diphtheria, tetanus, pertussis) dose 4 (recommended at 18 months). We used logistic regression to calculate adjusted odds ratios (aORs) of the association between epilepsy and vaccination, combining both provincial estimates using random effects meta -analysis. We included 16,558 2-year-olds (Manitoba, 653; Ontario, 15,905) and 13,004 7-year-olds (Manitoba, 483; Ontario, 12,521) with epilepsy. At age 2 years, the aOR for up-to-date vaccination among children with versus without epilepsy was 0.9 (95% confidence interval 0.8–1.1); at age 7 years it was 1.0 (0.9–1.1). Infants diagnosed with epilepsy before age 6 months were less likely to be up-to-date at age 2 years (0.9; 0.8–0.9), although this difference disappeared by age 7 years. Vaccine timeliness was similar between children with and without epilepsy for MMR dose 1 and DTaP dose 4. Overall, this study suggests that children with epilepsy are not significantly under-vaccinated compared to their peers without epilepsy. As children with epilepsy are at a higher risk of complications from vaccine-preventable diseases, vaccination in children with epilepsy should be optimized, especially early in life, as these children may not be able to rely on herd protection. [ABSTRACT FROM AUTHOR]

Cost savings associated with high-dose (HD) as compared to standard-dose (SD) influenza vaccination in the United States (US) Veteran's Health Administration (VHA) population have been attributed to better protection against hospitalization for cardiac and respiratory diseases. The relative contribution of each of these disease categories to the reported savings remains to be explored. During a recently completed study of HD versus SD vaccine effectiveness (conducted in the VHA over five respiratory seasons from 2010/11 through 2014/15), we collected cost data for all healthcare services provided at both VHA and Medicare-funded facilities. In that analysis, we compared the costs of vaccination and hospital care for patients admitted with either cardiovascular or respiratory disease. Treatment selection bias and other confounding factors were adjusted using an instrumental variable (IV) method. In this brief report we use the same study cohort and methods to stratify the results by patients admitted for cardiovascular disease (CVD) and those admitted for respiratory disease. We analyzed 3.5 million SD and 0.16 million HD person-seasons. The IV-adjusted rVEs were 14% (7–20%) against hospitalizations for CVD and 15% (5–25%) against respiratory hospitalizations. Net cost savings per HD recipient were $138 ($66–$200) for CVD related hospitalizations and $62 ($10–$107) for respiratory disease related hospitalizations. In the US VHA population, the reduction in hospitalizations for CVD over five respiratory seasons contributed twice the cost savings (per HD recipient) of the reduction in hospitalizations for respiratory disease. [ABSTRACT FROM AUTHOR]

Background Evidence suggests that repeated influenza vaccination may reduce vaccine effectiveness (VE). Using influenza vaccination program maturation (PM; number of years since program inception) as a proxy for population-level repeated vaccination, we assessed the impact on pooled adjusted end-season VE estimates from outpatient test-negative design studies. Methods We systematically searched and selected full-text publications from January 2011 to February 2020 (PROSPERO: CRD42017064595). We obtained influenza vaccination program inception year for each country and calculated PM as the difference between the year of deployment and year of program inception. We categorized PM into halves (cut at the median), tertiles, and quartiles and calculated pooled VE using an inverse-variance random-effects model. The primary outcome was pooled VE against all influenza. Results We included 72 articles from 11 931 citations. Across the 3 categorizations of PM, a lower pooled VE against all influenza for all patients was observed with PM. Substantially higher reductions were observed in older adults (≥65 years). We observed similar results for A(H1N1)pdm09, A(H3N2), and influenza B. Conclusions The evidence suggests that influenza VE declines with vaccination PM. This study forms the basis for further discussions and examinations of the potential impact of vaccination PM on seasonal VE. [ABSTRACT FROM AUTHOR]

Information on inappropriate empiric antimicrobial therapy (ET) in Canadian hospitals is scarce. All Manitobans 18 years of age and over who were admitted to a hospital in Winnipeg with a complicated urinary tract infection (cUTI) or complicated intra-abdominal infection (cIAI) from January 2006 to December 2014 were eligible for inclusion in this cohort study. The prevalence of inappropriate ET was 11% for cUTI patients and 9% for cIAI patients. The risk of receiving inappropriate ET was higher for older patients (cUTI patients 65 or older had 2-fold increased risk compared to younger patients; odds ratio 2.1, 95% confidence interval 1.3–3.6; this was 1.6 [0.7–3.5] for cIAI patients) and those hospitalized in the previous year: 1.5 (1.0–2.4) in cUTIs and 1.5 (0.6–3.4) in cIAIs. The risk for a hospital stay over 3 weeks was increased for inappropriate ET in cUTI patients, 2.3 (1.4–3.7), but not in cIAI patients, 0.9 (0.4–2.1). [ABSTRACT FROM AUTHOR]

Background: Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA.Methods: Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters.Results: Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination.Conclusion: This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine.Trial Registration: ClinicalTrials.gov NCT02514018.Funding: Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments. [ABSTRACT FROM AUTHOR]

Background: We assessed the effectiveness of the quadrivalent human papillomavirus vaccine (qHPV) vaccination program in Manitoba, Canada, in reducing incident anogenital warts (AGWs) and to what extent effectiveness depends on age at vaccination and number of doses.Methods: Female participants 9 years or older who received the qHPV in Manitoba between September 2006 and March 2013 (n = 31,464) through the publicly funded school-based program and a high-risk catch-up program were included. They were matched on age and area of residence to unvaccinated female participants. Information on incident AGWs was obtained from provincial administrative databases using validated algorithms. Using stratified Cox regression models, we estimate hazard ratios (HRs) for the association between qHPV and AGWs.Results: For female participants vaccinated at age 18 years or younger, receipt of qHPV was associated with a 40% reduction in AGW risk (HR, 0.6; 95% confidence interval [CI], 0.4-0.8). Further adjustment for socioeconomic and medical history did not alter this estimate. For women vaccinated at age 19 years or older, we saw an increase in AGW incidence, especially among those who were sexually active (HR, 2.8; 95% CI, 2.1-3.7). Among female participants vaccinated at age 18 years or younger, risk of AGWs was lowest among those who received 3 doses, corresponding to a vaccine effectiveness of 56% (95% CI, 30%-70%). For women vaccinated at older age, risk of AGWs remained increased regardless of the number of doses.Conclusions: Women vaccinated at an older (≥19 years) age may be less protected against AGWs, particularly if sexually active before vaccine administration. Further efforts should be targeted at increasing vaccine uptake among preadolescents before the initiation of sexual activity. [ABSTRACT FROM AUTHOR]

Background Few studies in North America have quantified the risks of second malignant neoplasms (SMNs) among survivors of childhood non-central nervous system (non-CNS) embryonal tumours due to their rarity. We aimed to investigate these risks by combining population-based data from the United States of America and Canada. Methods We evaluated patients with childhood non-CNS embryonal tumours reported to the Surveillance Epidemiology and End Results program and eight Canadian cancer registries from 1969 to 2010. Standardised incidence ratio (SIR) and cumulative incidence of SMNs were calculated. Subgroup analyses were conducted by the type of first primary cancer, age at first primary diagnosis and follow-up duration. Findings Of the 13,107 survivors, 190 SMNs were reported over 134,548 person-years of follow-up. The SIR for all SMNs combined was 6.4 (95% confidence interval [CI]: 5.5–7.4). Most site-specific SIRs were significantly increased, ranging from 36 (95% CI: 26–49) for bone and joint cancer to 3.1 (95% CI: 1.5–5.2) for brain tumour. The risk for second malignancies declined as the time elapsed from the first primary diagnosis and was less prominent for patients first diagnosed at age 1–4 years. Notably, rhabdomyosarcoma survivors had a higher risk for SMNs than those with other first primaries. The overall cumulative incidence of SMNs was 1.0% at 10 years, increasing to 2.2% at 20 years and 4.1% at 30 years. Interpretation Survivors with childhood non-CNS embryonal tumours faced an increased risk for SMNs compared to the general population. The risk variations observed in different patient categories may help target prevention strategies in high-risk subgroups. [ABSTRACT FROM AUTHOR]

Introduction Older adults are prioritized for influenza vaccination but also have lowered antibody responses to the vaccine. Higher-doses of influenza antigen may increase immune response and thus be more effective. Our objectives were to compare the efficacy and safety of the high-dose influenza vaccine to the standard-dose influenza vaccine in the elderly (age > 65). Methods Data sources : Randomized trials (RCTs) from Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley), ClinicalTrials.gov , reference lists of relevant articles, and gray literature. Study selection : Two reviewers independently identified RCTs comparing high-dose influenza vaccine (60 μg of hemagglutinin per strain) to standard-dose influenza vaccine (15 μg of hemagglutinin per strain) in adults over the age of 65 years. Data extraction : Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the Cochrane Risk of Bias tool. Results We included seven eligible trials; all were categorized as having a low ( n = 3) or unclear ( n = 4) risk of bias. Patients receiving the high-dose vaccine had significantly less risk of developing laboratory-confirmed influenza infections (Relative Risk 0.76, 95%CI 0.65 to 0.90; I 2 0%, 2 trials, 41,141 patients). Post-vaccination geometric mean titres and seroprotection rates were also higher in high-dose vaccine recipients. There were no protocol-defined serious adverse events in the included trials in either group. Conclusions In elderly adults, the high-dose influenza vaccine was well-tolerated, more immunogenic, and more efficacious in preventing influenza infections than the standard-dose vaccine. Further pragmatic trials are needed to determine if the higher efficacy translates into higher vaccine effectiveness in adults over the age of 65. [ABSTRACT FROM AUTHOR]

Background: A rigorous assessment of the risk of colorectal cancer (CRC) among prostate cancer (PC) survivors that controls for important confounding factors and competing risks is necessary to determine the risk of CRC in this population and to inform screening guidelines.Methods: With data from Manitoba, Canada, subjects diagnosed with PC as their first cancer between 1987 and 2009 were age-matched with up to 5 men with no history of invasive cancer on the PC diagnosis date. Subjects were followed to the date of diagnosis of CRC or another cancer, death, emigration, or the study endpoint (December 31, 2009). Competing risk proportional hazards models were used to compare the CRC incidence between those with PC and those without PC with the following model covariates: history of lower gastrointestinal endoscopy, frequency of health care visits, diabetes, and socioeconomic status. Mutually exclusive competing outcomes included CRC, another primary cancer, and death.Results: For a total of 559,081 person-years, 14,164 men with PC and 69,051 men without PC were followed. Men diagnosed with PC had an increased risk of a subsequent diagnosis of CRC (all CRC: hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.02-1.27; rectal cancer: HR, 1.36; 95% CI, 1.09-1.71). The treatment of PC with radiation was associated with an increased risk for rectal cancer (HR, 2.06; 95% CI, 1.42-2.99) in comparison with PC cases not treated with radiation.Conclusions: The risk of CRC is increased after a diagnosis of PC and is highest for rectal cancer among those treated with radiation. CRC screening should be considered soon after the diagnosis of PC, especially for men planning for radiotherapy. [ABSTRACT FROM AUTHOR]

Background. Canada's Sentinel Physician Surveillance Network links genetic, antigenic, and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent A(H1N1)pdm09 and late-season type B activity. Methods. VE was estimated as [1 - odds ratio] × 100% and compared vaccination status between individuals who tested positive (cases) and those who tested negative (controls) for influenza virus. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination inhibition assays. Results. Analyses included 1037 controls (of whom 33% were vaccinated) and 663 cases (of whom 14% were vaccinated). A total of 415 cases tested positive for A(H1N1)pdm09 virus, 15 tested positive for A(H3N2) virus, 191 tested positive for B/Yamagata-lineage virus, 6 tested positive for B/Victoria-lineage virus, and 36 tested positive for viruses of unknown subtype or lineage. A(H1N1)pdm09 viruses belonged to clade 6B, distinguished by a K163Q substitution, but remained antigenically similar to the A/California/07/2009-like vaccine strain, with an adjusted VE of 71% (95% confidence interval [CI], 58%-80%). Most B/Yamagata-lineage viruses (83%) clustered phylogenetically with the prior (ie, 2012-2013) season's B/Wisconsin/01/2010-like clade 3 vaccine strain, while only 17% clustered with the current (ie, 2013-2014) season's B/Massachusetts/02/2012-like clade 2 vaccine strain. The adjusted VE for B/Yamagata-lineage virus was 73% (95% CI, 57%-84%), with a lower VE obtained after partial calendar-time adjustment for clade-mismatched B/Wisconsin/01/2010-like virus (VE, 63%; 95% CI, 41%-77%), compared with that for clade-matched B/Massachusetts/02/2012-like virus (VE, 88%; 95% CI, 48%-97%). No A(H3N2) viruses clustered with the A/Texas/50/2012-like clade 3C.1 vaccine strain, and more than half were antigenically mismatched, but sparse data did not support VE estimation. Conclusions. VE corresponded with antigenically conserved A(H1N1)pdm09 and lineage-matched B/Yamagata viruses with clade-level variation. Surveillance linking genotypic, phenotypic, and epidemiologicmeasures of vaccine-virus relatedness and effectiveness could better inform predictions of vaccine performance and reformulation. [ABSTRACT FROM AUTHOR]

In 2010, Winnipeg, Canada, experienced an outbreak of serotype 12F invasive pneumococcal disease. Epidemiological and microbiological analysis found that, compared with other serotypes, persons with serotype 12F were more likely to be homeless and to engage in substance abuse.Background. In 2010, Winnipeg, Canada, experienced a doubling of invasive pneumococcal disease (IPD) rates, with a significant increase in the number of cases due to Streptococcus pneumoniae serotype 12F, which previously had accounted for very few cases each year.Methods. All serotype 12F IPD cases reported between September 2009 and January 2011 were reviewed. Pulsed-field gel electrophoresis (PFGE) and multilocus variable number tandem repeat analysis (MLVA) were conducted on all isolates. PFGE and MLVA patterns identified several possible clusters. Additional interviews were conducted to obtain information on risk factors and outcomes.Results. Between September 2009 and January 2011, 169 cases of IPD were identified. The number of IPD cases due to 12F serotype increased sharply from about 3–4 cases per year (6% of IPD cases) in 2007–2009 to 28 (29%) in 2010. All 12F isolates belonged to a single sequence type (ST218), and they were generally susceptible to penicillin and fluoroquinolones but not to erythromycin. Compared with cases caused by other serotypes, patients with serotype 12F were more likely to be homeless, reside in low-income inner-city communities, and engage in substance abuse, including intravenous and crack cocaine use. Subclusters identified using MLVA had even higher rates of homelessness and substance use.Conclusions. An immunization campaign targeting high-risk groups was undertaken with pneumococcal polysaccharide vaccine, and subsequently rates of serotype 12F decreased. To our knowledge, this is the largest documented community outbreak of serotype 12F IPD and the first report of an outbreak of IPD serotype 12F in a marginalized urban population in Canada. [ABSTRACT FROM AUTHOR]

BACKGROUND: We estimate vaccine effectiveness (VE) against both influenza A/subtypes and B/lineages in Canada for the 2011-2012 trivalent inactivated influenza vaccine (TIV) with components entirely unchanged from the 2010-2011 TIV and in the context of phenotypic and genotypic characterization of circulating viruses. METHODS: In a test-negative case-control study VE was estimated as [1-adjustedOddsRatio] x 100 for RT-PCR-confirmed influenza in vaccinated vs nonvaccinated participants. Viruses were characterized by hemagglutination inhibition (HI) and sequencing of antigenic sites of the hemagglutinin (HA) gene. RESULTS: There were 1507 participants. VE against A(H1N1)pdm09 was 80% (95% confidence interval [CI], 52%-92%): circulating viruses were HI-characterized as vaccine-matched and bore just 2 aminoacid (AA) differences from vaccine. VE against A/H3N2 was 51% (95% CI, 10%-73%): circulating viruses were HI-characterized as vaccine-related but bore ≥11AA differences from vaccine. VE against influenza B was 51% (95% CI, 26%-67%) in total: 71% (95% CI, 40%-86%) for lineage-matched B/Victoria and 27% (95% CI, -21% to 56%) for lineage-mismatched B/Yamagata. For both influenza A and B types, VE was similar among recipients of either 2010-2011 or 2011-2012 TIV alone, higher when vaccinated both seasons. CONCLUSIONS: Phenotypic and genotypic characterization of circulating and vaccine viruses enhances understanding of TIV performance, shown in 2011-2012 to be substantial against well-conserved A(H1N1)pdm09 and lineage-matched influenza B, suboptimal against genetic-variants of A/H3N2, and further reduced against lineage-mismatched influenza B. With unchanged vaccine components, protection may extend beyond a single season. [ABSTRACT FROM AUTHOR]

Partial cystectomy (PC) remains a viable alternative to radical cystectomy (RC) for management of invasive bladder cancer in approximately 5% of patients. We used a population-based database to examine practice patterns and recurrence after partial cystectomy. We obtained billing records of all partial and radical cystectomies performed for bladder cancer in Quebec from 1983 until 2005. Analysis included age, gender, year of surgery, surgeon’s age, hospital type, preoperative and postoperative visits with accompanying diagnoses and dates of recurrences salvage RC, and death. A total of 714 (30.4%) patients with invasive bladder cancer underwent PC. Majority of PC (65%) were performed in non-academic institutions. Pelvic lymphadenectomy was performed in only 163 patients (23%) and concomitant ureteral reimplantation was performed in 89 patients (13%). Of 714 patients, 52 (23.7%) required a salvage RC. Median time from PC to salvage RC was 17.6 months (range 1–240 months), respectively. Patients who underwent PC had similar 5-year overall survival compared with patients who underwent upfront RC (49.8% vs. 51%, p = 0.21). Rate of PC for invasive bladder cancer is significantly higher than expected. Pelvic lymphadenectomy is underutilized in bladder cancer patients treated with PC. Whether prevalent use of PC is due to less stringent selection criteria remains unknown. Since late recurrence is not uncommon, lifelong follow-up is recommended. [ABSTRACT FROM AUTHOR]

Objective: There is a lack of published evidence on factors associated with adherence (maintenance of cumulative vaccination) to seasonal influenza vaccination (SIV) in Manitoba, Canada. We sought to assess the associations., Methods: A cohort study utilizing Manitoba administrative health databases. Participants received SIV in 2010/11 influenza season, remained registered Manitoba residents and received at least one SIV during the 2011/12‒2019/20 seasons. We dichotomized adherence into "more adherent" (6‒9 SIVs) and "less adherent" (1‒5 SIVs) and used multivariable adjusted generalized estimating equation logistic regression models to assess association between adherence and socioeconomic, health-related, and primary care physician (PCP) characteristics, stratified by age group (< 5, 5‒17, 18‒44, 45‒64, ≥ 65) and sex. Results are adjusted odds ratios with 95% confidence intervals., Results: There were 152,493 participants. Males had lower odds of being more adherent except among ≥ 65-year-olds (1.03, 95% CI 1.01‒1.05). Compared with the lowest income quintile, those in higher income quintiles had higher odds of being more adherent. The odds mostly increased with increase in income quintile. Those with more contact with their PCP/hospitalization one year prior had higher odds of being more adherent. The odds increased with increased contact among those 18‒44, 45‒64 and ≥ 65 years old. Those who had PCP with more years of practice had higher odds of being more adherent. The odds increased as years of practice increased. These observations were mostly consistent irrespective of sex., Conclusion: Female gender, having higher income, having more contact with the health system, and having an experienced PCP may determine increased adherence to SIV in Manitoba. These findings require attention., (© 2024. The Author(s) under exclusive license to The Canadian Public Health Association.)

Background: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described., Methods: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up., Results: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC., Conclusions: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC., Competing Interests: Potential conflicts of interest . A. F. reports grants from the University of Calgary Eyes High Postdoctoral Fellowship and Canadian Institutes of Health Research Banting Postdoctoral Fellowship, and support for meetings and/or travel from a Trainee Travel Grant (Pediatric Academic Societies and Trainee travel grant), Alberta Children's Hospital Association, University of Calgary. L. A. reports grants from Pfizer. M. W. reports support for meetings and/or travel from US Acute Care Solutions (USACS), stock and a board of directors position for EM Device Lab. N. K. reports a leadership or fiduciary role for the Pediatric Emergency Care Applied Research, Pediatric Emergency Research Network; research funding from the National Institutes of Health (NIH), Health Resources and Services Administration (HRSA), and Patient-Centered Outcomes Research Institute (PCORI). R. M. reports royalties or licenses for Affinivax; consulting fees from GSK, Affinivax, and Merck; payment for lectures and support for meetings and/or travel from GSK; patents planned, issued, or pending for Boston Children's Hospital; being a member of the Affinivax board of directors; and stock options for Affinivax and Corner Therapeutics. S. M. M. reports grants from Sanofi, Merck, Pfizer National Minority Quality Forum (US); support for meetings and/or travel from Sanofi, Merck, GSK, Pfizer, CSL, Biosciences Association of Manitoba (BAM), and the National Minority Quality Forum (US); and participation on a Data and Safety Monitoring Board or Advisory board for Sanofi. T. A. F. reports grants from the National Heart, Lung, and Blood Institute (NHLBI) and leadership or fiduciary roles for the Society of Pediatric Research and the Pediatric Academic Societies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba, Canada is consistently low notwithstanding vaccine availability and free-of-charge vaccination. Despite, there is a lack of published evidence on the determinants of uptake of the vaccine. We sought to assess the association between SIV uptake and certain population and primary care physician (PCP) characteristics in Manitoba., Methods: We conducted a longitudinal study utilizing Manitoba administrative health databases. We summarized SIV uptake from 2000/01-2019/20 influenza seasons across subpopulations defined by socioeconomic, health-related and PCP characteristics. Utilizing multivariable generalized estimating equation logistic regression models, we assessed the association between SIV uptake and the socioeconomic, health-related and PCP characteristics, stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and sex. Results are adjusted odds ratios with associated 95 % confidence intervals., Results: SIV uptake percentage increased over time with 4.4 %, 13.1 %, 17.5 % and 21.7 % of < 5-year-olds, 2 %, 4.9 %, 9.7 % and 13.1 % of 5-17-year-olds, 5.4 %, 8.8 %, 10.7 % and 13.5 % of 18-44-year-olds, 16.8 %, 21.3 %, 23.6 % and 24.6 % of 45-64-year-olds receiving the SIV in 2000-2004, 2005-2009, 2010-2014 and 2015-2019, respectively. There was a decline among ≥ 65-year-olds from 58.5 % to 53.5 %. We observed a similar pattern across subpopulations. There were significantly increased odds of SIV uptake among females within the age groups ≥ 18 years, in higher income quintiles, mostly with increased contact with a PCP/hospitalization within age groups ≥ 18 years, among those who had older or female PCPs (the opposite observation among ≥ 65-year-olds) and whose PCP administered at least one SIV in prior influenza season. These observations were largely consistent irrespective of sex., Conclusion: SIV uptake in Manitoba appears to increase with age, and many socioeconomic, health-related and PCP characteristics appear to be associated with it. These findings may inform targeted vaccination programs to optimize influenza vaccination in Manitoba and similar Canadian jurisdictions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Mahmud has received unrestricted research grants from GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Roche-Assurex for unrelated studies, and fees as a consultant and advisory board member for GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Seqirus. Righolt has received an unrestricted research grant from Pfizer for an unrelated study. The other authors declare that they have no conflicts of interest]., (© 2024 The Authors.)

Significant racial/ethnic inequities in the uptake of differentiated influenza vaccines (DIVs) have been previously reported, though less is known about regional disparities. We conducted a retrospective longitudinal study (2014/15-2017/18 influenza seasons) among privately insured adults aged 65 + years in the US. The exposure was the beneficiary's area of residence (US Census Bureau division) and the outcome was the type of influenza vaccine: differentiated (high-dose [HDV], adjuvanted, recombinant, and cell-based) versus conventional standard-dose egg-based. Multilevel logistic regression modeling, guided by a causal diagram, was used to assess the influence of socio-demographics, medical, healthcare utilization, community, and vaccinator characteristics in confounding or mediating regional disparities. Among those vaccinated in physician offices, beneficiaries in the East North Central region were twice as likely to receive a DIV vs those in the South Atlantic, whereas those in the East and West South Central were least likely. Disparities became more pronounced in models adjusted for individual and community characteristics, suggesting that crude uptake estimates understate the true magnitude of disparities. A vaccinator's previous HDV use was most influential in explaining regional differences. Similar but less pronounced patterns emerged for vaccinations in pharmacies/facilities. Regional disparities remained even in fully adjusted models, pointing to currently poorly understood factors that may include quality of healthcare, client health literacy and engagement, and other political and cultural factors., (© 2023. W. Montague Cobb-NMA Health Institute.)

Background: Better CLL patient survival has been reported for specialized CLL clinics/hematologists (compared to other CLL patients). It is possible that improved survival is driven by a better prognosis of referred patients., Methods: We used logistic regression to calculate the odds ratios (ORs) and 95 % confidence intervals 95 %CIs) of the association between patient characteristics and CLL referral of all persons diagnosed in 2005-2016 with a pathologically-confirmed CLL or SLL., Results: Two-thirds of 1293 patients were referred to the CLL clinic. Referred patients were younger (16 % vs 44 % were 80 +) and in better health (47 % vs 56 % with a chronic diseases) than non-referred patients. Referral increased over time: in 2005-2010, about 60 % of patients were referred; in 2011-2016, this increased to 76 %. Gender did not affect referral (the OR for females is 1.0, 95 %CI 0.8-1.2), but age played a major role; CLL patients diagnosed at age 80 + were less likely to be referred than patients diagnosed < 60, 0.2 (0.1-0.3)., Conclusion: Because referral to Manitoba's specialized CLL clinic is associated with age and the patient's overall health before referral, one should be careful in interpreting differences in outcomes between CLL patients based on referral status alone., Competing Interests: Disclosure of financial relationships CHR has received an unrestricted research grant from Pfizer for an unrelated study. JBJ and VB have received unrestricted research grants from Lundbeck, Gilead and Janssen Pharmaceuticals for unrelated studies and sit on advisory boards for Gilead, Janssen, and Abbvie Pharmaceuticals. VB received consulting fees from AstraZeneca. SMM received research funding from Assurex, GSK, Merck, Pfizer, Roche and Sanofi for unrelated studies and is/was a member of advisory boards for GSK, Merck, Sanofi and Seqirus. None of the other authors have a financial relationship to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We investigated the role of individual, community and vaccinator characteristics in mediating racial/ethnic disparities in the uptake of differentiated influenza vaccines (DIVs; including high-dose, adjuvanted, recombinant and cell-based vaccines). We included privately-insured (commercial and Medicare Advantage) ≥65 years-old community-dwelling health plan beneficiaries in the US with >1 year of continuous coverage and who received ≥1 influenza vaccine during the study period (July 2014-June 2018). Of 2.8 million distinct vaccination claims, 60% were for DIVs; lower if received in physician offices (49%) compared to pharmacies/facilities (74%). Among those vaccinated in physician offices, non-whites had lower odds of receiving a DIV if they lived in a non-minority county (0.77;95%CI 0.75-0.80) and even lower odds if they lived in a minority county (0.62;0.60-0.63). Differences in education, household income, medical history, community and vaccinator characteristics did not fully explain the disparities. Similar patterns emerged for vaccinations in pharmacies/facilities, although disparities disappeared altogether after controlling for socio-economic and vaccinator characteristics. When vaccinated in physician offices, minority county residents were less likely to receive a DIV, especially for non-whites (0.72;0.67-0.78). These disparities disappeared for whites, but not for non-whites, after controlling for community and vaccinator characteristics. We found an alarming level of inequity in DIV vaccine uptake among fully insured older adults that could not be fully explained by differences in sociodemographic, medical, community, and vaccinator characteristics. New strategies are urgently needed to address these inequities., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SMM received research funding from Assurex, GSK, Merck, Pfizer, Roche and Sanofi for unrelated studies and is/was a member of advisory boards for GSK, Merck, Sanofi and Seqirus. CHR has received an unrestricted research grant from Pfizer for an unrelated study. MML, ET, and AC are employees of Sanofi Pasteur and may hold shares and/or stock options in the company., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Although pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006-2008., Methods: We assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies., Results: We included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: - 21.0, 24.0) in the period 15-364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15-364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6-11 years) than younger (0-5 years) children, it was lower at 12-13 years than after 14 years., Conclusion: VE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy., (© 2021. © Crown 2021 as represented by the Government of Ontario.)

Background: We studied lab-confirmed COVID-19 infection (LCCI) testing, incidence, and severity., Methods: We included all Manitoba residents and limited our severity analysis to LCCI patients. We calculated testing, incidence and vaccination rates between March 8, 2020 and June 1, 2021. We estimated the association between patient characteristics and testing (rate ratio [RR]; Poisson regression), including the reason for testing (screening, symptomatic, contact/outbreak asymptomatic), incidence (hazard ratio [HR]; Cox regression), and severity (prevalence ratio [PR], Cox regression)., Findings: The overall testing rate during the second/third wave was 570/1,000 person-years, with an LCCI rate of 50/1,000 person-years. The secondary attack rate during the second/third wave was 16%. Across regions, young children (<10) had the lowest positivity for symptomatic testing, the highest positivity for asymptomatic testing, and the highest risk of LCCI as asymptomatic contact. People in the lowest income quintile had the highest risk of LCCI, 1.3-6x the hazard of those in the highest income quintile. Long-term care (LTC) residents were particularly affected in the second wave with HRs>10 for asymptomatic residents., Interpretation: Although the severity of LCCI in children was low, they have a high risk of asymptomatic positivity. The groups most vulnerable to LCCI, who should remain a focus of public health, were residents of Manitoba's North, LTC facilities, and low-income neighbourhoods., Funding: Canada Research Chair Program., Competing Interests: CHR has received an unrestricted research grant from Pfizer for an unrelated study. SMM has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer and Roche-Assurex for unrelated studies. SMM has received fees as an advisory board member for GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur and Seqirus. None of the other authors have any conflicts of interest to disclose., (© 2021 The Authors. Published by Elsevier Ltd.)

Objectives: Limited time for seasonal influenza vaccine development means that the World Health Organization has to consider interim (early) rather than final vaccine effectiveness (VE) estimates in deciding influenza vaccine composition. We assessed agreement between interim and final VE estimates, and factors that may determine a substantial difference (≥10%) between point estimates., Methods: This was a mixed methods study. We systematically searched, identified, and matched interim/final VE studies of test-negative design (TND) type in outpatient settings after the 2009/10 influenza pandemic. The chi-square statistic (χ2) was used to assess the statistical significance of the difference between paired interim/final VE estimates. We calculated the difference between point estimates and used multivariable logistic regression to assess factors that may determine a substantial difference., Results: We identified 68 interim/final VE pairs. There was no statistically significant difference between almost all compared pairs. An inconsistent statistical model for interim/final VE estimation and interim VE estimation before the epidemic peak increased the odds of having a substantial difference between estimates., Conclusion: : Interim influenza VE appears to be sufficient for vaccine composition decision-making. Consistency in interim/final VE estimation, and interim VE estimation during/after epidemic peak may increase agreement between the VE estimates.

Background: Seasonal influenza vaccine (SIV) uptake among US adults aged 65 years or older remains suboptimal and stagnant. Further, there is growing concern around racial and ethnic disparities in uptake. We aimed to assess racial and ethnic disparities in overall SIV and in high-dose vaccine (HDV) uptake among Medicare beneficiaries during the 2015-16 influenza season and sought to identify possible mediators for observed disparities., Methods: We did a historical record-linkage cohort study using Medicare (a US national health insurance programme) databases, which included all older adults (≥65 years) enrolled in Medicare during the study period (July 1, 2015, to June 30, 2016). We excluded beneficiaries of Medicare Part C (managed care offered by private companies), and residents of long-term care facilities. The primary outcome was SIV receipt during the study period, classified into receipt of HDV and standard-dose vaccines (SDVs, representing all other SIVs). SIV uptake probabilities were estimated using competing-risk survival analysis methods. Mediation analyses were done to investigate potential mediators of the association between race and ethnicity and uptake., Findings: During the study period, of 26·5 million beneficiaries in the study cohort, 47·4% received a SIV, 52·7% of whom received HDV. Compared with white beneficiaries (49·4%), Hispanic (29·1%), Black (32·6%), and Asian (47·6%) beneficiaries were less likely to be vaccinated and, when vaccinated, were less likely to receive HDV (37·8% for Hispanic people, 41·1% for Black people, and 40·3% for Asian people, compared with 53·8% of white people who received HDV). Among those vaccinated, after accounting for region, income, chronic conditions, and health-care use, minority groups were 26-32% less likely to receive HDV, relative to white people (odds ratio [OR] 0·68 [95% CI 0·68-0·69] for Black people; OR 0·71 [0·71-0·72] for Asian people; and OR 0·74 [0·73-0·74] for Hispanic people)., Interpretation: Substantial racial and ethnic disparities in SIV uptake among Medicare beneficiaries aged 65 years or older are evident. New legislative, fiscal, and educational strategies are urgently needed to address these inequities., Funding: Sanofi Pasteur., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Despite improved understanding of the risks of influenza and better vaccines for older patients, influenza vaccination rates remain subpar, including in high-risk groups such as older adults, and demonstrate significant racial and ethnic disparities., Methods: This study considers demographic, clinical, and geographic correlates of influenza vaccination among Medicare Fee-for-Service (FFS) beneficiaries in 2015-2016 and maps the data on a geographic information system (GIS) at the zip code level., Results: Analyses confirm that only half of the senior beneficiaries evidenced a claim for receiving an inactivated influenza vaccine (IIV), with significant disparities observed among black, Hispanic, rural, and poorer beneficiaries. More extensive disparities were observed for the high-dose (HD) vaccine, with its added protection for older populations and confirmed economic benefit. Most white beneficiaries received HD; no non-white subgroup did so. Mapping of the data confirmed subpar vaccination in vulnerable populations with wide variations at the zip code level., Conclusion: Urgent and targeted efforts are needed to equitably increase IIV rates, thus protecting the most vulnerable populations from the negative health impact of influenza as well as the tax-paying public from the Medicare costs from failing to do so.

Background: In children with epilepsy, fever and illness are known triggers for seizure; therefore, clinicians and parents could be concerned that immunization-induced inflammation and fever could also trigger seizures. We sought to estimate the risk of emergency department (ED) visit or hospitalization for epilepsy/seizure and all causes after immunization in children younger than 7 years of age with epilepsy., Methods: We conducted a self-controlled case series of children diagnosed with epilepsy before their 7th birthday and immunized from 2005 to 2015 in Ontario (population 14.2 million) and Manitoba (population 1.3 million), Canada, using administrative healthcare data. We estimated the age- and season-adjusted relative incidence (aRI) of epilepsy/seizure-related and all-cause ED visits/hospitalizations during various risk periods 0-28 days after inactivated and live immunizations versus a control period 35-83 days postimmunization. Estimates from each province were analyzed separately and then combined in a random-effects meta-analysis., Results: The combined risk of epilepsy/seizure-related hospitalization/ED visit was increased 0-2 days after inactivated vaccines (aRI = 1.5, 95% confidence interval: 1.1-1.9) and 7-10 days after live vaccines (aRI = 1.9, 1.4-2.7). For all-cause ED visit/hospitalization, the combined aRI estimate was 0.9 (0.8-1.2) 0-2 days after inactivated vaccines and 1.3 (1.1-1.5) 7-10 days after live vaccines., Conclusions: The risk of epilepsy/seizure-related ED visit/hospitalization was modestly increased among children with epilepsy during peak periods of fever and inflammation following inactivated and live vaccines. These risks must be balanced against the risk of complications from vaccine-preventable diseases.

We sought to gain insights into the determinants of seasonal influenza vaccine (SIV) uptake by conducting an age-stratified analysis (18-64 and 65+) of factors associated with SIV uptake among at-risk adults registered to English practices. Records for at-risk English adults between 2011 and 2016 were identified using the Clinical Practice Research Datalink database. SIV uptake was assessed annually. The associations of patient, practice, and seasonal characteristics with SIV uptake were assessed via cross-sectional and longitudinal analyses, using mixed-effects and general estimating equation logistic regression models. Overall SIV uptake was 35.3% and 74.0% for adults 18-64 and 65+, respectively. Relative to white patients, black patients were least likely to be vaccinated (OR 18-64 : 0.82 (95% CI: 0.80, 0.85); OR 65+ : 0.59 (95% CI: 0.56, 0.62)), while Asian patients among 18-64 year olds were most likely to be vaccinated (OR 18-64 : 1.10 (95% CI: 1.07, 1.13)). Females were more likely than males to be vaccinated among 18-64 year olds (OR 18-64 : 1.19 (95% CI: 1.18, 1.20)). Greater socioeconomic deprivation was associated with decreased odds of uptake among older patients (OR 65+ : 0.74 (95% CI: 0.71, 0.77)). For each additional at-risk condition, odds of uptake increased (OR 18-64 : 2.33 (95% CI: 2.31, 2.36); OR 65+ : 1.39 (95% CI: 1.38, 1.39)). Odds of uptake were highest among younger patients with diabetes (OR 18-64 : 4.25 (95% CI: 4.18, 4.32)) and older patients with chronic respiratory disease (OR 65+ : 1.60 (95% CI: 1.58, 1.63)), whereas they were lowest among morbidly obese patients of all ages (OR 18-64 : 0.68 (95% CI: 0.67, 0.70); OR 65+ : 0.97 (95% CI: 0.94, 0.99)). Prior influenza season severity and vaccine effectiveness were marginally predictive of uptake. Our age-stratified analysis uncovered SIV uptake disparities by ethnicity, sex, age, socioeconomic deprivation, and co-morbidities, warranting further attention by GPs and policymakers alike., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MML reports financial and non-financial support from Sanofi Pasteur and University of Toronto. HB, AC, LS, ET, and RA are full-time employee of Sanofi Pasteur. SMM has received research grants and/or consulting fees from GlaxoSmithKline, Merck, Sanofi Pasteur, Pfizer and Roche-Assurex. SMM’s work is supported, in part, by funding from the Canada Research Chair Program., (© 2020 The Author(s).)

Objectives: Autism spectrum disorders (ASD) are among the leading causes of disabilities in children. We examined the annual prevalence and incidence rate of ASD between 2004 and 2015 in children aged 1 to 5 years residing in Manitoba., Methods: A population-based study was conducted using the Manitoba Population Research Data Repository. The study included children aged 1 to 5 years residing in Manitoba between 2004 and 2015. Standard identification algorithm was used to identify ASD cases from hospital abstracts and medical claims. Annual prevalence and incidence rates were calculated for the overall population and then stratified according to sex, region, and socio-economic status (SES). Multivariable negative binomial regression models, adjusted for sex, region, and SES, were used to examine changes in prevalence and incidence over study years., Results: Among children aged 1 to 5 years, 1685 ASD cases were diagnosed between 2004 and 2015. The crude ASD prevalence increased from 0.46% in 2004 to 0.97% in 2015 (p = 0.002). The crude incidence rate increased from 0.16% in 2004 to 0.39% in 2015 (p = 0.002). The increase in ASD prevalence and incidence was observed in all subgroups based on sex, region, and SES. The adjusted negative binomial model showed an annual relative risk increase, since 2004, for both prevalence and incidence of 1.69 (95% CI 1.56-1.83) and 1.84 (95% CI 1.62-2.09), respectively., Conclusion: During the period from 2004 to 2015, both prevalence and incidence rates of diagnosed ASD in preschoolers and toddlers residing in Manitoba increased significantly.

Background: In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines., Methods: We used electronic health databases to conduct a dynamic retrospective cohort study to assess narcolepsy incidence rates (IR) before and during pH1N1 virus circulation, and after pH1N1 vaccination campaigns in Canada, Denmark, Spain, Sweden, Taiwan, the Netherlands, and the United Kingdom. Using a case-control study design, we evaluated the risk of narcolepsy following AS03- and MF59-adjuvanted pH1N1 vaccines in Argentina, Canada, Spain, Switzerland, Taiwan, and the Netherlands. In the Netherlands, we also conducted a case-coverage study in children born between 2004 and 2009., Results: No changes in narcolepsy IRs were observed in any periods in single study sites except Sweden and Taiwan; in Taiwan incidence increased after wild-type pH1N1 virus circulation and in Sweden (a previously identified signaling country), incidence increased after the start of pH1N1 vaccination. No association was observed for Arepanrix-AS03 or Focetria-MF59 adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the case-control study nor for children born between 2004 and 2009 in the Netherlands case-coverage study for Pandemrix-AS03., Conclusions: Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Several genomic tests have recently been developed to identify the primary tumour in cancer of unknown primary tumour (CUP). However, the value of identifying the primary tumour in clinical practice for CUP patients remains questionable and difficult to prove in randomized trials., Objective: We aimed to assess the clinical and economic value of primary tumour identification in CUP using a retrospective matched cohort study., Methods: We used the Manitoba Cancer Registry to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients as having CUP if their primary tumour was found 6 months or more after initial diagnosis or never found during the course of disease. Otherwise, we considered patients to have metastatic cancer from a known primary tumour (CKP). We linked all patients with Manitoba Health databases to estimate their direct healthcare costs using a phase-of-care approach. We used the propensity score matching technique to match each CUP patient with a CKP patient on clinicopathologic characteristics. We compared treatment patterns, overall survival (OS) and phase-specific healthcare costs between the two patient groups and assessed association with OS using Cox regression adjustment., Results: Of 5839 patients diagnosed with metastatic cancer, 395 had CUP (6.8%); 1:1 matching created a matched group of 395 CKP patients. CUP patients were less likely to receive surgery, radiation, hormonal and targeted therapy and more likely to receive cytotoxic empiric chemotherapeutic agents. Having CUP was associated with reduced OS (hazard ratio [HR] 1.31; 95% confidence interval 1.1-1.58), but this lost statistical significance with adjustment for treatment differences. CUP patients had a significant increase in the mean net cost of initial diagnostic workup before diagnosis and a significant reduction in the mean net cost of continuing cancer care., Conclusion: Identifying the primary tumour in CUP patients might enable the use of more effective therapies, improve OS and allow more efficient allocation of healthcare resources.

Background: We examined whether a high-dose inactivated influenza vaccine was more efficacious in preventing hospitalizations than a standard-dose vaccine in the Veterans Health Administration (VHA) senior population., Methods: This study estimated the relative vaccine effectiveness (rVE) of high dose versus standard dose using a retrospective cohort of VHA patients 65 years of age or older in the 2015-2016 influenza season. To adjust for measured confounders, we matched each high-dose recipient with up to 4 standard-dose recipients vaccinated at the same location within a 2-week period and having 2 or more pre-existing medical comorbidities. We used the previous event rate ratio method (PERR), a type of difference-in-differences analysis, to adjust for unmeasured confounders., Results: We evaluated 104965 standard-dose and 125776 high-dose recipients; matching decreased the population to 49091 standard-dose and 24682 high-dose recipients. The matched, PERR-adjusted rVE was 25% (95% confidence interval [CI], 2%-43%) against influenza- or pneumonia-associated hospitalization, 7% (95% CI, -2% to 14%) against all-cause hospitalization, 14% (95% CI, -8% to 32%) against influenza- or pneumonia-associated outpatient visit, 5% (95% CI, 2%-8%) against all-cause outpatient visit, and 38% (95% CI, -5% to 65%) against laboratory-confirmed influenza., Conclusions: In protecting senior VHA patients against influenza- or pneumonia-associated hospitalization, a high-dose influenza vaccine is more effective than a standard-dose vaccine.

Background: The total direct cost of screening and treating all human papillomavirus-related diseases (HPV-RD) has not been measured in a single study. Accurate cost estimates are needed to inform decisions on intervention priorities and evaluate the cost-effectiveness of existing programs. We used province-wide clinical, administrative, and accounting databases to measure direct medical costs of HPV infection in Manitoba (Canada)., Methods: All persons 9 years or older with health insurance coverage in Manitoba between April 2000 and March 2015 were eligible. We identified all persons with an incident HPV-RD and aggregated all medical costs (in 2014 Canadian dollars) related to that condition, including prescription drugs, diagnostic procedures, in-hospital and outpatient treatment, and physician visits., Results: We found that the median cost of treating a case of anogenital warts was $130. An episode of cervical dysplasia had a median cost of $220, compared to $1300 for an episode of cervical carcinoma in situ. The cost of treating HPV-related invasive cancer varied from $15,000 for cervical cancer to $33,000 for oral cavity cancer. Overall, 80% ($145 million) of the total cost was attributable to HPV infection. Cervical screening and follow-up accounted for $96 million (66%) of all costs and this cost component has declined following the introduction of new screening guidelines., Conclusions: Overall, the average direct medical cost of HPV infection was $720 per newborn. The economic burden of HPV remains significant, although changes in cervical screening guidelines, prompted by the introduction of a public HPV vaccine program, appear to have promoted a promising trend towards lower costs.

Objectives: Canada does not have a national immunization registry. Diverse systems to record vaccine uptake exist, but these have not been systematically described. Our objective was to describe the immunization information systems (IISs) and non-IIS processes used to record childhood and adolescent vaccinations, and to outline the strengths and limitations of the systems and processes., Methods: We collected information from key informants regarding their provincial, territorial or federal organization's surveillance systems for assessing immunization coverage. Information collection consisted of a self-administered questionnaire and a follow-up interview. We evaluated systems against attributes derived from the literature using content analysis., Results: Twenty-six individuals across 16 public health organizations participated over the period of April to August 2015. Twelve of Canada's 13 provinces and territories (P/Ts) and two organizations involved in health service delivery for on-reserve First Nations people participated. Across systems, there were differences in data collection processes, reporting capabilities and advanced functionality. Commonly cited challenges included timeliness and data completeness of records, particularly for physician-administered immunizations. Privacy considerations and the need for data standards were stated as challenges to the goal of information sharing across P/T systems. Many P/Ts have recently implemented new systems and, in some cases, legislation to improve timeliness and/or completeness., Conclusion: Considerable variability exists among IISs and non-IIS processes used to assess immunization coverage in Canada. Although some P/Ts have already pursued legislative or policy initiatives to address the completeness and timeliness of information, many additional opportunities exist in the information technology realm.

Background: Streptococcus pneumoniaeis a major cause of community-acquired pneumonia and septicemia in adults. The global drug-susceptible capsular serotype 12F, clonal complex 218 caused several outbreaks in the United States between 1989 and 2008, as well as a recent large outbreak in Manitoba, Canada, that resulted in 36 cases of septicemia and 3 deaths. The evolutionary origin of the Canadian outbreak strain and its relationship to the historical US outbreak strains are not known., Methods: Whole-genome deep sequencing was performed on isolates from the Canadian outbreak (n = 36), the US outbreaks (n = 9), and nonoutbreak surveys (n = 21). Phylogenomic analysis and comparative genomics were used to assess evolutionary relationships and to detect gene content differences between the isolates., Results: The Canadian outbreak was closely related to sporadic cases that occurred preoutbreak in cross-border geographic regions in Manitoba, North Dakota, and Iowa. The emerging Canadian strain differed from US strains by acquisition of a cell-surface protein and macrolide resistance determinants via incorporation of a 5.3-kb mega cassette harboringmsrDandmefE Furthermore, during 11 months of transmission, this clone evolved rapidly and acquired fluoroquinolone resistance through precise stepwise mutations in bothparCandgyrA, and putative compensatory mutations inuraAorIMPDHunder drug selection. Alarmingly, this drug-resistant clone appears to have spread quickly to other regions of Canada and the United States, and replaced drug-susceptible strains., Conclusions: Whole-genome sequencing revealed an independent emergence and secondary adaptation of a new virulent and drug-resistant pneumococcal epidemic clone. Ongoing molecular surveillance is required, and measures to prevent its spread should be developed., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Females who receive the human papillomavirus (HPV) vaccine may believe they are protected from developing cervical cancer and no longer require screening. Concern has also been expressed that vaccinated females are those that would be screened regularly. This study assesses the Pap testing behavior of vaccinated and non-vaccinated females., Methods: For this population-based retrospective cohort study, vaccination and screening registries were linked for 3540 vaccinated females aged 15 years and over and 9592 matched non-vaccinated females. Conditional logistic regression, the Kaplan-Meier method and Cox regression were used to examine the association between vaccination and Pap testing., Results: Vaccinated females were more likely to have had a Pap test within the year prior to the index date than non-vaccinated females (15-19 years old: OR=1.38, 95% CI 1.20-1.59; 20+ years old: OR=2.34, 95% CI 1.98-2.76). In the three-year period after the index date, vaccinated females had a significantly higher cumulative probability of having a Pap test (83.3%) than non-vaccinated females (66.1%). Females who had a Pap test within three years prior to the index date were more likely to have a Pap test after the index date (vaccinated: HR=5.03, 95% CI 4.65-5.45; non-vaccinated HR=3.97, 95% CI 3.70-4.24). Being vaccinated had a significant effect on Pap testing (15-19 years old: HR=1.54, 95% CI 1.39-1.69; 20+ years old: HR=1.87, 95% CI 1.52-2.31). 80.1% of vaccinated females who had a Pap test prior to the index date also had one subsequent to it, compared to 70.1% for non-vaccinated females. 41.1% of females had not been vaccinated nor had a Pap test., Conclusion: The majority of vaccinated females continue to participate in screening, and do so at a higher rate than non-vaccinated females. Renewed efforts need to be made to include the large proportion of non-vaccinated, non-screened females in vaccination and/or screening., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We conducted a population-based study in Manitoba, Canada, to investigate whether use of inactivated trivalent influenza vaccine (TIV) during the 2008-09 influenza season was associated with subsequent infection with influenza A(H1N1)pdm09 virus during the first wave of the 2009 pandemic. Data were obtained from a provincewide population-based immunization registry and laboratory-based influenza surveillance system. The test-negative case-control study included 831 case-patients with confirmed influenza A(H1N1)pdm09 virus infection and 2,479 controls, participants with test results negative for influenza A and B viruses. For the association of TIV receipt with influenza A(H1N1)pdm09 virus infection, the fully adjusted odds ratio was 1.0 (95% CI 0.7-1.4). Among case-patients, receipt of 2008-09 TIV was associated with a statistically nonsignificant 49% reduction in risk for hospitalization. In agreement with study findings outside Canada, our study in Manitoba indicates that the 2008-09 TIV neither increased nor decreased the risk for infection with influenza A(H1N1)pdm09 virus.

Objectives: We compared the screening performance of conventional Pap cytology and two human papillomavirus (HPV) DNA assays, the original Hybrid Capture 2 (HC2) and an expanded version that tests for 4 additional HPV types (HC2+4; Qiagen Corporation), in the detection of cervical neoplasia among unscreened women in a primary care setting in a suburb of Kinshasa, Democratic Republic of the Congo., Methods: All women 30 years or older residing in the area were invited to participate, and 1528 were evaluated by Pap cytology and the two HPV assays, conducted at a European and US reference laboratory, respectively, followed by colposcopy. Cervical biopsies were obtained from all women with abnormal colposcopy and from 290 randomly chosen women with normal colposcopy (to correct for verification bias)., Results: Using a relative light unit of 1 as the cutoff for positivity, 169 and 168 (11%) women tested positive using HC2 and HC2+4, respectively. HC2 and HC2+4 were in agreement in 98.6% of cases (Kappa=0.94; 95% confidence interval: 0.91-0.96). Both assays were sensitive (~83%) and specific (~91%) for the detection of cervical intraepithelial neoplasia-2 or worse disease. Irrespective of the cutoff point used to define positivity, Pap cytology was both less sensitive and more specific than HC2 or HC2+4. For instance, cytology was 63% sensitive and 97% specific when a cutoff point of low-grade squamous intraepithelial lesions or worse was used., Conclusions: Among unscreened women, HC2 and HC2+4 had similar screening accuracy for cervical neoplasia, and both were more sensitive but less specific than Pap cytology., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background & Aims: There are limited data on mortality from colorectal cancer (CRC) among patients who have received colonoscopy examinations. We sought to determine CRC mortality among persons undergoing colonoscopies compared with the general population., Methods: We identified all individuals who had a colonoscopy as their first lower gastrointestinal endoscopy from April 1, 1987, to September 30, 2007 (24,342 men and 30,461 women), based on information from Manitoba's provincial physicians' billing claims database. Patients were followed until March 31, 2008, death, or migration out of the province (310,718 person-years). Individuals less than 50 years of age or more than 80 years of age at the index colonoscopy or those with prior sigmoidoscopy, inflammatory bowel disease, resective colorectal surgery, or CRC were excluded. CRC mortality after the index colonoscopy was compared with that of the general population by standardized mortality ratios (SMRs). Stratified analyses were performed to determine CRC mortality for different age groups at index colonoscopy and sex, duration of follow-up, medical specialty of the endoscopist, and site of CRC., Results: There was a 29% reduction in overall CRC mortality (SMR, 0.71; 95% confidence interval [CI], 0.61-0.82], a 47% reduction in mortality from distal CRC (SMR, 0.53; 95% CI, 0.42-0.67), and no reduction in mortality from proximal CRC (SMR, 0.94; 95% CI, 0.77-1.17). The reduction in mortality from distal CRC remained significant for follow-up beyond 10 years (SMR, 0.53; 95% CI, 0.31-0.84)., Conclusions: In Manitoba, colonoscopies significantly reduce mortality from CRC, but the benefit is not uniform for colorectal tumors that arise in different areas of the colon., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

It is only since the 1950s that most of the epidemiology studies on cancer have been conducted. The principal study designs for epidemiologic study of cancer etiology are case-control and cohort studies. These study designs have complimentary roles and distinct advantages and disadvantages. This chapter provides historical perspectives, description of the traditional and variant designs of case-control and cohort studies, and the relative advantages and disadvantages of these study designs.

Aim: To describe the nutritional status of children under-five years of age in Libya., Population and Methods: A secondary analysis of data of 5348 children taken from a national representative, two-stage, cluster-sample survey that was performed in 1995., Results: Prevalence rates of underweight, wasting, stunting, and overweight were determined using standard definitions in reference to newly established WHO growth charts. The study revealed that 4.3% of children were underweight, 3.7% wasted, 20.7% stunted, and 16.2% overweight. Seventy percent of children had normal weight. Undernutrition was more likely to be found in males, in rural areas, and in underprivileged groups. Overweight was more likely found in urban, privileged groups. Wasting was more common in arid regions; stunting was more common in mountainous regions of Al-Akhdar, Al-Gharbi, and in Sirt. Al-Akhdar had the highest prevalence of overweight., Conclusion: The country had a low prevalence of underweight and wasting, moderate prevalence of stunting, and high prevalence of overweight. The country is in the early stages of transition with evidence of dual-burden in some regions. Similar surveys are needed to verify secular trends of these nutritional problems, particularly overweight.

Animal and laboratory studies suggest that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce prostate cancer risk. The aim of this study was to investigate the association between NSAID use and prostate cancer in a high-risk population. We included 1299 men who were referred to our university's prostate cancer detection clinic for prostate biopsy between January 1999 and July 2003. Before transrectal ultrasonography and prostate biopsy, all men completed a self-administered questionnaire that included questions on drug use in the preceding 5 years. On average, NSAID users were older than non-users but there was no significant difference in mean baseline prostate-specific antigen (PSA). Four hundred and ninety-four (38%) had biopsy-confirmed prostate cancer. After adjustment for age, family history of prostate cancer and other potential confounders, use of aspirin was associated with a 42% reduction in the odds of prostate cancer detection [95% confidence interval (CI) 0.36-0.91]. Among cases, regular use of NSAIDs was inversely related to the risk of detection of more poorly differentiated cancers and cancers with higher percentage core involvement. These findings support other epidemiological and experimental evidence that suggests that aspirin may be useful in prostate cancer prevention. Further observational studies with adequate case definition and exposure measurements and careful adjustment for detection bias are warranted.