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AbstractObjectiveTo estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death).DesignTest negative design study.SettingOntario, Canada between 14 December 2020 and 19 April 2021.Participants324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2.InterventionsBNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine.Main outcome measuresLaboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes.ResultsOf 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation.ConclusionsTwo doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

Systemic lupus Erythematosus (SLE) is a chronic multi-system autoimmune disease that can affect a person’s physical, mental, and social life. It imposes a substantial economic burden up on patients, carers, healthcare systems, and wider society. This is the first study to examine the direct health care costs of SLE in Alberta using real-world data. Alberta maintains a publicly funded, universally available health care system. Health service use and direct healthcare costs of SLE and non-SLE cases were determined from inpatient hospital services, fee-for-physician services, emergency services, and ambulatory care services. All costs were estimated for calendar year 2016. Data were analysed using central measures specifically the mean to determine the annual costs of SLE and non-SLE. A total number of 10,932 (Male = 2,546; Female = 8,386), and 41,851,36 (Male = 21,157,76; Female = 20,693,60) of SLE and non-SLE cases, respectively were included in this study. The mean annual costs of SLE, and non-SLE per case were $7,740.19 (Male = $7,986.59; Female = $7,665.38), and $2,479.53 (Male = $2,265.57; Female = $2,698.30), (p < 0.001) respectively. The mean annual costs of fee-for-physician services (SLE = $2,160.03; non-SLE = $840.00) (p < 0.001), inpatient hospital services (SLE = $3,462.86; non-SLE = $1,007.29), (p < 0.001) emergency services (SLE = $440.28; non-SLE = $176.65), (p < 0.001) and ambulatory care services (SLE = $1,677.03; non-SLE = $455.05) (p < 0.001) per case were estimated. The findings showed that the costs of SLE were considerably high for patients and healthcare system. This highlights the importance of appropriate treatment and management of SLE. Further studies are required to fully investigate both the direct and indirect economic burden of SLE including out-of-pocket expenses, costs to patients and caregivers and productivity loss.

Background The purpose of this paper is to systematically review the literature on the relationship between socioeconomic status (SES) and influenza immunization and to examine how certain measures of SES may influence interpretations of this relationship. Methods We conducted a systematic review of existing peer-reviewed literature to evaluate the above relationship in the general population. Electronic databases (MEDLINE and EMBASE) were searched from January 2012 to May 2017 to identify English-language studies relevant to this review. Studies were included where influenza vaccination was explicitly reported as the dependent variable and SES as the independent variable. We limited our review to measures of SES that focus on education, income, social class, occupation, and deprivation. Studies that measured SES using other variables (e.g., race, ethnicity, geographic location, rural or urban status, or insurance status) were excluded. Studies were also excluded if they did not report on the human population or did not analyze original data. The population of interest included all age groups, levels of health status, and sociodemographic backgrounds. The review was also limited to World Bank high-income countries. Two authors independently screened full-text articles after obtaining a Kappa score of K =  0.867. The methodological quality of manuscripts was assessed using the appraisal tools developed by the Joanna Briggs Institute. Results were qualitatively reported and synthesized. Results Of the 42 articles included in this review, 52.4% ( n  = 22) found that higher levels of SES resulted in higher levels of influenza vaccination; 4.5% ( n  = 2) reported a negative association; and 14.3% ( n  = 6) found no association. Just over a quarter (26.2%, n  = 12) of articles reported mixed results. Conclusions There was consistently a relationship between SES and influenza immunization, which varied according to how SES was measured. It is recommended that authors be explicit in defining the SES concept they are trying to capture and that they utilize multiple measures of SES (e.g., education, income, class).

ObjectiveTo assess the impact of the COVID-19 pandemic on early childhood vaccination coverage in Alberta, Canada.SettingAlberta, a western Canadian province, which has a population of 4.4 million and approximately 50 000 births annually.DesignIn this retrospective cohort study, population-based administrative health data were analysed to determine the vaccination coverage for measles-containing, pertussis-containing and rotavirus vaccines.Primary outcome measureWe measured monthly and cumulative vaccine coverage. We assessed the absolute difference in monthly and cumulative coverage for each vaccine dose by comparing children due for vaccination in each month of 2019 and 2020, with follow-up to determine if missed doses were caught up later.ParticipantsWe included 114 178 children in the 2019 analysis cohort and 106 530 children in the 2020 analysis cohort.ResultsMonthly vaccination coverage in 2020 was higher than 2019 until March, when coverage significantly declined. Comparing April 2020 to 2019, coverage was 9.9% (95% CI 7.9% to 12.0%) lower for measles vaccine; 4.9% (95% CI 3.3% to 6.5%), 7.1% (95% CI 5.2% to 9.1%), 5.2% (95% CI 3.1% to 7.4%) and 8.8% (95% CI 6.6% to 10.9%) lower for first, second, third and fourth doses of pertussis-containing vaccine, respectively; and 4.0% (95% CI 2.3% to 5.7%), 7.1% (95% CI 5.1% to 9.2%) and 4.6% (95% CI 2.4% to 6.7%) lower for first, second and third doses of rotavirus vaccine, respectively. Monthly coverage improved during May to July 2020; however, some doses experienced a second decline during September to October 2020. The cumulative coverage analysis showed that the measles-containing vaccine had the largest difference in coverage at the end of follow-up.ConclusionsChildren who were due for vaccination early in the pandemic and in Fall 2020, especially those due for measles vaccination, may require additional catch-up.

Previously, we have demonstrated a high incidence and prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in the Canadian province of Manitoba. However, the epidemiology of inflammatory bowel disease (IBD) in other regions of Canada has not been defined. The aim of this study was to estimate the incidence and prevalence of CD and UC in diverse regions of Canada and the overall burden of IBD in Canada. We applied a common case identification algorithm, previously validated in Manitoba to the provincial health databases in British Columbia (BC), Alberta (AB), Saskatchewan (SK), Manitoba (MB), and Nova Scotia (NS) to determine the age-adjusted incidence rates per 100,000 person-years for 1998-2000 and prevalence per 100,000 for mid 2000 and to estimate the IBD burden in Canada. Poisson regression was used to assess differences in incidence rates and prevalence by gender, age, and province. The incidence rate for CD ranged from 8.8 (BC) to 20.2 (NS), and for UC ranged from 9.9 (BC) to 19.5 (NS). The prevalence of CD was approximately 15- to 20-fold higher than the incidence rate, ranging from 161 (BC) to 319 (NS). This was similar for the prevalence of UC, which ranged from 162 (BC) to 249 (MB). Adjusting for age and province, the female:male ratio for incidence ratio was 1.31 (p < 0.0001) for CD and 1.02 (n.s.) for UC and was mostly stable across the five provinces. Approximately 0.5% of the Canadian population has IBD. Canada has the highest incidence and prevalence of CD yet reported.

Under-reporting of pertussis cases is a longstanding challenge. We estimated the true number of pertussis cases in Ontario using multiple data sources, and evaluated the completeness of each source. We linked data from multiple sources for the period 2009 to 2015: public health reportable disease surveillance data, public health laboratory data, and health administrative data (hospitalizations, emergency department visits, and physician office visits). To estimate the total number of pertussis cases in Ontario, we used a three-source capture-recapture analysis stratified by age (infants, or aged one year and older) and adjusting for dependency between sources. We used the Bayesian Information Criterion to compare models. Using probable and confirmed reported cases, laboratory data, and combined hospitalizations/emergency department visits, the estimated total number of cases during the six-year period amongst infants was 924, compared with 545 unique observed cases from all sources. Using the same sources, the estimated total for those aged 1 year and older was 12,883, compared with 3,304 observed cases from all sources. Only 37% of infants and 11% for those aged 1 year and over admitted to hospital or seen in an emergency department for pertussis were reported to public health. Public health reporting sensitivity varied from 2% to 68% depending on age group and the combination of data sources included. Sensitivity of combined hospitalizations and emergency department visits varied from 37% to 49% and of laboratory data from 1% to 50%. All data sources contribute cases and are complementary, suggesting that the incidence of pertussis is substantially higher than suggested by routine reports. The sensitivity of different data sources varies. Better case identification is required to improve pertussis control in Ontario.

A school-based program with quadrivalent human papillomavirus (HPV) vaccination was implemented in Alberta in 2008. We assessed the impact of this program on Pap test cytology results using databases of province-wide vaccination and cervical cancer screening. We conducted a nested case–control study involving a cohort of women in Alberta born between 1994 and 1997 who had at least 1 Pap test between 2012 and 2015. Women with negative cytology results were controls. Women with low-grade (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion) and high-grade (atypical squamous cells, cannot rule out a high-grade lesion; or high-grade squamous intraepithelial lesion) cervical abnormalities were cases. Exposure status was assigned according to records of HPV vaccination. Odds ratios (ORs) for abnormal cytology results by vaccination status were adjusted for neighbourhood income, laboratory service, rural versus urban residency, and age. The total study population was 10 204. Adjusting for age, vaccinated women had a higher screening rate than unvaccinated women (13.0% v. 11.4%, p < 0.001). Among women who received full vaccination (≥ 3 doses), the adjusted OR for cervical abnormalities was 0.72 (95% confidence interval [CI] 0.63–0.82). For high-grade lesions, the adjusted OR was 0.50 (95% CI 0.30–0.85). With 2-dose HPV vaccination, the adjusted OR for cervical abnormalities was 1.08 (95% CI 0.84–1.38). Quadrivalent HPV vaccination significantly reduced high-grade cervical abnormalities but required 3 doses. Vaccination against HPV was associated with screening uptake. Population-based vaccination and screening programs should work together to optimize cervical cancer prevention.

The combination measles–mumps–rubella–varicella (MMRV) vaccine currently used in Canada (Priorix-Tetra) may increase the risk of febrile seizures relative to the separate vaccines (MMR and varicella) previously administered. We determined the risk of febrile seizure after the first dose of MMRV, as well as any additional risk for children at high risk for seizures because of pre-existing medical conditions. In this retrospective, population-based cohort study, we compared the risk of seizures after the first dose of MMRV with the risk after same-day administration of separate MMR and varicella vaccines (MMR+V) in children 12 to 23 months of age in the province of Alberta. We deterministically linked vaccination data to health service utilization data for seizures. We used Poisson regression, with adjustment for age and calendar year, to determine the risk for the full cohort and for high-risk children. The risk of seizures 7 to 10 days after vaccination was twice as high with MMRV as with MMR+V (relative risk [RR] 1.99, 95% confidence interval [CI] 1.30–3.05). The excess absolute risk of seizures was 3.52 seizures per 10 000 doses of MMRV relative to MMR+V. In high-risk children, the risk was not differentially higher for MMRV (RR 1.30, 95% CI 0.60–2.79). Despite an increased risk of febrile seizures following MMRV (compared with MMR+V), the absolute level of risk was small. Policy-makers need to balance these findings with the potential benefits of administering the combination vaccine or determine whether the choice of vaccine rests with clinicians and/or parents.

ObjectivesIn June 2015, Alberta, Canada instituted a universal publicly funded rotavirus vaccination programme (Rotarix, RV1), with vaccine doses scheduled for 2 and 4 months of age. Vaccination was restricted so that infants were only allowed to receive first dose between 6 and 20 weeks of age, and second dose before eight calendar months of age. We assessed the coverage and schedule non-compliance of rotavirus vaccination for babies born between June 2015 and August 2016, that is, since the inception of the publicly funded rotavirus vaccination programme, and determined factors associated with rotavirus vaccine uptake.DesignRetrospective cohort study using linked administrative health data.SettingAlberta, Canada.ParticipantsCohort of 66 689 children.Primary and secondary outcome measures(1) First and second dose rotavirus vaccination coverage, (2) percent of children non-compliant with recommended vaccine schedule and (3) adjusted ORs for factors associated with vaccination status.ResultsFor the 66 689 children included in the study, coverage levels for one-dose and two-dose rotavirus vaccination were 87% and 83%, respectively. In comparison, two-dose diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine coverage was 92%, despite having the same dosing schedule. Schedule non-compliance during the publicly funded programme was very low. We observed socioeconomic disparities in the uptake of the vaccine, with income, location of residence and number of children in the household all contributing to the odds of a child being vaccinated with rotavirus.ConclusionsCompliance to the recommended rotavirus schedule was very high, suggesting that even with the restrictive rotavirus vaccine schedule, the vaccine can be delivered on-time. However, rotavirus vaccine coverage remained lower than DTaP, a similarly scheduled childhood vaccination. We also observed socioeconomic disparities in vaccine uptake. These findings raise concerns about rotavirus protection in the groups at highest risk for gastrointestinal illness, including low-income and rural populations.

Vaccine safety signals require investigation, which may be done rapidly at the population level using ecological studies, before embarking on hypothesis-testing studies. Incidence rates were used to assess a signal of narcolepsy following AS03-adjuvanted monovalent pandemic H1N1 (pH1N1) influenza vaccination among children and adolescents in Sweden and Finland in 2010. We explored the utility of ecological data to assess incidence of narcolepsy following exposure to pandemic H1N1 virus or vaccination in 10 sites that used different vaccines, adjuvants, and had varying vaccine coverage. We calculated incidence rates of diagnosed narcolepsy for periods defined by influenza virus circulation and vaccination campaign dates, and used Poisson regression to estimate incidence rate ratios (IRRs) comparing the periods during which wild-type virus circulated and after the start of vaccination campaigns vs. the period prior to pH1N1 virus circulation. We used electronic health care data from Sweden, Denmark, the United Kingdom, Canada (3 provinces), Taiwan, Netherlands, and Spain (2 regions) from 2003 to 2013. We investigated interactions between age group and adjuvant in European sites and conducted a simulation study to investigate how vaccine coverage, age, and the interval from onset to diagnosis may impact the ability to detect safety signals. Incidence rates of narcolepsy varied by age, continent, and period. Only in Taiwan and Sweden were significant time-period-by-age-group interactions observed. Associations were found for children in Taiwan (following pH1N1 virus circulation) and Sweden (following vaccination). Simulations showed that the individual-level relative risk of narcolepsy was underestimated using ecological methods comparing post- vs. pre-vaccination periods; this effect was attenuated with higher vaccine coverage and a shorter interval from disease onset to diagnosis. Ecological methods can be useful for vaccine safety assessment but the results are influenced by diagnostic delay and vaccine coverage. Because ecological methods assess risk at the population level, these methods should be treated as signal-generating methods and drawing conclusions regarding individual-level risk should be avoided.