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Background: Influenza may contribute to coronary/cerebrovascular events and exacerbate underlying conditions. Methods: We used self‐controlled case series (SCCS) design to analyze data from US Veterans ≥18 years with coronary/cerebrovascular or exacerbation event +/−1 year of lab‐confirmed influenza (LCI) during 2010–2018. We estimated the incidence ratio (IR) (95% CI) of the event for risk interval (Days 1–7 post‐LCI) versus control interval (all other times +/−1 year of LCI) with fixed‐effects conditional Poisson regression. We included biomarker data for mediation analysis. Results: We identified 3439 episodes with coronary/cerebrovascular‐related hospitalizations. IRs (95% CI) for LCI risk versus control interval were STEMI 0.6 (0.1, 4.4), NSTEMI 7.3 (5.8, 9.2), ischemic stroke 4.0 (3.0, 5.4), hemorrhagic stroke 6.2 (3.4, 11.5), and coronary spasm 1.3 (0.5, 3.0). IR significantly increased for NSTEMI and ischemic stroke among those ≥ 65 years. IR for NSTEMI and ischemic stroke dropped 26% and 10%, respectively, when white blood cell (WBC) and platelet count were considered. LCI was significantly associated with exacerbation of preexisting asthma, chronic obstructive pulmonary disease, and congestive heart failure. Conclusions: We found significant association between LCI and hospitalization for NSTEMI, ischemic stroke, and hemorrhagic stroke, the latter possibly due to unaccounted time‐varying confounding in SCCS design. [ABSTRACT FROM AUTHOR]

Observational seasonal influenza relative vaccine effectiveness (rVE) studies employ a variety of statistical methods to account for confounding and biases. To better understand the range of methods employed and implications for policy, we conducted a brief literature review. Across 37 included rVE studies, 10 different types of statistical methods were identified, and only eight studies reported methods to detect residual confounding, highlighting the heterogeneous state of the literature. To improve the comparability and credibility of future rVE research, researchers should clearly explain methods and design choices and implement methods to detect and quantify residual confounding. [ABSTRACT FROM AUTHOR]

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]

Characterizing long‐term prescription data is challenging due to the time‐varying nature of drug use. Conventional approaches summarize time‐varying data into categorical variables based on simple measures, such as cumulative dose, while ignoring patterns of use. The loss of information can lead to misclassification and biased estimates of the exposure‐outcome association. We introduce a classification method to characterize longitudinal prescription data with an unsupervised machine learning algorithm. We used administrative databases covering virtually all 1.3 million residents of Manitoba and explicitly designed features to describe the average dose, proportion of days covered (PDC), dose change, and dose variability, and clustered the resulting feature space using K‐means clustering. We applied this method to metformin use in diabetes patients. We identified 27,786 metformin users and showed that the feature distributions of their metformin use are stable for varying the lengths of follow‐up and that these distributions have clear interpretations. We found six distinct metformin user groups: patients with intermittent use, decreasing dose, increasing dose, high dose, and two medium dose groups (one with stable dose and one with highly variable use). Patients in the varying and decreasing dose groups had a higher chance of progression of diabetes than other patients. The method presented in this paper allows for characterization of drug use into distinct and clinically relevant groups in a way that cannot be obtained from merely classifying use by quantiles of overall use.Distinction between stable and varying patterns of metformin use. [ABSTRACT FROM AUTHOR]

Background: Unmeasured confounders are commonplace in observational studies conducted using real-world data. Prior event rate ratio (PERR) adjustment is a technique shown to perform well in addressing such confounding. However, it has been demonstrated that, in some circumstances, the PERR method actually increases rather than decreases bias. In this work, we seek to better understand the robustness of PERR adjustment.Methods: We begin with a Bayesian network representation of a generalized observational study, which is subject to unmeasured confounding. Previous work evaluating PERR performance used Monte Carlo simulation to calculate joint probabilities of interest within the study population. Here, we instead use a Bayesian networks framework.Results: Using this streamlined analytic approach, we are able to conduct probabilistic bias analysis (PBA) using large numbers of combinations of parameters and thus obtain a comprehensive picture of PERR performance. We apply our methodology to a recent study that used the PERR in evaluating elderly-specific high-dose (HD) influenza vaccine in the US Veterans Affairs population. That study obtained an HD relative effectiveness of 25% (95% CI: 2%-43%) against influenza- and pneumonia-associated hospitalization, relative to standard-dose influenza vaccine. In this instance, we find that the PERR-adjusted result is more like to underestimate rather than to overestimate the relative effectiveness of the intervention.Conclusions: Although the PERR is a powerful tool for mitigating the effects of unmeasured confounders, it is not infallible. Here, we develop some general guidance for when a PERR approach is appropriate and when PBA is a safer option. [ABSTRACT FROM AUTHOR]

Several epidemiological studies have found an association between maternal antibiotics use during pregnancy and increased risk of certain cancer types, although conclusions differ between studies. We examined this association in a cohort study including 262 116 mother‐child pairs of Manitoba births between 1996 and 2013. Maternal antibiotics use during prepregnancy (6 months prior to pregnancy) and pregnancy periods was assessed. Children's cancer incidence was tracked up to the end of the follow‐up period (December 2015). We calculated incidence rate and used Cox regression to estimate adjusted hazard ratios (HRs). Antibiotics use during pregnancy was not associated with overall cancer (HR = 1.1, 95% confidence interval 0.9‐1.4), leukemias (1.3, 0.9‐1.8), or acute lymphocytic leukemia (1.1, 0.7‐1.6). The association between antibiotics use and overall cancer risk differed by trimester: 1.5 (1.1‐1.9) in the first, 0.8 (0.6‐1.0) in the second, and 1.1 (0.8‐1.5) in the third trimester. Further research is necessary to confirm the association between first‐trimester exposure and cancer risk after a better controlling of confounding factors. [ABSTRACT FROM AUTHOR]

The effectiveness of a vaccination program is influenced by its design and implementation details and by the target population characteristics. Using routinely collected population‐based individual‐level data, we assessed the effectiveness (against cervical dysplasia) of Manitoba's quadrivalent human papillomavirus (qHPV) routine school‐based vaccination program and a short‐lived campaign that targeted women at high‐risk of developing cervical cancer. Females ≥9 years old who received the qHPV vaccine in Manitoba (Canada) between September 1, 2006, and March 31, 2013 (N = 31,442) were matched on age and area of residence to up to three unvaccinated females. Cox proportional hazards models were used to estimate qHPV VE against high‐grade (HSILs) and low‐grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASCUS). Among 14–17‐year‐old participants who had Pap cytology after enrollment, the adjusted qHPV VE estimates were 30% (17–58%) and 36% (21–48%) against the detection of HSILs and LSILs, respectively. There was, however, no evidence of program effectiveness among females vaccinated at ≥18 years of age and among those with a history of abnormal cytology, who were mostly vaccinated as part of the high‐risk program. Estimates of VE for females vaccinated in the school‐based program are consistent with the expected benefits from qHPV vaccination. No similar benefits were detected among women vaccinated at an older age, and those with abnormal cytology, who were targeted by the high‐risk program. Further efforts should be targeted at achieving higher vaccine coverage among preadolescents, prior to the initiation of sexual activity. What's new? Vaccination with the quadrivalent human papillomavirus (qHPV) prevents infection with HPV types responsible for the vast majority of cervical cancers and genital warts. In Manitoba, the qHPV vaccine has been available in school‐based vaccination programs since 2008. This study shows that levels of protection against cervical dysplasia among adolescent girls vaccinated in Manitoba's routine school‐based qHPV vaccination program are similar to benefit levels estimated from randomized clinical trials. Women vaccinated at age 18 or older or who had a history of abnormal cytology did not experience comparable benefits, likely owing to a combination of factors, including prior HPV exposure. [ABSTRACT FROM AUTHOR]

Non‐Hodgkin lymphomas (NHL) are a group of cancers with highly heterogeneous biology and clinical features. Statins are increasingly prescribed to prevent cardiovascular diseases. Early evidence shows a preventive effect of statins for some cancers, but their effect on NHL risk is unclear. We conducted a population‐based nested case–control study involving 5,541 NHL cases and 27,315 controls matched for gender, age, place of residence and length of period of available prescription drug data. We assessed the use of statins prior to diagnosis (excluding the 12 months prior to the index date). We used conditional logistic regression models to estimate odds ratio (OR) and 95% confidence interval (CI) for use of any statin, adjusting for medical conditions, number of family physician visits for 5 years prior to index date, healthcare utilization, income and use of other medications. Over one‐quarter of cases and controls were prescribed statins. Ever‐use of any statin was associated with lower risk of Total NHL (OR = 0.82, 95% CI 0.76–0.89) and of certain subtypes including diffuse large B‐cell lymphomas (DLBCL, OR = 0.77, 95% CI 0.65–0.92), plasma cell neoplasms (PCN, OR = 0.76, 95% CI 0.63–0.91) and other B‐cell NHL (0.75, 0.59–0.95). Analysis by statin type suggested that the association was limited to high potency statin and lipophilic statin users. No clear duration or dose–response relationships were observed. Our findings provide evidence that statin use can reduce the risk of DLBCL and plasma cell lymphomas, but not other NHL types. Further studies are warranted to verify these associations and to examine the biological mechanisms. [ABSTRACT FROM AUTHOR]

Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case–control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population‐based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8–10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk‐set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories >15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90–1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88–1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95–1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73–0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC. [ABSTRACT FROM AUTHOR]

Evidence on the effect of statin use on non-Hodgkin lymphoma (NHL) is not clear. We conducted a systematic review and meta-analysis to examine the associations between statin use and NHL risk and survival. We searched multiple literature sources up to October 2014 and identified 10 studies on the risk of diagnosis with NHL and 9 studies on survival. Random effects model was used to calculate pooled odds ratio (PORs) for risk and pooled hazard ratio (PHR) for survival. Heterogeneity among studies was examined using the Tau-squared and the I-squared (I2 ) tests. Statin use was associated with reduced risk for total NHL (POR = 0.82, 95% CI 0.69-0.99). Among statin users, there was a lower incidence risk for marginal zone lymphoma (POR = 0.54, 95% CI 0.31-0.94), but this was not observed for other types of NHL. However, statin use did not affect overall survival (PHR = 1.02, 95% CI 0.99-1.06) or event-free survival (PHR = 0.99, 95% CI 0.87-1.12) in diffuse large B-cell lymphoma. There is suggestive epidemiological evidence that statins decrease the risk of NHL, but they do not influence survival in NHL patients. Copyright © 2015 John Wiley & Sons, Ltd. [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]

Epidemiological study findings regarding the association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of non-Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta-analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I-squared (I(2)) tests; and sources of heterogeneity were explored using subgroup and meta-regression analyses. A total of 17 studies (12 case-control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90-1.22] or NHL subtypes including B-cell lymphoma, T-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54-0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89-1.17). Use of non-aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01-1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study is to assess whether atypical antipsychotic drug (AAD) use is associated with increased risk of falling among older (≥65 years) nursing home (NH) residents. Methods We conducted a nested case-control study using Resident Assessment Instrument Minimum Data Set 2.0 (RAI-MDS©) for NHs to identify falls, and population-based administrative healthcare databases to measure drug use and other study covariates. Cases ( n = 626) were NH residents in Winnipeg, Canada, who had a fall between 1 April 2005 and 31 March 2007, and were matched to four controls on age, sex, and length of NH stay ( n = 2388). Results While the odds of falling were statistically greater for AAD users versus nonusers (OR = 1.6, 95% CI 1.1-2.3), this association was type and dose dependent. Compared to nonusers, the odds of falling were greater for high-dose (>150 mg/day) quetiapine users and for high-dose (>2 mg/day) risperidone users. On the other hand, olanzapine (regardless of dose), low-dose quetiapine, and low-dose risperidone use were not associated with increased fall risk. Furthermore, the effect of AAD use, in general, on the risk of falling was significantly greater for people with wandering problems (OR = 1.8, 95% CI 1.1-3.1). Conclusions Our findings suggest greater risk of falling with high-dose quetiapine use and with high-dose risperidone use among NH residents. In addition, the effect of AAD use was greater for people who frequently wander. Further research is needed to confirm these findings, and to address other important unanswered questions about the safest dose and duration of AAD use. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Mahmud et al. (2012) Outbreaks of influenza-like illness in long-term care facilities in Winnipeg, Canada. Influenza and Other Respiratory Viruses 10.1111/irv.12052 Background Outbreaks of influenza-like illness (ILI) are common in long-term care facilities (LTCFs) and result in significant morbidity and mortality among residents. Objectives We describe patterns of reported ILI outbreaks in LTCFs in Winnipeg, Canada, and examine LTCF and outbreak characteristics that influence the clinical outcomes of these outbreaks. Methods We analyzed the electronic records of all ILI outbreaks reported by LTCFs in Winnipeg from 2003 to 2011. Outbreak duration, ILI attack rates among staff and residents, and residents' death rates were calculated by presumed viral etiology, staff vaccination rates, type of influenza chemoprophylaxis used, and time to notification to public health. Results Of a total of 154 reported outbreaks, most ( N = 80) were attributed to influenza, and these outbreaks tended to have higher attack and death rates among LTCF residents compared with outbreaks caused by other respiratory viruses (12) or those of unknown etiology (62). About 92% of residents and 38% of staff of the average LTCFs were vaccinated. Chemoprophylaxis was used in 57·5% of influenza outbreaks. Regardless of presumed viral etiology, outbreaks reported within 3 days of onset ended sooner and had lower attack and mortality rates among residents. Conclusions Influenza-like illness outbreaks still occur among highly immunized LTCF residents, so in addition to vaccination of staff and residents, it is important to maintain competent infection control practices. Early identification and notification to public health authorities and possibly early initiation of control measures could improve clinical outcomes of ILI outbreaks. [ABSTRACT FROM AUTHOR]

The association between use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of prostate cancer remains controversial despite many observational epidemiological studies. We conducted a systematic meta-analysis of these studies to examine both the strength and the consistency of the association, and to explore sources of variability between studies. We searched 12 computerized literature databases for reports published before June 2008 and included any epidemiologic studies where the outcome was prostate cancer incidence or mortality, and the exposure was use of NSAIDs. Studies that met the inclusion criteria comprised 10 case-control and 14 cohort studies with a total of 24,230 prostate cancer cases. Studies that assessed the effect of aspirin use on total prostate cancer had a pooled odds ratio (POR) of 0.83 (95%CI: 0.77-0.89), whereas those that assessed the effect of aspirin on advanced prostate cancer had a POR of 0.81 (0.72-0.92). Studies that examined the effects of non-aspirin NSAIDs or all NSAIDs were less consistent but still suggestive of reduced risks. However, most reviewed studies were limited by exposure and disease misclassification, by inadequate information on dose and duration of use and by the possibility of screening and other biases. In conclusion, the epidemiologic evidence for a protective effect of aspirin and other NSAID use against prostate cancer is suggestive but not conclusive. There is a need for well-designed observational studies with adequate exposure measurements, accurate case definition, attention to latency effects, and careful adjustment for screening and other biases. [ABSTRACT FROM AUTHOR]