Mark Loeb

McMaster University, Hamilton, Ontario, Canada

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Publications (158)751.2 Total impact

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    ABSTRACT: Infection management in advanced dementia has important implications for (1) providing high-quality care to patients near the end of life and (2) minimizing the public health threat posed by the emergence of multidrug-resistant organisms (MDROs).
    JAMA Internal Medicine 08/2014; · 10.58 Impact Factor
  • Influenza and Other Respiratory Viruses 07/2014; · 1.47 Impact Factor
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    ABSTRACT: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D3 supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students.
    BMC Infectious Diseases 05/2014; 14(1):273. · 3.03 Impact Factor
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    ABSTRACT: Fewer Canadian seniors are vaccinated against pneumococcal disease than receive the influenza vaccine annually. Improved understanding of factors influencing pneumococcal vaccination among older adults is needed to improve vaccine uptake.
    BMC Public Health 05/2014; 14(1):442. · 2.08 Impact Factor
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    ABSTRACT: To describe T-cell and natural killer (NK) cell phenotypes within nursing home elderly. Nursing home elderly were recruited from four nursing homes in Hamilton, Ontario between September 2010 and December 2011. Healthy adults were recruited from McMaster University between September 2011 and December 2011. Nursing home elderly >=65 years were eligible; those on immunosuppressive medications were excluded. Healthy adults >=18-64 years were eligible. CD8+ and CD4+ T-cells% and their subsets, T-regs% and NK cell subset% were compared between the nursing home elderly and healthy adults. 262 nursing home elderly were enrolled; median age 87 years and 81% were female. 16 healthy adults were enrolled; median age 31 and 50% were female. There was no significant difference between CD8+ T-cell% in nursing home and healthy adults (median 17.1 versus 18.0, p = 0.56), however there were fewer naive CD8 + T-cell% (median 0.9 versus 5.2, p < 0.001), more terminally differentiated CD8 + T-cell% (median 7.3 versus 4.1, p = 0.004) and more senescent T-cell% (median 5.3 versus 3.1, p = 0.04) in the nursing home elderly. There were more CD4+ T-cell% in the nursing home elderly compared to healthy adults (median 45.5 versus 37.1, p = 0.001). Nursing home elderly had a higher CD4+/CD8+ ratio than healthy adults (2.6 versus 1.9, p = 0.048), higher T-reg% (median 1.8 versus 0.8, p < 0.001) and increased mature NK cell% (median 12.1 versus 5.4, p = 0.001) compared to healthy adults. Differences in naive CD8+ T-cells, terminally differentiated and senescent CD8+ T-cells, T-regs and NK cell subsets were similar to studies involving community dwelling elderly. In contrast, the CD4+/CD8+ ratio was higher in nursing home elderly.
    BMC Geriatrics 04/2014; 14(1):50. · 2.34 Impact Factor
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    ABSTRACT: Lack of appropriate reporting of methodological details has previously been shown to distort risk of bias assessments in randomized controlled trials. The same might be true for observational studies. The goal of this study was to compare the Newcastle-Ottawa Scale (NOS) assessment for risk of bias between reviewers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza. Cohort studies included in the systematic review and published between 2008-2011 were included. The corresponding or first authors completed a survey covering all NOS items. Results were compared with the NOS assessment applied by reviewers of the systematic review. Inter-rater reliability was calculated using kappa (K) statistics. Authors of 65/182 (36%) studies completed the survey. The overall NOS score was significantly higher (p < 0.001) in the reviewers' assessment (median = 6; interquartile range [IQR] 6-6) compared with those by authors (median = 5, IQR 4-6). Inter-rater reliability by item ranged from slight (K = 0.15, 95% confidence interval [CI] = -0.19, 0.48) to poor (K = -0.06, 95% CI = -0.22, 0.10). Reliability for the overall score was poor (K = -0.004, 95% CI = -0.11, 0.11). Differences in assessment and low agreement between reviewers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic reviews.
    BMC Medical Research Methodology 04/2014; 14(1):45. · 2.21 Impact Factor
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    ABSTRACT: Rationale: The microbial communities inhabiting the upper respiratory tract protect from respiratory infection. The maturity of the immune system is believed to be a major influence on the composition of the microbiome and, in youth, the microbiota and immune system are believed to mature in tandem. With age, immune function declines and susceptibility to respiratory infections is increases. Whether these changes contribute to the microbial composition of the respiratory tract is unknown. Objectives: Our goal was to determine whether the resident microbes of the upper respiratory tract differ between mid-aged adults (18-40 yrs) and the elderly (>65 yrs). Methods: Microbiomes of the anterior nares and oropharynx of elderly individuals were evaluated by 16S rRNA gene sequencing. These communities were compared to data on mid-aged adults obtained from the Human Microbiome Project. Measurements and Main Results: The microbiota of the elderly showed no associations with gender, co-morbidities, residence, or vaccinations. Comparisons of mid-aged adults and elderly demonstrated significant differences in the microbial composition of the anterior nares and oropharynx with age, including a population in the anterior nares of the elderly that more closely resembled the oropharynx than the anterior nares of adults. The elderly oropharyngeal microbiota were characterized by increased abundance of streptococci, specifically, Streptococcus salivarius group species, but not Streptococcus pneumoniae, carriage of which was low (<3% of participants) as demonstrated by PCR (4/123). Conclusions: The Microbial populations of the upper respiratory tract in mid-aged adults and the elderly differ; it is possible these differences contribute to the increased risk of respiratory infections experienced by the elderly.
    Annals of the American Thoracic Society. 03/2014;
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    ABSTRACT: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of 'high dose' (2000 IU/day) vs. 'standard dose' (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of 'high dose' vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI.Methods/design: This study is a pragmatic randomized controlled trial. Over 3 successive winters we will recruit 750 healthy children 1-5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids! Children will be randomized to the 'standard dose' or 'high dose' oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers and place Canada at the forefront of pediatric vitamin D health outcomes research.
    BMC Pediatrics 02/2014; 14(1):37. · 1.98 Impact Factor
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    ABSTRACT: Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.
    PLoS ONE 01/2014; 9(8):e104522. · 3.73 Impact Factor
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    ABSTRACT: Vaccination is an important strategy in the prevention of influenza, but immunologic response to vaccination can vary widely. Recent studies have shown an association between serum 25-hydroxyvitamin D (25[OH]D) levels and immune function. The purpose of this study was to determine if serum 25(OH)D level correlates with influenza vaccine immunogenicity in children and adolescents. We conducted a prospective cohort study of children age 3 to 15 years of age vaccinated with trivalent influenza vaccine (A/Brisbane/59/2007[H1N1]-like virus, A/Brisbane/10/2007 [H3N2]-like virus and B/Florida/4/2006-like virus) in Hutterite communities in Alberta, Saskatchewan and Manitoba. Serum 25(OH)D levels were measured at baseline and immunogenicity was assessed using hemagluttination inhibition (HAI) titers done at baseline and 3-5 weeks post vaccination. Logistic regression was used to assess the relationship between serum 25(OH)D level as both a continuous and dichotomous variable and seroprotection, seroconversion, fold increase in geometric mean titer (GMT) and post vaccination titer. A total of 391 children and adolescents were included in the study and 221 (57% had post-vaccination HAI titers. The median serum 25(OH)D level was 61.0 nmol/L (Interquartile range [IQR] 50.0, 71.0). No relationship was found between serum 25(OH)D level and seroprotection (post-vaccination titer ≥40 and ≥320) or seroconversion (post-vaccination titer ≥40 for participants with pre-vaccine titer <10 or four-fold rise in post-vaccination titer for those with a pre-vaccine titer ≥10). Serum 25(OH)D level was not associated with influenza vaccine immunogenicity in otherwise healthy children and adolescents. Other strategies to enhance influenza vaccine response should continue to be evaluated in this population. The role of serum 25(OH)D level in vaccine responsiveness in other populations, especially those hyporesponsive to influenza vaccination, requires further study.
    PLoS ONE 01/2014; 9(1):e83553. · 3.73 Impact Factor
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    ABSTRACT: BACKGROUND:A hip fracture causes bleeding, pain and immobility, and initiates inflammatory, hypercoagulable, catabolic and stress states. Accelerated surgery may improve outcomes by reducing the duration of these states and immobility. We undertook a pilot trial to determine the feasibility of a trial comparing accelerated care (i.e., rapid medical clearance and surgery) and standard care among patients with a hip fracture. METHODS:Patients aged 45 years or older who, during weekday, daytime working hours, received a diagnosis of a hip fracture requiring surgery were randomly assigned to receive accelerated or standard care. Our feasibility outcomes included the proportion of eligible patients randomly assigned, completeness of follow-up and timelines of accelerated surgery. The main clinical outcome, assessed by data collectors and adjudicators who were unaware of study group allocations, was a major perioperative complication (i.e., a composite of death, preoperative myocardial infarction, myocardial injury after noncardiac surgery, pulmonary embolism, pneumonia, stroke, and life-threatening or major bleeding) within 30 days of randomization. RESULTS:Of patients eligible for inclusion, 80% consented and were randomly assigned to groups (30 to accelerated care and 30 to standard care) at 2 centres in Canada and 1 centre in India. All patients completed 30-day follow-up. The median time from diagnosis to surgery was 6.0 hours in the accelerated care group and 24.2 hours in the standard care group (p < 0.001). A major perioperative complication occurred in 9 (30%) of the patients in the accelerated care group and 14 (47%) of the patients in the standard care group (hazard ratio 0.60, 95% confidence interval 0.26-1.39). INTERPRETATION:These results show the feasibility of a trial comparing accelerated and standard care among patients with hip fracture and support a definitive trial. Trial registration: ClinicalTrials.gov, no. NCT01344343.
    Canadian Medical Association Journal 11/2013; · 6.47 Impact Factor
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    Mark Loeb
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    ABSTRACT: Understanding mechanisms by which genetic variants predispose to complications of infectious diseases can lead to important benefits including the development of biomarkers to prioritize vaccination or prophylactic therapy. Family studies, candidate genes in animal models, and the absence of well-defined risks where the complications are rare all can point to genetic predisposition. The most common approach to assessing genetic risk is to conduct an association study, which is a case control study using either a candidate gene approach or a genome wide approach. Although candidate gene variants may focus on potentially causal variants, because other variants across the genome are not tested these studies frequently cannot be replicated. Genome wide association studies need a sizable sample and usually do not identify causal variants but variants which may be in linkage disequilibrium to the actual causal variant. There are many pitfalls that can lead to bias in such studies, including misclassification of cases and controls, use of improper phenotypes, and genotyping errors. These studies have been limited to common genes and rare variants may not be detected. As the use of next generation sequencing becomes more common, it can be anticipated that more variants will be confirmed. The purpose of this review article is to address the issue of genomics in infectious diseases with an emphasis on the host. Although there are a plentitude of studies that focus on the molecular characteristics of pathogens, there are far fewer studies that address the role of human genetics in the predisposition to infection or more commonly its complications. This paper will review both the approaches used to study host genetics in humans and the pitfalls associated with some of these methods. The focus will be on human disease and therefore discussion of the use of animal models will be limited to those where there are genes that have been replicated in humans. The paper will focus on common genetic variants that account for complex traits such as infectious diseases using examples from flaviviruses.
    Infection & chemotherapy. 09/2013; 45(3):253-259.
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    ABSTRACT: To determine the need of isolation precautions upon admission, we created and tested an algorithm based on a total of 474 patients with a history of carriage of an antibiotic-resistant organism. Using the algorithm upon patient admission reduced unnecessary isolations by almost 60% while maintaining a high sensitivity to predict persisting antibiotic-resistant organism colonization.
    American journal of infection control 07/2013; · 3.01 Impact Factor
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    ABSTRACT: To determine if newer influenza vaccines can safely improve seroprotection rates of older adults, we compared three licensed trivalent inactivated vaccines (TIVs) in a randomized, controlled trial with evaluator blinding. Participants were non-frail adults ≥ 65 y old, annually TIV-immunized. Study vaccines included intradermal (IDV), MF59-adjuvanted (ADV) and subunit (TIV) formulations of equal potency and strain composition. Blood was obtained before vaccination (V1) and 21 (V2) and 180 d (V3) afterward and tested by hemagglutination inhibition (HAI) assay. Safety diaries were completed daily by participants and specific tolerability questions were posed regarding injections and symptoms. In total, 911 participants were immunized and 887 (97.4%) completed V3. Groups had similar demographics. General symptom rates post-vaccination were similar among groups. Rates of injection site redness after IDV/ADV/TIV were 75%/13%/13% and rates of pain were 29%/38%/20%, respectively, but each vaccine was well tolerated, with symptoms causing little bother. Baseline antibody titers did not differ significantly among groups but B/Brisbane titers were too high for meaningful response assessments. At V2, seroprotection rates (HAI titer ≥ 40) were highest after ADV, the rate advantage over IDV and TIV being significant at 11.8% and 11.4% for H3N2 and 10.2% and 12.5% for H1N1, respectively. At day 180, seroprotection rates had declined ~25% and no longer differed significantly among groups. While IDV and TIV were also well tolerated, ADV induced modestly higher antibody titers in seniors to influenza A strains at 3 weeks but not 6 mo post-vaccination. Immune responses to IDV and TIV were similar in this population.
    Human vaccines & immunotherapeutics. 07/2013; 9(11).
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    ABSTRACT: Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains. We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk x 100%). We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%). The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.
    BMC Medicine 06/2013; 11(1):153. · 6.68 Impact Factor
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    ABSTRACT: Background. Vitamin D may be important for immune function. Studies to date have shown an inconsistent association between vitamin D and infection with respiratory viruses. The purpose of this study was to determine if serum 25-hydroxyvitamin D (25[OH]D) was associated with laboratory confirmed viral respiratory tract infections (RTIs) in children. Methods. Serum 25(OH)D levels were measured at baseline and children from Canadian Hutterite communities were followed prospectively during the respiratory virus season. Nasopharyngeal specimens were obtained if symptoms developed and infections were confirmed using polymerase chain reaction. The association between serum 25(OH)D and time to laboratory confirmed viral RTI was evaluated using a Cox proportional hazards model. Results. 743 children aged 3 to 15 years were followed between December 22, 2008 and June 23, 2009. The median serum 25(OH)D level was 62.0 nmol/L (interquartile range [IQR] 51.0, 74.0). A total of 229 participants (31%) developed at least one laboratory confirmed viral RTI. Younger age and lower serum 25(OH)D levels were associated with increased risk of viral RTI. Serum 25(OH)D levels lower than 75 nmol/L increased the increased the risk of viral RTI by 50% (Hazard ratio [HR] 1.51, 95% CI 1.10, 2.07, p=0.011) and levels lower than 50 nmol/L increased the risk by 70% (HR 1.67, 95% CI 1.16, 2.40, P=0.006). Conclusion. Lower serum 25(OH)D levels were associated with increased risk of laboratory confirmed viral RTI in children from Canadian Hutterite communities. Intervention studies evaluating the role of vitamin D supplementation to reduce the burden of viral RTIs are warranted.
    Clinical Infectious Diseases 05/2013; · 9.37 Impact Factor
  • Dominik Mertz, Mark Loeb
    Annals of surgery 04/2013; · 7.90 Impact Factor
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    ABSTRACT: This prospective cohort study, performed during the 2009 influenza A(H1N1) pandemic, was aimed to determine whether adults working in acute care hospitals were at higher risk than other working adults for influenza and to assess risk factors for influenza among health care workers (HCWs). We assessed the risk for influenza among 563 HCWs and 169 non-HCWs using PCR to test nasal swab samples collected during acute respiratory illness; results for 13 (2.2%) HCWs and 7 (4.1%) non-HCWs were positive for influenza. Influenza infection was associated with contact with family members who had acute respiratory illnesses (adjusted odds ratio [AOR]: 6.9, 95% CI 2.2-21.8); performing aerosol-generating medical procedures (AOR 2.0, 95% CI 1.1-3.5); and low self-reported adherence to hand hygiene recommendations (AOR 0.9, 95% CI 0.7-1.0). Contact with persons with acute respiratory illness, rather than workplace, was associated with influenza infection. Adherence to infection control recommendations may prevent influenza among HCWs.
    Emerging Infectious Diseases 04/2013; 19(4):606-15. · 6.79 Impact Factor
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    ABSTRACT: As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA-DR(-) MDSCs across three cohorts: healthy adults (19-59 years old), community-dwelling seniors (61-76 years old), and frail elderly (67-99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF-α, IL-6, and IL-1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age-related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age-related pathologies.
    Journal of leukocyte biology 01/2013; · 4.99 Impact Factor
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    ABSTRACT: To evaluate risk factors for severe outcomes in patients with seasonal and pandemic influenza. Systematic review. Observational studies reporting on risk factor-outcome combinations of interest in participants with influenza. Outcomes included death, ventilator support, admission to hospital, admission to an intensive care unit, pneumonia, and composite outcomes. Medline, Embase, CINAHL, Global Health, and the Cochrane Central Register of Controlled Trials to March 2011. Newcastle-Ottawa scale to assess the risk of bias. GRADE framework to evaluate the quality of evidence. 63 537 articles were identified of which 234 with a total of 610 782 participants met the inclusion criteria. The evidence supporting risk factors for severe outcomes of influenza ranged from being limited to absent. This was particularly relevant for the relative lack of data for non-2009 H1N1 pandemics and for seasonal influenza studies. Limitations in the published literature included lack of power and lack of adjustment for confounders was widespread: adjusted risk estimates were provided for only 5% of risk factor-outcome comparisons in 39 of 260 (15%) studies. The level of evidence was low for "any risk factor" (odds ratio for mortality 2.77, 95% confidence interval 1.90 to 4.05 for pandemic influenza and 2.04, 1.74 to 2.39 for seasonal influenza), obesity (2.74, 1.56 to 4.80 and 30.1, 1.74 to 2.39), cardiovascular diseases (2.92, 1.76 to 4.86 and 1.97, 1.06 to 3.67), and neuromuscular disease (2.68, 1.91 to 3.75 and 3.21, 1.84 to 5.58). The level of evidence was very low for all other risk factors. Some well accepted risk factors such as pregnancy and belonging to an ethnic minority group could not be identified as risk factors. In contrast, women who were less than four weeks post partum had a significantly increased risk of death from pandemic influenza (4.43, 1.24 to 15.81). The level of evidence to support risk factors for influenza related complications is low and some well accepted risk factors, including pregnancy and ethnicity, could not be confirmed as risks. Rigorous and adequately powered studies are needed.
    BMJ (online) 01/2013; 347:f5061. · 17.22 Impact Factor

Publication Stats

3k Citations
751.20 Total Impact Points

Institutions

  • 1997–2014
    • McMaster University
      • • Department of Pathology and Molecular Medicine
      • • Department of Clinical Epidemiology and Biostatistics
      • • Department of Medicine
      • • Faculty of Health Sciences
      Hamilton, Ontario, Canada
  • 2009–2013
    • SickKids
      • Division of Infectious Diseases
      Toronto, Ontario, Canada
    • Université de Sherbrooke
      • Center for Research on Aging
      Sherbrooke, Quebec, Canada
    • The University of Calgary
      • Department of Community Health Sciences
      Calgary, Alberta, Canada
  • 2010
    • St. Jude Children's Research Hospital
      Memphis, Tennessee, United States
  • 2005–2010
    • University of Toronto
      • Department of Family and Community Medicine
      Toronto, Ontario, Canada
  • 2007
    • Hamilton Health Sciences
      Hamilton, Ontario, Canada
  • 2006
    • University Health Network
      • Division of Experimental Therapeutics
      Toronto, Ontario, Canada
  • 2002–2004
    • Sunnybrook Health Sciences Centre
      • Division of Microbiology
      Toronto, Ontario, Canada
  • 2003
    • Mount Sinai Hospital, Toronto
      • Department of Microbiology
      Toronto, Ontario, Canada