Testing the joint health and safety committee assessment tool in the education sector.

Joint Health and Safety Committee (JHSC) effectiveness has been identified as an area of concern for Ontario's education sector. The JHSC Assessment Tool has been previously tested in hospitals with positive results. This study assessed the feasibility and usability of the JHSC Assessment Tool in the education sector. Members of multi-workplace JHSCs from Ontario school boards used the tool to assess their committees' effectiveness before, during and after a committee meeting with usability testing conducted pre and post meeting. Results suggested that the JHSC Assessment Tool was feasible to use during a regular JHSC meeting, groups were able to come to consensus on the majority of items, and usability scores were high overall. Participant feedback provided insight that informed the development of a version relevant to multi-workplace committees.

Workplace screening for hand dermatitis: a pilot study.

BACKGROUND: Health care workers (HCWs) are at increased risk for developing occupational skin disease (OSD) such as dermatitis primarily due to exposure to wet work. Identification of risk factors and workplace screening can help early detection of OSD to avoid the condition becoming chronic. AIMS: To determine risk factors and clinical findings for hand dermatitis using a workplace screening tool. METHODS: Employees at a large teaching hospital in Toronto, Canada, were invited to complete a two-part hand dermatitis screening tool. Part 1 inquired about hand hygiene practices and Part 2 comprised a visual assessment of participants' hands by a health professional and classification as (i) normal, (ii) mild dermatitis or (iii) moderate/severe dermatitis. Risk factors were determined using chi-square and Cochran-Armitage analysis on a dichotomous variable, where Yes represented either a mild or moderate/severe disease classification. RESULTS: There were 183 participants out of 643 eligible employees; response rate 28%. Mild or moderate/severe dermatitis was present in 72% of participants. These employees were more likely to work directly with patients, have worked longer in a health care setting, wash hands and change gloves more frequently, wear gloves for more hours per day, have a history of eczema or dermatitis and report a current rash on the hands or rash in the past 12 months. CONCLUSIONS: There was a high percentage of HCWs with dermatitis and risk factors for dermatitis. These findings argue for increased attention to prevention and early identification of hand dermatitis and support further testing of the workplace screening tool.

Epidemiology of vancomycin-resistant enterococci in Canadian hospitals (CANWARD study, 2007 to 2013).

Of 1,927 Enterococcus species isolates collected across Canada from 2007 to 2013, 80 (4.2%) were identified as vancomycin-resistant enterococci (VRE). VRE infections during this time tripled in Canadian hospitals, from 1.8% to 6.0% (P = 0.03). All VRE were Enterococcus faecium, with 90% possessing vanA. The prevalence of vanB decreased from 37.5% in 2007 to 0% in 2013 (P < 0.05). The VRE were multidrug resistant, but 70.6%, 86.3%, and 100% were susceptible to doxycycline, linezolid, and daptomycin, respectively.

In vitro activity of colistin (polymyxin E) against 3,480 isolates of gram-negative bacilli obtained from patients in Canadian hospitals in the CANWARD study, 2007-2008.

The in vitro activity of colistin was evaluated versus 3,480 isolates of gram-negative bacilli using CLSI broth microdilution methods. The MIC(90) of colistin was < or = 2 microg/ml against a variety of clinically important gram-negative bacilli, including Escherichia coli, Klebsiella spp., Enterobacter spp., Acinetobacter baumannii, and Pseudomonas aeruginosa. All multidrug-resistant (n = 76) P. aeruginosa isolates were susceptible to colistin (MIC, < or = 2 microg/ml). These data support a role for colistin in the treatment of infections caused by multidrug-resistant P. aeruginosa.

Quantifying the potential role of unmeasured confounders: the example of influenza vaccination.

BACKGROUND: The validity of non-randomized studies using healthcare databases is often challenged because they lack information on potentially important confounders, such as functional health status and socioeconomic status. In a study quantifying the effects of influenza vaccination among community-dwelling elderly we assessed whether additional information on not routinely available covariates was indeed associated with exposure to influenza vaccination and could, therefore, have led to residual confounding in healthcare databases. METHODS: We randomly selected 500 persons aged 65 years and older from the computerized Utrecht General Practitioner database. Information on exposure status and on demographics, co-morbidity status, prior healthcare use and medication use was extracted from the database. A questionnaire was used to obtain additional information on not routinely available risk factors [e.g. functional health status (SF-20), smoking status and alcohol consumption]. Missing data from the questionnaire was imputed and multivariable logistic regression analysis was applied to quantify the influence of covariates on the prediction of exposure to influenza vaccination. Within an existing dataset the potential impact of functional health status on the relation between influenza vaccination and mortality was simulated. RESULTS: We obtained questionnaire data from 365 of 500 (73%) subjects. The model including routinely available data from the database appeared accurate in predicting exposure to influenza vaccination (c-statistic 0.86, 95% CI: 0.82-0.89). Functional health status was the only additional characteristic measured with the questionnaire that was not similar in vaccinated and unvaccinated subjects. However, extending the multivariable regression model with functional health status did not significantly improve the prediction of exposure to influenza vaccination, nor did it affect the relation between influenza vaccination and mortality. CONCLUSION: The potential for unmeasured confounding on the association between influenza vaccination and health outcomes as quantified in healthcare databases seems small for non-randomized intervention studies within extensive and reliable databases.

Short-term exercise in aged Tg2576 mice alters neuroinflammation and improves cognition.

Exercise is a treatment paradigm that can ameliorate cognitive dysfunction in Alzheimer disease (AD) and AD mouse models. Since exercise is also known to alter the peripheral immune response, one potential mechanism for the cognitive improvement following exercise may be by modulating the inflammatory repertoire in the central nervous system. We investigated the effects of voluntary exercise in the Tg2576 mouse model of AD at a time-point at which pathology has already developed. Inflammatory mRNA markers are increased in sedentary Tg2576 mice versus non-transgenic controls. We demonstrate that short-term voluntary wheel running improved spatial learning in aged transgenic mice as compared to sedentary Tg2576 controls. Inflammatory profiles of the Tg2576 and non-transgenic mice were different following exercise with the non-transgenic mice showing a broader response as compared to the Tg2576. Notably, exercising Tg2576 exhibited increases in a few markers including CXCL1 and CXCL12, two chemokines that may affect cognition.

Macrolide resistance mechanisms among Streptococcus pneumoniae isolated over 6 years of Canadian Respiratory Organism Susceptibility Study (CROSS) (1998 2004).

BACKGROUND: Resistance to macrolides in Streptococcus pneumoniae arises primarily due to Erm(B) or Mef(A). Erm(B) typically confers high-level resistance to macrolides, lincosamides and streptogramin B (MLS(B) phenotype), whereas Mef(A) confers low-level resistance to macrolides only (M phenotype). The purpose of this study was to investigate the incidence of macrolide resistance mechanisms in Canadian isolates of S. pneumoniae obtained between 1998 and 2004. Furthermore, the genetic relatedness, serotype distribution and antibiotic susceptibility profile among S. pneumoniae isolates with dual erythromycin ribosomal methylase [Erm(B)] and efflux pump [Mef(A)] were analysed. METHODS: A total of 865 macrolide-resistant (erythromycin MIC > or = 1 mg/L) S. pneumoniae isolates were collected from the Canadian Respiratory Organism Susceptibility Study (CROSS) from 1998 to 2004. The presence of erm(B) and mef(A) was determined for each isolate by PCR; mutations in the genes coding for L4 and L22 ribosomal proteins and for 23S rRNA were identified by DNA sequencing. Each isolate containing both erm(B)- and mef(A)-mediated macrolide resistance was genotyped by PFGE and serotyped using the Quellung reaction with antisera. RESULTS: Of the 865 isolates studied, 404 (46.7%) were mef(A)-positive, 371 (42.9%) were erm(B)-positive, 50 (5.8%) were positive for both mef(A) and erm(B) and 40 (4.6%) were negative for both mef(A) and erm(B). Of the macrolide-resistant isolates negative for both mef(A) and erm(B), 22 (2.5%) contained 23S rRNA A2058G, A2059G or A2059C mutations, 7 (0.8%) contained 23S rRNA A2058G or A2059G mutations along with an S20N mutation in L4 ribosomal protein, and 1 isolate contained an E30K ribosomal protein mutation alone. Of the macrolide-resistant strains positive for both mef(A) and erm(B), 36 (72%) were multidrug-resistant (macrolide-, penicillin- and trimethoprim/sulfamethoxazole-resistant), 39 (78%) isolates belonged to serotype 19A or 19F and 36 (72%) belonged to one clonal complex (> or =80% genetic relatedness) genetically related to the Taiwan 19F-14 clone. CONCLUSIONS: The prevalence of efflux-based macrolide resistance in S. pneumoniae in Canada remained steady between 1998 and 2004. Macrolide resistance due to erm(B) decreased over the same time period, with a rapid increase in isolates with both erm(B) and mef(A) macrolide resistance.

Burden of upper respiratory illnesses among college and university students: 2002-2003 and 2003-2004 cohorts.

Upper respiratory illnesses, including colds and influenza-like illnesses, are common among college and university students. We have established an ongoing, serial cohort study to assess the occurrences of these illnesses among college and university students as well as the impact of these illnesses on overall health, school and work performance, and health care use. In this paper we report on the first 2 years of this study (2002-2003 and 2003-2004). For each year, more than 4000 students responded to the e-mail invitations to participate, and they provided more than 3000 person-seasons of follow-up information during the monthly surveys conducted November-April. In both years, colds and influenza-like illnesses were common and associated with significant numbers of bed days, reduced activity days, school and work loss, impaired school performance, and increased health care utilization. Efforts to prevent upper respiratory illnesses among college and university students could improve their health and reduce health care utilization during the winter months.

Do recommended high-risk adults benefit from a first influenza vaccination?

It is unknown whether a first influenza vaccination protects high-risk adults from severe morbidity and mortality during influenza epidemics. As part of the PRISMA nested case-control study, we aimed to evaluate the effectiveness of first-time and repeat influenza vaccinations in adult persons recommended for vaccination aged between 18 and 64 years during the 1999-2000 influenza A epidemic. After adjustments, 69% of hospitalizations for acute respiratory or cardiovascular disease or death were prevented in first-time vaccinees (95% percent confidence interval [95% CI]: 8-90%). The corresponding figure in persons who were vaccinated before was 85% (95% CI: 36-96%). Adult persons with high-risk medical conditions can substantially benefit from a first and repeat influenza vaccination prior to an epidemic.

Influence of clinical outcome and outcome period definitions on estimates of absolute clinical and economic benefits of influenza vaccination in community dwelling elderly persons.

Studies assessing the clinical and economic benefits of vaccination in the elderly have used different clinical outcomes (e.g. hospitalizations for pneumonia or influenza versus hospitalizations for respiratory and cardiovascular causes) and different outcome periods (e.g. peak versus total influenza season) on which to base estimates of clinical effectiveness and cost effectiveness. We explored the implications of these varying approaches by comparing two health economic analysis models of influenza vaccination of community-dwelling elderly persons. We developed computerized models using clinical data from 3 large US HMOs for the 1998-1999 and 1999-2000 influenza seasons. The primary health economic model used a broad definition of clinical events and outcome period and included hospitalizations for all respiratory and cardiovascular events that occurred during the entire influenza season. The alternative model used more restrictive definitions and included pneumonia or influenza hospitalizations occurring during the peak influenza season. The results of Monte Carlo simulation showed that, with the more inclusive primary model, influenza vaccination resulted in net medical care cost savings due to fewer respiratory or cardiovascular hospitalizations of Dollars 71/person vaccinated (5th-95th percentile Dollars 32-118) and net savings of Dollars 809/year of life saved (5th-95th percentile Dollars 331-1450). In contrast, the alternate model found costs of Dollars 3.50/person vaccinated (5th-95th percentile Dollars -11 to 5) and net costs of Dollars 91/year of life saved (5th-95th percentile Dollars -309 to 126). Our findings confirm that influenza vaccination of the elderly is most likely cost saving and supports policies and programs that advocate routine immunization of all persons 65 and older. They also highlight how different outcome definitions can influence the results of health economic analyses.

A nested case-control study of influenza vaccination was a cost-effective alternative to a full cohort analysis.

OBJECTIVE: In the absence of trial results that are applicable to the target population, nested case-control studies might be an alternative to full-cohort analysis. We compared relative and absolute estimates of associations in an influenza vaccine study using both designs. STUDY DESIGN AND SETTING: Data from elderly persons enrolled during six consecutive influenza seasons were used (147,551 person-periods). The endpoints "hospitalization for pneumonia or influenza" (P&I) or "death" were used combined and separately to define three types of cases. Controls for the case-control samples were randomly selected from the remainder of the total cohort at different ratios (1:1 to 1:4). Logistic regression analysis was used to assess adjusted vaccine effectiveness (VE). Sampling fractions were used to determine the number needed to treat to prevent one outcome. Receiver-operator-curve analysis was conducted to estimate the area under the curve (AUC) as a measure of discriminative capacity of the prognostic model. RESULTS: In all, 978 P and I hospitalizations and 1,339 deaths were observed. The adjusted estimates of relative estimates (VE, AUC) and their corresponding 95% confidence intervals were virtually the same using both study designs, notably when the case-control ratio was high (1:4). CONCLUSION: A nested case-control design can provide valid and precise estimates of associations and is a cost-effective alternative for full-cohort analysis.

Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the ataxin-7 gene. In humans, SCA7 is characterized by marked anticipation due to intergenerational repeat instability with a bias toward expansion, and is thus regarded as the most unstable of the polyglutamine diseases. To study the molecular basis of CAG/CTG repeat instability and its pathological significance, we generated lines of transgenic mice carrying either a SCA7 cDNA construct or a 13.5 kb SCA7 genomic fragment with 92 CAG repeats. While the cDNA transgenic mice showed little intergenerational repeat instability, the genomic fragment transgenic mice displayed marked intergenerational instability with an obvious expansion bias. We then went on to generate additional lines of genomic fragment transgenic mice, and observed that deletion of the 3' genomic region significantly stabilized intergenerational transmission of the SCA7 CAG92 repeat. These results suggest that cis-information present on the genomic fragment is driving the instability process. As the SCA7 genomic fragment contains a large number of replication-associated motifs, the presence of such sequence elements may make the SCA7 CAG repeat region more susceptible to instability. Small-pool and standard PCR analysis of tissues from genomic fragment mice revealed large repeat expansions in their brains and livers, but no such changes were found in any tissues from cDNA transgenic mice that have been shown to undergo neurodegeneration. As large somatic repeat expansions are absent from the brains of SCA7 cDNA mice, our results indicate that neurodegeneration can occur without marked somatic mosaicism, at least in these mice.

Confounding by indication in non-experimental evaluation of vaccine effectiveness: the example of prevention of influenza complications.

Randomised allocation of vaccine or placebo is the preferred method to assess the effects of the vaccine on clinical outcomes relevant to the individual patient. In the absence of phase 3 trials using clinical end points, notably post-influenza complications, alternative non-experimental designs to evaluate vaccine effects or safety are often used. The application of these designs may, however, lead to invalid estimates of vaccine effectiveness or safety. As patients with poor prognosis are more likely to be immunised, selection for vaccination is confounded by patient factors that are also related to clinical end points. This paper describes several design and analytical methods aimed at limiting or preventing this confounding by indication in non-experimental studies. In short, comparison of study groups with similar prognosis, restriction of the study population, and statistical adjustment for dissimilarities in prognosis are important tools and should be considered. Only if the investigator is able to show that confounding by indication is sufficiently controlled for, results of a non-experimental study may be of use to direct an evidence based vaccine policy.

Generalist and subspecialist physicians' knowledge, attitudes, and practices regarding influenza and pneumococcal vaccinations for elderly and other high-risk patients: a nationwide survey.

BACKGROUND: Influenza and pneumococcal vaccination rates remain too low. This survey assessed generalist and subspecialist physicians' knowledge, attitudes, and practices regarding influenza and pneumococcal vaccinations for high-risk patients. METHODS: A self-administered questionnaire was mailed to 6000 physicians randomly selected from a national database. RESULTS: After 3 mailings, 1874 physicians (32%) of the 5858 eligible responded. Although most physicians thought that it was very important for their high-risk patients be current on influenza and pneumococcal vaccinations, only 86% and 75% of generalists and subspecialists, respectively, very strongly recommended influenza vaccinations to their elderly patients and only 81% and 64%, respectively, very strongly recommended pneumococcal vaccinations to their elderly patients (P<.001 for both). After multivariate logistic regression, factors significantly associated with strongly recommending vaccinations to elderly patients in the influenza and pneumococcal vaccination models included female sex of provider, the provider having received an influenza vaccination, the provider's beliefs about vaccine effectiveness and cost-effectiveness, a patient's risk for illness, and ease of targeting patients. In addition, generalists were more likely than subspecialists to strongly recommend pneumococcal vaccinations to their patients. Patient reminders, special clinics, and standing orders were each used by fewer than 30% of respondents, although generalists were more likely than subspecialists to use such strategies. CONCLUSIONS: Nontrivial proportions of generalist and subspecialist physicians fail to strongly recommend influenza and pneumococcal vaccinations to their elderly and high-risk patients. Other effective strategies for promoting vaccine delivery are also used relatively infrequently. These findings suggest areas for improvement if vaccination rates are to reach national goals.

Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans.

This study developed methods and determined the impact of influenza vaccination on elderly persons in 3 large health plans: Kaiser Permanente Northwest, HealthPartners, and Oxford Health Plans. Data for the 1996-1997 and 1997-1998 seasons were extracted from administrative databases. Subjects were health plan members > or = 65 years old. Comorbid conditions collected from the preceding year were used for risk adjustment with logistic regression. The virus-vaccine match was excellent for year 1 and fair for year 2. Both years, during peak and total periods, vaccination reduced all causes of death and hospitalization for pneumonia and influenza: hospitalizations were reduced by 19%-20% and 18%-24% for years 1 and 2, respectively, and deaths were reduced by 60%-61% and 35%-39% for the same periods. These results show that all elderly persons should be immunized annually for influenza. The methods used in this study are an efficient cost-effective way to study vaccine impact and similar questions.

Live attenuated influenza virus vaccines: new options for the prevention of influenza.

Live attenuated influenza virus (LAIV) vaccines present new possibilities for the prevention and control of influenza. Administered intranasally, LAIV vaccines offer a needle-free route of administration. These investigational vaccines have also been shown to be safe and effective in children and healthy working adults. A 2-year placebo-controlled trial among young children (1996-1997 and 1997-1998 influenza seasons) demonstrated that LAIV vaccine was associated with a 92% reduction in laboratory-confirmed cases of influenza. Vaccination also significantly reduced episodes of otitis media and antibiotic use. In a placebo-controlled trial among healthy working adults during the 1997-1998 season, LAIV vaccine significantly reduced episodes of febrile upper respiratory tract illness and illness-associated work loss, health-care use, and antibiotic use. Seventy percent of study participants self-administered the vaccine. An economic analysis of the benefits of LAIV vaccine in this population suggests that the break-even cost for LAIV vaccine and its administration for healthy working adults would be about $39. For both children and healthy adults, LAIV vaccine provided substantial protection during the 1997-1998 season when the predominant circulating virus, the A/Sydney variant, was not contained in the vaccine. Studies are still underway to evaluate the potential incremental benefits of LAIV vaccine in addition to inactivated vaccine in high-risk populations. LAIV vaccines will be an important addition to the armamentarium for fighting influenza.

Bcl-2 family protein behavior in frontotemporal dementia implies vascular involvement.

Frontotemporal dementia (FTD) is a neurodegenerative disease associated with aging for which the etiology is unclear. Relatively little is known about the pathology of this disease, which has only recently been a topic of investigation for dementia researchers. Though the known pathology of FTD includes neuron loss, the mechanism of neuronal death is not known. In this study, the authors investigated apoptotic pathways as a possible mechanism of neuronal cell death in FTD. They evaluated immunoreactivity for Bcl-2 family protein members Bcl-x and Bax in postmortem frontal cortex from FTD, AD, and control cases. Bcl-x(L), Bcl-x(S), and Bax all exhibited altered immunoreactivity in FTD cases as compared with control cases. Bcl-x immunoreactivity varied widely among both controls and FTD cases. However, Bcl-x(L) showed strong white matter immunoreactivity in all FTD cases, whereas white matter immunoreactivity was absent in controls. These trends in Bcl-x immunoreactivity suggest a strong white matter involvement in the pathology of FTD. Bax immunoreactivity also varied across all cases. Bax immunoreactivity was observed in terminal transferase dUTP nick ending labeling (TUNEL) positive neurons in both FTD and AD cases. However, one notable finding was immunoreactivity to Bax in astrocytes of FTD cases, as well as endothelial cells of the cerebrovasculature. Neither astrocytic nor endothelial cell immunoreactivity to Bax was exhibited in control or AD cases. Because Bax is a pro-apoptotic protein, this finding suggests the presence of a cerebrovascular component in the pathology of FTD. These findings, coupled with the proposed functions of the Bcl-2 family proteins, suggest that an apoptotic pathway may be responsible for neuron, and possibly astrocyte, death in FTD.

Macrolide-resistant Streptococcus pneumoniae in Canada during 1998-1999: prevalence of mef(A) and erm(B) and susceptibilities to ketolides.

In this study (1998-1999), we collected 215 macrolide-resistant Streptococcus pneumoniae isolates from an ongoing Canadian Respiratory Organism Surveillance Study involving 23 centers representing all regions of Canada. The prevalence of erythromycin-resistant S. pneumoniae was 8% (215 of 2,688). Of the 215 isolates, 48.8% (105 of 215) were PCR positive for mef(A) and 46.5% (100 of 215) were PCR positive for erm(B). The ketolides telithromycin and ABT-773 demonstrated excellent activity against both mef(A) (MIC for 90% of strains [MIC(90)], 0.06 and 0.03 microg/ml, respectively) and erm(B) (MIC(90), 0.06 and 0.03 microg/ml, respectively) strains of S. pneumoniae.

Cost-benefit analysis of a strategy to vaccinate healthy working adults against influenza.

BACKGROUND: Influenza is a major cause of illness, disruption to daily life, and work absenteeism among healthy working adults aged between 18 and 64 years. This group is not included among the traditional priority groups for annual vaccination. Immunization rates remain low. OBJECTIVE: To assess the economic implications of a strategy for annual vaccination of this group. METHODS: Using the societal perspective, this cost-benefit analysis included the direct and indirect costs associated with vaccination as well as the direct and indirect costs prevented by vaccination. Clinical and economic variable estimates were derived primarily from the published literature. For this model, it was assumed that vaccination occurred in efficient, low-cost settings such as at the work site. Monte Carlo simulation was used to calculate the mean net costs or savings along with the 95% probability interval, and sensitivity analyses explored the sensitivity of the cost model to different values of the input variables. RESULTS: Vaccinating healthy working adults was on average cost saving, with mean savings of $13.66 per person vaccinated (95% probability interval: net savings of $32.97 to net costs of $2.18), with vaccination generating net savings 95% of the time. The model was most sensitive to the influenza illness rate, the work absenteeism rate due to influenza, and hourly wages. In the worst-case scenario vaccination was not cost saving. Vaccination also generated net costs to society during years with a poor vaccine-circulating virus strain match. In all of the other sensitivity analysis scenarios, vaccination was cost saving. CONCLUSION: Influenza vaccination of healthy working adults on average is cost saving. These findings support a strategy of routine, annual vaccination for this group, especially when vaccination occurs in efficient and low-cost sites.