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1.  The Urinary Cytokine/Chemokine Signature of Renal Hyperfiltration in Adolescents with Type 1 Diabetes 
PLoS ONE  2014;9(11):e111131.
Urinary cytokine/chemokine levels are elevated in adults with type 1 diabetes (T1D) exhibiting renal hyperfiltration. Whether this observation extends to adolescents with T1D remains unknown. Our first objective was to determine the relationship between hyperfiltration and urinary cytokines/chemokines in normotensive, normoalbuminuric adolescents with T1D using GFRcystatin. Our second aim was to determine the relationship between urine and plasma levels of inflammatory biomarkers, to clarify the origin of these factors.
Urine and serum cytokines/chemokines (Luminex platform) and GFRcystatin were measured in normofiltering (n = 111, T1D-N, GFR<135 ml/min/1.73 m2) and hyperfiltering (n = 31, T1D-H, GFR≥135 ml/min/1.73 m2) adolescents with T1D (ages 10–16), and in age and sex matched healthy control subjects (HC, n = 59).
We noted significant step-wise increases in urinary cytokine/chemokine excretion according to filtration status with highest levels in T1D-H, with parallel trends in serum analyte concentrations. After adjusting for serum glucose at the time of sampling, differences in urinary cytokine excretion were not statistically significant. Only serum IL-2 significantly differed between HC and T1D (p = 0.0076).
Hyperfiltration is associated with increased urinary cytokine/chemokine excretion in T1D adolescents, and parallel trends in serum cytokine concentration. The GFR-associated trends in cytokine excretion may be driven by the effects of ambient hyperglycemia. The relationship between hyperfiltration, glycemia, and variations in serum and urine cytokine expression and their impact on future renal and systemic vascular complications requires further study.
PMCID: PMC4230911  PMID: 25392936
2.  Use of mental health care for nonpsychotic conditions by immigrants in different admission classes and by refugees in Ontario, Canada 
Open Medicine  2014;8(4):e136-e146.
Most Canadian newcomers are admitted in the economic, family, or refugee class, each of which has its own selection criteria and experiences. Evidence has shown various risks for mental health disorders across admission classes, but the respective service-use patterns for people in these classes are unknown. In this study, we compared service use for nonpsychotic mental health disorders by newcomers in various admission classes with that of long-term residents (i.e., Canadian-born persons or immigrants before 1985) in urban Ontario.
In this population-based matched cross-sectional study, we linked health service databases to the Ontario portion of the Citizenship and Immigration Canada database. Outcomes were mental health visits to primary care physicians, mental health visits to psychiatrists, and emergency department visits or hospital admissions. We measured service use for recent immigrants (those who arrived in Ontario between 2002 and 2007; n = 359 673). We compared service use by immigrants in each admission class during the first 5 years in Canada with use by age- and sex-matched long-term residents. We measured likelihood of access to each service and intensity of use of each service using conditional logistic regression and negative binomial models.
Economic and family class newcomers were less likely than long-term residents to use primary mental health care. The use of primary mental health care by female refugees did not differ from that of matched long-term residents, but use of such care by male refugees was higher (odds ratio 1.14, 95% confidence interval 1.09–1.19). Immigrants in all admission classes were less likely to use psychiatric services and hospital services for mental health care. Exceptions were men in the economic and family classes, whose intensity of hospital visits was similar to that of matched long-term residents.
Immigrants in all admission classes generally used less care for nonpsychotic disorders than longterm residents, although male refugees used more primary care. Future research should examine how mental health needs align with service use, particularly for more vulnerable groups such as refugees.
PMCID: PMC4242791  PMID: 25426182
3.  Implementing and evaluating a program to facilitate chronic disease prevention and screening in primary care: a mixed methods program evaluation 
The objectives of this paper are to describe the planned implementation and evaluation of the Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care (BETTER 2) program which originated from the BETTER trial. The pragmatic trial, informed by the Chronic Care Model, demonstrated the effectiveness of an approach to Chronic Disease Prevention and Screening (CDPS) involving the use of a new role, the prevention practitioner. The desired goals of the program are improved clinical outcomes, reduction in the burden of chronic disease, and improved sustainability of the health-care system through improved CDPS in primary care.
The BETTER 2 program aims to expand the implementation of the intervention used in the original BETTER trial into communities across Canada (Alberta, Ontario, Newfoundland and Labrador, the Northwest Territories and Nova Scotia). This proactive approach provides at-risk patients with an intervention from the prevention practitioner, a health-care professional. Using the BETTER toolkit, the prevention practitioner determines which CDPS actions the patient is eligible to receive, and through shared decision-making and motivational interviewing, develops a unique and individualized ‘prevention prescription’ with the patient. This intervention is 1) personalized; 2) addressing multiple conditions; 3) integrated through linkages to local, regional, or national resources; and 4) longitudinal by assessing patients over time. The BETTER 2 program brings together primary care providers, policy/decision makers and researchers to work towards improving CDPS in primary care. The target patient population is adults aged 40–65. The reach, effectiveness, adoption, implementation, maintain (RE-AIM) framework will inform the evaluation of the program through qualitative and quantitative methods. A composite index will be used to quantitatively assess the effectiveness of the prevention practitioner intervention. The CDPS actions comprising the composite index include the following: process measures, referral/treatment measures, and target/change outcome measures related to cardiovascular disease, diabetes, cancer and associated lifestyle factors.
The BETTER 2 program is a collaborative approach grounded in practice and built from existing work (i.e., integration not creation). The program evaluation is designed to provide an understanding of issues impacting the implementation of an effective approach for CDPS within primary care that may be adapted to become sustainable in the non-research setting.
PMCID: PMC4194415  PMID: 25293785
Program evaluation; Chronic disease; Prevention; Screening; Clinical practice guidelines
4.  Antibiotic-resistant Escherichia coli in women with acute cystitis in Canada 
Trimethoprim-sulfamethoxazole (TMP-SMX) has been a traditional first-line antibiotic treatment for acute cystitis; however, guidelines do not recommend TMP-SMX in regions where Escherichia coli resistance exceeds 20%. While resistance is increasing, there are no recent Canadian estimates from a primary care setting to guide prescribing decisions.
A total of 330 family physicians assessed 752 women with suspected acute cystitis between 2009 and 2011. Physicians documented clinical features and collected urine for cultures for 430 (57.2%) women. The proportion of resistant isolates of E coli and exact binomial 95% CIs were estimated nationally, and compared regionally and demographically. These estimates were compared with those from a 2002 national study.
The proportion of TMP-SMX-resistant E coli was 16.0% nationally (95% CI 11.3% to 21.8%). This was not statistically higher than 2002 (10.9% [P=0.14]). TMP-SMX resistance was increased in women ≤50 years of age (21.4%) compared with older women (10.7% [P=0.037]). In women with no antibiotic exposure in the previous three months, TMP-SMX-resistant E coli remained more prevalent in younger women (21.8%) compared with older women (4.4% [P=0.003]). The proportion of ciprofloxacin-resistant E coli was 5.5% nationally (95% CI 2.7% to 9.9%), and was increased compared with 2002 (1.1% [P=0.036]). Ciprofloxacin resistance was highest in British Columbia (17.7%) compared with other regions (2.7% [P=0.003]), and was increased compared with 2002 levels in this province (0.0% [P=0.025]). Nitrofurantoin-resistant E coli levels were low (0.5% [95% CI 0.01% to 2.7%).
The proportion of TMP-SMX-resistant E coli causing acute cystitis in women in Canada remains below 20% nationally, but may exceed this level in premenopausal women. Ciprofloxacin resistance has increased, notably in British Columbia. Nitrofurantoin resistance levels are low across the country. These observations indicate that TMP-SMX and nitrofurantoin remain appropriate empirical antibiotic agents for treating cystitis in primary care settings in Canada.
PMCID: PMC3852451  PMID: 24421825
Acute cystitis; Antimicrobial resistance; E coli
5.  The Magnitude and Duration of Clostridium difficile Infection Risk Associated with Antibiotic Therapy: A Hospital Cohort Study 
PLoS ONE  2014;9(8):e105454.
Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and May 2012. Poisson regression models included covariates for time since admission, age, hospitalization history, disease pressure, and intensive care unit stay. Impacts of antibiotic use through time were modeled using 4 measures: current antibiotic receipt, time since most recent receipt, time since first receipt during a hospitalization, and duration of receipt. Over the 24-month study period, we identified 127 patients with new onset nosocomial CDI (incidence rate per 10,000 patient days [IR] = 5.86). Of the 4 measures, time since most recent receipt was the strongest independent predictor of CDI incidence. Relative to patients with no prior receipt of antibiotics in the last 30 days (IR = 2.95), the incidence rate of CDI was 2.41 times higher (95% confidence interval [CI] 1.41, 4.13) during antibiotic receipt and 2.16 times higher when patients had receipt in the prior 1–5 days (CI 1.17, 4.00). The incidence rates of CDI following 1–3, 4–6 and 7–11 days of antibiotic exposure were 1.60 (CI 0.85, 3.03), 2.27 (CI 1.24, 4.16) and 2.10 (CI 1.12, 3.94) times higher compared to no prior receipt. These findings are consistent with studies showing higher risk associated with longer antibiotic use in hospitalized patients, but suggest that the duration of increased risk is shorter than previously thought.
PMCID: PMC4144891  PMID: 25157757
6.  The Effect of Health-Facility Admission and Skilled Birth Attendant Coverage on Maternal Survival in India: A Case-Control Analysis 
PLoS ONE  2014;9(6):e95696.
Research in areas of low skilled attendant coverage found that maternal mortality is paradoxically higher in women who seek obstetric care. We estimated the effect of health-facility admission on maternal survival, and how this effect varies with skilled attendant coverage across India.
Using unmatched population-based case-control analysis of national datasets, we compared the effect of health-facility admission at any time (antenatal, intrapartum, postpartum) on maternal deaths (cases) to women reporting pregnancies (controls). Probability of maternal death decreased with increasing skilled attendant coverage, among both women who were and were not admitted to a health-facility, however, the risk of death among women who were admitted was higher (at 50% coverage, OR = 2.32, 95% confidence interval 1.85–2.92) than among those women who were not; while at higher levels of coverage, the effect of health-facility admission was attenuated. In a secondary analysis, the probability of maternal death decreased with increasing coverage among both women admitted for delivery or delivered at home but there was no effect of admission for delivery on mortality risk (50% coverage, OR = 1.0, 0.80–1.25), suggesting that poor quality of obstetric care may have attenuated the benefits of facility-based care. Subpopulation analysis of obstetric hemorrhage cases and report of ‘excessive bleeding’ in controls showed that the probability of maternal death decreased with increasing skilled attendant coverage; but the effect of health-facility admission was attenuated (at 50% coverage, OR = 1.47, 0.95–1.79), suggesting that some of the effect in the main model can be explained by women arriving at facility with complications underway. Finally, highest risk associated with health-facility admission was clustered in women with education 8 years.
The effect of health-facility admission did vary by skilled attendant coverage, and this effect appears to be driven partially by reverse causality; however, inequitable access to and possibly poor quality of healthcare for primary and emergency services appears to play a role in maternal survival as well.
PMCID: PMC4041636  PMID: 24887586
7.  Premature return to play and return to learn after a sport-related concussion 
Canadian Family Physician  2014;60(6):e310-e315.
To determine what proportion of patients experience an exacerbation of their symptoms as a result of premature return to play (RTP) and return to learn (RTL) following sport-related concussions.
Retrospective study of electronic medical records from the office-based practice of one family and sport medicine physician who had systematically provided recommendations for cognitive and physical rest based on existing consensus recommendations. Two blinded authors independently reviewed each chart, which included Sport Concussion Assessment Tool (SCAT) and SCAT2 symptom self-report forms to determine whether an athlete had returned to play or learn prematurely. If there was a discrepancy between the 2 reviewers then a third author reviewed the charts.
A sport medicine and family practice in Ontario. The physician assessed sport-related concussions after self-referral or referral from other primary care physicians, teams, and schools.
A total of 170 charts of 159 patients were assessed for sport-related concussion during a 5-year period (April 2006 to March 2011). All participants were students who were participating in sports at the time of injury. There were 41 concussions in elementary students, 95 concussions in high school students, and 34 concussions in college or university students.
Main outcome measures
Premature RTP and RTL were defined as chart records documenting the recurrence or worsening of symptoms that accompanied the patients’ RTP or RTL. Measures were compared using the earliest available SCAT forms and self-reporting.
In 43.5% of concussion cases, the patient returned to sport too soon and in 44.7% of concussion cases, the patient returned to school too soon. Patients with a history of previous concussion required more days of rest before being permitted to participate in any physical activity than those patients without a previous history of concussion. Elementary school students required fewer days of rest before being permitted to return to any physical activity compared with high school students and college or university students.
Currently, physicians recommend restrictions on mental and physical activity following sport-related concussion. This is done without clear guidelines as to what cognitive rest entails for students. Further research is required to determine how to implement a management plan for student athletes to facilitate complete recovery after concussion.
PMCID: PMC4055342  PMID: 24925965
9.  Unwalkable Neighborhoods, Poverty, and the Risk of Diabetes Among Recent Immigrants to Canada Compared With Long-Term Residents 
Diabetes Care  2013;36(2):302-308.
This study was designed to examine whether residents living in neighborhoods that are less conducive to walking or other physical activities are more likely to develop diabetes and, if so, whether recent immigrants are particularly susceptible to such effects.
We conducted a population-based, retrospective cohort study to assess the impact of neighborhood walkability on diabetes incidence among recent immigrants (n = 214,882) relative to long-term residents (n = 1,024,380). Adults aged 30–64 years who were free of diabetes and living in Toronto, Canada, on 31 March 2005 were identified from administrative health databases and followed until 31 March 2010 for the development of diabetes, using a validated algorithm. Neighborhood characteristics, including walkability and income, were derived from the Canadian Census and other sources.
Neighborhood walkability was a strong predictor of diabetes incidence independent of age and area income, particularly among recent immigrants (lowest [quintile 1 {Q1}] vs. highest [quintile 5 {Q5}] walkability quintile: relative risk [RR] 1.58 [95% CI 1.42–1.75] for men; 1.67 [1.48–1.88] for women) compared with long-term residents (Q1 to Q5) 1.32 [1.26–1.38] for men; 1.24 [1.18–1.31] for women). Coexisting poverty accentuated these effects; diabetes incidence varied threefold between recent immigrants living in low-income/low walkability areas (16.2 per 1,000) and those living in high-income/high walkability areas (5.1 per 1,000).
Neighborhood walkability was inversely associated with the development of diabetes in our setting, particularly among recent immigrants living in low-income areas.
PMCID: PMC3554289  PMID: 22988302
10.  A Monte Carlo simulation study comparing linear regression, beta regression, variable-dispersion beta regression and fractional logit regression at recovering average difference measures in a two sample design 
In biomedical research, response variables are often encountered which have bounded support on the open unit interval - (0,1). Traditionally, researchers have attempted to estimate covariate effects on these types of response data using linear regression. Alternative modelling strategies may include: beta regression, variable-dispersion beta regression, and fractional logit regression models. This study employs a Monte Carlo simulation design to compare the statistical properties of the linear regression model to that of the more novel beta regression, variable-dispersion beta regression, and fractional logit regression models.
In the Monte Carlo experiment we assume a simple two sample design. We assume observations are realizations of independent draws from their respective probability models. The randomly simulated draws from the various probability models are chosen to emulate average proportion/percentage/rate differences of pre-specified magnitudes. Following simulation of the experimental data we estimate average proportion/percentage/rate differences. We compare the estimators in terms of bias, variance, type-1 error and power. Estimates of Monte Carlo error associated with these quantities are provided.
If response data are beta distributed with constant dispersion parameters across the two samples, then all models are unbiased and have reasonable type-1 error rates and power profiles. If the response data in the two samples have different dispersion parameters, then the simple beta regression model is biased. When the sample size is small (N0 = N1 = 25) linear regression has superior type-1 error rates compared to the other models. Small sample type-1 error rates can be improved in beta regression models using bias correction/reduction methods. In the power experiments, variable-dispersion beta regression and fractional logit regression models have slightly elevated power compared to linear regression models. Similar results were observed if the response data are generated from a discrete multinomial distribution with support on (0,1).
The linear regression model, the variable-dispersion beta regression model and the fractional logit regression model all perform well across the simulation experiments under consideration. When employing beta regression to estimate covariate effects on (0,1) response data, researchers should ensure their dispersion sub-model is properly specified, else inferential errors could arise.
PMCID: PMC3999882  PMID: 24461057
Regression modelling; Linear regression; Beta regression; Variable-dispersion beta regression; Fractional Logit regression; Beta distribution; Multinomial distribution; Monte Carlo simulation
11.  Density, Destinations or Both? A Comparison of Measures of Walkability in Relation to Transportation Behaviors, Obesity and Diabetes in Toronto, Canada 
PLoS ONE  2014;9(1):e85295.
The design of suburban communities encourages car dependency and discourages walking, characteristics that have been implicated in the rise of obesity. Walkability measures have been developed to capture these features of urban built environments. Our objective was to examine the individual and combined associations of residential density and the presence of walkable destinations, two of the most commonly used and potentially modifiable components of walkability measures, with transportation, overweight, obesity, and diabetes. We examined associations between a previously published walkability measure and transportation behaviors and health outcomes in Toronto, Canada, a city of 2.6 million people in 2011. Data sources included the Canada census, a transportation survey, a national health survey and a validated administrative diabetes database. We depicted interactions between residential density and the availability of walkable destinations graphically and examined them statistically using general linear modeling. Individuals living in more walkable areas were more than twice as likely to walk, bicycle or use public transit and were significantly less likely to drive or own a vehicle compared with those living in less walkable areas. Individuals in less walkable areas were up to one-third more likely to be obese or to have diabetes. Residential density and the availability of walkable destinations were each significantly associated with transportation and health outcomes. The combination of high levels of both measures was associated with the highest levels of walking or bicycling (p<0.0001) and public transit use (p<0.0026) and the lowest levels of automobile trips (p<0.0001), and diabetes prevalence (p<0.0001). We conclude that both residential density and the availability of walkable destinations are good measures of urban walkability and can be recommended for use by policy-makers, planners and public health officials. In our setting, the combination of both factors provided additional explanatory power.
PMCID: PMC3891889  PMID: 24454837
12.  Association between socio-economic status and hemoglobin A1c levels in a Canadian primary care adult population without diabetes 
BMC Family Practice  2014;15:7.
Hgb A1c levels may be higher in persons without diabetes of lower socio-economic status (SES) but evidence about this association is limited; there is therefore uncertainty about the inclusion of SES in clinical decision support tools informing the provision and frequency of Hgb A1c tests to screen for diabetes. We studied the association between neighborhood-level SES and Hgb A1c in a primary care population without diabetes.
This is a retrospective study using data routinely collected in the electronic medical records (EMRs) of forty six community-based family physicians in Toronto, Ontario. We analysed records from 4,870 patients without diabetes, age 45 and over, with at least one clinical encounter between January 1st 2009 and December 31st 2011 and one or more Hgb A1c report present in their chart during that time interval. Residential postal codes were used to assign neighborhood deprivation indices and income levels by quintiles. Covariates included elements known to be associated with an increase in the risk of incident diabetes: age, gender, family history of diabetes, body mass index, blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, and fasting blood glucose.
The difference in mean Hgb A1c between highest and lowest income quintiles was -0.04% (p = 0.005, 95% CI -0.07% to -0.01%), and between least deprived and most deprived was -0.05% (p = 0.003, 95% CI -0.09% to -0.02%) for material deprivation and 0.02% (p = 0.2, 95% CI -0.06% to 0.01%) for social deprivation. After adjustment for covariates, a marginally statistically significant difference in Hgb A1c between highest and lowest SES quintile (p = 0.04) remained in the material deprivation model, but not in the other models.
We found a small inverse relationship between Hgb A1c and the material aspects of SES; this was largely attenuated once we adjusted for diabetes risk factors, indicating that an independent contribution of SES to increasing Hgb A1c may be limited. This study does not support the inclusion of SES in clinical decision support tools that inform the use of Hgb A1c for diabetes screening.
PMCID: PMC3890502  PMID: 24410794
13.  Feedback GAP: pragmatic, cluster-randomized trial of goal setting and action plans to increase the effectiveness of audit and feedback interventions in primary care 
Audit and feedback to physicians is a commonly used quality improvement strategy, but its optimal design is unknown. This trial tested the effects of a theory-informed worksheet to facilitate goal setting and action planning, appended to feedback reports on chronic disease management, compared to feedback reports provided without these worksheets.
A two-arm pragmatic cluster randomized trial was conducted, with allocation at the level of primary care clinics. Participants were family physicians who contributed data from their electronic medical records. The ‘usual feedback’ arm received feedback every six months for two years regarding the proportion of their patients meeting quality targets for diabetes and/or ischemic heart disease. The intervention arm received these same reports plus a worksheet designed to facilitate goal setting and action plan development in response to the feedback reports. Blood pressure (BP) and low-density lipoprotein cholesterol (LDL) values were compared after two years as the primary outcomes. Process outcomes measured the proportion of guideline-recommended actions (e.g., testing and prescribing) conducted within the appropriate timeframe. Intention-to-treat analysis was performed.
Outcomes were similar across groups at baseline. Final analysis included 20 physicians from seven clinics and 1,832 patients in the intervention arm (15% loss to follow up) and 29 physicians from seven clinics and 2,223 patients in the usual feedback arm (10% loss to follow up). Ten of 20 physicians completed the worksheet at least once during the study. Mean BP was 128/72 in the feedback plus worksheet arm and 128/73 in the feedback alone arm, while LDL was 2.1 and 2.0, respectively. Thus, no significant differences were observed across groups in the primary outcomes, but mean haemoglobin A1c was lower in the feedback plus worksheet arm (7.2% versus 7.4%, p<0.001). Improvements in both arms were noted over time for one-half of the process outcomes.
Appending a theory-informed goal setting and action planning worksheet to an externally produced audit and feedback intervention did not lead to improvements in patient outcomes. The results may be explained in part by passive dissemination of the worksheet leading to inadequate engagement with the intervention.
Trial registration NCT00996645
PMCID: PMC3878579  PMID: 24341511
14.  Improving chronic disease prevention and screening in primary care: results of the BETTER pragmatic cluster randomized controlled trial 
BMC Family Practice  2013;14:175.
Primary care provides most of the evidence-based chronic disease prevention and screening services offered by the healthcare system. However, there remains a gap between recommended preventive services and actual practice. This trial (the BETTER Trial) aimed to improve preventive care of heart disease, diabetes, colorectal, breast and cervical cancers, and relevant lifestyle factors through a practice facilitation intervention set in primary care.
Pragmatic two-way factorial cluster RCT with Primary Care Physicians’ practices as the unit of allocation and individual patients as the unit of analysis. The setting was urban Primary Care Team practices in two Canadian provinces. Eight Primary Care Team practices were randomly assigned to receive the practice-level intervention or wait-list control; 4 physicians in each team (32 physicians) were randomly assigned to receive the patient-level intervention or wait-list control. Patients randomly selected from physicians’ rosters were stratified into two groups: 1) general and 2) moderate mental illness. The interventions involved a multifaceted, evidence-based, tailored practice-level intervention with a Practice Facilitator, and a patient-level intervention involving a one-hour visit with a Prevention Practitioner where patients received a tailored ‘prevention prescription’. The primary outcome was a composite Summary Quality Index of 28 evidence-based chronic disease prevention and screening actions with pre-defined targets, expressed as the ratio of eligible actions at baseline that were met at follow-up. A cost-effectiveness analysis was conducted.
789 of 1,260 (63%) eligible patients participated. On average, patients were eligible for 8.96 (SD 3.2) actions at baseline. In the adjusted analysis, control patients met 23.1% (95% CI: 19.2% to 27.1%) of target actions, compared to 28.5% (95% CI: 20.9% to 36.0%) receiving the practice-level intervention, 55.6% (95% CI: 49.0% to 62.1%) receiving the patient-level intervention, and 58.9% (95% CI: 54.7% to 63.1%) receiving both practice- and patient-level interventions (patient-level intervention versus control, P < 0.001). The benefit of the patient-level intervention was seen in both strata. The extra cost of the intervention was $26.43CAN (95% CI: $16 to $44) per additional action met.
A Prevention Practitioner can improve the implementation of clinically important prevention and screening for chronic diseases in a cost-effective manner.
PMCID: PMC4225577  PMID: 24252125
Primary care; Family practice; Pragmatic trial; Chronic disease prevention; Cancer screening; Facilitation
15.  Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI 
Brain Injury  2013;27(12):1364-1376.
To longitudinally examine objective and self-reported outcomes for recovery of cognition, communication, mood and participation in adults with traumatic brain injury (TBI) and co-morbid post-traumatic sleep/wake disorders.
Prospective, longitudinal, single blind outcome study.
Ten adults with moderate–severe TBI and two adults with mild TBI and persistent symptoms aged 18–58 years. Six males and six females, who were 1–22 years post-injury and presented with self-reported sleep/wake disturbances with onset post-injury.
Individualized treatments for sleep/wake disorders that included sleep hygiene recommendations, pharmacological interventions and/or treatments for sleep apnea with follow-up.
Main outcome measures
Insomnia Severity Index, Beck Depression and Anxiety Inventories, Latrobe Communication Questionnaire, Speed and Capacity of Language Processing, Test of Everyday Attention, Repeatable Battery for the Assessment of Neuropsychological Status, Daily Cognitive-Communication and Sleep Profile.
Group analysis revealed positive trends in change for each measure and across sub-tests of all measures. Statistically significant changes were noted in insomnia severity, p = 0.0003; depression severity, p = 0.03; language, p = 0.01; speed of language processing, p = 0.007.
These results add to a small but growing body of evidence that sleep/wake disorders associated with TBI exacerbate trauma-related cognitive, communication and mood impairments. Treatment for sleep/wake disorders may optimize recovery and outcomes.
PMCID: PMC3809926  PMID: 24070180
Cognition; communication; mood; outcomes; sleep disorders; traumatic brain injury
16.  Female sex work interventions and changes in HIV and syphilis infection risks from 2003 to 2008 in India: a repeated cross-sectional study 
BMJ Open  2013;3(6):e002724.
We examined if increased spending and coverage of female sex worker (FSW) interventions were associated with declines in HIV or syphilis risk among young pregnant women (as a proxy for new infections in the general population) in the high-burden southern states of India.
Repeated cross-sectional analysis.
We used logistic regression to relate district-level spending, number of sexually transmitted infections (STIs) treated, FSWs reached or condoms distributed to the declines in the annual risk of HIV and syphilis from 2003 to 2008 among prenatal clinic attendees in the four high-HIV burden states of Andhra Pradesh, Karnataka, Maharashtra and Tamil Nadu.
386 961 pregnant women aged 15–24 years (as a proxy for incident infections in the adult population).
We examined National AIDS Control Organisation (NACO) data on 868 FSW intervention projects implemented between 1995 and 2008.
Primary and secondary outcome measures
HIV or syphilis infection.
HIV and syphilis prevalence declined substantially among young pregnant women. Each additional STI treated (per 1000 people) reduced the annual risk of HIV infection by −1.7% (95% CI −3.3 to −0.1) and reduced the annual risk of syphilis infection by −10.9% (95%CI −15.9 to −5.8). Spending, FSWs reached or condoms distributed did not reduce HIV risk, but each was significantly associated with reduced annual risk of syphilis infection. There were no major differences between the NACO-funded and Avahan-funded districts in the annual risk of either STI.
Targeted FSW interventions are associated with reductions in syphilis risk and STI treatment is associated with reduced HIV risk. Both more and less costly FSW interventions have comparable effectiveness.
PMCID: PMC3686231  PMID: 23794571
Public Health; Infectious Diseases
18.  Methodological approaches to population based research of screening procedures in the presence of selection bias and exposure measurement error: colonoscopy and colorectal cancer outcomes in Ontario 
The study describes the methodological challenges encountered in an observational study estimating the effectiveness of colonoscopy in reducing colorectal cancer (CRC) incidence and mortality.
Using Ontario provincial administrative data, we conducted a population-based retrospective cohort study to assess CRC incidence and mortality in a group of average-risk subjects aged 50–74 years who underwent colonoscopy between 1996–2000. We created two study cohorts; unselected and restricted. The unselected cohort consists of subjects aged 50–74 years who were eligible for CRC screening and who had the same primary care physician (PCP) during the period 1996–2000 with at least two years of follow-up. PCPs are general practioners/family physicians who are the main source of health care for Ontarians. The restricted cohort was a nested sample of unselected cohort who were alive and free of CRC as on January 1, 2001 and whose PCPs had at least 10 screen-eligible patients with a colonoscopy referral rate of more than 3%. We compared the outcomes in the two study cohorts; unselected vs. restricted. We then estimated the absolute risk reduction associated with colonoscopy in preventing CRC incidence and mortality in the restricted cohort, using traditional regression analysis, propensity score analysis and instrumental variable analysis.
The unselected cohort (N = 1,341,612) showed that colonoscopy was associated with an increase in CRC incidence (1.61% vs. 4.61%) and mortality (0.36% vs. 1.16%), whereas the restricted cohort (N = 1,089,998) showed that colonoscopy was associated with a reduction in CRC incidence (1.36% vs. 0.84%) and mortality (0.23% vs. 0.15%). For CRC incidence, the absolute risk reduction (ARR) associated with colonoscopy use was 0.52% in an unadjusted model, 0.53% in a multivariate logistic regression model, 0.54% in a propensity score-weighted outcome model, 0.56% in propensity score-matched model, and 0.60% using instrumental variable analysis. For CRC mortality, the ARR was 0.08% in the unadjusted model, multivariate logistic regression model and for a propensity score- weighted outcome model, 0.10% using propensity score matched model and 0.17% using the IVA model.
Colonoscopy use reduced the risk of CRC incidence and mortality in the restricted cohort. The study highlights the importance of appropriate selection of study subjects and use of analytic methods for the evaluation of screening methods using observational data.
PMCID: PMC3644489  PMID: 23617792
Colonoscopy; Propensity score analysis; Instrumental variable analysis
19.  Diabetes Screening Among Immigrants 
Diabetes Care  2012;35(4):754-761.
To examine diabetes screening, predictors of screening, and the burden of undiagnosed diabetes in the immigrant population and whether these estimates differ by ethnicity.
A population-based retrospective cohort linking administrative health data to immigration files was used to follow the entire diabetes-free population aged 40 years and up in Ontario, Canada (N = 3,484,222) for 3 years (2004–2007) to determine whether individuals were screened for diabetes. Multivariate regression was used to determine predictors of having a diabetes test.
Screening rates were slightly higher in the immigrant versus the general population (76.0 and 74.4%, respectively; P < 0.001), with the highest rates in people born in South Asia, Mexico, Latin America, and the Caribbean. Immigrant seniors (age ≥65 years) were screened less than nonimmigrant seniors. Percent yield of new diabetes subjects among those screened was high for certain countries of birth (South Asia, 13.0%; Mexico and Latin America, 12.1%; Caribbean, 9.5%) and low among others (Europe, Central Asia, U.S., 5.1–5.2%). The number of physician visits was the single most important predictor of screening, and many high-risk ethnic groups required numerous visits before a test was administered. The proportion of diabetes that remained undiagnosed was estimated to be 9.7% in the general population and 9.0% in immigrants.
Overall diabetes-screening rates are high in Canada’s universal health care setting, including among high-risk ethnic groups. Despite this finding, disparities in screening rates between immigrant subgroups persist and multiple physician visits are often required to achieve recommended screening levels.
PMCID: PMC3308303  PMID: 22357181
20.  Modeling the Cumulative Effects of Social Exposures on Health: Moving beyond Disease-Specific Models 
The traditional explanatory models used in epidemiology are “disease specific”, identifying risk factors for specific health conditions. Yet social exposures lead to a generalized, cumulative health impact which may not be specific to one illness. Disease-specific models may therefore misestimate social factors’ effects on health. Using data from the Canadian Community Health Survey and Canada 2001 Census we construct and compare “disease-specific” and “generalized health impact” (GHI) models to gauge the negative health effects of one social exposure: socioeconomic position (SEP). We use logistic and multinomial multilevel modeling with neighbourhood-level material deprivation, individual-level education and household income to compare and contrast the two approaches. In disease-specific models, the social determinants under study were each associated with the health conditions of interest. However, larger effect sizes were apparent when outcomes were modeled as compound health problems (0, 1, 2, or 3+ conditions) using the GHI approach. To more accurately estimate social exposures’ impacts on population health, researchers should consider a GHI framework.
PMCID: PMC3709312  PMID: 23528813
social determinants; socioeconomic position; multinomial regression; multilevel modeling; health inequities
21.  Food Fortification and Decline in the Prevalence of Neural Tube Defects: Does Public Intervention Reduce the Socioeconomic Gap in Prevalence? 
Objective: A significant decline in the prevalence of neural tube defects (NTD) through food fortification has been reported. Questions remain, however, about the effectiveness of this intervention in reducing the gap in prevalence across socioeconomic status (SES). Study Design: Using health number and through record linkage, children born in Ontario hospitals between 1994 and 2009 were followed for the diagnosis of congenital anomalies. SES quintiles were assigned to each child using census information at the time of birth. Adjusted rates and multivariate models were used to compare trends among children born in different SES groups. Results: Children born in low SES areas had significantly higher rates of NTDs (RR = 1.25, CI: 1.14–1.37). Prevalence of NTDs among children born in low and high SES areas declined since food fortification began in 1999 although has started rising again since 2006. While the crude decline was greater in low SES areas, after adjustment for maternal age, the slope of decline and SES gap in prevalence rates remained unchanged overtime. Conclusions: While food fortification is successful in reducing the prevalence of NTDs, it was not associated with removing the gap between high and low SES groups.
PMCID: PMC3709319  PMID: 23538728
neural tube defects; food fortification; socioeconomic status; health disparities
22.  Is asthma a vanishing disease? A study to forecast the burden of asthma in 2022 
BMC Public Health  2013;13:254.
Recent evidence regarding temporal trends of asthma burden has not been consistent, with some countries reporting decreases in prevalence of asthma. In Ontario, the province in Canada with the highest population, the prevalence of asthma rose at a rate of 0.5% per year between 1996 and 2005. These estimates were based on population-based health services use data spanning more than a decade and provide a powerful source to forecast the trends of asthma burden. The objective of this study was to use observed population trends data of asthma incidence and prevalence to forecast future disease burden.
The Ontario Asthma Surveillance Information System (OASIS) used health administrative databases to identify and track all individuals in the province with asthma. Individuals with asthma identified between April 1, 1996 and March 31, 2010 were included. Exponential smoothing models were applied to annual data to project incidence to the year 2022, prevalence was estimated by applying the cumulative projected incidence to the projected population.
While asthma incidence is falling, the absolute number of prevalent cases will continue to rise. We projected that almost 1 in 8 individuals in Ontario will have asthma by the year 2022, suggesting that asthma will continue to be a major burden on individuals and the health care system.
These projections will help inform health care planners and decision-makers regarding resource allocation to optimize asthma outcomes.
PMCID: PMC3626860  PMID: 23517452
23.  Unintended consequences of delisting routine eye exams on retinopathy screening for people with diabetes in Ontario, Canada 
Routine eye examinations for healthy adults aged 20–64 years were delisted from the Ontario Health Insurance Plan in 2004, but they continue to be insured for people with diabetes regardless of age. We sought to assess whether the delisting of routine eye examinations for healthy adults had the unintended consequence of decreasing retinopathy screening for adults with diabetes.
We used administrative data to calculate eye examinations for people with diabetes ages 40–64 years and 65 years and older in each 2-year period from 1998 to 2010. We examined differences by sex, income, rurality and type of health care provider. We used segmented linear regression to assess the change in trend before and after 2004.
For people with diabetes aged 65 years and older, eye examinations rose gradually from 1998 to 2010, with no substantial change between 2004 and 2006. For people with diabetes aged 40–65 years, there was an 8.7% (95% confidence interval [CI] 6.3%–11.1%) decrease in eye examinations between 2004 and 2006. Results were similar for all population subgroups. Ophthalmologic examinations decreased steadily for both age groups during the study period, and there was a decline in optometry examinations for people ages 40–65 years after 2004.
The delisting of routine eye examinations for healthy adults in Ontario had the unintended consequence of reducing publicly funded retinopathy screening for people with diabetes. More research is needed to understand whether patients are being charged for an insured service or to what degree misunderstanding has prevented patients from seeking care.
PMCID: PMC3576462  PMID: 23296581
24.  Does social disadvantage affect the validity of self-report for cervical cancer screening? 
The aim was to review the international literature on the validity of self-report of cervical cancer screening, specifically of studies that made direct comparisons among women with and without social disadvantage, based on race/ethnicity, foreign-born status, language ability, income, or education.
The databases of Medline, EBM Reviews, and CINAHL from 1990 to 2011 were searched using relevant search terms. Articles eligible for data extraction documented the prevalence of cervical cancer screening based on both self-report and an objective measure for women both with and without at least one measure of social disadvantage. The report-to-record ratio, the ratio of the proportion of study subjects who report at least one screening test within a particular time frame to the proportion of study subjects who have a record of the same test within that time frame, was calculated for each subgroup.
Five studies met the extraction criteria. Subgroups were based on race/ethnicity, education, and income. In all studies, and across all subgroups, report-to-record ratios were greater than one, indicative of pervasive over-reporting.
The findings suggest that objective measures should be used by policymakers, researchers, and public-health practitioners in place of self-report to accurately determine cervical cancer screening rates.
PMCID: PMC3558311  PMID: 23378784
vulnerable populations; early detection of cancer; vaginal smears; Pap test; reproducibility of results; validity

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