Determinants of neurological disease: Synthesis of systematic reviews.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally.

Efficacy and completion rates of rifapentine and isoniazid (3HP) compared to other treatment regimens for latent tuberculosis infection: a systematic review with network meta-analyses.

BACKGROUND: We conducted a systematic review and network meta-analysis (NMA) to examine the efficacy and completion rates of treatments for latent tuberculosis infection (LTBI). While a previous review found newer, short-duration regimens to be effective, several included studies did not confirm LTBI, and analyses did not account for variable follow-up or assess completion. METHODS: We searched MEDLINE, Embase, CENTRAL, PubMed, and additional sources to identify RCTs in patients with confirmed LTBI that involved a regimen of interest and reported on efficacy or completion. Regimens of interest included isoniazid (INH) with rifapentine once weekly for 12 weeks (INH/RPT-3), 6 and 9 months of daily INH (INH-6; INH-9), 3-4 months daily INH plus rifampicin (INH/RFMP 3-4), and 4 months daily rifampicin alone (RFMP-4). NMAs were performed to compare regimens for both endpoints. RESULTS: Sixteen RCTs (n = 44,149) and 14 RCTs (n = 44,128) were included in analyses of efficacy and completion. Studies were published between 1968 and 2015, and there was diversity in patient age and comorbidities. All regimens of interest except INH-9 showed significant benefits in preventing active TB compared to placebo. Comparisons between active regimens did not reveal significant differences. While definitions of regimen completion varied across studies, regimens of 3-4 months were associated with a greater likelihood of adequate completion. CONCLUSIONS: Most of the active regimens showed an ability to reduce the risk of active TB relative to no treatment, however important differences between active regimens were not found. Shorter rifamycin-based regimens may offer comparable benefits to longer INH regimens. Regimens of 3-4 months duration are more likely to be completed than longer regimens.

Systematic reviews of factors associated with the onset and progression of neurological conditions in humans: A methodological overview.

As a component of the National Population Health Study of Neurological conditions, systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 priority neurological conditions. Between 2011 and 2013, electronic databases and grey literature sources were searched to identify systematic reviews and primary studies reporting on the onset and progression of each condition. Inclusion was restricted to studies of humans reported in English or French. Additional condition-specific eligibility criteria were also applied. Titles and abstracts were screened by one reviewer with excluded records verified by a second reviewer. Full-text reports were screened independently by two reviewers. Disagreements were resolved by consensus or third party adjudication. Systematic reviews were quality appraised using the AMSTAR criteria, with only moderate and high quality reviews considered for inclusion. Primary studies were also sought to ensure that evidence from existing systematic reviews was supplemented with recent primary study findings (i.e., those published after the most recent systematic review). Evidence from primary studies was also considered if a systematic review was unavailable or of poor quality. Data were extracted using standardized forms. Where feasible, data were extracted independently by two reviewers. Otherwise, data were extracted by a single reviewer and independent data extraction by a second reviewer was conducted for a randomly selected sample of studies. An updated search was conducted in 2016 to identify systematic reviews published since the initial search in 2011-2013. A summary of the methodology used to conduct the systematic reviews is described. Illustrative results are provided for the risk of amyotrophic lateral sclerosis in relation to occupational exposure to lead and other heavy metals.

A systematic review of the risk factors associated with the onset and progression of primary brain tumours.

The overall aim of this systematic review was to identify risk factors for onset and natural progression, which were shown to increase, decrease, or have a null association with risk of primary brain tumour. For onset, the project was separated into two phases. The first phase consisted of a systematic search of existing systematic reviews and meta-analyses. Moderate to high methodological quality reviews were incorporated and summarized with relevant observational studies published since 2010, identified from a systematic search performed in phase 2. For natural progression, only the first phase was conducted. Standard systematic review methodology was utilized. Based on this review, various genetic variants, pesticide exposures, occupational farming/hairdressing, cured meat consumption and personal hair dye use appear to be associated with increased risk of onset amongst adults. The specific EGF polymorphsm 61-A allele within Caucasian populations and having a history of allergy was associated with a decreased risk. For progression, M1B-1 antigen was shown to increase the risk. High birth weight, pesticide exposure (childhood exposure, and parental occupational exposure) and maternal consumption of cured meat during pregnancy may also increase the risk of onset of childhood brain tumours. Conversely, maternal intake of pre-natal supplements (folic acid) appeared to decrease risk. Children with neurofibromatosis 2 were considered to have worse overall and relapse free survival compared to neurofibromatosis 1, as were those children who had grade III tumours compared to lesser grades.

Effectiveness of Personal Protective Equipment for Healthcare Workers Caring for Patients with Filovirus Disease: A Rapid Review.

BACKGROUND: A rapid review, guided by a protocol, was conducted to inform development of the World Health Organization's guideline on personal protective equipment in the context of the ongoing (2013-present) Western African filovirus disease outbreak, with a focus on health care workers directly caring for patients with Ebola or Marburg virus diseases. METHODS: Electronic databases and grey literature sources were searched. Eligibility criteria initially included comparative studies on Ebola and Marburg virus diseases reported in English or French, but criteria were expanded to studies on other viral hemorrhagic fevers and non-comparative designs due to the paucity of studies. After title and abstract screening (two people to exclude), full-text reports of potentially relevant articles were assessed in duplicate. Fifty-seven percent of extraction information was verified. The Grading of Recommendations Assessment, Development and Evaluation framework was used to inform the quality of evidence assessments. RESULTS: Thirty non-comparative studies (8 related to Ebola virus disease) were located, and 27 provided data on viral transmission. Reporting of personal protective equipment components and infection prevention and control protocols was generally poor. CONCLUSIONS: Insufficient evidence exists to draw conclusions regarding the comparative effectiveness of various types of personal protective equipment. Additional research is urgently needed to determine optimal PPE for health care workers caring for patients with filovirus.

The REporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD) Statement: Methods for Arriving at Consensus and Developing Reporting Guidelines.

OBJECTIVE: Routinely collected health data, collected for administrative and clinical purposes, without specific a priori research questions, are increasingly used for observational, comparative effectiveness, health services research, and clinical trials. The rapid evolution and availability of routinely collected data for research has brought to light specific issues not addressed by existing reporting guidelines. The aim of the present project was to determine the priorities of stakeholders in order to guide the development of the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. METHODS: Two modified electronic Delphi surveys were sent to stakeholders. The first determined themes deemed important to include in the RECORD statement, and was analyzed using qualitative methods. The second determined quantitative prioritization of the themes based on categorization of manuscript headings. The surveys were followed by a meeting of RECORD working committee, and re-engagement with stakeholders via an online commentary period. RESULTS: The qualitative survey (76 responses of 123 surveys sent) generated 10 overarching themes and 13 themes derived from existing STROBE categories. Highest-rated overall items for inclusion were: Disease/exposure identification algorithms; Characteristics of the population included in databases; and Characteristics of the data. In the quantitative survey (71 responses of 135 sent), the importance assigned to each of the compiled themes varied depending on the manuscript section to which they were assigned. Following the working committee meeting, online ranking by stakeholders provided feedback and resulted in revision of the final checklist. CONCLUSIONS: The RECORD statement incorporated the suggestions provided by a large, diverse group of stakeholders to create a reporting checklist specific to observational research using routinely collected health data. Our findings point to unique aspects of studies conducted with routinely collected health data and the perceived need for better reporting of methodological issues.

Asthma, type 1 and type 2 diabetes mellitus, and inflammatory bowel disease amongst South Asian immigrants to Canada and their children: a population-based cohort study.

BACKGROUND: There is a high and rising rate of immune-mediated diseases in the Western world. Immigrants from South Asia have been reported to be at higher risk upon arrival to the West. We determined the risk of immune-mediated diseases in South Asian and other immigrants to Ontario, Canada, and their Ontario-born children. METHODS: Population-based cohorts of patients with asthma, type 1 diabetes (T1DM), type 2 diabetes (T2DM), and inflammatory bowel disease (IBD) were derived from health administrative data. We determined the standardized incidence, and the adjusted risk of these diseases in immigrants from South Asia, immigrants from other regions, compared with non-immigrant residents of Ontario. The risk of these diseases in the Ontario-born children of immigrants were compared to the children of non-immigrants. RESULTS: Compared to non-immigrants, adults from South Asia had higher risk of asthma (IRR 1.56, 95%CI 1.51-1.61) and T2DM (IRR 2.59, 95%CI 2.53-2.65). Adults from South Asia had lower incidence of IBD than non-immigrants (IRR 0.32, 95%CI 0.22-0.49), as did immigrants from other regions (IRR 0.29, 95%CI 0.20-0.42). Compared to non-immigrant children, the incidence of asthma (IRR 0.66, 95%CI 0.62-0.71) and IBD (IRR 0.47, 95%CI 0.33-0.67) was low amongst immigrant children from South Asia. However, the risk in Ontario-born children of South Asian immigrants relative to the children of non-immigrants was higher for asthma (IRR 1.75, 95%CI 1.69-1.81) and less attenuated for IBD (IRR 0.90, 95%CI 0.65-1.22). CONCLUSION: Early-life environmental exposures may trigger a genetic predisposition to the development of asthma and IBD in South Asian immigrants and their Canada-born children.

Inflammatory bowel disease in immigrants to Canada and their children: a population-based cohort study.

OBJECTIVES: The risk of inflammatory bowel disease (IBD) contributed by the environment can be elucidated by assessing the risk in migrants from low prevalence to Western countries. The incidence of IBD in immigrants to Canada and their Canadian-born children was compared with nonimmigrants. METHODS: A population-based cohort of IBD patients derived from health administrative data was linked to immigration data to determine the standardized incidence of IBD in immigrants to Ontario, Canada, by region of birth between 1994 and 2010. The hazard contributed by younger age at immigration was determined. Incidence for Ontario-born children of immigrant mothers was compared with the children of nonimmigrants. RESULTS: In 2,144,660 immigrants, incidence of IBD was 7.3/100,000 person-years compared with 23.9/100,000 in 12,036,921 nonimmigrants (incidence rate ratio (IRR) 0.34, 95% CI 0.26-0.44). Incidence was lowest risk in East Asians (IRR 0.14, 95% CI 0.11-0.18) and highest in Western Europeans/North Americans (IRR 0.59, 95% CI 0.46-0.75). Increased age at immigration was associated with decreased risk of IBD (HR 0.986, 95% CI 0.982-0.990), a 14% increased risk per younger decade of life at immigration. Children of immigrants from the Middle East/North Africa, South Asia, Sub-Saharan Africa, and North America/Western Europe had similar risk of IBD as children of nonimmigrants; however, the incidence remained lower among children of immigrants from other regions. CONCLUSIONS: Younger age at arrival to Canada increased the risk of IBD in immigrants. Canadian-born children of immigrants from some regions assumed the high Canadian incidence of IBD, indicating that the underlying risk is activated with earlier life exposure to the Canadian environment in certain groups.

Changing age demographics of inflammatory bowel disease in Ontario, Canada: a population-based cohort study of epidemiology trends.

BACKGROUND: International cohort studies have reported increased incidence of inflammatory bowel disease (IBD) in recent years, and Canada has among the highest rates of IBD in the world. This study assessed incidence and prevalence of IBD in Ontario, the most populous province of Canada, to determine changing trends in age of onset. METHODS: We used a population-based cohort derived from validated health administrative data consisting of all Ontario residents living with IBD from 1999 to 2008. We determined trends over time using Poisson regression analysis, assessing rates in 10-year age groups, children, adults, and the elderly. RESULTS: In 2008, 68,071 people were living with IBD among 12,738,350 people (standardized prevalence 534.3 per 100,000 people). Between 1999 and 2008, standardized IBD incidence increased from 21.3 to 26.2 per 100,000 (2.3% per yr, P < 0.0001). Incidence of Crohn's increased from 9.6 to 12.1 per 100,000 (1.9% per yr, P < 0.0001). Ulcerative colitis incidence increased from 10.7 to 12.1 per 100,000 (2.0% per yr, P < 0.0001). For IBD, incidence increased significantly in people younger than 10 years of age (9.7% per yr, P < 0.0001), 10 to 19 years of age (3.8% per yr, P < 0.0001), 30 to 39 years of age (1.8% per yr, P = 0.0006), 40 to 49 years of age (2.8% per yr, P = 0.0001), and 50 to 59 years of age (2.8% per yr, P < 0.0001). Incidence was stable in patients older than 65 years of age at diagnosis (-0.1% per yr, P = 0.73). Although incidence did not change significantly over time in adults 20 to 29 years, IBD incidence peaked in this age group. CONCLUSIONS: Ontario has among the highest prevalence of IBD in the world. Incidence of IBD increased between 1999 and 2008, owing to increased incidence in children and adults, with stable rates in elderly people. These findings demonstrate the changing age demographics and growing burden of IBD in Ontario, Canada.

Incidence, outcomes, and health services burden of very early onset inflammatory bowel disease.

BACKGROUND & AIMS: The Paris pediatric modification of the Montreal classification defines very early onset inflammatory bowel disease (VEO-IBD) as a form of IBD distinct from that of older children. We compared the incidence and outcomes of VEO-IBD with those of IBD in older children. METHODS: We performed a population-based retrospective cohort study of all children diagnosed with IBD in Ontario, Canada, from 1994 through 2009. Trends in standardized incidence were calculated using Poisson regression. We compared outpatient and emergency department visits, hospitalizations, and surgeries among children diagnosed with IBD when they were younger than age 6, ages 6-9.9, and older than age 10 years. Multivariable models were adjusted for income and stratified by sex. RESULTS: The incidence of IBD increased from 9.4 per 100,000 children (95% confidence interval [CI], 8.2-10.8/100,000 children) in 1994 to 13.2 per 100,000 children (95% CI, 11.9-14.6/100,000 children) in 2009 (P < .0001). The incidence increased by 7.4% per year among children younger than 6 years old and 6-9.9 years old, and by 2.2% per year among children ≥10 years old. IBD-related outpatient visits were less frequent among children <6 years old than ≥10 years old (odds ratio for female patients, 0.67; 95% CI, 0.58-0.78; odds ratio for male patients, 0.86; 95% CI, 0.75-0.98). Hazard ratios [HRs] for hospitalization were lower for children <6 years old (female HR, 0.70; 95% CI, 0.56-0.87; male HR, 1.12; 95% CI, 0.94-1.33) than for older children. HRs for surgery among children <6 years old with Crohn's disease were 0.35 for female patients (95% CI, 0.16-0.78) and 0.59 for male patients (95% CI, 0.34-0.99). HRs for children <6 years old with ulcerative colitis were 0.88 for female patients (95% CI, 0.47-1.63) and 0.42 for male patients (95% CI, 0.21-0.85). There was no difference in hospitalization or surgery rates among children 6-9.9 years old vs those ≥10 years old. CONCLUSIONS: Based on a retrospective cohort study, the incidence of VEO-IBD increased from 1994 through 2009. Children diagnosed with IBD before they were 6 years old used fewer health services and had lower rates of surgery than children diagnosed when they were 10 years or older.

Quality improvement in pediatric inflammatory bowel disease: moving forward to improve outcomes.

In recent years, pediatric health care has embraced the concept of quality improvement to improve patient outcomes. As quality improvement efforts are implemented, network collaboration (where multiple centers and practices implement standardized programs) is a popular option. In a collaborative network, improvement in the conduct of structural, process and outcome quality measures can lead to improvements in overall health, and benchmarks can be used to assess and compare progress. In this review article, we provided an overview of the quality improvement movement and the role of quality indicators in this movement. We reviewed current quality improvement efforts in pediatric inflammatory bowel disease (IBD), as well as other pediatric chronic illnesses. We discussed the need to standardize the development of quality indicators used in quality improvement networks to assess medical care, and the validation techniques which can be used to ensure that process indicators result in improved outcomes of clinical significance. We aimed to assess current quality improvement efforts in pediatric IBD and other diseases, such as childhood asthma, childhood arthritis, and neonatal health. By doing so, we hope to learn from their successes and failures and to move the field forward for future improvements in the care provided to children with IBD.