Hypereosinophilic syndrome in Europe: Retrospective study of treatment patterns, clinical manifestations, and healthcare resource utilization.

BACKGROUND: The burden of hypereosinophilic syndrome (HES) in Europe is not well characterized. OBJECTIVE: To evaluate real-world patient characteristics, treatment patterns, clinical manifestations, and healthcare resource utilization for patients with HES from France, Germany, Italy, Spain, and the United Kingdom. METHODS: In this retrospective, noninterventional study, data for patients with a physician-confirmed diagnosis of HES were abstracted from medical chart reviews. Patients were aged 6 years or older at the time of HES diagnosis and had 1 or more years of follow-up from the index date (first clinic visit between January 2015 and December 2019). Data on treatment patterns, comorbidities, clinical manifestations, clinical outcomes, and healthcare resource utilization were collected from diagnosis or index date to end of follow-up. RESULTS: Data for 280 patients were abstracted from medical charts by 121 physicians treating HES, with multiple specialties. Most patients (55%) had idiopathic HES, and 24% had myeloid HES; the median number (interquartile range [IQR]) of diagnostic tests per patient was 10 (6-12). The most common comorbidities were asthma (45%) and anxiety or depression (36%). Most patients (89%) used oral corticosteroids; 64% used immunosuppressants or cytotoxic agents, and 44% used biologics. Patients had a median (IQR) of 3 clinical manifestations (1-5), most commonly constitutional (63%), lung (49%), and skin (48%). Twenty-three percent of patients experienced a flare, and 40% had a complete treatment response. Some patients (30%) were hospitalized with a median (IQR) stay of 9 days (5-15) for HES-related issues. CONCLUSION: Patients with HES across 5 European countries had a substantial disease burden despite extensive oral corticosteroids treatment, highlighting the need for additional targeted therapies.

Mortality inequalities of Black adults in Canada.

Background: Mortality rates in Canada have been shown to vary by population group (e.g., Indigenous peoples, immigrants) and social economic status (e.g., income levels). Mortality patterns for some groups, including Black individuals, are not as well known. The objective of this study was to assess cause-specific mortality for Black adults living in Canada. Methods: Mortality inequalities between Black and White cohort members were estimated by sex using Cox proportional hazard models, based on data from the 2001, 2006 and 2011 Canadian Census Health and Environment Cohorts (CanCHECs). The CanCHEC cycles were combined and followed for mortality between Census Day and December 31, 2016 or 2019, resulting in a follow-up period of 15.6, 13.6 or 8.6 years, depending on the CanCHEC cycle. Results: Ischemic heart disease mortality was the leading cause of death among adult Black males (12.9%) and females (9.8%), as it is for adult White males (16.4%) and females (12.4%). Despite reduced risk of all-cause mortality among Black males and females, compared with White cohort members, there was notable increased risk for some cause-specific mortality. For instance, in the age-adjusted model, among the 25 causes of death examined, Black males had an increased risk of dying from four causes (HIV/AIDS, prostate cancer, diabetes mellitus and cerebrovascular disease), compared with White males. Similarly, Black females were at an increased risk for 6 causes of death (HIV/AIDS, stomach cancer, corpus uteri cancer, lymphomas and multiple myeloma, diabetes mellitus, and endocrine disorders) out of the 27 causes of death examined. These relative increased risks persisted for most causes of death after adjustment for differences in important social determinants of health. Interpretation: Results showed substantial variability in the risk of dying by cause of death between Black and White cohort members. An important step in reducing health inequities is the routine identification and surveillance of different health outcomes by population groups. This study helps fill that information gap.

Trends in prevalence, treatment use, and disease burden in patients with eosinophilic granulomatosis with polyangiitis in Japan: real-world database analysis.

OBJECTIVES: Report the prevalence of eosinophilic granulomatosis with polyangiitis (EGPA) and describe oral corticosteroid (OCS) use and disease burden before and after mepolizumab approval in 2018 for EGPA in Japan. METHODS: Two retrospective studies (GSK IDs: 218083; 218084) used two databases: 1) the JMDC insurer database (Japanese health insurer claims) was used to report annual EGPA prevalence and OCS use in mepolizumab-treated patients; 2) Medical Data Vision database was used to report annual treatment use, OCS dose, relapses, and healthcare resource utilization (HCRU) in patients with EGPA. RESULTS: EGPA prevalence (95% confidence interval) increased from 4.2 (0.1, 23.4) in 2005 to 58.6 (53.2, 64.5) per 1,000,000 in 2020. Median OCS dose (mg/day) decreased from a range of 4.8-7.7 during 2010-2017 to 4.5-4.8 during 2018-2020 (lowest dose in 2020). The proportion of patients with prednisolone-equivalent daily OCS dose >10 mg decreased from 2017 (11.9%) to 2020 (10.3%), while the median dose halved. The proportion of patients with EGPA relapses (64.3% to 41.6%) and hospitalisation (27.8% to 23.6%) decreased from 2010 to 2020. CONCLUSIONS: EGPA prevalence increased between 2005 and 2020. With the introduction of mepolizumab for EGPA in 2018, real-world OCS use, relapses and HCRU decreased.

The Association Between High and Unnecessary Antibiotic Prescribing: A Cohort Study Using Family Physician Electronic Medical Records.

BACKGROUND: Approximately 25% of outpatient antibiotic prescriptions are unnecessary among family physicians in Canada. Minimizing unnecessary antibiotics is key for community antibiotic stewardship. However, unnecessary antibiotic prescribing is much harder to measure than total antibiotic prescribing. We investigated the association between total and unnecessary antibiotic use by family physicians and evaluated inter-physician variability in unnecessary antibiotic prescribing. METHODS: This was a cohort study based on electronic medical records of family physicians in Ontario, Canada, between April 2011 and March 2016. We used predefined expected antibiotic prescribing rates for 23 common primary care conditions to calculate unnecessary antibiotic prescribing rates. We used multilevel Poisson regression models to evaluate the association between total antibiotic volume (number of antibiotic prescriptions per patient visit), adjusted for multiple practice- and physician-level covariates, and unnecessary antibiotic prescribing. RESULTS: There were 499 570 physician-patient encounters resulting in 152 853 antibiotic prescriptions from 341 physicians. Substantial inter-physician variability was observed. In the fully adjusted model, we observed a significant association between total antibiotic volume and unnecessary prescribing rate (adjusted rate ratio 2.11 per 10% increase in total use; 95% CI 2.05-2.17), and none of the practice- and physician-level variables were associated with unnecessary prescribing rate. CONCLUSIONS: We demonstrated substantial inter-physician variability in unnecessary antibiotic prescribing in this cohort of family physicians. Total antibiotic use was strongly correlated with unnecessary antibiotic prescribing. Total antibiotic volume is a reasonable surrogate for unnecessary antibiotic use. These results can inform community antimicrobial stewardship efforts.

Do cancer incidence and mortality rates differ among ethnicities in Canada?

BACKGROUND: Cancer incidence rates have been shown to vary by ethnicity, and the increasing awareness of and interest in reporting ethnic health inequalities have been growing internationally. The objective of this study was to assess cancer incidence and mortality rates by ethnicity in Canada. DATA AND METHODS: The study used the 2006 Canadian Census Health and Environment Cohort, linked to the Canadian Cancer Registry and the Canadian Vital Statistics-Death Database, to determine cancer cases and mortality from 2006 to 2016. Ethnicity was categorized as non-Indigenous North American (NINA); European; Caribbean; Latin, Central and South American (LCSA); African; East Asian; South Asian; and West Central Asian and Middle Eastern. RESULTS: Europeans had the highest standardized incidence rates, while NINA had the highest mortality rates. Rates varied substantially by ethnicity and immigrant status. The top three cancers accounted for 46.5% to 61.9% of all new cancers, while the top three cancer deaths accounted for 36.1% to 61.9% of all deaths. The distribution of cancers within the top 10 cancers and the top 10 cancer deaths also differed; e.g., stomach cancer was found to be more prevalent in the East Asian, LCSA, African and Caribbean groups. Non-immigrant African males had the highest cancer incidence rates, and non-immigrant South Asian females had the highest mortality rates. DISCUSSION: There is considerable variability in cancer incidence and cancer mortality rates by ethnicity, and this study addresses the knowledge gap in Canada in this area. Establishing baseline indicators, such as cancer rates by ethnicity, is essential to understanding the differences within the diverse Canadian population and to informing targeted interventions that may help reduce health inequalities.

A systematic review and meta-analysis of the association between childhood infections and the risk of childhood acute lymphoblastic leukaemia.

BACKGROUND: To determine whether childhood infections were associated with the development of childhood acute lymphoblastic leukaemia (ALL). METHODS: We included studies that assessed any infection in childhood prior to the diagnosis of ALL in children aged 0-19 years compared to children without cancer. The primary analysis synthesised any infection against the odds of ALL, and secondary analyses assessed the frequency, severity, timing of infections, and specific infectious agents against the odds of ALL. Subgroup analyses by data source were investigated. RESULTS: In our primary analysis of 12 496 children with ALL and 2 356 288 children without ALL from 38 studies, we found that any infection was not associated with ALL (odds ratio (OR)=1.10, 95% CI: 0.95-1.28). Among studies with laboratory-confirmed infections, the presence of infections increased the odds of ALL by 2.4-fold (OR=2.42, 95% CI: 1.54-3.82). Frequency, severity, and timing of infection were not associated with ALL. CONCLUSIONS: The hypothesis put forward by Greaves and others about an infectious aetiology are neither confirmed nor refuted and the overall evidence remains inadequate for good judgement. The qualitative difference in the subgroup effects require further study, and future research will need to address the challenges in measuring infectious exposures.

Identifying diabetes cases from administrative data: a population-based validation study.

BACKGROUND: Health care data allow for the study and surveillance of chronic diseases such as diabetes. The objective of this study was to identify and validate optimal algorithms for diabetes cases within health care administrative databases for different research purposes, populations, and data sources. METHODS: We linked health care administrative databases from Ontario, Canada to a reference standard of primary care electronic medical records (EMRs). We then identified and calculated the performance characteristics of multiple adult diabetes case definitions, using combinations of data sources and time windows. RESULTS: The best algorithm to identify diabetes cases was the presence at any time of one hospitalization or physician claim for diabetes AND either one prescription for an anti-diabetic medication or one physician claim with a diabetes-specific fee code [sensitivity 84.2%, specificity 99.2%, positive predictive value (PPV) 92.5%]. Use of physician claims alone performed almost as well: three physician claims for diabetes within one year was highly specific (sensitivity 79.9%, specificity 99.1%, PPV 91.4%) and one physician claim at any time was highly sensitive (sensitivity 93.6%, specificity 91.9%, PPV 58.5%). CONCLUSIONS: This study identifies validated algorithms to capture diabetes cases within health care administrative databases for a range of purposes, populations and data availability. These findings are useful to study trends and outcomes of diabetes using routinely-collected health care data.

Mortality trends in women and men with COPD in Ontario, Canada, 1996-2012.

IMPORTANCE: COPD is the third leading cause of death worldwide. Mortality trends offer an indication of how well a society is doing in fighting a disease. OBJECTIVE: To examine trends in all-cause, lung cancer, cardiovascular and COPD mortalities in people with COPD, overall and in men and women. DESIGN, SETTING, PARTICIPANTS: Population, cohort study using health administrative data from Ontario, Canada, 1996 to 2011. EXPOSURE: A previously validated COPD case definition was used to identify all people with COPD. MAIN OUTCOMES AND MEASURES: All-cause, lung cancer, cardiovascular and COPD mortality rates were determined annually from 1996 to 2011 overall, and in men and women. All-cause trends were compared with all-cause trends in the non-COPD population. All rates were standardised to the 2006 Ontario population. RESULTS: The prevalence of COPD was 11.0% in 2011. Over the study period, all-cause mortality decreased significantly more in men with COPD than the non-COPD population. The same was not observed in women. COPD-specific and lung cancer mortalities, which started higher in men with COPD, decreased faster in them than in women with COPD with the two rates becoming more similar over time. Cardiovascular disease mortality declined at a relatively equal rate in both sexes. CONCLUSIONS AND RELEVANCE: Mortality in people with COPD has decreased; however, the decrease has been greater in men than in women. Public health interventions and medical care appear to be improving mortality in individuals with COPD but more research is needed to determine if they are benefiting both sexes equally.

Socioeconomic Status, Sex, Age and Access to Medications for COPD in Ontario, Canada.

Disparities in COPD health outcomes have been found with older individuals, men and those of lower socioeconomic status doing worse. We sought to determine if this was due to differences in access to COPD medications. We conducted a retrospective cohort study using population health administrative data from Ontario, Canada, a province with universal prescription drug coverage for older adults. All individuals with COPD aged 67 years and older in 2008 who were not taking inhaled long-acting bronchodilators or inhaled corticosteroids were followed for 2 years. Poisson regression was used to determine the effects of age, sex, and socioeconomic status on the likelihood of initiating one of these medications, after adjusting for potential confounders. Over the study period, 54,050 of 185,698 (29.1%) older individuals with COPD not previously taking any inhaled long-acting bronchodilators or corticosteroids were initiated on one or more of these medications. After adjustment, individuals of low socioeconomic status, measured using neighborhood income level quintiles, were slightly more likely to initiate COPD medications than those of high socioeconomic status (relative risk (RR) 1.05; 95% confidence interval (95% CI) 1.02-1.08). While men received COPD medication at a consistent rate across all age groups, the likelihood that a woman received medication decreased with increasing age. With the exception of older women, there was minimal disparity in prescription for COPD medications. Disparity in health outcomes among Ontario COPD patients is not clearly explained by differences in medication access by socioeconomic status, sex or age.

The chronic rhinosinusitis with nasal polyp patient journey in the United States and Europe.

In this letter to the editor, we present questionnaire-based data assessing the patient journey of adults with moderate-severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the USA and five European countries. These data highlight how long and difficult the patient journey with CRSwNP can be and how improved disease awareness among physicians could lead to more timely diagnosis and treatment, and hence improved management of patients.

Prevalence, incidence and healthcare burden of eosinophilic granulomatosis with polyangiitis in the UK.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease characterised by the combination of small-to-medium vessel vasculitis, blood and tissue eosinophilia, and asthma and/or sinonasal disease. This study estimated the prevalence and incidence of diagnosed EGPA in the United Kingdom (UK), and described the demographics, clinical characteristics and healthcare resource utilisation (HCRU) of this population. Methods: This retrospective longitudinal study of patients with newly diagnosed EGPA (index) (2005-2019) used the Clinical Practice Research Datalink AURUM and Hospital Episode Statistics databases. The primary outcomes were the annual prevalence (2005-2019) and incidence (2006-2019) of EGPA, and secondary outcomes included patient demographics and clinical characteristics, and HCRU in the year pre- and post-index (diagnosis). Results: Populations of patients with EGPA comprised 940 prevalent cases and 502 incident cases, of which 377 were linked to Hospital Episode Statistics. EGPA prevalence increased from 22.7 to 45.6 cases per 1 000 000 (2005-2019), driven by patients aged ≥18 years. Incidence ranged from 2.3 to 4.0 per 1 000 000 person-years (2006-2019). Pre-index, the most common clinical symptoms were respiratory related, and the most common comorbidities were asthma (80.6%) and nasal polyps (32.1%). Post-index, 19.1% had an EGPA-related inpatient stay (median length of stay 11.0 days) and 38.7% had five or more oral corticosteroid (OCS) prescriptions with a mean OCS possession ratio per patient of 47.0%. Conclusions: Although EGPA incidence in the UK remains relatively stable, prevalence is increasing, and HCRU and OCS use remain frequent, suggesting considerable healthcare burden for patients with EGPA.

Preeclampsia as a risk factor for diabetes: a population-based cohort study.

BACKGROUND: Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes. METHODS AND FINDINGS: We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n=22,933), GH alone (n=27,605), GDM alone (n=30,852), GDM+PEC (n=1,476), GDM+GH (n=2,100), or none of these conditions (n=925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio [HR]=2.08; 95% CI 1.97-2.19) and GH alone (HR=1.95; 95% CI 1.83-2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR=12.77; 95% CI 12.44-13.10); however, the co-presence of PEC or GH in addition to GDM further elevated this risk (HR=15.75; 95% CI 14.52-17.07, and HR=18.49; 95% CI 17.12-19.96, respectively). Data on obesity were not available. CONCLUSIONS: Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes. Please see later in the article for the Editors' Summary.

The Burden of Health-Related Out-of-Pocket Cancer Costs in Canada: A Case-Control Study Using Linked Data.

BACKGROUND: The burden of out-of-pocket costs among cancer patients/survivors in Canada is not well understood. The objective of this study was to examine the health-related out-of-pocket cost burden experienced by households with a cancer patient/survivor compared to those without, examine the components of health-related costs and determine who experiences a greater burden. DATA AND METHODS: This study used a data linkage between the Survey of Household Spending and the Canadian Cancer Registry to identify households with a cancer patient/survivor (cases) and those without (controls). The out-of-pocket burden (out-of-pocket costs measured relative to household income) and mean costs were described and regression analyses examined the characteristics associated with the household out-of-pocket burden and annual out-of-pocket costs. RESULTS: The health-related out-of-pocket cost burden and annual costs measured in households with a cancer patient/survivor were 3.08% (95% CI: 2.55-3.62%) and CAD 1600 (95% CI: 1456-1759), respectively, compared to a burden of 2.84% (95% CI: 2.31-3.38) and annual costs of CAD 1511 (95% CI: 1377-1659) measured in control households, respectively. Households with a colorectal cancer patient/survivor had a significantly higher out-of-pocket burden compared to controls (mean difference: 1.0%, 95% CI: 0.18, 0.46). Among both cases and controls, the lowest income quintile households experienced the highest health-related out-of-pocket cost burden. INTERPRETATION: Within a universal health care system, it is still relevant to monitor health-related out-of-pocket spending that is not covered by existing insurance mechanisms; however, this is not routinely assessed in Canada. We demonstrate the feasibility of measuring such costs in households with a cancer patient/survivor using routinely collected data. While the burden and annual health-related out-of-pocket costs of households with a cancer patient/survivor were not significantly higher than control households in this study, the routine measurement of out-of-pocket costs in Canada could be systemized, providing a novel, system-level, equity-informed performance indicator, which is relevant for monitoring inequities in the burden of out-of-pocket costs.

The web-based "Right Review" tool asks reviewers simple questions to suggest methods from 41 knowledge synthesis methods.

OBJECTIVES: To develop a web-based decision support tool that guides users through a series of simple questions for recommending knowledge synthesis methods suitable for their research question. STUDY DESIGN AND SETTING: We used findings from previous work to structure a set of questions along key dimensions of different knowledge synthesis methods. We developed the tool using four steps: (1) designing the tool, (2) conducting usability testing, (3) disseminating the tool, and (4) evaluating its real-world use. Steps 1-3 were conducted iteratively, and the tool was evaluated using the RE-AIM framework. RESULTS: The "Right Review" tool separates quantitative reviews and qualitative evidence synthesis (QES). Five questions are asked to select from among 26 methods for quantitative reviews, and 10 questions to select methods from among 15 QES. Conduct/reporting guidance and open-access examples are provided for each recommended method. The tool was disseminated to >4,600 users worldwide within 12 months. Evaluation results showed that the tool was fit-for-purpose and easy to use. CONCLUSION: The proliferation of knowledge synthesis methods makes it challenging for reviewers to select the "right" method. "Right Review" is a free, practical decision support tool that helps reviewers choose an appropriate method from 41 alternatives.

Infections and the development of childhood acute lymphoblastic leukemia: a population-based study.

An infectious trigger for childhood acute lymphoblastic leukemia is hypothesized and we assessed the association between the rate, type, and critical exposure period for infections and the development of acute lymphoblastic leukemia. We conducted a matched case-control study using administrative databases to evaluate the association between the rate of infections and childhood acute lymphoblastic leukemia diagnosed between the ages of 2-14 years from Ontario, Canada and we used a validated approach to measure infections. In 1600 cases of acute lymphoblastic leukemia, and 16 000 matched cancer-free controls aged 2-14 years, having >2 infections/year increased the odds of childhood acute lymphoblastic leukemia by 43% (odds ratio = 1.43, 95% confidence interval 1.13-1.81) compared to children with ≤0.25 infections/year. Having >2 respiratory infections/year increased odds of acute lymphoblastic leukemia by 28% (odds ratio =1.28, 95% confidence interval 1.05-1.57) compared to children with ≤0.25 respiratory infections/year. Having an invasive infection increased the odds of acute lymphoblastic leukemia by 72% (odds ratio =1.72, 95% confidence interval 1.31-2.26). Having an infection between the age of 1-1.5 years increased the odds of acute lymphoblastic leukemia by 20% (odds ratio = 1.20, 95% confidence interval 1.04-1.39). Having more infections increased the odds of developing childhood acute lymphoblastic leukemia and having an infection between the ages of 1-1.5 years increased the odds of childhood acute lymphoblastic leukemia.

Unnecessary antibiotic prescribing in a Canadian primary care setting: a descriptive analysis using routinely collected electronic medical record data.

BACKGROUND: Unnecessary antibiotic use in the community in Canada is not well defined. Our objective was to quantify unnecessary antibiotic prescribing in a Canadian primary care setting. METHODS: We performed a descriptive analysis in Ontario from April 2011 to March 2016 using the Electronic Medical Records Primary Care database linked to other health administrative data sets at ICES. We determined antibiotic prescribing rates (per 100 patient-physician encounters) for 23 common conditions and estimated rates of unnecessary prescribing using predefined expected prescribing rates, both stratified by condition and patient age group. RESULTS: The study included 341 physicians, 204 313 patients and 499 570 encounters. The rate of unnecessary antibiotic prescribing for included conditions was 15.4% overall and was 17.6% for those less than 2 years of age, 18.6% for those aged 2-18, 14.5% for those aged 19-64 and 13.0% for those aged 65 or more. The highest unnecessary prescribing rates were observed for acute bronchitis (52.6%), acute sinusitis (48.4%) and acute otitis media (39.3%). The common cold, acute bronchitis, acute sinusitis and miscellaneous nonbacterial infections were responsible for 80% of the unnecessary antibiotic prescriptions. Of all antibiotics prescribed, 12.0% were for conditions for which they are never indicated, and 12.3% for conditions for which they are rarely indicated. In children, 25% of antibiotics were for conditions for which they are never indicated (e.g., common cold). INTERPRETATION: Antibiotics were prescribed unnecessarily for 15.4% of included encounters in a Canadian primary care setting. Almost one-quarter of antibiotics were prescribed for conditions for which they are rarely or never indicated. These findings should guide safe reductions in the use of antibiotics for the common cold, bronchitis and sinusitis.

Incidence of infections after therapy completion in children with acute lymphoblastic leukemia or acute myeloid leukemia: a systematic review of the literature.

Infections are a common complication of treatment for pediatric acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Less is known about infections occurring after treatment. We performed a systematic review of the literature to assess the incidence of infections after therapy completion in children and young adults with ALL or AML. Twenty-eight studies, with 4138 patients, were included. Four studies reported infections in patients who did not undergo hematopoietic stem cell transplant (HSCT). Respiratory tract and urinary tract infections affected 9.9-72.5% and 2.9-19.8% of patients, respectively. Twelve studies reported infections in patients treated with HSCT. Late bacterial, viral and fungal infections affected 3.9-38.5%, 16.1-66.7%, and 0.2-41.7% of patients, respectively. Viral hepatitis affected 0.8-75.4% of patients from 12 studies. Our review suggests that infections are a frequent complication after treatment for leukemia in children, especially after HSCT and identifies several knowledge gaps in the current literature.

Long-Term Risk of Infections After Treatment of Childhood Leukemia: A Population-Based Cohort Study Using Administrative Health Data.

PURPOSE: Infections are a frequent complication during childhood leukemia treatment. Little is known about the infectious risk in survivors. We compared the relative rate (RR) of infections after treatment completion between pediatric leukemia survivors and the general population. METHODS: We performed a retrospective, population-based cohort study of children diagnosed with leukemia between 1992 and 2015 in Ontario, Canada, who were alive and relapse free 30 days after treatment completion (index date). Leukemia survivors were matched 5:1 with the general population by year of birth, sex, and rural status and stratified by initial treatment, including and excluding hematopoietic stem-cell transplantation (HSCT). The primary outcome was time to infections, as identified using validated diagnostic codes from administrative databases. Individuals were censored at the earliest of death, first relapse, loss to follow-up, or end of study. RESULTS: A total of 2,204 leukemia survivors were included and matched with 11,020 controls. The rate of infections was elevated after treatment completion compared with controls (RR, 1.51; 95% CI, 1.45 to 1.57) and at less than 1 year (RR, 1.77; 95% CI, 1.69 to 1.86); 1 to 4.99 years (RR, 1.66; 95% CI, 1.62 to 1.71), and 5 or more years (RR, 1.29; 95% CI, 1.22 to 1.36) from the index date. Among those whose initial treatment excluded HSCT, the rate remained elevated more than 5 years from the index date (RR, 1.29; 95% CI, 1.23 to 1.35). Infection-related death was significantly increased in leukemia survivors both among the entire cohort (hazard ratio, 149.3; 95% CI, 20.4 to 1,091.9) and among those without HSCT (hazard ratio, 92.7; 95% CI, 12.4 to 690.7). CONCLUSION: A significant association was found between a history of leukemia therapy and an increased risk of infections. Additional study is needed to establish which exposures in patients with leukemia lead to late infections.

Few studies exist examining methods for selecting studies, abstracting data, and appraising quality in a systematic review.

OBJECTIVES: The aim of the article was to identify and summarize studies assessing methodologies for study selection, data abstraction, or quality appraisal in systematic reviews. STUDY DESIGN AND SETTING: A systematic review was conducted, searching MEDLINE, EMBASE, and the Cochrane Library from inception to September 1, 2016. Quality appraisal of included studies was undertaken using a modified Quality Assessment of Diagnostic Accuracy Studies 2, and key results on accuracy, reliability, efficiency of a methodology, or impact on results and conclusions were extracted. RESULTS: After screening 5,600 titles and abstracts and 245 full-text articles, 37 studies were included. For screening, studies supported the involvement of two independent experienced reviewers and the use of Google Translate when screening non-English articles. For data abstraction, studies supported involvement of experienced reviewers (especially for continuous outcomes) and two independent reviewers, use of dual monitors, graphical data extraction software, and contacting authors. For quality appraisal, studies supported intensive training, piloting quality assessment tools, providing decision rules for poorly reported studies, contacting authors, and using structured tools if different study designs are included. CONCLUSION: Few studies exist documenting common systematic review practices. Included studies support several systematic review practices. These results provide an updated evidence-base for current knowledge synthesis guidelines and methods requiring further research.