DNA repair defects in cancer and therapeutic opportunities.

DNA repair and DNA damage signaling pathways are critical for the maintenance of genomic stability. Defects of DNA repair and damage signaling contribute to tumorigenesis, but also render cancer cells vulnerable to DNA damage and reliant on remaining repair and signaling activities. Here, we review the major classes of DNA repair and damage signaling defects in cancer, the genomic instability that they give rise to, and therapeutic strategies to exploit the resulting vulnerabilities. Furthermore, we discuss the impacts of DNA repair defects on both targeted therapy and immunotherapy, and highlight emerging principles for targeting DNA repair defects in cancer therapy.

Burnout among public health workers in Canada: a cross-sectional study.

BACKGROUND: This study presents the prevalence of burnout among the Canadian public health workforce after three years of the COVID-19 pandemic and its association with work-related factors. METHODS: Data were collected using an online survey distributed through Canadian public health associations and professional networks between November 2022 and January 2023. Burnout was measured using a modified version of the Oldenburg Burnout Inventory (OLBI). Logistic regressions were used to model the relationship between burnout and work-related factors including years of work experience, redeployment to pandemic response, workplace safety and supports, and harassment. Burnout and the intention to leave or retire as a result of the COVID-19 pandemic was explored using multinomial logistic regressions. RESULTS: In 2,079 participants who completed the OLBI, the prevalence of burnout was 78.7%. Additionally, 49.1% of participants reported being harassed because of their work during the pandemic. Burnout was positively associated with years of work experience, redeployment to the pandemic response, being harassed during the pandemic, feeling unsafe in the workplace and not being offered workplace supports. Furthermore, burnout was associated with greater odds of intending to leave public health or retire earlier than anticipated. CONCLUSION: The high levels of burnout among our large sample of Canadian public health workers and its association with work-related factors suggest that public health organizations should consider interventions that mitigate burnout and promote recovery.

Early (years) reactions: comparative analysis of early childhood policies and programs during the first wave of the COVID-19 pandemic.

BACKGROUND: During the first wave of COVID-19 there was little evidence to guide appropriate child and family programs and policy supports. METHODS: We compared policies and programs implemented to support early child health and well-being during the first wave of COVID-19 in Australia, Canada, the Netherlands, Singapore, the UK, and the USA. Program and policy themes were focused on prenatal care, well-baby visits and immunization schedules, financial supports, domestic violence and housing, childcare supports, child protective services, and food security. RESULTS: Significant heterogeneity in implementation of OECD-recommended policy responses was found with all of the included countries implementing some of these policies, but no country implementing supports in all of the potential areas. CONCLUSIONS: This analysis gives insight into initial government reactions to support children and families, and opportunities for governments to implement further supportive programs and policies during the current pandemic and future emergencies.

The Impact of Muscle and Adipose Tissue on Long-term Survival in Patients With Stage I to III Colorectal Cancer.

BACKGROUND: Computed tomography-derived body composition parameters are emerging prognostic factors in colorectal cancer. OBJECTIVE: This study aimed to determine the roles of sarcopenia, myosteatosis, and obesity as independent and overlapping parameters in stage I to III colorectal cancer. DESIGN: This is a retrospective cohort study from a prospectively collected database. Multivariate Cox proportional hazards models were performed to assess the associations between body composition parameters and survival. SETTINGS: All patients were seen in a tertiary care cancer center. PATIENTS: Adult patients with stage I to III colorectal cancer, undergoing curative resection from 2007 to 2009, were included. INTERVENTION: Computed tomography-derived quantification of skeletal muscle and adipose tissues was used to determine population-specific cutoffs for sarcopenia, myosteatosis, and total adiposity. MAIN OUTCOME MEASURES: Primary outcome measures were overall, recurrence-free, and cancer-specific survival. RESULTS: In the 968 patients included, there were a total of 254 disease recurrences and 350 deaths. Body mass index and CT-derived measures of adiposity did not result in worse survival outcomes. Sarcopenia was independently predictive of worse overall (HR, 1.45; 95% CI, 1.16-1.84), recurrence-free (HR, 1.32; 95% CI, 1.00-1.75), and cancer-specific survival (HR, 1.46; 95% CI, 1.09-1.94) in a multivariate model. Myosteatosis was also independently predictive of overall survival (HR, 1.53; 95% CI, 1.19-1.97). In a model considering joint effects of sarcopenia and myosteatosis, the presence of both predicted the worst overall (HR, 2.23; 95% CI, 1.62-3.06), recurrence-free (HR, 1.53; 95% CI, 1.06-2.21), and cancer-specific survival (HR, 2.40; 95% CI, 1.69-3.42) in a multivariate model. LIMITATIONS: The limitations of this study are inherent in retrospective observational studies. CONCLUSIONS: Sarcopenia and myosteatosis are independent predictors of worse survival in stage I to III colorectal cancer, and their joint effect is highly predictive of reduced overall, recurrence-free, and cancer-specific survival. See Video Abstract at http://links.lww.com/DCR/A923.

Change in Skeletal Muscle Following Resection of Stage I-III Colorectal Cancer is Predictive of Poor Survival: A Cohort Study.

BACKGROUND: Sarcopenia at time of diagnosis predicts worse survival outcomes. It is currently unknown how changes in muscle mass over time interact with sarcopenia in colorectal patients treated with curative intent. Objectives of this study were to quantify sarcopenia and skeletal muscle loss from time of diagnosis to end of surveillance and determine its effect on survival outcomes after completion of 2 years of surveillance. METHODS: Retrospective cohort study of stage I-III colorectal cancer patients from 2007-2009, who underwent resection and had preoperative and 2-year surveillance computed tomography scans, without recurrence during that time. Body composition analysis was done at both time points to determine lumbar skeletal muscle index, radiodensity and adiposity. Change over time was standardized as a percentage per year. Cox proportional hazard regression modeling was used for survival analysis. RESULTS: Of 667 patients included, median survival from surgery was 7.96 years, with 75 recurrences occurring after 2 years. On average patients lost muscle mass (-0.415%/year; CI -0.789, -0.042) and radiodensity (-5.76 HU/year; CI -6.74, -4.80), but gained total adipose tissue (7.06%/year; CI 4.34, 9.79). Patients with sarcopenia at diagnosis (HR 1.80; CI 1.13, 2.85) or muscle loss over time (HR 1.55; CI 1.01, 2.37) had worse overall survival, with significantly worse joint effect (HR 2.73; CI 1.32, 5.65). CONCLUSIONS: Sarcopenia at diagnosis combined with ongoing skeletal muscle loss over time resulted in significantly worse survival. Patients with these features who are recurrence-free at 2 years are more likely to have a non-colorectal cancer cause of death.

Low prioritization of latent tuberculosis infection-A systemic barrier to tuberculosis control: A qualitative study in Ontario, Canada.

BACKGROUND: Eliminating tuberculosis (TB) in low-incidence countries is an important global health priority, and Canada has committed to achieve this goal. The elimination of TB in low-incidence countries requires effective management and treatment of latent tuberculosis infection (LTBI). This study aimed to understand and describe the system-level barriers to LTBI treatment for immigrant populations in the Greater Toronto and Hamilton Area, Ontario, Canada. METHODS: A qualitative study that used purposive sampling to recruit and interview health system advisors and planners (n = 10), providers (n = 13), and clients of LTBI health services (n = 9). Data were recorded, transcribed verbatim, and analyzed using content analysis. RESULTS: Low prioritization of LTBI was an overarching theme that impacted four dimensions of LTBI care: management, service delivery, health literacy, and health care access. These factors explained, in part, inequities in the system that were linked to variations in health care quality and health care access. While some planners and providers at the local level were attempting to prioritize LTBI care, there was no clear pathway for information sharing. CONCLUSIONS: This multiperspective study identified barriers beyond the typical socioeconomic determinants and highlighted important upstream factors that hinder treatment initiation and adherence. Addressing these factors is critical if Canada is to meet the WHO's global call to eradicate TB in all low incidence settings.

Barriers to the Interpretation of Body Composition in Colorectal Cancer: A Review of the Methodological Inconsistency and Complexity of the CT-Defined Body Habitus.

BACKGROUND: Measurement of body composition by computed tomography (CT) is an advancing field. Sarcopenia, myosteatosis, and visceral obesity (VO) have been identified as predictive of survival in colorectal cancer (CRC). We performed a systematic review of contemporary studies to characterize this association and highlight methodological inconsistencies. METHODS: MEDLINE and PubMed were queried for articles published from January 2000 on, with populations of resectable CRC and with CT-measured body composition and survival data. The study quality was assessed by two independent reviewers using the Newcastle-Ottawa Scale. RESULTS: Twenty studies met inclusion criteria, with a total of 8895 patients. Only two of the studies scored as high quality and nine as moderate quality. The remaining nine studies scored as low quality. Ten studies considered sarcopenia and 12 considered visceral obesity (VO). Cutoff points to define sarcopenia, myosteatosis, and VO were identified by optimal stratification, quartiles, or median values. The prevalence of sarcopenia varied from 15 to 60%, which based on study population and cutoff value used. Sarcopenia was associated with worse overall and disease-free survival in eight of the included studies. Myosteatosis was considered in three studies with a prevalence of 19-78%. It was significantly predictive of worse overall and disease-free survival in all three studies. VO had a prevalence of 14-70% and was inconsistently predictive of survival outcomes. CONCLUSIONS: There is a lack of methodological consistency within the currently published literature. Despite this, sarcopenia and myosteatosis, but not VO, are consistently associated with worse survival outcomes, when population and cancer-specific cutoffs are utilized.

Assessment of Computed Tomography (CT)-Defined Muscle and Adipose Tissue Features in Relation to Short-Term Outcomes After Elective Surgery for Colorectal Cancer: A Multicenter Approach.

BACKGROUND: Sarcopenia, visceral obesity (VO), and reduced muscle radiodensity (myosteatosis) are suggested risk factors for postoperative morbidity in colorectal cancer (CRC), but usually are not concurrently assessed. Published thresholds used to define these features are not CRC-specific and are defined in relation to mortality, not postoperative outcomes. This study aimed to evaluate body composition in relation to length of hospital stay (LOS) and postoperative outcomes. METHODS: Pre-surgical computed tomography (CT) images were assessed for total area and radiodensity of skeletal muscle and visceral adipose tissue in a pooled Canadian and UK cohort (n = 2100). Sex- and age-specific values for these features were calculated. For 1139 of 2100 patients, LOS data were available, and sex- and age-specific thresholds for sarcopenia, myosteatosis, and VO were defined on the basis of LOS. Association of CT-defined features with LOS and readmissions was explored using negative binomial and logistic regression models, respectively. RESULTS: In the multivariable analysis, the predictors of LOS (P < 0.001) were age, surgical approach, major complications (incidence rate ratio [IRR] 2.42; 95% confidence interval [CI] 2.18-2.68), study cohort, and three body composition profiles characterized by myosteatosis combined with either sarcopenia (IRR, 1.27; 95% CI 1.12-1.43) or VO (IRR, 1.25; 95% CI 1.10-1.42), and myosteatosis combined with both sarcopenia and VO (IRR, 1.58; 95% CI 1.29-1.93). In the multivariable analysis, risk of readmission was associated with VO alone (odds ratio [OR] 2.66; 95% CI 1.18-6.00); P = 0.018), VO combined with myosteatosis (OR, 2.72; 95% CI 1.36-5.46; P = 0.005), or VO combined with myosteatosis and sarcopenia (OR, 2.98; 95% CI 1.06-5.46; P = 0.038). Importantly, the effect of body composition profiles on LOS and readmission was independent of major complications. CONCLUSION: The findings showed that CT-defined multidimensional body habitus is independently associated with LOS and hospital readmission.

An Online Drug Abuse Prevention Program for Adolescent Girls: Posttest and 1-Year Outcomes.

Early adolescent girls' rates of drug use have matched, and in some instances, surpassed boys' rates. Though girls and boys share risk factors for drug use, girls also have gender-specific risks. Tailored interventions to prevent girls' drug use are warranted. This study developed and tested a web-based, drug abuse prevention program for adolescent girls. The nationwide sample of 13- and 14-year-old girls (N = 788) was recruited via Facebook ads. Enrolled girls were randomly assigned to the intervention or control condition. All girls completed pretest measures online. Following pretest, intervention girls interacted with the 9-session, gender-specific prevention program online. The program aimed to reduce girls' drug use and associated risk factors by improving their cognitive and behavioral skills around such areas as coping with stress, managing mood, maintaining a healthy body image, and refusing drug use offers. Girls in both conditions again completed measures at posttest and 1-year follow-up. At posttest, and compared to girls in the control condition, girls who received the intervention smoked fewer cigarettes and reported higher self-esteem, goal setting, media literacy, and self-efficacy. At 1-year follow-up, and compared to girls in the control condition, girls who received the intervention reported engaging in less binge drinking and cigarette smoking; girls assigned to the intervention condition also had higher alcohol, cigarette, and marijuana refusal skills, coping skills, and media literacy and lower rates of peer drug use. This study's findings support the use of tailored, online drug abuse prevention programming for early adolescent girls.

Evaluation of the ability of standardized supports to improve public health response to syndromic surveillance for respiratory diseases in Canada.

BACKGROUND: Despite widespread implementation of syndromic surveillance systems within public health agencies, previous studies of the implementation and use of these systems have indicated that the functions and responses taken in response to syndromic surveillance data vary widely according to local context and preferences. The objective of the Syndromic Surveillance Evaluation Study was to develop and implement standardized supports in local public health agencies in Ontario, Canada, and evaluate the ability of these supports to affect actions taken as part of public health communicable disease control programs. METHODS: Local public health agencies (LPHA) in Ontario, which used syndromic surveillance based on emergency department visits for respiratory disease, were recruited and randomly allocated to the study intervention or control group. The intervention group health agencies received standardized supports in terms of a standardized aberrant event detection algorithm and a response protocol dictating steps to investigate and assess the public health significance of syndromic surveillance alerts. The control group continued with their pre-existing syndromic surveillance infrastructure and processes. Outcomes were assessed using logbooks, which collected quantitative and qualitative information about alerts received, investigation steps taken, and public health responses. The study was conducted prospectively for 15 months (October 2013 to February 2015). RESULTS: Fifteen LPHAs participated in the study (n = 9 intervention group, n = 6 control group). A total of 1,969 syndromic surveillance alerts were received by all LPHAs. Variations in the types and amount of responses varied by LPHA, in particularly differences were noted by the size of the health unit. Smaller health units had more challenges to both detect and mount a response to any alerts. LPHAs in the control group were more likely to declare alerts to have public health significance and to initiate any action. Regression models using repeated measures showed an interaction between the year (Year 1 versus Year 2) and the intervention as well as an interaction between year and sustained nature of the alert. Both of these were linked to the control health units reporting more "watchful waiting". CONCLUSIONS: This study raises questions about the effectiveness of using standardized protocols to improve the performance of syndromic surveillance in a decentralized public health system. Despite efforts to create standardized protocols and engage public health agencies in the process, no significant differences in the effective use of syndromic alerts were observed beyond year 1. It also raises questions about the minimum capacity of the agency and minimum population size that are required for an effective response.

Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.

Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3) proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG) protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1ß), two α-kleisins (RAD21L and REC8) and one STAG protein (STAG3) that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC). From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1ß, RAD21L and REC8) is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1ß, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis-specific cohesin complexes. Furthermore, our data suggests that STAG3 is required for structural changes of chromosomes that mediate chromosome pairing and synapsis, DNA repair and progression of meiosis.

Is the Legalization of Marijuana Associated With Its Use by Adolescents?

BACKGROUND: Growing moves in the U.S. toward relaxed laws surrounding adult use of marijuana raise concerns about concurrent increases in adolescent use of marijuana. OBJECTIVES: This study collected and analyzed primary data on the relationship between marijuana legalization status in U.S. states and adolescents' marijuana use. METHODS: Recruited through social networking sites and youth-services community agencies, a sample of 1,310 adolescents from 48 U.S. states and the District of Columbia reported their use of marijuana. Youths' use rates were compared with the marijuana legalization status of youths' states of residence. RESULTS: Study findings failed to show a relationship between adolescents' use of marijuana and state laws regarding marijuana use. Relationships were found for increased marijuana use by older youths, females, and non-Hispanic youths. Youths whose parents completed 2 or more years of college were less likely to report marijuana use than those whose parents completed fewer than 2 years of college. CONCLUSIONS: Albeit study findings do not support predictions of growing marijuana use by adolescents in states with liberalized adult use laws, further monitoring of adolescents' use with larger and more representative samples is needed.

Risk and protective factors associated with adolescent girls' substance use: Data from a nationwide Facebook sample.

BACKGROUND: Despite overall reductions in teenage substance use, adolescent girls' rates of substance use remain unacceptably high. This article examines whether girls' substance use is associated with general risk and protective factors (goal setting, problem solving, refusal skills, peer use, and self-efficacy) and gender-specific risk and protective factors (communication style, coping skills, self-esteem, body image, perceived stress, anxiety, and depression). METHODS: Cross-sectional data were collected in 2013 via online surveys from a nationwide sample of adolescent girls (N = 788), aged 13 and 14 years, who were recruited through Facebook. RESULTS: In multivariate analyses, controlling for correlates of adolescent substance use, 11 of the 13 general and gender-specific risk and protective factors were consistently associated with past-month alcohol, cigarette, and other drug use in the expected direction; past-month marijuana use was associated with 8 of the 13 factors. Refusal skills, peer use, coping, and depressive mood were most consistently and strongly associated with substance use. CONCLUSIONS: Substance abuse prevention programs targeting adolescent girls should focus on such general risk and protective factors as problem solving, refusal skills, peer influences, and self-efficacy, as well as such gender-specific risk and protective factors as communication style, coping, self-esteem, body image, perceived stress, and mood management.

Developing a Web-Based Intervention to Prevent Drug Use among Adolescent Girls.

OBJECTIVES: Girls' rates of drug use have met up with, and in some instances, surpassed boys' use. Though girls and boys share risk and protective factors associated with drug use, girls also have gender-specific risks. Interventions to prevent girls' drug use must be tailored to address the dynamics of female adolescence. METHODS: One such intervention, called RealTeen, is a 9-session, web-based drug abuse prevention program designed to address such gender-specific risk factors associated with young girls' drug use as depressed mood, low self-esteem, and high levels of perceived stress as well as general drug use risk factors of peer and social influences. Web-based delivery enables girls to interact with the program at their own pace and in a location of their choosing. IMPLICATIONS: This paper describes the processes and challenges associated with developing and programming a gender-specific, web-based intervention to prevent drug use among adolescent girls.

Barriers and opportunities faced by public health practitioners in using public health guidance on COVID-19: a knowledge translation exercise for the eCOVID-19 RecMap.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic prompted the scientific community to collaborate in an unprecedented way, with the rapid and urgent generation and translation of new knowledge about the disease and its causative agent. Iteratively, and at different levels of government and globally, population-level guidance was created and updated, resulting in the need for a living catalog of guidelines, the eCOVID-19 Recommendations Map and Gateway to Contextualization (RecMap). This article focuses on the approach that was used to analyze barriers and opportunities associated with using the RecMap in public health in Canada. STUDY DESIGN AND SETTING: A mixed qualitative and quantitative approach data were used to inform this knowledge mobilization project and inform feedback on implementation of the eCOVID-19 RecMap. This approach involved surveying 110 attendees from a public health webinar. Following this webinar, an evidence brief and series of case studies were created and disseminated to 24 Canadian public health practitioners who attended a virtual workshop. This workshop identified barriers and opportunities to improve RecMap use. RESULTS: This study helped to shed light on the needs that public health practitioners have when finding, using, and disseminating public health guidelines. Through the workshop that was conducted, opportunities for public health guidelines can be categorized into 4 categories: 1) information access, 2) awareness, 3) public health development, and 4) usability. Barriers that were identified can also be categorized into 4 categories: 1) usability, 2) information maintenance, 3) public health guidance, 4) awareness. CONCLUSION: This work will help to inform the development and organization of future public health guidelines, and the needs that public health practitioners have when engaging with them.

A comparative analysis of early child health and development services and outcomes in countries with different redistributive policies.

BACKGROUND: The social environment is a fundamental determinant of early child development and, in turn, early child development is a determinant of health, well-being, and learning skills across the life course. Redistributive policies aimed at reducing social inequalities, such as a welfare state and labour market policies, have shown a positive association with selected health indicators. In this study, we investigated the influence of redistributive policies specifically on the social environment of early child development in five countries with different political traditions. The objective of this analysis was to highlight similarities and differences in social and health services between the countries and their associations with other health outcomes that can inform better global early child development policies and improve early child health and development. METHODS: Four social determinants of early child development were selected to provide a cross-section of key time periods in a child's life from prenatal to kindergarten. They included: 1) prenatal care, 2) maternal leave, 3) child health care, and 4) child care and early childhood education. We searched international databases and reports (e.g. Organization for Economic Cooperation and Development, World Bank, and UNICEF) to obtain information about early child development policies, services and outcomes. RESULTS: Although a comparative analysis cannot claim causation, our analysis suggests that redistributive policies aimed at reducing social inequalities are associated with a positive influence on the social determinants of early child development. Generous redistributive policies are associated with a higher maternal leave allowance and pay and more preventive child healthcare visits. A decreasing trend in infant mortality, low birth weight rate, and under five mortality rate were observed with an increase in redistributive policies. No clear influence of redistributive policies was observed on breastfeeding and immunization rates. In the analysis of child care and early education, the lack of uniform measures of early child development outcomes was apparent. CONCLUSIONS: This paper provides further support for an association between redistributive policies and early child health and development outcomes, along with the organization of early child health and development services.

Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies.

BACKGROUND: Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza. PURPOSE: To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists. STUDY SELECTION: Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness. DATA EXTRACTION: Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: 74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine. LIMITATIONS: Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias. CONCLUSION: Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University.

Effect of aerobic exercise on cognition, academic achievement, and psychosocial function in children: a systematic review of randomized control trials.

INTRODUCTION: Although the effects of aerobic physical activity (APA) on children's physical health is well characterized, the effect of aerobic physical activity on cognition, academic achievement, and psychosocial function has not yet been established. This systematic review provides an overview of research elucidating the relationship between aerobic physical activity and children's cognition, academic achievement, and psychosocial function. METHODS: A systematic review of English articles was performed in April 2013 using MEDLINE, Cochrane, PsycINFO, SPORTDiscus, and EMBASE. Additional studies were identified through back-searching bibliographies. Only randomized control trials with an intervention of aerobic physical activity in children younger than 19 years that measured psychological, behavioral, cognitive, or academic outcomes were included. RESULTS: We found 8 relevant randomized control trials that met our inclusion criteria and extracted relevant data and evaluated the methodologic quality of the studies. Of the 8 studies identified, 2 studies were crossover randomized control trials studying the effects of acute aerobic physical activity on cognitive performance. Six studies were parallel-group randomized control studies, of which only 2 had a follow-up period of longer than 6 months. All studies showed that APA had a generally positive impact on children's cognition and psychosocial function. However, this relationship was found to be minimal in many studies and in some measures, no significant improvement was seen at all. There was no documentation of APA having any negative impact on children's cognition and psychosocial health, even in cases where school curriculum time was reassigned from classroom teaching to aerobic physical activity. CONCLUSION: APA is positively associated with cognition, academic achievement, behavior, and psychosocial functioning outcomes. More rigorous trials with adequate sample sizes assessing the impact of APA on children's cognitive abilities, psychosocial functioning, behavior, and academic achievement are needed, with standardized interventions, valid and reliable tools of measurement, and long-term follow-up for sustained cognitive and psychosocial outcomes.