SARS-CoV-2 seroprevalence and mental health of school staff: a cross-sectional study of schools from four areas of Montreal, Quebec in 2021.

OBJECTIVES: To assess the seroprevalence of infection-acquired SARS-CoV-2 and the mental health of school/daycare staff in the months after reopening of schools in Montreal, Quebec (Canada) in the Fall of 2020 and whether these varied by school and participant characteristics. DESIGN: A cross-sectional design based on a convenience sample of schools/daycares and staff was used as the originally planned longitudinal design was no longer feasible due to obstacles in recruitment, for example, teacher's strike. SETTING: Forty-nine schools/daycares in four Montreal neighbourhoods from March to October 2021. PARTICIPANTS: Three-hundred and sixty-two participants completed both questionnaires and serology tests. PRIMARY AND SECONDARY OUTCOME MEASURES: SARS-CoV-2 seroprevalence and prevalence of anxiety, depression, resilience and burnout/emotional exhaustion. RESULTS: The seroprevalence estimate made representative to the Quebec population of educators was 8.6% (95% CI 5.2 to 13.0). The adjusted seroprevalence in high school was 20% that of elementary school (aRR=0.20, 95% CI 0.07 to 0.58). Thirty per cent of seropositive staff were exposed to a household member with confirmed COVID-19. Prevalence of high emotional exhaustion/burnout was 35%, 44% and 53% in daycare, elementary school and high school staff, respectively. However, moderate/severe anxiety and depression and low resilience did not exceed 18%. After adjusting for confounders, being very afraid of catching COVID-19 at school was associated with moderate-severe anxiety, moderate-severe depression and high emotional exhaustion (aRR=4.4, 95% CI 2.2 to 8.9; aRR=2.8, 95% CI 1.5 to 5.4; aRR=2.2, 95% CI 1.6 to 3.0, respectively). CONCLUSION: The seroprevalence, anxiety and depression among school/daycare staff were comparable to the reported levels in the adult population of Quebec. The prevalence of emotional exhaustion/burnout was high across all school levels and exceeding the average across all occupations in the USA and in teachers in Germany.

Generalizability of anti-SARS-CoV-2 seroprevalence estimates to the Montréal pediatric population: a comparison between two weighting methods.

Seroprevalence studies on SARS-CoV-2 infections have been often based on study populations with non-random and non-representative samples, limiting the generalizability of their results. In this study, we investigated the representativity and the generalizability of the baseline (collected from October 16th, 2020, to April 18th, 2021) estimate of a pediatric seroprevalence study based in Montréal. We compared the change in the estimates of seroprevalence for two different weighting methods: marginal standardization and raking. The target population was the general pediatric population of Montréal and was based on 2016 Canadian census data. Study results show variation across the multiple weighting scenarios although both weighting methods performed similarly, each possessing its own strengths and weaknesses. However, we prefer raking due to its capacity to simultaneously weight for multiple underrepresented study population characteristics.

Mental Health Hospitalizations in Canadian Children, Adolescents, and Young Adults Over the COVID-19 Pandemic.

Importance: The COVID-19 pandemic resulted in multiple socially restrictive public health measures and reported negative mental health impacts in youths. Few studies have evaluated incidence rates by sex, region, and social determinants across an entire population. Objective: To estimate the incidence of hospitalizations for mental health conditions, stratified by sex, region, and social determinants, in children and adolescents (hereinafter referred to as youths) and young adults comparing the prepandemic and pandemic-prevalent periods. Design, Setting, and Participants: This Canadian population-based repeated ecological cross-sectional study used health administrative data, extending from April 1, 2016, to March 31, 2023. All youths and young adults from 6 to 20 years of age in each of the Canadian provinces and territories were included. Data were provided by the Canadian Institute for Health Information for all provinces except Quebec; the Institut National d'Excellence en Santé et en Services Sociaux provided aggregate data for Quebec. Exposures: The COVID-19-prevalent period, defined as April 1, 2020, to March 31, 2023. Main Outcomes and Measures: The main outcome measures were the prepandemic and COVID-19-prevalent incidence rates of hospitalizations for anxiety, mood disorders, eating disorders, schizophrenia or psychosis, personality disorders, substance-related disorders, and self-harm. Secondary measures included hospitalization differences by sex, age group, and deprivation as well as emergency department visits for the same mental health conditions. Results: Among Canadian youths and young adults during the study period, there were 218 101 hospitalizations for mental health conditions (ages 6 to 11 years: 5.8%, 12 to 17 years: 66.9%, and 18 to 20 years: 27.3%; 66.0% female). The rate of mental health hospitalizations decreased from 51.6 to 47.9 per 10 000 person-years between the prepandemic and COVID-19-prevalent years. However, the pandemic was associated with a rise in hospitalizations for anxiety (incidence rate ratio [IRR], 1.11; 95% CI, 1.08-1.14), personality disorders (IRR, 1.21; 95% CI, 1.16-1.25), suicide and self-harm (IRR, 1.10; 95% CI, 1.07-1.13), and eating disorders (IRR, 1.66; 95% CI, 1.60-1.73) in females and for eating disorders (IRR, 1.47; 95% CI, 1.31-1.67) in males. In both sexes, there was a decrease in hospitalizations for mood disorders (IRR, 0.84; 95% CI, 0.83-0.86), substance-related disorders (IRR, 0.83; 95% CI, 0.81-0.86), and other mental health disorders (IRR, 0.78; 95% CI, 0.76-0.79). Conclusions and Relevance: This cross-sectional study of Canadian youths and young adults found a rise in anxiety, personality disorders, and suicidality in females and a rise in eating disorders in both sexes in the COVID-19-prevalent period. These results suggest that in future pandemics, policymakers should support youths and young adults who are particularly vulnerable to deterioration in mental health conditions during public health restrictions, including eating disorders, anxiety, and suicidality.

Pandemic Stringency Measures and Hospital Admissions for Eating Disorders.

Importance: Hospitalizations for eating disorders rose dramatically during the COVID-19 pandemic. Public health restrictions, or stringency, are believed to have played a role in exacerbating eating disorders. Few studies of eating disorders during the pandemic have extended to the period when public health stringency restrictions were lifted. Objective: To assess the association between hospitalization rates for eating disorders and public health stringency during the COVID-19 pandemic and after the easing of public health restrictions. Design, Setting, and Participants: This Canadian population-based cross-sectional study was performed from April 1, 2016, to March 31, 2023, and was divided into pre-COVID-19 and COVID-19-prevalent periods. Data were provided by the Canadian Institute for Health Information and the Institut National d'Excellence en Santé et Services Sociaux for all Canadian provinces and territories. Participants included all children and adolescents aged 6 to 20 years. Exposure: The exposure was public health stringency, as measured by the Bank of Canada stringency index. Main Outcomes and Measures: The primary outcome was hospitalizations for a primary diagnosis of eating disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code F50), stratified by region, age group, and sex. Interrupted time series analyses based on Poisson regression were used to estimate the association between the stringency index and the rate of hospitalizations for eating disorders. Results: During the study period, there were 11 289 hospitalizations for eating disorders across Canada, of which 8726 hospitalizations (77%) were for females aged 12 to 17 years. Due to low case counts in other age-sex strata, the time series analysis was limited to females within the 12- to 17-year age range. Among females aged 12 to 17 years, a 10% increase in stringency was associated with a significant increase in hospitalization rates in Quebec (adjusted rate ratio [ARR], 1.05; 95% CI, 1.01-1.07), Ontario (ARR, 1.05; 95% CI, 1.03-1.07), the Prairies (ARR, 1.08; 95% CI, 1.03-1.13), and British Columbia (ARR, 1.11; 95% CI, 1.05-1.16). The excess COVID-19-prevalent period hospitalizations were highest at the 1-year mark, with increases in all regions: Quebec (RR, 2.17), Ontario (RR, 2.44), the Prairies (RR, 2.39), and British Columbia (RR, 2.02). Conclusion and Relevance: In this cross-sectional study of hospitalizations for eating disorders across Canada, hospitalization rates for eating disorders in females aged 12 to 17 years were associated with public health measure stringency. The findings suggest that future pandemic preparedness should consider implications for youths at risk for eating disorders and their resource and support needs.

Knowledge, attitude and practice (KAP) and risk factors on dengue fever among children in Brazil, Fortaleza: A cross-sectional study.

BACKGROUND: Dengue fever is a mosquito-borne viral disease that is associated with four serotypes of the dengue virus. Children are vulnerable to infection with the dengue virus, particularly those who have been previously infected with a different dengue serotype. Sufficient knowledge, positive attitudes, and proper practices (KAP) are essential for dengue prevention and control. This study aims to estimate the dengue seropositivity for study participants and to examine the association between households' dengue-related knowledge, attitudes, and practices (KAP), and children's risk of dengue seropositivity, while accounting for socioeconomic and demographic differences in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: This analysis was based on a cross-sectional study from Fortaleza, Brazil between November 2019, and February 2020. There were 392 households and 483 participant children who provided a sample of sufficient quality for serological analysis. The main exposure was a household's dengue-related knowledge, attitudes, and practices, assessed through a questionnaire to construct a composite KAP score categorized into three levels: low, moderate, and high. The main outcome is dengue immunoglobulin G(IgG) antibodies, collected using dried blood spots and assessed with Panbio Dengue IgG indirect ELISA (enzyme-linked immunosorbent assays) test commercial kits. The estimated crude dengue seroprevalence among participating children (n = 483) was 25%. Five percent of households (n = 20) achieved a score over 75% for KAP, sixty-nine percent of households (n = 271) scored between 50% and 75%, and twenty-six percent of households (n = 101) scored lower than 50%. Each KAP domain was significantly and positively associated with the others. The mean percentage scores for the three domains are 74%, 63%, and 39% respectively. We found high household KAP scores were associated with an increased adjusted relative risk (aRR) of seropositivity (aRR: 2.11, 95% CI: 1.11-4.01, p = 0.023). Household adult respondents' education level of elementary school or higher was negatively associated with children's risk of being seropositive (aRR: 0.65, 95% CI: 0.48-0.87, p = 0.005). The risk of seropositivity in older children (6-12 years old) was over 6 times that of younger children (2-5 years old) (aRR: 6.08, 95% CI: 3.47-10.64, p<0.001). Children living in households with sealed water tanks or no water storage had a lower risk of being seropositive (aRR: 0.73, 95% CI: 0.54-0.98, p = 0.035). CONCLUSIONS/SIGNIFICANCE: Our results provide insight into the prevalence of dengue seropositivity in Fortaleza, Brazil in children, and certain demographic and socioeconomic characteristics associated with children's risk of being seropositive. They also suggest that KAP may not identify those more at-risk for dengue, although understanding and enhancing households' KAP is crucial for effective community dengue control and prevention initiatives.

Infection-induced seroconversion and seroprevalence of SARS-CoV-2 among a cohort of children and youth in Montreal, Canada.

The EnCORE study is a prospective serology study of SARS-CoV-2 in a cohort of children from Montreal, Canada. Based on data from our fourth round of data collection (May-October 2022), we estimated SARS-CoV-2 seroprevalence and seroconversion. Using multivariable regression, we identified factors associated with seroconversion. Our results show that previously seronegative children were approximately 9-12 times more likely to seroconvert during the early Omicron-dominant period compared to pre-Omicron rounds. Unlike the pre-Omicron rounds, the adjusted rate of seroconversion among 2- to 4-year-olds was higher than older age groups. As seen previously, higher seroconversion rates were associated with ethnic/racial minority status.

Pre-Omicron seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies among a cohort of children and teenagers in Montréal, Canada.

OBJECTIVES: To use serological testing to assess the pre-Omicron seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montréal, Canada. DESIGN: This analysis is from a prospective cohort study of children aged 2-17 years (at baseline) that included blood spots for antibody detection. The serostatus of participants was determined by enzyme-linked immunosorbent assays using the receptor-binding domain from the spike protein and the nucleocapsid protein as antigens. We estimated seroprevalence, seroconversion rates, and the likelihood of seroreversion at 6 months and 1 year. RESULTS: The baseline (October 2020 to April 2021) seroprevalence was 5.8% (95% confidence interval [CI] 4.8-7.1), which increased to 10.5% (May to September 2021) and 11.0% (November 2021 to March 2022) for the respective follow-ups (95% CI 8.6-12.7; 95% CI 8.8-13.5). The crude rate of seroconversion over the study period was 12.8 per 100 person-years (95% CI 11.0-14.7). The adjusted hazard rates of seroconversion by child characteristics showed higher rates in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes in the lowest tercile of our study population. The likelihood of remaining seropositive at 6 months was 68% (95% CI 60-77%) and dropped to 42% (95% CI 32-56%) at 1 year. CONCLUSION: Serological studies continue to provide valuable contributions for infection prevalence estimates and help us better understand the dynamics of antibody levels after infection.

Institutional, therapeutic, and individual factors associated with 30-day mortality after COVID-19 diagnosis in Canadian long-term care facilities.

BACKGROUND: Canadian long-term care facility (LTCF) residents experienced higher death rates compared to other countries during the first wave of the COVID-19 pandemic. This cohort study analyzes the individual, therapeutic, and institutional factors associated with death in LTCFs. METHODS: Institutional data for 17 LTCFs in Montreal, Canada were obtained from local administrative registries. Individual data for 1197 residents infected by SARS-CoV-2 between February 23 and July 11, 2020 were obtained through chart reviews. A multivariable modified Poisson regression model, which accounted for LTCF clustering, was used to identify resident and facility covariates associated with 30-day mortality after COVID-19 diagnosis. RESULTS: Severe shortage of licensed practical nurses (RR 2.60 95% CI 1.20-5.61) and medium-sized facilities compared to smaller-sized facilities (RR 2.73 95% CI 1.23-6.07) were associated with 30-day mortality. Later COVID-19 diagnosis (RR 0.98 95% CI 0.97-0.99 per additional day) was associated with survival. Individual risk factors for death included age (RR 1.33 95% CI 1.23-1.45 per additional 10 years), male sex (RR 1.46 95% CI 1.24-1.71), functional impairment (RR 1.08 95% CI 1.04-1.12 per unit increase of SMAF), as well as a diagnosis of congestive heart failure (RR 1.31 95% CI 1.04-1.66) and neurocognitive disorder (RR 1.31 95% CI 1.01-1.70). Among severe cases, anticoagulation was associated with survival (RR 0.70 95% CI 0.51-0.96). CONCLUSIONS: This study identified practical nurse shortages and facility size as institutional risk factors for COVID-19 death. Anticoagulation was associated with survival among severe cases.

Behavioral risk factors associated with reported tick exposure in a Lyme disease high incidence region in Canada.

BACKGROUND: Tick-borne diseases, and especially Lyme Disease (LD), are on the rise in Canada and have been met with increasing public health concern. To face these emerging threats, education on the prevention of tick bites remains the mainstay of public health intervention. The objective of this study was to assess the adoption of preventive behaviors toward tick bites and LD and to investigate the association between behavioral risk factors and reported tick exposure in a Canadian, LD high incidence region (Estrie region, Quebec, Canada). METHODS: A cross-sectional study was conducted in 2018 which used a telephone questionnaire administered to a random sample of 10,790 adult residents of the study region. Questions investigated tick exposure, LD awareness, attitudes towards LD risk, outdoor and preventive behaviors, as well as antibiotic post-exposure prophylaxis (PEP) treatments in the case of a tick bite. Descriptive and multivariable analyses were carried out, considering the nine administrative subregions and the stratified survey design. RESULTS: The sub-regional prevalence of reported tick exposure in the previous year ranged from 3.4 to 21.9%. The proportion of respondents that adopted preventive behaviors varied from 27.0% (tick checks) to 30.1% (tick repellent) and 44.6% (shower after outdoor activities). A minority of respondents (15.9%) that sought healthcare after a tick bite received a PEP treatment. Performing tick checks (Odds ratio = 4.33), time spent outdoors (OR = 3.09) and living in a subregion with a higher public health LD risk level (OR = 2.14) were associated with reported tick exposure in multivariable models. CONCLUSIONS: This study highlights the low level of adoption of preventive behaviors against tick bites in a region where LD risk is amongst the highest in Canada. This suggests a concerning lack of improvement in LD prevention, as low levels of adoption were already reported in studies conducted in the last decade. Innovative and evidence-based approaches to improve education on ticks and tick-borne diseases and to promote behavior changes are urgently needed in Canada.

Seroprevalence of SARS-CoV-2 Antibodies Among Children in School and Day Care in Montreal, Canada.

Importance: Quebec prioritized in-person learning after the first wave of the COVID-19 pandemic, with school closures being implemented temporarily in selected schools or in hot-spot areas. Quebec's decision to keep most schools open was controversial, especially in Montreal, which was the epicenter of Canada's first and second waves; therefore, understanding the extent to which children were infected with SARS-CoV-2 provides important information for decisions about school closures. Objective: To estimate the seroprevalence of SARS-CoV-2 antibodies in children and teenagers in 4 neighborhoods of Montreal, Canada. Design, Setting, and Participants: This cohort study (the Enfants et COVID-19: Étude de séroprévalence [EnCORE] study) enrolled a convenience sample of children aged 2 to 17 years between October 22, 2020, and March 22, 2021, in Montreal, Canada. Exposures: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: The main outcome was seroprevalence of SARS-CoV-2 antibodies, collected using dried blood spots (DBSs) and analyzed with a research-based enzyme-linked immunosorbent assay (ELISA). Parents also completed an online questionnaire that included questions on self-reported COVID-19 symptoms and tests, along with sociodemographic questions. Results: This study included 1632 participants who provided a DBS sample from 30 day cares, 22 primary schools, and 11 secondary schools. The mean (SD) age of the children who provided a DBS sample was 9.0 (4.4) years; 801 (49%) were female individuals, with 354 participants (22%) from day cares, 725 (44%) from primary schools, and 553 (34%) from secondary schools. Most parents had at least a bachelor's degree (1228 [75%]), and 210 (13%) self-identified as being a racial or ethnic minority. The mean seroprevalence was 5.8% (95% CI, 4.6%-7.0%) but increased over time from 3.2% (95% CI, 0.7%-5.8%) in October to November 2020 to 8.4% (95% CI, 4.4%-12.4%) in March to April 2021. Of the 95 children with positive SARS-CoV-2 antibody results, 78 (82%) were not tested or tested negative with reverse transcription-polymerase chain reaction (RT-PCR) testing, and all experienced mild (49 [52%]) or no clinical symptoms (46 [48%]). The children of parents who self-identified as belonging to a racial and ethnic minority group were more likely to be seropositive compared with children of White parents (adjusted seroprevalence ratio, 1.9; 95% CI, 1.1-2.6). Conclusions and Relevance: These results provide a benchmark of the seroprevalence status in Canadian children. The findings suggest that there was more transmission occurring in children compared with what was being detected by RT-PCR, although children experienced few or mild symptoms. It will be important to continue monitoring the serological status of children, particularly in the context of new COVID-19 variants of concern and in the absence of mass vaccination campaigns targeting young children.

Seroprevalence of anti-SARS-CoV-2 antibodies among school and daycare children and personnel: protocol for a cohort study in Montreal, Canada.

INTRODUCTION: Further evidence is needed to understand the contribution of schools and daycares for the spread of COVID-19 in the context of diverse transmission dynamics and continually evolving public health interventions. The Enfants et COVID-19: Étude de séroprévalence (EnCORE) study will estimate the seroprevalence and seroconversion of SARS-CoV-2 among school and daycare children and personnel. In addition, the study will examine associations between seroprevalence and sociodemographic characteristics and reported COVID-19 symptoms and tests, and investigates changes in health, lifestyle and well-being outcomes. METHODS AND ANALYSIS: This study includes children and personnel from 62 schools and daycares in four neighbourhoods in Montreal, Canada. All children aged 2-17 years attending one of the participating schools or daycares and their parents are invited to participate, as well as a sample of personnel members. Participants respond to brief questionnaires and provide blood samples, collected via dried blood spot, at baseline (October 2020-March 2021) and follow-up (May-June 2021). Questionnaires include sociodemographic and household characteristics, reported COVID-19 symptoms and tests, potential COVID-19 risk factors and prevention efforts and health and lifestyle information. Logistic regression using generalised estimating equations will be used to estimate seroprevalence and seroconversion, accounting for school-level clustering. ETHICS AND DISSEMINATION: This study was approved by the research ethics boards of the Université de Montréal (CERSES) and the Centre Hospitalier Universitaire Sainte-Justine. Results will contribute to our knowledge about SARS-CoV-2 transmission in schools and daycares and will be made available to study participants and their families, school and public health decision-makers and the research community.

Machine learning and dengue forecasting: Comparing random forests and artificial neural networks for predicting dengue burden at national and sub-national scales in Colombia.

The robust estimate and forecast capability of random forests (RF) has been widely recognized, however this ensemble machine learning method has not been widely used in mosquito-borne disease forecasting. In this study, two sets of RF models were developed at the national (pooled department-level data) and department level in Colombia to predict weekly dengue cases for 12-weeks ahead. A pooled national model based on artificial neural networks (ANN) was also developed and used as a comparator to the RF models. The various predictors included historic dengue cases, satellite-derived estimates for vegetation, precipitation, and air temperature, as well as population counts, income inequality, and education. Our RF model trained on the pooled national data was more accurate for department-specific weekly dengue cases estimation compared to a local model trained only on the department's data. Additionally, the forecast errors of the national RF model were smaller to those of the national pooled ANN model and were increased with the forecast horizon increasing from one-week-ahead (mean absolute error, MAE: 9.32) to 12-weeks ahead (MAE: 24.56). There was considerable variation in the relative importance of predictors dependent on forecast horizon. The environmental and meteorological predictors were relatively important for short-term dengue forecast horizons while socio-demographic predictors were relevant for longer-term forecast horizons. This study demonstrates the potential of RF in dengue forecasting with a feasible approach of using a national pooled model to forecast at finer spatial scales. Furthermore, including sociodemographic predictors is likely to be helpful in capturing longer-term dengue trends.

Sustainable, healthy cities: protocol of a mixed methods evaluation of a cluster randomized controlled trial for Aedes control in Brazil using a community mobilization approach.

BACKGROUND: Dengue is increasing in its global presence with an estimated 4 billion people at-risk of infection in at least 128 countries. Despite the promising results of EcoHealth and community mobilization approaches to Aedes reduction, more evidence of their efficacy on reducing dengue risk is needed. The principal research question is to determine if interventions based upon community mobilization reduce the risk of dengue virus infection among children 3 to 9 years old compared to usual dengue control practice in Fortaleza, Brazil. METHODS: The present study will follow a pragmatic cluster randomized controlled trial (cRCT) design with randomization at the census tract level with equal allocation to the two arms. In each arm, there will be 34 clusters of 86 children between 3 to 9 years old for an expected total of 5848 children enrolled in the study, assuming a risk reduction of 29.5% based upon findings from a previous multi-site cRCT. The primary outcomes are rates of anti-dengue Immunoglobulin G (IgG) seroconversion and adult female Aedes density. The intervention is based upon a participatory health research approach, Socializing Evidence for Participatory Action (SEPA), where the research evidence is used to foster community engagement and ownership of the health issue and solution. Following allocation, intervention communities will develop and implement their own solutions that will likely include a wide variety of collective events and media approaches. Data collection activities over a period of 3 years include household visits for blood collection, household surveys, and entomological surveys; and qualitative activities including focus groups, in-depth interviews, and document analysis to evaluate the process, acceptability, fidelity, and sustainability of the intervention. Study participants will be aware of their assignment and all research staff will be blinded although the intervention assignment will likely be revealed to field staff through interaction with participants. DISCUSSION: The results of our study will provide evidence on community mobilization as an intervention for dengue control. We anticipate that if community mobilization is effective in Fortaleza, the results of this study will help develop evidence-based vector control programs in Brazil, and also in other countries struggling with Aedes-transmitted diseases. TRIAL REGISTRATION: ISRCTN66131315, registration date: 1 October 2018.

The Impact of Multiple Rounds of Indoor Residual Spraying on Malaria Incidence and Hemoglobin Levels in a High-Transmission Setting.

BACKGROUND: Indoor residual spraying (IRS) is widely used as a vector control measure, although there are conflicting findings of its effectiveness in reducing malaria incidence. The objective of this study was to estimate the effect of multiple IRS rounds on malaria incidence and hemoglobin levels in a cohort of children in rural southeastern Uganda. METHODS: The study was based upon a dynamic cohort of children aged 0.5-10 years enrolled from August 2011 to June 2017 in Nagongera Subcounty. Confirmed malaria infections and hemoglobin levels were recorded over time for each participant. After each of 4 rounds of IRS, malaria incidence, hemoglobin levels, and parasite density were evaluated and compared with pre-IRS levels. Analyses were carried out at the participant level while accounting for repeated measures and clustering by household. RESULTS: Incidence rate ratios comparing post-IRS to pre-IRS incidence rates for age groups 0-3, 3-5, and 5-11 were 0.108 (95% confidence interval [CI], .078-.149), 0.173 (95% CI, .136-.222), and 0.226 (95% CI, .187-.274), respectively. The mean hemoglobin levels significantly increased from 11.01 (pre-IRS) to 12.18 g/dL (post-IRS). CONCLUSIONS: Our study supports the policy recommendation of IRS usage in a stable and perennial transmission area to rapidly reduce malaria transmission.

Long-term etanercept retention patterns and factors associated with treatment discontinuation: a retrospective cohort study using Canadian claims-level data.

To examine 12-month retention rates over 6 years of etanercept patients in Canada, and to identify factors associated with treatment discontinuation. A retrospective cohort study was conducted using longitudinal prescription drug claims data from IQVIA Private Drug Plan database (PDP), Ontario Public Drug Plan database (OPDP), and Régie de l'assurance maladie du Québec database (RAMQ). Between 07/2008 and 06/2010, bio-naïve patients who initiated etanercept were identified and followed for 72 months. Twelve-month retention rates were estimated in one-year increments and factors associated with time to discontinuation over the 72-month period were identified using a Cox proportional hazards regression model. The study identified 4528 etanercept patients (61% female, 85% rheumatic diseases, and 15% psoriasis). Twelve-month etanercept retention rates increased significantly for patients following their first year on therapy (p < 0.0001), with 66% of patients retained at year 1 vs. 79, 82, 84, 83, and 79% at years 2, 3, 4, 5, and 6, respectively. 17.1% (n = 771) of patients were retained for the entire 72-month study. Patients with psoriasis were at increased risk (HR 1.199; p < 0.0001); while public drug coverage plan patients (OPDP HR 0.721; p < 0.0001 and RAMQ HR 0.537; p < 0.0001) were at decreased risk of treatment discontinuation. Twelve-month etanercept retention rates increased significantly for patients following their first year on therapy. Indication and drug coverage plan were associated with patients' time to etanercept discontinuation. With a better understanding of factors associated with retention, programs can be designed to address the specific needs of at-risk groups while supporting patients stable on therapy.

Impact of the Adalimumab Patient Support Program on Clinical Outcomes in Ankylosing Spondylitis: Results from the COMPANION Study.

INTRODUCTION: Adalimumab (ADA) is a tumor necrosis factor (TNF)-alpha inhibitor indicated for the treatment of inflammatory autoimmune diseases, including ankylosing spondylitis (AS). Patients receiving ADA in Canada are eligible to enroll in the AbbVie Care™ patient support program (AC-PSP), which provides personalized services, including care coach calls (CCCs). We estimated the likelihood of controlled disease in a cohort of AS patients treated with ADA enrolled in the AC-PSP and who received CCCs versus those who did not. METHODS: A longitudinal analysis using de-identified aggregate-level data collected through the AC-PSP was performed. A probabilistic matching algorithm was used to link patient-level records from the AC-PSP database to records from the QuintilesIMS longitudinal prescription transactions database. Patients were indexed on the date of their first prescription of ADA between January 2010 and October 2015. The AC-PSP database included patient assessments of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a measure of disease activity. Eligible patients had a baseline BASDAI assessment performed between 90 days before and 30 days after the index date, and a follow-up BASDAI assessment 6-18 months later. Poisson regression was used to estimate the adjusted relative risk (RR) of controlled disease (BASDAI < 4) at the time of follow-up, comparing patients who received CCCs with those who did not. RESULTS: In total 249 AS patients met eligibility criteria, and 123 (49%) received CCCs. Of the 249 patients, 184 (74%) had controlled disease (BASDAI < 4) at follow-up assessment, 98 (80%) in the CCC group and 86 (68%) in the no CCC group. Multivariable regression analysis demonstrated a 23% increased likelihood of controlled disease in patients who received CCCs relative to those who did not (RR = 1.23; 95% confidence interval, 1.06-1.42; p = 0.0055). CONCLUSION: AS patients receiving tailored services through the AC-PSP in the form of CCCs have an increased likelihood of controlled disease within 6-18 months. FUNDING: AbbVie.

Impact of Adalimumab Patient Support Program's Care Coach Calls on Clinical Outcomes in Patients with Crohn's Disease in Canada: An Observational Retrospective Cohort Study.

BACKGROUND: Adalimumab is an antitumour necrosis factor (TNFα) biologic therapy indicated for the treatment of Crohn's disease (CD). Patients receiving adalimumab in Canada are eligible to enroll in the AbbVie Care™ patient support program (AC-PSP), which provides personalized services, including care coach calls (CCCs). The objective of this study was to compare the likelihood of achieving clinical remission in a cohort of CD patients treated with adalimumab who did and did not receive CCCs. METHODS: A longitudinal analysis was performed using de-identified aggregate-level data collected through the AC-PSP. Patients were indexed on the date of their first injection of adalimumab between July 2010 and October 2014. The AC-PSP database included measurements of the Harvey-Bradshaw Index (HBI), a symptom-based measure of disease severity. Eligible patients had an initial HBI measurement performed between 90 days before and up to 30 days after the index date and a follow-up HBI measurement six to 18 months later. Adjusted relative risk (RR) of achieving remission (HBI ≤ 4) at the time of the follow-up was estimated comparing patients who received and did not receive CCCs. RESULTS: There were 381 CD patients who met eligibility criteria; 224 (59%) received CCCs, and 157 (41%) did not receive CCCs. Multivariate regression analysis demonstrated that CD patients receiving CCCs had a 17% increased likelihood of achieving HBI remission when compared with patients who did not receive CCCs (RR = 1.17; 95% CI, 1.03-1.34; P = 0.0192). CONCLUSIONS: This study provides preliminary evidence that a phone call intervention, aiming to improve the overall patient experience with adalimumab treatment, may increase the likelihood of HBI remission in patients taking adalimumab to manage CD.

Measures of Malaria Burden after Long-Lasting Insecticidal Net Distribution and Indoor Residual Spraying at Three Sites in Uganda: A Prospective Observational Study.

BACKGROUND: Long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are the primary vector control interventions used to prevent malaria in Africa. Although both interventions are effective in some settings, high-quality evidence is rarely available to evaluate their effectiveness following deployment by a national malaria control program. In Uganda, we measured changes in key malaria indicators following universal LLIN distribution in three sites, with the addition of IRS at one of these sites. METHODS AND FINDINGS: Comprehensive malaria surveillance was conducted from October 1, 2011, to March 31, 2016, in three sub-counties with relatively low (Walukuba), moderate (Kihihi), and high transmission (Nagongera). Between 2013 and 2014, universal LLIN distribution campaigns were conducted in all sites, and in December 2014, IRS with the carbamate bendiocarb was initiated in Nagongera. High-quality surveillance evaluated malaria metrics and mosquito exposure before and after interventions through (a) enhanced health-facility-based surveillance to estimate malaria test positivity rate (TPR), expressed as the number testing positive for malaria/number tested for malaria (number of children tested for malaria: Walukuba = 42,833, Kihihi = 28,790, and Nagongera = 38,690); (b) cohort studies to estimate the incidence of malaria, expressed as the number of episodes per person-year [PPY] at risk (number of children observed: Walukuba = 340, Kihihi = 380, and Nagongera = 361); and (c) entomology surveys to estimate household-level human biting rate (HBR), expressed as the number of female Anopheles mosquitoes collected per house-night of collection (number of households observed: Walukuba = 117, Kihihi = 107, and Nagongera = 107). The LLIN distribution campaign substantially increased LLIN coverage levels at the three sites to between 65.0% and 95.5% of households with at least one LLIN. In Walukuba, over the 28-mo post-intervention period, universal LLIN distribution was associated with no change in the incidence of malaria (0.39 episodes PPY pre-intervention versus 0.20 post-intervention; adjusted rate ratio [aRR] = 1.02, 95% CI 0.36-2.91, p = 0.97) and non-significant reductions in the TPR (26.5% pre-intervention versus 26.2% post-intervention; aRR = 0.70, 95% CI 0.46-1.06, p = 0.09) and HBR (1.07 mosquitoes per house-night pre-intervention versus 0.71 post-intervention; aRR = 0.41, 95% CI 0.14-1.18, p = 0.10). In Kihihi, over the 21-mo post-intervention period, universal LLIN distribution was associated with a reduction in the incidence of malaria (1.77 pre-intervention versus 1.89 post-intervention; aRR = 0.65, 95% CI 0.43-0.98, p = 0.04) but no significant change in the TPR (49.3% pre-intervention versus 45.9% post-intervention; aRR = 0.83, 95% 0.58-1.18, p = 0.30) or HBR (4.06 pre-intervention versus 2.44 post-intervention; aRR = 0.71, 95% CI 0.30-1.64, p = 0.40). In Nagongera, over the 12-mo post-intervention period, universal LLIN distribution was associated with a reduction in the TPR (45.3% pre-intervention versus 36.5% post-intervention; aRR = 0.82, 95% CI 0.76-0.88, p < 0.001) but no significant change in the incidence of malaria (2.82 pre-intervention versus 3.28 post-intervention; aRR = 1.10, 95% 0.76-1.59, p = 0.60) or HBR (41.04 pre-intervention versus 20.15 post-intervention; aRR = 0.87, 95% CI 0.31-2.47, p = 0.80). The addition of three rounds of IRS at ~6-mo intervals in Nagongera was followed by clear decreases in all outcomes: incidence of malaria (3.25 pre-intervention versus 0.63 post-intervention; aRR = 0.13, 95% CI 0.07-0.27, p < 0.001), TPR (37.8% pre-intervention versus 15.0% post-intervention; aRR = 0.54, 95% CI 0.49-0.60, p < 0.001), and HBR (18.71 pre-intervention versus 3.23 post-intervention; aRR = 0.29, 95% CI 0.17-0.50, p < 0.001). High levels of pyrethroid resistance were documented at all three study sites. Limitations of the study included the observational study design, the lack of contemporaneous control groups, and that the interventions were implemented under programmatic conditions. CONCLUSIONS: Universal distribution of LLINs at three sites with varying transmission intensity was associated with modest declines in the burden of malaria for some indicators, but the addition of IRS at the highest transmission site was associated with a marked decline in the burden of malaria for all indicators. In highly endemic areas of Africa with widespread pyrethroid resistance, IRS using alternative insecticide formulations may be needed to achieve substantial gains in malaria control.

Medication Persistence, Duration of Treatment, and Treatment-switching Patterns Among Canadian Patients Taking Once-daily Extended-release Methylphenidate Medications for Attention-Deficit/Hyperactivity Disorder: A Population-based Retrospective Cohort Study.

PURPOSE: We conducted a retrospective cohort study to compare medication use patterns of a long-acting extended-release methylphenidate (Osmotic Release Oral System [OROS(®)] methylphenidate, CONCERTA(®)) and Teva-methylphenidate (methylphenidate ER-C), a generic drug determined by the Canadian regulatory authority, Health Canada, to be bioequivalent to OROS(®) methylphenidate. METHODS: We established an OROS(®) methylphenidate-experienced and new-user population cohort to compare medication use patterns, including medication persistence, duration of therapy, and treatment-switching patterns. Multivariable log-binomial regression was used to adjust for confounders of the associations with persistence. FINDINGS: In the OROS(®) methylphenidate-experienced cohort (n = 21,940), OROS(®) methylphenidate was associated with a 70% higher rate of medication persistence at 12 months relative to methylphenidate ER-C (adjusted relative risk = 1.70; 95% CI, 1.64-1.77). In the new-user cohort (n = 20,410), OROS(®) methylphenidate had a 58% higher rate of medication persistence relative to methylphenidate ER-C (adjusted relative risk = 1.58; 95% CI, 1.51-1.65). Median duration of therapy was significantly longer in patients taking OROS(®) methylphenidate compared with those taking methylphenidate ER-C, and treatment-switching occurred significantly more frequently in patients taking methylphenidate ER-C compared with those taking OROS(®) methylphenidate. IMPLICATIONS: Significant differences were observed in how the medications were used by patients in the real-world setting. Because the data sources were administrative databases, it was not possible to control for all potentially important confounding variables. Although differences in medication persistence may not directly reflect differences in treatment efficacy, the findings are important because these products are used interchangeably in a number of Canadian provinces.

Forecasting malaria in a highly endemic country using environmental and clinical predictors.

BACKGROUND: Malaria thrives in poor tropical and subtropical countries where local resources are limited. Accurate disease forecasts can provide public and clinical health services with the information needed to implement targeted approaches for malaria control that make effective use of limited resources. The objective of this study was to determine the relevance of environmental and clinical predictors of malaria across different settings in Uganda. METHODS: Forecasting models were based on health facility data collected by the Uganda Malaria Surveillance Project and satellite-derived rainfall, temperature, and vegetation estimates from 2006 to 2013. Facility-specific forecasting models of confirmed malaria were developed using multivariate autoregressive integrated moving average models and produced weekly forecast horizons over a 52-week forecasting period. RESULTS: The model with the most accurate forecasts varied by site and by forecast horizon. Clinical predictors were retained in the models with the highest predictive power for all facility sites. The average error over the 52 forecasting horizons ranged from 26 to 128% whereas the cumulative burden forecast error ranged from 2 to 22%. CONCLUSIONS: Clinical data, such as drug treatment, could be used to improve the accuracy of malaria predictions in endemic settings when coupled with environmental predictors. Further exploration of malaria forecasting is necessary to improve its accuracy and value in practice, including examining other environmental and intervention predictors, including insecticide-treated nets.