Transmission dynamics of SARS-CoV-2 in British Columbia's largest school district during the second half of the 2020-2021 school year.

OBJECTIVES: To determine the extent and characteristics of in-school transmission of SARS-CoV-2 and determine risk factors for in-school acquisition of COVID-19 in one of Canada's largest school districts. METHODS: We conducted a retrospective chart review of all reportable cases of COVID-19 who attended a kindergarten-Grade 12 (K-12) school within the study area between January and June of the 2020-2021 school year. The acquisition source was inferred based on epidemiological data and, when available, whole genome sequencing results. Mixed effects logistic regression was performed to identify risk factors independently associated with in-school acquisition of COVID-19. RESULTS: Overall, 2877 cases of COVID-19 among staff and students were included in the analysis; of those, 9.1% had evidence of in-school acquisition. The median cluster size was two cases (interquartile range: 1). Risk factors for in-school acquisition included being male (adjusted odds ratio [aOR]: 1.59, 95% confidence interval [CI]: 1.17-2.17), being a staff member (aOR: 2.62, 95% CI: 1.64-4.21) and attending or working in an independent school (aOR: 2.28, 95% CI: 1.13-4.62). CONCLUSION: In-school acquisition of COVID-19 was uncommon during the study period. Risk factors were identified in order to support the implementation of mitigation strategies that can reduce transmission further.

RéSUMé: OBJECTIFS: Déterminer l'étendue et les caractéristiques de la transmission de la SRAS-CoV-2 en milieu scolaire, et déterminer les facteurs de risque de l'acquisition de la COVID-19 dans l'un des plus larges arrondissements scolaires du Canada. MéTHODES: Nous avons mené un examen rétrospectif des dossiers de tous les cas signalés de COVID-19 ayant fréquenté une école de niveau élémentaire, primaire ou secondaire dans la zone à l'étude entre janvier et juin de l'année scolaire 2020-2021. La source d'acquisition était inférée sur la base des données épidémiologiques et, lorsque disponibles, les résultats de séquençage du génome entier. Nous avons eu recours à des régressions logistiques multiniveaux pour identifier les facteurs indépendamment associés avec l'acquisition de la COVID-19 en milieu scolaire. RéSULTATS: Au total, 2 877 cas de COVID-19 parmi les employés et les élèves ont été inclus dans l'analyse; de ceux-ci, 9,1 % avaient acquis l'infection en milieu scolaire. La grosseur médiane des agrégats était de deux cas (écart interquartile : 1). Les risques facteurs de l'acquisition en milieu scolaire incluaient le fait d'être de sexe masculin (rapport de cotes ajusté [RCa] : 1,59, intervalle de confiance [IC] de 95% : 1,17-2,17), être un membre du personnel (RCa : 2,62, IC de 95% : 1,64-4,21) et fréquenter ou travailler dans une école indépendante (RCa : 2,28, IC de 95% : 1,13-4,62). CONCLUSION: Nos résultats suggèrent que l'acquisition de la COVID-19 en milieu scolaire était peu commune pendant la période d'étude. Des facteurs de risque ont été identifiés afin de supporter l'implémentation de mesures de contrôle pouvant réduire davantage la transmission.

Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer's Disease: Systematic Review and Network Metaanalysis.

BACKGROUND/OBJECTIVES: To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD). DESIGN: Systematic review and Bayesian network metaanalysis (NMA). SETTING: MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception-March 2016). PARTICIPANTS: Individuals with AD in randomized controlled trials (RCTs), quasi-RCTs, and nonrandomized studies. INTERVENTION: Any combination of donepezil, rivastigmine, galantamine, or memantine. MEASUREMENTS: Two reviewers independently screened titles, abstracts, and full-texts; abstracted data; and appraised risk of bias. RESULTS: Twenty thousand three hundred forty-three citations were screened, and 142 studies were included (110 RCTs, 21 non-RCTs, 11 cohort studies). NMA found that donepezil (Mini-Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53-2.24), donepezil+memantine (2.59, 95% CrI = 0.12-4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02-4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale-cognitive: MD = -3.29, 95% CrI = -4.57 to -1.99) and galantamine (MD = -2.13, 95% CrI = -3.91 to -0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = -5.23, 95% CrI = -8.72 to -1.56) improved behavior more than placebo. NMA found that donepezil (MD = -0.32, 95% CrI = -0.46 to -0.19), donepezil+memantine (MD = -0.57, 95% CrI = -0.95 to -0.21), oral rivastigmine (MD = -0.38, 95% CrI = -0.56 to -0.17), and galantamine (MD = -3.79, 95% CrI = -6.98 to -0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36-0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). CONCLUSION: An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.

Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effectiveness for mild cognitive impairment is unclear. We conducted a systematic review to examine the efficacy and safety of cognitive enhancers for mild cognitive impairment. METHODS: Our eligibility criteria were studies of the effects of donepezil, rivastigmine, galantamine or memantine on mild cognitive impairment reporting cognition, function, behaviour, global status, and mortality or harms. We identified relevant material by searching electronic databases (e.g., MEDLINE, Embase), the references of included studies, trial registries and conference proceedings, and by contacting experts. Two reviewers independently screened the results of the literature search, abstracted data and appraised risk of bias using the Cochrane risk-of-bias tool. RESULTS: We screened 15,554 titles and abstracts and 1384 full-text articles. Eight randomized clinical trials and 3 companion reports met our inclusion criteria. We found no significant effects of cognitive enhancers on cognition (Mini-Mental State Examination: 3 randomized clinical trials [RCTs], mean difference [MD] 0.14, 95% confidence interval [CI] -0.22 to 0.50; Alzheimer's Disease Assessment Scale - cognition subscale: 3 RCTs, standardized MD -0.07, 95% CI-0.16 to 0.01]) or function (Alzheimer's Disease Cooperative Study activities of daily living inventory: 2 RCTs, MD 0.30, 95% CI -0.26 to 0.86). Cognitive enhancers were associated with higher risks of nausea, diarrhea and vomiting than placebo. INTERPRETATION: Cognitive enhancers did not improve cognition or function among patients with mild cognitive impairment and were associated with a greater risk of gastrointestinal harms. Our findings do not support the use of cognitive enhancers for mild cognitive impairment.

Canadian oncogenic human papillomavirus cervical infection prevalence: systematic review and meta-analysis.

BACKGROUND: Oncogenic human papillomavirus (HPV) infection prevalence is required to determine optimal vaccination strategies. We systematically reviewed the prevalence of oncogenic cervical HPV infection among Canadian females prior to immunization. METHODS: We included studies reporting DNA-confirmed oncogenic HPV prevalence estimates among Canadian females identified through searching electronic databases (e.g., MEDLINE) and public health websites. Two independent reviewers screened literature results, abstracted data and appraised study quality. Prevalence estimates were meta-analyzed among routine screening populations, HPV-positive, and by cytology/histology results. RESULTS: Thirty studies plus 21 companion reports were included after screening 837 citations and 120 full-text articles. Many of the studies did not address non-response bias (74%) or use a representative sampling strategy (53%). Age-specific prevalence was highest among females aged < 20 years and slowly declined with increasing age. Across all populations, the highest prevalence estimates from the meta-analyses were observed for HPV types 16 (routine screening populations, 8 studies: 8.6% [95% confidence interval 6.5-10.7%]; HPV-infected, 9 studies: 43.5% [28.7-58.2%]; confirmed cervical cancer, 3 studies: 48.8% [34.0-63.6%]) and 18 (routine screening populations, 8 studies: 3.3% [1.5-5.1%]; HPV-infected, 9 studies: 13.6% [6.1-21.1%], confirmed cervical cancer, 4 studies: 17.1% [6.4-27.9%]. CONCLUSION: Our results support vaccinating females < 20 years of age, along with targeted vaccination of some groups (e.g., under-screened populations). The highest prevalence occurred among HPV types 16 and 18, contributing a combined cervical cancer prevalence of 65.9%. Further cancer protection is expected from cross-protection of non-vaccine HPV types. Poor study quality and heterogeneity suggests that high-quality studies are needed.

Interaction between organochlorines and the AHR gene, and risk of non-Hodgkin lymphoma.

BACKGROUND: Plasma organochlorines have been implicated to increase the risk of non-Hodgkin lymphoma (NHL), and interaction with the aryl hydrocarbon receptor gene (AHR) may modify this risk. METHODS: In this case-control study conducted in British Columbia, Canada, five single nucleotide polymorphisms (SNPs) of AHR were genotyped in 422 NHL cases and 459 controls to measure the association between individual SNPs, haplotypes, and risk of NHL. Pre-chemotherapy organochlorine levels were measured and gene-environment interaction analysis was performed. RESULTS: The IVS1 + 4640G/A SNP was significantly associated with NHL risk, with an odds ratio of 1.32 (95% CI = 1.05-1.65) for G/A or A/A genotypes compared to the G/G genotype. Interactions were observed with PCB 118, a known inducer of AHR, and chlordane-related analytes oxychlordane and trans-nonachlor, although no interactions were statistically significant after controlling for multiple comparisons. The observed interactions were consistent across NHL subtypes. CONCLUSION: Results suggest that the AHR gene may play a role in determining the risk of NHL with exposure to organochlorines, and highlight the importance of understanding gene-environment interactions.

Organochlorines and risk of non-Hodgkin lymphoma.

Organochlorine chemicals and polychlorinated biphenyls (PCBs) have been suspected as possible risk factors for non-Hodgkin lymphoma (NHL). We investigated PCBs and organochlorine pesticides and risk of NHL in a population-based case-control study in British Columbia, Canada. Congeners of PCBs (including dioxinlike congeners) and pesticides or pesticide metabolites were measured in plasma of 422 pretreatment cases and 460 control subjects. This is so far the largest study to examine organochlorines in plasma to date. Several dioxin-like PCB congeners were associated with increased risk of NHL, including dioxin-like PCB nos. 118 and 156 with odds ratios (OR) for the highest versus lowest quartile between 1.6 and 1.8. Several non-dioxin-like congeners also showed significant associations. The PCB congener with the strongest association was no. 180 with an OR for the highest versus the lowest quartile of 1.83 (95% confidence interval = 1.18-2.84). Six pesticide analytes also showed a significant association with NHL; beta-hexachlorocyclohexane, p,p'-DDE, hexachlorobenzene, mirex, oxychlordane and trans-nonachlor. The strongest association was found for oxychlordane, a metabolite of the pesticide chlordane (highest vs. lowest quartile OR = 2.68, 95% confidence interval = 1.69-4.24). Our results provide further evidence that organochlorines contribute to NHL risk.