Immunosuppression and cancer risk in kidney transplant recipients: A retrospective cohort study.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.

Uncovering the impact of COVID-19 on the place of death of cancer patients in South America.

The COVID-19 pandemic has significantly impacted healthcare systems worldwide, especially on the management of chronic diseases such as cancer. This study explores the effects of COVID-19 on cancer mortality trends in Brazil, Chile, and Peru. The monthly age-standardized mortality rates in different places of death (hospital/clinic or home) were estimated using vital statistics and death certificate databases. An interrupted time series analysis was performed for each country, using the date of lockdown implementation as the intervention point. Overall cancer mortality rates reduced after the implementation of pandemic restrictions, with a significant decrease in Brazil. In total, 75.3%, 55.4%, and 45.7% of deaths in Brazil, Peru, and Chile, respectively, occurred in hospitals. After lockdowns were implemented, at-home deaths increased in all countries, and in-hospital deaths correspondingly decreased only in Chile. Our results suggest that COVID-19 has significantly affected rates of cancer mortality and place of death in Latin America.

Prevalence of Alpha, Beta, and Gamma Human Papillomaviruses (HPV) in head and neck cancer patients and non-cancer controls and relation to behavioral factors.

OBJECTIVES: Human papillomaviruses (HPV) cause head and neck cancer (HNC) that is increasing in incidence in developed countries. We investigate the prevalence of alpha (α-), beta (ß)-, and gamma (γ) HPV among HNC cases and controls, and their relationship with sociodemographic, behavioral and oral health factors. METHODS: We obtained oral rinse and brush samples from incident HNC cases (n = 369) and hospital-based controls (n = 439), and tumor samples for a subsample of cases (n = 121). We genotyped samples using PCR with PGMY09-PGMY11 primers and Linear Array for α-HPV and type-specific multiplex (TS-MPG) for ß-HPV and γ-HPV. Sociodemographic and behavioral data were obtained from interviews. RESULTS: The prevalence of α-, ß-, and γ-HPV among controls was 14%, 56%, and 24%, respectively, whereas among cases was 42%, 50%, and 33%, respectively. Prevalence of α- and γ-HPV, but not ß-HPV, increased with the increase in sexual activity, smoking, and drinking habits. No HPV genus was associated with oral health. Tumor samples included HPV genotypes exclusively from the α-genus, mostly HPV16, in 80% of cases. CONCLUSIONS: The distribution of α- and γ-HPV, but not ß-HPV, seems to vary based on sociodemographic and behavioral characteristics. We did not observe the presence of cutaneous HPV in tumor tissues.

Protocol: carrageenan for the prevention of oral HPV infection - a feasibility randomised clinical trial.

INTRODUCTION: Head and neck cancers (HNCs) are a significant health burden worldwide. Oral human papillomavirus (HPV) infection is a major risk factor for HNCs. Unfortunately, currently available prophylactic vaccines have limited coverage and potential for HPV type replacement. Carrageenan, a natural product extracted from marine red algae, has demonstrated potency as an HPV inhibitor and could offer a potential alternative to prevent HPV-related diseases, including oral HPV infection. However, there is a lack of clinical studies on the effect of carrageenan on oral HPV infections. As a first step to address this gap, we propose a randomised controlled trial (RCT) to evaluate the feasibility of conducting a larger multicentric RCT to investigate the effect of a carrageenan mouthwash on oral HPV infection. METHODS AND ANALYSIS: We will conduct a placebo-controlled triple-blinded feasibility RCT with two parallel arms, each arm consisting of 20 participants. Participants will complete a single in-person visit at baseline and conduct biweekly follow-ups from home by completing a web-based questionnaire and sending saliva self-samples via mail. During the 6-month period trial, participants will gargle with the mouthwash morning and night, and around sexual activities. The study will evaluate several factors including recruitment and retention rates, the feasibility of data collection procedures, compliance with study procedures, acceptability of RCT procedures and intervention and safety data on carrageenan use in the oral cavity. We will estimate the standard deviation of outcome measures, including time to the incidence of oral HPV infection and time to clearance of prevalent oral HPV infection. The trial primary outcome is whether to proceed to a definitive trial based on prespecified progression criteria. ETHICS AND DISSEMINATION: The protocol was approved by the McGill University institutional review board. Study results will be presented at scientific conferences and published in academic journals. TRIAL REGISTRATION NUMBER: NCT05746988.

Neighbourhood social deprivation and risk of prostate cancer.

BACKGROUND: Striking geographic variations in prostate cancer incidence suggest an aetiological role for spatially-distributed factors. We assessed whether neighbourhood social deprivation, which can reflect limited social contacts, unfavourable lifestyle and environmental exposures, is associated with prostate cancer risk. METHODS: In 2005-2012, we recruited 1931 incident prostate cancer cases and 1994 controls in a case-control study in Montreal, Canada. Lifetime residential addresses were linked to an area-based social deprivation index around recruitment (2006) and about 10 years earlier (1996). Logistic regression estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Men residing in areas characterised by greater social deprivation had elevated prostate cancer risks (ORs of 1.54 and 1.60 for recent and past exposures, respectively; highest vs lowest quintiles), independently from area- and individual-level confounders and screening patterns. The increase in risk with recent high social deprivation was particularly elevated for high-grade prostate cancer at diagnosis (OR 1.87, 95% CI 1.32-2.64). Associations were more pronounced for neighbourhoods with higher proportions of separated/divorced or widowed individuals in the past, and with higher percentages of residents living alone recently. CONCLUSIONS: These novel findings, suggesting that neighbourhood-level social deprivation increases the risk of prostate cancer, point out to potential targeted public health interventions.

Chronotherapy in dentistry: A scoping review.

The circadian clock modulates almost all vital aspects of our physiology and metabolism, including processes relevant to dentistry, such as healing, inflammation and nociception. Chronotherapy is an emerging field aiming to improve therapeutic efficacy and decrease adverse effects on health outcomes. This scoping review aimed to systematically map the evidence underpinning chronotherapy in dentistry and to identify gaps in knowledge. We conducted a systematic scoping search using four databases (Medline, Scopus, CINAHL and Embase). We identified 3908 target articles screened by two blinded reviewers, and only original animal and human studies investigating the chronotherapeutic use of drugs or interventions in dentistry were included. Of the 24 studies included, 19 were human studies and five were animal studies. Chrono-radiotherapy and chrono-chemotherapy reduced treatment side effects and improved therapeutic response, leading to higher survival rates in cancer patients. Animal studies reported that tooth movement and periodontal tissue response to orthodontic forces follow a diurnal rhythm that might influence bone metabolism. Profound and prolonged local anesthesia could be achieved when injected in the evening. Although the overall quality of the included studies was low, chronotherapy applications in dentistry seem to have favourable outcomes, especially in head and neck cancer treatments.

How to use mixed methods in oral health research.

Wicked problems exist in the realm of oral health research. Due to their inherent complexity, using qualitative or quantitative methods alone may not be adequate for resolving them. Mixed methods approaches combine qualitative and quantitative methods, and thus, can provide a powerful tool for understanding and solving complex problems in dental public health. However, using mixed methods does not come without its challenges. This commentary outlines four main tips for researchers to consider when applying mixed methods to their research projects.

Association between the second- and fourth-digit ratio and oral squamous cell carcinoma.

OBJECTIVES: Using an established proxy measure of intra-utero testosterone and estrogen levels-the ratio of second- and fourth-digit lengths-we estimated its association with the oral cancer risk among a population from Southern India. MATERIAL AND METHODS: In a hospital-based case-control study, incident oral cancer cases (N = 350) and non-cancer controls (N = 371), frequency-matched by age and sex, were recruited from two major referral hospitals in Kerala, India. Structured interviews collected information on several domains of exposure via detailed life course questionnaires. Digit lengths were measured using a ruler in a standardized manner. Unconditional logistic regression was performed to estimate the odds ratios and 95% confidence intervals. RESULTS: Second- and fourth-digit ratio lower than 1, which indicates relatively higher intra-utero level of testosterone and lower intra-utero level of estrogen, was associated with higher oral cancer risk (OR = 1.60, 95% CI: 1.02-2.52), after accounting for several confounders. CONCLUSION: Our findings suggest that intra-utero hormonal levels measured by second- and fourth-digit ratio are associated with oral cancer risk. Further studies in different population should confirm these results.

Occupation as a measure of life course socioeconomic position and the risk of oral cancers in India.

OBJECTIVES: Evidence suggests that different indicators of socioeconomic position (SEP) contribute to oral cancer risk. Occupational status, as a measure of SEP, may be able to capture aspects of social hierarchy in societies in which employment is highly correlated with other social structures such as caste systems. Often in such societies, the life course of an individual is also influenced by this hierarchy. However, the influence of life course occupational status on the risk of oral cancer is not well understood. This study aims to identify the life course model that is best supported by the data using life course SEP-as represented by occupation-on oral cancer risk in a population in the South of India. METHODS: Data from the HeNCe Life study, Indian site were used. Incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kozhikode, Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age (5 years) and sex were recruited from the outpatient clinics at the same hospitals as the cases. Life grid-based structured interviews collected information on an array of exposures throughout the life course of the participant. Occupation was coded with the 1988 International Standard Classification of Occupations, transformed to the simplified European Socioeconomic Classification, and further dichotomized into advantageous and disadvantageous SEP at three different life periods (childhood, early adulthood and late adulthood). The analysis was conducted using the Bayesian relevant life course exposure model with a Dirichlet noninformative prior and a weakly informative Cauchy prior to the overall lifetime effect and confounders. RESULTS: Participants in disadvantaged SEP throughout their life had 3.6 times higher risk of oral cancer than those in advantaged SEP (OR = 3.6; 95% CrI = 1.6-7.2), after adjusting for potential confounders. While the crude and sex- and age-adjusted models showed a clear childhood sensitive period for this risk, the model further adjusted for behavioural factors could not distinguish the specific life course period best explained by data. CONCLUSION: Occupation status alone could provide a similar overarching risk estimate for oral cancer to those obtained from more complex measures of SEP.

Uncovering the impact of COVID-19 on the place of death of cancer patients in South America / Descobrindo o impacto da COVID-19 no local de morte de pacientes com câncer na América do Sul / Descubriendo el impacto de la COVID-19 en el local del fallecimiento de pacientes con cáncer en América del Sur

Abstract: The COVID-19 pandemic has significantly impacted healthcare systems worldwide, especially on the management of chronic diseases such as cancer. This study explores the effects of COVID-19 on cancer mortality trends in Brazil, Chile, and Peru. The monthly age-standardized mortality rates in different places of death (hospital/clinic or home) were estimated using vital statistics and death certificate databases. An interrupted time series analysis was performed for each country, using the date of lockdown implementation as the intervention point. Overall cancer mortality rates reduced after the implementation of pandemic restrictions, with a significant decrease in Brazil. In total, 75.3%, 55.4%, and 45.7% of deaths in Brazil, Peru, and Chile, respectively, occurred in hospitals. After lockdowns were implemented, at-home deaths increased in all countries, and in-hospital deaths correspondingly decreased only in Chile. Our results suggest that COVID-19 has significantly affected rates of cancer mortality and place of death in Latin America.

Resumo: A pandemia de COVID-19 impactou significativamente os sistemas de saúde ao redor do mundo, especialmente no manejo de doenças crônicas, como o câncer. Este estudo explora os efeitos da COVID-19 nas tendências de mortalidade por câncer no Brasil, Chile e Peru. As taxas de mortalidade mensais padronizadas por idade em diferentes locais de morte (hospital/clínica ou domicílio) foram estimadas usando estatísticas vitais e bancos de dados de atestados de óbito. Uma análise de série temporal interrompida foi realizada para cada país, tendo como ponto de intervenção a data de implementação do lockdown. As taxas gerais de mortalidade por câncer reduziram após a implementação das restrições, com uma queda significativa no Brasil. No total, 75,3%, 55,4% e 45,7% dos óbitos no Brasil, Peru e Chile, respectivamente, ocorreram em hospitais. Depois da implementação dos lockdowns, as mortes em domicílio aumentaram em todos os países, e as mortes hospitalares diminuíram de forma correspondente apenas no Chile. Nossos resultados sugerem que a COVID-19 afetou significativamente as taxas de mortalidade por câncer e o local de morte na América Latina.

Resumen: La pandemia de COVID-19 impactó significativamente los sistemas de salud de todo el mundo, sobre todo en el manejo de enfermedades crónicas, como el cáncer. Este estudio explora los efectos de la COVID-19 en las tendencias de mortalidad por cáncer en Brasil, Chile y Perú. Las tasas de mortalidad mensuales estandarizadas por edad en diferentes locales de fallecimiento (hospital/clínica o domicilio) se estimaron utilizando estadísticas vitales y base de datos de certificados de defunción. Se realizó un análisis de serie temporal interrumpida para cada país, teniendo como punto de intervención la fecha de implementación del lockdown. Las tasas generales de mortalidad por cáncer redujeron tras la implementación de las restricciones, con una disminución significativa en Brasil. En total, el 75,3% de los óbitos ocurrieron en hospitales en Brasil, el 55,4% en Perú y el 45,7% en Chile. Tras la implementación del lockdown, las muertes domiciliarias aumentaron en todos los países, y las muertes hospitalarias solo redujeron de forma correspondiente en Chile. Nuestros resultados sugieren que la COVID-19 afectó significativamente las tasas de mortalidad por cáncer y el local del fallecimiento en América Latina.

Genetic Mutations Associated with Inflammatory Response Caused by HPV Integration in Oropharyngeal Squamous Cell Carcinoma.

(1) Background: Head and neck cancer (HNC) ranks as the sixth most prevalent cancer in the world. In addition to the traditional risk factors such as alcohol and tobacco consumption, the implication of the human papillomavirus (HPV) is becoming increasingly significant, particularly in oropharyngeal cancer (OPC). (2) Methods: This study is based on a review analysis of different articles and repositories investigating the mutation profile of HPV-related OPC and its impact on patient outcomes. (3) Results: By compiling data from 38 datasets involving 8311 patients from 12 countries, we identified 330 genes that were further analyzed. These genes were enriched for regulation of the inflammatory response (RB1, JAK2, FANCA, CYLD, SYK, ABCC1, SYK, BCL6, CEBPA, SRC, BAP1, FOXP1, FGR, BCR, LRRK2, RICTOR, IGF1, and ATM), among other biological processes. Hierarchical cluster analysis showed the most relevant biological processes were linked with the regulation of mast cell cytokine production, neutrophil activation and degranulation, and leukocyte activation (FDR < 0.001; p-value < 0.05), suggesting that neutrophils may be involved in the development and progression of HPV-related OPC. (4) Conclusions: The neutrophil infiltration and HPV status emerge as a potential prognostic factor for OPC. HPV-infected HNC cells could potentially lead to a decrease in neutrophil infiltration. By gaining a better molecular understanding of HPV-mediated neutrophil immunosuppression activity, it is possible to identify a meaningful target to boost antitumor immune response in HNC and hence to improve the survival of patients with HNC.

Awareness regarding antimicrobial resistance and confidence to prescribe antibiotics in dentistry: a cross-continental student survey.

BACKGROUND: The antimicrobial resistance (AMR) crisis is a major global threat and one of its biggest drivers is the overuse of antibiotics in humans. Dentists are responsible for 5-10% antibiotic prescriptions worldwide and recent data suggest that knowledge and prescribing practices need improvement. METHODS: A cross-sectional web-survey was sent to dental students from six universities in Norway, Canada, and Brazil. Topics addressed covered awareness, confidence to prescribe antibiotics, and education needs. Data were presented descriptively and statistical testing was employed to compare group means when applicable. RESULTS: In total, 562 responses were collected across the three countries with a response rate of 28.6%. 'Antibiotic resistance' was among the highest priorities (scale 1-10) with an average of 8.86 (SEM ± 0.05), together with 'Gender inequality' (8.68 ± 0.07) and 'Climate change' (8.68 ± 0.07). Only 28.8% thought that Dentistry was engaged in national/international campaigns promoting awareness on the topic and 8.9% stated to have heard about the 'One Health' concept. Final year dental students showed an average confidence to prescribe antibiotics of 7.59 (± 0.14). Most students demonstrated interest in receiving additional education on all topics listed, with the three most pressing being 'antibiotic prescription for treatment of infections' (82.9%), 'drug interactions' (80.9%), and 'spread of antibiotic resistance' (79.6%). A trend was observed between higher awareness regarding the topic and higher confidence to prescribe. CONCLUSIONS: There is a need to revisit dental education on antibiotic resistance with a global perspective and to create more stewardship initiatives that promote awareness on the topic.

Interaction of HPV16 and Cutaneous HPV in Head and Neck Cancer.

OBJECTIVES: Human papillomavirus 16 (HPV16) is an established risk factor for Head and Neck Cancer (HNC). Recent reports have shown that genotypes from the beta (ß) and gamma (γ) genera, also known as cutaneous HPV, can be found in the oral cavity, but their role is largely unidentified. We investigated the interaction between oral HPV16 and cutaneous HPV in HNC. METHODS: We use data on incident HNC cases (n = 384) and frequency-matched hospital-based controls (n = 423) from the HeNCe Life study in Montreal, Canada. Participants were tested for alpha HPV and cutaneous genera using oral mouth rinse and brush samples. We used unconditional logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence interval (CI) as a measure of the effect between HPV and HNC and assessed the interaction between HPV genotypes on the multiplicative and additive scales. RESULTS: Prevalence of HPV infection was higher among cases (73%) than controls (63.4%), with cases more likely to be coinfected with more than a single genotype, 52.9% vs. 43.5%, respectively. Infection with HPV16 alone had a strong effect on HNC risk aOR = 18.2 [6.2, 53.2], while infection with any cutaneous HPV, but not HPV16, appeared to have the opposite effect aOR = 0.8 [0.6, 1.1]. The observed effect of joint exposure to HPV16 and any cutaneous HPV (aOR = 20.4 [8.3, 50.1]) was stronger than the expected effect based on an assumption of independent exposures but was measured with considerable imprecision. While the point estimate suggests a positive interaction between HPV16 and cutaneous HPV, results were imprecise with relative excess risk due to interaction (RERI) = 2.4 [-23.3, 28.2]. CONCLUSION: There could be biologic interaction between HPV16 and genotypes from cutaneous genera, which warrants further investigation. Although cutaneous HPVs are not usually found in tumor tissues, they are cofactors that could interact with HPV16 in the oral cavity and thus strengthen the latter's carcinogenic effect.

In Vitro Toxicity Evaluation of Carrageenan on Cells and Tissues of the Oral Cavity.

Carrageenan is a highly potent anti-human papillomavirus (HPV) agent with the potential for formulation as a mouthwash against oral HPV infection. However, its toxic effect on tissues of the oral cavity is currently unknown. This study aims to evaluate the safety of carrageenan on human cells and tissues of the oral cavity. Human salivary gland cells and reconstructed human oral epithelium (RHOE) were used for this in vitro study. The cells were subjected to 0.005-100 µg/mL of carrageenan for 4, 12, and 24 h in quadruplicate. RHOE were exposed to 100 µg/mL of carrageenan for 24 h in triplicate and stained with hematoxylin/eosin for histological analyses. All experiments had saline and 1% sodium dodecyl sulphate (SDS) as negative and positive controls, respectively. Carrageenan tissue toxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to quantify cell viability. Tissue toxicity was further evaluated histologically by an oral pathologist to assess morphological changes. Our data showed that carrageenan did not significantly decrease cell and tissue viability when compared to the positive control. The histological evaluation of the RHOE also showed no loss of viability of the carrageenan-treated sample compared to untreated tissue. In contrast, 1% SDS-treated RHOE showed extensive tissue destruction. Our experiments suggest that carrageenan is safe for use in the oral cavity.

Do cutaneous human papillomavirus genotypes affect head and neck cancer? Evidence and bias-correction from a case-control study.

BACKGROUND: Three genera of human papillomavirus (HPV) infect the oral cavity and oropharynx- alpha (α), beta (ß) and gamma (γ). While α-HPV infection is an established risk factor for head and neck cancers (HNC), the role of other genera remains unclear. We aimed to estimate the effect of α-, ß-, γ-HPV on HNC using a hospital-based case-control study. METHODS: We recruited incident HNC cases (396) and controls (439), frequency-matched by age and sex from four main referral hospitals in Montreal, Canada. We collected information on sociodemographic and behavior characteristics using in-person interviews, and tested rinse, brush and tumor specimens for HPV genotypes. We estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the effect of HPV on HNC using logistic regression, adjusting for confounding. We conducted probabilistic bias analysis to account for potential exposure misclassification, selection bias, and residual confounding. RESULTS: α-HPV genus had a strong effect on HNC, particularly HPV16 (aOR=22.6; 95% CI: 10.8, 47.2). ß-HPV was more common among controls (aOR=0.80; 95% 0.57, 1.11). After adjustment for HPV16, we found weaker evidence for γ-HPV (aOR= 1.29; 95% CI: 0.80, 2.08). Combined bias analyses for HPV16 increased the strength of the point estimate, but added imprecision (aOR=54.2, 95% CI: 10.7, 385.9). CONCLUSIONS: α-HPV, especially HPV16, appears to increase the risk for HNC, while there is little evidence for an effect of ß- or γ-HPV. ß-HPV may have a preventive effect, while γ-HPV may increase the risk of HNC, although to a lesser extent than that of α-HPV. Results for cutaneous HPV were imprecise and less conclusive. Due to possible epidemiologic biases, the true relation between HPV and HNC could be underestimated in the literature. Further improvement in current methods and more studies of the biologic mechanisms of the three genera in HNC development are warranted.

Life Course Tobacco Smoking and Risk of HPV-Negative Squamous Cell Carcinomas of Oral Cavity in Two Countries.

Background: Tobacco smoking remains one of the major risk factors for oral cavity cancers (OCC), a subgroup of head and neck cancer (HNC) less attributed to human papillomavirus (HPV) infection. Although a strong dose-dependent association between tobacco smoking and OCC exists, several important questions on the age-dependent effects of this habit remain unanswered. We investigated which life course hypothesis best describes the association between tobacco smoking and HPV-negative (HPV-ve ) OCC in Canada and India. Methods: We used data from the HeNCe Life study, a hospital-based case-control study conducted in Canada and India, using similar protocols. Cases were newly diagnosed subjects with primary squamous cell carcinomas of the head and neck region. Control subjects were patients with non-cancer selected from various outpatient clinics in a hospital located in the same catchment area as the cases and frequency-matched to cases according to age and sex. We collected information on an array of life course exposures using a structured questionnaire with the help of a life grid. Tobacco exposure (pack-years) during three life periods (≤ 30, 31-50, and >50 years of age) was calculated from the entire life course history of smoking. We used CDx brushes to collect oral exfoliated cells. Alpha HPV DNA detection and genotyping were performed for 36 HPV genotypes using the linear array. Participants who tested positive for HPV were excluded from the analysis. We used the Bayesian relevant life course exposure model (BRLM) to identify the life course hypothesis that best described the relationship between tobacco smoking and HPV-ve OCC. Results: We show evidence for a late-life sensitive period (>50 years of age) for tobacco smoking in relation to the risk of HPV-ve OCC in both Canada and India. An increase of 1 pack-year of tobacco smoking increased the risk of OCC by ~3% in both countries. Conclusion: Our findings from the Canadian and Indian data suggest that smoking tobacco after 50 years of age may carry a higher risk of developing oral cancer than earlier in life. Further studies are warranted to confirm the results.

Advancing a programme theory for community-level oral health promotion programmes for humanitarian migrants: a realist review protocol.

INTRODUCTION: Humanitarian migrants often suffer from poor health, including oral health. Reasons for their oral health conditions include difficult migration trajectories, poor nutrition and limited financial resources. Oral health promotion is crucial for improving oral health-related quality of life of humanitarian migrants. While community-level oral health promotion programmes for humanitarian migrants have been implemented (eg, in host countries and refugee camps), there is scant literature evaluating their transferability or effectiveness. Given that these programmes yield unique context-specific outcomes, the purpose of this study is to understand how community-level oral health promotion programmes for humanitarian migrants work, in which contexts and why. METHODS AND ANALYSIS: Realist review, a theory-driven literature review methodology, incorporates a causal heuristic called context-mechanism-outcome configurations to explain how programmes work, for whom, and under which conditions. Using Pawson's five steps of realist review (clarifying scope and drafting an initial programme theory; identifying relevant studies; quality appraisal and data extraction; data synthesis; and dissemination of findings), we begin by developing an initial programme theory using the references of a scoping review on the oral health of refugees and asylum seekers and through hand searching in Google Scholar. Following stakeholder validation of our initial programme theory, we will locate additional evidence by searching in four databases (Ovid Medline, Ovid Embase, Cochrane Library and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) to test and refine our initial programme theory into a middle-range realist programme theory. The resultant theory will explain how community-level oral health promotion programmes for humanitarian migrants work, for whom, in which contexts and why. ETHICS AND DISSEMINATION: Since this study is a review and no primary data collection will be involved, institutional ethics approval is not required. The findings of this study will be disseminated in peer-reviewed journals, local and international conferences, and via social media. TRIAL REGISTRATION NUMBER: CRD42021226085.

NSAID chronotherapy after impacted third molar extraction: a randomized controlled trial.

OBJECTIVES: Postoperative pain management impacts patients' quality of life and morbidity. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are widely used for this following a 3-doses-per-day regime. However, pain and inflammation follow a circadian rhythm, and animal models assessing the scheduling of NSAID administration (e.g., chronotherapy) have shown that while their use during the active phase of the day enhances postoperative recovery, their administration during the resting phase could have detrimental effects. This observation has led us to hypothesize that night administration of NSAID might be unnecessary in post-surgical scenarios. Therefore, a randomized clinical trial was conducted to test this hypothesis in surgical third molar extractions. MATERIALS AND METHODS: Seventy (18-35 years) healthy participants requiring surgical removal of impacted lower third molars were recruited and randomized into a double-blind placebo-controlled study. For three days postoperatively, the treatment group (n = 33) received ibuprofen (400 mg) at 8 AM, 1 PM, and a placebo at 8 PM, while the control group (n = 37) received ibuprofen (400 mg) at 8 AM, 1 PM, and 8 PM. Pain severity was assessed by visual analog scale (VAS) and healing indicators including facial swelling, mouth opening, and C-reactive protein blood levels were also measured. RESULTS: Pain VAS measures showed a circadian variation peaking at night. Also, no significant differences were observed between the two groups of the study in terms of postoperative pain scores (estimate: 0.50, 95% CI = [- 0.38, 1.39]) or any other healing indicator. CONCLUSIONS: Postoperative pain follows a circadian rhythm. Moreover, night administration of ibuprofen might not provide any significant benefits in terms of pain management and control of inflammation, and two doses during the day only could be sufficient for pain management after surgical interventions. KNOWLEDGE TRANSFER STATEMENT: Even though this study cannot rule out the possibility that a reduced regime is different than a standard regime, nocturnal doses of ibuprofen seem to have no clinical significance in the short term, and the results of this study provide evidence in favor of reducing ibuprofen administration from three doses to two doses only after third molar surgery.