Association between the Mode of Delivery and Vertical Transmission of Human Papillomavirus.

Human papillomavirus (HPV) can be vertically transmitted. Our objective was to measure the association between the mode of delivery and the detection of HPV in infants. We used data collected from pregnant women during the HERITAGE study. Self-collected vaginal samples from the first and third trimester were obtained for HPV testing. Specimens from oral, pharyngeal, conjunctival and anogenital mucosa were collected from infants 36-48 h after delivery and at 3 months of age. All samples were tested for HPV DNA by the Linear Array assay. Adjusted odd ratios (aOR) and 95% confidence interval (CI) were estimated using multivariate logistic regressions. From the 282 women revealed to be HPV-positive in both the first and third trimesters, 25 infants were born HPV-positive. The overall probability of transmission was 8.9% (25/282); 3.7% (3/81) in participants with a caesarean section and 10.9% (22/201) for those who delivered vaginally. Vaginal delivery increased the risk of HPV in infants compared to caesarean (aOR: 3.63, 95%CI: 1.03-12.82). Infants born after a caesarean with ruptured membranes were not at increased risk of HPV compared to infants born after an elective caesarean section with intact membranes (aOR: 1.31, 95%CI: 0.10-17.76). Our results support the hypothesis that transmission occurs mostly during the passage in the vaginal canal.

Clinically apparent Helicobacter pylori infection and the risk of incident Alzheimer's disease: A population-based nested case-control study.

INTRODUCTION: Our population-based study assessed whether clinically apparent Helicobacter pylori infection (CAHPI) is associated with the risk of Alzheimer's disease (AD). METHODS: We assembled a population-based cohort of all dementia-free subjects in the United Kingdom's Clinical Practice Research Datalink (UK CPRD), aged ≥50 years (1988-2017). Using a nested case-control approach, we matched each newly developed case of AD with 40 controls. Conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with CAHPI compared with no CAHPI during ≥2 years before the index date. We also used salmonellosis as a negative control exposure. RESULTS: Among 4,262,092 dementia-free subjects, 40,455 developed AD after a mean 11 years of follow-up. CAHPI was associated with an increased risk of AD (OR, 1.11; 95% CI, 1.01-1.21) compared with no CAHPI. Salmonellosis was not associated with the risk of AD (OR, 1.03; 95% CI, 0.82-1.29). DISCUSSION: CAHPI was associated with a moderately increased risk of AD. HIGHLIGHTS: CAHPI was associated with an 11% increased risk of AD in subjects aged ≥50 years. The increase in the risk of AD reached a peak of 24% a decade after CAHPI onset. There was no major effect modification by age or sex. Sensitivity analyses addressing several potential biases led to consistent results.

Incidence and Factors Associated With Mental Health Disorders in Patients With Rectal Cancer Post-Restorative Proctectomy.

BACKGROUND: Most patients with rectal cancer experience bowel symptoms post-restorative proctectomy. The incidence of mental health disorders post-restorative proctectomy and its association with bowel symptoms are unknown. OBJECTIVES: This study aimed 1) to describe the incidence of mental health disorders in patients who underwent restorative proctectomy for rectal cancer and 2) to study the association between incident mental health disorders and bowel dysfunction after surgery. DESIGN: This retrospective cohort study used the Clinical Practice Research Datalink and Hospital Episode Statistics databases. SETTINGS: The databases were based in the United Kingdom. PATIENTS: All adult patients who underwent restorative proctectomy for a rectal neoplasm between 1998 and 2018 were included. MAIN OUTCOME MEASURES: The primary outcome was an incident mental health disorder. The associations between bowel, sexual, and urinary dysfunctions and incident mental health disorders were studied using Cox proportional hazard regression models. RESULTS: In total, 2197 patients who underwent restorative proctectomy were identified. Of 1858 patients without preoperative bowel, sexual, or urinary dysfunction, 1455 had no preoperative mental health disorders. In this cohort, 466 patients (32.0%) developed incident mental health disorders following restorative proctectomy during 6333 person-years of follow-up. On multivariate Cox regression, female sex (adjusted HR 1.30; 95% CI, 1.06-1.56), metastatic disease (adjusted HR 1.57; 95% CI, 1.14-2.15), incident bowel dysfunction (adjusted HR 1.41, 95% CI, 1.13-1.77), and urinary dysfunction (adjusted HR 1.57; 95% CI, 1.16-2.14) were found to be associated with developing incident mental health disorders post-restorative proctectomy. LIMITATIONS: This study was limited by its observational study design and residual confounding. CONCLUSIONS: Incident mental health disorders after restorative proctectomy for rectal cancer are common. The presence of bowel and urinary functional impairment significantly increases the risk of poor psychological outcomes among rectal cancer survivors. CON LOS TRASTORNOS DE SALUD MENTAL EN PACIENTES CON CNCER DE RECTO POSTERIOR A PROCTECTOMA RESTAURADORA: ANTECEDENTES: La mayoría de los pacientes con cáncer de recto experimentan síntomas intestinales después de la proctectomía restauradora. Se desconoce la incidencia de trastornos de salud mental posteriores a la proctectomía restauradora y su asociación con síntomas intestinales.OBJETIVOS: Los objetivos de nuestro estudio son: a) describir la incidencia de trastornos de salud mental en pacientes sometidos a proctectomía restauradora por cáncer de recto; b) estudiar la asociación entre los trastornos de salud mental incidentes y la disfunción intestinal después de la cirugía.DISEÑO: Este fue un estudio de cohorte retrospectivo que utilizó las bases de datos Clinical Practice Research Datalink y Hospital Episode Statistics.ENTORNO CLÍNICO: Las bases de datos se basaron en el Reino Unido.PACIENTES: Se incluyeron todos los pacientes adultos que se sometieron a una proctectomía restauradora por una neoplasia rectal entre 1998 y 2018.PRINCIPALES MEDIDAS DE VALORACIÓN: El resultado primario fue un trastorno de salud mental incidente. Las asociaciones entre la disfunción intestinal, sexual y urinaria y los trastornos de salud mental incidentes se estudiaron utilizando modelos de regresión de riesgos proporcionales de Cox.RESULTADOS: En total, se identificaron 2.197 pacientes que se sometieron a proctectomía restauradora. De 1.858 pacientes sin disfunción intestinal, sexual o urinaria preoperatoria, 1.455 personas tampoco tenían trastornos de salud mental preoperatorios. En esta cohorte, 466 (32,0 %) pacientes desarrollaron trastornos de salud mental incidentes después de la PR durante 6333 años-persona de seguimiento. En la regresión multivariada de Cox, sexo femenino (HRa 1,30, IC 95% 1,06-1,56), enfermedad metastásica (HRa 1,57, IC 95% 1,14-2,15) e incidencia intestinal (HRa 1,41, IC del 95 %: 1,13 a 1,77) y la disfunción urinaria (aHR 1,57, IC del 95 %: 1,16 a 2,14) se asociaron con el desarrollo de trastornos de salud mental incidentes después de la proctectomía restauradora.LIMITACIONES: Este estudio estuvo limitado por el diseño del estudio observacional y la confusión residual.CONCLUSIÓN: Los trastornos de salud mental incidentes después de la proctectomía restauradora para el cáncer de recto son comunes. La presencia de deterioro funcional intestinal y urinario aumenta significativamente el riesgo de malos resultados psicológicos entre los sobrevivientes de cáncer de recto. (Traducción- Dr. Ingrid Melo ).

Human Papillomavirus Transmission and Persistence in Pregnant Women and Neonates.

Importance: The prevalence of human papillomavirus (HPV) infection during pregnancy and its risk of transmission to newborns are not well documented. Objective: To ascertain the prevalence of HPV in pregnant women, the risk of HPV detection in the placenta and in children at birth, and the probability that HPV detected at birth may persist in newborns. Design, Setting, and Participants: The Human Papillomavirus Perinatal Transmission and Risk of HPV Persistence Among Children (HERITAGE) study was a prospective cohort study that recruited participants between November 8, 2010, and October 16, 2016. Participant follow-up visits were completed on June 15, 2017. Participants, which included pregnant women of at least 18 years of age and at 14 weeks or earlier of gestation, were recruited from 3 academic hospitals in Montreal, Québec, Canada. Laboratory and statistical analysis were completed on November 15, 2022. Exposures: HPV DNA testing on self-collected vaginal and placental samples. Among children of mothers positive for HPV, conjunctival, oral, pharyngeal, and genital samples were collected for HPV DNA testing. Main Outcomes and Measures: Vaginal HPV DNA testing was done on self-collected vaginal samples obtained among pregnant women recruited during their first trimester of pregnancy and in the third trimester for those who had HPV-positive samples in the first trimester. HPV DNA testing was also done on placental samples (swabs and biopsies) collected after birth in all participants. HPV DNA testing among children included conjunctival, oral, pharyngeal, and genital samples collected in children of HPV-positive mothers at birth, 3 months, and 6 months of age. Results: A total of 1050 pregnant women (mean [SD] age, 31.3 [4.7] years) were included in this study. Prevalence of HPV in pregnant women at recruitment was 40.3% (95% CI, 37.3%-43.3%). Among the 422 HPV-positive women, 280 (66.4%) harbored at least 1 high-risk genotype, and 190 (45.0%) were coinfected with multiple genotypes. HPV was detected in 10.7% of placentas (92 of 860; 95% CI, 8.8%-12.9%) overall, but only 3.9% of biopsies (14 of 361) on the fetal side under the amniotic membrane were positive. Neonatal HPV detection (at birth and/or at 3 months) was 7.2% (95% CI, 5.0%-10.3%) overall, with the most frequent site of infection being the conjunctiva (3.2%; 95% CI, 1.8%-5.6%), followed by the mouth (2.9%; 95% CI, 1.6%-5.2%), the genital area (2.7%; 95% CI, 1.4%-4.9%), and the pharynx (0.8%; 95% CI, 0.2%-2.5%). Importantly, all HPV detected in children at birth cleared before the age of 6 months. Conclusions and relevance: In this cohort study, vaginal HPV was frequently detected in pregnant women. Perinatal transmission was infrequent, and in this cohort, no infection detected at birth persisted at 6 months. Although HPV was detected in placentas, it remains difficult to differentiate contamination vs true infection.

No time to grieve: Inuit loss experiences and grief practices in Nunavik, Quebec.

This article presents an overview of past and current grief rituals and practices and existing grassroots and institutional initiatives seeking to address the complex, prolonged, and traumatic grief experienced by many Inuit living in Quebec. While conducting a study seeking to identify the strengths, resources, and challenges for Nunavik's Inuit communities related to end-of-life care, results emerged concerning how family caregivers' grief related to the dying process was compounded by the sequelae of historic loss experiences (e.g., losses related to Canada's federal policies, including residential schools, forced relocations, and dog slaughters) and by present loss experiences (e.g., tragic and sudden deaths in local communities). To better support caregivers, an understanding of these grief experiences and a vision of bereavement care inclusive of community mobilization efforts to develop bereavement training and support is needed. We conclude with a discussion of a community capacity approach to bereavement care.

Common Vaccines and the Risk of Incident Dementia: A Population-based Cohort Study.

BACKGROUND: Observational studies suggesting that immunizations strongly decrease the risk of dementia had several methodological limitations. We assessed whether common vaccines are associated with the risk of dementia. METHODS: We assembled a population-based cohort of dementia-free individuals aged ≥50 years in the United Kingdom's Clinical Practice Research Datalink between 1988 and 2018. Using a nested case-control approach, we matched each patient with dementia with 4 controls. Conditional logistic regression yielded confounder-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of dementia associated with common vaccines >2 years before the index date compared with no exposure during the study period. Moreover, we applied a 10-year lag period and used active comparators (participation in breast or prostate cancer screening) to account for detection bias. RESULTS: Common vaccines were associated with an increased risk of dementia (OR, 1.38 [95% CI, 1.36-1.40]), compared with no exposure. Applying a 10-year lag period (OR, 1.20 [95% CI, 1.18-1.23]) and comparing versus prostate cancer screening (1.19 [ 1.11-1.27]) but not breast cancer screening (1.37 [1.30-1.45]) attenuated the risk increase. CONCLUSIONS: Common vaccines were not associated with a decreased risk of dementia. Unmeasured confounding and detection bias likely accounted for the observed increased risk.

Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis.

INTRODUCTION: Endoscopic healing is currently considered the main target in the management of ulcerative colitis (UC). There are conflicting data about the role of histology as a stricter treatment objective. We aim at evaluating the additional benefit of histologic remission over endoscopic remission. METHODS: We performed a prospective observational study at the McGill University Health Center. We enrolled adult patients with UC in clinical remission for at least 3 months undergoing a colonoscopy. Endoscopic disease activity was based on the Mayo endoscopic score. Rectal biopsies were obtained, and the histologic activity was evaluated using the Geboes score (active disease defined as Geboes score ≥ 3.1) with the addition of assessing the presence of basal plasmacytosis. Patients were followed up for 12 months for disease relapse defined as a partial Mayo score of > 2. At the time of relapse or end of follow-up, all patients underwent repeat endoscopic evaluation. The primary end point was clinical relapse. RESULTS: Two hundred fifty-three patients were included. The presence of basal plasmacytosis was associated with relapse (adjusted odd ratio = 2.07, 95% confidence interval [CI] 1.06-4.18, P = 0.042). Time to clinical relapse was significantly higher for patients with Mayo endoscopic score > 0 with adjusted hazard ratio = 2.65, 95% CI 1.31-5.39, and P = 0.007. Time to clinical relapse was not significantly higher for Geboes score ≥ 3.1 with adjusted hazard ratio = 1.29, 95% CI 0.67-2.49, and P = 0.45. DISCUSSION: Active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis is associated with relapse.

Perceptions of Inuit Women and Non-Inuit Healthcare Providers on the Implementation of Human Papillomavirus Self-Sampling as an Alternative Cervical Cancer Screening Method in Nunavik, Northern Quebec.

Human papillomavirus (HPV) self-sampling offers a cervical cancer (CC) screening alternative that can address certain barriers to the Papanicolaou test. As part of a larger community-based participatory project in Nunavik, Northern Québec, we travelled to two communities to gather perspectives from Inuit women and healthcare professionals (HCPs) on CC screening services and the possible implementation of HPV self-sampling. We held 10 group discussions with 28 Inuit women and 10 semi-structured interviews with 20 HCPs. The thematic analysis extracted themes reflecting one barrier and seven facilitators to accessing CC screening and the implementation of HPV self-sampling in Nunavik. Themes included, though not limited to, language and communication in health settings, access to culturally responsive educational resources on CC, and the noninvasive nature of HPV self-sampling. This study may serve to contribute to the co-development of a strategy for implementation that is designed according to the needs and priorities of the communities.

Risk factors for placental human papillomavirus infection.

OBJECTIVE: Human papillomavirus (HPV) has been associated with adverse pregnancy outcomes but placental HPV infection has been rarely studied. The objective was to determine the proportion of HPV-positive placentas and the associated risk factors among HPV-positive women during pregnancy. METHODS: We analysed data from pregnant women enrolled in HERITAGE cohort study between 2010 and 2016 with positive vaginal HPV infection during the first trimester of pregnancy (n=354). Placental swabs and biopsies were collected. HPV genotyping was performed using Linear Array. The predictors of placental HPV detection were identified by generalised estimating equations models. RESULTS: HPV was detected in 78 placentas (22.0%) (one among 96 caesarean sections and 77 among 258 vaginal deliveries). Overall, 91% of HPV-positive placentas were positive for a genotype that was detected in vaginal samples during pregnancy. Among women who delivered vaginally, abnormal cytology (adjusted OR (aOR) 1.78 (95% CI 1.02 to 3.10)), other genitourinary infection (aOR 2.41 (95% CI 1.31 to 4.44)), presence of multiple HPV genotypes in the first trimester (aOR 2.69 (95% CI 1.76 to 4.12)) and persistence of high-risk HPV infections during pregnancy (HPV-16/18: aOR 3.94 (95% CI 2.06 to 7.55) and other than HPV-16/18: aOR 2.06 (95% CI 1.05 to 4.02)) were independently associated with placental HPV. CONCLUSIONS: HPV was frequently detected in the placenta of women who delivered vaginally and may be associated with host immune response characteristics.

Ethnographic study of the barriers and facilitators to implementing human papillomavirus (HPV) self-sampling as a primary screening strategy for cervical cancer among Inuit women of Nunavik, Northern Quebec.

The rate of cervical cancer among Canadian Inuit women is higher than the national average. To date, early detection remains the best strategy for reducing the incidence of cervical cancer and its consequences. Thus, the aim of this study was to explore the barriers and facilitators in implementing human papillomavirus (HPV) self-sampling as a primary screening strategy for cervical cancer among Inuit women of Nunavik in Northern Quebec. A focused ethnographic approach was adopted. Inuit women of Nunavik participated in individual or group interviews during which a semi-structured interview guide was used to determine their perceptions of the barriers and facilitators to implementing HPV self-sampling as a primary screening strategy for cervical cancer. The data were analysed based on Paillé's grounded theory of qualitative analysis. Twenty-eight Inuit women participated in this study. Analysis revealed five subcategories of facilitators and four barriers. Inuit women may embrace the self-sampling method. Importantly, in order to be effective, these strategies must be culturally sensitive and adapted to women's preferences so as to increase sustainability. The results of this study provide the means for integrating the perspectives of Inuit women in implementing HPV self-sampling as a primary screening strategy for cervical cancer in Nunavik. Consideration of these facilitators and barriers might maximise the chance of success and optimise the screening participation rate.

Increased Prevalence of Myocardial Infarction and Stable Stroke Proportions in Patients with Inflammatory Bowel Diseases in Quebec in 1996-2015.

BACKGROUND: Chronic inflammatory diseases are linked to an increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is controversial. We therefore examined the risk of and risk factors for myocardial infarction (MI) and stroke in IBD patients. METHODS: We used the public health administrative database from the Province of Quebec, Canada, to identify IBD patients newly diagnosed between 1996 and 2015. The incidence and prevalence of MI and stroke in IBD patients were compared to those for the Canadian population. RESULTS: A cohort of 35,985 IBD patients was identified. The prevalence but not incidence rates of MI were higher in IBD patients (prevalence: 3.98%; incidence: 0.234) compared to the Canadian rates (prevalence: 2.0%; incidence: 0.220), while the prevalence and incidence rates of stroke were not significantly higher in the IBD patients (prevalence: 2.98%; incidence: 0.122, vs. Canadian rates: prevalence: 2.60%; incidence: 0.297). We identified age, female gender, hyperlipidemia, diabetes, and hypertension (p < 0.001 for each) as significant risk factors associated with MI and stroke in IBD. Exposure to biologics was associated with a higher incidence of MI (IRR: 1.51; 95% CI: 0.82-2.76; p = 0.07) in the insured IBD population. CONCLUSIONS: An increased prevalence but not incidence of MI and no increased risk of stroke were identified in this population-based IBD cohort.

Assessment of long-term bowel dysfunction after restorative proctectomy for neoplastic disease: A population-based cohort study.

BACKGROUND: The purpose of this study was to describe postoperative bowel dysfunction after restorative proctectomy, and to identify factors associated with its development. METHODS: Patients who underwent restorative proctectomy for rectal cancer between April 1998 and November 2018 were identified from the Hospital Episode Statistics database and linked to the Clinical Practice Research Datalink for postoperative follow-up. Bowel dysfunction was defined according to relevant symptom-based read codes and medication prescription-product codes. A Cox proportional hazards model was performed to identify factors associated with postoperative bowel dysfunction, adjusting for relevant covariates. RESULTS: In total, 2,197 patients were included. The median age was 70.0 (interquartile range: 62.0-77.0) years old, and the majority (59.2%) of patients were male. After a median follow-up of 51.6 (24.0-90.0) months, bowel dysfunction was identified in 620 (28.2%) patients. Risk factors for postoperative bowel dysfunction included extremes of age (<40 years old: adjusted hazards ratio 2.35, 95% confidence interval 1.18-4.65; 70-79 years old: adjusted hazards ratio 1.25, 95% confidence interval 1.03-1.52), radiotherapy (adjusted hazards ratio 1.94, 95% confidence interval 1.56-2.42), distal tumors (adjusted hazards ratio 1.62, 95% confidence interval 1.34-1.94), history of diverting ostomy (adjusted hazards ratio 1.58, 95% confidence interval 1.33-1.89), and anastomotic leak (adjusted hazards ratio 1.48, 95% confidence interval 1.06-2.05). A minimally invasive surgical approach was protective for postoperative bowel dysfunction (adjusted hazards ratio 0.68, 95% confidence interval 0.53-0.86). CONCLUSION: Bowel dysfunction was common after restorative proctectomy, and several patient, disease, and treatment-level factors were associated with its development.

Anti-TNF Therapy and the Risk of Herpes Zoster Among Patients With Inflammatory Bowel Disease.

BACKGROUND: The specific contribution of anti-TNF therapy to the onset of herpes zoster (HZ) in patients with inflammatory bowel disease (IBD) remains uncertain. Thus, the purpose of this nested case-control study was to explore whether the use of anti-TNF therapy is associated with an increased risk of HZ. METHODS: Using the Regie de l'Assurance Maladie du Québec, we identified incident cases of IBD between 1998 and 2015. We matched IBD cases of HZ with up to 10 IBD HZ-free controls on year of cohort entry and follow-up. Current use was defined as a prescription for anti-TNF therapy 60 days before the index date, with nonuse as the comparator. We conducted conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: The cohort consisted of 15,454 incident IBD patients. Over an average follow-up of 5.0 years, 824 patients were diagnosed with HZ (incidence of 9.3 per 1000 person-years). Relative to nonuse, current use of anti-TNF therapy was associated with an overall increased risk of HZ (OR, 1.5; 95% CI, 1.1-2.1). The risk was increased among those older than 50 years (OR, 2.1; 95% CI, 1.2-3.6) and those additionally using steroids and immunosuppressants (OR, 4.1; 95% CI, 2.3-7.2). CONCLUSIONS: Use of anti-TNF therapy was associated with an increased risk of HZ among patients with IBD, particularly among those older than 50 years and those on combination therapy. Prevention strategies for HZ ought to be considered for younger IBD patients commencing treatment.

Risk of gastric cancer in chronic obstructive pulmonary disease.

OBJECTIVE: Owing to the potential role of the gut-lung axis in carcinogenesis, we assessed the incidence of gastric cancer in patients with chronic obstructive pulmonary disease (COPD). METHODS: Using Quebec's administrative databases, we assembled a cohort of 118 913 patients aged 40 years and older with COPD from 1995 to 2015. We calculated age-standardized incidence rate ratio (IRR) and 95% confidence interval (CI) for gastric cancer, comparing patients with COPD to the Quebec general population. We evaluated temporal changes in incidence by calculating annual percentage change (APC) and stratified the analysis by anatomical site. RESULTS: Between 1995 and 2015, 279 patients with COPD developed gastric cancer (54.0 cases per 100 000 person-years). The overall age-standardized incidence rate in patients with COPD was comparable to the general population (IRR, 1.05; 95% CI, 0.79-1.39). However, the IRR increased over time (APC, 4.40%; P = 0.0101), due to the growing rate of gastric cancer in patients with COPD (APC, 1.90%; P = 0.2666) and the declining rate in the Quebec population (APC, -2.40%; P < 0.0001). CONCLUSIONS: The overall risk of gastric cancer in patients with COPD did not differ from the general population; however, the risk among patients has increased over the years. These findings provide insights as to whether long-term follow-up for gastric cancer risk in COPD is warranted.

Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth.

Importance: Preterm birth remains a leading cause of perinatal mortality and lifelong morbidity worldwide. The cause of most preterm births is unknown, although several infectious processes have been implicated. Objective: To assess whether human papillomavirus (HPV) infection, a frequent infection among women of childbearing age, is associated with preterm birth. Design, Setting, and Participants: The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal, Québec, Canada, among 899 pregnant women recruited between November 8, 2010, and October 16, 2016. Follow-up was completed on June 15, 2017. Statistical analysis was conducted from February 6, 2020, to January 21, 2021. Exposures: Vaginal HPV DNA detection in the first and third trimesters of pregnancy and placental HPV infection. Main Outcomes and Measures: The main outcome was preterm birth (defined as a live birth or stillbirth between 20 weeks and 0 days and 36 weeks and 6 days of gestation). The association between HPV DNA detection and preterm birth was measured using logistic regression. Odds ratios (ORs) and 95% CIs were adjusted by inverse probability of treatment weights of the propensity score. Results: The study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies. A total of 378 women (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester, and it was detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). Persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95% CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80), as was placental HPV infection (all preterm births: aOR, 2.53; 95% CI, 1.06-6.03; spontaneous preterm births: aOR, 2.92; 95% CI, 1.09-7.81). Results were similar when restricting the analysis to participants without a history of cervical intraepithelial neoplasia treatment. Conclusions and Relevance: The study's results suggest that persistent HPV-16/18 infection is associated with an increased risk of preterm birth, independent of cervical treatment. Future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

Infectious Disease Burden and the Risk of Alzheimer's Disease: A Population-Based Study.

BACKGROUND: Previous studies suggested a link between various infectious pathogens and the development of Alzheimer's disease (AD), posing the question whether infectious disease could present a novel modifiable risk factor. OBJECTIVE: To assess whether infectious disease burden due to clinically apparent infections is associated with an increased risk of AD. METHODS: We conducted a population-based nested case-control study using the United Kingdom Clinical Practice Research Datalink. We included all dementia-free subjects ≥50 years of age enrolling in the database between January 1988 and December 2017. Each case of AD identified during follow-up was matched with up to 40 controls. Conditional logistic regression estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with ≥1 infection diagnosed > 2 years before the index date compared with no infection during the study period. We further stratified by time since first infection and cumulative number of infections. RESULTS: The cohort included overall 4,262,092 individuals (mean age at cohort entry 60.4 years; 52% female). During a median follow-up of 10.5 years, 40,455 cases of AD were matched to 1,610,502 controls. Compared with having no burden of infectious disease, having a burden of infectious disease was associated with an increase in the risk of AD (OR, 1.05; 95% CI, 1.02 to 1.08). The risk increased with longer time since first infection, peaking after 12-30 years (OR, 1.11; 95% CI, 1.05-1.17). The risk did not increase with cumulative number of infections. CONCLUSION: The overall risk of AD associated with infectious disease burden was small but increased gradually with longer time since first infection.

No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015.

BACKGROUND: Crohn disease (CD) and ulcerative colitis (UC) have high health care expenditures because of medications, hospitalizations, and surgeries. We evaluated disease outcomes and treatment algorithms of patients with inflammatory bowel disease (IBD) in Québec, comparing periods before and after 2010. METHODS: The province of Québec's public health administrative database was used to identify newly diagnosed patients with IBD between 1996 and 2015. The primary and secondary outcomes included time to and probability of first and second IBD-related hospitalizations, first and second major surgery, and medication exposures. Medication prescriptions were collected from the public prescription database. RESULTS: We identified 34,644 newly diagnosed patients with IBD (CD = 59.5%). The probability of the first major surgery increased after 2010 in patients with CD (5 years postdiagnosis before and after 2010: 8% [SD = 0.2%] vs 15% [SD = 0.6%]; P < 0.0001) and patients with UC (6% [SD = 0.2%] vs 10% [SD = 0.6%] ;P < 0.0001). The probability of the second major surgery was unchanged in patients with CD. Hospitalization rates remained unchanged. Patients on anti-tumor necrosis factor (anti-TNF) medications had the lowest probability of hospitalizations (overall 5-year probability in patients with IBD stratified by maximal therapeutic step: 5-aminosalicylic acids 37% [SD = 0.6%]; anti-TNFs 31% [SD = 1.8%]; P < 0.0001). Anti-TNFs were more commonly prescribed for patients with CD after 2010 (4% [SD = 0.2%] vs 16% [SD = 0.6%]; P < 0.0001) in the public health insurance plan, especially younger patients. Corticosteroid exposure was unchanged before and after 2010. Immunosuppressant use was low but increased after 2010. The use of 5-ASAs was stable in patients with UC but decreased in patients with CD. CONCLUSIONS: The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs.

Fuzzy cognitive mapping with Inuit women: what needs to change to improve cervical cancer screening in Nunavik, northern Quebec?

BACKGROUND: Among Canadian Inuit, cervical cancer incidence and mortality rates are up to three times higher than the Canadian average. Cervical cancer is preventable through regular screening which, in Quebec, is opportunistic and requires physical examination and Papanicolaou ("Pap") smears. Since Human Papillomavirus (HPV) is the necessary cause of cervical cancer, HPV testing is a plausible screening alternative. HPV testing by self-sampling also addresses several barriers associated with physical examination and access to healthcare. In a participatory research paradigm, we worked with two communities of Nunavik to explore the possible implementation of HPV self-sampling. METHOD: Key community stakeholders formed an Advisory Committee to guide direct discussions with Inuit women. We presented available facts around cervical cancer, HPV and the female anatomy, and used Fuzzy Cognitive Mapping to collate women's views. A thematic analysis summarized data, adding links and weights to represent the relationship of each factor on the outcome: screening for cervical cancer. RESULTS: According to the 27 Inuit women who participated, the most influential factor in using health services was the cultural awareness of the healthcare provider. A significant barrier to screening was patient lack of information. The principal vector of change - the factor most likely to influence other factors - was the means of communication between the healthcare provider and the patient: visual communication was told to be the most effective. CONCLUSION: Fuzzy Cognitive Mapping is a practical tool for discussing possible health actions with stakeholders and to inform future research. The tool offers a visual aid for discussion across cultural and educational differences. It can help to build the partnerships that incorporate community voices into co-design of interventions that are relevant to and aligned with the needs of those who use them.

Antibodies to human papillomavirus types 6, 11, 16 and 18: Vertical transmission and clearance in children up to two years of age.

Background: There is a paucity of data on the dynamics of human papillomavirus (HPV) antibodies in children. We aimed to describe the vertical transmission and clearance of antibodies against HPV6, 11, 16 and 18 in children. Methods: We used data from pregnant women recruited into the HERITAGE cohort study between 2009 and 2012 who were positive for HPV-DNA at baseline. Dried blood spots were collected during the first trimester in pregnant participants, and at birth, 6, 12, and 24 months of age in children. The level of total immunoglobulin G (IgG) against HPV6, 11, 16 and 18 were measured using Luminex immunoassays. Spearman's coefficients were used to correlate HPV antibody levels between newborns and mothers. Panel and Kaplan-Meier graphics described antibody dynamics in the first 24 months of life. Findings: Antibodies from newborns and mothers (n = 58 pairs) were moderately to highly correlated with coefficients of 0·81 (95% confidence intervals (CI):0·70-0·88), 0·68 (95% CI:0·5-0·80), 0·90 (95% CI:0·83-0·94) and 0·85 (95% CI:0·76-0·91) against HPV6, 11, 16 and 18, respectively. In newborns seropositive at birth, anti-HPV antibodies were cleared by 80% and 100% at 12 and 24 months, respectively. Only two children presented detectable HPV antibodies at 24 months. The first child had no detectable antibodies at birth and the second presented increasing levels after two undetected measures. Interpretation: Correlation between mother and newborn IgG antibodies against HPV suggests vertical transfer. Most children cleared anti-HPV antibodies within six to 12 months. Funding: The Canadian Institutes of Health Research (CIHR).

The Mediating Role of Depressive Symptoms in the Association Between Food Insecurity and HIV Related Health Outcomes Among HIV-HCV Co-Infected People.

Food insecurity may lead to depressive symptoms, which are known to be associated with poor HIV related health outcomes. However, it is unclear to what extent food insecurity 'directly' affects these outcomes. We used data from the Food Security & HIV-HCV Sub-Study of the Canadian Co-Infection Cohort to assess the controlled direct effect. People experiencing severe food insecurity had 1.47 (95% CI 1.04-2.09) times the risk of having detectable HIV viral load and 0.94 (95% CI 0.87-1.02) fold change in CD4 count. After holding depressive symptoms constant, the association between severe food insecurity and HIV viral load was attenuated to a statistically non-significant level (RR 1.36, 95% CI: 0.95-1.96), whereas the association between severe food insecurity and CD4 count was unchanged. Depressive symptoms partially mediate the effect of severe food insecurity on HIV viral suppression; interventions focused on depressive symptoms alone may not be sufficient, however, to eliminate this effect.