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.

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Anaphylactic Reaction Among Patients With Type 2 Diabetes: A Multisite Population-Based Cohort Study.

Case reports and a pharmacovigilance analysis have linked glucagon-like peptide 1 receptor agonists (GLP-1 RAs) with anaphylactic reactions, but real-world evidence for this possible association is lacking. Using databases from the United Kingdom (Clinical Practice Research Datalink) and the United States (Medicare, Optum (Optum, Inc., Eden Prairie, Minnesota), and IBM MarketScan (IBM, Armonk, New York)), we employed a new-user, active comparator study design wherein initiators of GLP-1 RAs were compared with 2 different active comparator groups (initiators of dipeptidyl peptidase 4 (DPP-4) inhibitors and initiators of sodium-glucose cotransporter 2 (SGLT-2) inhibitors) between 2007 and 2019. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for an anaphylactic reaction. Database-specific HRs were pooled using random-effects models. Compared with the use of DPP-4 inhibitors (n = 1,641,520), use of GLP-1 RAs (n = 324,098) generated a modest increase in the HR for anaphylactic reaction, with a wide 95% CI (36.9 per 100,000 person-years vs. 32.1 per 100,000 person-years, respectively; HR = 1.15, 95% CI: 0.94, 1.42). Compared with SGLT-2 inhibitors (n = 366,067), GLP-1 RAs (n = 259,929) were associated with a 38% increased risk of anaphylactic reaction (40.7 per 100,000 person-years vs. 29.4 per 100,000 person-years, respectively; HR = 1.38, 95% CI: 1.02, 1.87). In this large, multisite population-based cohort study, GLP-1 RAs were associated with a modestly increased risk of anaphylactic reaction when compared with DPP-4 inhibitors and SGLT-2 inhibitors.

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.

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.

Androgen deprivation therapy for prostate cancer and the risk of bladder cancer: A systematic review of observational studies.

BACKGROUND: Recent interest has been geared towards the potential therapeutic and chemopreventive benefit of androgen deprivation therapy (ADT) for bladder cancer. As a result, several observational studies have investigated this potential association. Given the important side effects associated with ADT treatment, understanding the methodological strengths and weaknesses of the current evidence is warranted. OBJECTIVES: The objective of this systematic review was to examine the heterogeneity of the current observational studies on the association between ADT and bladder cancer by assessing the methodological strengths and limitations of these studies. MATERIAL AND METHODS: We systematically searched Medline, EMBASE, Healthstar, Cochrane Library Online, Science Citation Index, and Dissertation Abstracts Online, from inception to August 2019 to identify all observational studies investigating the association between ADT and bladder cancer. We assessed overall study quality using the ROBINS-I tool and evaluated the presence of other key pharmacoepidemiologic biases. RESULTS: Overall, our systematic review included 7 observational studies. Five studies reported a decreased risk of bladder cancer with ADT use, 1 study reported no association, and 1 study reported an increased risk. All studies had time-related biases, did not consider a lag period, and had potential residual confounding. Moreover, 1 study had potential detection bias, 6 included prevalent users, 3 had inadequate follow-up durations, 6 had exposure misclassification, and 5 used an inappropriate comparator. CONCLUSION: Taken together, future methodologically-rigorous studies addressing the limitations underlined in this systematic review are needed to evaluate the important potential association between ADT and bladder cancer.

Weight-lowering Effects of Glucagon-like Peptide-1 Receptor Agonists and Detection of Breast Cancer Among Obese Women with Diabetes.

BACKGROUND: It has been proposed that the weight loss associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may improve detection of breast cancer in patients undergoing this treatment. We aimed to determine whether the weight-lowering effects of GLP-1 RAs are associated with an increased detection of breast cancer among obese women with type 2 diabetes. METHODS: Using the UK Clinical Practice Research Datalink, we conducted a propensity score-matched cohort study among female obese patients with type 2 diabetes newly treated with antidiabetic drugs between 1 January 2007 and 31 January 2018. New users of GLP-1 RAs (n = 5,510) were matched to new users of second- to third-line noninsulin antidiabetic drugs (n = 5,510). We used time-dependent Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with different GLP-1 RA maximal weight loss categories (<5%, 5%-10%, >10%). RESULTS: Breast cancer incidence gradually increased with GLP-1 RA maximal weight loss categories, with the highest HR observed for patients achieving at least 10% weight loss (HR = 1.8, 95% CI = 1.1, 2.8). In secondary analyses, the HR for >10% weight loss was highest in the 2-3 years since treatment initiation (HR = 2.9, 95% CI = 1.2, 6.9). CONCLUSIONS: In this population-based study, the detection of breast cancer gradually increased with GLP-1 RA weight loss categories, particularly among those achieving >10% weight loss. These results are consistent with the hypothesis that substantial weight loss with GLP-1 RAs may improve detection of breast cancer among obese patients with type 2 diabetes.

Androgen Deprivation Therapy for Prostate Cancer and the Risk of Rheumatoid Arthritis: A Population-Based Cohort Study.

INTRODUCTION: Two recent observational studies have investigated the association between androgen deprivation therapy (ADT) and rheumatoid arthritis (RA), but generated discrepant findings and had important methodological limitations. Thus, the objective of this study was to determine whether the use of ADT is associated with an increased risk of RA in men with prostate cancer. PATIENTS AND METHODS: We conducted a population-based cohort study using the United Kingdom Clinical Practice Research Datalink. The cohort included all men, at least 40 years of age, newly diagnosed with prostate cancer between 1 January 1988 and 31 March 2014, with follow-up until 30 September 2014. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays and latency. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of RA, comparing use of ADT with non-use. Secondary analyses were conducted to assess whether the association varied according to ADT type and cumulative duration of use. Finally, we conducted several sensitivity analyses to assess the robustness of our findings. RESULTS: The cohort included 32,302 men followed for a median of 3.3 years. During follow-up, 63 patients were newly diagnosed with RA, generating an incidence rate of 46.5/100,000 person-years. Compared with non-use, the use of ADT was not associated with an increased risk of RA (HR 0.84, 95% CI 0.49-1.45). In secondary analyses, the association did not vary according to ADT type or with cumulative duration of use (p trend = 0.53). The results remained consistent in sensitivity analyses. CONCLUSION: In this population-based study, the use of ADT was not associated with an increased risk of RA in men with prostate cancer.

Testosterone Replacement Therapy and the Risk of Prostate Cancer in Men With Late-Onset Hypogonadism.

The association between the use of testosterone replacement therapy (TRT) and prostate cancer remains uncertain. Thus, we investigated whether TRT is associated with an increased risk of prostate cancer in men with late-onset hypogonadism. We used the UK Clinical Practice Research Datalink to assemble a cohort of 12,779 men who were newly diagnosed with hypogonadism between January 1, 1995, and August 31, 2016, with follow-up until August 31, 2017. Exposure to TRT was treated as a time-varying variable and lagged by 1 year to account for cancer latency, with nonuse as the reference category. During 58,224 person-years of follow-up, a total of 215 patients were newly diagnosed with prostate cancer, generating an incidence rate of 3.7 per 1,000 person-years. In time-dependent Cox proportional hazards models, use of TRT was not associated with an overall increased risk of prostate cancer (hazard ratio = 0.97; 95% confidence interval: 0.71, 1.32) compared with nonuse. Results remained consistent in secondary and sensitivity analyses, as well as in a propensity score-matched cohort analysis that further assessed the impact of residual confounding. Overall, the use of TRT was not associated with an increased risk of prostate cancer in men with late-onset hypogonadism.