Does the family physicians’ characteristics affect Cervical Cancer Screening rates?

Introduction While the effectiveness of cervical cancer-screening (CCS) programs is well accepted, concern is growing regarding Family physicians (FP) poor adherence to CCS guidelines resulting in over and under screening. In Canada, it is a FP responsibility to ensure that the CCS is done as per guidelines and with appropriate follow-up. Objectives and Approach To identify primary care physicians’ characteristics that are associated with over and under CCS for eligible women in Calgary, Alberta. We accessed the Calgary Laboratory Services data for 1475 FPs practicing in Calgary and linked it with the Physicians database of College of Physicians and Surgeons Alberta database. We then matched FP’s gender, country and year of medical school graduation, years since medical school graduation, certification in family medicine and their clinic address with their CCS testing patterns. Using doctors as their own controls, we compared data from 2010-2016 to determine practice variations in CCS patterns subsequent to guideline changes. Results We analyzed approximately 2,400,000 Pap test requisitions (approx. 300,000 per year) to identify screening patterns from 2010-2016 of 1475 family practitioners practicing in Calgary. Our preliminary results identified significant variations in the test ordering patterns of FPs. Approx. half of the male FPs were not performing CCS tests on their eligible female patients. Female FPs ordered more CCS tests than their male counterparts. FP trained in North America, were ordering more pap tests than FPS trained elsewhere. Decreased CSS was also observed among FPs practicing in Northeast Calgary. Conclusion/Implications We detected three CCS patterns: FPs who never perform CSS on eligible female patients; FPs who followed recommended guidelines for performing CCS tests and FPs who performed CCS tests, not following the guidelines. To ensure appropriate use of CSS, identifying intention-behavior relationships and innovative educational interventions for FPs are required

Sociodemographic correlates of cervical cancer screening rates in Calgary, AB: Matched Trend analysis of 2006, 2011 and 2016

Introduction Cervical Cancer Screening (CCS) has reduced the incidence and mortality rates of cervical cancer (CC). However, the benefits are distributed unevenly since 30% of eligible women have not been screened within three years in Alberta. Women who have never been screened or are screened irregularly are most at risk for CC. Objectives and Approach The aim of this study was to understand who gets CCS and who does not, in Calgary, Alberta and analyze the CC policy implications since 2006-2016. CCS information of women aged 25-69 were obtained from Calgary Laboratory Services for the years 2006, 2011 and 2016 and matched with Canadian Census data. Negative binomial regression and Generalized Estimating Equations were used to test associations of CCS rates with socio-demographic variables for eligible women. CCS spatial trends over the years was studied using the GIS Hotspot analysis. Results Major age and geographical variations were observed in CCS rates in Calgary. CCS rates in the recommended age groups varied from 40.6 % to 23.6 %. For age groups between 25 and 54, CCS rates were above 33\%, which implies that many women are having tests more than once every three years. Use was positively associated with median household income, education, Chinese ethnicity and negatively associated with ‘Black’ visible minority status. Women living in lower socio-economic areas of Calgary are screened at lower rates. Hotspot analysis maps revealed heterogeneous testing patterns in the city with relatively higher testing in the downtown, Southeast and Northwest quadrants of the city and relatively decreased CCS in the Northeast quadrant of Calgary Conclusion/Implications Screening programs need to be strengthened with greater focus on including specific demographic groups and reducing overuse. Understanding current testing patterns are important in assessing the benefit to harm ratio of CCS and for monitoring and evaluation of CCS program

Automated Paper Screening for Clinical Reviews Using Large Language Models

Objective: To assess the performance of the OpenAI GPT API in accurately and efficiently identifying relevant titles and abstracts from real-world clinical review datasets and compare its performance against ground truth labelling by two independent human reviewers. Methods: We introduce a novel workflow using the OpenAI GPT API for screening titles and abstracts in clinical reviews. A Python script was created to make calls to the GPT API with the screening criteria in natural language and a corpus of title and abstract datasets that have been filtered by a minimum of two human reviewers. We compared the performance of our model against human-reviewed papers across six review papers, screening over 24,000 titles and abstracts. Results: Our results show an accuracy of 0.91, a sensitivity of excluded papers of 0.91, and a sensitivity of included papers of 0.76. On a randomly selected subset of papers, the GPT API demonstrated the ability to provide reasoning for its decisions and corrected its initial decision upon being asked to explain its reasoning for a subset of incorrect classifications. Conclusion: The GPT API has the potential to streamline the clinical review process, save valuable time and effort for researchers, and contribute to the overall quality of clinical reviews. By prioritizing the workflow and acting as an aid rather than a replacement for researchers and reviewers, the GPT API can enhance efficiency and lead to more accurate and reliable conclusions in medical research.Comment: 15 pages, 2 figures, 4 table

Ethnic disparity and exposure to supplements rather than adverse childhood experiences linked to preterm birth in Pakistani women

Background: Adverse childhood experiences (ACEs) are associated with prenatal mental health and negative pregnancy outcomes in high income countries, but whether the same association exists in Pakistan, a low- to middle-income (LMI) country, remains unclear. Methods: Secondary data analyses of a prospective longitudinal cohort study examining biopsychosocial measures of 300 pregnant women at four sites in Karachi, Pakistan. A predictive multiple logistic regression model for preterm birth (PTB; i.e., \u3c37 weeks’ gestation) was developed from variables significantly (P \u3c 0.05) or marginally (P \u3c 0.10) associated with PTB in the bivariate analyses. Results: Of the 300 women, 263 (88%) returned for delivery and were included in the current analyses. The PTB rate was 11.1%. We found no association between ACE and PTB. Mother\u27s education (P = 0.011), mother\u27s ethnicity (P = 0.010), medications during pregnancy (P = 0.006), age at birth of first child or current age if primiparous (P = 0.049) and age at marriage (P = 0.091) emerged as significant in bivariate analyses. Mother\u27s ethnicity and taking medications remained predictive of PTB in the multivariate model. Limitations: Findings are limited by the relatively small sample size which precludes direct testing for possible interactive effects. Conclusions: In sum, pathways to PTB for women in LMI countries may differ from those observed in highincome countries and may need to be modelled differently to include behavioural response to emotional distress and socio-cultural contexts

Smoking in asthma is associated with elevated levels of corticosteroid resistant sputum cytokines—an exploratory study

<p>Background: Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.</p> <p>Objectives: To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.</p> <p>Methods: Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.</p> <p>Results: Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers wi</p> <p>Conclusion: Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.</p&gt

Morphometric characteristics of basal cell carcinoma peritumoral stroma varies among basal cell carcinoma subtypes

<p>Abstract</p> <p>Background</p> <p>The role that the peritumoral stroma plays in the growth of tumours is currently poorly understood. In this manuscript the morphometric characteristics of basal cell carcinoma subtypes and their associated peritumoral stromas are presented.</p> <p>Methods</p> <p>Ninety eight digitized basal cell carcinoma histology slides were categorized as infiltrative, nodular, or superficial subtypes, and were analysed using a combination of manual and computer-assisted approaches. The morphometric characteristics of the tumour nests and their associated peritumoral stroma were quantified, and the presence of a marked immune reaction or elastosis was noted.</p> <p>Results</p> <p>The tumour to stroma ratio was different among each tumour subtype. Elastosis was identified in a greater proportion of the infiltrative tumours.</p> <p>Conclusions</p> <p>Quantitative differences exist between the peritumoral stroma of basal cell carcinoma subtypes. Future work exploring the relation between these morphometric differences and biochemical variations in peritumoral stroma may further our understanding of the biology of carcinoma development.</p> <p>Trial Registration</p> <p>Not applicable.</p

Population genetics of cancer cell clones: possible implications of cancer stem cells

Abstract Background The population dynamics of the various clones of cancer cells existing within a tumour is complex and still poorly understood. Cancer cell clones can be conceptualized as sympatric asexual species, and as such, the application of theoretical population genetics as it pertains to asexual species may provide additional insights. Results The number of generations of tumour cells within a cancer has been estimated at a minimum of 40, but high cancer cell mortality rates suggest that the number of cell generations may actually be in the hundreds. Such a large number of generations would easily allow natural selection to drive clonal evolution assuming that selective advantages of individual clones are within the range reported for free-living animal species. Tumour cell clonal evolution could also be driven by variation in the intrinsic rates of increase of different clones or by genetic drift. In every scenario examined, the presence of cancer stem cells would require lower selection pressure or less variation in intrinsic rates of increase. Conclusions The presence of cancer stem cells may result in more rapid clonal evolution. Specific predictions from theoretical population genetics may lead to a greater understanding of this process.</p

Integrated Functional, Gene Expression and Genomic Analysis for the Identification of Cancer Targets

The majority of new drug approvals for cancer are based on existing therapeutic targets. One approach to the identification of novel targets is to perform high-throughput RNA interference (RNAi) cellular viability screens. We describe a novel approach combining RNAi screening in multiple cell lines with gene expression and genomic profiling to identify novel cancer targets. We performed parallel RNAi screens in multiple cancer cell lines to identify genes that are essential for viability in some cell lines but not others, suggesting that these genes constitute key drivers of cellular survival in specific cancer cells. This approach was verified by the identification of PIK3CA, silencing of which was selectively lethal to the MCF7 cell line, which harbours an activating oncogenic PIK3CA mutation. We combined our functional RNAi approach with gene expression and genomic analysis, allowing the identification of several novel kinases, including WEE1, that are essential for viability only in cell lines that have an elevated level of expression of this kinase. Furthermore, we identified a subset of breast tumours that highly express WEE1 suggesting that WEE1 could be a novel therapeutic target in breast cancer. In conclusion, this strategy represents a novel and effective strategy for the identification of functionally important therapeutic targets in cancer