Recommendations for a national agenda to substantially reduce cervical cancer

PURPOSE: Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening, provide an unprecedented opportunity to greatly reduce cervical cancer in the USA. Despite these advances, thousands of women continue to be diagnosed with and die of this highly preventable disease each year. This paper describes the initiatives and recommendations of national cervical cancer experts toward preventing and possibly eliminating this disease. METHODS: In May 2011, Cervical Cancer-Free America, a national initiative, convened a cervical cancer summit in Washington, DC. Over 120 experts from the public and private sector met to develop a national agenda for reducing cervical cancer morbidity and mortality in the USA. RESULTS: Summit participants evaluated four broad challenges to reducing cervical cancer: (1) low use of HPV vaccines, (2) low use of cervical cancer screening, (3) screening errors, and (4) lack of continuity of care for women diagnosed with cervical cancer. The summit offered 12 concrete recommendations to guide future national and local efforts toward this goal. CONCLUSIONS: Cervical cancer incidence and mortality can be greatly reduced by better deploying existing methods and systems. The challenge lies in ensuring that the array of available prevention options are accessible and utilized by all age-appropriate women-particularly minority and underserved women who are disproportionately affected by this disease. The consensus was that cervical cancer can be greatly reduced and that prevention efforts can lead the way towards a dramatic reduction in this preventable disease in our country

The Peripheral Blood Transcriptome Identifies the Presence and Extent of Disease in Idiopathic Pulmonary Fibrosis

<div><h3>Rationale</h3><p>Peripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. We hypothesize that peripheral blood biomarkers will identify disease in its early stages, and facilitate monitoring for disease progression.</p> <h3>Methods</h3><p>Gene expression profiles of peripheral blood RNA from 130 IPF patients were collected on Agilent microarrays. Significance analysis of microarrays (SAM) with a false discovery rate (FDR) of 1% was utilized to identify genes that were differentially-expressed in samples categorized based on percent predicted D_LCO and FVC.</p> <h3>Main Measurements and Results</h3><p>At 1% FDR, 1428 genes were differentially-expressed in mild IPF (D_LCO >65%) compared to controls and 2790 transcripts were differentially- expressed in severe IPF (D_LCO >35%) compared to controls. When categorized by percent predicted D_LCO, SAM demonstrated 13 differentially-expressed transcripts between mild and severe IPF (< 5% FDR). These include CAMP, CEACAM6, CTSG, DEFA3 and A4, OLFM4, HLTF, PACSIN1, GABBR1, IGHM, and 3 unknown genes. Principal component analysis (PCA) was performed to determine outliers based on severity of disease, and demonstrated 1 mild case to be clinically misclassified as a severe case of IPF. No differentially-expressed transcripts were identified between mild and severe IPF when categorized by percent predicted FVC.</p> <h3>Conclusions</h3><p>These results demonstrate that the peripheral blood transcriptome has the potential to distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted D_LCO, but not FVC.</p> </div

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Mental health service use by recent immigrants from different world regions and by non-immigrants in Ontario, Canada: a cross-sectional study

Abstract Background Given that immigration has been linked to a variety of mental health stressors, understanding use of mental health services by immigrant groups is particularly important. However, very little research on immigrants’ use of mental health service in the host country considers source country. Newcomers from different source countries may have distinct experiences that influence service need and use after arrival. This population study examined rates of use of primary care and of specialty services for non-psychotic mental health disorders by immigrants to Ontario Canada during their first five years after arrival. Service use by recent immigrants in broad source region groups representing all world regions was compared to use by age-matched Canadian-born or long term immigrants (called long term residents). Method This matched population-based cross-sectional study assessed likelihood of any use and counts of visits for each of primary care, psychiatric care and hospital care (emergency department visits or inpatient admissions) for non-psychotic mental health disorders from 1993–2012. Adult immigrants living in urban Ontario (n = 912,114) were categorized based on their nine world regions of origin. Sex-stratified conditional logistic regression models and negative binomial models were used to compare service use by immigrant region groups to their age-matched long term residents. Results Immigrant were more or less likely to access primary mental health care compared to age-matched long term residents, depending on their world region of origin. Regarding specialty mental health care (psychiatry and hospital care), immigrants from all regions used less than long term residents. Across the three mental health services, estimates of use by immigrant region groups compared to long term residents were among the lowest for newcomers from East Asian and Pacific (range: 0.16–0.82) and among the highest for persons from Middle East and North Africa (range: 0.56–1.23). Conclusion This population-based study showed lower use of mental health services by recent immigrants than long-term immigrants or native born individuals, with variation in immigrants’ use linked to world region of origin and type of mental health care. Variation across source region groups underscores the importance of identifying underlying individual characteristics that affect service use to make services more responsive to newcomers

In spite of the system: A qualitatively-driven mixed methods analysis of the mental health services experiences of LGBTQ people living in poverty in Ontario, Canada

Lesbian, gay, bisexual, trans, and/or queer (LGBTQ) people face barriers to accessing mental health care; however, we know little about service experiences of low income LGBTQ people. In this qualitatively-driven mixed methods study, over 700 women and/or trans people completed an internet survey, of whom 12 LGBTQ individuals living in poverty participated in interviews. Low income LGBTQ respondents saw more mental health professionals and had more unmet need for care than all other LGBTQ/income groups. Narrative analysis illustrated the work required to take care of oneself in the context of extreme financial constraints. These findings highlight the mechanisms through which inadequate public sector mental health services can serve to reproduce and sustain both poverty and health inequities.This project was funded by the Canadian Institutes for Health Research (http://www.cihrirsc.gc.ca/e/193.html), grant number MPO-105685 awarded to LER and LSS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Rural residence and risk for perinatal depression: a Canadian pilot study

Few studies have examined whether rural residence is associated with increased or decreased risk for postpartum depression (PPD). To address this research gap, this pilot study examined rates of depressive symptoms and perceived social support among women living in rural (population 12 similarly did not differ between groups. There were few statistically significant differences between groups on indicators of social connectedness; however, urban women reported significantly lower scores on measures of social network diversity and social capital than either the semi-rural or rural groups. This pilot study is limited by its small sample size; however, our data do not support the hypothesis that there are clinically important differences in risk for PPD associated with rural residence. Further studies examining potential relationships between indicators of social connectedness and perinatal mental health may be warranted