Access to colposcopy in the State of São Paulo, Brazil: probabilistic linkage study of administrative data

Cervical cancer screening is a multistage process, therefore access to both the primary test and subsequent diagnostic procedures is essential. Considering women undergoing screening on the public health system in the State of São Paulo, Brazil, we aimed to estimate the proportion of women accessing colposcopy within six months of an abnormal smear result. We retrieved records from two administrative databases, the Information System on Uterine Cervical Cancer (SISCOLO) that contains smear results and the Outpatient Information System of the Brazilian Unified National Health System (SIA/SUS) that records colposcopies. A reference cohort consisted of women, aged 25 years or older, with an abnormal smear result between May 1, 2014, and June 30, 2014. We excluded prevalent cases. We linked the reference cohort and records in the SIA/SUS extending to December 31, 2014. After excluding prevalent cases, 1,761 women with abnormal cytology results were left. A total of 700 (39.8%) women were linked to a colposcopy record within the follow-up period; this dropped to 671 (38.1%) women when follow-up was censored at six months. We could notice a slightly higher attendance in women living in the metropolitan region of São Paulo compared with residents of the rest of the state. We found no association between colposcopy attendance and age or cytology class. These results emphasize that access to colposcopy in the public health system in São Paulo is limited. This compromises the quality of screening, and the issue needs to be prioritized in service planning.

Birth cohort differences in height, weight and body mass index among Indian women aged 15-30 years: Analyses based on three cross-sectional surveys

Objective: To explore long-term trends in height, weight and body mass index (BMI) across birth cohorts among Indian women aged 15-30. Design: Nationally representative cross-sectional surveys. Setting: Data from three National Family Health Surveys conducted in 1998-99, 2005-06 and 2015-16. Height and weight were modeled jointly, employing a multivariate regression model with age and birth cohorts as explanatory variables. The largest birth cohort (born 1988-92) was the reference cohort. Stratified analyses by place of residence and by marital status and dichotomized parity were also performed. Participants: 437,753 non-pregnant women aged 15-30 years. Results: The rate of increase in height, weight and BMI differed across birth cohorts. The rate of increase was much lower for height than weight, which was reflected in an increasing trend in BMI across all birth cohorts. In the stratified analyses, increase in height was found to be similar across urban and rural areas. Rural women born in the latest birth cohort (1998-2001) were lighter, whereas urban women were heavier compared to the reference cohort. A relatively larger increase in regression coefficients were observed among women born between 1978-82 compared to women born between 1973-77 when considering unmarried and nulliparous ever-married women and, one cohort later (1983-87 vs. 1978-82), among parous ever-married women. Conclusion: As the rate of increase was much larger for weight than for height, increasing trends in BMI were observed across the birth cohorts. Thus, cohort effects show an important contributory role in explaining increasing trends in BMI among young Indian women.

Cancer Incidence and Risk of Multiple Cancers after Environmental Asbestos Exposure in Childhood—A Long-Term Register-Based Cohort Study

Objectives: To examine the asbestos-associated cancer incidence and the risk of multiple cancers in former school children exposed to environmental asbestos in childhood. Methods: A cohort of 12,111 former school children, born 1940–1970, was established using 7th grade school records from four schools located at a distance of 100–750 m in the prevailing wind direction from a large asbestos-cement plant that operated from 1928 to 1984 in Aalborg, Denmark. Using the unique Danish personal identification number, we linked information on employments, relatives’ employments, date of cancer diagnosis, and type of cancer and vital status to data on cohortees extracted from the Supplementary Pension Fund Register (employment history), the Danish Cancer Registry, and the Danish Civil Registration System. We calculated standardized incidence rates (SIRs) for asbestos-associated cancers, all cancers, and multiple cancers using rates for a gender and five-year frequency-matched reference cohort. Results: The overall incidence of cancer was modestly increased for the school cohort (SIR 1.07, 95% confidence interval (CI) 1.02–1.12) compared with the reference cohort. This excess was driven primarily by a significantly increased SIR for malignant mesothelioma (SIR 8.77, 95% CI 6.38–12.05). Former school children who had combined childhood environmental and subsequent occupational exposure to asbestos had a significantly increased risk of lung cancer. Within this group, those with additional household exposure by a relative had a significantly increased SIR for cancer of the pharynx (SIR 4.24, 95% CI 1.59–11.29). We found no significant difference in the number of subjects diagnosed with multiple cancers between the two cohorts. Conclusions: Our study confirms the strong association between environmental asbestos exposure and malignant mesothelioma and suggests that environmental asbestos exposure in childhood may increase the overall cancer risk later in life.

Obstructive Sleep Apnea and Risk of Suicide and Self-Harm: A Danish Nationwide Cohort Study

Study Objectives In this nationwide study, we used the unique Danish registries to estimate the risk of suicide and deliberate self-harm in patients with obstructive sleep apnea (OSA). Methods We identified all Danish citizens receiving a diagnosis of OSA between 1995 and 2015. As a reference cohort, we randomly selected 10 citizens for each patient, matched by sex and birth year. Using the Fine and Gray competing risk regression, we estimated the cumulative incidences of suicide, and Cox proportional regression analysis was used to compare the risk of suicide and deliberate self-harm in patients with OSA with the reference cohort. Results We identified 48,168 patients with OSA. A total of 135 patients had died by suicide, compared with 999 suicides in the reference cohort. Patients with OSA had an increased risk of dying by suicide when compared with the reference cohort (hazard ratio, 1.29; 95%CI, 1.07–1.55; and subhazard ratio, 1.23; 95%CI, 1.10-1.45). We identified 1,004 events of self-harm among patients with OSA, and 5,270 events in the reference group. The overall risk of self-harm was increased in patients with OSA when compared with the reference group (hazard ratio, 1.28; 95%CI, 1.19–1.37). Conclusion This is the first study to estimate the risk of suicide and deliberate self-harm in patients with OSA. We found that patients with OSA have an increased risk of both suicide and deliberate self-harm when compared with a large reference cohort, thereby highlighting the importance of a mental health screening in these patients.

Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study

Background and ObjectivesBody mass index (BMI) and height are important indices of health. We tested the association between these outcomes and clinical characteristics in Friedreich ataxia (FRDA), a progressive neuromuscular disorder.MethodsParticipants (N = 961) were enrolled in a prospective natural history study (Friedreich Ataxia Clinical Outcome Measure Study). Age- and sex-specific BMI and height Z-scores were calculated using CDC 2000 references for participants younger than 18 years. For adults aged 18 years or older, height Z-scores were also calculated, and absolute BMI was reported. Univariate and multivariate linear regression analyses tested the associations between exposures, covariates, and BMI or height measured at the baseline visit. In children, the superimposition by translation and rotation analysis method was used to compare linear growth trajectories between FRDA and a healthy reference cohort, the Bone Mineral Density in Childhood Study (n = 1,535 used for analysis).ResultsMedian age at the baseline was 20 years (IQR, 13–33 years); 49% (n = 475) were women. A substantial proportion of children (17%) were underweight (BMI-Z < fifth percentile), and female sex was associated with lower BMI-Z (β = −0.34, p < 0.05). In adults, older age was associated with higher BMI (β = 0.09, p < 0.05). Regarding height, in children, older age (β −0.06, p < 0.05) and worse modified Friedreich Ataxia Rating Scale (mFARS) scores (β = −1.05 for fourth quartile vs first quartile, p < 0.01) were associated with shorter stature. In girls, the magnitude of the pubertal growth spurt was less, and in boys, the pubertal growth spurt occurred later (p < 0.001 for both) than in a healthy reference cohort. In adults, in unadjusted analyses, both earlier age of FRDA symptom onset (=0.09, p < 0.05) and longer guanine-adenine-adenine repeat length (shorter of the 2 GAA repeats, β = −0.12, p < 0.01) were associated with shorter stature. Both adults and children with higher mFARS scores and/or who were nonambulatory were less likely to have height and weight measurements recorded at clinical visits.DiscussionFRDA affects both weight gain and linear growth. These insights will inform assessments of affected individuals in both research and clinical settings.

Comparison of three cohorts of COVID-19 patients with different severity: exposure to antihypertensive, antidiabetic and lipid-lowering agents

Aim: The association between COVID-19 disease severity and certain medicines for the treatment of chronic diseases is currently under discussion. We herein evaluated if previous exposure to antihypertensive, hypoglycaemic, and lipid-lowering drugs increases the risk of poorer COVID-19 outcomes. Methods: We performed a retrospective study on three cohorts of COVID-19 adult patients between March 2020 and May 2020 at the Vall d’Hebron University Hospital. Information relating to the patient lifestyle, comorbidities, and chronic exposures was retrieved from primary healthcare electronic records. Three cohorts were examined, namely patients who had died or required intensive care treatment (ICU/Death [ICU-D] Cohort), patients who required hospitalisation (Hospitalisation [HOSP] Cohort), and patients who only attended the emergency department (Emergencies [EM] Cohort). Descriptive statistics and a multivariate logistic regression model were used to investigate associations with drug exposure, where EM was employed as the reference cohort. Results: We included 1,778 patients: 417 (23.5%) from the ICU-D Cohort, 1,052 (59.2%) from the HOSP Cohort, and 309 (17.4%) from the EM Cohort. After multiple imputations and data adjustment by potential confounders, no statistically significant association was observed between the COVID-19 severity and the use of antihypertensives, hypoglycaemic agents, or lipid-lowering agents, with the exception of calcium channel blockers (CCB) (ICU-D Cohort: OR 2.23; CI 95% [1.03–4.83]; P = 0.042). Conclusions: Most results on lifestyle characteristics and comorbidities related to COVID-19 severity were in agreement with current knowledge, although some associated factors are nowadays a matter of controversy and further investigation is required.

Assessing the physical healthcare gap among patients with severe mental illness: large real-world investigation from Italy

Background One critical barrier to the uptake of mental health programmes is the so-called physical healthcare gap, a concern raised by the unattended physical comorbidity and early mortality of persons with severe mental illness. Aims To evaluate the extension of physical healthcare gap among persons with severe mental illness under chronic drug therapies. Method A population-based cohort study was carried out, using Lombardy healthcare utilisation databases. Prevalent patients treated with blood pressure-, lipid- or glucose-lowering agents were identified in January 2017. Among these, those who were receiving care for depression, schizophrenia, bipolar disorder or personality disorder formed the study cohort. A reference cohort was randomly selected from prevalent patients treated with chronic therapies without signs of severe mental disorders, to be matched with study cohort members for gender, age and number of previous contacts with the National Health System. One-year adherence to healthcare was measured through the proportion of days covered (drug adherence), and exposure to selected recommendations (clinical control adherence). Results The 55 162 patients with severe mental illness were less likely to have high adherence to blood pressure-lowering, lipid-lowering or antidiabetic agents than the reference cohort by −24% (95% CI −26 to −22%), −10% (95% CI −14 to −6%) and −25% (95% CI −29 to −21%), respectively. The 9250 patients with diabetes and severe mental illness had −18% (95% CI −22% to −13%) reduced likelihood to meet recommendations for the clinical management of diabetes, compared with the reference cohort. Conclusions Adherence to chronic drug therapies was sensibly worse among patients living with mental illness than those without signs of mental disorders.

OS11.5.A PATZ1 fusions define a novel molecularly distinct CNS tumor entity with a broad histological spectrum

BACKGROUND DNA methylation profiling has emerged as a useful tool for robust classification of rare CNS tumors with a broad morphological spectrum. Routine diagnostic molecular profiling performed in Heidelberg and at international collaborating centers revealed a small but recurring number of CNS tumors with fusions of the PATZ1 gene coupled to either MN1 or EWSR1, displaying a distinct genome-wide methylation profile; indicating that these tumors could form a seperate biological entity. MATERIAL AND METHODS We obtained genome-wide DNA-methylation array profiling of 68 primary CNS tumors. RNA-sequencing was perfomed on (n=23/68, 34%) of the tumor samples, including (n=6) from fresh frozen tissue used for gene expression profiling. For n=3 cases, whole exome sequencing (WES) data was generated, and gene panel sequencing data was available for n=13 cases, We systematically reevaluated the histopahthological features of 14 tumors, while immunohistochemical (IHC) staining with Ki-67, GFAP, MAP2, NeuN, Olig-2, Synaptophysin, S-100 and Vimentin was performed for (n=12) tumors. We finally collected clinical data to preliminarily characterize this novel tumor entity. RESULTS A selected analysis of the tumors in this novel cohort (n=68), compared with a reference cohort consisting of 15 other low- and high-grade glial and glioneuronal tumor classes, confirmed a clearly distinct grouping. No similarity was seen with the MN1:BEND2 and MN1:CXXC5-fused CNS-tumors. Analysis of Copy number profiles derived from the DNA-methylation data showed a mostly quite genome, with (n=64/65, 98%) of tumors showing copy number variations on Chromosome 22. RNA-sequencing detected PATZ1 fusions in all tumors sequenced (n=12; MN1:PATZ1, n=11; EWSR1:PATZ1). IGF2, PAX2 and GATA2, all genes involved in brain stem cell biology, were upregulated compared to a combined reference cohort of other glioma subtypes. DNA-sequencing showed no relevant alterations at the level of point mutations or small insertions/deletions. The tumors in our cohort showed polyphenotypic histologies along the glial spectrum, with a subset of tumors being diagnosed as Gliobastoma, WHO Grade 4 and bi- and multiphasic differentaion patterns being evident. IHC performed on tissue available did not favor a particular lineage, with most tumors showing immunopositivity to GFAP. Reverse translation of the gene expression data showed a potential role for NG2 as immunostaining marker. The median age was 11.0 years (0–80), (MN1:PATZ1 manifested at a younger age (median = 4 years) vs EWSR1:PATZ1 (median = 14 years)). Median PFS was 12 months. CONCLUSION We describe here a novel, molecularly distinct CNS tumor class with strikingly variable histopathologic morphology. We postulate that the PATZ1 fusions are a key driver of tumor initiation. Preliminary indications suggest an intermediate prognosis.

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function

Objectives: Longitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood. Methods: This retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated. Results: Pubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14–16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT. Conclusion: Our results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.