Excess Hazard Research Articles

Measurement of Radionuclides and their Impact on the Environment Around Asphalt Plants in Delta State

Measurement of radionuclides and their impact on the environment around asphalt plants in some selected Asphalt mixing plant within Delta State, Nigeria was carried out. The Background Ionizing Radiation and the GPS of the location was measured using a well calibrated Gamma scout; Geiger counter multi-radiation meter and a GARMIN GPS meter and the result obtained at Raycon, DLA and Neodede Hot Asphalt Mixing Plants for outdoor exposure, shows a total mean value of (0.01492±0.038) (mRh-1), (0.01497±0.037) (mRh-1) and (0.01413±0.014) (mRh-1) respectively. The total mean values obtained in the selected radiological centers were all above the world average BIR level of 0.013 (mR?-1) as recommended by UNSCEAR (2000). These results were used to calculate some hazard indices such as the Equivalent dose (ED) in mSv??1, the absorbed dose rate (ADR) in nGy??1, Annual Effective Dose Equivalent (AEDE) and Excess Life Cancer Risk (ELCR). All the values obtained for each Parameter were above the world permissible limits as given by UNSCEAR (2000). The average activity concentration of 40K, 238U and 232Th in the soil of the three study areas were (603.21±30.94) Bq/Kg, (5.70 ±0.678) Bq/Kg and (6.91 ± 0.405) Bq/Kg. For 40K the average activity concentration was high and above the world recommended limit of 420 Bq/Kg (UNSCEAR 2000). 238U and 232Th were below the world recommended limits which are 33 Bq/Kg and 45 Bq/Kg. respectively. The Activity Concentration results were used to calculate the following radiological parameters: Absorbed gamma dose rate (DR) in (nGy/h), Annual Effective Dose Equivalent AEDE in (?Svy-1), the Radium Equivalent (Raeq), Excess Life Cancer Risk (ELCR) and External Hazard Index. All the calculated radiological Values were above the recommended limit given by (UNSCEAR 2000). Water samples in the study areas was also collected and the average activi

Comparison of 2 Methods for Estimating Multiple Sclerosis-Related Mortality.

Determining whether multiple sclerosis (MS) causes death is challenging. Our objective was to contrast 2 frameworks to estimate probabilities of death attributed to MS (PMS) and other causes (Pother): the cause-specific framework (CSF), which requires the causes of death, and the excess mortality framework (EMF), which does not. We used data from the Observatoire Français de la Sclérose en Plaques (OFSEP, n = 37,524) and from a comparative subset where causes of death were available (4,004 women with relapsing-onset MS [R-MS]). In CSF, the probabilities were estimated using the Aalen-Johansen method. In EMF, they were estimated from the excess mortality hazard, which is the additional mortality among patients with MS as compared with the expected mortality in the matched general population. PMS values were estimated at 30 years of follow-up, (1) with both frameworks in the comparative subset, by age group at onset, and (2) with EMF only in the OFSEP population, by initial phenotype, sex, and age at onset. In the comparative subset, the estimated 30-year PMS values were greater using EMF than CSF: 10.9% (95% CI 8.3-13.6) vs 8.7% (6.4-11.8) among the youngest and 20.4% (11.3-29.5) vs 16.2% (8.7-30.2) for the oldest groups, respectively. In the CSF, probabilities of death from unknown causes ranged from 1.5% (0.7-3.0) to 6.4% (2.5-16.4), and even after their reallocation, PMS values remained lower with CSF than with EMF. The estimated probabilities of being alive were close using the 2 frameworks, and the estimated POther (EMF vs CSF) was 2.6% (2.5-2.6) vs 2.1% (1.2-3.9) and 18.1% (16.9-19.3) vs 26.4% (16.5-42.2), respectively, for the youngest and oldest groups. In the OFSEP population, the estimated 30-year PMS values ranged from 7.5% (6.4-8.7) to 24.0% (19.1-28.9) in patients with R-MS and from 25.4% (21.1-29.7) to 36.8% (28.3-45.3) in primary progressive patients, depending on sex and age. EMF has the great advantage of not requiring death certificates, their quality being less than optimal. Conceptually, it also seems more relevant because it avoids having to state, for each individual, whether death was directly or indirectly caused by MS or whether it would have occurred anyway, which is especially difficult in such chronic diseases.

Improved Long-Term Net Survival after Allogeneic Hematopoietic Cell Transplantation in Patients with Hematologic Malignancies over Two Decades

Allogeneic (allo-) hematopoietic cell transplantation (HCT) has evolved as a curative therapy for hematologic malignancies and diseases, with practice changes over the past 2 decades. This study aimed to evaluate the change in 5-year net survival (NS) of allo-HCT recipients in a population-based cohort over the past 2 decades, which allows the estimation of a more HCT-specific long-term survival rate by considering background mortality changes. This study included 42,064 patients with hematologic malignancies who underwent their first allo-HCT in Japan between 2000 and 2018 and were reported to the Transplant Registry Unified Management Program. We compared the 5-year NS after allo-HCT in 4 consecutive HCT periods (2000 to 2004, 2005 to 2008, 2009 to 2012, and 2013 to 2018). The 5-year NS of the latest period was estimated using the period analysis method. Adjusted excess hazard ratios (EHRs) for 5-year NS over the HCT period were analyzed using an EHR model. In addition to the analysis of all hematologic malignancies, adjusted 5-year NS for each major hematologic malignancy, including acute myelogenous leukemia, acute lymphoblastic leukemia (ALL), myelodysplastic syndrome, adult T cell leukemia/lymphoma, chronic myeloid leukemia (CML), and malignant lymphoma, was analyzed. The probability of adjusted 5-year NS after HCT improved significantly over time: 35% in 2000 to 2004, 39% in 2005 to 2008, 45% in 2009 to 2012, and 49% in 2013 to 2018. The adjusted EHRs were .90 (95% confidence interval [CI], .86 to .93) in the 2005 to 2008 period, .77 (95% CI, .74 to .80) in the 2009 to 2012 period, and .65 (95% CI, .63 to .68) in the 2013 to 2018 period, with the 2000 to 2004 period as the reference. The 5-year NS improved among all hematologic malignancies, with a significant improvement in CML and ALL. The changes in 5-year NS from the 2000 to 2004 period to the 2013 to 2018 period ranged from 46% to 66% in CML and from 41% to 59% in ALL. In addition to the large improvement of 1-year NS, smaller but continued improvement in NS between 1 and 5 years after transplantation was observed. NS at 5 years conditional on being alive at 1 year increased from 64% in 2000 to 2004 to 73% in 2013 to 2018. Even after subtracting the background mortality in the general population, we found a significant improvement in long-term allo-HCT-specific survival rates for patients with hematologic malignancies over the past 2 decades in Japan.

Socioeconomic status and cancer survival in Brazil: Analysis of population data from the municipalities of Aracaju and Curitiba, 1996–2012

IntroductionThe association between socioeconomic status and cancer prognosis has been demonstrated in several countries. Despite the existence of indirect evidence of this phenomenon in Brazil, few studies in this regard are available. ObjectivesThe objective of the present study is to analyse socioeconomic related survival gaps for patients diagnosed with breast, cervical, lung, prostate, and colorectal cancer in the cities of Aracaju (SE) and Curitiba (PR). MethodsUsing population-based data, we estimated net survival by tumour site, year of diagnosis, socioeconomic status and local of residence. Net survival estimation was done with multilevel parametric model allowing flexible spline functions do estimate excess mortality hazards. Results28,005 cases were included in survival analysis. Five-year net survival showed positive association with SES. Intermunicipal survival gaps favouring Aracaju where prominent for breast (reaching 16,1% in 5 years) ObjectivesStudy the impact of socioeconomic factors on cancer survival in two Brazilian capitals. Methods: Survival analysis using population-based cancer data including patients diagnosed with breast, lung, prostate, cervical and colorectal cancer between 1996 and 2012 in Aracaju and Curitiba. Outcomes were excessive mortality hazard (EMH) and 5- and 8-years net survival (NS). The association of race/skin color and socioeconomic level (SES) with EMH and net survival were analyzed using a multilevel regression model with flexible splines. Results28,005 cases were included, 6636 from Aracaju and 21,369 from Curitiba. NS for all diseases studied increased more prominently for Curitiba population. We observed NS gap between the populations of Aracaju and Curitiba that increased or remained stable during the study period, with emphasis on the growth of the difference in NS of lung and colon cancer (among men). Only for cervical cancer and prostate cancer there was a reduction in the intermunicipal gaps. 5-year NS for breast cancer in Aracaju ranged from 55.2% to 73.4% according to SES. In Curitiba this variation was from 66.5% to 83.8%. ConclusionThe results of the present study suggests widening of socioeconomic and regional inequalities in the survival of patients with colorectal, breast, cervical, lung and prostate cancers in Brazil during the 1990 s and 2000 s

Hospital surgical volume and colorectal cancer survival in Norway: A nationwide cohort study

BackgroundStudies of hospital surgical volume and colorectal cancer survival are inconclusive. We investigated whether surgical volume was associated with survival of patients operated for colorectal cancer in Norway. MethodsUsing Cancer Registry of Norway data, we compared excess mortality from colorectal cancer by hospital surgical volume among 26,989 colon and 9779 rectal cancer patients diagnosed 2009–2020 and followed-up to 31.12.2021. Hospitals were divided into terciles according to their three-year average annual surgical volume; colon: low (< 22), middle (22–73), high (> 73); rectal: low (< 17), middle (17–38), high (> 38). We estimated excess hazard ratios (EHR) with flexible parametric models adjusted for age, year, stage, surgical urgency and surgery location (within/outside patient’s residential health trust). ResultsLow-volume hospitals had the highest proportion of late-stage or acutely operated colon cancer patients. Colon cancer patients operated at low- versus high-volume hospitals had significantly increased crude excess mortality (EHR = 1.30; 95 % CI = 1.14–1.48) but no difference after adjustment for age, year, and stage (EHR = 0.97; 0.85–1.11). High-volume hospitals had the highest proportion of late-stage rectal cancer patients and patients operated outside their residential area. Rectal cancer patients operated at low- versus high-volume hospitals did not have significantly different excess mortality before (EHR = 0.84; 0.64–1.10) or after (EHR = 1.03; 0.79–1.35) adjustment for age, year, stage, surgical urgency and surgery location. After accounting for case-mix, hospital surgical volume was not associated with excess mortality from colon (P = 0.40) or rectal cancer (P = 0.22). ConclusionLow hospital surgical volume was not associated with poorer colorectal cancer survival.

Impact of cancer and other causes of death on mortality of cancer patients: A study based on Japanese population-based registry data.

Cancer registry data provide a very important source of information for improving our understanding of the epidemiology of various cancers. In this work, we estimated the 5-year crude probabilities of death from cancer and from other causes for five common cancers, namely stomach, lung, colon-rectum, prostate and breast, in Japan, using population-based registry data. Based on data on 344 676 patients diagnosed with one of these cancers between 2006 and 2008 in 21 prefectures participating in the Monitoring of Cancer Incidence in Japan (MCIJ) and followed-up for at least 5 years, we used a flexible excess hazard model to compute the crude probabilities of death for different combinations of sex, age and stage at diagnosis. For tumours diagnosed at the distant stage, as well as for regional lung tumours, the vast majority of deaths at 5 years in cancer patients were attributable to the disease itself (although this proportion was only around 60% in older prostate cancer patients). For localised and most regional tumours, the impact of other causes of death on the total mortality increased with age at diagnosis, especially for localised breast, colorectal and gastric cancer. By allowing the partition of the mortality experience of cancer patients into a cancer- and an other-cause-specific component, crude probability of death estimates provide insight into how the impact of cancer on mortality might differ among populations with different background mortality risks. This might be useful for informing discussions between clinicians and patients about treatment options.

Characterization of ovarian cancer survival by histotype and stage: A nationwide study in Norway.

Contemporary population-based data on ovarian cancer survival using current subtype classifications and by surgical status are sparse. We evaluated 1-, 3-, 5- and 7-year relative (and overall) survival, and excess hazards in patients with borderline tumors or invasive epithelial ovarian cancer diagnosed 2012 to 2021 in a nationwide registry-based cohort in Norway. Outcomes were evaluated by histotype, FIGO stage, cytoreduction surgery and residual disease. Overall survival was evaluated for non-epithelial ovarian cancer. Survival of women with borderline ovarian tumors was excellent (≥98.0% 7-year relative survival). Across all evaluated invasive epithelial ovarian cancer histotypes, 7-year relative survival for cases diagnosed with stages I or II disease was ≥78.3% (stage II high-grade serous). Survival for ovarian cancers diagnosed at stage ≥III differed substantially by histotype and time since diagnosis (eg, stage III, 5-year relative survival from 27.7% [carcinosarcomas] to 76.2% [endometrioid]). Overall survival for non-epithelial cases was good (91.8% 5-year overall survival). Women diagnosed with stage III or IV invasive epithelial ovarian cancer and with residual disease following cytoreduction surgery had substantially better survival than women not operated. These findings were robust to restriction to women with high reported functional status scores. Patterns for overall survival were similar to those for relative survival. We observed relatively good survival with early stage at diagnosis even for the high grade serous histotype. Survival for patients diagnosed at stage ≥III invasive epithelial ovarian cancer was poor for all but endometrioid disease. There remains an urgent need for strategies for risk reduction and earlier detection, together with effective targeted treatments.

Regional disparities in cancer survival in Iran: Insight from a National Surveillance of Cancer Survival in Iran (IRANCANSURV)

Background and objectivesWe aimed to investigate geographical disparity in cancer survival in 9 provincial population-based cancer registries in Iran from 2015 to 2016. Material and methodIn the current study, data from 90,862 adult patients (aged >15 years) diagnosed with cancer were retrieved from 9 population-based cancer registries across Iran. Five-year survival rates were estimated by applying relative survival approaches. We also applied the international cancer survival standard weights for age standardization. Finally, we calculated the excess hazard ratio (EHR) for each province adjusted for age, sex, and cancer sites to estimate the excess hazard ratio of mortality compared to the capital province (Tehran). ResultsThe largest gap in survival was observed in more curable cancer types, including melanoma (41.4%), ovary (32.3%), cervix (35.0%), prostate (26.7%), and rectum (21.4%), while the observed geographical disparity in lethal cancers such as lung, brain, stomach, and pancreas was less than 15%. Compared to Tehran, we found the highest excess hazard of death in Western Azerbaijan (EHR=1.60, 95% CI 1.51, 1.65), Kermanshah (EHR=1.52, 95% CI=1.44, 1.61), and Kerman (EHR=1.46, 95% CI=1.38, 1.53). The hazard ratio of death was almost identical in Isfahan (EHR=1.04, 95% CI=1.03, 1.06) and Tehran provinces. ConclusionProvinces with higher HDI had better survival rates. IRANCANSURV study showed regional disparities in cancer survival in Iran. Cancer patients in provinces with a higher Human Development Index (HDI) had a higher survival rate and lived longer compared to the patients in provinces with medium and low HDI regions.

Survival differences between the USA and an urban population from China for all cancer types and 20 individual cancers: a population-based study

The systematic comparison of cancer survival between China and the USA is rare. Here we aimed to assess the magnitude of survival disparities and disentangle the impact of the stage at diagnosis between a Chinese metropolitan city and the USA on cancer survival. We included 11,046 newly diagnosed cancer patients in Dalian Cancer Registry, China, 2015, with the follow-up data for vital status until December 2020. We estimated age-standardised 5-year relative survival and quantified the excess hazard ratio (EHR) of death using generalised linear models for all cancers and 20 individual cancers. We compared these estimates with 17 cancer registries' data from the USA, using the Surveillance, Epidemiology, and End Results database. We further estimated the stage-specific survival for five major cancers by region. Age-standardised 5-year relative survival for all patients in Dalian was lower than that in the USA (49.9% vs 67.9%). By cancer types, twelve cancers with poorer prognosis were observed in Dalian compared to the USA, with the largest gap seen in prostate cancer (Dalian: 55.8% vs USA: 96.0%). However, Dalian had a better survival for lung cancer, cervical cancer, and bladder cancer. Dalian patients had a lower percentage of stage Ⅰ colorectal cancer (Dalian: 17.9% vs USA: 24.2%) and female breast cancer (Dalian: 40.9% vs USA: 48.9%). However, we observed better stage-specific survival among stage Ⅰ-Ⅱ lung cancer patients in Dalian than in the USA. This study suggests that although the overall prognosis for patients was better in the USA than in Dalian, China, survival deficits existed in both countries. Improvement in cancer early detection and cancer care are needed in both countries. National Key R&D Program (2021YFC2501900, 2022YFC3600805), Major State Basic Innovation Program of the Chinese Academy of Medical Sciences (2021-I2M-1-010, 2021-I2M-1-046), and Talent Incentive Program of Cancer Hospital of Chinese Academy of Medical Sciences.

Dietary intake and cardiovascular outcomes in patients with chronic vascular disease: insights from the COMPASS trial cohort.

Patients with coronary artery disease (CAD) and patients with peripheral artery disease (PAD) are at risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There are limited data regarding dietary patterns and the risk of recurrent MACE and MALE in CAD and PAD patients. We aimed to identify dietary patterns associated with MACE and MALE in patients with CAD and/or PAD. We analysed data collected from patients enrolled into the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, in which diet was assessed by a short food frequency questionnaire (FFQ) at baseline. Two dietary pattern scores, the modified Alternate Healthy Eating Index (mAHEI) and Mediterranean Diet Score (mMDS), were calculated. We tested the association between mAHEI and mMDS and the incidence of MACE and/or MALE. The mean mAHEI score was 23.0 ± 7.7 (out of 70) overall and was similar comparing CAD and PAD patients. The incidence of MACE or MALE was 6.3% in the lowest diet quality quartile (as assessed by mAHEI) compared with 4.2% in the highest quartile over 30 months. In the fully adjusted model, the hazard ratio of a low diet quality (Quartile 1) compared with the highest (Quartile 4) for MACE or MALE was 1.27 (95% CI: 1.08-1.49; P = 0.004, Q1 vs. Q4). This excess hazard was primarily driven by higher MACE in both the CAD and PAD cohorts. Poor diet quality as assessed by the mAHEI is independently associated with a higher risk of recurrent MACE and MALE in patients with chronic CAD and/or PAD.

Asymptotic justification of maximum likelihood estimation for the proportional excess hazard model in analysis of cancer registry data

Asymptotic justification of maximum likelihood estimation for the proportional excess hazard model in analysis of cancer registry data

Cancer Survival and Travel Time to Nearest Reference Care Center for 10 Cancer Sites: An Analysis of 21 French Cancer Registries

The impact of several non-clinical factors on cancer survival is poorly understood. The aim of this study was to investigate the influence of travel time to the nearest referral center on survival of patients with cancer. The study used data from the French Network of Cancer Registries that combines all the French population-based cancer registries. For this study, we included the 10 most common solid invasive cancer sites in France between 1 January 2013 and 31 December 2015, representing 160,634 cases. Net survival was measured and estimated using flexible parametric survival models. Flexible excess mortality modelling was performed to investigate the association between travel time to the nearest referral center and patient survival. To allow the most flexible effects, restricted cubic splines were used to investigate the influence of travel times to the nearest cancer center on excess hazard ratio. Among the 1-year and 5-year net survival results, lower survival was observed for patients residing farthest from the referral center for half of the included cancer types. The remoteness gap in survival was estimated to be up to 10% at 5 years for skin melanoma in men and 7% for lung cancer in women. The pattern of the effect of travel time was highly different according to tumor type, being either linear, reverse U-shape, non-significant, or better for more remote patients. For some sites restricted cubic splines of the effect of travel time on excess mortality were observed with a higher excess risk ratio as travel time increased. For numerous cancer sites, our results reveal geographical inequalities, with remote patients experiencing a worse prognosis, aside from the notable exception of prostate cancer. Future studies should evaluate the remoteness gap in more detail with more explanatory factors.

Long-term excess mortality and net survival among elderly diffuse large B-cell lymphoma patients after front-line R-CHOP treatment.

In the era of immunochemotherapy, data on the long-term prognosis of elderly patients diagnosed with a diffuse large B-cell lymphoma (DLBCL) are scarce. In this population and on the longer term, other-cause mortality is an important competing risk that needs to be accounted for. Using clinical trial data and relative survival approaches, we estimated the 10-year net survival (NS) and we described the excess mortality hazard (EMH) due (directly or indirectly) to the DLBCL, over time and according to main prognosis factors using flexible regression modelling. The 10-year NS was 65% [59; 71]. Using the flexible modelling, we showed that the EMH decreases steeply after diagnosis. The variables 'performance status', 'number of extra-nodal sites' and the serum 'lactate dehydrogenase' were strongly associated with the EMH, even after adjustment on other important variables. EMH is very close to zero at 10 years for the whole population, so DLBCL patients do not experience an increased mortality compared to the general population in the long term. The number of extra-nodal sites was an important prognostic factor shortly after diagnosis, suggesting that it is correlated with an important but unmeasured prognostic factor that would lead to this selection effect over time.

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

BackgroundComparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer. MethodsWe analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases. ResultsFrom multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH1Gy) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH1Gy = 0.038 (95 % CI: −0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001. ConclusionThere is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors. ImpactA direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.

Expected life years compared to the general population.

For cohorts with long-term follow-up, the number of years lost due to a certain disease yields a measure with a simple and appealing interpretation. Recently, an overview of the methodology used for this goal has been published, and two measures have been proposed. In this work, we consider a third option that may be useful in settings in which the other two areinappropriate. In all three measures, the survival of the given dataset is compared to the expected survival in the general population which is calculated using external mortality tables. We thoroughly analyze the differences between the three measures, their assumptions, interpretation, and the corresponding estimators. The first measure is defined in a competing risk setting and assumes an excess hazard compared to the population, while the other two measures also allow estimation for groups that live better than the general population. In this case, the observed survival of the patients is compared to that in the population. The starting point of this comparison depends on whether the entry into the study is a hazard changing event (e.g.,disease diagnosis or the age at which the inclusion criteria were met). Focusing on the newly defined life years difference measure, we study the estimation of the variance and consider the possible challenges (e.g.,extrapolation) that occur in practice. We illustrate its use with a dataset of French Olympic athletes. Finally, an efficient R implementation has been developed for all three measures which make this work easily available to subsequentusers.

Trends in incidence of invasive vaginal cancer in France from 1990 to 2018 and survival of recently diagnosed women – A population-based study

ObjectiveThe aim of this study was to analyze trends in the incidence of vaginal cancer in France over a 28-year period and to present survival for recently-diagnosed women. MethodsFrench cancer registries provided data on invasive vaginal cancers diagnosed from 1990 to 2015 and followed up through June 2018. Trends in incidence were analyzed using a Poisson model with a bidimensional penalized spline of age and year at diagnosis. Net survival analysis was restricted to recently-diagnosed cases (2010–2015) and used a novel approach based on a bidimensional penalized spline of age and time-since-diagnosis to model excess mortality hazard. ResultsWith 162 new cases estimated in France in 2018, vaginal cancer represented 0.9 % of genital cancers in French women. In 2018, the world population age-standardized incidence rate was 0.2 per 100,000 person-years, median age at diagnosis was 75 years. The standardized incidence rate decreased significantly by 3 % per year (95 % CI, −3.8; −2.2) between 1990 and 2018 (0.4 cases per 100,000 person-year in 1990, vs 0.2 in 2018). Age-standardized net survival at 1 and 5 years after diagnosis was respectively 74 % and 45 %. ConclusionsThis study confirms that vaginal cancer is still a rare malignancy in France with 5-year net survival that remains low. We observed a consistent decrease in the incidence rate between 1990 and 2018. It may be too early to attribute these trends to a positive impact of vaccination campaigns against hrHPV infection, since vaginal cancer mainly affects older women and HPV vaccination has only been available since the early 2000s, and only targets young girls.

Association of Recent SARS-CoV-2 Infection With New-Onset Alcohol Use Disorder, January 2020 Through January 2022

The COVID-19 pandemic affects many diseases, including alcohol use disorders (AUDs). As the pandemic evolves, understanding the association of a new diagnosis of AUD with COVID-19 over time is required to mitigate negative consequences. To examine the association of COVID-19 infection with new diagnosis of AUD over time from January 2020 through January 2022. In this retrospective cohort study of electronic health records of US patients 12 years of age or older, new diagnoses of AUD were compared between patients with COVID-19 and patients with other respiratory infections who had never had COVID-19 by 3-month intervals from January 20, 2020, through January 27, 2022. SARS-CoV-2 infection or non-SARS-CoV-2 respiratory infection. New diagnoses of AUD were compared in COVID-19 and propensity score-matched control cohorts by hazard ratios (HRs) and 95% CIs from either 14 days to 3 months or 3 to 6 months after the index event. This study comprised 1 201 082 patients with COVID-19 (56.9% female patients; 65.7% White; mean [SD] age at index, 46.2 [18.9] years) and 1 620 100 patients with other respiratory infections who had never had COVID-19 (60.4% female patients; 71.1% White; mean [SD] age at index, 44.5 [20.6] years). There was a significantly increased risk of a new diagnosis of AUD in the 3 months after COVID-19 was contracted during the first 3 months of the pandemic (block 1) compared with control cohorts (HR, 2.53 [95% CI, 1.82-3.51]), but the risk decreased to nonsignificance in the next 3 time blocks (April 2020 to January 2021). The risk for AUD diagnosis increased after infection in January to April 2021 (HR, 1.30 [95% CI, 1.08-1.56]) and April to July 2021 (HR, 1.80 [95% CI, 1.47-2.21]). The result became nonsignificant again in blocks 7 and 8 (COVID-19 diagnosis between July 2021 and January 2022). A similar temporal pattern was seen for new diagnosis of AUD 3 to 6 months after infection with COVID-19 vs control index events. Elevated risk for AUD after COVID-19 infection compared with non-COVID-19 respiratory infections during some time frames may suggest an association of SARS-CoV-2 infection with the pandemic-associated increase in AUD. However, the lack of excess hazard in most time blocks makes it likely that the circumstances surrounding the pandemic and the fear and anxiety they created also were important factors associated with new diagnoses of AUD.

Individual frailty excess hazard models in cancer epidemiology.

Unobserved individual heterogeneity is a common challenge in population cancer survival studies. This heterogeneity is usually associated with the combination of model misspecification and the failure to record truly relevant variables. We investigate the effects of unobserved individual heterogeneity in the context of excess hazard models, one of the main tools in cancer epidemiology. We propose an individual excess hazard frailty model to account for individual heterogeneity. This represents an extension of frailty modeling to the relative survival framework. In order to facilitate the inference on the parameters of the proposed model, we select frailty distributions which produce closed-form expressions of the marginal hazard and survival functions. The resulting model allows for an intuitive interpretation, in which the frailties induce a selection of the healthier individuals among survivors. We model the excess hazard using a flexible parametric model with a general hazard structure which facilitates the inclusion of time-dependent effects. We illustrate the performance of the proposed methodology through a simulation study. We present a real-data example using data from lung cancer patients diagnosed in England, and discuss the impact of not accounting for unobserved heterogeneity on the estimation of net survival. The methodology is implemented in the R package IFNS.

Is the Social Gradient in Net Survival Observed in France the Result of Inequalities in Cancer-Specific Mortality or Inequalities in General Mortality?

In cancer net survival analyses, if life tables (LT) are not stratified based on socio-demographic characteristics, then the social gradient in mortality in the general population is ignored. Consequently, the social gradient estimated on cancer-related excess mortality might be inaccurate. We aimed to evaluate whether the social gradient in cancer net survival observed in France could be attributable to inaccurate LT. Deprivation-specific LT were simulated, applying the social gradient in the background mortality due to external sources to the original French LT. Cancer registries' data from a previous French study were re-analyzed using the simulated LT. Deprivation was assessed according to the European Deprivation Index (EDI). Net survival was estimated by the Pohar-Perme method and flexible excess mortality hazard models by using multidimensional penalized splines. A reduction in net survival among patients living in the most-deprived areas was attenuated with simulated LT, but trends in the social gradient remained, except for prostate cancer, for which the social gradient reversed. Flexible modelling additionally showed a loss of effect of EDI upon the excess mortality hazard of esophagus, bladder and kidney cancers in men and bladder cancer in women using simulated LT. For most cancers the results were similar using simulated LT. However, inconsistent results, particularly for prostate cancer, highlight the need for deprivation-specific LT in order to produce accurate results.

Twenty years of melanoma in Victoria, Queensland, and South Australia (1997 – 2016)

BackgroundGiven the high incidence of melanoma in Australia alongside high mortality with later stage disease, we investigated the populations and locations most at risk, to optimise public health activities in areas where intervention is most needed. This study examines trends and identifies significant prognostic factors and potential disparities in incidence, mortality and survival between population groups in Victoria, Queensland and South Australia. MethodsThe analysis includes data from the population-based cancer registries of the three states over a twenty-year period (1997–2016). Age-standardized and age-specific incidence rates were calculated, and long-term trends analysed using Joinpoint Regression. Five-year relative survival estimates for the study population were calculated using the cohort method and multivariable flexible parametric survival models were applied for each jurisdiction to calculate adjusted excess mortality hazard ratios for the key characteristics. ResultsThere were more males with melanoma than females in all the three states. Over 60% of the cases occurred in the 40–74 years age group. Most melanomas had a Breslow thickness less than or equal to 1.0 mm. For males, Victoria and Queensland had a statistically significant increasing trend whereas in South Australia there was a decreasing trend. For females, the incidence rate trend was stable in Victoria but significantly decreasing in South Australia. In Queensland there was an increasing and statistically significant trend from 2006 to 2016. Across all three states there was a reducing incidence rate in the youngest cohort, stabilizing incidence in the 40–59-year-old age group, and increasing in the oldest cohorts. Five-year relative survival decreased with increasing age and with Breslow thickness across all three jurisdictions. Males had between 43%− 46% excess mortality compared to females in all the three states. There was higher risk with increasing age and Breslow thickness, with the largest risk among the 75 + age group and those with a Breslow thickness of > 4 mm. ConclusionIt is the first time that data from these three registries has been analysed together in a uniform way, covering more than half of the Australian population. This study compares the epidemiology of melanoma across three states and provides a better understanding of trends and factors affecting outcome for Australians with melanoma. While there has been some improvement in aspects of incidence and mortality, this has not been evenly achieved across Australia.