Cumulative Risk Of Death Research Articles

CCND1 Amplification in Breast Cancer -associations With Proliferation, Histopathological Grade, Molecular Subtype and Prognosis

CCND1 is located on 11q13. Increased CCND1 copy number (CN) in breast cancer (BC) is associated with high histopathological grade, high proliferation, and Luminal B subtype. In this study of CCND1 in primary BCs and corresponding axillary lymph node metastases (LNM),we examine associations between CCND1 CN in primary BCs and proliferation status, molecular subtype, and prognosis. Furthermore, we studied associations between CCND1 CN and CNs of FGFR1 and ZNF703, both of which are located on 8p12. Fluorescence in situ hybridization probes for CCND1 and chromosome 11 centromere were used on tissue microarrays comprising 526 BCs and 123 LNM. We assessed associations between CCND1 CN and tumour characteristics using Pearson’s χ2 test, and estimated cumulative risks of death from BC and hazard ratios in analysis of prognosis. We found CCND1 CN ≥ 4 < 6 in 45 (8.6%) tumours, and ≥ 6 in 42 (8.0%). CCND1 CN (≥ 6) was seen in all molecular subtypes, most frequently in Luminal B (HER2−) (20/126; 16%). Increased CCND1 CN was associated with high histopathological grade, high Ki-67, and high mitotic count, but not prognosis. CCND1 CN ≥ 6 was accompanied by CN increase of FGFR1 in 6/40 cases (15.0%) and ZNF703 in 5/38 cases (13.2%). Three cases showed CN increase of all three genes. High CCND1 CN was most frequent in Luminal B (HER2−) tumours. Good correlation between CCND1 CNs in BCs and LNM was observed. Despite associations between high CCND1 CN and aggressive tumour characteristics, the prognostic impact of CCND1 CN remains unresolved.

Prioritizing COVID-19 vaccination. Part 1: Final size comparison between a single dose and double dose.

In response to the coronavirus disease 2019 (COVID-19) pandemic, Japan conducted mass vaccination. Seventy-two million doses of vaccine (i.e., for 36 million people if a double dose is planned per person) were obtained, with initial vaccination of the older population (≡ 65 years). Because of the limited number of vaccines, the government discussed shifting the plan to administering only a single dose so that younger individuals (<65 years) could also be vaccinated with one shot. This study aimed to determine the optimal vaccine distribution strategy using a simple mathematical method. After accounting for age-dependent relative susceptibility after single- and double-dose vaccination (vs and vd, respectively, compared with unvaccinated), we used the age-dependent transmission model to compute the final size for various patterns of vaccine distributions. Depending on the values of vs, the cumulative risk of death would be lower if all 72 million doses were used as a double dose for older people than if a single-dose program was conducted in which half is administered to older people and the other half is administered to adults (i.e., 1,856,000 deaths in the former program and 1,833,000-2,355,000 deaths [depending on the values of vs] in the latter). Even if 90% of older people were vaccinated twice and 100% of adults were vaccinated once, the effective reproduction number would be reduced from 2.50 to1.14. Additionally, the cumulative risk of infection would range from 12.0% to 54.6% and there would be 421,000-1,588,000deaths (depending on the values of vs). If an epidemic appears only after completing vaccination, vaccination coverage using a single-dose program with widespread vaccination among adults will not outperform a double-dose strategy.

Total Knee Arthroplasty: Is It Safe? A Single-Center Study of 4,124 Patients in South Korea.

Although total knee arthroplasty (TKA) is considered an effective treatment for knee osteoarthritis, it carries risks of complications. With a growing number of TKAs performed on older patients, understanding the cause of mortality is crucial to enhance the safety of TKA. This study aimed to identify the major causes of short- and long-term mortality after TKA and report mortality trends for major causes of death. A total of 4,124 patients who underwent TKA were analyzed. The average age at surgery was 70.7 years. The average follow-up time was 73.5 months. The causes of death were retrospectively collected through Korean Statistical Information Service and classified into 13 subgroups based on the International Classification of Diseases-10 code. The short- and long-term causes of death were identified within the time-to-death intervals of 30, 60, 90, 180, 180 days, and > 180 days. Standard mortality ratios (SMRs) and cumulative incidence of deaths were computed to examine mortality trends after TKA. The short-term mortality rate was 0.07% for 30 days, 0.1% for 60 days, 0.2% for 90 days, and 0.2% for 180 days. Malignant neoplasm and cardiovascular disease were the main short-term causes of death. The long-term (> 180 days) mortality rate was 6.2%. Malignant neoplasm (35%), others (11.7%), and respiratory disease (10.1%) were the major long-term causes of death. Men had a higher cumulative risk of death for respiratory, metabolic, and cardiovascular diseases. Age-adjusted mortality was significantly higher in TKA patients aged 70 years (SMR, 4.3; 95% confidence interval [CI], 3.3-5.4) and between 70 and 79 years (SMR 2.9; 95% CI, 2.5-3.5) than that in the general population. The short-term mortality rate after TKA was low, and most of the causes were unrelated to TKA. The major causes of long-term death were consistent with previous findings. Our findings can be used as counseling data to understand the survival and mortality of TKA patients.

Epidemiological and clinical features associated to the survival of COVID-19 patients in the department of Littoral in Benin from March to July 2020

The epidemiological, clinical and therapeutic outcomes of COVID-19 vary across countries from March 16th to July 30, 2020, 1805 cases were registered in Benin, and among these cases, about 36 deaths occurred. The aim of this work was to study the epidemiological and clinical features associated with the survival of people with COVID-19 in the Department of Littoral in Republic of Benin, from March to July 2020. This was an analytical cross-sectional study that involved 920 cases of COVID-19. The Kaplan Meier method was used to estimate the survival probability and the cumulative death risk in COVID-19 cases. The Cox model was able to identify associated factors with death caused by COVID-19. The median age was 37 (Q1=28; Q3=48) years ranging from 3 to 84; the sex ratio was 0.85 in women’s favor. Most of affected people had a university level of educational attainment (64.02%). The survival probability of patients was 99% 95%CI: [98.4-99.5] at seven days, and 97.7% 95%CI: [96.4-98.5] at 17 days and more. Age (RRadjusted; 95%CI: 6.29; [1.04-37.79]), educational attainment (RRadjusted; 95%CI: 0.11; [0.01-0.95]), place of treatment (RRadjusted; 95%CI: 18.70; [1.27-274.46]) and treatment received (RRadjusted; 95%CI: 238.46; [19.18-2963.77]) were significantly associated with treatment outcome. In conclusion, in the early stage of COVID-19 outreach in the Department of Littoral of Benin, a high level of education showed to be a protective factor against poor outcome of the treatment. Health education and promotion of school attendance remained key strategies to prevent disease in Benin. Key words: COVID-19, epidemiology, survival probability, associated factors.

Real-World Applicability of Commercial Chimeric Antigen Receptor T Cell Therapy Among Older Adults with Relapsed and/or Refractory Multiple Myeloma

Introduction: In 2021, the US FDA approved idecabtagene vicleucel, the first Chimeric Antigen Receptor-T cell (CAR-T) therapy for patients with relapsed/refractory multiple myeloma (MM) who had received at least four prior lines of therapy. Approval was based on phase II KARMMA trial of this drug showing a response rate of 73% and median progression free survival of 8.8 months; efficacy parameters considered transformative in this setting. Other CAR-T cell therapies are being tested in similar population. However, it is unknown what proportion of real world MM patients, particularly older adults, would be eligible for this treatment.Methods: We used the Flatiron Health Electronic Health Record (EHR) derived de-identified database to select patients newly diagnosed with MM from January 2011 to December 2016. We limited our cohort to those who received ≥1 line of myeloma treatment within 90 days of diagnosis. Lines of therapy (LoT) were ascertained using Flatiron oncologist-defined rules based on the addition of new anti-myeloma agents and gap periods during which no treatment was received. All patients were followed up to the initiation of fifth-line therapy, death or their last structured visit, whichever came earlier. We computed the cumulative incidence of initiating LoT therapy with death prior to fifth-line as the competing risk, remaining patients were censored at their last structured activity in the EHR. For patients initiating fifth LoT, we assessed their CAR-T eligibility using the following key inclusion criteria per the KARMMA trial (ECOG 0-1, GFR >45 ml/min, ANC > 1250 /mm3, Platelet >75k/mm3, ALT/AST <2.5 x upper limit, Bilirubin <2x upper limit, and active treatment for secondary cancer) extracting relevant variables within 90 days of the start of fifth line therapy. Differences in cumulative incidence rates were compared using univariate Fine-Gray's test. All p-values were two sided and the level of significance was 0.05.Results: A total of 4522 eligible patients were identified. The cohort was representative of population of MM patients and patterns of MM therapy in the US with a median age at diagnosis of 69 y (IQR 61-77) and 49% with age 70y or older, 54% males, and 63% non-Hispanic whites. Overall, 20% had ISS III disease, with 11% high risk cytogenetics 31% receiving initial therapy with proteasome inhibitor and immunomodulatory-based triplet therapy and 28% receiving stem cell transplant. In the overall cohort, the cumulative incidence of starting fifth LoT 8y from diagnosis was 28%, while the cumulative risk of death before initiating 5 th LoT was 53% (Figure). However, achievement of 5 th line therapy at 8y was much lower for older adults (35% for age<70y vs 20% for age ≥70y; p value <0.01, Figure), while the risk of death before achieving 5 th line therapy was higher among older patients (37% for age<70y vs 69% for age≥70y; p value <0.01). Among the patients reaching 5 th line therapy, only 44% would be eligible for CAR-T therapy based on the aforementioned eligibility criteria, which translates to about 8.9% of all newly diagnosed older adults ≥70y.Conclusion: Less than 10% of newly diagnosed older adults with MM are expected to be eligible for CAR-T therapy based on the current FDA approval and eligibility criteria. Meanwhile a much higher proportion of patients die before reaching CAR-T eligibility. These findings highlight the need to explore CAR-T cell therapy in earlier lines of disease and in a population that better represents real world patients to expand the applicability of this novel treatment. [Display omitted] DisclosuresGiri: CareVive: Honoraria, Research Funding; PackHealth: Research Funding. Costa: BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Adjuvant Radiotherapy in Patients With Pancreatic Adenocarcinoma. Is It Still Appealing in Clinical Trials? A Meta-analysis and Review of the Literature.

Pancreatic adenocarcinoma is a life-threatening disease with a rising frequency and the fourth leading cause of cancer death. This review aimed to assess the impact of postoperative radiotherapy through a meta-analysis of prospective randomized studies. Six studies met the inclusion criteria and were analyzed to calculate the cumulative risk of death (hazard ratio) in patients affected by pancreatic cancer treated with or without radiotherapy. Higgins' index was used to determine heterogeneity in between-study variability and, subsequently, the random-effects model was applied according to DerSimonian and Laird. Eight hundred and thirty-seven patients were analyzed (418 in the control arm and 419 in the treatment one), the hazard ratio for death after randomization was 0.92 (p=0.560, 95% confidence interval=0.70-1.22). When scrutinizing these studies, only one out of six showed a statistically significant benefit due to the addition of radiotherapy in the postoperative setting. We conclude that the use of adjuvant radiotherapy is not beneficial in treating all patients affected by pancreatic cancer but only for a subset of cases with potential residual local disease.

Multicenter Study of Outcomes Among Persons With HIV Who Presented to US Emergency Departments With Suspected SARS-CoV-2.

There is a need to characterize patients with HIV with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Multicenter registry of patients from 116 emergency departments in 27 US states. Planned secondary analysis of patients with suspected SARS-CoV-2, with (n = 415) and without (n = 25,306) HIV. Descriptive statistics were used to compare patient information and clinical characteristics by SARS-CoV-2 and HIV status. Unadjusted and multivariable models were used to explore factors associated with death, intubation, and hospital length of stay. Kaplan-Meier curves were used to estimate survival by SARS-CoV-2 and HIV infection status. Patients with both SARS-CoV-2 and HIV and patients with SARS-CoV-2 but without HIV had similar admission rates (62.7% versus 58.6%, P = 0.24), hospitalization characteristics [eg, rates of admission to the intensive care unit from the emergency department (5.0% versus 6.3%, P = 0.45) and intubation (10% versus 13.3%, P = 0.17)], and rates of death (13.9% versus 15.1%, P = 0.65). They also had a similar cumulative risk of death (log-rank P = 0.72). However, patients with both HIV and SARS-CoV-2 infections compared with patients with HIV but without SAR-CoV-2 had worsened outcomes, including increased mortality (13.9% versus 5.1%, P < 0.01, log-rank P < 0.0001) and their deaths occurred sooner (median 11.5 versus 34 days, P < 0.01). Among emergency department patients with HIV, clinical outcomes associated with SARS-CoV-2 infection are not worse when compared with patients without HIV, but SARS-CoV-2 infection increased the risk of death in patients with HIV.

794P Comparative study of effectiveness of Pap smear and visual inspection with acetic acid for screening of premalignant and malignant lesion of cervix in a tertiary care setup

Cervical cancer is one of the leading causes of death for women in developing world and it is a preventable cancer, if precancerous lesions are identified early and treated promptly. India accounts for nearly one-third of the global cervical cancer deaths, with women facing a 1.6% cumulative risk of developing cervical cancer and 1.0% cumulative death risk from cervical cancer. This high incidence of deaths in India is mainly due to its detection in advanced stage. Reduction in mortality of the disease is possible only by effective screening methods which is reachable to peripheries of our country.

Abstract 2531: Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort

Abstract Background: Although there is evidence pointing to the role of comorbidity and age in screening mammography outcomes among older women, the impact of functional decline on mortality in this population is unknown. Methods: We used data from 238,849 women in the Breast Cancer Surveillance Consortium-Medicare (BCSC) linked database from 1999-2015 who had at least one screening mammogram at ages 66-94 years. We estimated the 10-year cumulative incidence of breast cancer, breast cancer death, and non-breast cancer death by function-related indicator (FRI) which incorporated 16 claims-based items reflecting functional or health status in older people. In the analysis, FRI score was categorized as an ordinal variable (0, 1, and 2+) and a higher score indicated a higher burden of functional limitations. Fine and Gray proportional sub-distribution hazards models were applied with incident breast cancer and death treated as competing events. Risk estimates by FRI scores (0, 1, and 2+) were adjusted by age and NCI comorbidity index separately and stratified by these factors. Results: During a median follow-up of 101 months, 9,252 women were diagnosed with breast cancer. During follow-up, 406 women died of breast cancer and 41,640 died from non-breast cancer causes. The 10-year age-adjusted cumulative incidence of invasive breast cancer slightly decreased with increasing FRI score (FRI=0: 4.0%, 95% CI=3.8%-4.1%; FRI=1: 3.9%, 95% CI=3.7%-4.2%; FRI=2+: 3.5%, 95% CI=3.1%-3.9%). Risk of death from non-breast cancer causes increased with FRI score (FRI=0: 18.8%, 95% CI=18.5%-19.1%; FRI=1: 24.4%, 95% CI=23.9%-25.0%; FRI=2+: 39.8%, 95% CI=38.8%-40.9%). Risk of breast cancer death was low with minimal risk differences across FRI scores (FRI=0: 0.24%, 95%CI=0.20%-0.28%; FRI=1: 0.20%, 95%CI=0.14%-0.26%; FRI=2+: 0.30%, 95% CI=0.18%-0.42%). Risk estimates in NCI comorbidity index-adjusted models were largely similar to outcomes in age-adjusted models. Stratified analyses suggested similar patterns of risk estimates by FRI. Conclusion: Cumulative risk of death from non-breast cancer causes substantially increases with FRI score, suggesting that the potential of screening mammography to benefit older women is low among those with a high burden of functional limitation. Citation Format: Dongyu Zhang, Linn Abraham, Joshua Demb, Diana L. Miglioretti, Shailesh Advani, Brian L. Sprague, Louise M. Henderson, Tracy Onega, Karen Wernli, Louise C. Walter, Karla Kerlikowske, John T. Schousboe, Ellen S. O'Meara, Dejana Braithwaite. Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2531.

A Multi-State Model for Senior Patients with Diffuse Large B Cell Lymphoma

Introduction: Diffuse large B-cell lymphoma (DLCBL) is the most common lymphoid malignancy in the United States. The combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been shown to be effective and is considered as the standard therapy for DLBCL. However, outcomes remain heterogeneous and hence, more detailed analysis is required to correctly characterize the impact of clinical and socio-demographic factors on DLBCL-specific deaths.Data: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified 11,780 patients with DLBCL who were diagnosed between 2002 and 2009. 9,508 of these patients received at least a single therapy after diagnosis. In addition to treatment regimens, DLBCL histology, stage, presence of B-symptoms, history of anemia, extranodal primary site of involvement, Charlson comorbidity index and performance status were identified from the SEER data. Other predictors of poor survival available in the data were patient age, sex, race, geographic region of residence, marital status, year of diagnosis, and census tract-level characteristics such as urban status and education level, as a measure of socioeconomic status. Since all subjects were Medicare beneficiaries, all patients were older than 65 at diagnosis. The last day of follow-up was December 31, 2011.Methods: We developed a multi-state model to study the impact of clinical and socio-demographic factors on DLBCL-specific deaths. Given that senior patients die from many causes, a multi-state model is essential to correctly distinguish deaths due to DLBCL from deaths due to other causes and to identify risk factors affecting DLBCL-caused mortality. The AalenJohansen estimator, a generalization of Kaplan-Meier estimator, was used to estimate the likelihood of being in one of four health states: Alive after diagnosis, Alive after treatment, Dead due to DLBCL and Dead due to other causes (see the diagram, top left). A multivariable Cox proportional hazards regression model was fitted to each transition between the model states to identify significant risk factors affecting the time and rate of each transition. The findings are compared with the findings of the conventional overall survival model to discuss the advantages and necessity of using a more detailed multi-state modeling framework. Percentage of (DLBCL-specific and all cause) deaths within two years and median time to (DLBCL-specific death and overall survival) events are also used to evaluate the impact of identified risk factors.Results: 5,732 (69% due to DLBCL) and 7,599 (58% due to DLBCL) patients died within 2 years of their diagnosis and before the last day of follow-up, respectively.For patients receiving R-CHOP, the cumulative risk of DLBCL-specific death was exceeded by the cumulative risk of death due to other causes approximately 5.25 years after diagnosis and remained constant afterwards (see the figure, top right). Multivariable Cox regression analyses revealed that higher age, DLBCL stage and Charslon index categories are associated with an elevated risk of DLBCL-specific death both for patients with or without treatment. In addition, being married or female and having higher socioeconomic status are associated with a reduced risk of DLBCL-specific death for patients receiving treatment (see the table attached for the hazard ratios with 95% confidence intervals). As expected, treatment was shown to reduce the risk of DLBCL-specific death, with first-line therapy R-CHOP having the highest positive impact. Consistent with these findings, the factors with higher risk of DLBCL-specific death had lower median time to DLBCL-specific death and median overall survival duration and higher percentage of DLBCL-specific and all cause deaths within two years.Conclusions: Using a multi-state model, we identified increasing age, DLBCL stage and Charlson comorbidity index, being unmarried or male and low socioeconomic status as significant predictors for overall survival and DLBCL-specific mortality in the elderly population. As opposed to a standard survival model, the multi-state approach enables researchers to capture DLBCL-specific and other deaths separately within the same model and helps accurately examine the influence of factors on each transition. [Display omitted] DisclosuresFlowers:National Institutes Of Health: Research Funding; OptumRx: Consultancy; Onyx: Research Funding; Infinity: Research Funding; Abbvie: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Millennium/Takeda: Research Funding; Bayer: Consultancy; Gilead: Consultancy; Janssen Pharmaceutical: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Genentech/Roche: Consultancy, Research Funding; Clinical Care Options: Research Funding; Educational Concepts: Research Funding; Prime Oncology: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Research to Practice: Research Funding; V Foundation: Research Funding; Burroughs Welcome Fund: Research Funding; Celgene: Consultancy, Research Funding; Seattle Genetics: Consultancy; National Cancer Institute: Research Funding; Spectrum: Consultancy.

Breast cancer mortality after eight years of an improved screening program using digital breast tomosynthesis.

ObjectivesTo assess screening quality metrics and to describe mortality rates eight years after redesign of breast cancer screening and diagnosis pathways, and the introduction of digital breast tomosynthesis.SettingBreast Unit of the Toledo Health Area in the region of Castilla-La Mancha (Spain).MethodsWe recorded screening metrics and mortality data following the introduction of digital breast tomosynthesis in 2011 for screening and diagnosis pathways. We then compared the mortality between Toledo Health Area and the rest of Castilla-La Mancha, where digital breast tomosynthesis is not available.ResultsAll screening quality metrics improved following the introduction of digital breast tomosynthesis. The cancer detection rate significantly increased from 2.3 (95% confidence interval (CI): 1.9–3.6) to 4.5 per 1000 women (95% CI: 3.2–5.2) on average between the periods 2005–2009 and 2015–2018, while the recall rate significantly decreased from 7.0% (95% CI: 6.8%–8.2%) to 2.6% (95% CI: 2.0%–3.6%). Comparing breast cancer mortality rates for 2014–2018 in the Toledo Health Area with the rest of Castilla-La Mancha, which had similar cancer treatment access and management protocols but without digital breast tomosynthesis, the crude mortality rate was 17.79 (95% CI: 15.38 -20.19) vs. 24.76 per 100,000 (95% CI: 26.12–23.39), respectively. The cumulative risk of death was also significantly lower for the Toledo Health Area than for Castilla-La Mancha.ConclusionThe introduction of digital breast tomosynthesis improved screening quality indicators. Breast cancer mortality simultaneously decreased with respect to the rest of Castilla-La Mancha. Further research is needed to assess the long-term results, and the role that the redesign may have played in reducing mortality.

Modeling of Survival and Frequency of Cardiovascular-Related Hospitalization in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis.

IntroductionATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) demonstrated the efficacy and safety of tafamidis in transthyretin amyloid cardiomyopathy (ATTR-CM). Model-based analyses from ATTR-ACT can examine predictor effects on dose–response/exposure–response relationships.MethodsParametric hazard distributions were developed for all-cause mortality and frequency of cardiovascular-related hospitalization. Time-to-event models were fitted to survival data, and repeated time-to-event models were fitted to hospitalization data. Disease-specific characteristics were assessed as baseline predictors of event hazards.ResultsThere were 441 patients in this analysis. At month 30, 70.5% (tafamidis) and 57.1% (placebo) of patients were alive, with 154/441 deaths reported; 495 cardiovascular-related hospitalizations occurred. The cumulative risk of death was 42.1% (95% confidence interval [CI] 24.2–58.0) lower with tafamidis than with placebo, regardless of New York Heart Association (NYHA) class; significant predictors of decreased risk were genotype (wild-type), greater 6-Minute Walk Test (6MWT) distance, higher left ventricular ejection fraction (LVEF), and lower blood urea nitrogen (BUN) and N-terminal pro-B-type natriuretic peptide concentrations. The average cumulative risk of cardiovascular-related hospitalization up to 30 months was 40.8% (95% CI 31.0–49.7) lower with tafamidis in NYHA class I/II patients. Significant predictors of reduced risk were greater 6MWT distance, higher LVEF, and lower BUN and troponin I concentrations.ConclusionsTafamidis reduced cumulative mortality and hospitalization risk versus placebo in patients with ATTR-CM. Baseline predictors of outcome were consistent with the cardiovascular nature of the disease and suggested that earlier treatment may improve outcomes.Clinical Trials.gov IdentifierNCT01994889 (date of registration: November 26, 2013).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-021-00464-y.

Short-term effects of ambient temperature and pollutants on the mortality of respiratory diseases: A time-series analysis in Hefei, China

BackgroundThe air pollution has become an important environmental health problem due to its adverse health effect. The objective of this study was to investigate the effects of ambient temperature and pollutants on mortality of respiratory diseases (RD) in Hefei, China, a typical inland city. MethodsNonlinear exposure–response dependencies and delayed effects of urban daily mean temperature (DMT) and pollutants were evaluated by distributed lag non-linear models (DLNM). To further explore this effect, different genders and ages were also examined by stratified analysis. ResultsA total of 12876 deaths from RD were collected from January 1, 2014 to December 31, 2018 in Hefei, China. There was a U-shaped correlation between DMT and RD mortality, and the RD mortality rised by 11.6% (95% CI: 2.2–22.0%) when the DMT was 35.8 °C (reference temperature is 20 °C). The results show that risk of death with short-term exposure to elevated concentrations of PM10 and SO2 was not significant. The maximum hysteresis and cumulative relative risk (RR) of RD mortality were 1.012 (95% CI: 1.003 ~ 1.021, lag 0 day) and 1.072 (95% CI: 1.014 ~1.133, lag 10 days) for each 10 μg/m3 augment in NO2; 1.005 (95% CI: 1.001–1.009, lag 0 day) and 1.027 (95% CI: 1.004–1.051, lag 10 days) for each 10 μg/m3 augment in O3; a negative association between CO exposure and the cumulative risk of death was observed (RR = 0.964, 95% CI: 0.935–0.993, lag 07 days). Subgroup analysis showed the effect of high temperatures, NO2, O3 and CO exposure was still statistically significant for the elderly and male. ConclusionThe present study found that short-term exposure to high temperature, NO2, O3 and CO were significantly associated with the risk of RD mortality and male as well as elderly are more susceptible to these factors.

Competitive Risk Analysis of Prognosis in Patients With Cecum Cancer: A Population-Based Study.

Background:The presence of competing risks means that the results obtained using the classic Cox proportional-hazards model for the factors affecting the prognosis of patients diagnosed with cecum cancer (CC) may be biased.Objective:The purpose of this study was to establish a competitive risk model for patients diagnosed with CC to evaluate the relevant factors affecting the prognosis of patients, and to compare the results with the classical COX proportional risk model.Methods:We extracted data on patients diagnosed with CC registered between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The univariate analysis utilized the cumulative incidence function and Gray’s test, while a multivariate analysis was performed using the Fine-Gray, cause-specific (CS), and Cox proportional-hazards models.Results:The 54463 eligible patients diagnosed with CC included 24387 who died: 12087 from CC and 12300 from other causes. The multivariate Fine-Gray analysis indicated that significant factors affecting the prognosis of patients diagnosed with CC include: age, race, AJCC stage, differentiation grade, tumor size, surgery, radiotherapy, chemotherapy and regional lymph nodes metastasis. Due to the presence of competitive risk events, COX model results could not provide accurate estimates of effects and false-negative results occurred. In addition, COX model misestimated the direction of association between regional lymph node metastasis and cumulative risk of death in patients diagnosed with CC. Competitive risk models tend to be more advantageous when analyzing clinical survival data with multiple endpoints.Conclusions:The present study can help clinicians to make better clinical decisions and provide patients diagnosed with CC with better support.

21-Gene Assay and Breast Cancer Mortality in Ductal Carcinoma In Situ.

The inability to identify individuals with ductal carcinoma in situ (DCIS) who are at risk of breast cancer (BC) mortality have hampered efforts to reduce the overtreatment of DCIS. The 21-gene recurrence score (RS) predicts distant metastases for individuals with invasive BC, but its prognostic utility in DCIS is unknown. We performed a population-based analysis of 1362 individuals of DCIS aged 75 years or younger at diagnosis treated with breast-conserving therapy. We examined the association between a high RS (defined a priori as >25) and the risk of BC mortality by using a propensity score-adjusted model accounting for the competing risk of death from other causes, testing for interactions. All statistical tests were 2-sided. With 16 years median follow-up, 36 (2.6%) died of BC, and 200 (14.7%) died of other causes. The median value of the RS was 15 (range = 0-84); 29.6% of individuals had a high RS. A high RS was associated with an 11-fold increased risk of BC mortality (hazard ratio = 11.27, 95% confidence interval [CI] = 3.00 to 42.33; P < .001) in women aged 50 years or younger at diagnosis treated with breast-conserving surgery alone, culminating in a 9.4% (95% CI = 2.3% to 22.5%) 20-year risk of BC death. For women with a high RS, treatment with radiotherapy was associated with a 71% (hazard ratio = 0.29, 95% CI = 0.10 to 0.89; P = .03) relative and a 5% absolute reduction in the 20-year cumulative risk of death from BC. The 21-gene RS predicts BC mortality in DCIS and combined with age (50 years or younger) at diagnosis can identify individuals for whom radiotherapy reduces the risk of death from BC.

Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy-The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group.

Simple SummaryPhiladelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is rare in children, but outcomes are still poor. The aim of our study was to analyze the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post induction treatment of Philadelphia chromosome positive ALL) in Poland between the years 2012 and 2019. Our treatment outcomes are still disappointing compared to those in other reports. Improvements in supportive care and emphasis placed on the determination of MRD at successive time points, which will impact decisions on therapy, may be required.The treatment of children with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is currently unsuccessful. The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post-induction treatment of Philadelphia chromosome positive ALL) in 15 hemato-oncological centers in Poland between the years 2012 and 2019. The study group included 31 patients, aged 1–18 years, with newly diagnosed ALL Ph+. All patients received TKIs. Imatinib was used in 30 patients, and ponatinib was applied in one child due to T315I and M244V mutation. During therapy, imatinib was replaced with dasatinib in three children. The overall survival of children with ALL Ph+ treated according to the EsPhALL2010 protocol was 74.1% and event-free survival was 54.2% after five years. The cumulative death risk of the study group at five years was estimated at 25.9%, and its cumulative relapse risk was 30%. Our treatment outcomes are still disappointing compared to other reports. Improvements in supportive care and emphasis placed on the determination of minimal residual disease at successive time points, which will impact decisions on therapy, may be required.

CRAX: A simple cardiovascular risk assessment tool to predict risk of acute myocardial infarction or death

BackgroundDetermining the risk of cardiovascular events is essential to optimize patient management. Methods and Results5842 individuals underwent SPECT myocardial perfusion imaging (MPI) with 4.4 ± 1.2 years of follow-up. Models (the CRAX tool) were derived to predict the cumulative risk of death and acute myocardial infarction (AMI) at 1, 3, and 5 years using clinical and MPI variables. Predictors of AMI and death included age, number of hospitalizations in the 3 years preceding MPI, and left ventricular ejection fraction (LVEF). Additional predictors of death were the use of pharmacological stress, and global stress total perfusion deficit (sTPD), while transient ischemic dilation (TID), and ischemic total perfusion deficit (iTPD) change were predictive of AMI. CRAX predictions were significantly (P < .001) more accurate than clinical variables or MPI results alone, resulting in a significant net reclassification improvement (NRI, 7.5% for AMI, 14.5% death) compared to clinical variables alone. Accuracy for predicting major adverse cardiac events (MACE, comprising all-cause death, AMI, unstable angina, late revascularization) was comparable to that of AMI or death. ConclusionsCRAX is a risk assessment tool that predicts the risk of AMI, death, or MACE, and improves prediction compared to clinical variables or MPI results alone.

Real-world long-term outcomes in individuals at clinical risk for psychosis: The case for extending duration of care.

BackgroundMost services for individuals at Clinical High Risk for Psychosis (CHR-P) provide short-term clinical care. This study determines the real-world and long-term clinical outcomes beyond transition to psychosis in a large cohort of CHR-P individuals.MethodRetrospective RECORD-compliant real-world Electronic Health Records (EHR) cohort study in secondary mental health care (the South London and the Maudsley -SLaM- NHS Foundation Trust). All CHR-P patients accessing the CHR-P service at SLaM in the period 2001–2018 were included. Main outcomes were long-term cumulative risk of first: (i) developing an ICD-10 psychotic disorder (primary outcome), receiving a treatment with (iia) antipsychotic medication, (iib) benzodiazepines, (iic) other psychotropic medications, (iid) psychotherapy, receiving an (iiia) informal or (iiib) compulsory admission into a mental health hospital, and the time to these events; (iiic) number of days spent in hospital and (iv) cumulative risk of death for any reason and age/gender Standardised Mortality Ratio (SMR). Data were extracted from the EHR and analysed with Kaplan Meier failure functions, Cox and zero-inflated negative binomial regressions.Findings600 CHR-P patients (80.43% Attenuated Psychotic Symptoms, APS; 18.06%, Brief and Limited Intermittent Psychotic Symptoms, BLIPS, 1.51% Genetic Risk and Deterioration Syndrome) were included (mean age 22.63 years, range 13–36; 55.33% males; 46.44% white, mean duration of untreated attenuated psychotic symptoms 676.32 days, 1105.40 SD). The cumulative risk to first psychosis was 0.365 (95%CI 0.302–0.437) at 11 years; first antipsychotic 0.777 (95%CI 0.702–0.844) at 9 years; first benzodiazepine 0.259 (95%CI 0.183–0.359) at 12 years; first other types of medications 0.630 (95%CI 0.538–0.772) at 9 years; first psychotherapy 0.814 (95%CI 0.764–0.859) at 9 years; first informal admission 0.378 (95%CI 0.249–0.546) at 12 years; first compulsory admission 0.251 (95%CI 0.175–0.352) at 12 years; those admitted spent on average 94.84 (SD=169.94) days in hospital; the cumulative risk of death for any reason was 0.036 (95%CI 0.012–0.103) at 9 years, with an SMR of 3.9 (95%CI 1.20–6.6). Compared to APS, BLIPS had a higher risk of developing psychosis, being admitted compulsorily into hospital, receiving antipsychotics and benzodiazepines and lower probability of receiving psychotherapy. Other prognostic factors of long-term outcomes included age, symptoms severity, duration of untreated attenuated psychotic symptoms, ethnicity and employment status.InterpretationDuration of care provided by CHR-P services should be expanded to address long-term real-world outcomes.FundingThis study was supported by the King's College London Confidence in Concept award from the Medical Research Council (MRC) (MC_PC_16048) to PF-P. GSP is supported by the Alicia Koplowitz Foundation. HB is supported by a National Institute for Health Research Maudsley Biomedical Research Centre studentship.

Mortality Effects of Hypothetical Interventions on Physical Activity and TV Viewing.

Long-term effects of physical activity and television (TV) viewing on mortality have been inferred from observational studies. The associations observed do not allow for inferences about the effects of population interventions and could be subject to bias due to time-varying confounding. Using data from the Australian Diabetes, Obesity and Lifestyle Study, collected in 1999-2000 (T0), 2004-2005 (T1), and 2011-2012 (T2), we applied the parametric g-formula to estimate cumulative risks of death under hypothetical interventions on physical activity and/or TV viewing determined from self-report while adjusting for time-varying confounding. In the 6377 participants followed up for 13 yr from 2004 to 2005 to death or censoring in 2017, 781 participants died. The observed cumulative risk of death was 12.2%. The most effective hypothetical intervention was to increase weekly physical activity to >300 min (risk ratio (RR), 0.66 (0.46-0.86) compared with a "worst-case" scenario; RR, 0.83 (0.73-0.94) compared with no intervention). Reducing daily TV viewing to <2 h in addition to physical activity interventions did not show added survival benefits. Reducing TV viewing alone was least effective in reducing mortality (RR, 0.85 (0.60-1.10) compared with the worst-case scenario; RR, 1.06 (0.93-1.20) compared with no intervention). Our findings suggested that sustained interventions to increase physical activity could lower all-cause mortality over a 13-yr period, and there might be limited gain from intervening to reduce TV viewing time in a relatively healthy population.

Risk of hepatocellular carcinoma in Danish outpatients with alcohol-related cirrhosis

Accurate estimates of hepatocellular carcinoma (HCC) risk in patients with cirrhosis are important to guide surveillance strategies. We described HCC risk among outpatients with alcohol-related cirrhosis and contrasted the risk of death from HCC with the risk of death from variceal bleeding or trauma. This was a nationwide, registry-based historical cohort study between 2006 and 2018. We included all Danish outpatients with a hospital diagnosis of alcohol-related cirrhosis, except those with cancer, those with chronic viral hepatitis or autoimmune liver disease, and those older than 80 years. We followed them through 2018 and described the cumulative risk of HCC and the cumulative risk of death from HCC, variceal bleeding, or trauma. Of the 4,553 patients included, 181 developed HCC and 2,274 died. The cumulative risk of HCC was 0.9% (95% CI 0.7-1.3) after 1 year, 3.6% (95% CI 3.0-4.2) after 5 years, and 6.0% (95% CI 5.1-7.0) after 10 years, or approximately 0.7% per year. Male sex, older age, and decompensated cirrhosis predicted a higher HCC risk. After 10 years, 6.9% of deaths in the cohort could be attributed to HCC, whereas 6.5% could be attributed to variceal bleeding, and 5.0% to trauma. In 2006-2018, Danish outpatients with alcohol-related cirrhosis had an HCC risk of 0.7% per year, and they were nearly as likely to die from variceal bleeding or from trauma as from HCC. The implications are that many potentially harmful examinations are required for every HCC found through surveillance, so interventions targeting the prevention of other causes of death might be more cost-effective. We described the risk of hepatocellular carcinoma (HCC, the most common form of liver cancer originating in the liver) in Danish outpatients with cirrhosis due to harmful alcohol consumption. Accurate data on that risk are important for patient counselling and decisions about screening for HCC. The risk was about 0.7% per year, which is lower than might be expected and suggests that many potentially harmful screening examinations are required for every HCC found through surveillance.