The Prevalence of Frailty in Cancer Patients and Mortality Prediction With a Novel Frailty Index Based Clinical Algorithm-A Multicenter, Prospective, Observational Study

Abstract Purpose To investigate the prediction capacity and status of frailty in Chinese cancer patients in national level, through establishing a novel prediction algorithm. Methods The percentage of frailty in different ages, provinces and tumor type groups of Chinese cancer patients were revealed. The predictioncapacity of frailty on mortality of Chinese cancer patients was analyzed by FI-LAB that is composed of routine laboratory data from accessible blood test and calculated as the ratio of abnormal factors in 22 variables. Establishment of a novel algorithm MCP(mortality of cancer patients)to predict the five-year mortality in Chinese cancer patients was accomplished and its prediction capacity was tested in the training and validation sets using ROC analysis. ResultsWe found that the increased risk of death in cancer patients can be successfully identified through FI-LAB. The univariable and multivariable Cox regression were used to evaluate the effect of frailty on death. In the 5-year follow-up, 20.6% of the 2959 participants (age = 55.8 ± 11.7 years; 43.5% female) were dead while the mean FI-LAB score in baseline was 0.23 (standard deviation = 0.13; range = 0 to 0.73).Frailty (after adjusting for gender, age, and other confounders) could be directly correlated with increased risk of death, with a hazard ratio of 12.67 (95% confidence interval CI: 7.19, 22.31) in comparison with those without frailty. In addition, MCP algorithm presented an area under the ROC (AUC) of 0.691 (95% CI: 0.659-0.684) and 0.648 (95% CI: 0.613-0.684) in the training and validation set, respectively. Conclusion Frailty is common in cancer patients and FI-LAB has high prediction capacity on mortality. The MCP algorithm is a good supplement for frailty evaluation and mortality prediction in cancer patients.

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EFFECTS OF SMOKING ON THE DISEASE PROGNOSIS IN CANCER PATIENTS

Problems in oncology ◽

10.37469/0507-3758-2019-65-3-321-329 ◽

2019 ◽

Vol 65 (3) ◽

pp. 321-329

Author(s):

David Zaridze ◽

Anush Mukeriya

Keyword(s):

Smoking Cessation ◽

Cancer Patients ◽

Malignant Tumors ◽

Scientific Data ◽

Second Primary ◽

Primary Tumors ◽

Smoking Intensity ◽

Risk Of Death ◽

Disease Prognosis ◽

Increased Risk

Smoking not only increases the risk of the development of malignant tumors (MT), but affects the disease prognosis, mortality and survivability of cancer patients. The link between the smoking of cancer patients and increased risk of death by all diseases and oncological causes has been established. Mortality increases with the growth of the smoking intensity, i.e. the number of cigarettes, smoked per day. Smoking is associated with the worst general and oncological survivability. The statistically trend-line between the smoking intensity and survivability was observed: each additional unit of cigarette consumption (pack/year) leads to the Overall Survival Reduction by 1% (p = 0.002). The link between smoking and the risk of developing second primary tumors has been confirmed. Smoking increases the likelihood of side effects of the antitumor therapy both drug therapy and radiation therapy and reduces the treatment efficacy. The smoking cessation leads to a significant improvement in the prognosis of a cancer patient. Scientific data on the negative effect of smoking on the prognosis of cancer patients have a major clinical importance. The treatment program for cancer patients should include science-based methods for the smoking cessation. The latter is fundamentally important, taking into account that the smoking frequency among cancer patients is much higher than in the population.

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Comparison of Cancer Patients to Non-Cancer Patients among COVID-19 Inpatients at a National Level

Cancers ◽

10.3390/cancers13061436 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1436

Author(s):

Alain Bernard ◽

Jonathan Cottenet ◽

Philippe Bonniaud ◽

Lionel Piroth ◽

Patrick Arveux ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Mortality Risk ◽

Hospital Admissions ◽

National Level ◽

Administrative Database ◽

Hospital Death ◽

Solid Cancer ◽

Hematological Cancer ◽

Risk Of Death

(1) Background: Several smaller studies have shown that COVID-19 patients with cancer are at a significantly higher risk of death. Our objective was to compare patients hospitalized for COVID-19 with cancer to those without cancer using national data and to study the effect of cancer on the risk of hospital death and intensive care unit (ICU) admission. (2) Methods: All patients hospitalized in France for COVID-19 in March–April 2020 were included from the French national administrative database, which contains discharge summaries for all hospital admissions in France. Cancer patients were identified within this population. The effect of cancer was estimated with logistic regression, adjusting for age, sex and comorbidities. (3) Results: Among the 89,530 COVID-19 patients, we identified 6201 cancer patients (6.9%). These patients were older and were more likely to be men and to have complications (acute respiratory and kidney failure, venous thrombosis, atrial fibrillation) than those without cancer. In patients with hematological cancer, admission to ICU was significantly more frequent (24.8%) than patients without cancer (16.4%) (p < 0.01). Solid cancer patients without metastasis had a significantly higher mortality risk than patients without cancer (aOR = 1.4 [1.3–1.5]), and the difference was even more marked for metastatic solid cancer patients (aOR = 3.6 [3.2–4.0]). Compared to patients with colorectal cancer, patients with lung cancer, digestive cancer (excluding colorectal cancer) and hematological cancer had a higher mortality risk (aOR = 2.0 [1.6–2.6], 1.6 [1.3–2.1] and 1.4 [1.1–1.8], respectively). (4) Conclusions: This study shows that, in France, patients with COVID-19 and cancer have a two-fold risk of death when compared to COVID-19 patients without cancer. We suggest the need to reorganize facilities to prevent the contamination of patients being treated for cancer, similar to what is already being done in some countries.

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Systemic Capillary Leak Syndrome (Clarkson Syndrome) in Cancer Patients: A Systematic Review

Journal of Clinical Medicine ◽

10.3390/jcm7110418 ◽

2018 ◽

Vol 7 (11) ◽

pp. 418 ◽

Cited By ~ 2

Author(s):

Jae Shin ◽

Keum Lee ◽

I. Lee ◽

Ji Oh ◽

Dong Kim ◽

...

Keyword(s):

Cancer Patients ◽

Case Reports ◽

Laboratory Data ◽

Capillary Leak Syndrome ◽

Treatment Modalities ◽

Capillary Leak ◽

Contributing Factors ◽

Systemic Capillary Leak Syndrome ◽

Increased Risk ◽

Anti Cancer

Systemic capillary leak syndrome (SCLS) is a rare disease characterized by shock caused by capillary hyperpermeability. The disease can occur in cancer patients and effective therapeutic strategies have not been established yet. The aim of the study was to analyze the clinical and laboratory data, treatment modalities, and mortality rate of patients and to identify contributing factors leading to mortality of SCLS in cancer. We searched MEDLINE (inception to July 2018) and of 4612 articles, we identified 62 case reports on SCLS associated with cancer or cancer-related drugs in a total of 53 articles. SCLS was associated with cancer itself in 43.6%, with anti-cancer agents in 51.6% and bone marrow transplantation (BMT) in 4.8%. Among anti-cancer agents, granulocyte-colony stimulating factor (G-CSF) was the most frequently associated drug (14.6%), followed by interleukin (IL)-2 (11.4%). The most common associated malignancies were hematologic (61.3%) with non-Hodgkin lymphoma (22.7%) and multiple myeloma (12.9%) being the leading causes. Common symptoms and signs included dyspnea (27.4%), edema (67.7%), hypotension (32.2%), pleural effusion (29.0%), ascites (22.7%), oliguria (22.7%), and weight gain (21.0%). Patients with SCLS were treated with steroids (59.7%), volume replacement (33.8%), diuretics (24.2%), inotropes (9.6%), methylxanthines (12.8%), β2 agonists (4.8%), while intravenous immunoglobulins (IVIG) were administered in 2 patients (3.2%) only. Among sixteen deaths during follow-up, four were directly attributed to SCLS. Hematologic malignancies were associated with an increased risk for mortality (hazard ratio (HR) 8.820, 95% confidence interval (CI) 1.126–69.063, p = 0.038). Taken together, SCLS can be one important adverse event in cancer patients and careful monitoring of fluid volume is required in the management of SCLS.

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THE EFFECTS OF FRAILTY, POLYPHARMACY, AND COGNITION ON HEALTH OUTCOMES: A STUDY ON INTERRAI RESIDENTIAL CARE DATA

Innovation in Aging ◽

10.1093/geroni/igz038.330 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S86-S86

Author(s):

Macy Zou ◽

Ronald Kelly ◽

Betty Chinda ◽

Mckenzie Braley ◽

Tony Zhang ◽

...

Keyword(s):

Older Adults ◽

Health Outcomes ◽

Residential Care ◽

Frailty Index ◽

Interactive Effects ◽

Deficit Accumulation ◽

Emergency Visits ◽

Ongoing Research ◽

Risk Of Death ◽

Increased Risk

Abstract Frailty Index (FI), polypharmacy and cognition status are significant health concerns in older adults. We conducted this study to investigate the interplay of frailty, polypharmacy, and cognition, in determining health outcomes. InterRAI Residential Care (RAI-RC MDS2.0) data were retrieved from residential care homes in Surrey, BC, Canada. Older residents (65+ years) who had RAI-RC records between 2016 and 2018 were used in the analysis (n=976). A deficit accumulation-based FI was generated using 36 variables. Information on polypharmacy and cognition were obtained by accounting the total number of medications and the cognitive performance scale. Information on falls, emergency visits, and mortality were followed. Multivariate Cox proportional hazard models were used to examine the effects of these variables on different outcomes. The FI showed a near Gaussian distribution (median= 0.370 mean= 0.372 SD= 0.143), and increased linearly with age on a logarithm scale (R=0.75, p<0.001). Residents with cognitive impairment showed a higher level of the FI (KW= 863.3, p<0.001). A higher FI was associated with an increased risk of death (HR=15.2 p=0.006) and emergency visits (HR=2.72 p=0.048), adjusting for age, sex, medications, and education levels. Frailty, polypharmacy, and cognition levels are associated and have interactive effects on health outcomes. Ongoing research is to validate the findings with large samples in different health settings, and to understand the underlying processes of the effect. The close relationships between frailty, polypharmacy, and cognition with health outcomes call for effective integrated strategies for healthcare of older adults with multiple complex health problems.

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Genetic Variations in the PI3K/PTEN/AKT/mTOR Pathway Are Associated With Clinical Outcomes in Esophageal Cancer Patients Treated With Chemoradiotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2008.17.6297 ◽

2009 ◽

Vol 27 (6) ◽

pp. 857-871 ◽

Cited By ~ 119

Author(s):

Michelle A.T. Hildebrandt ◽

Hushan Yang ◽

Mien-Chie Hung ◽

Julie G. Izzo ◽

Maosheng Huang ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Patients ◽

Clinical Outcomes ◽

Genetic Variations ◽

Chemotherapeutic Agents ◽

Response To Therapy ◽

Nucleotide Polymorphisms ◽

Chemotherapeutic Regimen ◽

Risk Of Death ◽

Increased Risk

Purpose The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. Patients and Methods Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. Results We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes—AKT2 and FRAP1—were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). Conclusion These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen.

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Incidence and risk of congestive heart failure risk in renal cell cancer (RCC) and non-RCC patients treated with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.316 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 316-316 ◽

Cited By ~ 2

Author(s):

C. J. Richards ◽

Y. Je ◽

F. A. Schutz ◽

S. M. Dallabrida ◽

J. J. Moslehi ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Cancer Patients ◽

Renal Cell Cancer ◽

Renal Cell ◽

Kinase Inhibitor ◽

Cell Cancer ◽

Tumor Type ◽

High Grade ◽

Increased Risk

316 Background: Sunitinib is a multitargeted receptor tyrosine kinase inhibitor that is widely used in the treatment of renal cell cancer (RCC) and several other malignancies. Congestive heart failure (CHF) has been reported with sunitinib, but the overall incidence and relative risk (RR) remain undefined. We preformed an up-to-date comprehensive meta-analysis to determine the risk of developing serious CHF in patients with both RCC and non-RCC tumors treated with sunitinib. Methods: Medline databases were searched for articles from January 1966 to September 2010. Eligible studies were limited to phase II and III trials of sunitinib in cancer patients with any primary tumor type and adequate safety profile reporting. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI), using random-effects models. Results: A total of 5,497 patients were included. Overall incidence for all-grade and high-grade CHF in sunitinib-treated patients was 4.9% (95% CI, 1.6–14.1%) and 1.8% (95% CI, 0.8–3.9%), respectively. The RR of all-grade and high-grade CHF in sunitinib-treated patients compared to placebo-treated ones was 1.81 (95% CI, 1.30–2.50; p<0.0001) and 3.17 (95% CI, 1.12–8.97; p=0.030), respectively. On subgroup analysis there was no difference observed in the CHF incidence for RCC vs. non-RCC patients. No evidence of publication bias was observed. Conclusions: This is the first comprehensive report to demonstrate that sunitinib use is associated with an increased risk of significant heart failure in cancer patients. [Table: see text]

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Impact of precancer multimorbidity clusters on survival and functional outcomes after cancer in older patients.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.7_suppl.291 ◽

2016 ◽

Vol 34 (7_suppl) ◽

pp. 291-291 ◽

Cited By ~ 1

Author(s):

Kelly Kenzik ◽

Joshua Richman ◽

Erin E. Kent ◽

Maria Pisu ◽

Smita Bhatia

Keyword(s):

Cancer Patients ◽

Survey Data ◽

Cancer Diagnosis ◽

Functional Impairment ◽

Regression Models ◽

Poverty Level ◽

Risk Of Death ◽

Increased Risk ◽

After Cancer ◽

The Impact

291 Background: While multimorbidity clustering is a significant problem in older adults, the impact of clusters present prior to cancer on post-diagnosis survival and function is unknown. We used SEER-Medicare Health Outcomes Survey data for 4583 cancer patients to address this research gap. Methods: Patients with prostate (1741), breast (BC: 1345), colorectal (CRC: 904) and lung (593) cancer with pre- and post-diagnosis survey data were included. Surveys assessed comorbidity and activities of daily living (ADLs). Previously defined multimorbidity clusters were cardiovascular disease (CVD), skeletal, metabolic, pulmonary + major depressive disorder (MDD), and gastrointestinal (GI) + MDD. Cox regression models estimated hazard ratios (HR) for death after cancer diagnosis. Among those without pre-cancer ADL impairment, modified Poisson regression models estimated relative risk (RR) for developing post-cancer functional impairment (ADL ≤ 4). Models controlled for age, race, education, poverty level, stage, and treatment (radiation, surgery). Results: Median age at cancer diagnosis was 74y (65-103). Post-diagnosis mortality: After 6y median follow-up, mortality was 30%; 5y survival was 74%.Prostate, BC and CRC patients with pre-diagnosis CVD clusters were at increased risk of death compared to those without CVD cluster (HR 1.9, 2.0, 1.7, respectively, p < 0.05). Compared to those without the cluster, prostate and BC patients with metabolic cluster were at increased risk (HR 1.7, 1.9, respectively, p < 0.05) and prostate cancer patients with pulmonary conditions + MDD or GI + MDD (HR 1.9, 2.1, respectively, p < 0.05) were at increased risk. Post-diagnosis functional impairment: Prevalence of moderate functional impairment at a median of 1y after cancer diagnosis was 31%. Prostate, lung, and CRC survivors with GI + MDD had a significant RR of developing impairment (RR 1.8, 1.8, and 1.7, p < 0.001). For BC patients, those with skeletal cluster had a 2.1 RR (p < 0.001). Conclusions: Specific multimorbidity clusters prior to cancer are associated with post-cancer mortality and ADL impairment and identify at-risk groups where interventions can be instituted to decrease morbidity and mortality.

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Serum Sulfhydryl Groups, Malondialdehyde, Uric Acid, and Bilirubin as Predictors of Adverse Outcome in Heart Failure Patients due to Ischemic or Nonischemic Cardiomyopathy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6693405 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Celina Wojciechowska ◽

Wojciech Jacheć ◽

Ewa Romuk ◽

Anna Ciszek ◽

Patryk Bodnar ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Uric Acid ◽

Cox Regression ◽

Laboratory Data ◽

Sulfhydryl Groups ◽

Nonischemic Cardiomyopathy ◽

Oxidative Stress Biomarkers ◽

Risk Of Death ◽

Increased Risk

Oxidative stress plays a significant role in the pathogenesis of heart failure (HF). The aim of the study was to investigate the prognostic value of oxidation-reduction (redox) markers in patients with HF due to ischemic and nonischemic cardiomyopathy. The study included 707 patients of HF allocated into two groups depending on ethology: ischemic cardiomyopathy (ICM) ( n = 435 ) and nonischemic cardiomyopathy (nICM) ( n = 272 ), who were followed up for one year. The endpoint occurrence (mortality or heart transplantation) in a 1-year follow-up was similar in the ICM and nICM group. The predictive value of endpoint occurrence of oxidative stress biomarkers such as the serum protein sulfhydryl groups (PSH), malondialdehyde (MDA), uric acid (UA), bilirubin, and MDA/PSH ratio and other clinical and laboratory data were assessed in both groups (ICM and nICM) separately using univariate and multivariate Cox regression analyses. In multivariate analysis, the higher concentrations of UA ( p = 0.015 , HR = 1.024 , 95% CI (1.005-1.044)) and MDA ( p = 0.004 , HR = 2.202 , 95% CI (1.296-3.741)) were significantly associated with adverse prognosis in patients with ICM. Contrastingly, in patients with nICM, we observed that higher bilirubin concentration ( p = 0.026 , HR = 1.034 , 95% CI (1.004-1.064)) and MDA/PSH ratio ( p = 0.034 , HR = 3.360 , 95% CI (1.096-10.302)) were significantly associated with increased risk of death or HT. The results showed the association of different oxidative biomarkers on the unfavorable course of heart failure depending on etiology.

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Socio-economic and rural-urban differences in healthcare and catastrophic health expenditures among cancer patients in China: analysis of the China Health and Retirement Longitudinal Study

10.21203/rs.3.rs-889381/v1 ◽

2021 ◽

Author(s):

Yang Zhao ◽

Shenglan Tang ◽

Wenhui Mao ◽

Tomi F Akinyemiju

Keyword(s):

Longitudinal Study ◽

Cancer Treatment ◽

Cancer Patients ◽

Service Utilization ◽

Rural Areas ◽

Urban Areas ◽

Healthcare Service ◽

Service Use ◽

Increased Risk ◽

Chinese Cancer Patients

Abstract Background In China, cancer deaths account for one-fifth of all deaths and exert a heavy toll on patients, families, healthcare systems, and society as a whole. This study aims to examine socio-economic and rural-urban differences in treatment, healthcare service utilization and catastrophic health expenditure (CHE) among Chinese cancer patients, and to investigate the relationship between different treatment types and healthcare service use as well as incidence of CHE. Methods We analyzed a nationally representative sample from the China Health and Retirement Longitudinal Study including 17,224 participants in 2011 and 19,569 participants in 2015. Multivariable regression models were performed to investigate the association of cancer treatments with healthcare service utilization and CHE. Results The age-adjusted prevalence of cancer is 1.37% for 2011 and 1.84% for 2015. Approximately half of the cancer patients utilized treatment for their disease, with a higher proportion of urban residents (54%) than rural residents (46%) receiving cancer treatment in 2015. CHE declined by 22% in urban areas (25% in 2011 and 19% in 2015) but increased by 31% in rural areas (25% in 2011 to 33% in 2015). There was a positive relationship between cancer treatment and outpatient visit (OR = 2.098, 95% CI = 1.453, 3.029), admission to hospital (OR = 1.961, 95% CI = 1.346, 2.857) and CHE (OR = 1.796, 95% CI = 1.231, 2.620). Chemotherapy and surgery were each associated with a 2-fold increased risk of CHE. Conclusions Meaningful changes to improve health insurance benefit packages are needed to ensure universal, affordable and patient-centered health coverage for the Chinese cancer patients.

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Effect of Anxiety and Depression on Survival of Cancer Patients, a 13 Year Follow-up

Asian Pacific Journal of Cancer Care ◽

10.31557/apjcc.2021.6.1.9-13 ◽

2021 ◽

Vol 6 (1) ◽

pp. 9-13

Author(s):

Suriati Mohamed Saini ◽

Susan Tan Mooi Koon ◽

Mohamad Adam Bujang ◽

Gerard Lim Chin Chye ◽

Shalisah Sharip ◽

...

Keyword(s):

Depressive Symptoms ◽

Cancer Patients ◽

Depression Scale ◽

Cox Proportional Hazards ◽

Anxiety Symptoms ◽

High Rate ◽

Anxiety And Depression ◽

Risk Of Death ◽

Increased Risk

Introduction: Anxiety and depression occur at a high rate in cancer patients. However, debate remains regarding the effect of anxiety and depression on cancer survival. Objective: This study aimed to determine the effect of anxiety and depressive symptoms on the survival of cancer patients. Methods: The subjects consisted of 112 cancer patients who attended the Oncology and Radiotherapy outpatient clinic Hospital Kuala Lumpur, Malaysia, in 1999. Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) questionnaire at inception. Information on patients’ mortality status for extended 13 years follow-up (in 2011) was obtained from the National Registration Department death records. Overall survival for each anxiety and depressive symptoms scores in HADS at 13 years was calculated using Cox proportional hazards regression analysis. Results: Cancer patients experienced more anxiety (83%) compared to depressive symptoms (40.2%). The mean (S.D.) HADS scores for depressive symptoms were 9.9 (2.5), and the anxiety symptoms score was 12.6 (2.1). At 13 years, half of the patients (50.9%) had died. No significant effect of anxiety (p=0.399, 95% C.I.= 6.2-8.4) or depressive symptoms at inception (p=0.749, 95% C.I.= 5.9-8.4) towards cancer patients’ survival was found at 13 years follow-up. Conclusion: The occurrence of anxiety symptoms among cancer patients in this study was 2-folds higher than depressive symptoms. However, no significant increased risk of death was found in cancer patients with anxiety or depressive symptoms at 13 years follow-up. It may imply that as time extended, survival in cancer patients may be related to various interacting elements, and intervening health factors are of importance.

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