Prevalence Of Breast Cancer Patients Research Articles

The prevalence of mild cognitive impairment in breast cancer patients receiving chemotherapy according to the criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA).

Breast cancer patients receiving chemotherapy can develop cognitive impairment. There is no gold standard for defining cognitive impairment. We applied the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) to determine its prevalence in breast cancer patients receiving adjuvant chemotherapy and examine differences between patients with and without MCI. We used pre-existing cognitive data on 5 neuropsychological test outcomes (verbal memory, processing speed, executive functioning, and verbal fluency) gathered from 240 breast cancer patients who received adjuvant conventional (n = 154) or high-dose chemotherapy (n = 86). Assessments occurred 6 or 12months post-chemotherapy and results were compared with data from 66 women without cancer. MCI was defined by the following: (i) presence of concern regarding a change in cognition, (ii) impairment in one or more cognitive tests (1.5 standard deviation below a normative mean), (iii) preservation of independence in functional abilities, and (iv) the absence of dementia. Twenty percent (n = 49) of breast cancer patients who received chemotherapy (conventional therapy n = 29 (12%), high-dose therapy = 20 (8.3%)) met the criteria for MCI, compared with 7.6% (n = 5) of controls. Prevalence was significantly different between patients and controls (P = 0.020, and corrected for IQ P < 0.001). Patients with MCI had significant lower education levels (P < 0.002) and premorbid IQ (P = 0.001) compared with patients without MCI. Twenty percent of breast cancer patients treated with chemotherapy met NIA-AA criteria for MCI, compared with 7.6% of the controls. These criteria, which include formal test performance as well as a person's symptoms and functional status, can be useful in clinical practice and scientific research.

The Association of PTEN Gene Mutations with the Breast Cancer Risk: A Systematic Review and Meta-analysis.

Breast cancer (BC) is the most common malignancy in women in western countries. A significant part of malignant cases is caused by genetic mutation. Mutations in the gene phosphatase and tensin homologue deleted on chromosome (PTEN) have been proven in various malignancies. The present study was conducted with the aim of investigating the prevalence of BC due to PTEN gene mutation, as well as estimating the chance of developing BC due to the occurrence of PTEN gene mutation. The present study was conducted using a systematic review method based on PRISMA 2020 statements. The search was done in PubMed, Web of Science (WOS), Scopus, and direct scientific databases. The search was performed using the keywords breast cancer, breast malignancy, PTEN, polymorphism, mutation, variant, and their equivalents. Statistical analysis was performed using the second version of Comprehensive Meta-Analysis Software. A total of 2138 articles were collected. After removing duplicate articles, checking the title and abstract, and then checking the full text of the documents, finally 64 articles were approved and entered the systematic review process. Analysis of these studies with a sample size of 231,179 showed the prevalence of breast cancer patients with PTEN mutations. The combined results of 64 studies showed that the prevalence of PTEN mutations has a 3.3 (95% CI 2.2-5) in BC patients, and an analysis of 6 studies showed that the odds ratio of developing BC due to PTEN mutation is 3.7 (95% CI 1.1-11.9). The results of this study show that mutation in the PTEN gene increases the chance of developing BC. However, it was found that a small part of patients gets BC due to the occurrence of mutation in this gene.

221 Prevalence of breast cancer patients with distant metastases at the time of presentation – A retrospective cohort study

Abstract Introduction About 8% of new breast cancer patients have distant metastases at presentation.[1] Current local practice is to perform staging CT on selected patients. The aim of this study was to investigate the prevalence of distant metastases in a cohort of newly diagnosed breast cancer. Methods A single-institution retrospective analysis of prospectively collected database of all newly diagnosed patients between January and June 2019 (pre-covid era). Patients with previous history of breast cancer were excluded. Data was collated from hospital medical records. SPSS version 21 was used for analysis. Results A total of 85 patients with a mean age of 66±15.593 were included. Tumour size ranged from 1.4 to 83mm. 22.4% were ER Negative, 14.8% HER2 positive and 37.3% node positive. Almost half of the patients (49.4%) underwent staging investigations at first presentation. The incidence of distant metastases within 1 year of presentation was 10.6% (9/85). 4/9 (44.4%) presented late with symptoms greater than 3 months duration. On applying one-way ANOVA to compare means, distant metastases at presentation was significantly related to grade (p-value= 0.002) and nodal status (p-value=0.006). There was no statistically significant relationship to age, ER/HER-2 status, tumour size or duration of symptoms. Conclusions Metastatic breast cancer at presentation in our cohort appears concordant with the literature. Distant metastases within a year of presentation is significantly related to grade independent of nodal status, and staging investigations should be considered in early breast cancer patients with higher tumour grade irrespective of other factors. 1. https://pubmed.ncbi.nlm.nih.gov/35018787/

Hematologic toxicities, sarcopenia, and body composition change in breast cancer patients undergoing neoadjuvant chemotherapy.

Evaluation of body composition and sarcopenia status could provide evidence for more sensitive prediction of chemotherapy toxicities and support mitigation of the negative impacts of chemotherapy. This study evaluated associations among hematologic toxicities, sarcopenia, and body composition change in breast cancer patients undergoing neoadjuvant chemotherapy. This retrospective cohort study employed data from 298 breast cancer patients undergoing neoadjuvant chemotherapy. We evaluated two abdominal computed tomography scans before and after neoadjuvant chemotherapy to identify body composition change. As hematologic toxicities, severe (grade 3 or 4) anemia, neutropenia, and thrombocytopenia were assessed throughout the treatment period using Common Terminology Criteria for Adverse Events (version 5.0). Participants experienced severe neutropenia (23.5%), anemia (7.1%), and thrombocytopenia (0.7%) during chemotherapy. After chemotherapy, the group with sarcopenia had double the anemia prevalence of the group without sarcopenia (p < 0.001). The group with anemia had significantly decreased skeletal muscle index (SMI, p = .0013) and subcutaneous fat index (SFI, p = .0008). Almost 50% of the sarcopenia group treated with an AC-T (weekly) regimen (combined anthracycline and cyclophosphamide followed by a weekly taxane) had neutropenia. Multiple logistic regression showed that the AC-T (weekly) group had higher neutropenia prevalence than other regimen groups. Our findings of higher anemia prevalence in breast cancer patients with sarcopenia and decreased SMI and SFI after neoadjuvant chemotherapy provide evidence of a relationship between anemia and body composition change. Early screening and combined consideration of body composition change, sarcopenia status, and chemotherapy regimen could improve clinical outcomes.

A systematic review and meta-analysis of the prevalence of depression among breast cancer patients in Sub-Saharan Africa

Background: Breast cancer is linked to neuropsychiatric conditions, particularly depression, which lowers life expectancy. Studies from Sub-Saharan Africa, however, have revealed conflicting prevalence rates of depression. Objective: To assess the combined prevalence of breast cancer-related depression among patients in Sub-Saharan Africa. Methods: The following search terms—depression, depressive disorders, breast cancer, mammary cancer, mammary adenocarcinoma and breast carcinoma, and Sub-Saharan African—were used to conduct a systematic search for English articles on depression published in PubMed, Scopus, Web of Science, African Journal Online, and Google Scholar. A meta-command was used to combine the results of different studies on depression linked to breast cancer through a random effects model at a 95% confidence interval in Stata software (version 17). Results: After the elimination of duplicates, 9,272 articles were still found after the electronic search yielded 12051 results. A number of 19 articles were still available after abstract and title screening, and they underwent full-text screening. A number of 10 articles were removed for a variety of reasons, including the lack of the full text (n=2), incorrect publication type (n=2), and not reporting the full outcome of interest (n=6). In Sub-Saharan Africa, the combined prevalence of breast cancer patients was 60%. (95CI, 0.51-0.69). The prevalence rates of depression among breast cancer patients in East Africa, South Africa, and West Africa were reported as 64% (95CI, 0.51-0.75), 60% (95CI, 0.53-0.67), and 55%. (95CI, 0.36-0.73), respectively. Conclusion: In Sub-Saharan Africa, about 6 in 10 cancer patients experience depression. Since depression negatively affects the quality of life, it is important to properly diagnose depression in order to treat it effectively with the fewest possible side effects.

Nursing Intervention Model to Overcome Psychosocial Problems of Breast Cancer Patients: A Literature Review

Chronic disease, such as breast cancer is a disease that requires comprehensive treatment and takes a long time. The prevalence of breast cancer patients continues to be high in number so that it will cause psychosocial problems such as social problems, anxiety, and even depression. This study aims to identify appropriate nursing interventions to address psychosocial problems in breast cancer patients. literature review was used in this study. Article searches were conducted in six journal databases, namely PubMed, JSTOR, Taylor, Willey Online, Sage, and Google Scholar. Seven articles were found that matched the inclusion of criteria. Results of this review show that social support interventions, palliative support, psychological interventions, home care, home visits, virtual reality and music therapy, relaxation techniques and motivational support, psychological therapy programs via offline and telephone, Adapted Physical Activity and Diet (APAD), Aromatherapy Plus Music Therapy can be performed on cancer patients to help reduce psychosocial problems so that the patient's quality of life will improve.

195 (PB-108) Poster - Clinical benefit and tolerability of CDK4/6 inhibitors in the treatment of breast cancer advanced in the geriatric population – real life data from a Hospital Center

Background: Several phase 3 clinical trials have demonstrated the benefit of CDK4/6 inhibitors (iCDK4/6) associated with endocrine therapy on survival outcomes, with a manageable toxicity profile. Despite the high prevalence of breast cancer patients over 65 years, this population is usually underrepresented in trials, which leads to an extrapolation of data from younger and healthier patients. However, the geriatric population is heterogeneous in terms of comorbidities and performance status. The aim of this study is to evaluate the clinical benefit (CB) and toxicities of ribociclib (R) and palbociclib (P) in the elderly population of our Center.

1719P Peripheral neuropathy and nail dystrophy induced by taxanes: The impact of cryotherapy on the prevention and control of symptoms

Chemotherapy-induced peripheral neuropathy (CIPN) and nail disorders (ND) are highly prevalent in patients treated with taxanes. We aimed to evaluate the effectiveness of using frozen gloves (FG) in the prevention of these symptoms and their prevalence in breast cancer patients during treatment.

Overview of obesity and breast cancer in brazil: 24 years of follow up

Rationale: Obesity is one of the major public health challenges of the 21st century. The prevalence of obesity is growing exponentially across all age groups and on all continents and it is associated with morbidities such as cardiovascular disease, diabetes mellitus type 2, dyslipidemia, hypertension and cancer. There is a higher risk of developing breast cancer in postmenopausal obese women, and with worse outcome for women of all ages. OBJECTIVES: To evaluate obesity prevalence in breast cancer patients and its association with recovering, survival, death, age, Human Epidermal Growth Factor Receptor 2 (HER2) and anti-human KI67 antibody(KI67).

Previously diagnosed multiple primary malignancies in patients with breast carcinoma in Western Sweden between 2007 and 2018

PurposeMultiple primary malignancies (MPMs) caused by breast cancer treatment are well described, but only few studies to date describe which other previous primary malignancies (OPPMs) occur before breast cancer. The purpose of the present study was to evaluate the prevalence of OPPMs in patients with breast cancer between 2007 and 2018 in Western Sweden.MethodsPatient selection was performed using both pathology reports at Sahlgrenska University Hospital (Sweden) and the Swedish Cancer Registry. All newly diagnosed breast cancer patients were screened for presence of OPPM.ResultsIn total, 8031 breast cancer patients were diagnosed at Sahlgrenska University Hospital between 2007 and 2018. The prevalence of breast cancer patients with OPPMs (n = 414) increased from on average 2.6% to 8.2% during this 12-year period and ranged from 17 to 59 patients annually. The most striking increase in prevalence was found among the gynecological tumors (endometrium and ovarian adenocarcinomas), malignant melanomas and gastrointestinal malignancies. These findings were validated using data of the Swedish Cancer Registry.ConclusionsThe overall survival rates for cancer patients have improved tremendously during the past 40 years, in part due to individually tailored therapies and screening programs. Our study revealed an increasing trend of OPPMs in breast cancer patients.

Overview of obesity and breast cancer in Brazil: 24 year of follow up.

e13580 Background: Obesity is one of the major public health challenges of the 21st century. The prevalence of obesity is growing exponentially across all age groups and on all continents and it is associated with morbidities such as cardiovascular disease, diabetes mellitus type 2, dyslipidemia, hypertension and cancer. There is a higher risk of developing breast cancer in postmenopausal obese women, and with worse outcome for women of all ages. Objectives: To evaluate obesity prevalence in breast cancer patients and its association with recovering, survival, death, age, Human Epidermal Growth Factor Receptor 2 (HER2) and anti-human KI67 antibody(KI67). Methods: A retrospective cohort study was performed between 1994 and 2018 at the Breast Cancer Department, São Paulo State Government Women's Health Reference Center (Perola Byington Hospital), São Paulo, Brazil with 8824 breast cancer patients. From those, 2899 patients were excluded because they did not have description of weight and/or Body Mass Index (BMI). Survival analysis was performed according to BMI groups. Results: The participants had mean (SD) age of 54 (12.0) years and weight of 70 (15.0) kg. There were 769 (13%) deaths and the mean survival was 20 (2.0) years. 1787 (30%) participants were stratified in obese (BMI≥30Kg/m2) and 4138 (70%) non-obese Obese were older (p &lt; 0,001) and had a higher frequency of HER2 negative (p &lt; 0,04) than non-obese women. There were not a significant difference in frequencies of KI67, recovering and survival between groups. The prevalence of obesity was not different over 24 years. Conclusions: There was a relevant prevalence of obesity in breast cancer patients, which was associated with HER2 negative and age, but not with recovering or survival.

Abstract P2-09-11: Prevalence of patients with indication of genetic evaluation for hereditary breast and ovarian syndrome in the Brazilian cohort study - AMAZONA III

Abstract INTRODUCTION: The evaluation of an individual with risk of hereditary breast cancer is based on the patient's family history and the characteristics of the neoplasia. BRCA1 and BRCA 2 are the most common genes associated with hereditary predisposition for breast or ovarian cancer. The evaluation of an individual with risk of hereditary breast cancer is key to identify patients with indication to BRCA test. Recent studies in US suggests that 31 to 34% of patients with breast cancer should be referred for genetic evaluation. In Brazil, the proportion of BC patients with indication to genetic evaluation is unknown. OBJECTIVE: To describe the prevalence of breast cancer patients enrolled in the AMAZONA III study with indication for genetic evaluation considering the criteria for hereditary breast and ovarian cancer syndrome (HBOC). METHOD: We evaluated the database of the AMAZONA III observational, prospective cohort study which included 2950 patients newly diagnosed with BC in the period of 2016-18 within 23 Brazilian sites. The criteria used to select patients who should be referred for genetic testing were extracted from the National Comprehensive Cancer Network (NCCN) guideline 2018. The characteristics of interest were summarized through descriptive statistics. RESULTS: A total of 1094 (37%) BC patients had at least one criteria for HBOC syndrome test. The most common criteria for testing was age equal or inferior 45 years (27%), BC diagnosis under 50 years and family history of breast cancer (13.5%). From the 2950 enrolled patients, 651 (22%) had the information about whether an evaluation of BRCA test was performed. Of them only 45 (6.9%) performed BRCA test, one patient from public health system and the others from private health system and from those tested 18 (40%) had an identified pathogenic mutation. CONCLUSION: A high proportion of patients diagnosed with BC in Brazil have a criteria for HBOC syndrome testing. Nonetheless a few patients have access to genetic counseling and BRCA test, especially in the public health system. Therefore its critical to implement health policies to facilitate the access to specialized care in hereditary cancer. Frequency of each criteria regarding all 2950 patientsTotal - n (%)Missing - n (%)&amp;lt;=45 years806 (27.32)62 (2.10)&amp;lt;= 60 years and molecular subtype triple negative234 (7.93)681 (23.08)Family history of ovarian cancer101 (3.42)214 (7.25)&amp;lt;= 50 years and family history of breast cancer388 (13.15)214 (7.25)&amp;lt;= 50 years and personal history of breast cancer26 (0.88)142 (4.81)Personal history of ovarian cancer4 (0.14)142 (4.81) Citation Format: Alessandra BorbaAnton de Souza, Daniela Rosa, Antonio LuiZ Frasson, Felipe Pereira Zerwes, Nathalia Cunha Rossato, Patricia Asthon-Prolla, Sergio Simon, Jose Bines, Carlos Barrios, Alessandra Morelle, Carlos AlbertoSampaio Filho, Max Mano, Rafaela Gomes, Gustavo Werutsky. Prevalence of patients with indication of genetic evaluation for hereditary breast and ovarian syndrome in the Brazilian cohort study - AMAZONA III [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-11.

Abstract 3474: Prevalence of BRCA1 and BRCA2 small mutation and large genomic rearrangements in breast cancer patients visiting a genetic counseling clinic

Abstract BACKGROUND: This study was conducted to investigate mutation prevalence of the BRCA1 and BRCA2 genes in breast cancer patients, including both small mutations and large genomic rearrangements (LGRs) following the patients in the process of genetic counseling. METHODS: A total of 358 breast cancer patients who visited genetic counseling clinic and screened for BRCA1/2 mutation at the National Cancer Center were included. Among the non-carriers by direct sequencing, a subset of patients who were agreed on participation of the research were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay. Clinico-pathologic characteristics of cancer were evaluated thorough medical record review and characteristics for those who found BRCA mutation through MLPA were described. RESULTS: 53 (14.8%) mutation carriers were identified. The frequency of BRCA small mutations in specific subgroups was as follows: 18.0% of patients with a family history, 12.8% of early-onset breast cancer, and 20.6% of bilateral breast cancer patients. MLPA identified BRCA1 LGRs in 3 (1.5%) out of 204 patients with BRCA1 and BRCA2 small mutation-negative results. Those with LGRs showed higher probabilities of BRCA mutation carriers estimated by risk assessment models and receptor negatives of tumor immunohistochemistry. CONCLUSIONS: The prevalence of BRCA1/2 mutation prevalence in breast cancer patients with family history or personal risk factors were comparable to previous Korean studies. MLPA to screen for mutations in the BRCA1 gene could be recommended for breast cancer patients negative for small mutations. To specify proper targets of MLPA, probabilities of carrying BRCA1/2 mutation and tumor receptor status could be considered. Citation Format: Ji Yeon Sohn, Boyoung Park, Kyong-Ah Yoon, Soo Jin Park, Moo Hyun Lee, Eun Hae Cho, Keun Seok Lee, Myong Cheol Lim, Sun-Young Kong, Eun Sook Lee. Prevalence of BRCA1 and BRCA2 small mutation and large genomic rearrangements in breast cancer patients visiting a genetic counseling clinic. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3474.

PCN299 - The Clinical and Economic Burden of Skeletal Related Events in Austria, Czech Republic, Germany, Greece, Italy, Spain and Switzerland: A Comparison Between the use of Denosumab and Zoledronic acid in Patients With Breast Cancer and Bone Metastases

To estimate the total number of skeletal-related events (SREs) prevented, related hospital burden and direct medical expenditure when denosumab is used instead of zoledronic acid for SRE prevention in seven European countries. A model was developed combining country-specific breast cancer mortality data from the World Health Organization or from local registries, the proportion of metastatic breast cancer patients with bone metastases (BMs) at high risk of developing SREs from published literature, the prevalence of breast cancer with BMs was derived assuming a steady state approach (with incidence equivalent to mortality of metastatic disease), and the average survival for metastatic breast cancer patients from published literature. Annual SRE rates from a European observational retrospective study and the treatment effect observed in a head-to-head clinical trial of denosumab versus zoledronic acid were used to estimate the total number of predicted SREs by treatment option. Country-specific findings from two retrospective studies were used to estimate the total number of hospitalisations, inpatient days and direct medical costs associated with the management of SREs. Across all countries, the estimated prevalence of breast cancer patients with BMs was 87,592 patients: Austria, 3,253; Czech Republic, 3,509; Germany, 37,895; Greece, 4,639; Italy, 27,767; Spain, 7,553; and Switzerland, 2,975. When denosumab was the selected treatment option, 36,324 SREs were estimated to be avoided per year compared with the use of zoledronic acid, which would save 24,110 hospitalisations, 536,551 inpatient days and 206,605,754€ of direct medical costs (2014 costs in €: Austria, 23,890,554; Czech Republic, 5,779,856; Germany, 60,659,628; Greece, 15,941,728; Italy, 39,998,970; Spain, 17,249,548; and Switzerland, 43,085,469). Denosumab’s clinical superiority in the prevention of SREs over zoledronic acid could result in significant savings in the number and duration of hospitalisations, reducing direct medical costs associated with the management of SREs in Europe.

A Cross-sectional Study Examining the Risk Factors Associated with Lymphedema and its Prevalence in Breast Cancer Patients after Level 3 Axillary Lymph Node Dissection

A Cross-sectional Study Examining the Risk Factors Associated with Lymphedema and its Prevalence in Breast Cancer Patients after Level 3 Axillary Lymph Node Dissection

A Cross-Sectional Study Examining the Risk Factors Associated with Lymphedema and its Prevalence in Breast Cancer Patients after Level 3 Axillary Lymph Node Dissection

Objective: To determine the prevalance of lymphedema after breast cancer treatment with level 3 axillary lymph node dissection (ALND) and to evaluate the risk factors which underlie this condition. Material and Methods: A total of 190 women >18-years-old who underwent breast cancer treatment with level 3 ALND >6 months ago were included in this cross-sectional study. The sociodemographic and clinical characteristics of all of the patients were recorded, and all patients were evaluated for lymphedema of the upper extremity by a circumferential measurement method. Results: On examination, 79 (41.5%) women had lymphedema with a mean development time of 12.7±26.62 months. After univariate analysis, the patients’ age, body mass index (BMI), and number of metastatic lymph nodes (LNs) were found to increase the development of lymphedema. In addition, chemotherapy, breast or chest wall radiotherapy, and axillary radiotherapy also played a role. In the multivariate model, BMI (OR=5.491; 95% CI: 1.382-21.82), metastatic LNs (OR=0.314; 95% CI: 0.118-0.839), axillary radiotherapy (OR=15.34; 95% CI: 5.526-42.581), chemotherapy (OR=5.325; 95% CI: 1.48-19.153), and age (OR=1.044; 95% CI: 1.007-1.083) were significantly associated with an increased risk of lymphedema. Conclusion: This study demonstrated that there was a higher lymphedema prevalence ratio of 41.5% in breast cancer patients who underwent level 3 ALND and found that the risk factors for lymphedema development were axillary radiotherapy, chemotherapy, number of metastatic LNs, age, and BMI.

Factors Associated with the Development of Chronic Pain after Surgery for Breast Cancer: A Prospective Cohort from a Tertiary Center in the United States

Chronic pain has been shown to affect up to 60% of patients undergoing surgery for breast cancer. Besides younger age, other risk factors for the development of chronic pain have not been consistent in previous studies. The objective of the current investigation was to detect the prevalence and risk factors for the development of chronic pain after breast cancer surgery by examining a patient population from a tertiary cancer center in the United States. The study was a prospective observational cohort study. Subjects were evaluated at least 6 months after the surgical procedure. Subjects responded to the modified short form Brief pain inventory and the short form McGill pain questionnaire to identify and characterize pain. Demographic, surgery, cancer treatment, and perioperative characteristics were recorded. Propensity matching regression analysis were used to examine risk factors associated with the development of chronic pain. 300 patients were included in the study. 110 reported the presence of chronic pain. Subjects with chronic pain reported median (interquartile range [IQR]) rating of worst pain in the last 24 hours of 4 (2-5) and a median (IQR) rating on average pain in the last 24 hours of 3 (1-4) on a 0-10 numeric rating scale. Independent risk factors associated with the development of chronic pain were age, OR (95% CI) of 0.95 (0.93-0.98) and axillary lymph node dissection, 7.7 (4.3-13.9) but not radiation therapy, 1.05(0.56-1.95). After propensity matching for confounding covariates, radiation was still not associated with the development of chronic pain. Chronic pain after mastectomy continues to have a high prevalence in breast cancer patients. Younger age and axillary lymph node dissection but not radiation therapy are risk factors for the development of chronic pain. Preventive strategies to minimize the development of chronic pain are highly desirable.