A Multicenter Randomized Controlled Trial of Intensive Group Therapy for Tobacco Treatment in HIV-Infected Cigarette Smokers.

BACKGROUND: Tobacco use has emerged as the leading killer of persons living with HIV (PLWH) in the United States. Little is known about the efficacy of tobacco treatment strategies in PLWH. DESIGN: Randomized controlled trial comparing Positively Smoke Free (PSF), an intensive group therapy intervention targeting HIV-infected smokers, to brief advice to quit. All participants were offered a 12-week supply of nicotine patches. METHODS: A cohort of 450 PLWH smokers, recruited from HIV-care centers in the Bronx, New York, and Washington, DC, were randomized 1:1 into the PSF or brief advice to quit conditions. PSF is an 8-session program tailored to address the needs and concerns of HIV-infected smokers and delivered by a trained smoking cessation counselor and PLWH ex-smoker peer pair. The primary outcome was biochemically confirmed, 7-day point-prevalence abstinence at 6 months. RESULTS: In the intention to treat analysis, PSF condition subjects had nearly double the quit rate of controls, 13% vs. 6.6% [odds ratio = 2.10 (95% confidence interval = 1.10 to 4.14), P = 0.04], at 3 months, but no significant difference in abstinence was observed at 6 months. PSF participants exhibited lower nicotine dependence and higher self-efficacy to resist smoking temptations at both 3 and 6 months compared with controls. Lower educational attainment, current cocaine use, past use of nicotine patches, and higher distress tolerance were significant predictors of continued smoking at 6 months. CONCLUSIONS: These findings suggest a role for group therapy among tobacco treatments for PLWH smokers, but strategies to augment the durability of early effects are needed.

Gender Differences among Smokers Living with HIV.

Tobacco use has emerged as a leading cause of death among persons living with HIV (PLWH) who smoke cigarettes. In contrast to the general population where smoking prevalence in men exceeds that in women, large surveys have shown similar smoking rates among male and female PLWH. There are important behavioral and biological differences between male and female smokers, but little is known about the relationships between tobacco use and gender in PLWH. Herein, the authors present a detailed examination of gender differences in smokers living with HIV (N = 267; 54% male, 46% female) recruited in 2 tobacco treatment trials. The authors found higher rates of heavy smoking and other substance use in men. Women were more likely to have used pharmacotherapy during quit attempts. Asthma rates were markedly higher in female smokers. There were no significant differences in a range of psychobehavioral domains or in cessation rates between male and female smokers living with HIV.

Association Between Statin Use and Endometrial Cancer Survival.

OBJECTIVE: To evaluate the association of 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) use and concordant polypharmacy with disease-specific survival from endometrial cancer. METHODS: A retrospective cohort study was conducted of 985 endometrial cancer cases treated from January 1999 through December 2009 at a single institution. Disease-specific survival was estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to study factors associated with survival. All statistical tests were two-sided and performed using Stata. RESULTS: At the time of analysis, 230 patients (22% of evaluable patients) died of disease and median follow-up was 3.28 years. Disease-specific survival was greater (179/220 [81%]) for women with endometrial cancer taking statin therapy at the time of diagnosis and staging compared with women not using statins (423/570 [74%]) (log rank test, P=.03). This association persisted for the subgroup of patients with nonendometrioid endometrial tumors who were statin users (59/87 [68%]) compared with nonusers (93/193 [43%]) (log rank test, P=.02). The relationship remained significant (hazard ratio 0.63, 95% confidence interval [CI] 0.40-0.99) after adjusting for age, clinical stage, radiation, and other factors. Further evaluation of polypharmacy showed an association between concurrent statin and aspirin use with an especially low disease-specific mortality (hazard ratio 0.25, 95% CI 0.09-0.70) relative to those who used neither. CONCLUSION: Statin and aspirin use was associated with improved survival from nonendometrioid endometrial cancer.

Loneliness in HIV-infected smokers.

Loneliness is common in persons living with HIV (PLWH). Lonely people smoke at higher rates than the general population, and loneliness is a likely contributor to the ongoing smoking epidemic among PLWH. We explored factors associated with loneliness in a cohort of 272 PLWH smokers enrolled in two separate tobacco treatment trials. Loneliness was independently associated with lack of a spouse or partner, lower educational attainment, "other or unknown" HIV exposure category, depression, anxiety, recent alcohol consumption, and higher daily cigarette consumption. Referral to group therapy reduced loneliness, whereas referral to an individual web-based tobacco treatment did not.

Do spiritual patients want spiritual interventions?: A qualitative exploration of underserved cancer patients' perspectives on religion and spirituality.

OBJECTIVE: This study examines religion and spirituality among advanced cancer patients from an underserved, ethnically-diverse population by exploring patient conceptualizations of religion and spirituality, the role of religion and spirituality in coping with cancer, and patient interest in spiritual support. METHOD: Qualitative semi-structured interviews were conducted with patients who had participated in a study of a "mind-body" support group for patients with all cancer types. Analysis based on grounded theory was utilized to identify themes and theoretical constructs. RESULTS: With regard to patient conceptualizations of religion and spirituality, three categories emerged: (1) Spirituality is intertwined with organized religion; (2) Religion is one manifestation of the broader construct of spirituality; (3) Religion and spirituality are completely independent, with spirituality being desirable and religion not. Religion and spirituality played a central role in patients' coping with cancer, providing comfort, hope, and meaning. Patients diverged when it came to spiritual support, with some enthusiastic about interventions incorporating their spiritual values and others stating that they already get this support through religious communities. SIGNIFICANCE OF RESULTS: Spirituality plays a central role in the cancer experience of this underserved ethnically-diverse population. While spirituality seems to be a universal concern in advanced cancer patients, the meaning of spirituality differs across individuals, with some equating it with organized religion and others taking a more individualized approach. It is important that psychosocial interventions are developed to address this concern. Future research is needed to further explore the different ways that patients conceptualize spirituality and to develop spiritually-based treatments that are not "one size fits all."

Contemplative self healing in women breast cancer survivors: a pilot study in underserved minority women shows improvement in quality of life and reduced stress.

BACKGROUND: Among underserved, largely minority women who were breast cancer survivors, this pilot project was designed to evaluate the quality of life outcomes of a 20 week Contemplative Self-Healing Program. METHODS: Women previously treated for stage I-III breast cancer were assessed before and after the 20 week program with the FACT-G, FACT-B, FACIT-Spirituality, ECOG, and the Impact of Events Scale. They participated in a 20-week intervention involving guided meditation and cognitive-affective-behavioral learning. RESULTS: With an average age of 63, 62% of the participants were African-American or Latino. With an average of 5.4 years since the diagnosis of breast cancer, 72% had an ECOG performance status of 1. 57% were currently working. Their baseline FACT-G was 80.5 ± 15.1, and their baseline Impact of Events Scale was 26.3 ± 18.9. The within-patient improvement on the FACT-G was 4.6 ± 10.9 (p = .01); in parallel the FACT-B improved by 2.8 ± 12.8 points (p = .03). The Impact of Events Scale improved by 6.6 ± 15.5 points (p = .01). There was significant within-patient improvement on both the avoidance scale (3.8 ± 9.2) and on the intrusion scale (2.9 ± 7.9). Patients who attended more sessions and conducted more home practice had greater improvements in quality of life. CONCLUSION: Persons receiving a 20-session contemplative self healing intervention showed improved quality of life, with a clinically and statistically significant increase in the FACT-G. In addition, this population showed a significant reduction in post-traumatic stress symptoms assessed by the Impact of Events Scale. TRIAL REGISTRATION: Clinical Trials Gov NCT00278837.

Self-efficacy to quit in HIV-infected smokers.

INTRODUCTION: Tobacco use is epidemic among persons living with HIV (PLWH), and several studies have shown self-efficacy (SE) to be a predictor of successful cessation. This study examined sociobehavioral correlates of SE and its predictive value for successful cessation in a group of PLWH smokers. METHODS: The study was conducted on combined patient data from 2 separate randomized controlled trials of tobacco treatment for PLWH smokers. Both trials utilized the same SE scale at the same timepoints, and both had the same smoking cessation endpoint (biochemically confirmed, 7-day, point prevalence abstinence at 3 months). Univariate and multivariate techniques were used to analyze the merged dataset. RESULTS: Baseline SE data were available for 272 subjects. The Self-Efficacy/Temptations Scale-Long Form demonstrated good internal reliability with overall and subscale Cronbach's alpha of .77-.92. Younger age, HIV risk other than injection drug use, recent alcohol use, and higher scores for anxiety, depression, loneliness, and nicotine dependence were all significantly correlated with lower baseline SE. Posttreatment SE was significantly predictive of successful cessation, whereas baseline SE was not. Subjects randomized to the treatment interventions were significantly more likely to quit (AOR = 2.99 [1.26-7.01], p = .01), and logistic regression suggested a possible mediating effect of posttreatment SE. CONCLUSIONS: SE is tightly correlated with a number of modifiable affective and behavioral factors in PLWH smokers, and measures aimed at increasing the SE to abstain in such individuals may enhance the effect of targeted tobacco treatment strategies.

Obesity and age at diagnosis of endometrial cancer.

OBJECTIVE: Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. METHODS: A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. RESULTS: A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, P<.001). This association persisted after multivariable adjustment (R=0.181, P<.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. CONCLUSIONS: Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. LEVEL OF EVIDENCE: II.

Metformin use and endometrial cancer survival.

OBJECTIVE: Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancers using metformin has been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). METHODS: We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. RESULTS: Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio=0.54, 95% CI: 0.30-0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and the presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. CONCLUSION: Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.

Chronic myeloid leukemia (CML): association of treatment satisfaction, negative medication experience and treatment restrictions with health outcomes, from the patient's perspective.

BACKGROUND: The availability of the tyrosine-kinase inhibitor (TKI), imatinib, and later introduction of second generation TKIs, dasatinib and nilotinib, have not only improved clinical outcomes of patients with chronic myeloid leukemia (CML), but also provide multiple therapeutic options for CML patients. Despite the widespread use of these oral therapies, little is known about the impact of different treatment regimens on patient-reported outcomes (PROs) among CML patients. The objective of this study was to assess the impact of patient-reported treatment restrictions and negative medication experiences (NMEs) on satisfaction and other health outcomes among patients with CML treated with oral TKIs. METHODS: Participants recruited from survey panels and patient networks in the United States (US) and Europe completed an online questionnaire. Respondents included adults (≥ 18 years) with chronic-phase CML currently on TKI treatment. Study variables included treatment difficulty (i.e., difficulty in following treatment regimens), CML dietary/dosing requirements, NMEs, and validated PROs assessing treatment satisfaction, health-related quality of life (HRQoL), activity impairment, and non-adherence. Structural equation models assessed associations among variables, controlling for covariates. RESULTS: 303 patients with CML (US n=152; Europe n=151; mean age 51.5 years; 46.2% male) completed the questionnaire. Approximately 30% of patients reported treatment difficulties; treatment difficulty was higher among nilotinib (63.3%) than among dasatinib (2.6%) or imatinib (19.2%) treated patients (p<0.0001). Non-adherence was generally low; however, patients on nilotinib vs. imatinib reported missing doses more often (p<0.05). Treatment satisfaction was associated with significantly increased HRQoL (p<0.05) and lower activity impairment (p<0.01). NMEs were associated with decreased treatment satisfaction (p<0.01) and HRQoL (p<0.05), and greater activity impairment (p<0.01). Higher overall treatment restrictions were associated with greater treatment difficulty (p<0.001), which correlated with non-adherence (p<0.01). CONCLUSIONS: Treatment satisfaction and NMEs are important factors associated with HRQoL among patients with CML. Increased treatment restrictions and associated difficulty may affect adherence with TKIs. Choosing a CML treatment regimen that is simple and conveniently adaptable in patients' normal routine can be an important determinant of HRQoL and adherence.

Efficacy of an emergency department-based multicomponent intervention for smokers with substance use disorders.

The efficacy of brief emergency department (ED)-based interventions for smokers with concurrent alcohol or substance use is unknown. We performed a subgroup analysis of a trial enrolling adult smokers in an urban ED, focusing on subjects who screened positive for alcohol abuse or illicit drug use. Subjects receiving usual care (UC) were given a smoking cessation brochure; those receiving enhanced care (EC) got the brochure, a brief negotiated interview, 6 weeks of nicotine patches, and a telephone call. Follow-up occurred at 3 months. Of 340 subjects in the parent study, 88 (25.9%) reported a substance use disorder. At 3 months, substance users receiving EC were more likely to be tobacco-abstinent than those receiving UC (14.6% versus 0%, p = .015), and to self-identify as nonsmokers (12.5% v. 0%, p = .03). This finding suggests that concurrent alcohol or substance use should not prevent initiation of tobacco dependence treatment in the ED.

A randomized controlled trial of a tailored group smoking cessation intervention for HIV-infected smokers.

BACKGROUND: More than half of the persons living with human immunodeficiency virus (HIV; PLWH) in the US smoke cigarettes, and tobacco use is responsible for considerable morbidity and mortality in this group. Little is known about the efficacy of tobacco treatment strategies in PLWH. DESIGN: Randomized controlled trial comparing Positively Smoke Free (PSF), an intensive group-therapy intervention targeting HIV-infected smokers, to standard care. METHODS: A cohort of 145 PLWH smokers, recruited from an HIV-care center in the Bronx, New York, were randomized 1:1 into the PSF program or standard care. All were offered a 3-month supply of nicotine replacement therapy. PSF is an 8-session program tailored to address the needs and concerns of HIV-infected smokers. The sessions were cofacilitated by a graduate student and an HIV-infected peer. The primary outcome was biochemically confirmed, 7-day point-prevalence abstinence at 3 months. RESULTS: In the intention-to-treat analysis, PSF condition subjects had nearly double the quit rate of controls (19.2% vs. 9.7%, P = 0.11). In the complete case, as-treated analysis, assignment to PSF was associated with increased odds of quitting (odds ratio(adj) 3.55, 95% confidence interval 1.04 to 12.0). Latino ethnicity and lower loneliness score were predictive of abstinence. The subjects in the PSF condition exhibited significant decreases in daily cigarette consumption and significant increases in self-efficacy and in motivation to quit. Attendance of ≥7 sessions was associated with higher quit rates. CONCLUSIONS: These findings suggest a positive effect of PSF on cessation rates in PLWH smokers. Loneliness and self-efficacy are influential factors in the smoking behaviors of PLWH.

Cigarette smoking behaviors and beliefs in persons living with HIV/AIDS.

OBJECTIVE: To measure biopsychosocial domains related to tobacco use in persons living with HIV/AIDS (PLWHAs). METHODS: Cross-sectional interview study of 60 PLWHA smokers randomly selected from an HIV clinic. RESULTS: Participants averaged 14.4 cigarettes daily. Sixty-five percent were moderately or highly nicotine dependent, and most were motivated to quit. Substance use and depression were very common. Most reported that smoking helped them cope with depression, anxiety, and anger. Twenty-seven percent thought (mistakenly) that smoking raised their T-cell counts and/or helped fight infections. Referrals to quitlines or cessation programs were uncommon. CONCLUSIONS: Smoking among PLWHAs is a challenging problem requiring targeted intervention strategies.

Provider beliefs and practices relating to tobacco use in patients living with HIV/AIDS: a national survey.

The entire online HIV Medical Association US registry was invited to complete a questionnaire regarding beliefs and practices related to smoking in persons living with HIV/AIDS (PLWHAs). 363/486 returned completed questionnaires. Respondents from 43 states reported caring for 76,570 PLWHAs. Only 22.9% had ever received formal tobacco treatment training. Respondents generally agreed that smoking is an important issue in PLWHAs, but reported low levels of cessation-promoting activities. Providers with larger patient panels, "primarily HIV" practices, and formal cessation training had higher questionnaire scores, indicating stronger beliefs in the harms of smoking, benefits of quitting, and effectiveness of cessation strategies.

A randomized trial of a multicomponent cessation strategy for emergency department smokers.

OBJECTIVES: The objective was to determine the efficacy of an emergency department (ED)-based smoking cessation intervention. METHODS: This study was a randomized trial conducted from January 2006 to September 2007 at an urban ED that treats 90,000 adults per year. Discharged adults who smoked at least 10 cigarettes per day were randomized to 1) usual care, receiving a smoking cessation brochure; or 2) enhanced care, receiving the brochure, a motivational interview (MI), nicotine patches, and a phone call at 3 days. Interventions were performed by a peer educator trained in tobacco treatment. Blinded follow-up was performed at 3 months. RESULTS: A total of 338 subjects were enrolled, mean (±SD) age was 40.2 (±12.0) years, 51.8% were female, and 56.5% were either self-pay or Medicaid. Demographic and clinical variables were comparable between groups. Enhanced and usual care arms showed similar cessation rates at 3 months (14.7% vs. 13.2%, respectively). The proportion of subjects making a quit attempt (69.2% vs. 66.5%) and decrease in daily cigarette use (five vs. one; all p > 0.05) were also similar. In logistic modeling, factors associated with quitting included any tobacco-related International Classification of Diseases, ninth revision (ICD-9), code for the ED visit (odds ratio [OR]= 3.42, 95% confidence interval [CI] = 1.61 to 7.26) or subject belief that the ED visit was tobacco-related (OR = 2.47, 95% CI = 1.17 to 5.21). Conversely, subjects who reported having a preexisting tobacco-related illness were less likely to quit (OR = 0.22, 95% CI = 0.10 to 0.50). CONCLUSIONS: The primary endpoint was negative, reflecting a higher-than-expected quit rate in the control group. Subjects whose ED visit was tobacco-related, based either on physician diagnosis or subject perception, were more than twice as likely to quit. These data suggest that even low-intensity screening and referral may prompt substantial numbers of ED smokers to quit or attempt to quit.

Career burnout among pediatric oncologists.

BACKGROUND: Burnout is a work-related syndrome consisting of emotional exhaustion, depersonalization, and diminished feelings of personal accomplishment. Physicians who care for patients with life-threatening illnesses are at high risk for developing burnout. This survey evaluates the prevalence of burnout among pediatric oncologists, and assesses risk factors associated with the development of burnout. PROCEDURE: A questionnaire was sent via email to 1,047 practicing pediatric oncologists. The survey included the 22 question Maslach Burnout Inventory (MBI), as well as questions regarding work-related and lifestyle-related factors associated with developing burnout. RESULTS: Four hundred ten pediatric oncologists (40%) responded to the survey. Thirty-eight percent of pediatric oncologists had high levels of burnout on the MBI, while 72% had at least moderate levels of burnout. Women (47% vs. 32%, P < 0.004) and physicians practicing for <10 years (50% vs. 33%, P < 0.004) had significantly higher rates of burnout. Physicians who reported satisfaction with their lives outside of work were less likely to have burnout (odds ratio 0.238, 0.143-0.396, P < 0.001). The availability of a forum for debriefing, and services for physicians affected by burnout were both associated with lower rates of burnout (24% vs. 46%, P < 0.001 and 23% vs. 46%, P < 0.001). Thirty-six percent of respondents reported their institution has a forum for debriefing and 40% of respondents reported their institution has services available for physicians experiencing symptoms of burnout. CONCLUSIONS: Approximately three quarters of pediatric oncologists experience burnout. Further research is needed on the effectiveness of interventions aimed at preventing and treating work-related burnout.

Psychosocial needs of ethnic minority, inner-city, pediatric cancer patients.

PURPOSE: Limited data are available regarding the psychosocial impact of cancer on families of culturally diverse backgrounds living in medically underserved communities. The unique psychosocial needs of families of children with cancer from an ethnically diverse inner-city population is the focus of this study. METHODS: The prevalence of psychosocial needs among a multi-cultural, inner-city sample of children and adolescents with cancer and their parents was assessed using a modified version of the Psychosocial Needs Assessment Survey. All patients were recruited from the Children's Hospital at Montefiore located in Bronx, NY, a designated medically underserved community. RESULTS: Seventy-eight percent of parents reported unmet informational needs. The three most commonly endorsed informational needs by parents and children were regarding dietary management of acute side effects, late effects of having cancer and secondary cancer prevention. Less educated parents reported greater unmet supportive, practical, and spiritual needs than those with more education. Fathers had greater informational and practical needs than mothers and younger parents had more practical needs than older parents. Endorsement of spiritual needs was lower for both children and parents compared with supportive, informational, or practical needs. CONCLUSIONS: Given the high prevalence of reported unmet informational needs, efforts should be made to provide patients and families with education tailored to their informational needs and level of education. This population may benefit from psychoeducational interventions, including community-based informational and peer support groups. Such interventions may augment efforts to lessen health gaps experienced in this population.

Randomized controlled trial of yoga among a multiethnic sample of breast cancer patients: effects on quality of life.

PURPOSE: This study examines the impact of yoga, including physical poses, breathing, and meditation exercises, on quality of life (QOL), fatigue, distressed mood, and spiritual well-being among a multiethnic sample of breast cancer patients. PATIENTS AND METHODS: One hundred twenty-eight patients (42% African American, 31% Hispanic) recruited from an urban cancer center were randomly assigned (2:1 ratio) to a 12-week yoga intervention (n = 84) or a 12-week waitlist control group (n = 44). Changes in QOL (eg, Functional Assessment of Cancer Therapy) from before random assignment (T1) to the 3-month follow-up (T3) were examined; predictors of adherence were also assessed. Nearly half of all patients were receiving medical treatment. RESULTS: Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates (P < .0001). Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL (P < .008), emotional well-being (P < .015), social well-being (P < .004), spiritual well-being (P < .009), and distressed mood (P < .031). Sixty-nine percent of intervention participants attended classes (mean number of classes attended by active class participants = 7.00 +/- 3.80), with lower adherence associated with increased fatigue (P < .001), radiotherapy (P < .0001), younger age (P < .008), and no antiestrogen therapy (P < .02). CONCLUSION: Despite limited adherence, this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors. Among patients not receiving chemotherapy, yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL.