Faouzi Azzouz

Predictors of Aromatase Inhibitor Discontinuation as a Result of Treatment-Emergent Symptoms in Early-Stage Breast Cancer

PURPOSE Aromatase inhibitors (AIs) are effective for treatment of hormone receptor-positive breast cancer, but adherence and persistence with therapy are poor. Predictors of treatment discontinuation are not clearly defined. It is unknown whether patients with intolerable toxicity from one AI are able to tolerate another. PATIENTS AND METHODS Women with early-stage breast cancer initiating AI therapy were enrolled onto a multicenter, prospective, open-label randomized trial of exemestane versus letrozole. Patients completed symptom questionnaires at baseline and serially during therapy. Patients who developed AI-associated intolerable symptoms and discontinued treatment were given the option to switch to the other study AI after a 2- to 8-week washout period. RESULTS Of the 503 enrolled women, 32.4% discontinued initial AI therapy within 2 years because of adverse effects; 24.3% discontinued specifically because of musculoskeletal symptoms. Median time to treatment discontinuation as a result of any symptom was 6.1 months (range, 0.1 to 21.2 months) and was significantly shorter in patients randomly assigned to exemestane (hazard ratio [HR], 1.5; 95% CI, 1.1 to 2.1; P = .02). Younger age and taxane-based chemotherapy were associated with higher likelihood of treatment discontinuation (HR, 1.4; 95% CI, 1.02 to 1.9; P = .04; and HR, 1.9; 95% CI, 1.00 to 3.6; P = .048, respectively). Of the 83 patients who chose to switch to the second AI, 38.6% continued the alternate AI for a median of 13.7 months. CONCLUSION Premature discontinuation of initial AI therapy as a result of symptoms is common, although more than one third of patients may be able to tolerate a different AI medication. Additional research is needed to identify predictive tools and interventions for AI-associated treatment-emergent symptoms.

Variation in polyp detection rates at screening colonoscopy

BACKGROUND Variation in polyp detection among endoscopists has been used to justify the need for establishing quality standards for colonoscopy performance. OBJECTIVE To measure variation in polyp detection rates (PDRs) among endoscopists who perform screening colonoscopy and to identify associated factors. DESIGN Cross-sectional analysis of summary-level data. SETTING Endoscopy practices in central Indiana. SUBJECTS Twenty-five endoscopists and their patients. MAIN OUTCOME MEASUREMENTS Mean procedure time (MPT); proportions of patients with any polyp, any adenoma, any polyp > or =1.0 cm, and multiple adenomas; and variation in PDRs and identification of outliers. Multiple linear regression analysis identified factors that accounted for the variation in PDRs. RESULTS A total of 2664 screening colonoscopies (1108 women and 1556 men) were performed. The mean patient age was 59 years; the mean proportion of women was 42%; the MPT was 17.1 minutes. Adenoma detection rates ranged from 7% to 44% (P < .001) and from 0% to 13% for large polyps, which was not statistically significant (P = .07). For all polyp categories, only 1 to 3 high outlier endoscopists (ie, higher than mean PDRs) were identified. Models that included the number of procedures, mean age, percentage of women, and MPT accounted for 36% to 56% of the variation in PDRs. In all models, only MPT was significantly associated with PDRs. LIMITATIONS Whether each endoscopists cohort was at comparable risk for colorectal neoplasia was uncertain. In comparison with individual-level data, analysis of summary-level data is limited. CONCLUSIONS PDRs vary widely among endoscopists, although only a few (high) outliers were identified. Variation in PDRs was associated only with MPT. Further research is needed to determine the clinical importance of and reasons for this variation.

Improving the quality of life of patients with prostate carcinoma: a randomized trial testing the efficacy of a nurse-driven intervention.

Treatments for clinically localized prostate carcinoma are accompanied by sexual, urinary, and bowel dysfunction and other sequelae that can result in significant distress and reduced well being. Methods capable of improving quality of life are needed that can be integrated into clinical practice. To address this need, a nurse‐driven, cancer care intervention was developed and tested.

A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders.

CONTEXT The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy. OBJECTIVE To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects. DESIGN A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical characteristics following best-estimate procedures. SETTING Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009. PARTICIPANTS Offspring aged 12 to 21 years in families with a proband with BP (n = 141, designated as cases) and similarly aged offspring of control parents (n = 91). MAIN OUTCOME MEASURE Lifetime DSM-IV diagnosis of a major affective disorder (BP type I; schizoaffective disorder, bipolar type; BP type II; or major depression). RESULTS At a mean age of 17 years, cases showed a 23.4% lifetime prevalence of major affective disorders compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in controls (adjusted P = .007). No significant difference was seen in the prevalence of other affective, anxiety, disruptive behavior, or substance use disorders. Among case subjects manifesting major affective disorders (n = 33), there was an increased risk of anxiety and externalizing disorders compared with cases without mood disorder. In cases but not controls, a childhood diagnosis of an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of major affective disorders. CONCLUSIONS Childhood anxiety and externalizing diagnoses predict major affective illness in adolescent offspring in families with probands with BP.

A cognitive behavioral intervention for symptom management in patients with advanced cancer.

PURPOSE/OBJECTIVES To evaluate the effectiveness of a cognitive behavioral intervention in decreasing symptom severity in patients with advanced cancer undergoing chemotherapy. DESIGN Prospective, randomized clinical trial based on cognitive behavioral theory. SETTING Six urban cancer centers in the midwestern United States. SAMPLE 124 patients 21 years of age or older were recruited and randomized to receive conventional care or conventional care and an intervention. Participants were newly diagnosed with stage III, stage IV, or recurrent cancer (solid tumor or non-Hodgkin lymphoma), undergoing chemotherapy, cognitively intact, and able to read and speak English. METHODS Data were gathered via telephone interviews at baseline and 10 and 20 weeks after randomization. Nurses with experience in oncology delivered a five-contact, eight-week intervention aimed at teaching patients problem-solving techniques to affect symptom severity. MAIN RESEARCH VARIABLES Gender, site of cancer, age, symptom severity and depressive symptoms at baseline, group (i.e., experimental versus control), and total symptom severity. FINDINGS Patients in the experimental group and those with lower symptom severity at baseline had significantly lower symptom severity at 10 and 20 weeks; the experimental difference at 20 weeks occurred primarily in those 60 years of age and younger. Depressive symptoms at baseline predicted symptom severity at 20 weeks; however, age, gender, and site of cancer did not affect symptom severity at either time point. CONCLUSIONS A cognitive behavioral intervention to teach problem-solving skills can be effective for patient symptom self-management during and following an intervention. IMPLICATIONS FOR NURSING Problem-solving strategies should be included in educational programs for patients with advanced cancer, particularly those 60 years of age and younger.

Accuracy of subjective hot flush reports compared with continuous sternal skin conductance monitoring

OBJECTIVE: To compare 2 subjective and 1 objective method for assessing hot flush frequency: prospective paper hot flush diaries, prospective electronic event markers, and the Biolog ambulatory sternal skin conductance monitor. METHODS: Fifty-five breast cancer survivors provided two 24-hour periods of data, 1 week apart, at baseline before being randomized for an intervention study. Women completed a prospective paper hot flush diary and pressed an event marker to subjectively record each hot flush they experienced while wearing a sternal skin conductance monitor. RESULTS: Sensitivity was uniformly low (< 50%) for both subjective methods at each week. The estimated probability that a woman would record a true monitor-verified hot flush subjectively by diary or event marker was between 36% and 50% of the time if she was awake and between 22% and 42% of the time if she was asleep. Underreporting of diary hot flushes consequently resulted in more than 50% missing severity and bother ratings. Specificity was high (96–98%) for both the diary and event marker, for both weeks, and for both waking and sleeping times. The positive predictive value was low (34–52%), and negative predictive value was high (94–97%). This indicates that, rather than overreporting hot flushes when they did not exist, women tended to underreport hot flushes when they did exist. CONCLUSION: Use of prospective paper hot flush diaries and electronic event markers may seriously underestimate hot flush frequency and result in missed intensity and bother ratings. LEVEL OF EVIDENCE: II-2

Cerebral Palsy After Perinatal Arterial Ischemic Stroke

The frequency of cerebral palsy, degree of disability, and predictors of disability were assessed in children in a perinatal arterial stroke database. Risk factors were assessed at the univariate level using the Pearson χ2 and Fisher exact test and at the multivariate level using logistic regression analysis. Seventy-six of 111 children with perinatal stroke (68%) had cerebral palsy, most commonly hemiplegic (66/76; 87%). Multivariate analysis of the entire cohort showed both delayed presentation (OR,9.96; 95% CI, 3.10-32.02) and male sex (OR, 2.55; 95% CI, 1.03-6.32) were associated with cerebral palsy. In subgroup multivariate analyses: in children with neonatal presentation, bilateral infarcts were associated with triplegia or quadriplegia (OR, 5.33; 95% CI, 1.28-22.27); in children with unilateral middle cerebral artery infarcts, delayed presentation (OR, 10.60; 95% CI, 2.28-72.92) and large-branch infarction (OR, 8.78; 95% CI, 2.18-43.67) were associated with cerebral palsy. These data will aid physicians in planning long-term rehabilitative care for children with perinatal stroke.

Social Support and Symptom Distress in Adolescents/Young Adults With Cancer

The purpose of this secondary analysis was to describe the relationships of friend, family, and health care provider social support to pain, fatigue, depressed mood, and insomnia in adolescents and young adults with cancer using the Adolescent Resilience Model. Specific aims of the study were to describe the relationships of 3 separate sources of perceived support—friends, family, and health care providers to the symptom-related distress of pain, fatigue, depressed mood, and insomnia.

Psychometric Properties of the Herth Hope Index in Adolescents and Young Adults with Cancer

The Herth Hope Index (HHIndex), originally developed for adults, was examined for appropriateness in two studies of adolescents and young adults with cancer—those at various stages of treatment (N = 127) and those newly diagnosed (N = 74). The internal consistency reliability (Cronbach’s alpha) of the index was .84 and .78, respectively, in the two samples. Construct validity was supported by discriminant correlations in the moderate to low range between the HHIndex and measures of uncertainty in illness and symptom distress, and by moderate convergent correlations with measures of resilience (self-esteem, self-confidence, and self-transcendence) and quality of life (index of well-being). A four-step factor analysis procedure was done, and confirmatory factor analysis suggested that a one-factor solution best fit the data in this population. Findings indicate that the HHIndex is a reliable measure of hope in adolescents and young adults with cancer. Evidence of discriminant and convergent validity in measuring hope in adolescents and young adults with cancer was also generated. Further exploration of the HHIndex factor structure in adolescents and young adults is needed.

Music imagery for adults with acute leukemia in protective environments: a feasibility study

BackgroundPatients receiving intensive chemotherapy can experience increased distressed related to both the cancer diagnosis and treatment isolation. If not addressed, distress can lead to anxiety, depression, and post-traumatic stress disorder. The purpose of this study was to determine the feasibility and possible benefits of a music imagery intervention for patients hospitalized in a protective environment for the treatment of acute leukemia or high-grade non-Hodgkin’s lymphoma.Materials and methodsAdults receiving intensive myelosuppressive chemotherapy in a protective environment were randomized to standard care or standard care plus music imagery. The music imagery sessions occurred twice weekly for up to eight sessions. Patients were encouraged to use the music imagery daily.ResultsThe principal criteria of feasibility were rate of consent, rate of completion of scheduled sessions, and rate of questionnaire completion. Forty-nine out of 78 patients consented, a 63% consent rate. Seventy-two percent of all scheduled music imagery sessions were completed. The rate of questionnaire completion was 60% with missing data because of illness severity and early discharge. The principal outcomes of benefit (e.g., efficacy) were positive and negative affects, fatigue, and anxiety. Both groups improved over time on all outcomes (all p < 0.001). However, a subgroup of individuals with low baseline negative affect who received the intervention reported significantly less anxiety at discharge than individuals with low baseline negative affect who did not receive the intervention.ConclusionsMusic imagery is feasible for adults with acute leukemia in protected environments. Patients with lower initial distress may benefit from a music imagery program in terms of reduced anxiety at discharge.