Assessing Depressive Symptoms in Patients With Cancer Treated With Interleukin-2: A Comparison of 2 Measures.

BACKGROUND: High-dose interleukin-2 is a therapy available for individuals with renal cell carcinoma; however, it can produce adverse effects, specifically depressive symptoms. There is limited information regarding the trajectory of depressive symptoms and measurement-based care assessment of depressive symptoms. OBJECTIVE: The purpose was to describe the trajectory of depressive symptoms and compare 2 depression measures. METHODS: A descriptive, mixed-method case study approach was used to describe the longitudinal trajectory of depressive symptoms The qualitative assessment included a journal entry and an interview. The quantitative depression symptom severity measures included the 8-item self-report Patient-Reported Outcomes Measurement Information System Depression and the 30-item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C). RESULTS: Ten cases were enrolled. The maximum number of interleukin-2 doses that any patient received within a single hospitalization ranged from 4 to 12. Mean scores on the 8-item Patient-Reported Outcomes Measurement Information System Depression showed no changes in depressive symptoms from pretreatment to posttreatment, nor across hospitalizations. Mean total scores on the IDS-C increased from "normal" to "mild severity" depressive symptom range across all treatment cycles, suggesting transient depressive symptoms within hospitalizations. Qualitative data from the case supported the IDS-C increase, suggesting that the patient developed depressive symptoms pretreatment to posttreatment. CONCLUSIONS: Understanding the trajectory of depressive symptoms allows for the identification of critical time points when depressive symptoms present and change across treatment. It is critical to use measurement-based care using validated measures to assess for the presence and changes in depressive symptoms. IMPLICATIONS FOR PRACTICE: Validated self-report or clinician-rated depression symptom measures should be used to document the presence or absence of depressive symptoms in this population.

Phenotypic heterogeneity of genomic disorders and rare copy-number variants.

BACKGROUND: Some copy-number variants are associated with genomic disorders with extreme phenotypic heterogeneity. The cause of this variation is unknown, which presents challenges in genetic diagnosis, counseling, and management. METHODS: We analyzed the genomes of 2312 children known to carry a copy-number variant associated with intellectual disability and congenital abnormalities, using array comparative genomic hybridization. RESULTS: Among the affected children, 10.1% carried a second large copy-number variant in addition to the primary genetic lesion. We identified seven genomic disorders, each defined by a specific copy-number variant, in which the affected children were more likely to carry multiple copy-number variants than were controls. We found that syndromic disorders could be distinguished from those with extreme phenotypic heterogeneity on the basis of the total number of copy-number variants and whether the variants are inherited or de novo. Children who carried two large copy-number variants of unknown clinical significance were eight times as likely to have developmental delay as were controls (odds ratio, 8.16; 95% confidence interval, 5.33 to 13.07; P=2.11×10(-38)). Among affected children, inherited copy-number variants tended to co-occur with a second-site large copy-number variant (Spearman correlation coefficient, 0.66; P<0.001). Boys were more likely than girls to have disorders of phenotypic heterogeneity (P<0.001), and mothers were more likely than fathers to transmit second-site copy-number variants to their offspring (P=0.02). CONCLUSIONS: Multiple, large copy-number variants, including those of unknown pathogenic significance, compound to result in a severe clinical presentation, and secondary copy-number variants are preferentially transmitted from maternal carriers. (Funded by the Simons Foundation Autism Research Initiative and the National Institutes of Health.).

Repetitive nonsuicidal self-injury as experiential avoidance among a community sample of adolescents.

OBJECTIVE: This study examined the relationship between experiential avoidance, functionally equivalent behaviors, and repetitive nonsuicidal self-injury (NSSI/RNSSI) among adolescents. METHOD: Self-report questionnaires from adolescents (N = 211) from 3 school-based samples were employed to assess three forms of experiential avoidance (thought suppression, alexithymia, and avoidance/cognitive fusion), various aspects of self-mutilating behaviors, and the existence of functionally equivalent behaviors (disordered eating, substance abuse, suicidal ideation/behaviors). RESULTS: Results indicated one third of participants reported a history of NSSI and 16% reported engaging in RNSSI in the past 6 months. Female adolescents were twice as likely as males to report a history of RNSSI. Unwanted inner experiences, thought suppression, and alexithymia differentiated adolescents with a history of NSSI from their counterparts. Functionally equivalent behaviors occurred more frequently among those with a history of NSSI and increased in severity as NSSI increased, particularly suicidal ideation and behaviors. However, results for patterns of avoidance were not as consistent for males as females, which questions the broad application of this model. CONCLUSIONS: NSSI continues to be surprisingly common among adolescents in the community. NSSI, particularly repetitive forms, appears to be strongly related to common forms of experiential avoidance, moreso for female adolescents. Results also illustrate the importance of conceptualizing and treating self-injury as a form of experiential avoidance.

Ethical use of tissue samples in genetic research.

Many centrally based cancer protocols have begun to address the ethical issues concerning tissue banking for genetic research. A multidisciplinary subcommittee of the Madigan Army Medical Center Institutional Review Board was established to determine the scope of the problem and offer a concise, user-friendly policy with guidelines on how to control and monitor the use of stored tissue for future genetic and molecular research. Our institution participates in 69 Southern Oncology Group or National Surgical Adjuvant Breast and Bowel Project protocols and 47 Children's Oncology Group protocols. Of these protocols, 22 of 69 and 36 of 47, respectively, asked for tissue to be stored for future biologic study. Only 4 of 69 and 3 of 47, respectively, deal with specific consent for future genetic/biologic research. The multidisciplinary committee developed a policy that dealt with the following areas: exempt status, waived consent, informed consent, deceased status, family studies, and information flow. An algorithm was created to establish a system of checks and balances concerning privacy, protection and an appeals process.

Pilot evaluation of citalopram for the relief of hot flashes.

Symptoms associated with premature menopause are a significant problem for women with a history of breast cancer who cannot take hormone replacement therapy. Thus, effective nonhormonal alternatives are needed to manage hot flashes, the most prevalent symptom of menopause. Previous studies have defined that venlafaxine, an anti-depressant, is an effective treatment for such hot flashes. Based on suggestive anecdotal information, we set out to evaluate, in a pilot trial, whether the antidepressant citalopram might be a good nonhormonal treatment option to add to our armamentarium for controlling hot flashes. A prospective pilot study was developed in which patients were studied for 5 weeks, with the first week used to establish a baseline, followed by 4 weeks of treatment with citalopram. During the first week of treatment, 10 mg/day of citalopram was taken while 20 mg/day was taken during each of the following three weeks. Hot-flash diaries were completed daily, symptom diaries and quality-of-life items were completed weekly and the Profile of Mood States was completed at baseline and at week 5. Evaluable patients who completed the study had a mean hot-flash frequency reduction of 58% and a mean hot-flash score reduction of 64% from baseline to week 5. The patients finishing the study also reported decreased anger, tension and depression, as well as improved mood. This pilot trial suggests that citalopram may be an effective non-hormonal treatment for hot flashes in women who can tolerate it.

Relationship between the extent of histologic villous mineralization and stillbirth in aneuploid and euploid fetuses.

OBJECTIVE: To describe the relationship between the degree of placental histologic villous mineralization (VM) and stillbirth in aneuploid and euploid fetuses. METHODS: The extent of VM for aneuploid and gestational age-matched euploid placentas was graded semiquantitatively on a 0 to 3 scale based on the number of terminal or stem villi containing mineralizations in forty x10 fields of view. The extent of VM was analyzed in relation to fetal status at delivery (liveborn or stillborn) for both aneuploid and euploid fetuses. RESULTS: For 14 available aneuploid placentas, grade 0 or 1 VM was recorded for seven aneuploid specimens, of which two were stillborn. Grade 2 or 3 VM was recorded for seven aneuploid specimens, of which six were stillborn. Fourteen gestational age-matched euploid placentas served as controls. Grade 0 or 1 VM was observed in nine euploid specimens, of which four were stillborn. Grade 2 or 3 VM was observed in five euploid specimens, of which four were stillborn. For aneuploid fetuses, stillbirth was significantly more frequent with grade 2 or 3 VM compared with grade 0 or 1 VM (chi(2) = 4.667, P <.05). This relationship did not exist for euploid fetuses (chi(2) = 1.659, P >.05). CONCLUSION: Histologic VM is not a universal finding in, or exclusive to, stillbirths. Aneuploid but not euploid stillbirths show increased histologic VM compared with livebirths. This may implicate impaired placental or circulatory function as a mechanism for death in aneuploid fetuses.