A qualitative exploration of the feasibility and acceptability of Meaning-Centered Psychotherapy for Cancer Caregivers.

OBJECTIVE: Caregivers of patients with cancer are at significant risk for existential distress. Such distress negatively impacts caregivers' quality of life and capacity to serve in their role as healthcare proxies, and ultimately, contributes to poor bereavement outcomes. Our team developed Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C), the first targeted psychosocial intervention that directly addresses existential distress in caregivers. METHOD: Nine caregivers of patients with glioblastoma multiforme (GBM) enrolled in a pilot randomized controlled trial evaluating the feasibility, acceptability, and effects of MCP-C, and completed in-depth interviews about their experience in the therapy. One focus group with three MCP-C interventionists was also completed. RESULTS: Four key themes emerged from interviews: (1) MCP-C validated caregivers' experience of caregiving; (2) MCP-C helped participants reframe their "caregiving identity" as a facet of their larger self-identity, by placing caregiving in the context of their life's journey; (3) MCP-C enabled caregivers to find ways to assert their agency through caregiving; and (4) the structure and sequence of sessions made MCP-C accessible and feasible. Feedback from interventionists highlighted several potential manual changes and overall ways in which MCP-C can help facilitate caregivers' openness to discussing death and engaging in advanced care planning discussions with the patient. SIGNIFICANCE OF RESULTS: The overarching goal of MCP-C is to allow caregivers to concurrently experience meaning and suffering; the intervention does not seek to deny the reality of challenges endured by caregivers, but instead to foster a connection to meaning and purpose alongside their suffering. Through in-depth interviews with caregivers and a focus group with MCP interventionists, we have refined and improved our MCP-C manual so that it can most effectively assist caregivers in experiencing meaning and purpose, despite inevitable suffering.

Prognostic awareness and communication preferences among caregivers of patients with malignant glioma.

OBJECTIVE: Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis, yet many families facing malignant glioma have poor prognostic awareness (PA), or the awareness of the patient's incurable disease and shortened life expectancy. Accurate PA is associated with favorable medical outcomes at end-of-life for patients and psychosocial outcomes for informal caregivers (ICs) through bereavement. To date, however, no study has specifically examined PA among MG ICs and the information they receive that shapes their awareness. METHODS: Thirty-two ICs of patients with malignant glioma completed a semi-structured assessment of their awareness of the incurability and life expectancy of their loved one's illness, and to understand their sources of prognostic information and preferences for communication of prognostic information. RESULTS: Twenty-two (69%) ICs had full PA-awareness of the incurability of malignant glioma and accurate estimates of their loved ones' life expectancy. Twenty-three (72%) felt that prognostic information was extremely or very important to possess, and 16 (50%) desired more prognostic information. The majority of ICs received prognostic information from physicians and the Internet. Qualitative analyses revealed that many ICs had difficulty navigating medical encounters in which they concurrently wanted to elicit prognostic information from physicians and protect patients from such information. CONCLUSIONS: Accurate and timely PA is necessary for ICs to serve as critical members of health care teams. Interventions are needed to foster ICs' skills in navigating prognostic communication with patients and health care providers and thereby improve their ability to advocate for their loved one's wishes.

BRAF V600E mutation in Juvenile Xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease.

The family of juvenile xanthogranuloma family neoplasms (JXG) with ERK-pathway mutations are now classified within the "L" (Langerhans) group, which includes Langerhans cell histiocytosis (LCH) and Erdheim Chester disease (ECD). Although the BRAF V600E mutation constitutes the majority of molecular alterations in ECD and LCH, only three reported JXG neoplasms, all in male pediatric patients with localized central nervous system (CNS) involvement, are known to harbor the BRAF mutation. This retrospective case series seeks to redefine the clinicopathologic spectrum of pediatric CNS-JXG family neoplasms in the post-BRAF era, with a revised diagnostic algorithm to include pediatric ECD. Twenty-two CNS-JXG family lesions were retrieved from consult files with 64% (n = 14) having informative BRAF V600E mutational testing (molecular and/or VE1 immunohistochemistry). Of these, 71% (n = 10) were pediatric cases (≤18 years) and half (n = 5) harbored the BRAF V600E mutation. As compared to the BRAF wild-type cohort (WT), the BRAF V600E cohort had a similar mean age at diagnosis [BRAF V600E: 7 years (3-12 y), vs. WT: 7.6 years (1-18 y)] but demonstrated a stronger male/female ratio (BRAF V600E: 4 vs WT: 0.67), and had both more multifocal CNS disease ( BRAFV600E: 80% vs WT: 20%) and systemic disease (BRAF V600E: 40% vs WT: none). Radiographic features of CNS-JXG varied but typically included enhancing CNS mass lesion(s) with associated white matter changes in a subset of BRAF V600E neoplasms. After clinical-radiographic correlation, pediatric ECD was diagnosed in the BRAF V600E cohort. Treatment options varied, including surgical resection, chemotherapy, and targeted therapy with BRAF-inhibitor dabrafenib in one mutated case. BRAF V600E CNS-JXG neoplasms appear associated with male gender and aggressive disease presentation including pediatric ECD. We propose a revised diagnostic algorithm for CNS-JXG that includes an initial morphologic diagnosis with a final integrated diagnosis after clinical-radiographic and molecular correlation, in order to identify cases of pediatric ECD. Future studies with long-term follow-up are required to determine if pediatric BRAF V600E positive CNS-JXG neoplasms are a distinct entity in the L-group histiocytosis category or represent an expanded pediatric spectrum of ECD.

Association of breast cancer and cervical cancer incidence with income and education among whites and blacks.

Data from the 1969-71 Third National Cancer Survey were used to study the association of cancer incidence with income and education as indicated by census tract of residence. Also considered was the effect of adjustment for differences in socioeconomic distribution on the observed excess risk of cervial cancer and lower risk of breast cancer among black women compared to white women. Strong positive associations with both income and education were found, with the rates based on 19,344 breast cancer cases among white women. These observations were noted in most geographic areas studied. The relative risk showed little apparent relationship to age. The rates based on 1,570 cases among black women indicated a strong positive association with education but not with income. Socioeconomic adjustment reduced by almost one-half the black-white difference in breast cancer rates, and education had a stronger effect than did income. White women continued to have a significantly higher rate after such adjustment. Conversely, the incidence of cancer of the cervix showed strong negative associations with each of the two variables among both the 3,802 cases in white women and 954 cases in black women. The negative gradient decreased with age and was apparent in almost all the areas. The excess risk among black women was reduced by two-thirds with socioeconomic adjustment, though the rates remained significantly different. Income had a stronger association than did education with cervical cancer incidence.

Serum micronutrients and the subsequent risk of oral and pharyngeal cancer.

To investigate the relationship between serum micronutrients and the subsequent risk of oral and pharyngeal cancer, a nested case-control study was conducted within a cohort of 25,802 adults in Washington County, MD, whose blood samples were collected in 1974 and stored at -70 degrees C for subsequent assays. The serum levels of nutrients in 28 individuals who developed oral and pharyngeal cancer during 1975 to 1990 were compared with levels in 112 matched controls. Serum levels of all individual carotenoids, particularly beta-carotene, were lower among subjects who developed oral and pharyngeal cancer. The risks of this malignancy decreased substantially with increasing serum level of each individual carotenoid. Persons in the highest tertile of total carotenoids had about one-third the cancer risk as those in the lowest tertile. High serum levels of alpha-tocopherol also were related to a low oral cancer risk in later years, but the risks were elevated significantly with increasing serum levels of gamma-tocopherol and selenium. The findings from this study are consistent with many previous epidemiological investigations of dietary factors for oral and pharyngeal cancer and provide further evidence for the potential role of carotenoids and alpha-tocopherol in the chemoprevention of these malignancies.

The neuropathological findings in irreversible coma. A critque of the "respirator".

1. Postmortem examinations were made on 240 of the 459 cases succumbing (52 percent of the deaths) in the Collaborative Study on Cerebral Survival; the central nervous system was examined in 226 cases. 2. The autopsy was performed on an average of 15.3 hours after death. 3. The mean weight of the brains was 1450 plus or minus 196 grams; the mean weight of the brains of patients on whom resuscitation was stopped, presumably on the basis of "cerebral death," was greater than that of the patients succumbing to cardiac failure. There was a tendency for the brain to increase in weight about 24 hours after the initiation of resuscitative measures. At that time, swelling, discoloration, softening, congestion, and brain herniations also became more prominent. 4. On the basis of a survey of American neuropathologists and the data from this study, the entity commonly termed "respirator brain" may be confirmed. This is a dynamic process that is complicated by concurrent postmortem changes. The respirator brain requires time (approximately 24 hours) for maturation; many patients die a cardiac death during the metamorphosis. If the patient survives for 3 to 4 days, the percentage dying with typical respirator brains is less, and more patients have electroencephalograms with biological activity. 5. The following clinical factors tend to be associated with an increased number of respirator brains: A. Cerebral trauma B. Subnormal body timperature C. Low systolic blood pressure D. Dilated pupils E. Pupils unresponsive to light F. Absence of cephalic reflexes G. Electrocerebral Silence (ECS) 6. The following factors have no apparent effect on the number of respirator brains or tend to be associated with fewer respirator brains: A. Severe drug intoxications B. Small reacting pupils C. Medications D. Presence of spinal reflexes E. Presence of biological activity (BA) in the electroencephalogram 7. A set of common criteria for a respirator brain was used to test the following: A. The local and consultant neuropathologist's diagnosis of respirator brain B. The significance of critical perfusion pressure and critical oxygen tension in respirator brain C. The role of cardiac output in the production of a respirator brain 8. Since a respirator brain is an imperfectly defined entity, an exact correlation with any combination of clinical and EEG findings could not be expected. The use of a standardized measurement of CBF seems a logical and promising confirmatory test for respirator brain.

Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis: a longitudinal study.

OBJECTIVE: To investigate the relationship between magnetic resonance imaging regional lesion burden and cognitive performance in multiple sclerosis (MS) over a 4-year follow-up period. DESIGN: Twenty-eight patients with MS underwent magnetic resonance imaging and took the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis at baseline, 1-year, and 4-year follow-up. An automated 3-dimensional lesion detection method was used to identify MS lesions within anatomical regions on proton density T2-weighted images. The relationship between magnetic resonance imaging regional lesion volumes and the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis results was examined using regression analyses. RESULTS: At all time points, frontal lesion volume represented the greatest proportion of total lesion volume, and the percentage of white matter classified as lesion was also highest in frontal and parietal regions. On neuropsychological testing, when compared with age- and educational level-matched control subjects, patients with MS showed significant impairment on tests of sustained attention, processing speed, and verbal memory (P<.001). Performance on these measures was negatively correlated with MS lesion volume in frontal and parietal regions at baseline, 1-year, and 4-year follow-up (R = -0.55 to -0.73, P<.001). CONCLUSIONS: Multiple sclerosis lesions show a propensity for frontal and parietal white matter. Lesion burden in these areas was strongly associated with performance on tasks requiring sustained complex attention and working verbal memory. This relationship was consistent over a 4-year period, suggesting that disruption of frontoparietal subcortical networks may underlie the pattern of neuropsychological impairment seen in many patients with MS.

Risk factors for oral and pharyngeal cancer in Shanghai, with emphasis on diet.

A population-based case-control study of oral and pharyngeal cancer was conducted in Shanghai, China, from 1988 to 1990, in which 204 (115 male, 89 female) incident cases and 414 (269 male, 145 female) controls were interviewed. Cigarette smoking and alcohol consumption, as well as occupational exposures to asbestos and to petroleum products and the use of kerosene stoves in cooking, were associated with increased risk of oral and pharyngeal cancer. In addition, more cases than controls reported having chronic oral diseases and false teeth. Dietary intakes of 42 major foods and selected salt-preserved or deep-fried foods during the past 10 years, ignoring any recent changes, were measured by a structured quantitative food questionnaire. After adjusting for known etiological factors, risks decreased with increasing intake of fruits, particularly oranges and tangerines, and some vegetables, including dark yellow vegetables and Chinese white radish. Men in the highest tertile of intake of these fruits and vegetables had about 30-50% the risk of those in the lowest tertile, with a less pronounced effect among women. A new finding was an excess risk associated with high consumption of salt-preserved meat and fish. The findings from this study provide further evidence that dietary factors play an important role in the development of oral and pharyngeal cancer.

The relationship of birth weight and intrauterine diagnostic ultrasound exposure.

Imaging with ultrasound is common in obstetric practice. Several laboratory animal studies have shown retardation in fetal growth after experimental ultrasound exposure. This investigation was conducted to determine whether human fetuses exposed to diagnostic ultrasound (sonography) have a greater risk of growth retardation than fetuses not so exposed. This retrospective cohort study compares the birth weights of 1598 exposed and 944 unexposed single live births at the Johns Hopkins Hospital in Baltimore, Maryland during calendar year 1981. Confounding variables, defined as those associated with both exposure status and birth weight outcome, were included in multivariable analysis. Both exposure to more than one ultrasound procedure and first exposure during the third trimester were associated with a reduction in birth weight. However, the most consistent effect associated with birth weight appeared to be the indication for an ultrasound examination. The relationship of ultrasound exposure and reduced birth weight appeared to be due to shared common risk factors, which lead to both exposure and a reduction in birth weight.

Symptom awareness and blood glucose estimation in diabetic adults.

Self-regulation of diabetes depends in part on common-sense models of symptoms and blood glucose fluctuations. Symptom perception and subjective estimation of blood glucose were studied in 52 adult, difficult-to-control, non-insulin-dependent diabetics using a structured interview and laboratory blood-glucose measurement. Most patients believed they could detect hyperglycemia. Symptoms linked by patients to hyperglycemic and hypoglycemic episodes did overlap with symptoms traditionally associated with those states. Some patients may experience dysphoria during glycemic swings to which multiple symptom labels are applicable, although prominent exceptions and idiosyncratic symptoms were evident. Estimation of current blood glucose using an ordinal scale suggested some capacity for discriminating blood glucose levels. Numerical estimates of Chemstrip values were correlated with actual values, but far too inaccurately for purposes of self-regulation. Research is needed to clarify whether subjective symptom perception and blood glucose estimation helps or hinders self-regulation of diabetes.

Race and primary open-angle glaucoma.

A comparison of racial distributions for three groups of patients showed that 115 of 140 patients (81.6%) with open-angle glaucoma, 221 of 392 patients (56.4%) with ocular hypertension, and 1,028 of 2,109 patients (48.7%) in a random sample were black. Average age at diagnosis was significantly (P = .006) higher for whites than for blacks (69.1 years vs 63.7 years). Black patients with primary open-angle glaucoma had a significantly larger mean cup-disk ratio (P less than or equal to .002) and a higher but not significantly higher mean intraocular pressure at the time of diagnosis. Advanced glaucomatous visual field loss was more frequent at the time of diagnosis in blacks (43 of 129 patients or 33.3%) than in whites (five of 27 patients or 18.5%), but this difference was not significant.

Sensory processing, cardiovascular reactivity, and the Type A coronary-prone behavior pattern.

This study investigated the hypothesis that two modes of sensory processing known to elicit integrated patterns of cardiovascular reactivity will arouse exaggerated responses in Type A coronary-prone individuals. 15 Type A and 10 Type B male college students performed on two tasks calling for sensory intake and sensory rejection, respectively, while being monitored for heart rate, blood pressure, and vasomotor response. Contrary to prediction, the tasks failed to differentiate the groups, although each task appeared to elicit the expected pattern of cardiovascular response across groups. It is suggested that sensory processing tasks per se may be insufficiently challenging to elicit the characteristic hyperresponsivity of the Type A.

Decision-making ability and advance directive preferences in nursing home patients and proxies.

We studied 39 nursing home patients and proxies to assess their decision-making capability and preferences regarding advance directives (ADs) or "living wills." Most patients willingly stated preferences; over half opted to forego burdensome measures when death appeared imminent. Patients perceived as decisionally capable were more likely to forego life-sustaining measures than those of questionable capability. The vast majority of proxies disapproved of using life-sustaining measures, even in some cases with limited knowledge of patients' preferences.

A cohort mortality study of painters and allied tradesmen.

A cohort study was conducted of the membership of a large international union of painters and allied tradesmen. The union membership consisted of both painters and associated trades such as glaziers and tile and carpet layers. The study examined the mortality experience of 57 175 current and former union members in four states (California, Missouri, New York, and Texas) in the United States (US) from 1975 through 1979. No excess mortality was observed for the total union membership when compared to that of all US white males. When the study population was subdivided by the trade affiliation, members of locals comprised primarily of painters exhibited a significant elevation in mortality from all malignant neoplasms, lung cancer, and stomach cancer, compared to all US white males. To reduce the impact of potential nonoccupational differences between the study population and all US white males, the data were also analyzed using the entire cohort as the standardization population. Significant elevations continued to be observed for all malignant neoplasms and lung cancer among the membership of painting locals compared to other locals. In addition there was a statistically significant difference in mortality from leukemia and cancer of the bladder observed between the groups.

Estimating the prevalence of depression in family practice using variant methods.

Prevalence estimates for depression in primary care vary depending on diagnostic methods and classification criteria. The present study assessed the prevalence of depression in new, female, family practice patients using self-report and office visit data. Psychological and somatic symptoms and physician interventions were used to create classification criteria. Prevalence was higher by self-report than by physician assessment. The single checklist item "depression" appeared to yield a valid prevalence estimate. Agreement between self-report and physician recognition was low. Prevalence estimates were enhanced when single-visit patients were excluded. The findings suggest that patients who report depression by questionnaire may differ from those admitting depression to physicians; therefore, patient and physician characteristics are likely to contribute to the underrecognition of depression in primary care.

Relationship of fMRI activation to clinical trial memory measures in Alzheimer disease.

BACKGROUND: Functional MRI (fMRI) has shown promise as a tool to characterize altered brain function in Alzheimer disease (AD) and for use in proof of concept clinical trials. FMRI studies of subjects with AD have demonstrated altered hippocampal and neocortical activation while encoding novel stimuli compared to older controls. However, the relationship between fMRI activation and performance on standardized clinical trial memory measures has not been fully investigated. OBJECTIVE: To determine whether patterns of activation during an associative-memory fMRI paradigm correlate with performance on memory measures used in AD clinical trials. METHODS: Twenty-nine subjects with AD underwent neuropsychological testing, including the AD Assessment Scale (ADAS-Cog), and an associative-encoding fMRI paradigm. Scores were entered as regressors in SPM2 analyses of the differential fMRI activation to novel-vs-repeated (NvR) stimuli. To account for cerebral atrophy, native-space structure-function analyses were performed with subjects' high-resolution structural images. RESULTS: Performance on the ADAS-Cog verbal memory component, and the ADAS-Cog total score, correlated with NvR activation in left superior temporal (p = 0.0003; r = -0.51) and left prefrontal (p = 0.00001; r = -0.63) cortices. In a subgroup with more extensive neuropsychological testing (n = 14), performance on the Free and Cued Selective Reminding Test was correlated with activation in these same regions. fMRI activation remained correlated with performance even when accounting for atrophy. CONCLUSIONS: The relationship between functional MRI (fMRI) activation and standardized memory measures supports the potential use of fMRI to investigate regional mechanisms of treatment response in clinical trials of novel therapies for Alzheimer disease. .