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.

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.

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.

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. .

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.

Prospective study of occupational asthma to laboratory animal allergens: stability of airway responsiveness to methacholine challenge for one year.

The stability of airway hyperresponsiveness was studied in a group of 178 young adults working with laboratory animals. At the time of their entry into the study, 132 of 178 subjects (74%) had less than 20% response to the inhalation of 25 mg/ml methacholine, whereas 26 (15%) had a methacholine dose causing a 20% fall in forced expiratory volume in 1 second after fewer than 80 breath units. The distribution of methacholine responsiveness did not differ at 6 months and 1 year; 155 of 178 volunteers (90.4%) responded during the repeated challenges to doses within one dilution of their results at entry. One hundred forty-one subjects were consistently unreactive during the year, and 17 were consistently reactive. Approximately equal numbers gained and lost reactivity. Those with consistently positive responses to methacholine were more likely to have skin test reactivity and chest symptoms. The presence of consistent chest symptoms was loosely associated with consistent methacholine responsiveness; 55% of those with consistent hyperresponsive airways had symptoms, and 24% of those who consistently had symptoms had hyperresponsive airways. We concluded that the methacholine response is relatively stable during the course of a year in laboratory animal workers who remain at their jobs and that the presence of a positive skin test response to laboratory animals or of chest symptoms does not change the pattern of stable responsiveness.

Comparative epidemiology of selected midline congenital abnormalities.

We present comparative epidemiologic characteristics of five congenital abnormalities that have been suggested to result from midline abnormal developmental disturbances: esophageal atresia with or without tracheoesophageal fistula (EA/TEF), imperforate anus with or without fistula (IA/F), omphalocele (OM), bladder exstrophy (BE), and diaphragmatic hernia (DH). The purpose was to assess the extent of epidemiologic similarities among these five defects. Data were collected as part of a population-based case-control study of infants with these defects born to mothers residing in Maryland, Washington, D.C., or Northern Virginia from 1980 through 1987. The estimated annual birth prevalences (per 10,000 live births) and 95% confidence intervals (CI) of these five defects were 0.40 (0.26-0.61) for BE, 1.34 (1.08-1.67) for OM, 1.59 (1.29-1.95) for DH, 2.11 (1.76-2.53) for EA/TEF, and 2.97 (2.55-3.46) for IA/F. The birth prevalence of IA/F and DH increased between 1980 and 1987. In contrast to the other four defects, DH showed a significant male preponderance (rate ratio 1.57, 95% CI 1.03-2.47), a significant white excess (rate ratio white:other, 1.56, 95% CI 1.00-2.48), and a lower proportion of multiple associated defects (30% vs. 46-61%). We concluded from this study that the descriptive epidemiology of diaphragmatic hernia is different from that of the other four defects. This finding may imply differences in etiologic and pathogenetic mechanisms underlying DH.

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.

Characteristics of asthma mortality and morbidity in African-Americans.

The percent rise in the number of asthma deaths was analyzed using data from the National Center of Health Statistics and compared for African-Americans and Caucasians. The rate of increase for African-Americans in the period 1979-1983 was nearly twice that of Caucasians, and the difference among genders for Caucasians was significantly higher for females. In Baltimore a high percentage (29%) of adult asthma patients (86.8% African-American) seen in an emergency room (ER) and living in the inner city had frequent visits (6 or more annually) to the ER. One-third of the patients used the ER exclusively for asthma management, and 39% delayed for at least 48 hr after onset of symptoms before seeking medical assistance. One-fourth had daily symptoms, and 11% of those regularly employed had missed 10 or more days annually because of asthma. Among the high ER users, 39% required more than one annual hospitalization for management of acute exacerbation of asthma symptoms. Risk factors for mortality and morbidity among inner-city and minority populations as well as potential areas of intervention are discussed.

Risk factors for increased airway responsiveness to methacholine challenge among laboratory animal workers.

As a first step in a prospective study of the incidence of asthma to laboratory animals, a group of 364 adults 18 to 48 yr of age who were beginning employment with laboratory animals were evaluated in terms of their past history, health status, allergy, and airway responsiveness to methacholine. At entry to the study, 269 had previous occupational contact with animals, 109 had chest symptoms in the previous year, 168 had a history of allergic symptoms to laboratory animals (any with asthmatic responses were systematically excluded), and 118 had positive immediate skin tests (29 had positive skin tests to laboratory animals). When defined as a PD20FEV1 of 80 breath units or less, 18.4% of these young adults had methacholine hyperresponsiveness (HRA). Significant risk factors for HRA were found to be younger age, female sex, lower educational level, a history of allergic symptoms to laboratory animals, and a history of chest symptoms. Positive skin tests to laboratory animals were present in 8% of workers; this was not a significant risk factor for HRA although positive skin tests to pollen and household allergens were. Previous work experience was a risk factor, especially among those with allergic symptoms, and a trend toward self-selection was suggested in that the rate of HRA was lowest in workers with more than 2 yr of experience or with two or more previous jobs with laboratory animals.

A population-based case-control study of cancers of the nasal cavity and paranasal sinuses in Shanghai.

A population-based case-control study of cancer of the nasal cavity and sinuses, involving interviews of 60 incident cases and 414 controls, was conducted in Shanghai. Cigarette smoking was associated with a mild elevation in risk of squamous-cell carcinoma but not cancers of other cell types. Occupational exposures to wood and silica dusts and to petroleum products, and the use of wood and straw as cooking fuel, were linked to moderate increases in risk, while 4-fold or greater increases were associated with a history of chronic nasal diseases, including those occurring 10 or more years prior to cancer diagnosis. Dietary analyses revealed a significant protective effect of consumption of allium vegetables, oranges and tangerines, with a 50% reduced risk of nasal cancer among individuals in the highest intake group of these foods. Consumption of salt-preserved vegetables, meat and fish was associated with a significantly increased risk of nasal cancer in a dose-response fashion, with a 5-fold excess observed for the heaviest intake of these salted foods. These findings suggest that dietary factors may contribute to the development of nasal cancer.

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 effect of filtered-coffee consumption on plasma lipid levels. Results of a randomized clinical trial.

OBJECTIVE: --To determine the effect of filtered-coffee consumption on plasma lipoprotein cholesterol levels in healthy men. DESIGN: --Randomized controlled trial with an 8-week washout period followed by an 8-week intervention period during which men were randomly assigned to drink 720 mL/d of caffeinated coffee, 360 mL/d of caffeinated coffee, 720 mL/d of decaffeinated coffee, or no coffee. SETTING: --Outpatient clinical research center in a university medical center. PARTICIPANTS: --One hundred healthy male volunteers. OUTCOME MEASURE: --Changes in plasma lipoprotein cholesterol levels during the intervention period. RESULTS: --Men who consumed 720 mL of caffeinated coffee daily had mean increases in plasma levels of total cholesterol (0.24 mmol/L, P = .001), low-density lipoprotein cholesterol (0.17 mmol/L, P = .04), and high-density lipoprotein cholesterol (0.08 mmol/L, P = .03). No significant changes in these plasma lipoprotein levels occurred in the other groups. Compared with the group who drank no coffee the group who drank 720 mL/d of caffeinated coffee had increases in plasma levels of total cholesterol (0.25 mmol/L, P = .02), low-density lipoprotein cholesterol (0.15 mmol/L, P = .17), and high-density lipoprotein cholesterol (0.09 mmol/L, P = .12) after adjustment for changes in diet. CONCLUSION: --Consumption of 720 mL/d of filtered, caffeinated coffee leads to a statistically significant increase in the plasma level of total cholesterol, which appears to be due to increases of both low-density lipoprotein and high-density lipoprotein cholesterol levels.

Effect of BCG on the risk of leprosy in an endemic area: a case control study.

The effect of BCG on the risk of leprosy was measured using a case-control design in an area endemic for the disease. In this study, 397 newly diagnosed cases and 669 controls matched for age, sex and locality were selected from a defined population. Information on exposure to BCG, contact with another case of leprosy, and relevant socioeconomic variables were obtained from the subjects. Having infectious (multibacillary) and noninfectious (paucibacillary) contacts in the household increased the risk of disease 11.7 times (p less than 0.001) and 2.7 times (p less than 0.001), respectively. Overall, the protection offered by BCG was not significant (odds ratio = 0.8; p = 0.17). However, BCG appeared to increase the risk for indeterminate leprosy (adjusted odds ratio = 2.7; p = 0.09) while protecting against borderline disease (adjusted odds ratio = 0.39; p = 0.03). It is possible that BCG causes a shift in the overall cell-mediated immune response, thus increasing the risk for milder and transient forms of leprosy while protecting against more serious forms. These findings may have important implications for the design and interpretation of vaccine trials. Namely, trials should be designed to measure the protective efficacy of vaccines against the more serious forms of leprosy, which have the greatest public health significance.

Body fat patterning in women with endometrial cancer.

It has long been known that the risks of some cancers, including endometrial, are associated with obesity. Recent evidence suggests that body fat distribution patterns also affect the risk of developing some diseases. A question that remains is whether cancers are associated with specific distributions of body fat. In this study, women with endometrial cancer were compared to community controls of similar age and race. Participants were interviewed and then measured to determine fat distribution patterns defined by the waist-to-hip circumference ratio. Women with upper body fat distribution had a 3.2-fold (95% confidence limits 1.2, 8.9) higher risk of endometrial cancer than women with lower body fat distribution even with correction for age, parity, and smoking. Obese women with an upper body fat pattern had a 5.8-fold (confidence limits 1.7, 19.9) higher risk of endometrial cancer than nonobese/lower body fat patterned women. Obese women who never smoked had a 3.3-fold statistically significant higher risk of endometrial cancer than nonobese women who never smoked. Current smokers had lower risks than their nonsmoking counterparts. The 3-fold increased risk of endometrial cancer associated with upper body fat did not disappear with adjustment for obesity and smoking.

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.

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.

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.

The spectrum of anxiety disorders in family practice.

The spectrum ranges from fearful concerns about illness to clinical anxiety disorders, such as phobias, panic attacks, generalized anxiety, post-traumatic stress disorder and adjustment disorder. Anxiety and fear are often associated with hospitalization, heart disease, insomnia, and somatopsychic syndromes. Determining the cause of the anxiety may help the physician plan the treatment approach. In selected cases, benzodiazepines are useful adjuncts to therapy.

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.