Is there a role for survivorship care plans in advanced cancer?

PURPOSE: The Institute of Medicine (2006) has recommended that cancer survivors completing treatment receive a survivorship care plan (SCP). The survivorship needs in advanced cancer have been overlooked and understudied. The potential role of SCPs for survivors with advanced or metastatic cancer is unknown and was explored in this study. METHODS: We conducted two focus groups of survivors with advanced or metastatic cancer. Participants reviewed a sample JourneyForward™ SCP modified for advanced cancer. Sessions were audiotaped and transcribed; transcripts and field notes were evaluated using inductive content analysis. RESULTS: Sixteen survivors with metastatic cancer participated: 12 (75 %) were female, 15 (94 %) were white, and median age was 66 (range 55-80); 9 participants had breast cancer, 4 colon, 2 prostate, and 1 ovarian cancer. Participants believed that an SCP would be most helpful after initial diagnosis and treatment, but not as helpful once the cancer progressed. They thought a "cancer care plan" focusing solely on the current management would be better to concisely summarize the treatment plan and time frame for the next segment of care for those with advanced cancer. Most participants endorsed the need to have written information to reinforce verbal information received during medical visits since it was difficult to remember information provided. Participants expected their oncologist to assume primary responsibility for coordination of the care plan, but anticipated an important supportive role for primary care providers. To this end, they emphasized the need for better communication between providers. CONCLUSIONS: A cancer care plan developed by the oncologist, similar to an SCP but more focused on current management, may be more useful for survivors with advanced cancer. Exploring this topic in larger groups of more diverse survivors with advanced cancer will help to elucidate the details a written plan of care should contain, and how to promote effective coordination between oncology and primary care providers. IMPLICATIONS FOR CANCER SURVIVORS: There are many transitions of care along the cancer journey. A written plan of care, similar to an SCP, may be useful for survivors with advanced cancer.

Psychiatric and neuropsychological characterization of Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) is a rare, single-gene, malformation syndrome that includes central polydactyly, hypothalamic hamartoma, bifid epiglottis, endocrine dysfunction, and other anomalies. The syndrome has variable clinical manifestations and is inherited in an autosomal dominant pattern. We sought to determine whether psychiatric disorders and/or neuropsychological impairment were characteristic of PHS. We prospectively conducted systematic neuropsychiatric evaluations with 19 PHS subjects ranging in age from 7 to 75 years. The evaluation included detailed clinical interviews, clinician-rated and self-report instruments, and a battery of neuropsychological tests. Seven of 14 adult PHS subjects met diagnostic criteria for at least one DSM-IV Axis I disorder. Three additional subjects demonstrated developmental delays and/or neuropsychological deficits on formal neuropsychological testing. However, we found no characteristic psychiatric phenotype associated with PHS, and the frequency of each of the diagnoses observed in these subjects was not different from that expected in this size sample. The overall frequency of psychiatric findings among all patients with PHS cannot be compared to point prevalence estimates of psychiatric disease in the general population because of biased ascertainment. This limitation is inherent to the study of behavioral phenotypes in rare disorders. The general issue of psychiatric evaluation of rare genetic syndromes is discussed in light of this negative result.

A curriculum for teaching psychiatric research bioethics.

Psychiatric research has received intense ethical scrutiny during the past decade. Changes in how studies are designed, reviewed by ethics boards, conducted, and reported in the literature have created a need for a systematic approach to teaching psychiatric research ethics to clinical researchers in training. The purpose of this article is to describe a model curriculum and comprehensive background reading list for training in psychiatric research bioethics. The curriculum was designed as an interactive seminar in a research fellowship program but can be adapted and incorporated into existing medical school and psychiatry residency training curricula. Participants in the seminar provide formal and informal evaluations of each session and the seminar as a whole. The seminar, now in it's third year, has been regularly attended and highly regarded by the NIMH research fellows who have participated. In response to recommendations by the participants, the content and organization of the seminar has been modified. Clinical research is both scientifically and ethically complex. Our initial experience with a formal curriculum in psychiatric research bioethics suggests that this educational activity has been both meaningful and relevant for psychiatrists training to be clinical investigators.

Neuroimaging in delirium and related conditions.

Delirium is one of the most fascinating and poorly understood syndromes in medicine. To a large extent, attempts to study the pathophysiology of delirium have been hampered by the many different types of delirium and their variable symptom expression. The emergence of sophisticated brain imaging methodologies has made it possible to move beyond diagnostic considerations and investigate the neurobiology of specific symptom clusters observed in delirium and related conditions. In this review, neuroimaging findings of relevance to delirium are interpreted in relation to phenomenologically similar symptom states as well as clinical diagnoses. A promising approach in this regard is to combine neuroimaging techniques with symptom-provoking pharmacologic challenge paradigms. Such symptom-oriented neuroimaging studies hold particular promise for improving our understanding of the pathophysiology of delirium and its treatment.

IRB review of psychiatric medication discontinuation and symptom-provoking studies.

Federal regulations governing human subjects research call for additional protections for the "mentally disabled." However, there is currently no consensus definition of mental disability or guidelines for how these research subjects should be protected. This ambiguity complicates the work of institutional review boards (IRBs) charged with the review and approval of protocols involving psychiatric medication discontinuation and symptom provocation. It is particularly important for these studies to be reviewed within the larger context of the research program in which they are conducted. The author proposes a process for IRB review of these studies, which includes the implementation of additional safeguards for subjects determined by the IRB to be vulnerable. Recommendations also are made for training psychiatric clinical investigators in issues related to research bioethics.

Neuropsychiatric toxicity associated with cytokine therapies.

The cytokines interleukin-2 and interferon-alpha are potent biological agents used to treat malignancy, infectious diseases, and neurodegenerative disorders. While these medications show substantial therapeutic promise, the neuropsychiatric toxicity associated with these agents is often treatment-limiting. The pathophysiology of this toxicity is not well delineated, and adverse effects to the central nervous system are often misdiagnosed by clinicians. This report reviews the preclinical and clinical literature describing the morbidity associated with these agents and suggests appropriate clinical management strategies and future directions for research.

Conditioned immune response to interferon-gamma in humans.

We determined whether a classical conditioning paradigm may be used to condition immunologic responses in normal human subjects receiving an optimal immunostimulating dose of recombinant human interferon-gamma (rhIFN-gamma). We conducted a placebo-controlled, double-blind study of 31 normal volunteers in order to determine whether an initially immune-neutral stimulus, oral propylene glycol (PG), could eventually elicit an immune response as a consequence of its being paired with a known immunostimulatory dose and schedule of rhIFN-gamma. Subjects were randomly assigned to one of three groups: (A) rhIFN-gamma injections paired with PG; (B) normal saline injections paired with PG; (C) rhIFN-gamma injections alone. During the 4-week study, subjects received progressively fewer injections so that, by the final week of the study, no injections were given and groups A and B received only PG. The principal outcome measures were serum concentrations of quinolinic acid (QUIN) and neopterin, two nonspecific but sensitive markers of immune activation, and expression of Fc receptors (CD64) on peripheral blood mononuclear cells. RhIFN-gamma injections produced significant and predictable alterations in each of the measured immune parameters. No group B subject made an immune response. Mean serum QUIN levels were significantly higher at the end of week three for subjects in the experimental condition (group A) than for subjects receiving rhIFN-gamma alone (group C) despite receiving identical doses of rhIFN-gamma. Similarly, the predicted decay in mean serum neopterin levels from the end of week 1 to the end of week 2 was seen in group C but not in group A. The exposure of group A to PG blunted the decline of CD64 expression in week four. The data suggest that the pairing of an unconditioned stimulus (rhIFN-gamma) and a conditioned stimulus (PG) permits the conditioned stimulus alone to prolong a cytokine-induced response in normal humans.

Professional integrity in clinical research.

In response to public concern over abuses in human medical experimentation, the dominant approach to the ethics of clinical research during the past 30 years has been regulation, particularly via institutional review board review and approval of scientific protocols and written consent forms. However, the effectiveness of regulatory mechanisms in ensuring the ethical conduct of clinical research is limited. Little attention has been devoted to the nature and role of professional integrity of physician investigators, a conscientious framework for guiding investigators in the socially important but morally complex activity of clinical research. Professional integrity is vital in forging an ethically sound relationship between investigators and patient volunteers, a relationship that differs in important ways from the patient-physician relationship in standard clinical practice. We examine critically 2 models of the moral identity of physician investigators, the investigator as clinician and the investigator as scientist; in neither of these 2 models can the physician investigator eliminate completely the moral conflicts posed by clinical research. The professional integrity of physician investigators depends on a coherent moral identity that is proper to the enterprise of clinical research. The roles of clinician and scientist must be integrated to manage conscientiously the ethical complexity, ambiguity, and tensions between the potentially competing loyalties of science and care of volunteer patients.

Fluoxetine in the treatment of premenstrual dysphoria.

We performed a double-blind, placebo-controlled, crossover trial of fluoxetine in 17 women with prospectively confirmed PMS who also met criteria for premenstrual dysphoric disorder (PMDD). A subset of 10 women with PMDD and an additional 10 controls participated in a single-dose m-chlorophenylpiperazine (m-CPP) challenge during the follicular and luteal phases of the menstrual cycle. We evaluated the ability of the acute behavioral response to luteal phase m-CPP administration to predict therapeutic response to fluoxetine. compared with baseline, fluoxetine, but not placebo, treatment significantly improved both emotional and physical symptoms. We identified 11 (65%) fluoxetine responders who no longer met diagnostic criteria for PMDD during fluoxetine but remained symptomatic during placebo treatment. In addition, acute symptomatic improvement also occurred following m-CPP administration in 7 of 10 women with PMDD. The small number of m-CPP nonresponders did not respond to fluoxetine either. Our findings confirm that fluoxetine is an effective treatment of PMDD.

Peripheral measures of arginine vasopressin, atrial natriuretic peptide and adrenocorticotropic hormone in premenstrual syndrome.

Because of the unique combination of physical (e.g. bloating, water retention) and psychological (e.g. mood, memory) symptoms associated with premenstrual syndrome (PMS), various hypothalamic and pituitary hormones have been implicated in the pathophysiology of PMS. We measured plasma adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) across the menstrual cycle in 19 women with PMS and 12 normal women. AVP concentrations were lower throughout the menstrual cycle in symptomatic PMS patients compared with PMS patients during asymptomatic cycles and normal women. No differences in ACTH and ANP were observed between patients and controls. However, ACTH and ANP were positively and significantly correlated with each other in women with PMS but not in controls. These findings contribute to a growing list of menstrual cycle-independent findings in women with PMS and suggest that there may be an underlying neurobiological vulnerability that predisposes some women to experience somatic and mood dysregulation in the luteal phase of the menstrual cycle.

Relationship between skeletal muscle intracellular ionized magnesium and measurements of blood magnesium.

The current laboratory approach to assessing magnesium status is based on determining the concentration of total Mg ((Mg)) in serum or plasma. This strategy is problematic in that the amount of Mg in blood is less than 1% of total body Mg and does not accurately reflect (Mg) in other tissues. Furthermore, the (Mg) of blood does not distinguish biologically active, ionized Mg from the bound fraction. The goal of this study was to determine intracellular ionized Mg ((Mg++)i) of skeletal muscle in vivo and to compare results with the (Mg) of blood constituents. (Mg++)i was determined in resting skeletal muscle by using phosphorus 31 magnetic resonance (31P-MR) spectroscopy. (Mg) was measured in serum (S(Mg)), serum ultrafiltrate (UF(Mg)), mononuclear blood cells (MBC(Mg)), and red blood cells (RBC(Mg)) by using atomic absorption spectroscopy or a colorimetric assay. In a sample of 60 healthy adult subjects, skeletal muscle (Mg++)i = 557 +/- 97 mumol/L (mean +/- SD); S(Mg) = 0.78 +/- 0.09 mmol/L; UF(Mg) = 0.60 +/- 0.12 mmol/L; MBC(Mg) = 13.8 +/- 2.3 mmol/L; and, RBC(Mg) = 1.92 +/- 0.33 mmol/L. A significant negative correlation was found between (Mg++)i and S(Mg) (r = -0.43, p < 0.05). S(Mg) was significantly lower (p < 0.05) and (Mg++)i significantly higher (p < 0.05) in women than in men, but neither was related to age. These findings provide new insight into the relationship between blood Mg measures and (Mg++)i of the largest soft tissue mass of the human body.

Skeletal muscle intracellular ionized magnesium measured by 31P-NMR spectroscopy across the menstrual cycle.

OBJECTIVE: The hormonal regulation of magnesium (Mg) metabolism is poorly understood. Preliminary evidence suggests that reproductive hormones may influence Mg concentrations in various tissues. The purpose of this study was to determine if Mg concentrations in blood and muscle are affected by the phase of the menstrual cycle. METHODS: Magnesium measures were obtained from 16 women over the course of one complete menstrual cycle. The principal outcome measure was intracellular ionized Mg ([Mg++]i) in skeletal muscle as measured by 31P nuclear magnetic resonance spectroscopy. Three blood measures (serum, red blood cell, and mononuclear blood cell) of total Mg ([Mg]) were also obtained. RESULTS: Mean Mg concentrations were stable across the menstrual cycle with no evidence of a menstrual cycle phase effect for any of the measures. Furthermore, skeletal muscle [Mg++]i was not correlated with any blood measure of [Mg]. CONCLUSION: These results suggest that physiologic fluctuations in reproductive hormones do not influence either blood [Mg] or skeletal muscle [Mg++]i in healthy, regularly cycling women.

Magnesium measures across the menstrual cycle in premenstrual syndrome.

The purpose of this study was to evaluate blood magnesium (Mg) measures across the menstrual cycle in women with premenstrual syndrome (PMS) and control women. Longitudinal determinations of plasma, red blood cell (RBC) and mononuclear blood cell (MBC) Mg were made in 26 women with prospectively confirmed PMS and in a control group of 19 women. Data were analyzed using analysis of variance with repeated measures and Spearman rank correlations. Significant diagnostic group effects were observed for RBC and MBC Mg concentrations (p < 0.05). These effects reflected lower Mg concentrations in PMS patients at each sampling time. No significant effects were observed for either plasma Mg or MBC Mg content, nor were there significant time by diagnosis effects for any of the measures. Consistent with earlier studies, we found decreased RBC Mg concentrations and additionally observed decreased MBC Mg concentrations in women with PMS. However, neither of these relative deficits were confined to the luteal phase.