Development of a plain-language guide for discussing breast cancer genetic counseling and testing with patients with limited health literacy.

PURPOSE: Due to limited health literacy and resulting ineffective communication between healthcare professionals and patients, not all eligible patients are offered breast cancer genetic counseling and testing. We aimed to develop a plain-language guide to increase effective communication about genetic counseling and testing with breast cancer patients with limited health literacy. METHODS: Together with oncological healthcare professionals, we drafted a list of jargon words frequently used during (breast) cancer genetic counseling. In a focus group interview with breast cancer counselees with limited health literacy, who had received genetic counseling before, we reformulated these words in plain language. Low-literate individuals, who are not familiar with breast cancer care or genetic counseling, reflected on the draft of the guide. Completeness, acceptability, and perceived usability were tested in an online questionnaire among healthcare professionals. RESULTS: The result is a plain-language guide for genetic counseling and testing with 33 frequently used jargon words and a reformulation of these words in plain language. Acceptability and perceived usefulness of the guide among healthcare professionals (n = 58) were high. CONCLUSION: The plain-language guide provides opportunities to facilitate communication about genetic counseling and testing with patients with limited health literacy and could enhance opportunities for patients to make informed decisions to participate in genetic testing. As the intention from healthcare professionals to use the plain-language guide is high, implementation of the guide in a real-life setting seems promising.

Referral to cancer genetic counseling: do migrant status and patients' educational background matter?

Participation rates in cancer genetic counseling differ among populations, as patients with a lower educational background and migrant patients seem to have poorer access to it. We conducted a study to determine the present-day educational level and migrant status of counselees referred to cancer genetic counseling. We assessed personal characteristics and demographics of 731 newly referred counselees. Descriptive statistics were used to describe these characteristics. The results show that about 40% of the counselees had a high educational level and 89% were Dutch natives. Compared to the Dutch population, we found a significant difference in educational level (p = < 0.01) and migrant status (p = < 0.001). This suggests disparities in cancer genetic counseling and as a result of that, suboptimal care for vulnerable groups. Limited health literacy is likely to pose a particular challenge to cancer genetic counseling for counselees with a lower education or a migrant background. Our study points to considerable scope for improvement in referring vulnerable groups of patients for cancer genetic counseling.

Breast cancer genetic counseling among Dutch patients from Turkish and Moroccan descent: participation determinants and perspectives of patients and healthcare professionals.

Lower participation rates in cancer genetic counseling are observed among different ethnic minorities. The goal of our study is to gain insight into determinants of Turkish and Moroccan patients' participation in breast cancer genetic counseling and DNA testing, from the point of view of healthcare professionals and patients. Questionnaire-based telephone interviews about awareness, perceptions, and reasons for (non-) participation in cancer genetic counseling were conducted with 78 Dutch breast cancer patients from Turkish and Moroccan descent. The interviews were held in Arabic, Berber, Turkish, or Dutch by bilingual research assistants. Additionally, 14 breast cancer patients participated in one of two focus group meetings, and two focus groups were held with 11 healthcare professionals. SPSS and QSR Nvivo were used to examine the quantitative and qualitative data, respectively. Half of the total group of patients (N = 78) and 79% of patients eligible for genetic counseling and testing (N = 33) were aware of the possibility of genetic counseling. The most important determinants for nonparticipation in genetic counseling were experienced difficulties in patient-doctor communication, cultural factors (e.g., social norms), limited health literacy, limited knowledge of the family cancer history, and anxiety about cancer. Religious beliefs and knowing personal and family members' breast cancer risks were motives to obtain genetic counseling. Despite the fact that our study showed that Moroccan and Turkish women reported several personal motives to obtain genetic counseling and testing (GCT), patients and healthcare professionals experience significant language and health literacy difficulties, which make it harder to fully access health care such as genetic counseling and testing.

Active approach for breast cancer genetic counseling during radiotherapy: long-term psychosocial and medical impact.

Genetic counseling and DNA testing (GCT) for breast cancer is increasingly being actively offered to newly diagnosed patients. Little is known about the consequences of such an approach. Therefore, the long-term psychosocial and medical impact of referring breast cancer patients for GCT during an early phase of treatment was studied. A group of 112 breast cancer patients who had been actively offered GCT during adjuvant radiotherapy 7-14 years earlier, returned a self-report questionnaire. We compared their experiences with a group of 127 breast cancer patients who had not met the criteria for GCT. In total, 239 women participated in this long-term follow-up study (72% response rate). Nearly 75% of them had received regular mammography surveillance in the past 3 years. Preventive surgery was reported more often in the counseling group (specifically in the BRCA1/2 mutation carriers). Like the comparative group, only a minority of patients who had received GCT were experiencing high levels of depression (5%) or psychological distress (14%). Breast cancer patients can be actively approached and referred for GCT at the beginning of their radiotherapy without a threat to psychological functioning in the long term.

Who is being referred to cancer genetic counseling? Characteristics of counselees and their referral.

Both physician and patient play a role in the referral process for cancer genetic counseling. Access to such counseling is not optimal because some eligible patients are not being reached by current referral practice. We aimed to identify factors associated with the initiator of referral. During a 7-month period, we recorded demographic characteristics like gender, personal and family history of cancer, ethnicity and eligibility for genetic testing for 406 consecutive counselees using a specially designed questionnaire. Counselees were seen in a university hospital or a community hospital (n = 7) in the Netherlands. We also recorded educational level of each counselee, clinical setting and who initiated referral. Descriptive statistics were used to describe the counselees' general characteristics. We analysed the association between counselee characteristics and the initiator of referral by logistic regression. The majority of counselees seemed to have initiated referral themselves but were indeed eligible for genetic testing. In comparison to the general population in the Netherlands, the counselees had a higher level of education, and there were fewer immigrants, although a higher level of education was not found to be a facilitating factor for referral. The clinical setting where a counselee was seen was associated with initiator of referral, although this relationship was not straightforward. There is a complex interaction between clinical setting and initiator of referral, which warrants further research to elucidate the factors involved in this relationship. Patients seen in cancer genetic counseling do not reflect the general population in terms of educational level or ethnicity.

BRCA testing of breast cancer patients: medical specialists' referral patterns, knowledge and attitudes to genetic testing.

This study explores knowledge about hereditary breast cancer, attitudes about BRCA testing and referral pattern to a family cancer clinic among medical specialists. A total of 92 questionnaires were completed by surgeons (38), medical oncologists (29), radiation oncologists (13) and radiologists (12). The response rate was 51%. A substantial (11-56%) proportion of medical specialists do not refer patients who meet current criteria for BRCA testing. Although questions on inheritance were less well answered, overall knowledge was good. They had a positive attitude, but were concerned about the distress DNA testing might cause to family members. The majority (75%) stated that the best time for referral is after adjuvant therapy or during follow-up, but another important determinant was the patient's wish or need (12%). Further studies are needed to gain insight into the actual referral process, while ongoing training of medical specialists about genetic aspects of breast cancer is also necessary.

Chronic unpredictable stress causes attenuation of serotonin responses in cornu ammonis 1 pyramidal neurons.

In the present study, serotonin (5-HT) responses of hippocampal pyramidal cornu ammonis 1 (CA1) neurons were studied in rats subjected twice daily for 21 days to unpredictable stressors. In hippocampal tissue from thus stressed rats mRNA expression of the 5-HT(1A) receptor and mineralo- as well as glucocorticoid receptors were examined with in situ hybridization. On average, stressed rats displayed increased adrenal weight and attenuated body weight gain compared with controls, supporting that the animals had experienced increased corticosterone levels due to the stress exposure. One day after the last stressor, under conditions that corticosterone levels were low (predominant mineralocorticoid receptor activation), the 5-HT(1A) receptor mediated hyperpolarization of CA1 neurons in response to 10 microM 5-HT was significantly reduced compared with controls. Basal membrane properties of CA1 cells in stressed rats were comparable to those of controls. The 5-HT(1A) receptor mRNA expression was not changed after chronic stress exposure, in any of the hippocampal areas. A small but significant increase in mineralocorticoid receptor mRNA expression was observed after stress in the dentate gyrus, while glucocorticoid receptor expression was unchanged. The data indicate that unpredictable stress exposure for 3 weeks results in suppression of 5-HT(1A) receptor-mediated responses, possibly due to posttranslational modification of the receptor.

Hippocampal and hypothalamic function after chronic stress.

Hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis is often observed in association with and even prior to the onset of major depression. It is presently unclear (1) which molecular and cellular processes contribute to hyperactivity of parvocellular hypothalamic neurons (key regulators of the HPA system) and (2) how HPA axis hyperactivity can lead to attenuation of central serotonergic transmission, a crucial factor in the onset of clinical symptoms. In an attempt to address these issues in an experimental model we used rats exposed to chronic unpredictable stressors, a paradigm causing prolonged HPA-axis hyperactivity. In the first study spontaneous and evoked GABA-mediated input to parvocellular neurons in the paraventricular hypothalamic nucleus was recorded with the whole cell patch-clamp technique. The frequency, but not other properties, of spontaneous GABA-mediated inhibitory postsynaptic currents was reduced after chronic stress, resulting in a reduced amplitude of the evoked GABA current. This potentially would disinhibit parvocellular neurons, provided that other inputs are unchanged. In the second study, responses of CA1 hippocampal neurons to serotonin were recorded with microelectrodes. It appeared that the membrane hyperpolarization caused by activation of serotonin-1A receptors is attenuated in tissue from chronically stressed rats. However, no apparent changes in expression of the serotonin-1A or corticosteroid receptors were observed. This supports the notion that chronic stress eventually results in attenuation of serotonergic responsiveness by a mechanism not involving transcriptional regulation of the receptor. Follow-up studies will need to examine whether treatment with corticosteroid receptor antagonists can normalize the attenuated transmission after chronic stress.

Hippocampal serotonin responses in short and long attack latency mice.

Short and long attack latency mice, which are selected based on their offensive behaviour in a resident-intruder model, differ in their neuroendocrine regulation as well as in aspects of their brain serotonin system. Previous studies showed that the binding capacity and expression of serotonin-1A receptors in the hippocampal CA1 field of long attack latency mice are significantly lower than that found in short attack latency mice. We tested whether the functional responses of CA1 hippocampal cells to serotonin are also reduced in long attack latency mice. To this end, serotonin-induced changes in the membrane potential and input resistance were recorded in vitro with microelectrodes in CA1 pyramidal neurones of long and short attack latency mice. The data show that in long attack latency mice, along with a reduction of the serotonin-1A receptor mRNA expression, the serotonin-induced membrane hyperpolarization and decrease in resistance are attenuated. Basal membrane properties of CA1 neurones in the two.mice lines were comparable. Plasma corticosterone levels in response to a novelty stress were elevated in long compared to short attack latency mice and inversely related to the serotonin-induced responses. We tentatively conclude that long attack latency mice show attenuated functional responses to serotonin in the hippocampus, possibly linked to a chronic perturbation of hormonal levels.

Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights.

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

Microgravity reduces sleep-disordered breathing in humans.

To understand the factors that alter sleep quality in space, we studied the effect of spaceflight on sleep-disordered breathing. We analyzed 77 8-h, full polysomnographic recordings (PSGs) from five healthy subjects before spaceflight, on four occasions per subject during either a 16- or 9-d space shuttle mission and shortly after return to earth. Microgravity was associated with a 55% reduction in the apnea-hypopnea index (AHI), which decreased from a preflight value of 8.3 +/- 1.6 to 3.4 +/- 0.8 events/h inflight. This reduction in AHI was accompanied by a virtual elimination of snoring, which fell from 16.5 +/- 3.0% of total sleep time preflight to 0.7 +/- 0.5% inflight. Electroencephalogram (EEG) arousals also decreased in microgravity (by 19%), and this decrease was almost entirely a consequence of the reduction in respiratory-related arousals, which fell from 5.5 +/- 1.2 arousals/h preflight to 1.8 +/- 0.6 inflight. Postflight there was a return to near or slightly above preflight levels in these variables. We conclude that sleep quality during spaceflight is not degraded by sleep-disordered breathing. This is the first direct demonstration that gravity plays a dominant role in the generation of apneas, hypopneas, and snoring in healthy subjects.

Ageing and the circadian and homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and temperature rhythms.

1. The circadian timing system has been implicated in age-related changes in sleep structure, timing and consolidation in humans. 2. We investigated the circadian regulation of sleep in 13 older men and women and 11 young men by forced desynchrony of polysomnographically recorded sleep episodes (total, 482; 9 h 20 min each) and the circadian rhythms of plasma melatonin and core body temperature. 3. Stage 4 sleep was reduced in older people. Overall levels of rapid eye movement (REM) sleep were not significantly affected by age. The latencies to REM sleep were shorter in older people when sleep coincided with the melatonin rhythm. REM sleep was increased in the first quarter of the sleep episode and the increase of REM sleep in the course of sleep was diminished in older people. 4. Sleep propensity co-varied with the circadian rhythms of body temperature and plasma melatonin in both age groups. Sleep latencies were longest just before the onset of melatonin secretion and short sleep latencies were observed close to the temperature nadir. In older people sleep latencies were longer close to the crest of the melatonin rhythm. 5. In older people sleep duration was reduced at all circadian phases and sleep consolidation deteriorated more rapidly during the course of sleep, especially when the second half of the sleep episode occurred after the crest of the melatonin rhythm. 6. The data demonstrate age-related decrements in sleep consolidation and increased susceptibility to circadian phase misalignment in older people. These changes, and the associated internal phase advance of the propensity to awaken from sleep, appear to be related to the interaction between a reduction in the homeostatic drive for sleep and a reduced strength of the circadian signal promoting sleep in the early morning.

Attenuated amplitude of circadian and sleep-dependent modulation of electroencephalographic sleep spindle characteristics in elderly human subjects.

Sleep spindles are 12-15 Hz electroencephalographic (EEG) oscillations characteristic of non-rapid eye movement (non-REM) sleep. Sleep EEG recordings (total 252 episodes; duration, 9 h 20 min each) distributed across the circadian cycle were analyzed in eight young and eight elderly human subjects. In the young subjects, sleep spindle amplitude, frequency, duration and incidence displayed significant circadian modulation, with the highest spindle incidence and amplitude and the lowest spindle frequency coincident with circadian phases associated with times of habitual sleep. In the elderly subjects, overall amplitude, duration, and incidence were reduced, and only spindle frequency exhibited a detectable circadian modulation. The results demonstrate that a circadian process modulates sleep spindle characteristics and that the strength of this circadian modulation is reduced with age.