Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse.

Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. Here, we employ single-cell assays for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identify pre-existing and treatment-persistent cell subpopulations that possess regenerative potential when subjected to treatment. We find distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent cells are able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal as yet unrecognized molecular predictors of treatment response. This suggests that the application of single-cell methods with high analytical resolution in pre-clinical models may powerfully inform clinical decision-making.

Physicians' self-assessment of cancer pain treatment skills--more training required.

PURPOSE: Adequate pain control is essential in cancer treatment. We surveyed Finnish physicians' perception on their skills and training needs on palliative pain management. METHODS: A structured questionnaire with multiple choices and open ended questions was used for collecting data in 2006-2008. Of 720 physicians participating, 59 were working in oncology and 661 physicians in internal medicine, geriatrics, and primary health care. RESULTS: The principles of the WHO guidelines of cancer pain management were not well known. Forty-six percent of oncologists and 32% of other physicians (P < 0.0001) knew the analgesic ladder consisting of three steps. Forty-seven percent of oncologists and 61% of other physicians considered pain treatment of cancer patients being well managed in Finland. Only 24% of oncologists and 5% of other physicians considered the education in palliative care being currently at a satisfactory level. Oncologists reported a need of training in interaction and communication skills, ethical questions, and palliative home care. The other physicians expressed the strongest need for training in pain management and palliative care. CONCLUSIONS: To have more confidence in treating cancer, pain physicians would benefit in training and education in palliative care. It should be systematically included both in general and specialist training and continuous medical education.

Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.

Common pattern of language impairment in vascular dementia and in Alzheimer disease.

The authors studied language performance patterns in early stages of vascular dementia and Alzheimer disease. The objective was to clarify to what extent dissolution of language in vascular dementia is similar to that in Alzheimer disease. Both structured language tests (comprehension, repetition, reading, and naming tasks) and nonstructured language tests (object and picture description) were employed. The structured tasks evidenced impairment on complex auditory comprehension and on picture naming for both dementia groups, whereas oral reading and single word repetition did not differentiate the patients from matched control subjects. On the unstructured narrative tasks, both patient groups showed normal fluency, but content analysis revealed that the patients with dementia produced fewer semantic units (themes) than the control subjects. In summary, both patient groups showed impairment, specifically on semantically mediated language tasks. According to the present results, language impairment in vascular dementia resembles that observed in Alzheimer disease. Semantically mediated functions are among the most sensitive language measures in differentiating early stages of both vascular dementia and Alzheimer disease from normal aging.

Prolonged impairment in activities of daily living due to postdural puncture headache after diagnostic lumbar puncture.

To assess the incidence of postdural puncture headache and its effects on patients' activities of daily living, we interviewed 325 adult patients subjected to a diagnostic lumbar puncture during a 1-year period. Two hundred and eighteen (67%) of the subjects replied to the questionnaire; 41 (19%) of these were diagnosed as having suffered a postdural puncture headache. Impairment of the activities of daily living persisting for 1 week or more was experienced by 16 (7%) of the subjects.

Backlash in the treatment of cancer pain: use of opioid analgesics in a Finnish general hospital in 1987, 1991, and 1994.

Finland belongs to the group of countries in which the consumption of strong opioids is low. This seems to reflect the general quality of cancer pain treatment. During the last 10 years, many efforts have been made to improve the treatment of cancer pain in Finland. To assess one parameter of change, the present study compared the quantity of opioid and nonopioid analgesics used in the treatment of terminal cancer pain in a Finnish general hospital in 1987, 1991, and 1994. Specifically, the records of all patients who died of cancer in Kymenlaakso Central Hospital (KCH) in 1991 and in 1994 and during the last 6 months of 1987 were reviewed to acquire information about the use of analgesic medication. The total proportion of cancer patients receiving analgesic medication on a regular basis was 39% in 1987, 63% in 1991, and 52% in 1994. The mean daily dose of strong opioids changed from 24 mg in 1987 to 58 mg in 1991, and to 43 mg in 1994. These data suggest a possible backlash in prescribing practices during recent years. In spite of various efforts to improve the treatment of cancer pain, the medical records demonstrate a decline in prescribing of the drugs needed for this treatment.

Picture naming deficits in vascular dementia and Alzheimer's disease.

Picture naming deficits in Alzheimer's disease (AD) have been extensively studied but less is known about anomia in vascular dementia (VaD). We tested sources of anomia in these two dementia types by administering an extensive naming battery to 10 patients with VaD, 13 patients with probable AD, and 20 healthy age- and education-matched controls. Both dementia groups evidenced a semantic component in their anomia but the semantic deficit was more clearcut in the patients with AD than in the patients with VaD even though the groups were matched on dementia severity. Case-by-case analyses showed considerable performance variability but confirmed that when anomia is present, it commonly has a semantic component in both VaD and AD.

Pain as an early symptom in cancer.

OBJECTIVE: This study investigated the prevalence and causes of pain at the early stages of cancer. DESIGN AND PATIENTS: A total of 378 newly diagnosed (0-6 months from diagnosis) unselected cancer patients were asked to respond to a questionnaire on pain and other symptoms; RESULTS: 240 patients (64%) answered. Of these, 66 patients (28%) reported pain and were examined in the pain clinic. Thirty patients had pain caused by direct tumor growth, and 44 had pain secondary to cancer or its treatment. In 12 of 66 patients, the pain was unrelated to cancer. Fifteen patients had two or more different types of pain simultaneously. CONCLUSION: The results of this study indicate that awareness of pain and its management at early stages of cancer are essential.