A comparison of cognitive function, sleep and activity levels in disease-free breast cancer patients with or without cancer-related fatigue syndrome.

Chronic fatigue is a feature in a subset of women successfully treated for breast cancer but is not well characterised. This study examines differences in objective cognitive function, activity levels and sleep in disease-free women who do and do not meet criteria for cancer-related fatigue syndrome (CRFS)

Development of Prognosis in Palliative care Study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study

OBJECTIVE: To develop a novel prognostic indicator for use in patients with advanced cancer that is significantly better than clinicians' estimates of survival. DESIGN: Prospective multicentre observational cohort study. SETTING: 18 palliative care services in the UK (including hospices, hospital support teams, and community teams). PARTICIPANTS: 1018 patients with locally advanced or metastatic cancer, no longer being treated for cancer, and recently referred to palliative care services. MAIN OUTCOME MEASURES: Performance of a composite model to predict whether patients were likely to survive for "days" (0-13 days), "weeks" (14-55 days), or "months+" (>55 days), compared with actual survival and clinicians' predictions. RESULTS: On multivariate analysis, 11 core variables (pulse rate, general health status, mental test score, performance status, presence of anorexia, presence of any site of metastatic disease, presence of liver metastases, C reactive protein, white blood count, platelet count, and urea) independently predicted both two week and two month survival. Four variables had prognostic significance only for two week survival (dyspnoea, dysphagia, bone metastases, and alanine transaminase), and eight variables had prognostic significance only for two month survival (primary breast cancer, male genital cancer, tiredness, loss of weight, lymphocyte count, neutrophil count, alkaline phosphatase, and albumin). Separate prognostic models were created for patients without (PiPS-A) or with (PiPS-B) blood results. The area under the curve for all models varied between 0.79 and 0.86. Absolute agreement between actual survival and PiPS predictions was 57.3% (after correction for over-optimism). The median survival across the PiPS-A categories was 5, 33, and 92 days and survival across PiPS-B categories was 7, 32, and 100.5 days. All models performed as well as, or better than, clinicians' estimates of survival. CONCLUSIONS: In patients with advanced cancer no longer being treated, a combination of clinical and laboratory variables can reliably predict two week and two month survival

The Prognosis in Palliative care Study II (PiPS2): A prospective observational validation study of a prognostic tool with an embedded qualitative evaluation

BACKGROUND: Prognosis in Palliative care Study (PiPS) models predict survival probabilities in advanced cancer. PiPS-A (clinical observations only) and PiPS-B (additionally requiring blood results) consist of 14- and 56-day models (PiPS-A14; PiPS-A56; PiPS-B14; PiPS-B56) to create survival risk categories: days, weeks, months. The primary aim was to compare PIPS-B risk categories against agreed multi-professional estimates of survival (AMPES) and to validate PiPS-A and PiPS-B. Secondary aims were to assess acceptability of PiPS to patients, caregivers and health professionals (HPs). METHODS AND FINDINGS: A national, multi-centre, prospective, observational, cohort study with nested qualitative sub-study using interviews with patients, caregivers and HPs. Validation study participants were adults with incurable cancer; with or without capacity; recently referred to community, hospital and hospice palliative care services across England and Wales. Sub-study participants were patients, caregivers and HPs. 1833 participants were recruited. PiPS-B risk categories were as accurate as AMPES [PiPS-B accuracy (910/1484; 61%); AMPES (914/1484; 61%); p = 0.851]. PiPS-B14 discrimination (C-statistic 0.837) and PiPS-B56 (0.810) were excellent. PiPS-B14 predictions were too high in the 57-74% risk group (Calibration-in-the-large [CiL] -0.202; Calibration slope [CS] 0.840). PiPS-B56 was well-calibrated (CiL 0.152; CS 0.914). PiPS-A risk categories were less accurate than AMPES (p<0.001). PiPS-A14 (C-statistic 0.825; CiL -0.037; CS 0.981) and PiPS-A56 (C-statistic 0.776; CiL 0.109; CS 0.946) had excellent or reasonably good discrimination and calibration. Interviewed patients (n = 29) and caregivers (n = 20) wanted prognostic information and considered that PiPS may aid communication. HPs (n = 32) found PiPS user-friendly and considered risk categories potentially helpful for decision-making. The need for a blood test for PiPS-B was considered a limitation. CONCLUSIONS: PiPS-B risk categories are as accurate as AMPES made by experienced doctors and nurses. PiPS-A categories are less accurate. Patients, carers and HPs regard PiPS as potentially helpful in clinical practice. STUDY REGISTRATION: ISRCTN13688211

Identification of functional genetic variation in exome sequence analysis

Recent technological advances have allowed us to study individual genomes at a base-pair resolution and have demonstrated that the average exome harbors more than 15,000 genetic variants. However, our ability to understand the biological significance of the identified variants and to connect these observed variants with phenotypes is limited. The first step in this process is to identify genetic variation that is likely to result in changes to protein structure and function, because detailed studies, either population based or functional, for each of the identified variants are not practicable. Therefore algorithms that yield valid predictions of a variant’s functional significance are needed. Over the past decade, several programs have been developed to predict the probability that an observed sequence variant will have a deleterious effect on protein function. These algorithms range from empirical programs that classify using known biochemical properties to statistical algorithms trained using a variety of data sources, including sequence conservation data, biochemical properties, and functional data. Using data from the pilot3 study of the 1000 Genomes Project available through Genetic Analysis Workshop 17, we compared the results of four programs (SIFT, PolyPhen, MAPP, and VarioWatch) used to predict the functional relevance of variants in 101 genes. Analysis was conducted without knowledge of the simulation model. Agreement between programs was modest ranging from 59.4% to 71.4% and only 3.5% of variants were classified as deleterious and 10.9% as tolerated across all four programs

Can the Cancer-related Fatigue Case-definition Criteria Be Applied to Chronic Medical Illness? A Comparison between Breast Cancer and Systemic Sclerosis

OBJECTIVE: Fatigue is a crucial determinant of quality of life across rheumatic diseases, but the lack of agreed-upon standards for identifying clinically significant fatigue hinders research and clinical management. Case definition criteria for cancer-related fatigue were proposed for inclusion in the International Classification of Diseases. The objective was to evaluate whether the cancer-related fatigue case definition performed equivalently in women with breast cancer and systemic sclerosis (SSc) and could be used to identify patients with chronic illness-related fatigue. METHODS: The cancer-related fatigue interview (case definition criteria met if ≥ 5 of 9 fatigue-related symptoms present with functional impairment) was completed by 291 women with SSc and 278 women successfully treated for breast cancer. Differential item functioning was assessed with the multiple indicator multiple cause model. RESULTS: Items 3 (concentration) and 10 (short-term memory) were endorsed significantly less often by women with SSc compared with cancer, controlling for responses on other items. Omitting these 2 items from the case definition and requiring 4 out of the 7 remaining symptoms resulted in a similar overall prevalence of cancer-related fatigue in the cancer sample compared with the original criteria (37.4% vs 37.8%, respectively), with 97.5% of patients diagnosed identically with both definitions. Prevalence of chronic illness-related fatigue was 36.1% in SSc using 4 of 7 symptoms. CONCLUSION: The cancer-related fatigue criteria can be used equivalently to identify patients with chronic illness-related fatigue when 2 cognitive fatigue symptoms are omitted. Harmonized definitions and measurement of clinically significant fatigue will advance research and clinical management of fatigue in rheumatic diseases and other conditions

Cancer Trajectories at the End of Life: is there an effect of age and gender?

<p>Abstract</p> <p>Background</p> <p>Few empirical data show the pattern of functional decline at the end of life for cancer patients, especially among older patients.</p> <p>Methods</p> <p>In a mortality follow-back survey (the Italian Survey of the Dying of Cancer – ISDOC) a random sample of 1,271 lay caregivers were interviewed, at a mean of 234 days after bereavement. The main outcome was number of days before death when the patient experienced a permanent functional decline.</p> <p>Results</p> <p>1,249 (98%) caregivers answered the question about patient's function. The probability to be free from a functional disability was high (94%) 52 weeks before death, but was lower for older age groups (15% for those aged 85 or more) and women (8%). It remained stable until 18 weeks before death, then fell to 63% at 12 weeks and 49% at 6 weeks before death (among those aged 85 or more the figures were 50% and 41%). The pattern was consistent across sub-groups, except for patients affected by Central Nervous System tumors who experienced a longer, slower functional decline.</p> <p>Conclusion</p> <p>This study provides empirical support for the declining trajectory in cancer, and suggests that the decline commences at around 12 weeks in all age groups, even among patients over 85 years.</p

The effects of the Islamic revolution and the gulf war on Iran's economy

The Islamic revolution, followed by the eight-year Gulf war, has caused severe disruption and extensive changes in the structure of the Iranian economy. This thesis is concerned with an analytical study of Iran’s economy In the period from the Shah's western-style modernisation to the Islamic revolution and the war with Iraq. Thus, the thesis provides first, an overview of the economic development and industrialisation activity under the Shah, which glides a yardstick for understanding the post-revolutionary economy. Secondly, the thesis examines the concept of Islamic economics as articulated by the prominent contemporary Shi'i figures that continue to influence the post-revolutionary economic policies. Thirdly, the major part of the thesis devotes considerable attention to the study and evaluation of the post-revolutionary economy, focusing on agriculture, industry, foreign and domestic trade. Islamic balancing, public finance, the oil sector and the oil war. The latter was a determining factor in the continuation of the Gulf war. The appraisal and the overall picture of the post-revolutionary economy makes bleak reading. The negative Impact of the revolution and the war has left Iran with a shattered infrastructure and a moribund industrial base. Unprecedented destruction of wealth, both in human and non-human terms, has further exacerbated the pre-revolutionary economic problems. The politico-religious government has not been able to address the country's economic Ills effectively, partly owing to self -imposed constraints. A lack of active and structured economic policies has adversely affected all sectors of the economy, in particular, agriculture. While facing the daunting task of post-war reconstruction, Iran, more than ever before, is dependent on trading oil in exchange for basic commodities and consumer goods

Does training with amplitude modulated tones affect tone-vocoded speech perception?

Temporal-envelope cues are essential for successful speech perception. We asked here whether training on stimuli containing temporal-envelope cues without speech content can improve the perception of spectrally-degraded (vocoded) speech in which the temporal-envelope (but not the temporal fine structure) is mainly preserved. Two groups of listeners were trained on different amplitude-modulation (AM) based tasks, either AM detection or AM-rate discrimination (21 blocks of 60 trials during two days, 1260 trials; frequency range: 4Hz, 8Hz, and 16Hz), while an additional control group did not undertake any training. Consonant identification in vocoded vowel-consonant-vowel stimuli was tested before and after training on the AM tasks (or at an equivalent time interval for the control group). Following training, only the trained groups showed a significant improvement in the perception of vocoded speech, but the improvement did not significantly differ from that observed for controls. Thus, we do not find convincing evidence that this amount of training with temporal-envelope cues without speech content provide significant benefit for vocoded speech intelligibility. Alternative training regimens using vocoded speech along the linguistic hierarchy should be explored

Patients with advanced cancer and depression report a significantly higher symptom burden than non-depressed patients

OBJECTIVE: Clinical observations indicate that patients with advanced cancer and depression report higher symptom burden than nondepressed patients. This is rarely examined empirically. Study aim was to investigate the association between self-reported depression disorder (DD) and symptoms in patients with advanced cancer controlled for prognostic factors. METHOD: The sample included 935 patients, mean age 62, 52% males, from an international multicentre observational study (European Palliative Care Research Collaborative - Computerised Symptom Assessment and Classification of Pain, Depression and Physical Function). DD was assessed by the Patient Health Questionnaire-9 and scored with Diagnostic and Statistical Manual of Mental Disorder-5 algorithm for major depressive disorder, excluding somatic symptoms. Symptom burden was assessed by summing scores on somatic Edmonton Symptom Assessment Scale (ESAS) symptoms, excluding depression, anxiety, and well-being. Item-by-item scores and symptom burden of those with and without DD were compared using nonparametric Mann-Whitney U tests. The relative importance of sociodemographic, medical, and prognostic factors and DD in predicting symptom burden was assessed by hierarchical, multiple regression analyses. Result Patients with DD reported significantly higher scores on ESAS items and a twofold higher symptom burden compared with those without. Factors associated with higher symptom burden were as follows. DIAGNOSIS: lung (β = 0.15, p < 0.001) or breast cancer (β = 0.08, p < 0.05); poorer prognosis: high C-reactive protein (β = 0.08, p < 0.05), lower Karnofsky Performance Status (β = -0.14, p < 0.001), and greater weight loss (β = -0.15, p < 0.001); taking opioids (β = 0.11, p < 0.01); and having DD (β = 0.23, p < 0.001). The full model explained 18% of the variance in symptom burden. DD explained 4.4% over and above that explained by all the other variables. Significance of results Depression in patients with advanced cancer is associated with higher symptom burden. These results encourage improved routines for identifying and treating those suffering from depression