Development of the measure of ovarian symptoms and treatment concerns: aiming for optimal measurement of patient-reported symptom benefit with chemotherapy for symptomatic ovarian cancer

OBJECTIVE: The aim of this study was to determine the optimal patient-reported outcome measure (PROM) for assessing symptom benefit in trials of palliative chemotherapy for women with symptomatic ovarian cancer. METHODS: Candidate PROMs were EORTC QLQ-C30 plus ovarian-specific QLQ-OV28, Functional Assessment of Cancer Therapy-Ovarian (FACT-O), FACT Ovarian Symptom Index (FOSI), and gynecologic cancer-specific Symptom Representation Questionnaire. Predefined optimality criteria were inclusion of all symptoms necessary for the specified purpose, recall period covering typical length of palliative chemotherapy, numerical item rating scales, and all necessary symptoms included in a single symptom index. Qualitative and quantitative methods were applied to data from stage 1 of the Gynecologic Cancer Intergroup Symptom Benefit Study to determine the set of necessary symptoms and to objectively assess candidate PROMs against the optimality criteria. RESULTS: Ten necessary symptoms were identified: pain, fatigue, abdominal bloating/discomfort, sleep disturbance, bowel disturbance, nausea and vomiting, shortness of breath, poor appetite, urinary symptoms, and weight changes. Although QLQ-C30 and QLQ-OV28 together cover all these symptoms, they split them into numerous scales, dissipating potential symptom-benefit signal. Conversely, FACT-O does not cover all necessary symptoms and contains many other HRQoL-related items and treatment side effects, diluting potential symptom-benefit signal when summed into scales. Item response scales and composite scoring of all candidate PROMs were suboptimal to our specific purpose. We therefore developed a new PROM, the Measure of Ovarian Symptoms and Treatment (MOST) concerns, to provide optimal measurement for the specified purpose. CONCLUSIONS: This article documents the development of the MOST, a new PROM designed to assess patient-reported benefits and burden as end points in clinical trials of palliative chemotherapy for women with symptomatic ovarian cancer. The validity, reliability, and statistical efficiency of the MOST, relative to the best candidate scales of existing PROMs, will be assessed in the stage 2 of Gynecologic Cancer Intergroup Symptom Benefit Study

Gynecologic oncology patients' satisfaction and symptom severity during palliative chemotherapy

BACKGROUND: Research on quality and satisfaction with care during palliative chemotherapy in oncology patients has been limited. The objective was to assess the association between patient's satisfaction with care and symptom severity and to evaluate test-retest of a satisfaction survey in this study population. METHODS: A prospective cohort of patients with recurrent gynecologic malignancies receiving chemotherapy were enrolled after a diagnosis of recurrent cancer. Patients completed the Quality of End-of-Life care and satisfaction with treatment scale (QUEST) once upon enrollment in an outpatient setting and again a week later. Patients also completed the Mini-Mental Status Exam, the Hospital Anxiety/Depression Scale, a symptom severity scale and a demographic survey. Student's t-test, correlation statistics and percent agreement were used for analysis. RESULTS: Data from 39 patients were analyzed. Mean (SD) quality of care summary score was 41.95 (2.75) for physicians and 42.23 (5.42) for nurses (maximum score was 45; p = 0.76 for difference in score between providers). Mean (SD) satisfaction of care summary score was 29.03 (1.92) for physicians and 29.28 (1.70) for nurses (maximum score was 30; p = 0.49 for difference between providers). Test-retest for 33 patients who completed both QUEST surveys had high percent agreement (74–100%), with the exception of the question regarding the provider arriving late (45 and 53%). There was no correlation between quality and satisfaction of care and symptom severity. Weakness was the most common symptom reported. Symptom severity correlated with depression (r = 0.577 p < 0.01). There was a trend towards a larger proportion of patients reporting pain who had three or more prior chemotherapy regimens (p = 0.075). Prior number of chemotherapy regimens or time since diagnosis was not correlated with symptom severity score. Anxiety and depression were correlated with each other (r = 0.711, p < 0.01). There was no difference in symptom severity score at enrollment between those patients who have since died (n = 19) versus those who are still alive. CONCLUSION: The QUEST Survey has test-retest reliability when used as a written instrument in an outpatient setting. However, there was no correlation between this measure and symptom severity. Patient evaluation of care may be more closely related to the interpersonal aspects of the health care provider relationship than it is to physical symptoms

Opioids Switching with Transdermal Systems in Chronic Cancer Pain

<p>Abstract</p> <p>Background</p> <p>Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy</p> <p>Objective</p> <p>To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment.</p> <p>Methods</p> <p>A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks</p> <p>Results</p> <p>Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 ± 20.5 (mean ± SD) to 3.75 ± 8.06, and 33.8 ± 18.9 to 3.75 ± 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment.</p> <p>Conclusion</p> <p>Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.</p

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Supporting carers to manage pain medication in cancer patients at the end of life: A feasibility trial

Background: Carers of people with advanced cancer play a significant role in managing pain medication, yet they report insufficient information and support to do so confidently and competently. There is limited research evidence on the best ways for clinicians to help carers with medication management. Aims: To develop a pain medicines management intervention (Cancer Carers Medicines Management) for cancer patients’ carers near the end of life and evaluate feasibility and acceptability to nurses and carers. To test the feasibility of trial research procedures and to inform decisions concerning a full-scale randomised controlled trial. Design: Phase I-II clinical trial. A systematic, evidence-informed participatory method was used to develop CCMM: a nurse-delivered structured conversational process. A two-arm, cluster randomised controlled feasibility trial of Cancer Carers Medicines Management was conducted, with an embedded qualitative study to evaluate participants’ experiences of Cancer Carers Medicines Management and trial procedures. Setting: Community settings in two study sites. Participants: Phase I comprises 57 carers, patients and healthcare professionals and Phase II comprises 12 nurses and 15 carers. Results: A novel intervention was developed. Nurses were recruited and randomised. Carer recruitment to the trial was problematic with fewer than predicted eligible participants, and nurses judged a high proportion unsuitable to recruit into the study. Attrition rates following recruitment were typical for the study population. Cancer Carers Medicines Management was acceptable to carers and nurses who took part, and some benefits were identified. Conclusion: Cancer Carers Medicines Management is a robustly developed medicines management intervention which merits further research to test its effectiveness to improve carers’ management of pain medicines with patients at the end of life. The study highlighted aspects of trial design that need to be considered in future research

Trends in non-metastatic prostate cancer management in the Northern and Yorkshire region of England, 2000–2006

Background: Our objective was to analyse variation in non-metastatic prostate cancer management in the Northern and Yorkshire region of England. Methods: We included 21 334 men aged ⩾55, diagnosed between 2000 and 2006. Principal treatment received was categorised into radical prostatectomy (11%), brachytherapy (2%), external beam radiotherapy (16%), hormone therapy (42%) and no treatment (29%). Results: The odds ratio (OR) for receiving a radical prostatectomy was 1.53 in 2006 compared with 2000 (95% CI 1.26–1.86), whereas the OR for receiving hormone therapy was 0.57 (0.51–0.64). Age was strongly associated with treatment received; radical treatments were significantly less likely in men aged ⩾75 compared with men aged 55–64 years, whereas the odds of receiving hormone therapy or no treatment were significantly higher in the older age group. The OR for receiving radical prostatectomy, brachytherapy or external beam radiotherapy were all significantly lower in the most deprived areas when compared with the most affluent (0.64 (0.55–0.75), 0.32 (0.22–0.47) and 0.83 (0.74–0.94), respectively) whereas the OR for receiving hormone therapy was 1.56 (1.42–1.71). Conclusions: This study highlights the variation and inequalities that exist in the management of non-metastatic prostate cancer in the Northern and Yorkshire region of England

New Alzheimer Amyloid β Responsive Genes Identified in Human Neuroblastoma Cells by Hierarchical Clustering

Alzheimer's disease (AD) is characterized by neuronal degeneration and cell loss. Aβ42, in contrast to Aβ40, is thought to be the pathogenic form triggering the pathological cascade in AD. In order to unravel overall gene regulation we monitored the transcriptomic responses to increased or decreased Aβ40 and Aβ42 levels, generated and derived from its precursor C99 (C-terminal fragment of APP comprising 99 amino acids) in human neuroblastoma cells. We identified fourteen differentially expressed transcripts by hierarchical clustering and discussed their involvement in AD. These fourteen transcripts were grouped into two main clusters each showing distinct differential expression patterns depending on Aβ40 and Aβ42 levels. Among these transcripts we discovered an unexpected inverse and strong differential expression of neurogenin 2 (NEUROG2) and KIAA0125 in all examined cell clones. C99-overexpression had a similar effect on NEUROG2 and KIAA0125 expression as a decreased Aβ42/Aβ40 ratio. Importantly however, an increased Aβ42/Aβ40 ratio, which is typical of AD, had an inverse expression pattern of NEUROG2 and KIAA0125: An increased Aβ42/Aβ40 ratio up-regulated NEUROG2, but down-regulated KIAA0125, whereas the opposite regulation pattern was observed for a decreased Aβ42/Aβ40 ratio. We discuss the possibilities that the so far uncharacterized KIAA0125 might be a counter player of NEUROG2 and that KIAA0125 could be involved in neurogenesis, due to the involvement of NEUROG2 in developmental neural processes

Estimating the prevalence of food risk increasing behaviours in UK kitchens

© 2017 Jones et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Foodborne disease poses a serious threat to public health. In the UK, half a million cases are linked to known pathogens and more than half of all outbreaks are associated with catering establishments. The UK Food Standards Agency (FSA) has initiated the UK Food Hygiene Rating Scheme in which commercial food establishments are inspected and scored with the results made public. In this study we investigate the prevalence of food risk increasing behaviours among chefs, catering students and the public. Given the incentive for respondents to misreport when asked about illegal or illicit behaviours we employed a Randomised Response Technique designed to elicit more accurate prevalence rates of such behaviours. We found 14% of the public not always hand-washing immediately after handling raw meat, poultry or fish; 32% of chefs and catering students had worked within 48 hours of suffering from diarrhoea or vomiting. 22% of the public admitted having served meat “on the turn” and 33% of chefs and catering students admitted working in kitchens where such meat was served; 12% of the public and 16% of chefs and catering students admitted having served chicken at a barbeque when not totally sure it was fully cooked. Chefs in fine-dining establishment were less likely to wash their hands after handling meat and fish and those who worked in award winning restaurants were more likely to have returned to work within 48 hours of suffering from diarrhoea and vomiting. We found no correlation between the price of a meal in an establishment, nor its Food Hygiene Rating Score, and the likelihood of any of the food malpractices occurring

APP Intracellular Domain Impairs Adult Neurogenesis in Transgenic Mice by Inducing Neuroinflammation

A devastating aspect of Alzheimer's disease (AD) is the progressive deterioration of memory due to neuronal loss. Amyloid precursor protein (APP) occupies a central position in AD and APP-derived amyloid-β (Aβ) peptides are thought to play a pivotal role in disease pathogenesis. Nonetheless, it is becoming clear that AD etiology is highly complex and that factors other than Aβ also contribute to AD pathogenesis. APP intracellular domain (AICD) is generated together with Aβ and we recently showed that AICD transgenic mice recapitulate pathological features of AD such as tau hyperphosphorylation, memory deficits and neurodegeneration without increasing the Aβ levels. Since impaired adult neurogenesis is shown to augment memory deficits in AD mouse models, here we examined the status of adult neurogenesis in AICD transgenic mice.We previously generated transgenic mice co-expressing 59-residue long AICD fragment and its binding partner Fe65. Hippocampal progenitor cell proliferation was determined by BrdU incorporation at 1.5, 3 and 12 months of age. Only male transgenic and their respective wilt type littermate control mice were used. We find age-dependent decrease in BrdU incorporation and doublecortin-positive cells in the dentate gyrus of AICD transgenic mice suggesting impaired adult neurogenesis. This deficit resulted from decreased proliferation and survival, whereas neuronal differentiation remained unaffected. Importantly, this impairment was independent of Aβ since APP-KO mice expressing AICD also exhibit reduced neurogenesis. The defects in adult neurogenesis are prevented by long-term treatment with the non-steroidal anti-inflammatory agents ibuprofen or naproxen suggesting that neuroinflammation is critically involved in impaired adult neurogenesis in AICD transgenic mice.Since adult neurogenesis is crucial for spatial memory, which is particularly vulnerable in AD, these findings suggest that AICD can exacerbate memory defects in AD by impairing adult neurogenesis. Our findings further establish that AICD, in addition to Aβ, contributes to AD pathology and that neuroinflammation plays a much broader role in AD pathogenesis than previously thought

Improving behaviour in self-testing (IBIS): Study on frequency of use, consequences, information needs and use, and quality of currently available consumer information (protocol)

<p>Abstract</p> <p>Background</p> <p>Self-tests are available to consumers for more than 25 conditions, ranging from infectious diseases to cardiovascular risk factors. Self-tests are defined as in-vitro tests on body materials such as blood, urine, faeces, or saliva that are initiated by consumers to diagnose a particular disorder or risk factor without involving a medical professional. In 2006, 16% of a sample of Dutch Internet users had ever used at least one self-test and 17% intended to use a self-test in the future. The objectives of this study are to determine (1) the frequency of self-test use, (2) the consumers' reasons for using or not using a self-test, (3) the information that is used by self-testers in the different self-test stages and the consumers' interpretation of the quality of this information, (4) the consumers' response to self-test results in terms of their confidence in the result, reassurance by the test result, and follow-up behaviour, (5) the information consumers report to need in the decision making process of using or not using a self-test, and in further management on the basis of the self-test result, and (6) the quality of the currently available consumer information on a selected set of self-tests.</p> <p>Methods</p> <p>Mixed methods study with (1) a cross-sectional study consisting of a two-phase Internet-questionnaire, (2) semi-structured interviews with self-testers and consumers who intend to use a self-test, and (3) the assessment of the quality of consumer information of self-tests. The Health Belief Model and the Theory of Planned Behaviour will serve as the theoretical basis for the questionnaires and the interview topic guides.</p> <p>Conclusions</p> <p>The self-testing area is still in a state of flux and therefore it is expected that self-test use will increase in the future. To the best of our knowledge, this is the first study which combines quantitative and qualitative research to identify consumers' information needs and use concerning self-testing, and the consumers' actual follow-up behaviour based on the self-test result, and simultaneously investigates the quality of the currently available consumer information. The results of this study will be used as an input in developing consumer information on self-testing.</p