Pain in castration-resistant prostate cancer with bone metastases: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Bone metastases are a common painful and debilitating consequence of castration-resistant prostate cancer (CPRC). Bone pain may predict patients' prognosis and there is a need to further explore CRPC patients' experiences of bone pain in the overall context of disease pathology. Due to the subjective nature of pain, assessments of pain severity, onset and progression are reliant on patient assessment. Patient reported outcome (PRO) measures, therefore, are commonly used as key endpoints for evaluating the efficacy of CRPC treatments. Evidence of the content validity of leading PRO measures of pain severity used in CRPC clinical trials is, however, limited.</p> <p>Methods</p> <p>To document patients' experience of CRPC symptoms including pain, and their impact on health-related quality of life (HRQL), semi-structured in-depth qualitative interviews were conducted with 17 patients with CRPC and bone metastases. The content validity of the Present Pain Intensity (PPI) scale from the McGill Pain Questionnaire (MPQ), and the 'Average Pain' and 'Worst Pain' items of the Brief Pain Inventory Short-Form (BPI-SF) was also assessed.</p> <p>Results</p> <p>Patients with CRPC and bone metastases present with a constellation of symptoms that can have a profound effect on HRQL. For patients in this study, bone pain was the most prominent and debilitating symptom associated with their condition. Bone pain was chronic and, despite being generally well-managed by analgesic medication, instances of breakthrough cancer pain (BTcP) were common. Cognitive debriefing of the selected PRO measures of pain severity highlighted difficulties among patients in understanding the verbal response scale (VRS) of the MPQ PPI scale. There were also some inconsistencies in the way in which the BPI-SF 'Average Pain' item was interpreted by patients. In contrast, the BPI-SF 'Worst Pain' item was well understood and interpreted consistently among patients.</p> <p>Conclusions</p> <p>Study findings support the importance of PRO measures of pain severity as key endpoints for evaluating the efficacy of treatments for CRPC, particularly for patients with bone metastases where episodes of BTcP are common. Qualitative evidence from CRPC patients supports the content validity of the BPI-SF ''Worst Pain' item and promotes use of this item for measuring pain severity in this population.</p

Chronic condition self-management support: proposed competencies for medical students

Author version made available in accordance with the publisher's policy.Objective Governments and the medical profession are concerned that there continues to be less than optimal health outcomes despite escalating expenditure on health services from the effect of the ageing population with chronic illnesses. In this context, doctors will need to have knowledge and skills in effective Chronic Condition Management (CCM) and Chronic Condition Self-Management (CCSM). Method A national workshop of representatives of eight medical schools from the CCSM Special Interest Group (SIG) of the Australian and New Zealand Association on Medical Education (ANZAME) met in September 2004, to consider curriculum content in CCM and CCSM. Results The workshop recommended that the Committee of Deans of Australian Medical Schools (CDAMS) and the Commonwealth Department of Health and Ageing (DoHA) consider the identification and possible development of a specific curriculum for CCM and CCSM within the curricula of Australian Medical Schools. Discussion Consideration needs to be given to the changing nature of medical practice and that as part of this; doctors of the future will need skills in team participation, continuity of care, self-management support and patient-centered collaborative care planning. Doctors will also need skills to assist patients to better adhere to medical management, lifestyle behaviour change and risk factor reduction, if optimal health outcomes are to be achieved and costs are to be contained

Association between mortality from suicide in England and antidepressant prescribing: an ecological study

BACKGROUND: Antidepressant prescribing has been increasing in England. Studies in other countries suggest that while this may be associated with reduced suicide rates, it may also be associated with increased fatal poisoning from antidepressant drugs. We therefore conducted an ecological study to assess the association between prescription rates for antidepressants and suicide or fatal antidepressant-related poisoning in England. METHODS: The Office for National Statistics provided information on the number of suicides, antidepressant-related poisoning deaths and populations for England between 1993 and 2002. The Department of Health supplied data on prescriptions for all antidepressants dispensed in England. Associations between prescriptions and deaths were assessed using Spearman's rank correlation coefficient. RESULTS: There were 46,747 suicides, 3,987 deaths involving tricyclic antidepressants and 430 involving selective serotonin re-uptake inhibitors and other antidepressants. Increased antidepressant prescribing was statistically associated with a fall in suicide rates (Spearman's r(s )= -0.73, p = 0.02) and fatal poisoning involving tricyclic antidepressants (r(s )= -0.64, p = 0.05). In contrast, increased prescribing of selective serotonin re-uptake inhibitors and other antidepressants was statistically associated with an increase in fatal poisoning involving these drugs (r(s )= 0.99, p < 0.001). CONCLUSION: Increased prescribing of antidepressants may indicate improved diagnosis and treatment of depression in primary care. Our analysis suggests that this was accompanied by lower suicide rates. A decrease in poisoning deaths involving tricyclic antidepressants may suggest a change in preference for using serotonin reuptake inhibitors and other antidepressant drugs for high-risk patients. This may also partially explain the increase in deaths involving these drugs. Due to the ecological nature of the design, we cannot say conclusively whether reduced suicide rates are a direct consequence of increased antidepressant prescribing rates. To confirm these associations, individual level data on prescribing and suicide is needed

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Health-related quality of life in pain-free or mildly symptomatic patients with metastatic hormone-resistant prostate cancer following treatment with the specific endothelin A receptor antagonist zibotentan (ZD4054)

Purpose: Zibotentan (ZD4054) is a specific endothelin A receptor antagonist in clinical development for the treatment of hormone-resistant prostate cancer (HRPC). In a Phase II trial in patients with pain-free or mildly symptomatic metastatic HRPC, zibotentan was well tolerated with a promising signal for prolonged overall survival compared with placebo. As part of this trial, the impact of zibotentan compared with placebo on health-related quality of life (HRQoL) was assessed. Methods: Patients were randomized to receive once-daily oral zibotentan 10 or 15 mg, or matching placebo. Patients were allocated to one of two questionnaires; the Functional Assessment of Cancer Therapy-Prostate (FACT-P) or the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), supplemented by PR25, specific for prostate cancer. Questionnaires were completed at baseline and every 4 weeks until disease progression when study treatment was discontinued. Results: Compliance with questionnaire completion was >90% (286 of 312 patients) of the intention-to-treat population at baseline. Of baseline completers who were available for assessment (i.e., had not clinically progressed), 89% (164 of 184) and 83% (73 of 88) completed questionnaires at 12 and 24 weeks, respectively. HRQoL scores from both questionnaires were high at baseline and remained high throughout the study, with scores being similar in the zibotentan and placebo groups. However, some floor and ceiling effects were seen in the EORTC QLQ-C30 questionnaire. Conclusions: High-baseline HRQoL scores were maintained throughout treatment with zibotentan. The FACT-P instrument was selected to further assess the impact of zibotentan on HRQoL in the Phase III clinical trial program

Patient-Reported Outcomes in Rheumatoid Arthritis: Assessing the Equivalence of Electronic and Paper Data Collection

Background: The questionnaires used in clinical research have often been developed and validated using paper, and in such cases it is necessary to show that the electronic versions are equivalent to the originals. Objective: To determine if electronic versions of questionnaires assessing severity and impact of rheumatoid arthritis (RA) are equivalent to the original paper versions. Methods: Patients (n - 43; 31 female) aged 32-83 years (25 aged <60 years) took part in a single session during which they completed paper and electronic assessments in randomized order, with an interval of 45 minutes between the two modes. Electronic assessments were set up on a Palm TX handheld device. Assessments included measures of pain, fatigue, disability, and health status. Results: Scores were similar between the two modes. All effect sizes for electronic-paper differences were <0.2, and there was no overall tendency for one mode to show higher scores than the other. Intraclass correlation coefficients (ICCs) ranged from 0.72 to 0.96, and were generally similar to reported retest reliabilities of the scales in their paper versions. The Disability Index of the Health Assessment Questionnaire (HAQ-DI) showed an ICC of 0.96. ICCs for the EQ-5D health status scale were utility: 0.79; profile: 0.91; visual analog scale: 0.75. Most patients reported that both modes were easy to use. In general, patients preferred the electronic version over the paper, and this was true for the older as well as the younger patients. Conclusions: Electronic versions of questionnaires assessing severity and impact of RA provide data that correspond closely to those of paper originals, are easy to use, and are acceptable to patients.Patient-preference, Quality-of-life-rating-scales, Rheumatoid-arthritis, Assessment, Utility-measurement.

Quality of life in type 2 diabetic patients is affected by complications but not by intensive policies to improve blood glucose or blood pressure control (UKPDS 37)

OBJECTIVE - To determine in patients with type 2 diabetes the effects on quality of life (QOL) of therapies for improving blood glucose control and for improving blood pressure (BP) control, diabetic complications, and hypoglycemic episodes. RESEARCH DESIGN AND METHODS - We performed two cross- sectional studies of patients enrolled in randomized controlled trials of 1) an intensive blood glucose control policy compared with a conventional blood glucose control policy, and 2) a tight BP control policy compared with a less tight BP control policy. Also undertaken was a longitudinal study of patients in a randomized controlled trial of an intensive blood glucose control policy compared with a conventional blood glucose control policy. Subjects' QOL was assessed before or at the time of randomization and from 6 months to 6 years after randomization. Two cross-sectional samples of type 2 diabetic patients were randomized to therapies for blood glucose control: 1) 2,431 patients, mean age 60, duration from randomization 8.0 years, completed a 'specific' questionnaire coveting four aspects of QOL, and 2) 3,104 patients, mean age 62, duration from randomization 11 years, completed a 'genetic' QOL measure. Of these samples, 628 and 747 patients, respectively, were also randomized to therapies for BP control. A sample of 122 nondiabetic control subjects, average age 62, were also given the specific questionnaire. A longitudinal sample of 374 type 2 diabetic patients randomized to either intensive or conventional blood glucose policies, mean age at randomization 52, were given the specific questionnaire. Sample sizes at 6 months and 1, 2, 3, 4, 5, and 6 years after randomization were 322, 307, 280, 253, 225, 163, and 184, respectively. The specific questionnaire assessed specific domains of QOL, including mood disturbance (Profile of Mood State), cognitive mistakes (Cognitive Failures Questionnaire), symptoms, and work satisfaction; the generic questionnaire (EQ5D) assessed general health. Both questionnaires were self-administered. RESULTS - The cross-sectional studies showed that allocated therapies were neutral in effect, with neither improvement nor deterioration in QOL scores for mood, cognitive mistakes, symptoms, work satisfaction, or general health. The longitudinal study also showed no difference in QOL scores for the specific domains assessed, other than showing marginally more symptoms in patients allocated to conventional than to intensive policy in the cross-sectional studies, patients who had had a macrovascular complication in the last year had worse general health, as measured by the generic questionnaire, than those without complications, with scale scores median 60 and 78 respectively (P = 0.0006) and tariff scores median 0.73 and 0.83 respectively (P = 0.0012); more problems with mobility, 64 and 36%, respectively (P &lt; 0.0001); and more problems with usual activities, 48 and 28% respectively (P = 0.0023). As measured by the specific questionnaire, they also showed reduced vigor (P = 0.0077). Patients who had had a microvascular complication in the last year reported more tension (P = 0.0082) and total mood disturbance (P = 0.0054), as measured by the specific questionnaire, than patients without complications. Patients treated with insulin who had had two or more hypoglycemic episodes during the previous year reported more tension (P = 0.0023), more overall mood disturbance (P = 0.0009), and less work satisfaction (P = 0.0042), as measured by the specific questionnaire, than those with no hypoglycemic attacks, after adjusting for age, duration from randomization, systolic BP, HbA(1c), and sex in a multivariate polychotomous regression. CONCLUSIONS - In patients with type 2 diabetes, complications of the disease affected QOL, whereas therapeutic policies shown to reduce the risk of complications had no effect on QOL. It cannot be discerned whether frequent hypoglycemic episodes affect QOL, or whether patients with certain personality traits or many symptoms also reported increased numbers of hypoglycemic attacks.</p