Consistency of Financial Interest Disclosures in the Biomedical Literature: The Case of Coronary Stents

Background Disclosure of authors' financial interests has been proposed as a strategy for protecting the integrity of the biomedical literature. We examined whether authors' financial interests were disclosed consistently in articles on coronary stents published in 2006. Methodology/Principal Findings We searched PubMed for English-language articles published in 2006 that provided evidence or guidance regarding the use of coronary artery stents. We recorded article characteristics, including information about authors' financial disclosures. The main outcome measures were the prevalence, nature, and consistency of financial disclosures. There were 746 articles, 2985 authors, and 135 journals in the database. Eighty-three percent of the articles did not contain disclosure statements for any author (including declarations of no interests). Only 6% of authors had an article with a disclosure statement. In comparisons between articles by the same author, the types of disagreement were as follows: no disclosure statements vs declarations of no interests (64%); specific disclosures vs no disclosure statements (34%); and specific disclosures vs declarations of no interests (2%). Among the 75 authors who disclosed at least 1 relationship with an organization, there were 2 cases (3%) in which the organization was disclosed in every article the author wrote. Conclusions/Significance In the rare instances when financial interests were disclosed, they were not disclosed consistently, suggesting that there are problems with transparency in an area of the literature that has important implications for patient care. Our findings suggest that the inconsistencies we observed are due to both the policies of journals and the behavior of some authors

Distinctive aspects of consent in pilot and feasibility studies

Prior to a main randomized clinical trial, investigators often carry out a pilot or feasibility study in order to test certain trial processes or estimate key statistical parameters, so as to optimize the design of the main trial and/or determine whether it can feasibly be run. Pilot studies reflect the design of the intended main trial, whereas feasibility studies may not do so, and may not involve allocation to different treatments. Testing relative clinical effectiveness is not considered an appropriate aim of pilot or feasibility studies. However, consent is no less important than in a main trial as a means of morally legitimizing the investigator's actions. Two misperceptions are central to consent in clinical studies-therapeutic misconception (a tendency to conflate research and therapy) and therapeutic misestimation (a tendency to overestimate possible benefits and/or underestimate possible harms associated with participation). These phenomena may take a distinctive form in pilot and feasibility studies, owing to potential participants' likely prior unfamiliarity with the nature and purposes of such studies. Thus, participants may confuse the aims of a pilot or feasibility study (developing or optimizing trial design and processes) with those of a main trial (testing treatment effectiveness) and base consent on this misconstrual. Similarly, a misunderstanding of the ability of pilot and feasibility studies to provide information that will inform clinical care, or the underdeveloped nature of interventions included in such studies, may lead to inaccurate assessments of the objective possibility of benefit, and weaken the epistemic basis of consent accordingly. Equipoise may also be particularly challenging to grasp in the context of a pilot study. The consent process in pilot and feasibility studies requires a particular focus, and careful communication, if it is to carry the appropriate moral weight. There are corresponding implications for the process of ethical approval

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Potential antitumor effects of nitrogen-containing bisphosphonate in hormone receptor negative breast cancer patients with bone metastases

<p>Abstract</p> <p>Background</p> <p>This retrospective study evaluated, according to hormone receptor status, the antitumor effects of bisphosphonate especially on survival and disease progression in breast cancer patients with metastatic bone disease.</p> <p>Methods</p> <p>Of 317 patients with initial bone metastasis and known breast cancer subtypes, 230 patients (72.6%) had hormone receptor (HR) positive tumors, and 87 patients (27.4%) had HR negative tumors. We assessed the primary outcome of overall survival (OS), after adjusting for other factors, comparing a group that received bisphosphonates (BPs) with a group that did not receive it.</p> <p>Results</p> <p>87.8% of HR positive and 69.0% of HR negative patients received BPs with a median number of 17.7 cycles. Although BPs treatment made no survival benefit in HR positive group, HR negative patients showed a significant prolonged survival when they received BPs treatment (hazard ratio = 0.56 [95% CI 0.34 to 0.91], <it>P </it>= 0.019). In multivariate analysis, disease free interval > 2 years (<it>P </it>= 0.036), a sum of metastatic sites < 3 (<it>P </it>= 0.034), and BP treatments (<it>P </it>= 0.007) were significant factors for survival in HR negative patients.</p> <p>Conclusion</p> <p>Bisphosphonate treatment can result in a survival benefit in metastatic breast cancer patients with HR negative tumors.</p

Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease

Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07–1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06–1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials

Sexual dysfunction and fertility-related distress in young adults with cancer over 5 years following diagnosis: study protocol of the Fex-Can Cohort study

BACKGROUND: There is a lack of firm knowledge regarding sexual problems and fertility-related distress in young adults following a diagnosis with cancer. Establishing such understanding is essential to identify patients in need of specific support and to develop cancer care accordingly. This study protocol describes the Fex-Can Cohort study, a population-based prospective cohort study investigating sexual dysfunction and fertility-related distress in young adults diagnosed with cancer in Sweden. The primary objective of the study is to determine the prevalence and predictors of sexual dysfunction and fertility-related distress following a cancer diagnosis in young adulthood compared to prevalence rates for the general population. Further aims are to investigate the trajectories of these issues over time, the co-existence between sexual dysfunction and fertility-related distress, and the relation between these issues and body image, anxiety and depression, health-related quality of life, self-efficacy related to sexuality and fertility, and fertility-related knowledge. METHODS: Participants in the Fex-Can Cohort will be identified via the Swedish National Quality Registries for Brain Tumors, Breast Cancer, Gynecological Oncology, Lymphoma, and Testicular Cancer. All patients diagnosed at the ages of 18-39, during a period of 18 months, will be invited to participate. Established instruments will be used to measure sexual function (PROMIS SexFS), fertility-related distress (RCAC), body image (BIS), anxiety and depression (HADS), and health-related quality of life (QLQ-C30); Self-efficacy and fertility-related knowledge will be assessed by study-specific measures. The survey will be administered to participants at baseline (approximately 1.5 year after diagnosis) and at 3 and 5 years post-diagnosis. Registry data will be used to collect clinical variables. A comparison group of 2000 young adults will be drawn from the Swedish population register (SPAR) and subsequently approached with the same measures as the cancer group. DISCUSSION: The study will determine the prevalence and predictors of sexual dysfunction and fertility-related distress in young men and women with cancer. The findings will form a basis for developing interventions to alleviate sexual problems and fertility-related distress in young adults with cancer in the short and long term. TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was therefore not obtained

Relationship between CD4 count and quality of life over time among HIV patients in Uganda: A cohort study

© 2015 Mwesigire et al. Background: Immunological markers (CD4 count) are used in developing countries to decide on initiation of antiretroviral therapy and monitor HIV/AIDS disease progression. HIV is an incurable chronic illness, making quality of life paramount. The direct relationship between quality of life and CD4 count is unclear. The purpose of this study is to determine the relationship between change in CD4 count and quality of life measures in a Ugandan cohort of people living with HIV. Methods: We prospectively assessed quality of life among 1274 HIV patients attending an HIV clinic within a national referral hospital over a period of 6months. Quality of life was measured using an objective measure, the Medical Outcomes Study HIV health survey summarized as Physical Health Score and Mental Health Score and a subjective measure, the Global Person Generated Index. Generalized estimating equations were used to analyze the data. The primary predictor variable was change in CD4 count, and the outcome was quality of life scores. We controlled for sociodemographic characteristics, clinical factors and behavioral factors. Twenty in-depth interviews were conducted to assess patient perception of quality of life and factors influencing quality of life. Results: Of the 1274 patients enrolled 1159 had CD4 count at baseline and six months and 586 (51%) received antiretroviral therapy. There was no association found between change in CD4 count and quality of life scores at univariate and multivariate analysis among the study participants whether on or not on antiretroviral therapy. Participants perceived quality of life as happiness and well-being, influenced by economic status, psychosocial factors, and health status. Conclusions: Clinicians and policy makers cannot rely on change in immunological markers to predict quality of life in this era of initiating antiretroviral therapy among relatively healthy patients. In addition to monitoring immunological markers, socioeconomic and psychosocial factors should be underscored in management of HIV patients

Declining Sleep Quality among Nurses: A Population-Based Four-Year Longitudinal Study on the Transition from Nursing Education to Working Life

Background: Several studies have established impaired sleep is a common problem among nurses. Overworked, fatigued and stressed nurses are at a higher risk of making mistakes that threaten patient safety as well as their own health. The aim of the present study was to longitudinally monitor the development of sleep quality in nurses, starting from the last semester at the university, with three subsequent annual follow-ups once the nurses had entered working life. Methodology/Principal Findings: Nationwide, longitudinal questionnaire study of nursing students and newly qualified nurses in Sweden. The results imply a continuous decline in sleep quality among nurses during the three years of follow-up, starting from their last semester of nursing education and continuing for three years into their working life. The most pronounced short-term decline in sleep quality seems to occur in the transition between student life and working life. Conclusion/Significance: This finding is important since it may affect the quality of care and the health of nurses negatively