Differences in Self-Rated Versus Parent Proxy–Rated Vision-Related Quality of Life and Functional Vision of Visually Impaired Children

PURPOSE: To investigate disagreement between children's self-reported vision-related quality of life (VQoL) and functional vision (FV), and their parents' proxy-reports. DESIGN: Cross-sectional study. METHODS: 152 children aged 7-18 years with visual impairment (VI) (defined by the World Health Organization), and their parents, were recruited from 22 National Health Service (NHS) Ophthalmology Departments in the United Kingdom. Age-appropriate versions of 2 vision-specific instruments capturing VQoL and FV, were administered to children alongside modified versions for completion by parents on behalf of their child (i.e. parent proxy-report). Disagreement between self- and parent proxy-report was examined using the Bland-Altman (BA) method, and a threshold of disagreement based on 0.5 standard deviation. Disagreement was analysed according to participants' age, gender and clinical characteristics, using logistic regression analyses. RESULTS: Children rated themselves as having better outcomes than their parents did, although parents both under- and over-estimated their child's VQoL (mean score difference = 7.7). With each year of increasing age, there was a 1.18 (1.04 - 1.35) higher odds of children self-rating their VQoL better than their parents (p = 0.013). Although parents consistently under-estimated their child's FV (mean score difference = -4.7), no characteristics were significantly associated with differences in disagreement. CONCLUSIONS: Disagreement between child self-report on the impact of VI, and their parents' proxy-reports varies by age. This implies that self-report from children must remain the gold standard. Where self-reporting is not possible, parent proxy-reports may provide useful insights, but must be interpreted with caution

Level of impaired control predicts outcome of moderation-oriented treatment for alcohol problems

Aims To examine the ability of the Impaired Control Scale (ICS) to predict outcome of moderation-oriented treatment for alcohol problems and to compare this predictive ability directly with that of a widely used measure of alcohol dependence, the Severity of Alcohol Dependence Questionnaire (SADQ). Design Prospective follow-up study. Setting Out-patient treatment centres. Participants A combined sample 154 problem drinkers taking part in two clinical trials of Moderation-oriented Cue Exposure in the UK and Australia. Clients were followed-up 6 (UK) and 8 (Australia) months after the end of reatment. Measurements Outcome was categorized by combining drinking behaviour at follow-up with changes on the Alcohol Problems Questionnaire from before treatment to follow-up. Controlling for research site, baseline scores on Part 2 of the ICS (substitution method) and the SADQ-C were entered in logistic regression analyses with three outcome dichotomies as dependent variables. Findings Five per cent of clients were abstinent at follow-up, 13% non-problem drinkers, 25% much improved, 24% somewhat improved and 34% unimproved. Location of treatment and ICS2 scores were significant predictors of whether or not clients achieved a successful outcome (abstinence or non-problem drinking). Using a cut-point of 25 on the ICS, two-thirds of outcomes were classified correctly as either treatment successes or failures. SADQ-C score was not a significant predictor of treatment outcome. Conclusions The ICS predicts outcome of moderation-oriented treatment among moderately dependent problem drinkers recruited mainly via newspaper advertisements. The ICS should replace the SADQ as the basis for advice to clients in this population of problem drinkers regarding whether or not a moderation goal of treatment should be pursued

"Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer

BACKGROUND: In a significant proportion of metastatic breast cancer (MBC) patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance), it is generally believed that the chance of achieving clinical benefit (CB) with further endocrine therapy is minimal. METHODS: Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS™ software for statistical analysis. RESULTS: In oestrogen receptor (ER) positive MBC patients with assessable disease, CB was achieved in 159 (71.3%) (1(st )line) patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2(nd )line), 46.1% (on 3(rd )line) and 20% (on 4(th )line) with a median duration of response (DOR) in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64(28.7%) patients had de novo resistance on 1(st )line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2(nd )line) and 22.2% (on 3(rd )line) with a median DOR in those with CB of 22.7 months and 14 months respectively. CONCLUSION: The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4(th )line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1(st )line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances

Evidence in Practice – A Pilot Study Leveraging Companion Animal and Equine Health Data from Primary Care Veterinary Clinics in New Zealand

Veterinary practitioners have extensive knowledge of animal health from their day-to-day observations of clinical patients. There have been several recent initiatives to capture these data from electronic medical records for use in national surveillance systems and clinical research. In response, an approach to surveillance has been evolving that leverages existing computerized veterinary practice management systems to capture animal health data recorded by veterinarians. Work in the United Kingdom within the VetCompass program utilizes routinely recorded clinical data with the addition of further standardized fields. The current study describes a prototype system that was developed based on this approach. In a 4-week pilot study in New Zealand, clinical data on presentation reasons and diagnoses from a total of 344 patient consults were extracted from two veterinary clinics into a dedicated database and analyzed at the population level. New Zealand companion animal and equine veterinary practitioners were engaged to test the feasibility of this national practice-based health information and data system. Strategies to ensure continued engagement and submission of quality data by participating veterinarians were identified, as were important considerations for transitioning the pilot program to a sustainable large-scale and multi-species surveillance system that has the capacity to securely manage big data. The results further emphasized the need for a high degree of usability and smart interface design to make such a system work effectively in practice. The geospatial integration of data from multiple clinical practices into a common operating picture can be used to establish the baseline incidence of disease in New Zealand companion animal and equine populations, detect unusual trends that may indicate an emerging disease threat or welfare issue, improve the management of endemic and exotic infectious diseases, and support research activities. This pilot project is an important step toward developing a national surveillance system for companion animals and equines that moves beyond emerging infectious disease detection to provide important animal health information that can be used by a wide range of stakeholder groups, including participating veterinary practices

Prevention of Breast cancer with tamoxifen:preliminary findings from the italian randomised trial among hysterectomised women

Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, Rotmensz N, Boyle P. SourceEuropean Institute of Oncology, Milan, Italy. Abstract BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy

Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents

BACKGROUND: High dose estrogens (HDEs) were frequently used as endocrine agents prior to the introduction of tamoxifen which carries fewer side effects. Due to the development of resistance to available endocrine agents in almost all women with metastatic breast cancer, interest has renewed in the use of HDEs as yet another endocrine option that may have activity. We report our experience with one of the HDEs ("ethinylestradiol" 1 mg daily) in advanced breast cancer (locally advanced and metastatic) in post-menopausal women who had progressed on multiple endocrine agents. PATIENTS AND METHODS: According to a database of advanced breast cancer patients seen in our Unit since 1998, those who had complete set of information and fulfilled the following criteria were studied: (1) patients in whom further endocrine therapy was deemed appropriate i.e., patients who have had clinical benefit with previous endocrine agents or were not fit or unwilling to receive chemotherapy in the presence of potentially life-threatening visceral metastases; (2) disease was assessable by UICC criteria; (3) were treated with "ethinylestradiol" until they were withdrawn from treatment due to adverse events or disease progression. RESULTS: Twelve patients with a median age of 75.1 years (49.1 – 85 years) were identified. Majority (N = 8) had bony disease. They had ethinylestradiol as 3(rd )to 7(th )line endocrine therapy. One patient (8%) came off treatment early due to hepato-renal syndrome. Clinical benefit (objective response or durable stable disease for ≥ 6 months) was seen in 4 patients (33.3%) with a median duration of response of 10+ (7–36) months. The time to treatment failure was 4 (0.5–36) months. CONCLUSION: Yet unreported, high dose "ethinylestradiol" is another viable therapeutic strategy in heavily pre-treated patients when further endocrine therapy is deemed appropriate. Although it tends to carry more side effects, they may not be comparable to those of other HDEs (such as diethylstilbestrol) or chemotherapy

Caffeine Inhibits EGF-Stimulated Trophoblast Cell Motility through the Inhibition of mTORC2 and Akt.

Impaired trophoblast invasion is associated with pregnancy disorders such as early pregnancy loss and preeclampsia. There is evidence to suggest that the consumption of caffeine during pregnancy may increase the risk of pregnancy loss; however, little is known about the direct effect of caffeine on normal trophoblast biology. Our objectives were to examine the effect of caffeine on trophoblast migration and motility after stimulation with epidermal growth factor (EGF) and to investigate the intracellular signaling pathways involved in this process. Primary first-trimester extravillous trophoblasts (EVT) and the EVT-derived cell line SGHPL-4 were used to study the effect of caffeine on EGF-stimulated cellular motility using time-lapse microscopy. SGHPL-4 cells were further used to study the effect of caffeine and cAMP on EGF-stimulated invasion of fibrin gels. The influence of caffeine and cAMP on EGF-stimulated intracellular signaling pathways leading to the activation of Akt were investigated by Western blot analysis. Caffeine inhibits both EGF-stimulated primary EVT and SGHPL-4 cell motility. EGF stimulation activates phosphatidylinositol 3-kinase, and Akt and caffeine inhibit this activation. Although cAMP inhibits both motility and invasion, it does not inhibit the activation of Akt, indicating that the effects of caffeine seen in this study are independent of cAMP. Further investigation indicated a role for mammalian target of rapamycin complex 2 (mTORC2) as a target for the inhibitory effect of caffeine. In conclusion, we demonstrate that caffeine inhibits EGF-stimulated trophoblast invasion and motility in vitro and so could adversely influence trophoblast biology in vivo

Hard measures for soft stuff: citizenship indicators and educational policy under the Lisbon Strategy

How far is the European Union a vehicle for inclusion and empowerment of a new range of policy actors in education? This article explores the role of actors in policy formation through a case study. It examines European Union attempts since 2000 to develop indicators of ‘active citizenship’ and ‘education and training for active citizenship’. It is based on two main sources: policy documents on the development of indicators and benchmarks; and a case study of an exercise (2005-07) to develop such indicators, initiated by the European Commission’s Directorate General for Education and Culture. It shows that policy actors have attempted to take advantage of the Open Method of Coordination, often seen as a neo-liberal control mechanism, to ensure that citizenship remains on the policy agenda

Task-Shifting and Task-Sharing in Neurosurgery: An International Survey of Current Practices in Low- and Middle-Income Countries.

BACKGROUND: Because nearly 23,000 more neurosurgeons are needed globally to address 5 million essential neurosurgical cases that go untreated each year, there is an increasing interest in task-shifting and task-sharing (TS/S), delegating neurosurgical tasks to nonspecialists, particularly in low- and middle-income countries (LMICs). This global survey aimed to provide a cross-sectional understanding of the prevalence and structure of current neurosurgical TS/S practices in LMICs. METHODS: The survey was distributed to a convenience sample of individuals providing neurosurgical care in LMICs with a Web-based survey link via electronic mailing lists of continental societies and various neurosurgical groups, conference announcements, e-mailing lists, and social media platforms. Country-level data were analyzed by descriptive statistics. RESULTS: The survey yielded 127 responses from 47 LMICs; 20 countries (42.6%) reported ongoing TS/S. Most TS/S procedures involved emergency interventions, the top 3 being burr holes, craniotomy for hematoma evacuation, and external ventricular drain. Most (65.0%) believed that their Ministry of Health does not endorse TS/S (24.0% unsure), and only 11% believed that TS/S training was structured. There were few opportunities for TS/S providers to continue medical education (11.6%) or maintenance of certification (9.4%, or receive remuneration (4.2%). CONCLUSIONS: TS/S is ongoing in many LMICs without substantial structure or oversight, which is concerning for patient safety. These data invite future clinical outcomes studies to assess effectiveness and discussions on policy recommendations such as standardized curricula, certification protocols, specialist oversight, and referral networks to increase the level of TS/S care and to continue to increase the specialist workforce

Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio