"Me's me and you's you": Exploring patients' perspectives of single patient (n-of-1) trials in the UK

BACKGROUND: The n-of-1 trial offers a more methodologically sound approach to determining optimum treatment for an individual patient than "trials of therapy" routinely conducted in clinical practice. However, such methodology is rarely used in the UK. This pilot study explores the acceptability of n-of-1 trials to patients in the UK. METHODS: Patients with osteoarthritis of the knee were recruited to their own 12-week n-of-1 trial comparing either two knee supports or an NSAID with simple analgesic. Patients were interviewed at the start and completion of their trial to explore reasons for participation, understanding of the trial design and experiences of participation. Daily diaries were completed to inform future treatment. RESULTS: Nine patients participated (5 supports, 4 drugs). Patients were keen to participate, believing that the trial may lead to personal gains such as improved symptom control and quality of life. However, recruitment to the pharmacological comparison was more difficult since this could also entail risk. All patients were eager to complete the trial, even when difficulties were encountered. Completing the daily diary provided some patients with greater insight into their condition, which allowed them to improve their self-management. The n-of-1 trial design was viewed as a 'logical' design offering an efficient method of reaching a personalised treatment decision tailored to suit individual needs and preferences. CONCLUSION: This pilot study suggests that patients perceive the n-of-1 trial as an acceptable approach to the individualisation of treatment. In addition, further benefits over and above any gained from the interventions can be derived from involvement in such a study

Individualised and complex experiences of integrative cancer support care: combining qualitative and quantitative data

Objectives: The widespread use of complementary therapies alongside biomedical treatment by people with cancer is not supported by evidence from clinical trials. We aimed to use combined qualitative and quantitative data to describe and measure individualised experiences and outcomes. Materials and methods In three integrative cancer support centres (two breast cancer only) in the UK, consecutive patients completed the individualised outcome questionnaire Measure Yourself Concerns and Wellbeing (MYCaW) before and after treatment. MYCaW collects quantitative data (seven-point scales) and written qualitative data and the qualitative data were analysed using published categories. Results: Seven hundred eighty-two participants, 92% female, mean age 51 years, nominated a wide range of concerns. Psychological and emotional concerns predominated. At follow-up, the mean change (improvement) in scores (n = 588) were: concern 1, 2.06 (95% CI 1.92–2.20); concern 2, 1.74 (95% CI 1.60–1.90); and well-being, 0.64 (95% CI 0.52–0.75). The most common responses to ‘what has been the most important aspect for you?’ were ‘receiving complementary therapies on an individual or group basis’ (26.2%); ‘support and understanding received from therapists’ (17.1%) and ‘time spent with other patients at the centres’ (16.1%). Positive (61.5%) and negative (38.5%) descriptions of ‘other things affecting your health’ correlated with larger and smaller improvement in concerns and well-being, respectively. Conclusions: In a multicentre evaluation, the MYCaW questionnaire provides rich data about patient experience, changes over time and perceptions of what was important to each individual with cancer within that experience. It is unlikely that meaningful evaluations of this complex intervention could be carried out by quantitative methods alone

Microvolt T-wave alternans as a predictor of mortality and severe arrhythmias in patients with left-ventricular dysfunction: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Studies have demonstrated that the use of implantable cardioverter defibrillators (ICDs) is effective for the primary prevention of arrhythmic events but due to imposing costs, there remains a need to identify which patients will derive the greatest benefit. Microvolt T-wave alternans (MTWA) has been proposed to assist in this stratification.</p> <p>Methods</p> <p>We systematically searched the literature using MEDLINE, EMBASE, Current Contents, the Cochrane Library, INAHTA, and the Web of Science to identify all primary prevention randomized controlled trials and prospective cohort studies with at least 12 months of follow-up examining MTWA as a predictor of mortality and severe arrhythmic events in patients with severe left-ventricular dysfunction. The search was limited to full-text English publications between January 1990 and May 2007. The primary outcome was a composite of mortality and severe arrhythmias. Data were synthesized using Bayesian hierarchical models.</p> <p>Results</p> <p>We identified no trials and 8 published cohort studies involving a total of 1,946 patients, including 332 positive, 656 negative, 84 indeterminate, and 874 non-negative (which includes both positive and indeterminate tests) MTWA test results. The risk of mortality or severe arrhythmic events was higher in patients with a positive MTWA compared to a negative test (RR = 2.7, 95% credible interval (CrI) = 1.4, 6.1). Similar results were obtained when comparing non-negative MTWA to a negative test.</p> <p>Conclusion</p> <p>A positive MTWA test predicts mortality or severe arrhythmic events in a population of individuals with severe left ventricular dysfunction. However, the wide credible interval suggests the clinical utility of this test remains incompletely defined, ranging from very modest to substantial. Additional high quality studies are required to better refine the role of MTWA in the decision making process for ICD implantation.</p

Perceived needs and satisfaction with care in people with multiple sclerosis: A two-year prospective study

<p>Abstract</p> <p>Background</p> <p>Considering the costs of multiple sclerosis (MS), it is crucial that the health-related services supplied are in accordance with needs as they are perceived by people with MS (PwMS). Satisfaction with care is related to quality of care and can provide health care providers with the means for improvement. The aim was to explore the perceived needs and satisfaction with care amongst PwMS over a two-year period, also taking sex and disease severity into consideration.</p> <p>Methods</p> <p>The sample consisted of 219 outpatients at a MS specialist clinic. Data on perceived needs and satisfaction with care were collected every six months using a questionnaire which included various dimensions of care. The data was analysed for the whole sample and on an individual level, as well as in subgroups with regard to sex and disease severity.</p> <p>Results</p> <p>There were no statistically significant variations in the proportion of PwMS with perceived needs concerning different health-related services during the study period. However, individual variations were found with regard to both perceived needs and satisfaction with care. Few PwMS perceived a continuous need for a specific service. However, the majority perceived a need for rehabilitation, assistive devices, transportation service for the disabled, psychosocial support/counselling and information on social insurance/vocational rehabilitation at least sometimes. Severe MS was associated with a greater perceived need for almost all the services studied and women experienced a need for psychosocial support/counselling to a greater extent than men. In relation to the different categories of health care staff, PwMS were most satisfied with nurses with regard to all dimensions of care. They were least satisfied with the availability of psychosocial support/counselling; and information about social insurance/vocational rehabilitation.</p> <p>Conclusion</p> <p>Despite the large proportion of individuals with mild disease severity in our sample, a considerable number of needs were identified of which many, on an individual level, varied over time. Key services demanded by PwMS were identified. Also the level of satisfaction with care varied and areas with a potential for improvement were identified such as the availability of rehabilitation services including an increase in the supply of psychosocial support and counselling.</p

Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines

Introduction: Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. Methods: We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Results: Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. Conclusions: As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral heterogeneity of individual breast tumors. Additionally, normal human mammary epithelial cell lines fail to retain much of the cellular diversity found in human breast tissues and are enriched for differentiation states that are a minority in breast tissues, although they do exhibit features of bi-potent basal progenitor cells. These findings suggest that collections of cell lines representing multiple cell types can be used to model the cellular heterogeneity of tissues

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

Coping strategies of women with postpartum depression symptoms in rural Ethiopia: a cross-sectional community study

Background: Most women with postpartum depression (PPD) in low- and middle-income countries remain undiagnosed and untreated, despite evidence for adverse effects on the woman and her child. The aim of this study was to identify the coping strategies used by women with PPD symptoms in rural Ethiopia to inform the development of socio-culturally appropriate interventions. Methods: A population-based, cross-sectional study was conducted in a predominantly rural district in southern Ethiopia. All women with live infants between one and 12 months post-partum (n = 3147) were screened for depression symptoms using the validated Patient Health Questionnaire, 9 item version (PHQ-9). Those scoring five or more, ‘high PPD symptoms’, (n = 385) were included in this study. The Brief Coping with Problems Experienced (COPE-28) scale was used to assess coping strategies. Construct validity of the brief COPE was evaluated using confirmatory factor analysis. Results: Confirmatory factor analysis of the brief COPE scale supported the previously hypothesized three dimensions of coping (problem-focused, emotion-focused, and dysfunctional). Emotion-focused coping was the most commonly employed coping strategy by women with PPD symptoms. Urban residence was associated positively with all three dimensions of coping. Women who had attended formal education and who attributed their symptoms to a physical cause were more likely to use both problem-focused and emotion-focused coping strategies. Women with better subjective wealth and those who perceived that their husband drank too much alcohol were more likely to use emotion-focused coping. Dysfunctional coping strategies were reported by women who had a poor relationship with their husbands. Conclusions: As in high-income countries, women with PPD symptoms were most likely to use emotion-focused and dysfunctional coping strategies. Poverty and the low level of awareness of depression as an illness may additionally impede problem-solving attempts to cope. Prospective studies are needed to understand the prognostic significance of coping styles in this setting and to inform psychosocial intervention development