Development of a core information set for colorectal cancer surgery: a consensus study

Objective ‘Core information sets’ (CISs) represent baseline information, agreed by patients and professionals, to stimulate individualised patient-centred discussions. This study developed a CIS for use before colorectal cancer (CRC) surgery. Design Three phase consensus study: (1) Systematic literature reviews and patient interviews to identify potential information of importance to patients, (2) UK national Delphi survey of patients and professionals to rate the importance of the information, (3) international consensus meeting to agree on the final CIS. Setting UK CRC centres. Participants Purposive sampling was conducted to ensure CRC centre representation based upon geographical region and caseload volume. Responses were received from 63/81 (78%) centres (90 professionals). Adult patients who had undergone CRC surgery were eligible, and purposive sampling was conducted to ensure representation based on age, sex and cancer location (rectum, left and right colon). Responses were received from 97/267 (35%) patients with a wide age range (29–87), equal sex ratio and cancer location. Attendees of the international Tripartite Colorectal Conference were eligible for the consensus meeting. Outcomes Phase 1: Information of potential importance to patients was extracted verbatim and operationalised into a Delphi questionnaire. Phase 2: Patients and professionals rated the importance information on a 9-point Likert scale, and resurveyed following group feedback. Information rated of low importance were discarded using predefined criteria. Phase 3: A modified nominal group technique was used to gain final consensus in separate consensus meetings with patients and professionals. Results Data sources identified 1216 pieces of information that informed a 98-item questionnaire. Analysis led to 50 and 23 information domains being retained after the first and second surveys, respectively. The final CIS included 11 concepts including specific surgical complications, short and long-term survival, disease recurrence, stoma and quality of life issues. Conclusions This study has established a CIS for professionals to discuss with patients before CRC surgery

Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT)

Polymeric cytotoxic conjugates are being developed with the aim of preferential delivery of the anticancer agent to tumour. MAG-CPT comprises the topoisomerase I inhibitor camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide ( average molecular weight 18 kDa, 10% CPT by weight). It was administered as a 30-min infusion once every 4 weeks to patients with advanced solid malignancies. The objectives of our study were to determine the maximum tolerated dose, dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document responses to this treatment. The starting dose was 30 mgm(-2) (dose expressed as mg equivalent camptothecin). In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mgm(-2). Dose-limiting toxicities were myelosuppression, neutropaenic sepsis, and diarrhoea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mgm(-2). The half-lives of both MAG-CPT and released CPT were prolonged (46 days) and measurable levels of MAG-CPT were retrieved from plasma and urine 4 weeks after treatment. However, subsequent pharmacodynamic studies of this agent have led to its withdrawal from clinical development

Identifying bereaved subjects at risk of complicated grief: Predictive value of questionnaire items in a cohort study

<p>Abstract</p> <p>Background</p> <p>Bereavement is a condition which most people experience several times during their lives. A small but noteworthy proportion of bereaved individuals experience a syndrome of prolonged psychological distress in relation to bereavement. The aim of the study was to develop a clinical tool to identify bereaved individuals who had a prognosis of complicated grief and to propose a model for a screening tool to identify those at risk of complicated grief applicable among bereaved patients in general practice and palliative care.</p> <p>Methods</p> <p>We examined the responses of 276 newly bereaved individuals to a variety of standardised and ad hoc questionnaire items eight weeks post loss. Inventory of Complicated Grief (ICG-R) was used as a gold standard of distress at six months after bereavement. Receiver operating characteristic (ROC) curves analysis was performed for all scales and items regarding ICG-R score. Sensitivity, specificity and area under curve (AUC) were calculated for scales and items with the most promising ROC curve analyses.</p> <p>Results</p> <p>Beck's Depression Inventory (BDI) was the scale with the highest AUC (0.83) and adding a single item question ('Even while my relative was dying, I felt a sense of purpose in my life') gave a sensitivity of 80% and specificity of 75%. The positive/negative predictive values for this combination of questions were 70% and 85%, respectively. With this screening tool bereaved people could be categorized into three groups where group 1 had 7%, group 2 had 23% and group 3 had 64% propensity of suffering from complicated grief six months post loss.</p> <p>Conclusions</p> <p>This study shows that the BDI in combination with a single item question eight weeks post loss may be used for clinical screening for risk of developing complicated grief after six months. The feasibility and clinical implications of the screening tool has to be tested in a clinical setting.</p

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Cesarean section rate in Iran, multidimensional approaches for behavioral change of providers: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The cesarean section rate has been steadily rising from 35% in 2000 to 40% in 2005 in Iran. The objective of this study was to identify barriers of reduce the cesarean section rate in Iran, as perceived by obstetricians and midwives as the main behavioral change target groups.</p> <p>Methods</p> <p>A qualitative study with purposive sampling was designed in which data were collected through in-depth interviews and document analyses. Hospitals were selected on the bases of being public and or private and their response to the ministry's C-section reduction interventions. The hospital director, obstetricians and midwives from each hospital were included in the study. The classification of barriers suggested by Grol and Wensing was used for the thematic analysis.</p> <p>Results</p> <p>After 26 in-depth interviews and document analyses, the barriers were identified as: financial, insurance and judicial problems at the <it>economic and political context </it>level; the type and ownership of hospitals, absence of an on call physician, absence of clear job-descriptions for obstetricians and midwives, too many interventions in the delivery process and shortage of human resources and facilities at the <it>organizational context </it>level; distrust and insufficient collaborations between obstetricians and midwives from macro to micro level at the <it>social context </it>level; attitudes toward complications of C-section, reduced capabilities of obstetricians, midwives and residents at the <it>individual professional </it>level; and finally, at the <it>innovation </it>level, vaginal delivery is time consuming, imposes high stress levels and is unpredictable.</p> <p>Conclusion</p> <p>Changing service providers' behavior is not possible through presentation of scientific evidence alone. A multi-level and multidisciplinary approach using behavior change theories is unavoidable. In future studies, the effect of the barriers should be determined to help policy makers recognize the most effective interventional package.</p

Mothers' accounts of their stillbirth experiences and of their subsequent relationships with their living infant:an interpretative phenomenological analysis

BACKGROUND: Due to contradictory findings regarding the effects of seeing and holding stillborn infants on women's worsening mental health symptoms, there is a lack of clear of guidance in stillbirth bereavement care. Although some current research examines this phenomenon we are still not certain of the meaning of such experiences to women and what effects there may be on her subsequent parenting. Thus the present study focuses on the meaning of the stillbirth experience to women and its influence on the subsequent pregnancy and subsequent parenting from the mothers' own experiences. METHODS: A purposive sample of six women who experienced a stillbirth during their first pregnancy and who then went on to give birth to a living child after a further pregnancy, took part in email interviews, providing rich and detailed experiential narratives about both the stillbirth itself, and their relationship with their living child. An Interpretive Phenomenological Analysis was carried out in order to focus on mothers making sense of such experiences. RESULTS: Analysis of written accounts led to the development of three overarching themes. In 'Broken Canopy', 'How This Happened' and 'Continuing Bonds', their accounts revealed an ongoing process where women accepted a new 'unsafe' view of the world, re-evaluated their view of self and others, and established relationships with both the deceased and the living infant. CONCLUSIONS: This study provided an insight into the stillbirth experience of mothers and its meaning to them with an existential focus. Typically the mother struggled with the contradictory process of accepting the existence of her deceased baby (this baby once lived) while being aware of the nonexistence (this baby). Meeting the dead baby was a crucial point at which the mother started processing her grief. The importance of individual differences in dealing with stressful situations was highlighted in terms of attachment strategies. Subsequent parenting experiences of mothers were very much influenced by their own previous experiences. Although some mothers managed to integrate this trauma into their life some remained very concerned and anxious about future and this anxiety then translated into their parenting experiences

Bank performance and executive pay: tournament or teamwork

We investigate the relationship between the dispersion of executive pay and bank performance/valuation by examining two competing theories, the tournament theory (hierarchical wage structure) and the equity fairness theory (compressed wage structure). The key variable of executive pay dispersion is measured using a hand-collected dataset composed of 63 banks from OECD countries and 29 banks from developing countries. The dataset covers the period 2004 to 2012. By combining and modifying a translog profit function and a pay-dispersion model, we are able to address the potential problems of relying on reduced-form estimation. In our subsample of developed and civil law countries, where bank performance is measured by either Tobin’s Q or by the price-to-book ratio, the overall impact of executive pay dispersion is mostly negative, and we find supporting evidence for the equity fairness theory, except for very high levels of dispersion. There is a non-linear effect, as banks perform best when there is either very low or very high executive pay dispersion. For developing country sample banks, greater executive pay dispersion has a negative impact on bank profit. In our subsample of common law countries, however, we find no evidence of a significant impact of executive pay dispersion on bank performance. We conclude that lower executive pay dispersion, a proxy for teamwork, is mostly effective in enhancing bank performance in a significant section of sample banks, i.e., civil law and developing countries

The variable influence of dispersant on degradation of oil hydrocarbons in subarctic deep-sea sediments at low temperatures (0-5 °C)

The microbial degradation of petroleum hydrocarbons at low temperatures was investigated in subarctic deep-sea sediments in th e Faroe Shetland Channel (FSC). The effect of the marine oil dispersant, Superdispersant 25 on hydrocarbon degradation was also examined. Sediments collected at 500 and 1000 m depth were spiked with a model oil containing 20 hydrocarbons and incubated at ambient temperature (5 and 0 °C, respectively) with and without marine dispersant. Treatment of sediments with hydrocarbons resulted in the enrichment of Gammaproteobacteria, and specifically the genera Pseudoalteromonas, Pseudomonas, Halomonas, and Cobetia. Hydrocarbon degradation was faster at 5 °C (500 m) with 65-89% of each component degraded after 50 days compared to 0-47% degradation at 0 °C (1000 m), where the aromatic hydrocarbons fluoranthene, anthracene, and Dibenzothiophene showed no degradation. Dispersant significantly increased the rate of degradation at 1000 m, but had no effect at 500 m. There was no statistically significant effect of Superdispersant 25 on the bacterial community structure at either station. These results show that the indigenous bacterial community in the FSC has the capacity to mitigate some of the effects of a potential oil spill, however, the effect of dispersant is ambiguous and further research is needed to understand the implications of its use