Managing relapsed refractory lymphoma with palliative oral chemotherapy: A multicentre retrospective study.

PEP-C (prednisolone, etoposide, procarbazine and cyclophosphamide) is an orally administered daily chemotherapy regimen used with palliative intent in relapsed refractory lymphoma. To our knowledge, no data on PEP-C have been reported since the original group described the regimen. Here we present a multicentre retrospective cohort reporting our use of PEP-C in 92 patients over an 8-year period. We find that even heavily pretreated lymphoma can respond to PEP-C, particularly low-grade lymphoma (including mantle cell) and lymphoma that was sensitive to the previous line of systemic therapy (chemosensitive). These characteristics may help in the selection of patients likely to derive benefit. The median overall survival of patients with chemosensitive lymphoma treated with PEP-C is 217 days. Within the limitations of a retrospective cohort, we find that PEP-C is well tolerated: the most common toxicity leading to discontinuation is marrow suppression. We suggest that PEP-C should be considered for patients with relapsed refractory lymphoma in two settings: first, where there is no licensed alternative; and second, where the licensed alternative is an intravenous drug and the patient would prefer to choose an oral chemotherapy option

Positivism and the peace/power dialectic: feminist reflections in a transnational age

Human rights have often been described as the ‘morality of the law.’ Decades of feminist critique have exposed the foundations of law as deeply biased and patriarchal. And yet the idea that almost all legal philosophers are or should be positivists continues to hold sway in some quarters. The claim of this chapter is that the positivist paradigm of law, the idea that a law is valid if it emanates from a particular recognised source, provides a de minimis standard for the basis of legal relations and a starting point for critique, but offers little more. In this reductionist sense then it may be appropriate to state that everyone who engages with law is de facto a positivist. However, in an increasingly complex, diversified and pluralistic society where the transcendence of national borders and processes of globalisation neither recognise nor sustain state specific Grundnormen, legal positivism faces challenges and realities which will not and cannot leave the fundaments of the positivist paradigm unchanged. Rather, examination of the positivist paradigm through the transnational lenses of both human rights and feminist critique demonstrates that the metaphysical austerity lauded by proponents of the positivist position as a virtue, leaves it barren and inadequate to respond to the deep structural inequalities of the law. The patriarchal assumptions of the norms constituting the positivist paradigm must be challenged. The role played by human rights in providing the positivist position with a moral conscience and an opportunity to address not yet imagined atrocities and quotidian injustices in an increasingly globalised society must be critically analysed. In carrying out such a critical examination, this chapter conceptualises and historically establishes positivism at the apex of what is introduced as the peace/power dialectic. The conclusion is that whilst positivism as a historical methodology for peace may not have been (on a generous reading) malicious in establishing the economy of exclusions that it relies on, including gender, race, social class, sexuality and ability, the maintenance of the positivist position as legal truth and the position of power might well be

Code of practice for electrical energy storage systems

The purpose of this Code of Practice is to provide a reference to practitioners on the safe, effective and competent application of electrical energy storage systems. It also provides an understanding of the common terms and operating modes of electrical energy storage systems. Building on the IET’s technical briefing: Electrical Energy Storage: an Introduction this will also provide detailed information on the specification, design, installation, commissioning, operation and maintenance of an energy storage system. The scope covers all types of electrical and electrochemical energy storage systems; integration into low voltage power systems; industrial, commercial and domestic applications and systems aligned with existing standards, regulations and guidance

Children’s future-oriented cognition

Children's future-oriented cognition has become a well-established area of research over the last decade. Future-oriented cognition encompasses a range of processes, including those involved in conceiving the future, imagining and preparing for future events, and making decisions that will affect how the future unfolds. We consider recent empirical advances in the study of such processes by outlining key findings that have yielded a clearer picture of how future thinking emerges and changes over childhood. Our interest in future thinking stems from a broader interest in temporal cognition, and we argue that a consideration of developmental changes in how children understand and represent time itself provides a valuable framework in which to study future-oriented cognition

Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson\u27s disease (PD MED): A large, open-label, pragmatic randomised trial

\ua9 2014 Elsevier Ltd. Background Whether initial treatment for Parkinson\u27s disease should consist of levodopa, dopamine agonists, or monoamine oxidase type B inhibitors (MAOBI) is uncertain. We aimed to establish which of these three classes of drug, as initial treatment, provides the most effective long-term control of symptoms and best quality of life for people with early Parkinson\u27s disease. Methods In this pragmatic, open-label randomised trial, patients newly diagnosed with Parkinson\u27s disease were randomly assigned (by telephone call to a central office; 1:1:1) between levodopa-sparing therapy (dopamine agonists or MAOBI) and levodopa alone. Patients and investigators were not masked to group assignment. Primary outcomes were the mobility dimension on the 39-item patient-rated Parkinson\u27s disease questionnaire (PDQ-39) quality-of-life scale (range 0-100 with six points defined as the minimally important difference) and cost-effectiveness. Analysis was intention to treat. This trial is registered, number ISRCTN69812316. Findings Between Nov 9, 2000, and Dec 22, 2009, 1620 patients were assigned to study groups (528 to levodopa, 632 to dopamine agonist, 460 to MAOBI). With 3-year median follow-up, PDQ-39 mobility scores averaged 1\ub78 points (95% CI 0\ub75-3\ub70, p=0\ub7005) better in patients randomly assigned to levodopa than those assigned to levodopa-sparing therapy, with no increase or attrition of benefit during 7 years\u27 observation. PDQ-39 mobility scores were 1\ub74 points (95% CI 0\ub70-2\ub79, p=0\ub705) better in patients allocated MAOBI than in those allocated dopamine agonists. EQ-5D utility scores averaged 0\ub703 (95% CI 0\ub701-0\ub705; p=0\ub70002) better with levodopa than with levodopa-sparing therapy; rates of dementia (hazard ratio [HR] 0\ub781, 95% CI 0\ub761-1\ub708, p=0\ub714), admissions to institutions (0\ub786, 0\ub763-1\ub718; p=0\ub74), and death (0\ub785, 0\ub769-1\ub706, p=0\ub717) were not significantly different, but the upper CIs precluded any substantial increase with levodopa compared with levodopa-sparing therapy. 179 (28%) of 632 patients allocated dopamine agonists and 104 (23%) of 460 patients allocated MAOBI discontinued allocated treatment because of side-effects compared with 11 (2%) of 528 patients allocated levodopa (p<0\ub70001). Interpretation Very small but persistent benefits are shown for patient-rated mobility scores when treatment is initiated with levodopa compared with levodopa-sparing therapy. MAOBI as initial levodopa-sparing therapy was at least as effective as dopamine agonists. Funding UK National Institute for Health Research Health Technology Assessment Programme and UK Department of Health

Critical care usage after major gastrointestinal and liver surgery: a prospective, multicentre observational study

Background Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy. Results Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51–19.97) than planned admissions (OR: 2.32, 95% CI: 1.43–3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8–51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI. Conclusions After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies

Safety of Nonsteroidal Anti-inflammatory Drugs in Major Gastrointestinal Surgery: A Prospective, Multicenter Cohort Study

Background Significant safety concerns remain surrounding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) following gastrointestinal surgery, leading to wide variation in their use. This study aimed to determine the safety profile of NSAIDs after major gastrointestinal surgery. Methods Consecutive patients undergoing elective or emergency abdominal surgery with a minimum one-night stay during a 3-month study period were eligible for inclusion. The administration of any NSAID within 3 days following surgery was the main independent variable. The primary outcome measure was the 30-day postoperative major complication rate, as defined by the Clavien–Dindo classification (Clavien–Dindo III–V). Propensity matching with multivariable logistic regression was used to produce odds ratios (OR) and 95 % confidence intervals. Results From 9264 patients, 23.9 % (n = 2212) received postoperative NSAIDs. The overall major complication rate was 11.5 % (n = 1067). Following propensity matching and adjustment, use of NSAIDs were not significantly associated with any increase in major complications (OR 0.90, 0.60–1.34, p = 0.560). Conclusions Early use of postoperative NSAIDs was not associated with an increase in major complications following gastrointestinal surgery