Processes of consent in research for adults with impaired mental capacity nearing the end of life: systematic review and transparent expert consultation (MORECare_Capacity statement).

BACKGROUND: Involving adults lacking capacity (ALC) in research on end of life care (EoLC) or serious illness is important, but often omitted. We aimed to develop evidence-based guidance on how best to include individuals with impaired capacity nearing the end of life in research, by identifying the challenges and solutions for processes of consent across the capacity spectrum. METHODS: Methods Of Researching End of Life Care_Capacity (MORECare_C) furthers the MORECare statement on research evaluating EoLC. We used simultaneous methods of systematic review and transparent expert consultation (TEC). The systematic review involved four electronic databases searches. The eligibility criteria identified studies involving adults with serious illness and impaired capacity, and methods for recruitment in research, implementing the research methods, and exploring public attitudes. The TEC involved stakeholder consultation to discuss and generate recommendations, and a Delphi survey and an expert 'think-tank' to explore consensus. We narratively synthesised the literature mapping processes of consent with recruitment outcomes, solutions, and challenges. We explored recommendation consensus using descriptive statistics. Synthesis of all the findings informed the guidance statement. RESULTS: Of the 5539 articles identified, 91 met eligibility. The studies encompassed people with dementia (27%) and in palliative care (18%). Seventy-five percent used observational designs. Studies on research methods (37 studies) focused on processes of proxy decision-making, advance consent, and deferred consent. Studies implementing research methods (30 studies) demonstrated the role of family members as both proxy decision-makers and supporting decision-making for the person with impaired capacity. The TEC involved 43 participants who generated 29 recommendations, with consensus that indicated. Key areas were the timeliness of the consent process and maximising an individual's decisional capacity. The think-tank (n = 19) refined equivocal recommendations including supporting proxy decision-makers, training practitioners, and incorporating legislative frameworks. CONCLUSIONS: The MORECare_C statement details 20 solutions to recruit ALC nearing the EoL in research. The statement provides much needed guidance to enrol individuals with serious illness in research. Key is involving family members early and designing study procedures to accommodate variable and changeable levels of capacity. The statement demonstrates the ethical imperative and processes of recruiting adults across the capacity spectrum in varying populations and settings.

End of life care: how do we move forward?

Death and dying are inevitable. High quality and accessible palliative and end of life care can help people who are facing progressive life-threatening and life-limiting illness, and those dear to them, by focusing on their quality of life and addressing the problems associated with their situation. This paper draws attention to the scale of the challenge, some of the key areas we could address and the shifts in culture, mindset and leadership approach that are needed.

Single-port versus conventional laparoscopic total extra-peritoneal inguinal hernia repair: a prospective, randomized, controlled clinical trial.

BACKGROUND: The advantage of single-port total extra-peritoneal (TEP) inguinal hernia repair over the conventional technique is still debatable. Our objective was to compare the outcomes of TEP inguinal hernia repair using either a single-port or conventional surgical technique, in two blind randomized groups of patients. METHODS: In this prospective, randomized, double-blind, controlled clinical trial, 100 patients undergoing surgery for unilateral inguinal hernia were randomized into two groups: One group underwent conventional laparoscopic TEP inguinal hernia repair, while the other was selected for single-port TEP repair. Primary endpoint is postoperative pain (VAS), while secondary endpoints are recurrence, chronic pain and complications. RESULTS: From 100 patients, 49 underwent single-port hernia TEP repair, 50 had conventional three-port TEP hernia repair, and one patient declined to participate after randomization. The two groups were comparable in terms of patient demographics and operative findings. Mean operative time was 49.1(±13.8) min in the conventional group and 54.1(±14.4) min in the single-port group (p = 0.08). Mean hospital stay was 19.7(±5.8) h in the conventional group and 20.5(±6.4) h in the single-port group (p = 0.489). No major complications and no recurrence reported at 11-month follow-up. No statistically significant difference noted in postoperative pain between the two groups at regular intervals. CONCLUSIONS: The outcomes after laparoscopic TEP inguinal hernia repair with a single-port device are similar but not superior to the conventional technique.

Intelligent speed assistance for serious speeders: the results of the Dutch Speedlock trial.

One of the most important policy questions regarding Intelligent Speed Assistance (ISA) is whether or not it should be implemented, and if so how. In 2010 the Dutch Ministry of Infrastructure and the Environment decided to perform a field operational test to investigate the possibility of using ISA as a penalty system for serious speed offenders. This paper presents the results of this research, focusing on the effects on road safety. The results show that the two types of ISA systems that were tested have a huge effect on driver behavior and have the potential to improve road safety by reducing the level of speeding, mean speed, as well as the standard deviation of speed. However, the users show little sign of learning after the systems are turned off. Moreover, the serious offenders frequently use the emergency button to override the system which might seriously affect the efficacy of the system.

Predicting survival time in noncurative patients with advanced cancer: a prospective study in China.

BACKGROUND: Accurate prediction of prognosis for cancer patients is important for good clinical decision making in therapeutic and care strategies. The application of prognostic tools and indicators could improve prediction accuracy. OBJECTIVE: This study aimed to develop a new prognostic scale to predict survival time of advanced cancer patients in China. METHODS: We prospectively collected items that we anticipated might influence survival time of advanced cancer patients. Participants were recruited from 12 hospitals in Shanghai, China. We collected data including demographic information, clinical symptoms and signs, and biochemical test results. Log-rank tests, Cox regression, and linear regression were performed to develop a prognostic scale. RESULTS: Three hundred twenty patients with advanced cancer were recruited. Fourteen prognostic factors were included in the prognostic scale: Karnofsky Performance Scale (KPS) score, pain, ascites, hydrothorax, edema, delirium, cachexia, white blood cell (WBC) count, hemoglobin, sodium, total bilirubin, direct bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (ALP) values. The score was calculated by summing the partial scores, ranging from 0 to 30. When using the cutoff points of 7-day, 30-day, 90-day, and 180-day survival time, the scores were calculated as 12, 10, 8, and 6, respectively. CONCLUSIONS: We propose a new prognostic scale including KPS, pain, ascites, hydrothorax, edema, delirium, cachexia, WBC count, hemoglobin, sodium, total bilirubin, direct bilirubin, AST, and ALP values, which may help guide physicians in predicting the likely survival time of cancer patients more accurately. More studies are needed to validate this scale in the future.

Recognizing that it is part and parcel of what they do: teaching palliative care to medical students in the UK.

In their first year of work, newly qualified doctors will care for patients who have palliative care needs or who are dying, and they will need the skills to do this throughout their medical career. The General Medical Council in the United Kingdom has given clear recommendations that all medical students should receive core teaching on relieving pain and distress together with caring for the terminally ill. However, medical schools provide variable amounts of this teaching; some are able to deliver comprehensive programmes whilst others deliver very little. This paper presents the results of a mixed methods study which explored the structure and content of palliative care teaching in different UK medical schools, and revealed what coordinators are trying to achieve with this teaching. Nationally, coordinators are aiming to help medical students overcome the same fears held by the lay public about death, dying and hospices, to convey that the palliative care approach is applicable to many patients and is part of every doctors' role, whatever their specialty. Although facts and knowledge were thought to be important, coordinators were more concerned with attitudes and helping individuals with the transition from medical student to foundation doctor, providing an awareness of palliative medicine as a specialty and how to access it for their future patients.

A description of CT features of Clostridium difficile infection of the small bowel in four patients and a review of literature.

Clostridium difficile associated disease is an increasingly common cause of morbidity and mortality. Pseudomembranous colitis following hospital-administered antibiotic treatment is the most common symptomatic manifestation. Small bowel enteritis caused by C. difficile, however, is rarely described. Here, we present a series of four patients with hospital-acquired small bowel enteritis caused by C. difficile, discuss its CT and histopathological features, and review the current literature.

Patients' constructions of disability in metastatic spinal cord compression.

Metastatic spinal cord compression (MSCC) is characterised by poor prognosis and serious physical disability. Patients have complex rehabilitation needs, but the evidence on rehabilitation is sparse. This study aimed to ascertain the constructions placed upon disability by patients with MSCC. The method consisted of a series of nine process-tracing, longitudinal case studies, involving 58 interviews with 9 patients, 6 carers and 29 staff in one National Health Service region. A context-mechanism-outcome configuration was adopted as a conceptual basis for data collection, together with a constant comparative method of data analysis. Patients' orientation to disability incorporated two apparently inconsistent attitudes. Patients acknowledged that their situation had changed and that their future plans would need to accommodate altered circumstances. However, they also resisted the idea of themselves as disabled, wanting to retain an image of themselves as resourceful and resilient. Patients used a number of strategies to reconcile the tension between these two positions. The illusions incorporated into the 'failure to acknowledge' pole of this orientation are self-protective and, like other positive illusions, have psychological benefits. Providing effective and acceptable support to patients living with disability relies on professional responses that are able to sustain patients' sense of their own competence.

A Delphi study to develop the Association for Palliative Medicine consensus syllabus for undergraduate palliative medicine in Great Britain and Ireland.

The Association for Palliative Medicine (APM) produced a previous undergraduate palliative medicine syllabus in 1992. This study describes the process of developing the new APM consensus syllabus against the background of changes in medical education and palliative medicine since 1992. The syllabus was derived by means of a Delphi study carried out amongst experts in palliative medicine across Britain and Ireland. Forty-three participants agreed to take part. Three rounds of the Delphi study took place. Consensus (75% agreement) was achieved in over 90% of the outcomes. The new syllabus is broken down into the following sections: basic principles, physical care, psychosocial care, culture, language, religious and spiritual issues, ethics and legal frameworks. Learning outcomes are categorised as essential or desirable. Using a Delphi study, we have developed a consensus syllabus for undergraduate palliative medicine. This is sufficiently flexible to allow all medical schools to ensure that their students achieve the essential learning outcomes by the time they graduate, whereas those with more generous curricular space will additionally be able to deliver selected desirable learning outcomes.

Interventions for noisy breathing in patients near to death.

BACKGROUND: Noisy breathing (death rattle) occurs in 23 to 92% of people who are dying. The cause of death rattle remains unproven but is presumed to be due to an accumulation of secretions in the airways. It is therefore managed physically (repositioning and clearing the upper airways of fluid with a mechanical sucker) or pharmacologically (with anticholinergic drugs). OBJECTIVES: To describe and assess the evidence for the effectiveness of interventions used to treat death rattle in patients close to death. SEARCH STRATEGY: Randomised controlled trials (RCTs), before and after studies and interrupted time series (ITS) studies in adults and children with death rattle were sought by MEDLINE (1966 to 2007), EMBASE (1980 to 2007), CINAHL (1980 to 2007), the Cochrane Pain, Palliative and Supportive Care Trials Register and the Cochrane Central Register of Controlled Trials. In addition, the reference lists of all relevant trials and reports were checked and investigators who are known to be researching this area were contacted for unpublished data or knowledge of the grey literature. SELECTION CRITERIA: RCTs, controlled before and after studies and ITS reporting the outcome of pharmacological and non-pharmacological interventions for treating death rattle. DATA COLLECTION AND ANALYSIS: Data was extracted by two independent review authors and trials were quality scored. There was insufficient data to carry out an analysis. MAIN RESULTS: Thirty studies were identified, of which only one study met the inclusion criteria. This small study was a randomised placebo-controlled trial of the use of hyoscine hydrobromide in patients with death rattle. Hyoscine hydrobromide tended to reduce death rattle compared to placebo but this was not significant. A larger randomised study, comparing atropine, hyoscine butylbromide and scopolamine, is in progress. AUTHORS' CONCLUSIONS: There is currently no evidence to show that any intervention, be it pharmacological or non-pharmacological, is superior to placebo in the treatment of death rattle. We acknowledge that in the face of heightened emotions when death is imminent, it is difficult for staff not to intervene. It is therefore likely that the current therapeutic options will continue to be used. However, patients need to be closely monitored for lack of therapeutic benefit and adverse effects while relatives need time, explanation and reassurance to relieve their fears and concerns. There is a need for more well-designed multi-centre studies with objective outcome measures and the ability to recruit sufficient numbers.

The sound of death rattle II: how do relatives interpret the sound?

BACKGROUND: In an earlier study, we found that some bereaved relatives (five out of 12 interviewed) found it distressing to hear the sound of death rattle, but the remainder did not. In this paper, we report a second study in which we explored how a different group of relatives interpreted the sound of death rattle when they heard it. METHOD: We conducted face-to-face semi-structured interviews with 25 bereaved relatives using the principles of grounded theory. RESULTS: Seventeen of the 25 bereaved relatives interviewed had heard the sound of death rattle. Ten relatives were distressed by the sound, but seven were not. Some relatives regarded the sound of death rattle as a useful warning sign that death was imminent. Their interpretation of the sound was influenced by the patient's appearance, being less concerned if the patient was not obviously disturbed. Relatives were distressed when they thought that the sound of death rattle indicated that the patient might be drowning or choking. These concerns were reinforced by seeing fluid dribble from the dying patient's mouth. CONCLUSION: This study confirms the previous finding that not all relatives are distressed by the sound of death rattle. It also demonstrates that relatives interpret the sound in a variety of ways, some matter of fact and some distressing. We suggest that effective communication is helpful in uncovering relatives' interpretation of death rattle and dispelling unwarranted fears.

Potential for drug interactions involving cytochrome P450 in patients attending palliative day care centres: a multicentre audit.

AIM: To determine the potential for drug interactions involving cytochrome P450 (CYP) in patients receiving palliative day care. METHODS: Drugs used by patients attending four specialist palliative day care centres were reviewed to identify combinations that could result in a pharmacokinetic interaction via any of the five main human forms of CYP. RESULTS: Of 160 patients, 145 (91%) were prescribed at least one drug that was a substrate, inhibitor or inducer of one of the five main CYP isoforms. Twenty-four drug combinations, involving 34 patients, could have given rise to a clinically important interaction. CONCLUSIONS: Prescribers should be aware that in this group of patients, one in five are at risk of a clinically important CYP-mediated drug interaction.

Palliative care: a suitable setting for undergraduate interprofessional education.

Effective delivery of high-quality palliative care requires effective interprofessional teamworking by skilled health and social care professionals. Palliative care is therefore highly suitable for sowing the seeds of interprofessional teamworking in early professional education. This paper describes experiences of running undergraduate interprofessional workshops in palliative care for medical, nursing, social work, physiotherapy and occupational therapy students. These workshops are unusual in three respects: first, the involvement of family carers mean that these learning experiences are rooted in clinical reality; secondly, there is no attempt to 'tidy up' the story for the students; thirdly, unlike many undergraduate interprofessional programmes, these workshops have been sustained over several years. Evaluation of these workshops demonstrate that students value and enjoy the opportunity to work together; they find the experience moving, informative and interesting. Feedback from carers showed that they appreciated the opportunity to present their real-life experiences to students. Our evidence suggests that palliative care is a suitable subject for undergraduate interprofessional education.

Fall incidence in a state psychiatric hospital in Singapore.

The results of a retrospective study of fall incidence during a 1-year period in a psychiatric hospital in Singapore are reported, involving 309 patients who fell one or more times during their stay. The profile of inpatients involved in falls was identified. Data were derived from standard incident forms completed whenever patients had a fall. A total of 348 falls were identified for the 1-year period. Results revealed higher fall rates in younger male epileptic patients; elderly female patients, age 70 and older with depression or dementia; individuals with concomitant medical conditions; and patients taking three types of medication. The majority of falls occurred when the activity level was high in the ward. Young epileptic patients and elderly depressed patients were prone to repeated falls. These results have the potential to assist in identifying patients at high risk and in designing and implementing strategies to prevent such incidents.

Identification of lactic acid bacteria from chili bo, a Malaysian food ingredient.

Ninety-two strains of lactic acid bacteria (LAB) were isolated from a Malaysian food ingredient, chili bo, stored for up to 25 days at 28 degreesC with no benzoic acid (product A) or with 7,000 mg of benzoic acid kg-1 (product B). The strains were divided into eight groups by traditional phenotypic tests. A total of 43 strains were selected for comparison of their sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) whole-cell protein patterns with a SDS-PAGE database of LAB. Isolates from product A were identified as Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus farciminis, Pediococcus acidilactici, Enterococcus faecalis, and Weissella confusa. Five strains belonging to clusters which could not be allocated to existing species by SDS-PAGE were further identified by 16S rRNA sequence comparison. One strain was distantly related to the Lactobacillus casei/Pediococcus group. Two strains were related to Weissella at the genus or species level. Two other strains did not belong to any previously described 16S rRNA group of LAB and occupied an intermediate position between the L. casei/Pediococcus group and the Weissella group and species of Carnobacterium. The latter two strains belong to the cluster of LAB that predominated in product B. The incidence of new species and subspecies of LAB in chili bo indicate the high probability of isolation of new LAB from certain Southeast Asian foods. None of the isolates exhibited bacteriocin activity against L. plantarum ATCC 14917 and LMG 17682.

Activation of caspase-1 in the nucleus requires nuclear translocation of pro-caspase-1 mediated by its prodomain.

The interleukin-1beta-converting enzyme-like protease precursor, pro-caspase-1, has an N-terminal prodomain that is removed during cleavage activation of the protease. Here we show that tumor necrosis factor treatment of HeLa cells induced apoptosis without detectable proteolytic activation of caspase-1 in the cytosol. Instead, tumor necrosis factor induced the translocation of pro-caspase-1 to the nucleus where it was proteolytically activated, releasing the intact prodomain. We identified a nuclear localization signal in the prodomain, which was required for translocation of both pro-caspase-1 as well as its prodomain to the nucleus. Surprisingly, transfected MCF-7 carcinoma or embryonic kidney 293T cells expressing the prodomain alone underwent apoptosis. These results show that death signal-induced nuclear targeting is a novel activity of a caspase prodomain and indicate that caspase-1 and its prodomain may have hitherto unsuspected nuclear functions in apoptosis.