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.

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.

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.

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.

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.

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.

Increased hypothalamic somatostatin expression in mice transgenic for bovine or human GH.

Acute studies of GH removal by hypophysectomy or GH replacement in adult rats have shown that GH has a positive influence on its hypothalamic inhibitory hormone somatostatin (SRIH). The present study was undertaken to assess the effect of lifelong exposure to elevated GH on the development and differentiation of SRIH-producing hypothalamic neurons, including comparison of differing GH levels and heterologous species of GH. Expression of somatostatin peptide and mRNA was evaluated using respective immunocytochemistry and in situ hybridization in brains of transgenic mice bearing constructs of either human (hGH) or bovine (bGH) linked to metallothionein (MT) promoter or bGH linked to phosphoenolpyruvate carboxykinase (PEPCK) promoter. Nontransgenic littermates served as controls. All transgenic constructs resulted in high levels of circulating heterologous GH and significantly elevated body weights. Both bGH levels and body weights were higher in PEPCK-bGH than in MT-bGH mice; mean weights were not different between MT-bGH and MT-hGH mice. Numbers of SRIH-immunoreactive neurons in the hypophysiotropic periventricular nucleus (PeN) of transgenic mice showed a two-fold increase (P < 0.01) relative to control animals; the number of SRIH-positive cells in the medial basal hypothalamus (MBH) was comparable for transgenic and control mice. Total SRIH mRNA in situ hybridization intensity also showed a two-fold increase (P < 0.05) in the PeN of all transgenic mice compared with controls, and was not elevated in the MBH. The higher levels of GH produced in PEPCK-bGH transgenic mice led to greater weight gain, but not to greater SRIH expression than in other GH-transgenic mice, suggesting that the increased SRIH cell number and mRNA in the PeN of MT-GH-transgenic mice may represent a plateau of maximal feedback stimulation. The results indicate that lifelong elevated heterologous GH in mice stimulates hypothalamic SRIH expression markedly. It is not known whether this mechanism is direct or indirect via a mediator of GH such as IGF, but the heterologous GH appears to be specific to these hypophysiotropic neurons.

Effects of a muscarinic antagonist on various components of female sexual behavior in the rat.

The effects of the muscarinic antagonist scopolamine on lordosis, solicitation, pacing, approach, attractivity, and activity were evaluated in ovariectomized rats brought into sexual receptivity with estrogen and progesterone. Systemic (1 mg/rat) or intraventricular (10 micrograms bilaterally) administration of scopolamine significantly reduced the incidence of lordosis and solicitation behaviors and disrupted typical pacing of sexual contacts with a stimulus male. In addition, females avoided contact with a stimulus male, but not a stimulus female, following intraventricular infusion of scopolamine. The levels of general activity and frequencies of sexual contacts were similar in females treated intraventricularly with scopolamine and vehicle solutions. Consequently, scopolamine disrupted various components of sexual behavior, including lordosis, solicitation, pacing, and approach, without altering female attractivity or general activity.

Characteristics of the spinal nucleus of the bulbocavernosus are influenced by genotype in the house mouse.

Sex differences and differences related to genotype have been observed in the nervous system. These observations provide the opportunity to relate differences in neural structure to functional differences. The spinal nucleus of the bulbocavernosus (SNB) was examined in castrated and gonadally intact male house mice from the following 3 genotypes: C57B1/6J, DBA/2J, and the B6D2F1 (F1) hybrid (resulting from a cross between a C57B1/6J female and a DBA/2J male). The number and size of SNB neurons were determined from thionin-stained thick sections from spinal cords of these mice. The gonadally intact DBA males had significantly fewer SNB motoneurons than either the C57 or F1 males, but no strain differences were observed for the size of SNB cells. Castration of adults significantly reduced SNB neuronal number, but not somatic area, in the C57s (the maternal strain) and reduced somatic area, but not neuronal number, in the DBAs (the paternal strain). Both characteristics of the SNB were reduced by castration in the F1 hybrid. Thus, the size and number of SNB neurons appear to be inherited independently and the influence of gonadal hormones on these traits varies with genotype.

Carbachol phase shifts the circadian rhythm of locomotor activity in the Djungarian hamster.

The effects of light on the circadian system may involve the neurotransmitter acetylcholine (ACh). The purpose of the present study was to determine whether carbachol, a cholinergic agonist, mimics the phase-shifting effects of light on the circadian rhythm of locomotor activity (CRLA) in the Djungarian hamster. Phase response curves (PRCs) were measured for blind animals injected intracerebroventricularly with either vehicle or carbachol at different circadian times. Carbachol produced significant phase delays in the CRLA when administered at circadian time (CT) 12-16 and small, but significant phase advances when given at CT 8. No consistent phase shifts were observed in response to carbachol injections at other circadian times. Phase shifts produced by carbachol injections at CT 8 and 12 were similar for both sighted and blind animals. Light pulses to sighted hamsters produced phase advances at CT 20 and phase delays at CT 12. Both the carbachol PRC and the PRC for light pulses in the Djungarian hamster have phase delay regions in the early subjective night. However, these two PRCs have different phase advance regions. These results indicate that carbachol mimics some of the effects of light on the circadian system in the Djungarian hamster and support the hypothesis that cholinergic mechanisms may play a role in mediating some of the phase-shifting effects of light on the circadian clock of mammals.

Administration of carbachol into the lateral ventricle and suprachiasmatic nucleus (SCN) produces dose-dependent phase shifts in the circadian rhythm of locomotor activity.

The cholinergic agonist, carbachol, induces phase-dependent shifts in the timing of the circadian rhythm of locomotor activity (CRLA). The effects of carbachol injections into the lateral ventricles of hamsters were compared between circadian times that produce phase delays vs. phase advances in the CRLA. The shape of the dose-response curves and the ED50 for carbachol injections were similar for the two injection times. The second experiment demonstrated the dose-dependence of phase advances produced by carbachol injections into the area of the suprachiasmatic nucleus. These results indicate that carbachol exerts similar dose-dependent actions for both phases advances and phase delays.

Environmental influences on masculine sexual behavior in mice.

Retention of masculine copulatory behaviors following castration varies among B6D2F1 male mice. In the present study, we examined the effect of test environment and the amount of behavioral testing after castration, on retention of copulatory responses in castrated B6D2F1 male mice. Results showed that weekly behavioral testing after castration was not necessary for the retention of ejaculatory reflexes. However, the test environment had a major effect. Following castration, 26% of the males completely stopped showing ejaculatory responses when tested in the test arenas. When these males were tested in their home cages, 75% achieved at least one ejaculatory response in four home cage tests. Castrated males that continued to copulate in the test arena situation also achieved ejaculatory reflexes in their home cages. These results indicate that for some B6D2F1 males, the retention of sexual behaviors after castration is influenced by environmental factors.

Hormonal restoration of masculine sexual behavior in long-term castrated B6D2F1 mice.

In contrast to the facilitative effects reported for other rodents, testosterone treatment at the time of castration previously was reported to inhibit masculine sexual behavior in male B6D2F1 mice. Males of this genotype vary in their behavioral response to castration. Some castrates retain sexual behaviors for many weeks after surgery, whereas others do not. In the present study, we sought to determine the effects of exogenous steroid hormone treatment on castrated B6D2F1 mice that had ceased to show copulatory behavior. Testosterone propionate and estradiol benzoate restored copulatory behavior to precastration levels in B6D2F1 males that did not retain sexual behaviors after castration.

Mate preference and avoidance in female rats following treatment with scopolamine.

The effects of the muscarinic antagonist, scopolamine, on the behavior of female rats in a mate preference test were determined. Ovariectomized rats were primed with sufficient doses of estradiol benzoate (0.25 micrograms for 3 days) and progesterone (500 micrograms) to activate full sexual receptivity. Beginning 15 min after intraperitoneal injection of saline (0.4 ml/kg) or scopolamine hydrochloride (1 mg/kg), females were tested in an arena divided into three compartments. Females treated with scopolamine clearly avoided a compartment occupied by a gonadally intact stimulus male, instead preferring a compartment occupied by a castrated male or an empty neutral compartment. Direct contact with an intact male was a critical feature of this avoidance because females treated with scopolamine did not avoid intact males that were confined within a chamber that prevented physical contact between the male and female. Results indicate that female rats treated with scopolamine avoid direct physical contact with sexually active males, possibly due to an alteration in sexual motivation and/or the aversive nature of this interaction.

Retention of masculine sexual behavior following castration in male B6D2F1 mice.

The reduction of masculine sexual behavior following castration varies widely among genotypes. In contrast to the loss of sexual behavior by castrated males of other strains, males of the B6D2F1 genotype retain the ejaculatory reflex for many weeks after castration. The present study examined this retention phenomenon. Masculine sexual behaviors were measured before and after castration or sham operation in male C57BL/6J, DBA/2J, and B6D2F1 mice. Castrated C57BL/6J and DBA/2J males showed a rapid decline in copulatory behavior. In contrast, 30% of the B6D2F1 males continued to ejaculate 25 weeks after castration. Regardless of whether or not sexual behaviors were retained, levels of plasma testosterone and hypothalamic nuclear estrogen receptors were reduced by castration. These results suggest that the intra- and inter-strain differences in the retention of sexual behavior following castration are not due to differences in levels of steroid hormones. Further, some B6D2F1 males retain the ability to copulate in the absence of gonadal hormone levels required for the maintenance of sexual behavior in other genotypes.

Midazolam, a short-acting benzodiazepine, resets the circadian clock of the hamster.

Treatment with the short-acting benzodiazepine, triazolam, has been found to induce changes in both behavioral and endocrine circadian rhythms in hamsters. The objective of this study was to determine if these effects of triazolam could be generalized to other short-acting benzodiazepines. Therefore, the effects of midazolam on the biological clock of the hamster were examined in detail. A phase-response curve and a dose-response curve were measured to determine the effects of a single intraperitoneal injection of midazolam on the circadian clock of hamsters free-running in constant light. Midazolam injections produced maximal phase advances at circadian time (CT) 6 and 9 and maximal phase delays at CT 15 and 21. Doses of 2.5 mg or larger produced phase shifts that were significantly different from those produced by the vehicle controls. In addition, the phase-shifting effects of midazolam were completely blocked by administration of the benzodiazepine receptor antagonist, RO 15-1788, indicating that the phase-shifting actions of midazolam are mediated via benzodiazepine receptors. These results indicate that the previously reported effects of triazolam on the circadian clock can be generalized to other short-acting benzodiazepines.

The first year of an independent hospice in Hong Kong.

Two hundred and ninety-nine patients admitted to the Bradbury Hospice, Hong Kong, during the period from 1 June 1992 to 31 May 1993 were studied. While a majority of the patients held realistic expectations of the hospice service, a small percentage expected cure, prolongation of life or even euthanasia. Physical symptoms were the main concern in a vast majority of patients, the commonest being pain. Only 1.7% regarded psycho-social problems as their main distress. Morphine was widely used for pain control, although 68% of patients required co-analgesics or palliative radiotherapy as well. Morphine was also the mainstay of treatment for dyspnoea. It might be worthwhile for hospices to be equipped with oxygen, as approximately 71% of our patients with dyspnoea as their main distress benefited from oxygen therapy. Many patients expressed fear of death; more worried about suffering. While 17.7% were assessed to be in the stage of acceptance on admission, 14.7% expressed self-pity when their search for meaning failed. Although many patients were atheists, a majority of patients with religious beliefs found that they could get support from their faith. A significant number of patients believed in Shumei. Increased knowledge of this religion would be helpful in taking care of these patients.

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.

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.

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.