Local analgesics do not cause any direct nerve damage unless they are injected intraneurally or given in higher concentrations than that which is commercially available. Several different laboratory models have proven

that all local analgesics can be neurotoxic but that lidocaine and tetracaine are potentially more neurotoxic than bupivacaine [17]. The pathogenesis Inhibitors,research,lifescience,medical of local analgesics-induced local tissue toxicity is poorly understood. There appears to be a relationship between concentration and neurotoxicity. In 1985, Ready et al. [18] evaluated the neurotoxic effects of single injections of local analgesics in rabbits. They reported that spinal cord histopathology remained normal and that persistent neurologic deficits were not seen with clinically used concentrations of tetracaine, lidocaine, bupivacaine, or chloroprocaine. However, histopathologic changes and neurologic deficits did occur with higher concentrations of tetracaine (1%, up to 8%) and lidocaine (8%, Inhibitors,research,lifescience,medical up to 32%). It was found that high concentrations of lidocaine (and tetracaine) caused neural injury. Notably, in this model, extensive neurologic impairment was not necessarily accompanied by equally extensive

lesions in the spinal cord and nerve roots, thus demonstrating the need for multiple models Inhibitors,research,lifescience,medical to fully Ceritinib datasheet assess neurotoxicity. Particularly, the highest concentration of bupivacaine (3.3%) was not consistently associated with comparable neural damage. Peripheral nerve injury is a rare complication of regional anesthesia. The pathogenesis of local analgesics-induced local tissue toxicity is poorly understood. The mechanism of this enhanced toxicity remains to be established, but it may be related to an effect of

diverse vasoconstriction Inhibitors,research,lifescience,medical on anesthetic exposure [19]. Ischemia is one of the possible causative mechanisms which may result from changes in peripheral blood flow caused by a vasopressor adjuvant such as epinephrine. Some believe Inhibitors,research,lifescience,medical that this neurological damage is a result of spinal cord ischemia either due to prolonged hypotension during surgery or as a consequence of arterial constriction resulting from and the use of epinephrine in the local anesthetics solution [20]. The use of additives in the solution also has been implicated as contributing factors. The pressure of the injected agent may cause nonspecific pressure-related nerve damage. An immune-mediated mechanism may be possible as suggested by others [4, 16]. In Brummett’s study, rat sciatic nerves were harvested at either 24 hours or 14 days after injection and analyzed for perineural inflammation and nerve damage. When compared with the saline control group, the bupivacaine group had significantly higher perineural inflammation scores at 24 hours. Nerves in the bupivacaine and dexmedetomidine group showed less perineural inflammation at 24 hours when compared to the bupivacaine group.

8). Thus, the changes in total MBP (located in both mature OL cell bodies/processes and myelin sheaths) may not accurately represent myelin formation. Our data suggested that the myelination models from both tissue Verteporfin in vivo sources are rather reproducible; however, the variation across different cell culture preparations appeared to be higher in the cortex-derived cultures. This slight difference may be partially attributed to the method that we

used for myelin quantification. In the spinal cord derived cultures, most MBP+ Inhibitors,research,lifescience,medical subjects were myelinated fibers but not OL cell bodies and processes, therefore, the quantifications were rather straightforward. In contrast, since both the number and intensity of OL cell bodies/processes immunostained with MBP increased in the cortex-derived cultures and they need Inhibitors,research,lifescience,medical to be manually deleted before the areas measurement by ImageJ software, it is not surprising that variations

are more noticeable. Our next goal was to validate the myelination culture as a potential in vitro model to study hypomyelination and demyelination. First, we demonstrated that TNFα and IL-1β, two of the proinflammatory cytokines that have been implicated in mediating hypomyelination in PVL (Pang Inhibitors,research,lifescience,medical et al. 2003; Huleihel et al. 2004), significantly impaired myelination in the spinal cord derived culture. Both TNFα and IL-1β were used at relatively low concentration (10 ng/ml) but with prolonged exposure to mimic the in vivo scenario. Interestingly, the markedly impaired myelination was also associated with changes in Inhibitors,research,lifescience,medical OL behavior, that is, random disperse of MBP by OLs in TNFα-treated culture and increased reactivity of MBP in OL bodies in IL1β-treated culture, rather than directly damage OLs, suggesting that proinflammatory cytokines may interfere with myelination by changing OL functions. It is now recognized that myelination is a rather

complicated process that is regulated at many levels, it not only depends on the quality and quantity of mature OLs that can be affected by any alterations in OL development (i.e., OL specification, balance between proliferation and apoptosis, migration, Inhibitors,research,lifescience,medical and differentiation; Piaton et al. 2010), but also signals derived from neurons/axons (i.e., adhesive molecules, Notch pathway, LINGO-1) (Fancy et al. 2011; Kotter et al. 2011). For these aspects, our cell culture model will be very useful in investigating the role of both OLs and axons that may contribute to myelination below deficit following exposure to certain putative insults (cytokines, oxidative damage, hypoxia-ischemia, etc.) relevant to PVL. Finally, demyelination was successfully reproduced in the myelination co-culture by exposure to LPC and MOG antibody plus complement, two widely used demyelinating insults. In the present study, LPC-induced demyelination was observed at least three days after the exposure and obviously involved in OL degeneration (Fig.

Specific objectives – Describe the average profile of healthcare resource consumption of a retrospective cohort (buy ATM Kinase Inhibitor patients who died from malignant neoplasm) in the last 30 days of life by diagnosis and age group. – Quantify and compare the costs of the use of healthcare resources in the cohorts of patients with and without SAIATU intervention. – Compare quality of life in Inhibitors,research,lifescience,medical the cohorts of patients with and without SAIATU intervention. Methods/design Hypothesis

The intervention of SAIATU (a resource for the social support of end-of-life patients) improves efficiency in the use of healthcare resources in end-of-life patients, decreasing the consumption of hospital resources and increasing the home-based activities conducted by Primary Care in the last 30 days of life. Location and date of study The study will be conducted in the provinces of Guipúzcoa. Period of study: Inhibitors,research,lifescience,medical September 2012 – October 2013. Study design The study was designed in two phases. Phase 1: RETROSPECTIVE study to register a control cohort of patients who died from malignant neoplasm The objective of this study is to determine the baseline risk of the principal variable, consumption of resources in the population of patients Inhibitors,research,lifescience,medical who die from malignant neoplasm. Thus, the study characterises, by primary diagnosis (criteria

and rules established by the International Statistical Classification of Diseases 10 [ICD-10] [26]) and age, the behaviour of different malignant Inhibitors,research,lifescience,medical neoplasms, with regard to resource consumption: number of visits to or consultations with Primary Care, number of external consultations, number of visits to hospital emergency departments, number of hospital admissions, average length of stay, and days in home hospitalisation. Time of study: time series of 4 years, to be determined based on Osakidetza records and the mortality register. Based on the results of this

study and on the hypothesis of the decrease in, and improved efficiency of, resource consumption through the intervention of support programs, formulated as a result of the retrospective observational study carried out, the sample size of cohorts and Inhibitors,research,lifescience,medical subgroups will be defined for Phase 2: PROSPECTIVE cohort study. For this analysis, the error will be established at α=5% with a statistical significance of 80% (error β=20%). The sample size of each subgroup n will be the maximum of the sample sizes obtained for the comparison of means or proportions of Chlormezanone the main variables in each subgroup. For the comparison of two means: n=2Zα/2+Zβ∧2*S∧2/d∧2 (1) where: Zα/2=1.960Zβ=0.842 (2) S2=variance in the quantitative variable of the control group d=Minimum value of the difference to be detected (quantitative values) For the comparison of two proportions: n=2p*q∧2Zα/2+Zβ∧2/pA−pB∧2 (3) where: Zα/2=1.960Zβ=0.842 (4) p=Mean of the two proportions pA y pB The parameters will be analysed with the statistical software SPSS 15.0 for Windows.

It #GSK2118436 chemical structure randurls[1|1|,|CHEM1|]# seems that in the future, TAVI will not be offered to some of the most severely ill patients who have had very short survival times despite successful TAVI. Screening is routinely performed for carotid and coronary atherosclerosis. Renal function is

evaluated and optimized if possible, and pulmonary function is critically assessed. Intraoperative management has progressed considerably with regard Inhibitors,research,lifescience,medical to stroke avoidance and pulmonary complications. Myocardial protection and management of the significant diastolic dysfunction routinely seen in these patients is better understood. Postoperative care has undergone a complete revolution in the last 10 years. Our patients receive care 24 hours a day by our in-house, Inhibitors,research,lifescience,medical full-time CV surgical intensivist team. This has led to superior management of the postoperative period. Programmatic goals to avoid ventilator-dependent pneumonia, ICU-acquired infections, sepsis, and excessive blood usage have all had incremental benefit. Aggressive and early management of hemodynamic instability with prompt availability Inhibitors,research,lifescience,medical of echocardiography has assisted these patients. Early mobilization, nutritional support, and a formal perioperative physical therapy program have aided recovery. Thus, significant improvements in care have lowered the historical

morbidity and mortality of these elderly patients. The commitment to a collaborative team-based approach is essential for the care of these critically ill patients. Expansion of Indications for TAVI Expanding the role of TAVI from treatment of inoperable patients with aortic stenosis to other less-sick populations has been studied in two randomized prospective trials. Inhibitors,research,lifescience,medical In the PARTNER Cohort A trial for high-risk patients, described in detail above, the conventional AVR results were competitive with TAVI at 1 year in terms of mortality.6 However, excess stroke and paravalvular leaks remain a

problem in TAVI patients. The ultimate magnitude Inhibitors,research,lifescience,medical of these problems and the risk of progressive aortic insufficiency will be answered by ongoing follow-up for the Cohort A, such as the 2-year data mentioned above for the Cohort B patients. In a study of stroke after TAVI in 253 patients, Tay et al.17 showed that while the incidence of stroke was highest in the first 24 hours, it remained high for 2 months post-procedure. Proposed mechanisms Ergoloid for perioperative strokes included embolization of atheromatous or calcific debris and periprocedural hypotension. Later strokes were attributed to thrombus formation on the prosthesis or in periprosthetic spaces. The STACCATO trial18 compared transapical TAVI with surgical AVR in elderly patients (mean age: TAVI 80±3.6 and AVR 82±4.4 years), all of whom had severe aortic stenosis but who were otherwise not at an elevated risk for surgical AVR. The mean STS score was 3.3.

More precisely, the reactions rates together with specific reaction identifiers are exported to a .csv file. This format can easily be interpreted by an OVL (OMIX Visualization Language) script in order to equip default network diagrams with markups according to the obtained results. Via OVL scripts it is, for instance, possible to access and change visual properties (color, shape, line width) of network entities or to assign data to them.

The customized metabolic flux charts can then be exported by OMIX into different Inhibitors,research,lifescience,medical bitmap and vector graphic formats such as .png, .jpg and .svg. Within the Flux-P project we currently provide ready-to-use OMIX network diagrams for B. subtilis, C. glutamicum, E. coli, P. putida and S. cerevisiae, along with an OVL script offering two different markup variants: – Visualization of a single result data set, where the line width of the reaction arrows is adjusted to the specific flux. – Visualization of multiple result data sets, where the actual values Inhibitors,research,lifescience,medical of the reactions rates are assigned to the arrows representing the respective reaction (see Figure 5). Figure 5 Metabolic flux charts of the B. subtilis central carbon metabolism. The flux chart presents data from two flux Epigenetics Compound Library clinical trial distributions with the reactions rates plotted next to the reaction arrows. The Inhibitors,research,lifescience,medical flux values are

given in mmol gCDW-1 h-1 and are calculated … Note that these OVL scripts work solely on the exported flux distributions, that is, they are completely independent from Flux-P and can be used in other application contexts. In Inhibitors,research,lifescience,medical the future, the visualization of calculated flux Inhibitors,research,lifescience,medical distributions with OMIX shall be integrated more seamlessly into the Flux-P workflow. Depending on the future development of OMIX this will require either the development of a special

plugin or simply the definition of an additional jETI service should OMIX become programmatically or remotely accessible. 2.5. Flux-P: MFA Workflows Metalloexopeptidase with Bio-jETI For Flux-P, we used the Bio-jETI technology [22] to make FiatFlux-Headless functions available as a collection of platform-independent remote services and to build user-specific MFA workflows. Bio-jETI is a framework for service integration and workflow development in the bioinformatics domain that has been used in a number of different projects (cf., e.g., [27,28,29]) and is continuously evolving as new service libraries and service and software technologies become established. It is based on the jETI tool integration platform [24] and the jABC modeling framework [25]. 2.6. Integration of Flux Analysis Services The jETI technology can be used to make file-based command-line or Java applications remotely available.

L1-deficient mice have significantly lower body weight compared to wild-type

mice at 1 day (*P = 0.021, n = 5), 1 week (***P < 0.001, n = 5), 2 weeks (***P < ... At 1 day and at 1, 2, 4, and 8 weeks postnatally, mice were deeply anesthetized with a mixture of ketamine (150 mg/kg) and xylazine (10 mg/kg) and perfused intracardially with saline for 1 min. For ChAT activity (all time points) and immunoblot analyses (2- and 4-week-old mice), the brain was quickly removed from the skull and the septum and caudate-putamen (CPu) were dissected on ice. The isolated tissue was frozen in liquid nitrogen and stored at −70°C. Tissues were homogenized in 1:10 wet w/v ice-cold lysis Inhibitors,research,lifescience,medical buffer (20 mM Tris-Cl, 0.25 M sucrose, 1 mM EDTA, 1 mM EGTA, pH 7.4) containing

a protease inhibitor cocktail (Calbiochem, La Jolla, CA). The homogenates were centrifuged at 12,000 g for 15 min at 4°C, and the supernatant was used for ChAT activity Inhibitors,research,lifescience,medical assays and western blot analyses. The protein concentration was determined using the Bio-Rad Protein Assay (Bio-Rad, Heracles, CA). For immunohistochemistry and stereological analyses, deeply anesthetized mice at 2 and 4 weeks were perfused intracardially with saline, followed by a fixative composed of 12.5% picric acid and 2% paraformaldehyde in 0.1 M phosphate buffer. Inhibitors,research,lifescience,medical Brains were removed, postfixed overnight, and cryoprotected in a 30% sucrose solution. Culture of primary septal neurons To demonstrate that L1 can Inhibitors,research,lifescience,medical increase ChAT activity in a dose-dependent manner, we used well-characterized rat primary septal neurons (Burgess and Aubert 2006; Burgess et al. 2009). Timed-pregnant Sprague selleck products Dawley rats were obtained from Charles River Laboratories (St. Constant, Quebec, Canada). They were housed individually and received food and water ad libitum for 2 days prior to embryo retrieval. Embryos at gestation day 17 were retrieved from Sprague Dawley rats and cells from the septal area of the basal forebrain were prepared as detailed previously (Burgess and Aubert 2006; Burgess et al. 2009), with slight modifications from Hefti et al. (1989) and

Pongrac and Rylett (1998). Briefly, septal cells were plated in 10% serum. Inhibitors,research,lifescience,medical After 1 h, the medium containing unattached cells was removed and replaced by serum-free medium supplemented with N-2 and containing L1-Fc [0, 5, 25, 50 μM] (Loers et al. 2005). Cells were Astemizole maintained in culture for 4 days, yielding ~98% pure neuronal population. Western blot analysis Standards and samples (10 μg protein/sample) were separated by 10% SDS-PAGE and transferred to a nitrocellulose membrane. The membrane was blocked in 5% skim milk for 1 h and then incubated for 2 h with a rabbit anti-L1 antibody [1:2000] (a generous gift from Dr. Stallcup et al. 1985) in Tris-buffered saline and tween (TBST). For the detection of ChAT, the membrane was blocked with 0.1% BSA for 1 h and then incubated overnight with the goat anti-ChAT antibody [1:2000] (AP144P, Chemicon, Temecula, CA) in TBST.

Table 2 ANCOVA results of COMT Met and DAT1 10R on all dimensions of the ANPS Figure 1 Means and Standard errors of means (SEM) of the ANCOVA for the Sadness dimension of the ANPS dependent on the significant interaction of COMT Met and DAT1 10R. Age was inserted as covariate into the ANOVA. Discussion In a large, healthy sample, Inhibitors,research,lifescience,medical we assessed the effects of functional polymorphisms in the COMT and the DAT1 gene, which regulate synaptic levels of DA in the brain and modulate central DA function. We hypothesized an interaction

of the two prominent polymorphisms COMT Val158Met and DAT1 VNTR on individual Crizotinib concentration differences in NEM as represented by the subscales Sadness, Anger, and Fear of the ANPS. This hypothesis was confirmed by a significant interaction of COMT Met and DAT1 10R leading to lowest scores on the personality dimension Sadness in carriers of the Val/Val and 9R/9R genotype configuration. The interaction on the Inhibitors,research,lifescience,medical dimension Fear

was not significant but on a descriptive level a trend toward lower Fear levels of Val/Val and 9R/9R carriers was observed. Previous studies supporting the “Yin and Yang principle of COMT Val158Met” showed that Inhibitors,research,lifescience,medical the Val/Val genotype, characterized by high enzyme activity leading to efficient dopamine clearance from the synaptic cleft (Chen et al. 2004), is associated with PEM (e.g., Bressan et al. 2002) whereas the Met allele is related to NEM (e.g., Drevets et al. 2001) and lower enzyme activity, resulting in elevated DA levels in the synaptic cleft. Also in the present study the observed

Inhibitors,research,lifescience,medical significant main effect of the Met/Met genotype on Sadness supports the association of the Met allele with NEM. The DA Inhibitors,research,lifescience,medical availability is further modulated through the occurrence of the individual DAT1 variant. The 9R/9R genotype corresponding to lower transcription rate and therefore lower amount of DAT1 protein results in higher DA levels through a slower reuptake of DA into the presynapse (VanNess et al. 2005). However, it has to be mentioned that a recent meta-analysis by Costa et al. (Costa et al. 2011) did not corroborate a significant association between the DAT1 VNTR and DAT1 availability in the striatum. Despite the heterogeneity between the studies and the unknown mechanism how the polymorphism influences DAT1 expression affecting cognition and emotionality, the investigated genetic variants impact the personality dimension Sadness in the investigated sample. Interestingly, dependent on the rare 9R/9R genotype (10R-carriers), the Val/Val genotype (Met-carriers) influences personality toward less NEM. By contrast, the presence of at least one 10R allele seems to suppress the beneficial effect of the Val-allele on NEM.

48 A functional polymorphism in the promoter region of monoamine oxidase A gene (MAOA) resulting in a low expressing genotype has been found to interact with childhood sexual abuse to increase risk of alcoholism, and especially antisocial personality disorder (ASPD) occurring in the context of EX 527 clinical trial Alcohol Use Disorders in women.49 Other environmental factors influencing vulnerability include price, availability, early life stress exposures, and underage drinking.50 For example, alcohol prohibition from

1920 to 1933 in the US led to a large decrease in alcoholism and associated cirrhosis. Also, onset of drinking in the early adolescent Inhibitors,research,lifescience,medical or préadolescent years is a strong risk factor. However, the interactions of such factors with gene effects are even less well understood. The pharmacogenetics of pharmacotherapy Inhibitors,research,lifescience,medical Treatment of addiction encompasses two main phases: acute detoxification and maintenance. Maintenance treatment is aimed at maintaining abstinence, or harm reduction. Supportive therapy plays a vital role and this may include cognitive therapy and self-help groups. Categories of pharmacotherapeutics include: Detoxification (eg, benzodiazepines in alcoholism and clonidine in opiate withdrawal ) Agonist (eg, methadone, levo-alpha-acetyl-methadol(LAAM]) Partial agonist (eg, buprenorphine for opioid addiction) Antagonist (eg, naltrexone Inhibitors,research,lifescience,medical in alcoholism) Anticraving (eg,

bupropion and homotaurine in alcoholism) Aversive (eg, disulfiram). Because each of these drugs targets specific proteins and small molecules, there is considerable potential for specific pharmacogenetics of treatment response. Each of these drugs is also subject to metabolism, leading to a role for pharmacogenetic variation such as the cytochrome p450 2,6 which predicted response to bupropion in nicotine

Inhibitors,research,lifescience,medical dependence.51 The OPRM1 Asn40Asp polymorphism has, Inhibitors,research,lifescience,medical in addition to its disease associations, also been associated with naltrexone treatment response in alcoholism and as recently replicated in a large clinical trial, the COMBINE study.52 The role of OPRM1 in smoking has been studied in relation to nicotine replacement therapy. Nicotine increases the release of β-endorphins indirectly releasing dopamine and leading to pleasurable sensations Liothyronine Sodium associated with smoking, as shown by several studies both in rats and humans. In a randomized study, 320 smokers of European ancestry were treated with a nicotine transdermal patch or nasal spray over a 6-month period and 41% of Asp40 carriers remained abstinent at the end of 6 months as compared with 30% of Asn40/Asn40 homozygotes.53 However, the effect of genotype disappeared after treatment cessation. Another gene that may predict nicotine treatment response is cytochrome P450 2B6 (CYP2B6) which predicted treatment response with bupropion, which is metabolized by this enzyme. In a study of 426 smokers of European ancestry, participants with the low activity allele reported increased craving and higher relapse rate.

An intervention directed at durability- of response is considered preventive. The question is once well, how can we stay well and can we reduce the risk of relapse (of the same episode) or recurrence (of a new episode) through some longer term approaches to treatment? Interventions are also preventive if they target the excessive levels of disability that often characterize the mental disorders of older people. As we learn more about the risk factors, etiology, and pathophysiology of mental disorders in late life, it is conceivable that preventive interventions could be directed toward delaying Inhibitors,research,lifescience,medical the onset of disease or even preventing

the onset entirely.20 Infrastructure considerations for public check details health model studies In order to carry out such studies, whether they are treatment studies, preventive interventions, or rehabilitative interventions, Inhibitors,research,lifescience,medical we need to identify the structural barriers in the ways in which research is organized and to innovate approaches to address these barriers. Researchers Inhibitors,research,lifescience,medical and their laboratories are largely based in academic health centers.

The role of the academic health center is being redefined in the context of health care system reorganization, and access to patients has become problematic. Patient-oriented research is seen as a particularly fragile enterprise Inhibitors,research,lifescience,medical at this point in time.21,22 There are important opportunities emerging, however. Many academic health centers are part of clinical systems that include community hospitals, primary care and specialty care office practices, and capitated contracts. The nonacademic settings of these Inhibitors,research,lifescience,medical large networks

are where the majority of patients are located. The new challenge for the field is how to turn these clinical and administrative networks into research networks for the development and management of intervention trials. At the same time, the parallel challenge is how to identify the critical elements of academically based protocols and paradigms, and adapt Resminostat them for use in the broader community. Advancement for academic investigators is based on research productivity, usually measured by significant publications and success in developing extramural funding. Large-scale, longitudinal, public-health-oriented studies typically have a very long period of time before important publications are developed, and they usually involve the participation of a large number of investigators. Individual intellectual contributions can be difficult to assess in such projects. If there is a commitment to developing this type of research, the challenge for the field is how to adapt promotion and tenure policies to this situation so as to properly recognize individual contributions.

Recognising complexity A distinction between BMS-387032 in vitro generalist and specialist palliative care

was drawn where staff felt there were “very specific problems that we have with individuals having exhausted our repertoire” [3:42], specifically in relation to symptom control and complex ethical issues. Examples included managing hydration and nutrition, Inhibitors,research,lifescience,medical and in exploring “when do you stop? Have we made the right decision? … they [palliative care specialists] come along and they say “yes, yes, you should withdraw that, yes you’re not helping them, that should come down, you’re just prolonging the suffering” it helps because you think well, that’s not just my decision and they are experts at this”. [2:12] Stroke staff reported that access to specialist advice was useful in providing “reassurance” [2:13] and to “support clinical decision-making” [3:24]. Discussions about involvement of specialists Inhibitors,research,lifescience,medical in this area tended not to focus on partnership

working through the addition of other, additional clinical perspectives or information. The focus was the provision of reassurance to the stroke team that appropriate decisions had been reached. This may reflect a lack of clarity about the clinical validity of specialist palliative care with regard to the needs of stroke patients: “The difficulty with that Inhibitors,research,lifescience,medical is, there’s no specialism within the specialism. [1:9]” Recognising dying Reflecting advances in palliative care theory, difficulties in identifying a precise time point or phase

when patients required palliative care were highlighted. “At the moment I’ve got four patients on our floor who’ve been unconscious Inhibitors,research,lifescience,medical for three or four days and I’m sitting with the families saying “I just don’t know”. Now, would this be a time for palliative care? Inhibitors,research,lifescience,medical I don’t think so, because they may recover, but then again they may not. [3:36]” As a consequence, decisions to formally assign a patient as requiring palliative care were “very slow in the making. Almost to the point where the patient has almost passed away when the decision [to commence palliative care] is made” [3:13]. Data on decision-making focused primarily on who made decisions and the team context of decision-making, rather than on what basis decisions were made. Responsibility click here appeared to rest with the medical lead, although the decisions were couched in general terms, rather than an active decision to commence end of life care. “…it’s the consultant, that actually says “we’re changing direction here”. Maybe from the information we’ve given him, but it’s very often them that take the lead in “OK, it’s time to go” and we can sway that decision, but I think ultimately it’s the consultant that will say “this is the direction we’re going in”.