Barriers to Advance Care Planning at the End of Life: An Explanatory Systematic Review of Implementation Studies

ContextAdvance Care Plans (ACPs) enable patients to discuss and negotiate their preferences for the future including treatment options at the end of life. Their implementation poses significant challenges.ObjectiveTo investigate barriers and facilitators to the implementation of ACPs, focusing on their workability and integration in clinical practice.DesignAn explanatory systematic review of qualitative implementation studies.MethodsDirect content analysis, using Normalization Process Theory, to identify and characterise relevant components of implementation processes.Results13 papers identified from 166 abstracts were included in the review. Key factors facilitating implementation were: specially prepared staff utilizing a structured approach to interactions around ACPs. Barriers to implementation were competing demands of other work, the emotional and interactional nature of patient-professional interactions around ACPs, problems in sharing decisions and preferences within and between healthcare organizations.ConclusionsThis review demonstrates that doing more of the things that facilitate delivery of ACPs will not reduce the effects of those things that undermine them. Structured tools are only likely to be partially effective and the creation of a specialist cadre of ACP facilitators is unlikely to be a sustainable solution. The findings underscore both the challenge and need to find ways to routinely incorporate ACPs in clinical settings where multiple and competing demands impact on practice. Interventions most likely to meet with success are those that make elements of Advance Care Planning workable within complex and time pressured clinical workflows.     

Effects of DPP-4 inhibitors on the heart in a rat model of uremic cardiomyopathy

Background

Uremic cardiomyopathy contributes substantially to mortality in chronic kidney disease (CKD) patients. Glucagon-like peptide-1 (GLP-1) may improve cardiac function, but is mainly degraded by dipeptidyl peptidase-4 (DPP-4).

Methodology/Principal Findings

In a rat model of chronic renal failure, 5/6-nephrectomized [5/6N] rats were treated orally with DPP-4 inhibitors (linagliptin, sitagliptin, alogliptin) or placebo once daily for 4 days from 8 weeks after surgery, to identify the most appropriate treatment for cardiac dysfunction associated with CKD. Linagliptin showed no significant change in blood level AUC(0-∞) in 5/6N rats, but sitagliptin and alogliptin had significantly higher AUC(0-∞) values; 41% and 28% (p = 0.0001 and p = 0.0324), respectively. No correlation of markers of renal tubular and glomerular function with AUC was observed for linagliptin, which required no dose adjustment in uremic rats. Linagliptin 7 µmol/kg caused a 2-fold increase in GLP-1 (AUC 201.0 ng/l*h) in 5/6N rats compared with sham-treated rats (AUC 108.6 ng/l*h) (p = 0.01). The mRNA levels of heart tissue fibrosis markers were all significantly increased in 5/6N vs control rats and reduced/normalized by linagliptin.

Conclusions/Significance

DPP-4 inhibition increases plasma GLP-1 levels, particularly in uremia, and reduces expression of cardiac mRNA levels of matrix proteins and B-type natriuretic peptides (BNP). Linagliptin may offer a unique approach for treating uremic cardiomyopathy in CKD patients, with no need for dose-adjustment.     

Highly pathogenic avian influenza virus H5N1 infection in a long-distance migrant shorebird under migratory and non-migratory states

Corticosterone regulates physiological changes preparing wild birds for migration. It also modulates the immune system and may lead to increased susceptibility to infection, with implications for the spread of pathogens, including highly pathogenic avian influenza virus (HPAIV) H5N1. The red knot (Calidris canutus islandica) displays migratory changes in captivity and was used as a model to assess the effect of high plasma concentration of corticosterone on HPAIV H5N1 infection. We inoculated knots during pre-migration (N = 6), fueling (N = 5), migration (N = 9) and post-migration periods (N = 6). Knots from all groups shed similar viral titers for up to 5 days post-inoculation (dpi), peaking at 1 to 3 dpi. Lesions of acute encephalitis, associated with virus replication in neurons, were seen in 1 to 2 knots per group, leading to neurological disease and death at 5 to 11 dpi. Therefore, the risk of HPAIV H5N1 infection in wild birds and of potential transmission between wild birds and poultry may be similar at different times of the year, irrespective of wild birds'' migratory status. However, in knots inoculated during the migration period, viral shedding levels positively correlated with pre-inoculation plasma concentration of corticosterone. Of these, knots that did not become productively infected had lower plasma concentration of corticosterone. Conversely, elevated plasma concentration of corticosterone did not result in an increased probability to develop clinical disease. These results suggest that birds with elevated plasma concentration of corticosterone at the time of migration (ready to migrate) may be more susceptible to acquisition of infection and shed higher viral titers—before the onset of clinical disease—than birds with low concentration of corticosterone (not ready for take-off). Yet, they may not be more prone to the development of clinical disease. Therefore, assuming no effect of sub-clinical infection on the likelihood of migratory take-off, this may favor the spread of HPAIV H5N1 by migratory birds over long distances.     

Renal effects of the novel selective adenosine A1 receptor blocker SLV329 in experimental liver cirrhosis in rats

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A(1) receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A(1) receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (-36.5%, p<0.05), especially in those receiving furosemide (-41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A(1) receptor antagonists are clinically beneficial at different stages of liver cirrhosis.     

Incenp and an aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis

BACKGROUND: In animal cells, cytokinesis begins shortly after the sister chromatids move to the spindle poles. The inner centromere protein (Incenp)has been implicated in both chromosome segregation and cytokinesis, but it is not known exactly how it mediates these two distinct processes. RESULTS: We identified two Caenorhabditis elegans proteins, ICP-1 and ICP-2, with significant homology in their carboxyl termini to the corresponding region of vertebrate Incenp. Embryos depleted of ICP-1 by RNA-mediated interference had defects in both chromosome segregation and cytokinesis. Depletion of the Aurora-like kinase AIR-2 resulted in a similar phenotype. The carboxy-terminal region of Incenp is also homologous to that in Sli15p, a budding yeast protein that functions with the yeast Aurora kinase Ipl1p. ICP-1 bound C. elegans AIR-2 in vitro, and the corresponding mammalian orthologs Incenp and AIRK2 could be co-immunoprecipitated from cell extracts. A significant fraction of embryos depleted of ICP-1 and AIR-2 completed one cell division over the course of several cell cycles. ICP-1 promoted the stable localization of ZEN-4 (also known as CeMKLP1), a kinesin-like protein required for central spindle assembly. CONCLUSIONS: ICP-1 and AIR-2 are part of a complex that is essential for chromosome segregation and for efficient completion of cytokinesis. We propose that this complex acts by promoting dissolution of sister chromatid cohesion and the assembly of the central spindle.     

Oxygenated machine perfusion mitigates surface antigen expression and improves preservation of predamaged donor livers

The aim of the present study was to evaluate the potential benefit of machine preservation with the Belzer MPS or HTK solution, compared to standard cold storage, after procurement of marginal livers from non-heart beating donors in an experimental pilot study. Livers from male Wistar rats (250-300 g bw) were harvested after 60 min of cardiac arrest, flushed via the portal vein and cold stored submerged in HTK for 24 h at 4 degrees C while other organs were subjected to oxygenated machine perfusion with HTK or Belzer's MPS at 5 ml/min at 4 degrees C. Cold perfusion of livers with the non-colloidal HTK was not compromised by the lack of oncotic agents and there was no rise in vascular resistance during the 24 h of machine preservation with HTK or the colloidal Belzer MPS. Viability of the livers was assessed after the cold preservation period by warm reperfusion in vitro. Oxygenated machine perfusion was found to significantly increase viability of the livers vs simple cold storage with respect to portal vascular resistance upon reperfusion, enzyme release as well as functional recovery of oxygen utilization or bile production. Moreover, tissue antigen expression of ICAM-1 or histocompatibility antigen class II could be markedly reduced by oxygenated perfusion preservation as compared to cold storage. It is concluded that predamaged organs should preferably be preserved by oxygenated machine perfusion thus minimizing functional alterations and immunogenicity of the graft. In this setup HTK appeared equally effective as Belzer's MPS for machine preservation.     

Kleisins: a superfamily of bacterial and eukaryotic SMC protein partners

We describe a superfamily of eukaryotic and prokaryotic proteins (kleisins) that includes ScpA, Scc1, Rec8, and Barren. Scc1 interacts with SMC proteins through N- and C-terminal domains to form a ring-like structure. Since these are the only domains conserved among kleisins, we suggest that ring formation with SMC proteins may define this family.     

Purification and properties of extracellular dextranase from a Bacillus sp

Bacterial strains in the genus Bacillus were isolated from natural soil samples and screened for production of extracellular dextranases (E.C.3.2.1.11). One strain, determined by 16sRNA analysis as Paenibacillus illinoisensis exhibiting stable dextranase activity, was chosen for further analysis, and the dextranase from it was purified 733-fold using salt and PEG precipitations, two-phase extraction and DEAE-Sepharose chromatography with a total yield of 19%. The purified enzyme had three isoforms, with molecular masses of 76, 89 and 110kDa and isoelectric points of 4.95, 4.2 and 4.0, respectively. The mixture of the three dextranase isoforms has a broad pH optimum around pH 6.8 and a temperature optimum at 50 degrees C. The N-terminal sequence (Ala-Ser-Thr-Gly-Lys) was identical between the isoforms. No sequence homology with the known dextranases in the protein databanks was found.     

Periodontal conditions in individuals with Down's syndrome

Periodontal disease in Down's syndrome (DS) population seems to be a more common and serious problem than caries. The aim of this study was to assess the state of periodontal structures in patients with DS. The Community Periodontal Index of Treatment Needs was used for periodontal status assessment in 71 DS subjects aged 9-34 years. A control group consisted of 71 age- and sex-matched healthy individuals. Both groups were divided into three age groups: 9-15 (n = 24); 16-25 (n = 32); and 26-34 (n = 15) years. The results showed a similar percentage of subjects with bleeding and calculus. The intact periodontium was significantly higher in control than in DS (16.9% vs. none; p < 0.01). Deep pockets were more frequent in DS group than in the control group (14.1% vs. 1.4%; p < 0.01). The mean number of sextants with healthy tissue was lower, and of those with bleeding, calculus and shallow pockets significantly higher in DS patients than in controls (p < 0.01), so all DS subjects required some periodontal treatment (p < 0.01). It can be concluded that the severity of periodontal disease and the treatment needs seem to be significantly greater in DS than in healthy subjects.