National audit of continence care for older people: results of a pilot study*

INTRODUCTION AND AIM: Bladder and bowel problems are common in the elderly and are associated with a considerable morbidity and impact on quality of life. Inequalities in service provision and access to services have been recognized but there has been no systematic approach to measuring the quality of continence care for older people. This study aimed to develop quality standards, to assess the reliability and utility of the resulting audit package and to report on the standards of care provided in primary care, secondary care and care home setting. METHOD: Fifteen sites in secondary care, primary care and in long-term care settings were randomly selected to pilot the audit package. Data collectors completed audit questionnaires relating to the structure [organization] of care, the outcomes of care, and the process of care for 20 subjects with urinary incontinence and 10 subjects with faecal or double incontinence. RESULTS: The audit tool was reliable (median kappa score of 0.7). Access to integrated continence services, as defined by Good Practice in Continence Services was inadequate. Eighty-five per cent of hospitals had no written policy for continence care. There were deficiencies in obtaining information, in carrying out basic and specialist examinations and investigations and in determining the cause of incontinence. There was a high prevalence of catheter use in secondary care settings. CONCLUSION: The pilot has indicated significant inadequacies in continence care and demonstrates that in many sites the National Service Framework milestone for integrated continence services has not been met. A national audit of continence care is required to determine the extent of inadequate continence care.     

Comparison of Cox and Gray's survival models in severe sepsis

BACKGROUND: Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate. OBJECTIVES: To construct and compare Gray's model and two different Cox models in a large sepsis cohort. To determine whether hazards for death after sepsis were nonproportional. To explore how well the different survival modeling approaches describe these data. DESIGN: Analysis of combined data from the treatment and placebo arms of a large, negative, sepsis trial. SETTING: Intensive care units at 136 U.S. medical centers. SUBJECTS: A total of 1090 adults aged 18 yrs or older with signs and symptoms of severe sepsis and documented or probable Gram-negative infection. MEASUREMENTS: We considered 27 potential baseline risk factors and modeled survival over the 28 days after the onset of sepsis. We tested proportionality in single-variable Cox analysis using Schoenfeld residuals and log-log plots. We constructed a traditional multivariable Cox model, a multivariable Cox model with time-varying covariates, and a multivariable Gray's model. RESULTS: In single-variable analyses, 20 of the 27 potential factors were significantly associated with mortality, and 10 of 20 had nonproportional hazards. In multivariate analysis, all three models retained a very similar set of significant covariates (two models retained the identical set of nine variables, and the third differed only in that it retained the same nine plus a tenth variable). Four of the nine common covariates had nonproportional hazards. Of the three models, Gray's model best captured these changing hazard ratios over time. CONCLUSION: We confirm that many of the important predictors of mortality in severe sepsis are nonproportional and find that Gray's model seems best suited for modeling survival in this condition.     

Effect of dialysis on interference by cefoxitin with determination of creatinine

Interference by cefoxitin with determination of creatinine is less with the Technicon SMAC than with other commercial analytical systems. The SMAC assay involves a single-point kinetic method with dialysis, whereas most other commercial methods are multipoint kinetic without dialysis. The apparent creatinine concentration measured for aqueous solutions of cefoxitin was 73 mmol of creatinine per mole of cefoxitin with the SMAC, 135 mmol/mol with a manual method. Furthermore, we determined for the SMAC that the average fraction of creatinine dialyzed was 0.128 and for cefoxitin, 0.064. Thus, the concentration of and interference by cefoxitin in the reaction mixture for SMAC are reduced by half (i.e., the apparent creatinine concentration for cefoxitin with the manual system multiplied by 0.5 is essentially that noted with the SMAC: 68 vs 73). Thus we conclude that the diminished interference be cefoxitin with determination of creatinine by SMAC is primarily ascribable to the dialysis step.     

The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway

Purpose

Protecting the heart from ischaemia-reperfusion (IR) injury is a major goal in patients presenting with an acute myocardial infarction. Pyroptosis is a novel form of cell death in which caspase 1 is activated and cleaves interleukin 1β. VX-785 is a highly selective, prodrug caspase 1 inhibitor that is also clinically available. It has been shown to be protective against acute IR in vivo rat model, and therefore might be a promising possibility for future cardioprotective therapy. However, it is not known whether protection by VX-765 involves the reperfusion injury salvage kinase (RISK) pathway. We therefore investigated whether VX-765 protects the isolated, perfused rat heart via the PI3K/Akt pathway and whether protection was additive with ischaemic preconditioning (IPC).

Methods

Langendorff-perfused rat hearts were subject to ischaemia and reperfusion injury in the presence of 30 μM VX-765, with precedent IPC, or the combination of VX-765 and IPC.

Results

VX-765 reduced infarct size (28 vs 48% control; P?<?0.05) to a similar extent as IPC (30%; P?<?0.05). The PI3 kinase inhibitor, wortmannin, abolished the protective effect of VX-765. Importantly in the model used, we were unable to show additive protection with VX-765 + IPC.

Conclusions

The caspase 1 inhibitor, VX-765, was able to reduce myocardial infarction in a model of IR injury. However, the addition of IPC did not demonstrate any further protection.

     

Conduction Time Oscillations Precede the Spontaneous Termination of Human Atrioventricular Reciprocating Tachycardia

Prior clinical research indicates that conduction slowing is the primary mechanism leading to the spontaneous termination of reentrant tachycardia in humans. Yet, some experimental models indicate that cycle length oscillations and enhanced conduction are important prerequisites. The role of oscillations in conduction times and enhanced conduction in the spontaneous termination of human reentrant tachycardia has not been adequately investigated.The electrophysiologic features preceding the spontaneous termination of orthodromic atrioventricular (AV) reciprocating tachycardia (RT) were evaluated in 21 patients, each of whom had a sustained (>60 seconds) and a spontaneously terminating (10 beats and 60 seconds) episode of AVRT during the same electrophysiologic study. Atrio-His, His-ventricular, interventricular, ventriculoatrial and atrial conduction times were measured for each beat of spontaneously terminating AVRT and for paired beats of sustained AVRT. Beats of spontaneously terminating and sustained tachycardia were pooled and Hadi multivariate outlier analysis was used to identify whether significant beat-to-beat alterations in conduction times preceded the spontaneous termination of reentry.Cycle lengths of sustained (348±62 msec) and spontaneously terminating AVRT (351±70 msec) were similar. Significant beat-to-beat oscillations in conduction times preceded the spontaneous termination of AVRT in 10 of the 21 (48%) patients. An apparent enhancement in atrio-His or ventriculoatrial conduction times immediately preceded the spontaneous termination of AVRT in 11 patients (52%), while an apparent conduction delay occurred in only 2 patients (10%). Moreover, significant oscillations in conduction times were present in 9 of the 11 patients (82%) with enhanced conduction, but only in 1 of the 10 (10%) remaining patients (p=0.002.Conduction time oscillations, which are related to apparent enhancement in atrio-His or ventriculoatrial conduction, frequently precede the spontaneous termination of reentry in humans.     

Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta in patients with myeloma

The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44(+)) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor beta(1) (TGFbeta(1)) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGFbeta(1). As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon-gamma neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123-) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon-gamma to future immunotherapy trials involving these patients should be considered.     

Neural correlates of the emergence of consciousness of thirst

Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4 ml/min). Ten humans were neuroimaged by positron-emission tomography (PET) and four by functional MRI (fMRI). PET images were made 25 min after beginning infusion, when the sensation of thirst began to enter the stream of consciousness. The fMRI images were made when the maximum rate of increase of thirst occurred. The PET results showed regional cerebral blood flow changes similar to those delineated when thirst was maximal. These loci involved the phylogenetically ancient areas of the brain. fMRI showed activation in the anterior wall of the third ventricle, an area that is key in the genesis of thirst but is not an area revealed by PET imaging. Thus, this region plays as major a role in thirst for humans as for animals. Strong activations in the brain with fMRI included the anterior cingulate, parahippocampal gyrus, inferior and middle frontal gyri, insula, and cerebellum. When the subjects drank water to satiation, thirst declined immediately to baseline. A precipitate decline in intensity of activation signal occurred in the anterior cingulate area (Brodmann area 32) putatively related to consciousness of thirst. The intensity of activation in the anterior wall of the third ventricle was essentially unchanged, which is consistent with the fact that a significant time (15-20 min) would be needed before plasma Na concentration changed as a result of water absorption from the gut.     

Directing cell migration with asymmetric micropatterns

This report shows that the direction of polarization of attached mammalian cells determines the direction in which they move. Surfaces micropatterned with appropriately functionalized self-assembled monolayers constrain individual cells to asymmetric geometries (for example, a teardrop); these geometries polarize the morphology of the cell. After electrochemical desorption of the self-assembled monolayers removes these constraints and allows the cells to move across the surface, they move toward their blunt ends.     

Multidrug-Resistant Organism Infections in Patients with Left Ventricular Assist Devices

Left ventricular assist devices improve survival prospects in patients with end-stage heart failure; however, infection complicates up to 59% of implantation cases. How many of these infections are caused by multidrug-resistant organisms is unknown. We sought to identify the incidence, risk factors, and outcomes of multidrug-resistant organism infection in patients who have left ventricular assist devices.We retrospectively evaluated the incidence of multidrug-resistant organisms and the independent risk factors associated with them in 57 patients who had permanent left ventricular assist devices implanted at our institution from May 2007 through October 2011. Outcomes included death, transplantation, device explantation, number of subsequent hospital admissions, and number of subsequent admissions related to infection. Infections were categorized in accordance with criteria from the Infectious Diseases Council of the International Society for Heart and Lung Transplantation.Multidrug-resistant organism infections developed in 18 of 57 patients (31.6%)—a high incidence. We found 3 independent risk factors: therapeutic goal (destination therapy vs bridging), P=0.01; body mass index, P=0.04; and exposed velour at driveline exit sites, P=0.004. We found no significant differences in mortality, transplantation, or device explantation rates; however, there was a statistically significant increase in postimplantation hospital admissions in patients with multidrug-resistant organism infection. To our knowledge, this is the first report in the medical literature concerning multidrug-resistant organism infection in patients who have permanent left ventricular assist devices.