Unbearability of suffering at the end of life: the development of a new measuring device, the SOS-V

AbstractBackgroundUnbearable suffering is an important issue in end-of-life decisions. However, there has been no systematic, prospective, patient-oriented research which has focused on unbearable suffering, nor is there a suitable measurement instrument. This article describes the methodological development of a quantitative instrument to measure the nature and intensity of unbearable suffering, practical aspects of its use in end-stage cancer patients in general practice, and studies content validity and psychometric properties.MethodsRecognizing the conceptual difference between unbearability of suffering and extent or intensity of suffering, we developed an instrument. The compilation of aspects considered to be of importance was based on a literature search. Psychometric properties were determined on results of the first interviews with 64 end-stage cancer patients that participated in a longitudinal study in the Netherlands.ResultsThe instrument measures five domains: medical signs and symptoms, loss of function, personal aspects, aspects of environment, and nature and prognosis of the disease. Sixty nine aspects were investigated, and an overall score was asked. In 64 end-stage cancer patients the instrument was used in total 153 times with an average interview time varying from 20-40 minutes. Cronbachs alpha's of the subscales were in majority above 0.7. The sum scores of (sub)scales were correlated strongly to overall measures on suffering.ConclusionThe SOS-V is an instrument for measuring the unbearability of suffering in end-stage cancer patients with good content validity and psychometric properties, which is feasible to be used in practice. This structured instrument makes it possible to identify and study unbearable suffering in a quantitative and patient-oriented way

Improved Clinical Outcomes With Early Anti-Tumour Necrosis Factor Alpha Therapy in Children With Newly Diagnosed Crohn's Disease: Real-world Data from the International Prospective PIBD-SETQuality Inception Cohort Study.

BACKGROUND AND AIMS: Treatment guidelines for paediatric Crohn's disease [CD] suggest early use of anti-tumour necrosis factor alpha [anti-TNFα] in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort. METHODS: Children with newly diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF [<90 days after diagnosis] and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission [SSFR] without treatment intensification [specified as SSFR*] and sustained steroid-free mild/inactive disease without treatment intensification [specified as SSFMI*]. Penalised logistic regression model-based standardisation was applied to estimate the relative risks [RR] of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients, based on presence of predictors of poor outcome [POPOs] and disease activity at diagnosis. RESULTS: In total, 331 children (median age 13.9 years [IQR 12.2-15.3]) were enrolled, with 135 [41%] receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* [30% vs 14%, p <0.001] and SSFMI* [69% vs 33%, p <0.001], with RRs of 2.95 [95% CI 1.63-5.36] and 4.67 [95% CI 2.46-8.87], respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared with mild/inactive disease at diagnosis (5.50 [95% CI 2.51-12.05] vs 2.91 [95% CI 0.92-9.11]), and those with any POPO compared with no POPO (5.05 [95% CI 2.45-10.43] vs 3.41 [95% CI 0.54-21.7]). CONCLUSION: In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients

Low Numbers of FOXP3 Positive Regulatory T Cells Are Present in all Developmental Stages of Human Atherosclerotic Lesions

BACKGROUND: T cell mediated inflammation contributes to atherogenesis and the onset of acute cardiovascular disease. Effector T cell functions are under a tight control of a specialized T cell subset, regulatory T cells (Treg). At present, nothing is known about the in situ presence of Treg in human atherosclerotic tissue. In the present study we investigated the frequency of naturally occurring Treg cells in all developmental stages of human atherosclerotic lesions including complicated thrombosed plaques. METHODOLOGY: Normal arteries, early lesions (American Heart Association classification types I, II, and III), fibrosclerotic plaques (types Vb and Vc) and 'high risk' plaques (types IV, Va and VI) were obtained at surgery and autopsy. Serial sections were immunostained for markers specific for regulatory T cells (FOXP3 and GITR) and the frequency of these cells was expressed as a percentage of the total numbers of CD3+ T cells. Results were compared with Treg counts in biopsies of normal and inflammatory skin lesions (psoriasis, spongiotic dermatitis and lichen planus). PRINCIPLE FINDINGS: In normal vessel fragments T cells were virtually absent. Treg were present in the intima during all stages of plaque development (0.5-5%). Also in the adventitia of atherosclerotic vessels Treg were encountered, in similar low amounts. High risk lesions contained significantly increased numbers of Treg compared to early lesions (mean: 3.9 and 1.2%, respectively). The frequency of FOXP3+ cells in high risk lesions was also higher compared to stable lesions (1.7%), but this difference was not significant. The mean numbers of intimal FOXP3 positive cells in atherosclerotic lesions (2.4%) was much lower than those in normal (24.3%) or inflammatory skin lesions (28%). CONCLUSION: Low frequencies of Treg in all developmental stages of human plaque formation could explain the smoldering chronic inflammatory process that takes place throughout the longstanding course of atherosclerosis

Measurement-Induced Entanglement for Excitation Stored in Remote Atomic Ensembles

A critical requirement for diverse applications in Quantum Information Science is the capability to disseminate quantum resources over complex quantum networks. For example, the coherent distribution of entangled quantum states together with quantum memory to store these states can enable scalable architectures for quantum computation, communication, and metrology. As a significant step toward such possibilities, here we report observations of entanglement between two atomic ensembles located in distinct apparatuses on different tables. Quantum interference in the detection of a photon emitted by one of the samples projects the otherwise independent ensembles into an entangled state with one joint excitation stored remotely in 10^5 atoms at each site. After a programmable delay, we confirm entanglement by mapping the state of the atoms to optical fields and by measuring mutual coherences and photon statistics for these fields. We thereby determine a quantitative lower bound for the entanglement of the joint state of the ensembles. Our observations provide a new capability for the distribution and storage of entangled quantum states, including for scalable quantum communication networks .Comment: 13 pages, 4 figures Submitted for publication on August 31 200

The transient response of ice volume to orbital forcing during the warm Late Pliocene

Examining the nature of ice sheet and sea level response to past episodes of enhanced greenhouse gas forcing may help constrain future sea level change. Here, for the first time, we present the transient nature of ice sheets and sea level during the late Pliocene. The transient ice sheet predictions are forced by multiple climate snapshots derived from a climate model set up with late Pliocene boundary conditions, forced with different orbital forcing scenarios appropriate to two Marine Isotope Stages (MISs), MIS KM5c, and K1. Our results indicate that during MIS KM5c both the Antarctic and Greenland ice sheets contributed to sea level rise relative to present and were relatively stable. Insolation forcing between the hemispheres was out of phase during MIS K1 and led to an asynchronous response of ice volume globally. Therefore, when variations of precession were high, inferring the behavior of ice sheets from benthic isotope or sea level records is complex

Hospital care for children and young adults in the last year of life: a population-based study

BACKGROUND: To help design population-based pediatric palliative care services, we sought to describe the hospital care received in the last year of life by children and young adults who died. We also determined the proportion with complex chronic conditions (CCCs) and tested whether the use of hospital services increased as the date of death drew nearer. METHODS: For all deaths occurring under 25 years of age from 1990 to 1996 in Washington State, USA, we linked death certificate information to hospital utilization records and analyzed the timing and duration of hospitalizations and the nature of hospital procedures during the year prior to death. RESULTS: Of the 8 893 deaths, 25 % had CCCs. Among infants with CCCs, 84 % were hospitalized at the time of death and 50 % had been mechanically ventilated during their terminal admission. Among the 458 CCC neonates dying under a week of age, 92% of all days of life were spent in the hospital; among the 172 CCC neonates dying during the second to fourth weeks of life, 85 % of all days of life were spent hospitalized; among the 286 CCC infants dying during the second to twelfth month of life, 41 % of all days of life were spent hospitalized. Among children and young adults with CCCs, 55 % were hospitalized at the time of death, and 19 % had been mechanically ventilated during their terminal admission. For these older patients, the median number of days spent in the hospital during the year preceding death was 18, yet less than a third of this group was hospitalized at any point in time until the last week of their lives. The rate of hospital use increased as death drew near. For subjects who had received hospital care, 44 % had governmental insurance as the source of primary payment. CONCLUSIONS: Infants who died spent a substantial proportion of their lives in hospitals, whereas children and adolescents who died from CCCs predominantly lived outside of the hospital during the last year of life. To serve these patients, pediatric palliative and end-of-life care will have to be provided in an integrated, coordinated manner both in hospitals and home communities

Increased searching and handling effort in tall swards lead to a Type IV functional response in small grazing herbivores

Understanding the functional response of species is important in comprehending the species’ population dynamics and the functioning of multi-species assemblages. A Type II functional response, where instantaneous intake rate increases asymptotically with sward biomass, is thought to be common in grazers. However, at tall, dense swards, food intake might decline due to mechanical limitations or if animals selectively forage on the most nutritious parts of a sward, leading to a Type IV functional response, especially for smaller herbivores. We tested the predictions that bite mass, cropping time, swallowing time and searching time increase, and bite rate decreases with increasing grass biomass for different-sized Canada geese (Branta canadensis) foraging on grass swards. Bite mass indeed showed an increasing asymptotic relationship with grass biomass. At high biomass, difficulties in handling long leaves and in locating bites were responsible for increasing cropping, swallowing, and searching times. Constant bite mass and decreasing bite rate caused the intake rate to decrease at high sward biomass after reaching an optimum, leading to a Type IV functional response. Grazer body mass affected maximum bite mass and intake rate, but did not change the shape of the functional response. As grass nutrient contents are usually highest in short swards, this Type IV functional response in geese leads to an intake rate that is maximised in these swards. The lower grass biomass at which intake rate was maximised allows resource partitioning between different-sized grazers. We argue that this Type IV functional response is of more importance than previously thought

Carbon nanoparticles in lateral flow methods to detect genes encoding virulence factors of Shiga toxin-producing Escherichia coli

The use of carbon nanoparticles is shown for the detection and identification of different Shiga toxin-producing Escherichia coli virulence factors (vt1, vt2, eae and ehxA) and a 16S control (specific for E. coli) based on the use of lateral flow strips (nucleic acid lateral flow immunoassay, NALFIA). Prior to the detection with NALFIA, a rapid amplification method with tagged primers was applied. In the evaluation of the optimised NALFIA strips, no cross-reactivity was found for any of the antibodies used. The limit of detection was higher than for quantitative PCR (q-PCR), in most cases between 104 and 105 colony forming units/mL or 0.1–0.9 ng/μL DNA. NALFIA strips were applied to 48 isolates from cattle faeces, and results were compared to those achieved by q-PCR. E. coli virulence factors identified by NALFIA were in very good agreement with those observed in q-PCR, showing in most cases sensitivity and specificity values of 1.0 and an almost perfect agreement between both methods (kappa coefficient larger than 0.9). The results demonstrate that the screening method developed is reliable, cost-effective and user-friendly, and that the procedure is fast as the total time required is <1 h, which includes amplification

Home visit improves knowledge, self-care and adhesion in heart failure: randomized Clinical Trial HELEN-I

OBJECTIVE: To verify the effect of an educative nursing intervention composed of home visits and phone calls on patients' knowledge about the disease, self-care and adhesion to the treatment. METHODS: Randomized clinical trial with patients with recent hospitalization caused by decompensated heart failure. There were two groups: the intervention group, which has received four home visits and four phone calls to reinforce the guidelines during six months of follow up; and the control group, which has received conventional follow up with no visits or phone calls. RESULTS: Two hundred patients were randomized (101 in the intervention group and 99 in the control group). After six months, a significant improvement was observed in self-care and knowledge about the disease in the intervention group (P=0.001 and P<0.001), respectively; the adhesion to the treatment, measured and compared between the groups, was significantly higher in the intervention group (P=0.001). CONCLUSION: the strategy of home visits to patients who were recently hospitalized with decompensated heart failure was effective in improving the outcomes assessed and its implementation deserves to be considered in Brazil aiming at avoiding unplanned hospitalizations. NCT-0121386