'Unbearable suffering': a qualitative study on the perspectives of patients who request assistance in dying

BACKGROUND One of the objectives of medicine is to relieve patients' suffering. As a consequence, it is important to understand patients' perspectives of suffering and their ability to cope. However, there is poor insight into what determines their suffering and their ability to bear it. PURPOSE To explore the constituent elements of suffering of patients who explicitly request euthanasia or physician-assisted suicide (EAS) and to better understand unbearable suffering from the patients' perspective. PATIENTS AND METHODS A qualitative study using in-depth face-to-face interviews was conducted with 31 patients who had requested EAS. The grounded theory approach was used to analyse the data. RESULTS Medical, psycho-emotional, socio-environmental and existential themes contributed to suffering. Especially fatigue, pain, decline, negative feelings, loss of self, fear of future suffering, dependency, loss of autonomy, being worn out, being a burden, loneliness, loss of all that makes life worth living, hopelessness, pointlessness and being tired of living were constituent elements of unbearable suffering. Only patients with a psychiatric (co)diagnosis suffered unbearably all the time. CONCLUSIONS Unbearable suffering is the outcome of an intensive process that originates in the symptoms of illness and/or ageing. According to patients, hopelessness is an essential element of unbearable suffering. Medical and social elements may cause suffering, but especially when accompanied by psycho-emotional and existential problems suffering will become 'unbearable'. Personality characteristics and biographical aspects greatly influence the burden of suffering. Unbearable suffering can only be understood in the continuum of the patients' perspectives of the past, the present and expectations of the future.This study was supported by the Dutch Cancer Society (grant number KUN2007-03736)

Increased gravitational force reveals the mechanical, resonant nature of physiological tremor

Human physiological hand tremor has a resonant component. Proof of this is that its frequency can be modified by adding mass. However, adding mass also increases the load which must be supported. The necessary force requires muscular contraction which will change motor output and is likely to increase limb stiffness. The increased stiffness will partly offset the effect of the increased mass and this can lead to the erroneous conclusion that factors other than resonance are involved in determining tremor frequency. Using a human centrifuge to increase head-to-foot gravitational field strength, we were able to control for the increased effort by increasing force without changing mass. This revealed that the peak frequency of human hand tremor is 99% predictable on the basis of a resonant mechanism. We ask what, if anything, the peak frequency of physiological tremor can reveal about the operation of the nervous system.This work was funded by a BBSRC Industry Interchange Award to J.P.R.S. and R.F.R. C.J.O. was funded by BBSRC grant BB/I00579X/1. C.A.V. was funded by A∗Midex (Aix-Marseille Initiative of Excellence

In vitro inhibition of Eimeria tenella invasion of epithelial cells by phytochemicals

Resistance to coccidiostats and possible future restrictions on their use raise the need for alternative methods of reducing coccidiosis in poultry. The aim of this study was to evaluate the effect of selected phytochemicals on Eimeria tenella sporozoite invasion in vitro. Four phytochemicals were selected on the basis that they reduce the virulence of Eimeria spp. and/or provide immune modulatory benefits to host cells: betaine, carvacrol, curcumin and Echinacea purpurea extract (EP). Madin–Darby bovine kidney (MDBK) cells were covered by medium containing phytochemicals at the highest concentration which was non-toxic to the cells. Salinomycin 50 μg/ml was positive control; negative control was medium only. E. tenella (Houghton strain) sporozoites were added to wells and after incubation for 2, 4 or 20 h at 37 °C, cells were fixed and stained with hematoxylin–eosin. Ten evenly spaced fields per well were photographed and the percentage of cells invaded by sporozoites was calculated and normalized to the control. At 2 h, carvacrol, curcumin and EP showed a significantly lower percentage of sporozoite invasion than the untreated control; in contrast, betaine treatment represented a significantly higher invasion percentage. Combining carvacrol with EP inhibited E. tenella invasion more effectively than applying the compounds individually, but the further addition of curcumin did not reduce invasion further. In conclusion, this study shows that invasion of MDBK epithelial cells by E. tenella sporozoites is inhibited in the presence of carvacrol, curcumin, or EP and enhanced by betaine. There may be potential for developing these phytochemicals as anti-coccidial feed or water additives for poultry

Performance and usability of pre-operative prediction models for 30-day peri-operative mortality risk: a systematic review

Estimating pre-operative mortality risk may inform clinical decision-making for peri-operative care. However, pre-operative mortality risk prediction models are rarely implemented in routine clinical practice. High predictive accuracy and clinical usability are essential for acceptance and clinical implementation. In this systematic review, we identified and appraised prediction models for 30-day postoperative mortality in non-cardiac surgical cohorts. PubMed and Embase were searched up to December 2022 for studies investigating pre-operative prediction models for 30-day mortality. We assessed predictive performance in terms of discrimination and calibration. Risk of bias was evaluated using a tool to assess the risk of bias and applicability of prediction model studies. To further inform potential adoption, we also assessed clinical usability for selected models. In all, 15 studies evaluating 10 prediction models were included. Discrimination ranged from a c-statistic of 0.82 (MySurgeryRisk) to 0.96 (extreme gradient boosting machine learning model). Calibration was reported in only six studies. Model performance was highest for the surgical outcome risk tool (SORT) and its external validations. Clinical usability was highest for the surgical risk pre-operative assessment system. The SORT and risk quantification index also scored high on clinical usability. We found unclear or high risk of bias in the development of all models. The SORT showed the best combination of predictive performance and clinical usability and has been externally validated in several heterogeneous cohorts. To improve clinical uptake, full integration of reliable models with sufficient face validity within the electronic health record is imperative

Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates

<div><p>Conventional control and eradication strategies for bovine tuberculosis (BTB) face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle.</p><p>Twenty-four mixed breed calves (<i>Bos taurus</i>) aged 4–6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live <i>M</i>. <i>bovis</i> BCG (Danish 1331), formalin-inactivated <i>M</i>. <i>bovis</i> BCG, heat-killed <i>M</i>. <i>bovis</i> or PBS/Montanide™ (control). Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live <i>M</i>. <i>bovis</i> BCG.</p><p>The animals in the heat-killed <i>M</i>. <i>bovis</i> group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed <i>M</i>. <i>bovis</i> group.</p><p>In conclusion, the parenteral heat-killed <i>M</i>. <i>bovis</i> vaccine proved to be clearly immunogenic in cattle in the present study, urging further evaluation of the vaccine in challenge studies using virulent <i>M</i>. <i>bovis</i> and assessment of vaccine efficacy in field conditions.</p></div

Effects of Dementia-Care Mapping on Residents and Staff of Care Homes:A Pragmatic Cluster-Randomised Controlled Trial

BACKGROUND: The effectiveness of dementia-care mapping (DCM) for institutionalised people with dementia has been demonstrated in an explanatory cluster-randomised controlled trial (cRCT) with two DCM researchers carrying out the DCM intervention. In order to be able to inform daily practice, we studied DCM effectiveness in a pragmatic cRCT involving a wide range of care homes with trained nursing staff carrying out the intervention. METHODS: Dementia special care units were randomly assigned to DCM or usual care. Nurses from the intervention care homes received DCM training and conducted the 4-months DCM-intervention twice during the study. The primary outcome was agitation, measured with the Cohen-Mansfield agitation inventory (CMAI). The secondary outcomes included residents’ neuropsychiatric symptoms (NPSs) and quality of life, and staff stress and job satisfaction. The nursing staff made all measurements at baseline and two follow-ups at 4-month intervals. We used linear mixed-effect models to test treatment and time effects. RESULTS: 34 units from 11 care homes, including 434 residents and 382 nursing staff members, were randomly assigned. Ten nurses from the intervention units completed the basic and advanced DCM training. Intention-to-treat analysis showed no statistically significant effect on the CMAI (mean difference between groups 2·4, 95% CI −2·7 to 7·6; p = 0·34). More NPSs were reported in the intervention group than in usual care (p = 0·02). Intervention staff reported fewer negative and more positive emotional reactions during work (p = 0·02). There were no other significant effects. CONCLUSIONS: Our pragmatic findings did not confirm the effect on the primary outcome of agitation in the explanatory study. Perhaps the variability of the extent of implementation of DCM may explain the lack of effect. TRIAL REGISTRATION: Dutch Trials Registry NTR2314

Quantification of a shelter cat population: Trends in intake, length of stay and outcome data of cats in seven Dutch shelters between 2006 and 2021

Shelter metrics can be used by shelters for self-assessment to optimise the health of their animal population and to identify risk factors for disease outbreaks. However, there is a need for a wider scope of these shelter metrics, as evidenced by the interest from shelters in the benchmarking of shelter progress and the development of national best practices. For the first time, Dutch shelter data were used retrospectively to signal trends using potentially reliable metrics for the analysis of shelter data. The aims of this study were to apply relevant metrics describing the different phases of shelter management for shelter cats (i.e., intake, stay and outcome) and a retrospective analysis of shelter data over the period between 2006 and 2021. Seven of the approximately 120 Dutch animal shelters participated in this study. Quantitative data on the intake of more than 74,000 shelter cats (e.g., stray cats, cats surrendered by their owners and cats obtained from other sources) and their outcomes (i.e., cats rehomed, returned to their owners, deceased, or otherwise lost) have been analysed. Metrics such as rehoming rate, return to owner rate, rates for mortality and euthanasia, length of stay and risk-based live release rate were determined. The main findings of the study during this 16-year period were that, over time, the number of cats per 1000 residents admitted to Dutch shelters was reduced by 39%, the number of feline euthanasia cases decreased by approximately 50%, the length of stay showed a reducing trend, while the return to owner and the risk-based live release rate increased. The shelter metrics examined in this study could be helpful in monitoring and evaluating the management, consequent health, and well-being of cats in shelters and eventually measuring progress of shelters both in the Netherlands and at a European level

Від коваріацій до каузальності. Відкриття структур залежностей у даних

Проаналізовано сучасну методологію виводу каузальних моделей та структур систем імовірнісних залежностей із статистичних даних пасивних спостережень. Висвітлено можливості, проблеми, застереження та обмеження методів індуктивної ідентифікації каузальних відношень в апараті марковських властивостей та баєсових мереж. Виділено кілька ступенів каузальних моделей згідно з рівнем їх обґрунтованості та адекватності джерелу даних. Сформульовано статистичний паттерн, який зводить обґрунтування висновку про каузальний характер зв’язку двох змінних до тестування набору статистичних фактів (не)залежності.Проанализирована современная методология вывода каузальных моделей и структур систем вероятностных зависимостей из статистических данных пассивных наблюдений. Освещены возможности, проблемы, оговорки и ограничения методов индуктивной идентификации каузальных отношений в аппарате марковских свойств и байесовых сетей. Выделены несколько ступеней каузальных моделей согласно уровню их обоснованности и адекватности источнику данных. Сформулирован статистический паттерн, который сводит обоснование вывода о каузальном характере связи двух переменных к тестированию набора статистических фактов (не)зависимости.The current methodology of output casual models and structures of systems of probabilistic dependencies of stafistical data of passive observation is analysed. The problems, features, traps and limitations of the methods of the inductive identification of casual relation in the unit of marcov properties and bayesias nets are highlighted. Several stages of casual models according to the level of their validity and adequacy of the data source are emphasized. The statistical pattern, which brings the justification of a finding about casual nature of the connections between two variables to the test of a set of statistical facts of (in)dependency is formulated

Calendar 2015

Item does not contain fulltextBACKGROUND: Children of patients with young onset dementia (YOD) who are confronted with a parent who has a progressive disease, often assist in caregiving tasks, which may have a great impact on their lives. The objective of the present study is to explore the experiences of children living with a young parent with dementia with a specific focus on the children's needs. METHODS: Semi-structured interviews with 14 adolescent children between the ages of 15 and 27 years of patients with YOD were analyzed using inductive content analysis. Themes were identified based on the established codes. RESULTS: The emerging categories were divided into three themes that demonstrated the impact of dementia on daily life, different ways of coping with the disease, and children's need for care and support. The children had difficulties managing all of the responsibilities and showed concerns about their future. To deal with these problems, they demonstrated various coping styles, such as avoidant or adaptive coping. Although most children were initially reluctant to seek professional care, several of them expressed the need for practical guidance to address the changing behavior of their parent. The children felt more comfortable talking to someone who was familiar with their situation and who had specific knowledge of YOD and the available services. CONCLUSION: In addition to practical information, more accessible and specific information about the diagnosis and the course of YOD is needed to provide a better understanding of the disease for the children. These findings underline the need for a personal, family-centered approach

Hearing Impairment Is Associated with Smaller Brain Volume in Aging

Although recent studies show that age-related hearing impairment is associated with cerebral changes, data from a population perspective are still lacking. Therefore, we studied the relation between hearing impairment and brain volume in a large elderly cohort. From the population-based Rotterdam Study, 2,908 participants (mean age 65 years, 56% female) underwent a pure-tone audiogram to quantify hearing impairment. By performing MR imaging of the brain we quantified global and regional brain tissue volumes (total brain volume, gray matter volume, white matter (WM) volume, and lobe-specific volumes). We used multiple linear regression models, adjusting for age, sex, head size, time between hearing test and MR imaging, and relevant cognitive and cardiovascular covariates. Furthermore, we performed voxel-based morphometry to explore sub-regional differences. We found that a higher pure-tone threshold was associated with a smaller total brain volume [difference in standardized brain volume per decibel increase in hearing threshold in the age-sex adjusted model: -0.003 (95% confidence interval -0.004; -0.001)]. Specifically, WM volume was associated. Both associations were more pronounced in the lower frequencies. All associations were consistently present in all brain lobes in the lower frequencies and in most lobes in the higher frequencies, and were independent of cognitive function and cardiovascular risk factors. In voxel-based analyses we found associations of hearing impairment with smaller white volumes and some smaller and larger gray volumes, yet these were statistically non-significant. Our findings demonstrate that hearing impairment in elderly is related to smaller total brain volume, independent of cognition and cardiovascular ris