322 research outputs found
Implementation of knowledge-based palliative care in acute care settings : obstacles, opportunities and experiences
Background and aim: Quality improvement is continuously ongoing at different levels in
our healthcare system. In Sweden, as in other countries, guidelines are important for quality
improvement in healthcare, since they summarize the best available evidence. Improved
living conditions and enhanced treatments for a variety of diseases have resulted in increased
longevity and the need for palliative care has therefore also increased. A high proportion of
deaths occur in acute care settings, where the care has been described as inadequate for dying
patients. In 2013, the National Board of Health and Welfare published A National knowledgebased guidance for good palliative care in end-of-life care and just prior to this in 2012, the
Regional Cancer Centre published the National clinical practice guideline for palliative care.
The overarching aim of this thesis was to study implementation of knowledge-based
palliative care in acute care settings.
Methods and results of the studies: The first and second studies covered aspects that were
to be taken into account for the implementation of the documents described above. In study I,
national policy documents in Sweden were reviewed for quality indicators relevant to
palliative care and end-of-life care. In study II, perceptions regarding national palliative care
guidelines were investigated and obstacles to and opportunities for implementing these
guidelines in acute care hospitals were identified through interviews with local politicians,
chief medical officers and healthcare professionals. The results showed scarce knowledge of
the two documents at all levels of the healthcare organisation. Palliative care was primarily
described as end-of- life care. The environment and culture in hospitals, with heavy
workload, poor communication and poor teamwork, were described as obstacles for
implementation. However, staff emphasised a need for training and support in palliative care
through theoretical knowledge and mentoring to develop clinical skills. An implementation
strategy for the use of the Integrated Palliative care Outcome Scale (IPOS) was developed.
The strategy included information, training and facilitation to support the use of the scale.
The implementation was performed at three acute care settings and, to gain a broader
understanding of the strategy, it was also tested at a palliative care unit. The evaluation of the
strategy, presented in study III and IV, was conducted through multiple methods. The
findings showed varying prevalence of completed IPOS, indicating shortcomings in
implementation.
Conclusion: The awareness of the two documents on palliative care varied at all levels in the
healthcare organisation, being predominantly low among healthcare professionals in acute
care settings. The feasibility of the performed implementation strategy was considered
questionable and the components need to be further explored to enhance the impact of
implementation and thereby improve the use of IPOS in acute care settings
Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance
Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 ± 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10- and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10- or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR
Omicron Variant Generates a Higher and More Sustained Viral Load in Nasopharynx and Saliva Than the Delta Variant of SARS-CoV-2
The Omicron variant of SARS-CoV-2 spreads more easily than earlier variants, possibly as a result of a higher viral load in the upper respiratory tract and oral cavity. Hence, we investigated whether the Omicron variant generates a higher viral load than that of the Delta variant in saliva and nasopharynx. Both specimens were collected from 52 Omicron and 17 Delta cases at two time points one week apart and analyzed by qRT-PCR. Viral load was measured as 10 log RNA genome copies per 1000 human cells according to the WHO reference standard. We found that Omicron cases carried a higher viral load and had more sustained viral shedding compared to the Delta cases, especially in the nasopharynx
Higher levels of unmet support needs in spouses are associated with poorer quality of life - a descriptive cross-sectional study in the context of palliative home care.
Funder: Linnaeus UniversityBACKGROUND: Family caregivers often report having unmet support needs when caring for someone with life-threatening illness. They are at risk for psychological distress, adverse physical symptoms and negatively affected quality of life. This study aims to explore associations between family caregivers' support needs and quality of life when caring for a spouse receiving specialized palliative home care. METHODS: A descriptive cross-sectional design was used: 114 family caregivers completed the Carer Support Needs Assessment Tool (CSNAT) and the Quality of Life in Life-Threatening Illness - Family caregiver version (QOLLTI-F) and 43 of them also answered one open-ended question on thoughts about their situation. Descriptive statistics, multiple linear regression analyses, and qualitative content analysis, were used for analyses. RESULTS: Higher levels of unmet support needs were significantly associated with poorer quality of life. All CSNAT support domains were significantly associated with one or more quality of life domains in QOLLTI-F, with the exception of the QoL domain related to distress about the patient condition. However, family caregivers described in the open-ended question that their life was disrupted by the patient's life-threatening illness and its consequences. Family caregivers reported most the need of more support concerning knowing what to expect in the future, which they also described as worries and concerns about what the illness would mean for them and the patient further on. Lowest QoL was reported in relation to the patient's condition, and the family caregiver's own physical and emotional health. CONCLUSION: With a deeper understanding of the complexities of supporting family caregivers in palliative care, healthcare professionals might help to increase family caregivers' QoL by revealing their problems and concerns. Thus, tailored support is needed
11q deletion or ALK activity curbs DLG2 expression to maintain an undifferentiated state in neuroblastoma
High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of undifferentiated neural crest-derived progenitors through the repression of DLG2, a candidate tumor suppressor gene in neuroblastoma. DLG2 is expressed in the murine "bridge signature'' that represents the transcriptional transition state when neural crest cells or Schwann cell precursors differentiate to chromaffin cells of the adrenal gland. We show that the restoration of DLG2 expression spontaneously drives neuroblastoma cell differentiation, high-lighting the importance of DLG2 in this process. These findings are supported by genetic analyses of high-risk 11q deletion neuroblastomas, which identified genetic lesions in the DLG2 gene. Our data also suggest that further exploration of other bridge genes may help elucidate the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to neuroblastomas
Circulating markers of extracellular matrix remodelling in severe COVID-19 patients
Background
Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 patients.
Methods
Serial blood samples were obtained from two cohorts of hospitalised COVID-19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3-month follow-up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60-day total mortality and pulmonary pathology after 3-months. We also evaluated the direct effect of inactivated SARS-CoV-2 on the release of the different ECM mediators in relevant cell lines.
Results
Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium-binding protein A12 and YKL-40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3-months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS-CoV-2 suggesting a direct link between these mediators and the causal agent of COVID-19.
Conclusion
Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL-40 in the pathogenesis of severe COVID-19
Rationale for a Swedish cohort consortium
We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.Peer reviewe
Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients
The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated to trigger this detrimental process. The complement system is a key player in innate immunity. Despite a few reports of local complement activation, there is a lack of evidence that the degree of systemic complement activation occurs early in COVID-19 patients, and whether this is associated with respiratory failure. This study shows that a number of complement activation products are systemically, consistently, and long-lastingly increased from admission and during the hospital stay. Notably, the terminal sC5b-9 complement complex was associated with respiratory failure. Thus, complement inhibition is an attractive therapeutic approach for treatment of COVD-19
Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity
Background: Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron have been interpreted as indicating the need for a third vaccine dose for protection. However, there is little information about early immune responses to Omicron infection in double vaccinated individuals.
Methods: We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 double-vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively.
Findings: Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the receptor-binding domain (RBD) of Omicron protein and spike peptide-induced interferon gamma in whole blood. Both the Omicron- and the Delta-infected patients had a mild and transient increase in inflammatory parameters.
<p<Interpretation: The results suggest that two vaccine doses are sufficient to mount a rapid and potent immune response upon infection in healthy individuals of with the Omicron variant
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