An individually adjusted approach for communicating epidemiological results on health and lifestyle to patients.

If scientific research on modifiable risk factors was more accessible to the general population there is a potential to prevent disease and promote health. Mobile applications can automatically combine individual characteristics and statistical models of health to present scientific information as individually tailored visuals, and thus there is untapped potential in incorporating scientific research into apps aimed at promoting healthier lifestyles. As a proof-of-concept, we develop a statistical model of the relationship between Self-rated-health (SRH) and lifestyle-related factors, and a simple app for conveying its effects through a visualisation that sets the individual as the frame of reference. Using data from the 6th (n = 12 981, 53.4% women and 46.6% men) and 7th (n = 21 083, 52.5% women and 47.5% men) iteration of the Tromsø population survey, we fitted a mixed effects linear regression model that models mean SRH as a function of self-reported intensity and frequency of physical activity (PA), BMI, mental health symptoms (HSCL-10), smoking, support from friends, and HbA1c ≥ 6.5%. We adjusted for socioeconomic and demographic factors and comorbidity. We designed a simple proof-of-concept app to register relevant user information, and use the SRH-model to translate the present status of the user into suggestions for lifestyle changes along with predicted health effects. SRH was strongly related to modifiable health factors. The strongest modifiable predictors of SRH were mental health symptoms and PA. The mean adjusted difference in SRH between those with 10-HSCL index = 1.85 (threshold for mental distress) and HSCL-10 = 1 was 0.59 (CI 0.61-0.57). Vigorous physical activity (exercising to exhaustion ≥ 4 days/week relative to sedentary) was associated with an increase on the SRH scale of 0.64 (CI 0.56-0.73). Physical activity intensity and frequency interacted positively, with large PA-volume (frequency ⨯ intensity) being particularly predictive of high SRH. Incorporating statistical models of health into lifestyle apps have great potential for effectively communicating complex health research to a general audience. Such an approach could improve lifestyle apps by helping to make the recommendations more scientifically rigorous and personalised, and offer a more comprehensive overview of lifestyle factors and their importance.

Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) is a paediatric cancer driven either by fusion proteins (e.g., PAX3-FOXO1) or by mutations in key signalling molecules (e.g., RAS or FGFR4). Despite the latter providing opportunities for precision medicine approaches in RMS, there are currently no such treatments implemented in the clinic. METHODS: We evaluated biologic properties and targeting strategies for the FGFR4 V550L activating mutation in RMS559 cells, which have a high allelic fraction of this mutation and are oncogenically dependent on FGFR4 signalling. Signalling and trafficking of FGFR4 V550L were characterised by confocal microscopy and proteomics. Drug effects were determined by live-cell imaging, MTS assay, and in a mouse model. RESULTS: Among recently developed FGFR4-specific inhibitors, FGF401 inhibited FGFR4 V550L-dependent signalling and cell proliferation at low nanomolar concentrations. Two other FGFR4 inhibitors, BLU9931 and H3B6527, lacked potent activity against FGFR4 V550L. Alternate targeting strategies were identified by RMS559 phosphoproteomic analyses, demonstrating that RAS/MAPK and PI3K/AKT are essential druggable pathways downstream of FGFR4 V550L. Furthermore, we found that FGFR4 V550L is HSP90-dependent, and HSP90 inhibitors efficiently impeded RMS559 proliferation. In a RMS559 mouse xenograft model, the pan-FGFR inhibitor, LY2874455, did not efficiently inhibit growth, whereas FGF401 potently abrogated growth. CONCLUSIONS: Our results pave the way for precision medicine approaches against FGFR4 V550L-driven RMS.

Biodistribution of Poly(alkyl cyanoacrylate) Nanoparticles in Mice and Effect on Tumor Infiltration of Macrophages into a Patient-Derived Breast Cancer Xenograft.

We have investigated the biodistribution and tumor macrophage infiltration after intravenous injection of the poly(alkyl cyanoacrylate) nanoparticles (NPs): PEBCA (poly(2-ethyl-butyl cyanoacrylate), PBCA (poly(n-butyl cyanoacrylate), and POCA (poly(octyl cyanoacrylate), in mice. These NPs are structurally similar, have similar PEGylation, and have previously been shown to give large variations in cellular responses in vitro. The PEBCA NPs had the highest uptake both in the patient-derived breast cancer xenograft MAS98.12 and in lymph nodes, and therefore, they are the most promising of these NPs for delivery of cancer drugs. High-resolution magic angle spinning magnetic resonance (HR MAS MR) spectroscopy did not reveal any differences in the metabolic profiles of tumors following injection of the NPs, but the PEBCA NPs resulted in higher tumor infiltration of the anti-tumorigenic M1 macrophages than obtained with the two other NPs. The PEBCA NPs also increased the ratio of M1/M2 (anti-tumorigenic/pro-tumorigenic) macrophages in the tumors, suggesting that these NPs might be used both as a vehicle for drug delivery and to modulate the immune response in favor of enhanced therapeutic effects.

MITF depletion elevates expression levels of ERBB3 receptor and its cognate ligand NRG1-beta in melanoma.

The phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway is frequently hyper-activated upon vemurafenib treatment of melanoma. We have here investigated the relationship between SRY-box 10 (SOX10), forkhead box 3 (FOXD3) and microphthalmia-associated transcription factor (MITF) in the regulation of the receptor tyrosine-protein kinase ERBB3, and its cognate ligand neuregulin 1-beta (NRG1-beta). We found that both NRG1-beta and ERBB3 mRNA levels were elevated as a consequence of MITF depletion, induced by either vemurafenib or MITF small interfering RNA (siRNA) treatment. Elevation of ERBB3 receptor expression after MITF depletion caused increased activation of the PI3K pathway in the presence of NRG1-beta ligand. Together, our results suggest that MITF may play a role in the development of acquired drug resistance through hyper-activation of the PI3K pathway.

User participation in district psychiatry. The social construction of 'users' in handovers and meetings.

An ideal in mental health care is user participation. This implies inclusion and facilitation by clinicians to enable users to participate in decisions about themselves and in the design of suitable treatment. However, much of the work of clinicians consists of handovers and other meetings where patients are not present. It is therefore interesting to study how the patient perspective is handled in such meetings and whether it forms a basis for user participation. We conducted fieldwork in three different inpatient wards in Norwegian District Psychiatric Centres. We used an interactional perspective in our analysis, where speech acts, framing and footing were key concepts. The findings show that the talk in the handovers and meetings contained five main themes and that there was a clear correlation between what was said and how it was said, and whether clinicians related to the content in a decisive, person-centred or indecisive manner. We discuss potential participation statuses for patients and their limited opportunity to influence the talk and possible decisions about themselves. Our conclusion is that handover meetings primarily function as an aid in organising clinicians' work and could ultimately be seen as counteracting user participation.

Cancer survivors' experiences of humour while navigating through challenging landscapes--a socio-narrative approach.

AIM: Humour is seen as a health-promoting coping strategy when dealing with life stress. The aim is to elucidate how adult cancer survivors experience and evaluate the significance of humour in daily life, from diagnosis through their entire illness trajectory, and to gain a broader understanding of humour as part of stress-coping processes during the experience of cancer as a life-threatening illness. METHOD: A socio-narrative approach was chosen to study the humorous stories and their use in everyday contexts. Fourteen participants aged 23-83 with a variety of experiences across diagnoses, times since diagnosis, prognoses and life situations were interviewed. FINDINGS: Participants described humour as helpful and utilised its capacity to deal with difficult situations or related distress, although fluctuations in the course of the illness coincided with two extremes: humour that disappeared and humour that returned. Their use of humour was related to three key themes: facing a life-threatening situation, togetherness and communication, and living with the situation. CONCLUSION: Depending on the aim, humour contributes variously through the stress-coping process within the distinctions of emotion-, problem- and meaning-focused coping. Humour served to relieve the anxiety burden, enhance problem-solving ability, safeguard important relationships, communicate difficult topics, regain identity and help significant others to cope, even enabling the richness of life to help living with the risk. Humour should be considered as a significant engaging coping strategy by which the cancer survivors seek to manage their situation throughout the illness trajectory.

Good coercion: patients' moral evaluation of coercion in mental health care.

The use of coercion in mental health care is not self-evident and requires moral justification. A joint understanding is difficult to achieve, because patients and health professionals often evaluate coercion differently. The present study aims to discuss patients' 'moral' evaluation of coercion. We believe that such a focus can form the basis for a better and more differentiated understanding of how we evaluate coercion. This is a qualitative study based on participant observation and interviews with patients. In order to focus specifically on the moral evaluation of coercion, we looked within patients' narratives to examine whether we could differentiate between how they experienced coercion and how they morally evaluated its use, and how they envision/describe good coercion. We found that patients differentiated implicitly between experiences and moral evaluation. The findings have been ordered into three types of reactions: agreeing and accepting, fighting or resisting, and resignation. Further reflection upon patients' positive and negative moral evaluations of coercion resulted in the formulation of different concrete elements at three levels: threshold elements, process elements, and empathic elements. These elements helped us to understand what these patients considered 'good coercion'. The implications are that good clinical practice cannot be separated from the formal, moral evaluation of coercion. A differentiated moral understanding of coercion can form the basis for better and more sensitive communication about coercion among all those involved. A more respectful dialogue on the moral evaluation of coercion might also raise awareness during both the decision-making process and the actual practising of coercion.

'When coercion moves into your home'--a qualitative study of patient experiences with outpatient commitment in Norway.

The use of coercion on people with mental health problems is a serious intervention, and a reduction in its use is a declared goal in mental healthcare. Yet, many countries have introduced expanded powers of coercion in recent years, including outpatient commitment (OC). However, the evidence of the effectiveness of OC is inconclusive, and little is known about how patients experience OC schemes. The objective of this qualitative study was to explore (i) patients' experiences with OC, and (ii) how routines in care and health services affect patients' everyday living. The data were collected in 2011-2012 and included 11 qualitative in-depth interviews with patients subject to OC. The study used a narrative approach to interviews and a thematic narrative analysis. Participants generally complied with the OC requirements because of the clear and secure framework of OC, and also because they believed that the alternative would be involuntary hospitalisation. No one reported physical force, but coercion was experienced as limitation of freedom of action through excessive control and little patient influence or participation in their own treatment. Factors affecting patients' freedom of action under OC should be taken into account when the imposition of an OC order is considered.

Medication and participation: A qualitative study of patient experiences with antipsychotic drugs.

Patient autonomy is recognised within mental healthcare, although the capacity to participate in one's own treatment planning is often reduced during a psychotic crisis. The patient may not be sufficiently competent to give consent or express preferences at the time treatment decisions are made. Nine participants were interviewed shortly after a crisis. We discussed participation in the treatment planning and recovery process with particular emphasis on interactions with professionals and understanding treatment. The participants recognised the need for drugs and mental healthcare but emphasised the need for better cooperation and communication. To facilitate the development of patient autonomy, we recommend an increased emphasis on providing information and participating in a dialogue about drug treatment options. This could counteract many of the negative experiences reported. The use of debriefing during hospitalisation and following coercion can be a practical tool for clarifying patient preferences and mutual understanding.

Intensive care nurses' involvement in the end-of-life process--perspectives of relatives.

In this article, we report findings from a qualitative study that explored how the relatives of intensive care unit patients experienced the nurses' role and relationship with them in the end-of-life decision-making processes. In all, 27 relatives of 21 deceased patients were interviewed about their experiences in this challenging ethical issue. The findings reveal that despite bedside experiences of care, compassion and comfort, the nurses were perceived as vague and evasive in their communication, and the relatives missed a long-term perspective in the dialogue. Few experienced that nurses participated in meetings with doctors and relatives. The ethical consequences imply increased loneliness and uncertainty, and the experience that the relatives themselves have the responsibility of obtaining information and understanding their role in the decision-making process. The relatives therefore felt that the nurses could have been more involved in the process.

Family members' experiences of "wait and see" as a communication strategy in end-of-life decisions.

PURPOSE: The aim of this study is to examine family members' experiences of end-of-life decision-making processes in Norwegian intensive care units (ICUs) to ascertain the degree to which they felt included in the decision-making process and whether they received necessary information. Were they asked about the patient's preferences, and how did they view their role as family members in the decision-making process? METHODS: A constructivist interpretive approach to the grounded theory method of qualitative research was employed with interviews of 27 bereaved family members of former ICU patients 3-12 months after the patient's death. RESULTS: The core finding is that relatives want a more active role in end-of-life decision-making in order to communicate the patient's wishes. However, many consider their role to be unclear, and few study participants experienced shared decision-making. The clinician's expression "wait and see" hides and delays the communication of honest and clear information. When physicians finally address their decision, there is no time for family participation. Our results also indicate that nurses should be more involved in family-physician communication. CONCLUSIONS: Families are uncertain whether or how they can participate in the decision-making process. They need unambiguous communication and honest information to be able to take part in the decision-making process. We suggest that clinicians in Norwegian ICUs need more training in the knowledge and skills of effective communication with families of dying patients.

[Hyperammonemia during parenteral nutrition of intensive-care patients]. / Hyperammoniämie bei der parenteralen Ernährung von Intensivpflegepatienten.

Metabolic features of parenteral feeding with conventional amino acid solutions were examined in 47 patients over a long period. 30 patients were kept alive by artificial respiration. The metabolic parameters ammonium, blood urea nitrogen, GOT, alkaline phosphatase were carried out, in 6 patients the pattern of amino acids was analysed. All patients showed a significant increase of ammonium during the course of parenteral feeding. The amino acids demonstrated pattern of imbalance. The other other parameters were not changed significantly. Traumatic, hypoxic or toxic liver damage might influence the reduction of liver function.