Delivering end-of-life care for patients with cancer at home: Interviews exploring the views and experiences of general practitioners

Many patients with terminal cancer wish to die at home and general practitioners in the United Kingdom have a critical role in providing this care. However, it has been suggested general practitioners lack confidence in end-of-life care. It is important to explore with general practitioners their experience and perspectives including feelings of confidence delivering end-of-life care to people with cancer. The aim of this study was to explore general practitioners experiences of providing end-of-life care for people with cancer in the home setting and their perceptions of confidence in this role as well as understanding implications this has on policy design. A qualitative study design was employed using semi-structured interviews and analysed using thematic analysis. Nineteen general practitioners from London were purposively sampled from eight general practices and a primary care university department in 2018–2019, supplemented with snowballing methods. Five main themes were constructed: (a) the subjective nature of defining palliative and end-of-life care; (b) importance of communication and managing expectations; (c) complexity in prescribing; (d) challenging nature of delivering end-of-life care; (e) the unclear role of primary care in palliative care. General practitioners viewed end-of-life care as challenging; specific difficulties surrounded communication and prescribing. These challenges coupled with a poorly defined role created a spread in perceived confidence. Experience and exposure were seen as enabling confidence. Specialist palliative care service expansion had important implications on deskilling of essential competencies and reducing confidence levels in general practitioners. This feeds into a complex cycle of causation, leading to further delegation of care.     

Rapalogs induce non-apoptotic,autophagy-dependent cell death in HPV-negative TP53 mutant head and neck squamous cell carcinoma

TP53 is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSCC). Patients with HPV-negative TP53 mutant HNSCC have the worst prognosis, necessitating additional agents for treatment. Since mutant p53 causes sustained activation of the PI3K/AKT/mTOR signaling pathway, we investigated the effect of rapalogs RAD001 and CCI-779 on HPV-negative mutTP53 HNSCC cell lines and xenografts. Rapalogs significantly reduced cell viability and colony formation. Interestingly, rapalogs-induced autophagy with no effect on apoptosis. Pretreatment with autophagy inhibitors, 3-methyladenine (3-MA) and ULK-101 rescued the cell viability by inhibiting rapalog-induced autophagy, suggesting that both RAD001 and CCI-779 induce non-apoptotic autophagy-dependent cell death (ADCD). Moreover, rapalogs upregulated the levels of ULK1 and pULK1 S555 with concomitant downregulation of the mTORC1 pathway. However, pretreatment of cells with rapalogs prevented the ULK-101-mediated inhibition of ULK1 to sustained autophagy, suggesting that rapalogs induce ADCD through the activation of ULK1. To further translate our in vitro studies, we investigated the effect of RAD001 in HPV-negative mutTP53 (HN31 and FaDu) tumor cell xenograft model in nude mice. Mice treated with RAD001 exhibited a significant tumor volume reduction without induction of apoptosis, and with a concomitant increase in autophagy. Further, treatment with RAD001 was associated with a considerable increase in pULK1 S555 and ULK1 levels through the inhibition of mTORC1. 3-MA reversed the effect of RAD001 on FaDu tumor growth suggesting that RAD001 promotes ACDC in HPV-negative mutTP53 xenograft. This is the first report demonstrating that rapalogs promote non-apoptotic ADCD in HPV-negative mutTP53 HNSCC via the ULK1 pathway. Further studies are required to establish the promising role of rapalogs in preventing the regrowth of HPV-negative mutTP53 HNSCC.     

Just a Spoonful of Sugar Helps the Messages Go Down: Using Stories and Vicarious Self-Affirmation to Reduce e-Cigarette Use

ABSTRACT

While prior research has demonstrated the benefits of self-affirming individuals prior to exposing them to potentially threatening health messages, the current study assesses the feasibility of inducing self-affirmation vicariously through the success of a character in a narrative. In Study 1, college-age participants who regularly use e-cigarettes (N = 225) were randomly assigned to read one of two versions of a story depicting a college student of their own gender. The versions were identical except in the vicarious self-affirmation (VSA) condition, the main character achieves success (i.e., honored with a prestigious award) before being confronted by a friend about the dangers associated with their e-cigarette use; whereas in the vicarious control condition, the achievement is mentioned after the risk information. Results of the posttest and 10-day follow-up demonstrated that VSA reduced messages derogation, while increasing self-appraisal and perceived risk. The effect of VSA on e-cigarette outcomes was moderated by frequency of use, with heavier users benefiting the most. Study 2 (N = 152) confirmed that traditional value affirmation works with our stimuli on a comparable population.     

The Role of the Medical Expert in the Retrospective Assessment of Testamentary Capacity

Objectives:Physicians and other mental health experts are increasingly called on to assist the courts with the determination of testamentary capacity. We aim to improve the understanding of the retrospective assessment of testamentary capacity for medical experts in order to provide more useful reports for the court’s determinations and to provide a methodology for the retrospective assessment of testamentary capacity.Method:Medical experts with experience in the retrospective assessment of testamentary capacity collaborated with lawyers who practice estate litigation. The medical literature on the assessment of testamentary capacity was reviewed and integrated. The medical experts provided a clinical perspective, while the lawyers ensured that the case law and legal perspective were integrated into this review.Results:The focus and limitations of the medical expert are outlined including the need to be objective, nonpartisan, and fair. For the benefit of the court, the medical expert should describe the nature and severity of relevant medical, psychiatric, and cognitive disorders, and how they may impact on the specific criteria for testamentary capacity as defined by the leading case of Banks v Goodfellow. Medical experts should opine only on the issue of vulnerability to influence and defer to the court to determine the facts of the case regarding any influence that may have been exerted.Conclusions:Although the ultimate determination of testamentary capacity is a legal one, medical experts can help the court achieve the most informed legal decision by providing relevant information on clinical issues that may impact the criteria for testamentary capacity.     

Analysis of proximal bone margins in diabetic foot osteomyelitis by conventional culture,DNA sequencing and microscopy

Multiple approaches were employed to detect pathogens from bone margins associated with Diabetic Foot Osteomyelitis (DFO). Intra‐operative bone specimens of 14 consecutive subjects with suspected DFO were collected over a six‐month study period from Liverpool Hospital. Infected bone and a proximal bone margins presumed to be ‘clean/non‐infected’ were collected. Bone material was subjected to conventional culture, DNA sequencing and microscopy. In total, eight of 14 (57%) proximal bone margins had no growth by conventional culture but were identified in all proximal bone specimens by DNA sequencing. Proximal margins had lower median total microbial counts than infected specimens, but these differences were not statistically significant. Pathogens identified by sequencing in infected specimens were identified in proximal margins and the microbiomes were similar (ANOSIM = 0.02, p = 0.59). Using a combination of SEM and/or PNA‐FISH, we visualized the presence of microorganisms in infected bone specimens and their corresponding proximal margins of seven patients (50%) with DFO. We identify that bacteria can still reside in what seems to be proximal ‘clean’ margins. The significance and implications of clinical outcomes requires further analysis from a larger sample size that incorporates differences in surgical and post‐operative approaches, correlating any outcomes back to culture‐sequence findings.     

Attention,Externalizing, and Internalizing Problems of Youth Exposed to Parental Incarceration

Few studies have examined the effects of parental incarceration (PI) on outcomes above and beyond other risk and adverse childhood experiences (ACEs). The objectives of this study were to (1) the associations between PI and mental health problems (attention, externalizing, internalizing, and total behavioral problems) and (2) the mediating role of current socioeconomic status and cumulative ACEs. An observational and cross-sectional design was employed. Analyses included hierarchical multivariable linear regression modeling. The analytic sample included 613 adolescents (11–17?years). On average, youth exposed to PI experienced three times as many ACEs compared with youth unexposed. Youth exposed to PI were more likely to have behavioral problems than their unexposed peers. The main effect for all models was attenuated by current economic hardship as well as exposure to increasing numbers of ACEs. Exposure to PI can be viewed as a marker of accumulative risk for intervention since youth impacted by PI are more likely to experience behavioral difficulties and associated adverse childhood experiences. Due to the associated adversity that impact youth exposed to PI, mental health providers need to be able to identify and screen for symptoms associated with trauma.     

Conserved pan-cancer microenvironment subtypes predict response to immunotherapy

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