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.     

Patient characteristics,anaesthetic workload and techniques in the UK: an analysis from the 7th National Audit Project (NAP7) activity survey

Detailed contemporary knowledge of the characteristics of the surgical population, national anaesthetic workload, anaesthetic techniques and behaviours are essential to monitor productivity, inform policy and direct research themes. Every 3–4 years, the Royal College of Anaesthetists, as part of its National Audit Projects (NAP), performs a snapshot activity survey in all UK hospitals delivering anaesthesia, collecting patient-level encounter data from all cases under the care of an anaesthetist. During November 2021, as part of NAP7, anaesthetists recorded details of all cases undertaken over 4 days at their site through an online survey capturing anonymous patient characteristics and anaesthetic details. Of 416 hospital sites invited to participate, 352 (85%) completed the activity survey. From these, 24,177 reports were returned, of which 24,172 (99%) were included in the final dataset. The work patterns by day of the week, time of day and surgical specialty were similar to previous NAP activity surveys. However, in non-obstetric patients, between NAP5 (2013) and NAP7 (2021) activity surveys, the estimated median age of patients increased by 2.3 years from median (IQR) of 50.5 (28.4–69.1) to 52.8 (32.1–69.2) years. The median (IQR) BMI increased from 24.9 (21.5–29.5) to 26.7 (22.3–31.7) kg.m^–2. The proportion of patients who scored as ASA physical status 1 decreased from 37% in NAP5 to 24% in NAP7. The use of total intravenous anaesthesia increased from 8% of general anaesthesia cases to 26% between NAP5 and NAP7. Some changes may reflect the impact of the COVID-19 pandemic on the anaesthetic population, though patients with confirmed COVID-19 accounted for only 149 (1%) cases. These data show a rising burden of age, obesity and comorbidity in patients requiring anaesthesia care, likely to impact UK peri-operative services significantly.     

Phase I and pharmacokinetic study of veliparib,a PARP inhibitor,and pegylated liposomal doxorubicin (PLD) in recurrent gynecologic cancer and triple negative breast cancer with long-term follow-up

Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.     

Use of Alternative Designs and Data Sources for Pediatric Trials

Abstract

Children are considered a vulnerable group and as such are granted additional protection as research subjects. Research projects using children as research subjects are justifiable if the answer to the scientific question of the study cannot be obtained by enrolling adult subjects (cf. scientific necessity). Thus, there is an ethical obligation to explore innovative analytical strategies that seek balance between the feasibility of conducting a trial and maximizing the utilization of data on efficacy and safety. On this note, there is enthusiasm for implementing some less popular but efficient alternative designs for confirmatory pediatric trials. Within the pediatric extrapolation paradigm, examples of such designs, other than purely based on pharmacokinetic/pharmacodynamic data, are described in this article along with their advantages and disadvantages. This article will also discuss how to incorporate alternative data sources in the analysis of pediatric clinical trials. A discussion of existing approaches and a road-map to their utilization will be provided. Real case examples on the use of the approaches are provided.     

Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases

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