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.     

Synthesis,bioconjugation and stability studies of [18F]ethenesulfonyl fluoride

Fluorine‐18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [¹⁸F]ethenesulfonyl fluoride ([¹⁸F]ESF) and its Michael conjugation with amino acids and proteins. The synthesis of [¹⁸F]ESF was optimised using a microfluidic reactor under both carrier‐added (c.a.) and no‐carrier‐added (n.c.a.) conditions, affording, in a straightforward procedure, 30‐50% radiochemical yield (RCY) for c.a. [¹⁸F]ESF and 60‐70% RCY for n.c.a. [¹⁸F]ESF. The conjugation reactions were performed at room temperature using 10 mg/mL precursor in aqueous/organic solvent mixtures for 15 min. The radiochemical stability of the final conjugates was evaluated in injectable formulation and rat serum, and resulted strongly substrate dependent and generally poor in rat serum. Therefore, in this work we have optimised a straightforward synthesis of [¹⁸F]ESF and its Michael conjugation with model compounds, without requiring chromatographic purification. However, given the general low stability of the final products, further studies will be required for improving conjugate stability, before assessing the use of this PG for PET imaging.     

Assessment of predicted enzymatic activity of α‐N‐acetylglucosaminidase variants of unknown significance for CAGI 2016

The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α‐N‐acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to .61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population‐scale analysis of disease epidemiology and rare variant association analysis.     

Smoking, a weak predictor of periodontitis in older adults

BACKGROUND: The impact of smoking habits on periodontal conditions in older subjects is poorly studied. AIMS: To assess if a history of smoking is associated with chronic periodontitis and medical history in older subjects. MATERIAL AND METHODS: The medical and dental history was collected from 1084 subjects 60-75 years of age. Smoking history information was obtained from self-reports. Periodontal variables [clinical probing depth (PD)>/=5.0 mm, clinical attachment levels (CALs) >/=4.0 mm], and radiographic evidence of alveolar bone loss were assessed. RESULTS: 60.5% had never smoked (NS), 32.0% were former smokers (FS) (mean smoke years: 26.1 years, SD+/-13.1), and 7.5% were current smokers (CS) (mean smoke years 38.0 years, (SD+/-12.1). The proportional distribution of CAL >/=4.0 mm differed significantly by smoking status (NS and CS groups) (mean difference: 12.1%, 95% confidence interval (CI): 1.5-22.6, p<0.02). The Mantel-Haenszel common odds ratio between smoking status (CS+FS) and periodontitis (>20% bone loss) was 1.3 (p<0.09, 95% CI: 0.9-2.0) and changed to 1.8 (p<0.02, 95% CI: 1.3-2.7) with 30 years of smoking as cutoff. A weak correlation between number of years of smoking and CAL>/=4.0 mm was demonstrated (r(2) values 0.05 and 0.07) for FS and CS, respectively. Binary logistic forward (Wald) regression analysis demonstrated that the evidence of carotid calcification, current smoking status, gender (male), and the number of remaining teeth were explanatory to alveolar bone loss. CONCLUSIONS: A clinically significant impact on periodontal conditions may require 30 years of smoking or more. Tooth loss, radiographic evidence of carotid calcification, current smoking status, and male gender can predictably be associated with alveolar bone loss in older subjects.     

Radiation doses of indirect and direct digital cephalometric radiography

AIM: The aim of this study was to measure organ doses and calculate the effective dose for indirect and direct digital cephalometric exposures. MATERIAL AND METHODS: Indirect digital cephalometric exposures were made of a Rando phantom head using a Cranex Tome multipurpose unit with storage phosphor plates from Agfa and the direct digital (Charge Coupled Device, CCD) exposures were made with a Proline Ceph CM unit. Exposure settings were 70 kV and 4 mAs for indirect digital exposures. Direct digital exposures were made with 70 kV, 10 mA and a total scanning time of 23 s. TLD700 dosemeters were used to measure organ doses, and the effective doses were calculated with (effective dose(sal)) and without inclusion of the salivary glands. A pilot study was carried out to compare diagnostic image quality of both imaging modalities. RESULTS: Effective doses were 1.7 microSv for direct digital and 1.6 microSv for indirect digital cephalometric imaging. When salivary glands were included in the calculation, effective doses(sal) were 3.4 microSv and 2.2 microSv respectively. Organ doses were higher for direct digital imaging, except for the thyroid gland, where the organ doses were comparable. Diagnostic image quality of indirect and direct digital cephalometric images seemed comparable. CONCLUSION: Effective dose and effective dose(sal) were higher for direct digital cephalometric exposure compared with indirect digital exposure. Organ doses were higher for direct digital cephalography. From preliminary data, it may be presumed that diagnostic image quality of indirect and direct digital cephalometric images are comparable.     

The role of the nasopharyngeal airway for obstructive sleep apnea in syndromic craniosynostosis

Syndromic craniosynostosis is known to be associated with obstructive sleep apnea (OSA), which can often present in infancy. Although multifactorial, a predominant contributing factor is midface hypoplasia. Nasal continuous positive airway pressure has proven to be an effective treatment modality but may be poorly tolerated in certain cases. This study looks at the effectiveness of bypassing midface obstruction with a nasopharyngeal airway (NPA). Twenty-seven children with syndromic craniosynostosis with confirmed moderate to severe OSA were initially treated with an NPA. The mean age of NPA insertion was 12.3 months (range, 0.5-48 mo). Seventeen had severe OSA, and 10 had moderate OSA preinsertion. Post-NPA insertion, 26 of 27 children (96%) demonstrated an improvement in sleep severity scores, resulting in 3 with moderate OSA and 24 with mild OSA. There was a significant improvement in mean oxygen saturation, mean number of saturation dips greater than 4% per hour, percentage time spent less than 90% SpO2, and number of pulse rate rises per hour. There were no significant differences in mean pulse rate. The NPA was well tolerated by this patient group, with 24 of 26 children retaining it for at least 6 weeks. We believe that an NPA is therefore an effective first-line treatment modality in the management of OSA in children with syndromic craniosynostosis. It is well tolerated by the patient and may obviate the need for continuous positive airway pressure or tracheostomy.     

Congenital gallbladder duplication: Preoperative diagnosis by ultrasonography

Congenital gallbladder duplication, an uncommon but potentially complicating malformation, is rarely diagnosed preoperatively. A case in which the diagnosis was achieved by real-time ultrasonography is presented and correlated with hepatobiliary scintigraphy. The efficacy of these diagnostic modalities is discussed, and the available literature is reviewed.The opinions expressed herein are the private views of the authors and do not reflect the official policy of the United States Air Force.