Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/guidance on the use of clinically assisted hydration in patients with advanced cancer.

PURPOSE: The provision of clinically assisted hydration (CAH) in patients with advanced cancer is controversial, and there is a paucity of specific guidance and so a diversity in clinical practice. Consequently, the Palliative Care Study Group of the Multinational Association of Supportive Care in Cancer (MASCC) formed a sub-group to develop evidence-based guidance on the use of CAH in patients with advanced cancer. METHODS: This guidance was developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews/trials, respectively. RESULTS: Due to the paucity of evidence, the sub-group was not able to develop a prescribed guideline, but was able to generate a number of "expert opinion statements": these statements relate to assessment of patients, indications for CAH, contraindications for CAH, procedures for initiating CAH, and reassessment of patients. CONCLUSIONS: This guidance provides a framework for the use of CAH in advanced cancer, although every patient requires individualised management.

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

BACKGROUND: This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. OBJECTIVES: To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). SEARCH METHODS: For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. SELECTION CRITERIA: The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. DATA COLLECTION AND ANALYSIS: The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. MAIN RESULTS: In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. AUTHORS' CONCLUSIONS: There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

An evaluation of routine specialist palliative care for patients on the Liverpool Care Pathway.

INTRODUCTION: This report describes a service evaluation of the 'added value' of routine specialist palliative care team (SPCT) involvement with patients on the Liverpool Care Pathway for the Dying Patient (LCP). METHODS: In the authors' hospital, patients that are commenced on the LCP are routinely referred to the SPCT. They are reviewed on the day of referral and then at least every other day, depending on the clinical situation. The data for this report was obtained by reviewing the SPCT's clinical database and the patients' LCP proformas. RESULTS: The SPCT intervened in the care of 80% of 158 newly referred patients, e.g. for alteration of continuous subcutaneous infusion (23%) or alteration of use of non-pharmacological interventions (21%). Furthermore, 11% of patients were taken off the LCP, around one quarter of whom were later put back on. CONCLUSIONS: The authors' model of care could overcome many of the issues relating to the LCP and would ameliorate the developing vacuum of care for patients at the end of life.

The WHO guidelines: the new and the old.

PURPOSE OF THE REVIEW: The original World Health Organisation (WHO) cancer pain guidelines were published in 1986 and used globally. Updated guidance was released in 2018. This review compares the 'old' with the 'new' with a closer look at the relevance of the WHO analgesic ladder in the current climate. RECENT FINDINGS: The new guidelines provide a more evidence based, rigorously developed document including recommendations relating to radiotherapeutic management. There is a more detailed focus on safe opioid prescribing, opioid stewardship and the importance of integrating pain management expertise early on in the cancer journey. There remains a lack of evidence for certain therapies despite their widespread use particularly in relation to adjuvants. The pitfalls of the original renowned analgesic ladder are highlighted including a recognition that omitting 'step 2' is safe, feasible and cost effective. SUMMARY: The new guidelines offer more detailed recommendations relevant to clinical practice with a strong focus on safety of opioid prescribing making it relevant in the current climate. The original WHO analgesic ladder is no longer recommended as a strict protocol for cancer pain management.

Clinical nurse specialist prescribing in a cancer centre supportive and palliative care team.

OBJECTIVE: To provide insight into the prescribing practices of three independent nurse prescribers (INPs)/clinical nurse specialists (CNSs) working in a supportive and palliative care team (SPCT) in a district general hospital and a specialist tertiary cancer centre in the UK. METHODS: A prospective review of all consultations and the prescribing activity arising from the consultations (and reasons for non-prescribing following a consultation) of 3 INPs/CNSs between 1 August 2018 and 31 October 2018. RESULTS: Four hundred ninety-three consultations were undertaken on 186 individual patients. Two hundred forty-seven consultations representing 50% resulted in changes to a prescription, and 123 of those consultations representing 50% of prescriptions written resulted in the prescribing of an opioid for moderate-to-severe pain. CONCLUSIONS: This service evaluation demonstrates the potential for INPs in SPCTs to provide comprehensive symptom control while enabling CNSs to practice with a greater degree of autonomy leading to enhanced job satisfaction. On the basis of our experience, we would encourage all palliative care CNSs to undergo training to become INPs (if available).

Deprescribing in palliative care.

The use of multiple medications is common in palliative care, putting patients at risk of adverse events and a high tablet burden. Deprescribing is the process of reviewing and stopping potentially inappropriate medications in order to improve quality of life. Barriers to deprescribing exist meaning many patients will take multiple medications despite being in the final months of life. The OncPal deprescribing guideline is a useful tool to support the process for patients with a limited life expectancy. There is evidence for the safety of stopping certain medications, particularly those aimed at primary prevention. A systematic process of reviewing individual medications and their appropriateness is recommended.

The Effect of High-Intensity Ultraviolet Light to Elicit Microalgal Cell Lysis and Enhance Lipid Extraction.

Currently, the energy required to produce biofuel from algae is 1.38 times the energy available from the fuel. Current methods do not deliver scalable, commercially viable cell wall disruption, which creates a bottleneck on downstream processing. This is primarily due to the methods depositing energy within the water as opposed to within the algae. This study investigates ultraviolet B (UVB) as a disruption method for the green algae Chlamydomonas reinhardtii, Dunaliella salina and Micractinium inermum to enhance solvent lipid extraction. After 232 seconds of UVB exposure at 1.5 W/cm², cultures of C. reinhardtii (culture density 0.7 mg/mL) showed 90% disruption, measured using cell counting, correlating to an energy consumption of 5.6 MJ/L algae. Small-scale laboratory tests on C. reinhardtii showed bead beating achieving 45.3 mg/L fatty acid methyl esters (FAME) and UV irradiation achieving 79.9 mg/L (lipids solvent extracted and converted to FAME for measurement). The alga M. inermum required a larger dosage of UVB due to its thicker cell wall, achieving a FAME yield of 226 mg/L, compared with 208 mg/L for bead beating. This indicates that UV disruption had a higher efficiency when used for solvent lipid extraction. This study serves as a proof of concept for UV irradiation as a method for algal cell disruption.

A model of the biogeographical journey from Proto-pan to Pan paniscus.

Pan paniscus is unique in the group of African apes because of its range south of the Congo River. Examination of the bio-geographical journey of the genus Pan to the species P. paniscus is important when discussing the evolution of African apes. This paper is a review of the paleo-geographic events, the zoogeography, and faunal sorting which influenced P. paniscus divergence from the Proto-pan ancestor within the recent Miocene through Pliocene Epochs, approximately 10-2 MYA. Finally, by elucidating modern day evidence of food plant forms in the southern periphery exploited by P. paniscus in the forest/savanna mosaic habitat, we are able to conclude with those extrinsic events that most influenced the occurrence and distribution of P. paniscus.

The impact of aneurysmal subarachnoid hemorrhage on functional outcome.

Despite advances in the management of aneurysmal subarachnoid hemorrhage (SAH), a significant percentage of survivors are left with persistent cognitive, behavioral, and emotional changes that affect their day-to-day lives. This article describes outcome at 3 months after aneurysmal SAH in 61 patients, using the Extended Glasgow Outcome Scale (GOSE) and the Functional Status Examination (FSE). The GOSE provides a measure of overall functional outcome but does not address the specifics of functional limitations. The FSE, in addition to identifying functional limitations, provides insight into factors contributing to them and the extent to which SAH survivors perceive them as affecting their day-to-day activities. The findings of this study demonstrate that SAH survivors have considerable limitations in functional status in almost all areas of daily living at 3 months following SAH. The limitations were attributed to a variety of physical, cognitive, and emotional factors, and they were reported to be moderately to severely bothersome in almost half of the individuals. The findings highlight the need for appropriate rehabilitation, education, and support for SAH survivors and their families to enhance coping and improve quality of life, given the substantial and persistent impact of SAH.

Regulator of G-Protein Signalling-14 (RGS14) Regulates the Activation of αMß2 Integrin during Phagocytosis.

Integrin-mediated phagocytosis, an important physiological activity undertaken by professional phagocytes, requires bidirectional signalling to/from αMß2 integrin and involves Rap1 and Rho GTPases. The action of Rap1 and the cytoskeletal protein talin in activating αMß2 integrins, in a RIAM-independent manner, has been previously shown to be critical during phagocytosis in mammalian phagocytes. However, the events downstream of Rap1 are not clearly understood. Our data demonstrate that one potential Rap1 effector, Regulator of G-Protein Signalling-14 (RGS14), is involved in activating αMß2. Exogenous expression of RGS14 in COS-7 cells expressing αMß2 results in increased binding of C3bi-opsonised sheep red blood cells. Consistent with this, knock-down of RGS14 in J774.A1 macrophages results in decreased association with C3bi-opsonised sheep red blood cells. Regulation of αMß2 function occurs through the R333 residue of the RGS14 Ras/Rap binding domain (RBD) and the F754 residue of ß2, residues previously shown to be involved in binding of H-Ras and talin1 head binding prior to αMß2 activation, respectively. Surprisingly, overexpression of talin2 or RAPL had no effect on αMß2 regulation. Our results establish for the first time a role for RGS14 in the mechanism of Rap1/talin1 activation of αMß2 during phagocytosis.