The Prognosis in Palliative care Study II (PiPS2): A prospective observational validation study of a prognostic tool with an embedded qualitative evaluation.

BACKGROUND: Prognosis in Palliative care Study (PiPS) models predict survival probabilities in advanced cancer. PiPS-A (clinical observations only) and PiPS-B (additionally requiring blood results) consist of 14- and 56-day models (PiPS-A14; PiPS-A56; PiPS-B14; PiPS-B56) to create survival risk categories: days, weeks, months. The primary aim was to compare PIPS-B risk categories against agreed multi-professional estimates of survival (AMPES) and to validate PiPS-A and PiPS-B. Secondary aims were to assess acceptability of PiPS to patients, caregivers and health professionals (HPs). METHODS AND FINDINGS: A national, multi-centre, prospective, observational, cohort study with nested qualitative sub-study using interviews with patients, caregivers and HPs. Validation study participants were adults with incurable cancer; with or without capacity; recently referred to community, hospital and hospice palliative care services across England and Wales. Sub-study participants were patients, caregivers and HPs. 1833 participants were recruited. PiPS-B risk categories were as accurate as AMPES [PiPS-B accuracy (910/1484; 61%); AMPES (914/1484; 61%); p = 0.851]. PiPS-B14 discrimination (C-statistic 0.837) and PiPS-B56 (0.810) were excellent. PiPS-B14 predictions were too high in the 57-74% risk group (Calibration-in-the-large [CiL] -0.202; Calibration slope [CS] 0.840). PiPS-B56 was well-calibrated (CiL 0.152; CS 0.914). PiPS-A risk categories were less accurate than AMPES (p<0.001). PiPS-A14 (C-statistic 0.825; CiL -0.037; CS 0.981) and PiPS-A56 (C-statistic 0.776; CiL 0.109; CS 0.946) had excellent or reasonably good discrimination and calibration. Interviewed patients (n = 29) and caregivers (n = 20) wanted prognostic information and considered that PiPS may aid communication. HPs (n = 32) found PiPS user-friendly and considered risk categories potentially helpful for decision-making. The need for a blood test for PiPS-B was considered a limitation. CONCLUSIONS: PiPS-B risk categories are as accurate as AMPES made by experienced doctors and nurses. PiPS-A categories are less accurate. Patients, carers and HPs regard PiPS as potentially helpful in clinical practice. STUDY REGISTRATION: ISRCTN13688211.

Prognostic tools or clinical predictions: Which are better in palliative care?

PURPOSE: The Palliative Prognostic (PaP) score; Palliative Prognostic Index (PPI); Feliu Prognostic Nomogram (FPN) and Palliative Performance Scale (PPS) have all been proposed as prognostic tools for palliative cancer care. However, clinical judgement remains the principal way by which palliative care professionals determine prognoses and it is important that the performance of prognostic tools is compared against clinical predictions of survival (CPS). METHODS: This was a multi-centre, cohort validation study of prognostic tools. Study participants were adults with advanced cancer receiving palliative care, with or without capacity to consent. Key prognostic data were collected at baseline, shortly after referral to palliative care services. CPS were obtained independently from a doctor and a nurse. RESULTS: Prognostic data were collected on 1833 participants. All prognostic tools showed acceptable discrimination and calibration, but none showed superiority to CPS. Both PaP and CPS were equally able to accurately categorise patients according to their risk of dying within 30 days. There was no difference in performance between CPS and FPN at stratifying patients according to their risk of dying at 15, 30 or 60 days. PPI was significantly (p<0.001) worse than CPS at predicting which patients would survive for 3 or 6 weeks. PPS and CPS were both able to discriminate palliative care patients into multiple iso-prognostic groups. CONCLUSIONS: Although four commonly used prognostic algorithms for palliative care generally showed good discrimination and calibration, none of them demonstrated superiority to CPS. Prognostic tools which are less accurate than CPS are of no clinical use. However, prognostic tools which perform similarly to CPS may have other advantages to recommend them for use in clinical practice (e.g. being more objective, more reproducible, acting as a second opinion or as an educational tool). Future studies should therefore assess the impact of prognostic tools on clinical practice and decision-making.

Musculoskeletal disorders of the upper extremities: the use of epidemiologic approaches in industrial settings.

This article illustrates the use of a simple questionnaire in identifying those sections of a work force at risk for musculoskeletal disorders and chronic discomfort of the upper extremities. Two research studies are described. The first, conducted in a chicken-processing factory, illustrates the use of self-administered questionnaires in the assessment of the musculoskeletal health of the work force and in the identification of groups of workers who may be at increased risk and for whom ergonomic reappraisal of the tasks performed may be beneficial. A second study of retail trade staff suggests that chronic musculoskeletal discomfort is widespread. The article further considers the importance of such data for those persons concerned with the allocation of health care. The need to consider the broader spectrum of musculoskeletal health from discomfort to clinical disorder is stressed.

The actions of adenosine and some analogues on evoked and potassium stimulated release at skeletal and autonomic neuromuscular junctions.

The actions of the nucleosides adenosine, 1-methyladenosine, 1-methylisoguanosine and 2-chloradenosine on transmitter release at the mammalian neuromuscular junction and the vas deferens have been examined. All the nucleosides depressed the evoked release of acetylcholine at the neuromuscular junction, the order of potency being 2-chloroadenosine greater than 1-methylisoguanosine greater than 1-methyladenosine much greater than adenosine. This correlated reasonably with the potency of these compounds in depressing spinal reflexes in anaesthetized mice (Buckle and Spence 1981). Neither adenosine (0.5 and 1.0 mmol l-1) or 1-methylisoguanosine (10 and 20 mumol l-1) had any effect on the elevation of minature endplate potential frequency caused by 12 mmol l-1 K+ at the neuromuscular junction. In the guinea-pig vas deferens, however, 1-methylisoguanosine and adenosine were approximately equipotent in depressing overflow of radioactively labelled noradrenaline. The actions of the nucleosides have been compared with their effects on adenylate cyclase and their ability to resist uptake and deamination. It is concluded that the relative potencies of the nucleosides are not determined solely by their ability to survive in the extracellular fluid.

The site of action of muscle relaxant purine nucleosides.

The effects of a series of purine nucleosides, including the novel marine natural product 1-methylisoguanosine, have been examined on muscle relaxation in conscious animals and on spinal reflexes and neuromuscular transmission in mice anaesthetized with sodium pentobarbitone. 1-Methylisoguanosine (5--15 mumol kg--1) and 2-chloroadenosine (1--5 mumol kg--1), both of which cause muscle relaxation in conscious animals, depressed both mono- and polysynaptic spinal reflexes but did not affect neuromuscular transmission. At much higher doses (300 mumol kg--1) both compounds did depress neuromuscular transmission. Adenosine and 1-methyladenosine did not produce muscle relaxation in conscious animals and only slightly depressed polysynaptic reflexes at the highest doses tested (300 mumol kg--1). Theophylline 50 mumol kg--1 enhanced polysynaptic reflexes and antagonized the depression of these reflexes by 1-methylisoguanosine. Neither adenosine nor 1-methylisoguanosine affected the development of tension by isolated diaphragm muscles in vitro. It is concluded that the muscle relaxant purine nucleosides 2-chloroadenosine and 1-methylisoguanosine produce their effects primarily by depressing activity in the central nervous system. Transmission at the neuromuscular junction is not affected at doses in the range of those producing muscle relaxation.