Factors associated with emergency admission for people dying from cancer in Northern Ireland: an observational data linkage study.

BACKGROUND: Many people living with cancer are admitted as an emergency, some just prior to diagnosis and others in their last year of life. Factors associated with accessing emergency care for people dying of cancer are complex and not well understood. This can make it difficult to have the resources and staffing in place to best care for individuals in their last year of life and their families. METHODS: This study uses routinely collected administrative data from people who died of cancer in N. Ireland (NI) during 2015 and explores how personal characteristics (e.g., gender, age) and disease related factors (e.g., tumour site, cancer stage at initial diagnosis) were associated with having an emergency admission to hospital in the last year and the last 28 days of their lives, using multivariate logistic regression. RESULTS: Almost three in four people had at least one emergency admission in the last year of life, and over one in three had an emergency admission the last 28 days of life. Patterns were similar for both time outcomes with males, people with haematological, lung or brain cancers, younger persons, those diagnosed with late-stage cancer, and people diagnosed close to time of death, being significantly more likely to have an emergency admission. While there was no significant association between deprivation and emergency admission rates, those living in urban areas were more likely to have an emergency admission in their last month of life compared to rural dwellers. Late diagnosis was evident with 538 people (12.8% of all deaths from cancer) being diagnosed within one month of death and 1242 (29%) within 3 months of death. CONCLUSION: The high level of emergency admissions points to gaps in routine end-of-life care, and the need for additional training for hospital staff including frontline emergency department (ED) staff who are often the 'gatekeepers' to emergency inpatient care for people living with cancer. The levels of late diagnosis indicate a need for increased population awareness of cancer symptoms and system change to promote earlier diagnosis.

Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy believed to be caused by the bovine spongiform encephalopathy agent, an abnormal isoform of the prion protein (PrP(sc)). At present there is no specific or effective treatment available for any form of CJD. Pentosan polysulphate (PPS), a large polyglycoside molecule with weak heparin-like activity, has been shown to prolong the incubation period of the intracerebral infection when administered to the cerebral ventricles in a rodent scrapie model. PPS also prevents the production of further PrP(sc) in cell culture models. These properties of PPS prompted its cerebroventricular administration in a young man with vCJD. Long-term continuous infusion of PPS at a dose of 11 microg/kg/day for 18 months did not cause drug-related side effects. Follow-up CT scans demonstrated progressive brain atrophy during PPS administration. Further basic and clinical research is needed in order to address the issue of efficacy of PPS in vCJD and in other prion diseases.

Total synthesis of (+/-)-martinellic acid.

A 14-step synthesis of martinellic acid (1) that proceeds in 3% overall yield has been completed using the reaction of aniline 11 with Meldrum's acid-activated vinylcyclopropane 4 to give vinyl pyrrolidinone 12, condensation of aldehyde 13 with N-benzylglycine to form an azomethine ylide that cyclizes to give 14, selective reduction of 14 to amino alcohol 16 with LiBH(4) and MeOH, and guanidine formation by reaction of a cyanamide with 3-methyl-2-buten-1-amine in hexafluoro-2-propanol at 120 degrees C as key steps. [structure: see text]

Phase 1 of an in vitro neurotoxicological pre-validation trial.

In the absence of a formal in vitro alternative model for neurotoxicity testing, the CellTox Centre, in collaboration with the University of Salford, FRAME and the EEC, has set up an initial pre-validation trial of a three-tiered scheme that was originally proposed in 1989. Using a cell battery of neuroblastomas and primary neural cultures (Tier I) and primary astrocytes (Tier III) an initial set of 20 chemicals (out of a reference set of 40 chemicals) has been assessed for neurotoxicity using a multiple end point assay system. The methods used were relatively simple, rapid and inexpensive, and the chemical end points were easily quantified. The results of the pre-validation trial have enabled us to revise the first tier of the proposed tiered system for full micro-validation.

Use of astrocytes for in vitro neurotoxicity testing.

The use of primary cultures of astrocytes as indicators of toxic potential was assessed using 20 selected compounds. Multiple endpoints were used to evaluate astrocyte reactions. Trypan blue dye exclusion and total cellular protein content of the cells were used as general indices. EC(50) values from the trypan blue experiments could be used to rank toxicity of compounds in a manner that correlates well with known toxicity for compounds that have specific astrocyte toxicities. Neurone specific neurotoxicants had no measurable effects on astrocytes indicating that this system differentiates gliotoxicity from neurotoxicity. Protein content, and content of the astrocyte specific glial fibrillary acidic protein (GFAp), were seen to increase at lower doses of gliotoxic compounds. This phenomenon appears to be similar to reactive gliosis in vivo, as assessed by immunostaining, and is an extremely sensitive indication of cellular damage. Support studies using astrocyte uptake of 2-deoxy glucose showed a similar pattern of activation in the cells as protein increases. This has been confirmed using the nonisotopic technique of MTT reduction.

Electromyographic activity of selected shoulder muscles in commonly used therapeutic exercises.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate and compare the muscle activity of the supraspinatus, infraspinatus, teres minor, and lower trapezius muscles during commonly prescribed therapeutic exercises in subjects with and without shoulder pathology. SUBJECTS: Twenty healthy subjects (9 male, 11 female) and 20 subjects with recurrent unilateral shoulder pain and weakness (14 male, 6 female), aged 18 to 40 years (mean = 28, SD = 5.8), participated in this study. METHODS: Subjects performed each of the following exercises using a hand-held weight: prone lateral (external) rotation, sidelying lateral rotation, and arm elevation in the scapular plane. Indwelling fine-wire electrodes recorded electromyographic (EMG) activity during each exercise. The EMG activity in five phases of concentric contraction of each exercise was averaged and divided into three equal time intervals. Mean EMG values normalized to maximal activity for the entire phase of concentric contraction and for each of the three intervals were used in subsequent analyses. RESULTS: Two-way repeated-measures analyses of variance (ANOVAs) revealed between-group differences only in the prone lateral rotation exercise. Compared with subjects without shoulder pathology, subjects with shoulder pain showed significantly greater EMG activity in the infraspinatus muscle and less activity in the supraspinatus muscle during this exercise. CONCLUSION AND DISCUSSION: These results suggest that the pattern of muscle activation during specific shoulder movements in patients with shoulder pain may be related to pathology. Future studies are needed to determine whether an imbalance in neuromuscular control is a factor contributing directly to shoulder dysfunction or whether such an imbalance is secondary to some pathology.

The impact of a PCR assay for candidemia on antifungal drug prescribing in critical care: an interrupted time series pilot study.

SUMMARY OBJECTIVE: To evaluate the feasibility of conducting a definitive study to assess the impact of introducing a rapid PCR-based test for candidemia on antifungal drug prescribing. METHOD: Prospective, single centre, interrupted time series study consisting of three periods of six months' duration. The assay was available during the second period, during which the PCR assay was available for routine use by physicians Monday-Friday with guaranteed 24-h turnaround time. For each period total antifungal drug use, expressed as treatment-days, was recorded and an adjustment was made to exclude estimated use for proven candidemia. Also, during the intervention period, antifungal prescribing decisions for up to 72 h after each PCR result became available were recorded as either concordant or discordant with that result. RESULTS: While overall antifungal use remained relatively stable throughout, after adjustment for candidemia, there was a 38% reduction in use following introduction of the PCR test; however, this was nonsignificant at the 95% level. During the intervention period overall concordance between the PCR result and prescribing decisions was 84%. CONCLUSIONS: The PCR assay for candidemia was requested, prescribing decisions were generally concordant with the results produced and there was an apparent decrease in antifungal prescription, although this was sustained even after withdrawal of the intervention; these findings should be more thoroughly evaluated in a larger trial.