The challenges of symptom management for patients with multimorbidity in research and practice: A thematic review

Introduction: Multimorbidity, the presence of multiple coexisting diseases or conditions, afflicts the majority of older adults, and is associated with increased mortality and healthcare utilization. In addition, multimorbidity negatively impacts quality of life and increases symptom burden. Yet, there is a dearth of evidence on how to best manage symptoms in patients with multimorbidity.

Methods: We conducted a thematic review of approaches to symptom management in multimorbidity.

Results: Research in this area has been hampered by inconsistent definitions of multimorbidity and challenges in outcome measurement. Investigations of symptom management strategies in specific disease states, like cancer, typically exclude medically complex patients. In the absence of evidence, the American Geriatrics Society's recommendations for the care of adults with multimorbidity provide a useful starting point for clinicians. We present a case to demonstrate how the AGS recommendations can be tailored to the situation of symptom management in patients with multimorbidity. We also present suggestions for future research directions.

Discussion: Multimorbidity is an incredibly common and overlooked problem in our healthcare system, and only stands to increase in relevance as patients live longer and have the opportunity to accrue a greater burden of chronic illness. A comprehensive approach to patients with multimorbidity includes focusing on patient preferences, carefully interpreting the available evidence (including both the benefits and potential harms), and thinking critically about the burden of any treatment. Taking time to elicit patient goals and preferences, and apprise patients of their prognosis if they want to know, are especially important in symptom management discussions with patients with multimorbidity.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Transaxial tomography with thallium-201 for detecting remote myocardial infarction: Comparison with planar imaging

Transaxial tomograhic imaging with thallium-201 was compared with standard, planar imaging in 38 patients with remote myocardial infarction and in 15 normal patients. Tomographic images were reconstructed from 64 views collected by a gamma camera that rotated about the anterior circumference of the patient's chest. A series of consecutive transverse-section images which encompassed the cardiac volume were reconstructed at a 6 mm plane spacing by filtered back-projection. No correction was made for attenuation losses. The set of transverse-section images was reformatted by 3-dimensional interpolation to obtain tomograms along the long and short axes of the myocardium. Tomographic and planar images were interpreted qualitatively.

Overall, tomography detected 33 of 38 (87%) prior infarctions whereas planar imaging detected 24 of 38 (63 %) (p = 0.01). Improvement of the tomographic imaging method occurred only in the combined subset of transmural inferior and subendocardial infarctions, and not in transmural anterior infarctions. Peak increases in creatinine phosphokinase were smaller in patients detected only by tomography compared with those detected by both the planar and the tomographic approach (3.1 × normal versus 10.4 × normal, p = 0.04). Five patients (13%) with prior infarction were not detected by either approach. For 6 of the 9 patients detected by tomography alone, realignment of the image data along the short and long axes of the heart was essential for making the diagnosis. Fourteen of 15 patients without infarction were normal on both planar and tomographic imaging. A single normal patient had a defect detected by both techniques, yielding a specificity of 93% for each.

We conclude that transaxial tomography significantly improves the detection of thallium-201 myocardial perfusion defects in patients with prior myocardial infarction.     

Intracerebroventricular infusion of interleukin 1 rapidly decreases peripheral cellular immune responses.

Low doses (50-200 pg or 3.1-12.4 fmol) of interleukin 1 (IL-1) infused into the brain of rats produced rapid suppression of various cellular immune responses in peripheral lymphocytes of rats. Fifteen minutes after infusion of purified IL-1 beta into the lateral ventricle, natural killer cell activity, response to phytohemagglutinin stimulation, and interleukin 2 production were markedly suppressed in lymphocytes isolated from blood and spleen. These effects were due to infusion of IL-1 into brain since they did not occur when IL-1 was infused into the cisterna magna (essentially posterior to brain) or was injected intraperitoneally. Effects of IL-1 in brain could be blocked by simultaneous infusion of alpha-melanocyte-stimulating hormone, which is known to block the biological actions of IL-1. To stimulate release of endogenous IL-1 in brain, lipopolysaccharide was infused; this produced similar effects as IL-1, and these effects also were blocked by alpha-melanocyte-stimulating hormone. At longer intervals after infusion of IL-1 and lipopolysaccharide (3, 6, and 24 hr), immune responses returned to baseline or remained suppressed; i.e., "rebound" immunopotentiation did not occur. Finally, IL-1 infusion suppressed cellular immune responses in adrenalectomized animals, thereby showing that the effects of central IL-1 on peripheral cellular immune responses were, at least in part, independent of the stimulatory effect of IL-1 on secretion of adrenal hormones. These results indicate a link from brain to peripheral immune responses by means of action of a cytokine acting in the brain.     

Effect of matrigel on the tumorigenicity of human breast and ovarian carcinoma cell lines

The effect of Matrigel, a solubilised tissue basement membrane extract, has been investigated on the tumorigenicity of 3 breast (MCF-7, T47D and MDA.MB.231) and 5 ovarian [PEO1, PEO1 cDDPr, PEO4, PEO14 and OV(hyg)CAR3] carcinoma cell lines. In the absence of Matrigel, the PEO14 and MDA.MB.231 cell lines produced take rates of 30% and 50%, respectively, while the other cell lines either did not develop or only occasionally developed as tumours. With Matrigel, 100% take rates were achieved for 7 of the 8 cell lines (MCF-7, T47D, MDA.MB.231, PEO1, PEO1 cDDPr, PEO4 and PEO14); in the remaining cell line [OV(hyg)CAR3] 2/6 (33%) tumours grew. Xenografts established with Matrigel could be transferred into recipient animals and grown in the absence of Matrigel, suggesting that Matrigel is necessary only for initial establishment of tumours. Furthermore, cells which had been re-established from a T47D xenograft and then inoculated into mice without Matrigel showed a take rate greater than that of the original cell line but less than that of the xenograft. In conclusion, Matrigel has proven to be extremely useful in establishing a variety of cell lines as xenografts. © 1996 Wiley-Liss, Inc.     

D2 dopamine receptor gene and obesity

The prevalence of Taql A D₂ dopamine receptor (DRD2) alleles was determined in 73 obese women and men. In this sample with a mean body mass index of 35.1, the A1 (minor) allele of the DRD2 gene was present in 45.2% of these nonalcohol, nondrug abusing subjects. The DRD2 A1 allele was not associated with a number of cardiovascular risk factors examined, including blood lipids (cholesterol, high-density lipoprotein [HDL]- and low-density lipoprotein [LDL]-cholesterol, and triglycerides). However, phenotypic factors characterized by the presence of parental history and postpuberty onset of obesity as well as carbohydrate preference were associated with obese subjects carrying the A1 allele. The cumulative number of these three factors was positively and significantly (p < .0002) related to A1 allelic prevalence. The data showing an association of the minor allele of the DRD2 gene with phenotypic characteristics suggest that this gene, located on q22–q23 region of chromosome 11, confers susceptibility to a subtype of this disorder. © 1994 by John Wiley & Sons, Inc.