Older adult participation in cancer clinical trials: A systematic review of barriers and interventions

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.     

Breast cancer incidence and early diagnosis in a family history risk and prevention clinic: 33-year experience in 14,311 women

Breast Cancer Research and Treatment - Women at increased familial breast cancer risk have been offered screening starting at an earlier age and increased frequency than national Screening...     

Risk factors for non-haemorrhagic stroke in patients with coronary heart disease and the effect of lipid-modifying therapy with pravastatin

OBJECTIVE: To determine the relative importance of recognised risk factors for non-haemorrhagic stroke, including serum cholesterol and the effect of cholesterol-lowering therapy, on the occurrence of non-haemorrhagic stroke in patients enrolled in the LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease) study. DESIGN: The LIPID study was a placebo-controlled, double-blind trial of the efficacy on coronary heart disease mortality of pravastatin therapy over 6 years in 9014 patients with previous acute coronary syndromes and baseline total cholesterol of 4-7 mmol/l. Following identification of patients who had suffered non-haemorrhagic stroke, a pre-specified secondary end point, multivariate Cox regression was used to determine risk in the total population. Time-to-event analysis was used to determine the effect of pravastatin therapy on the rate of non-haemorrhagic stroke. RESULTS: There were 388 non-haemorrhagic strokes in 350 patients. Factors conferring risk of future non-haemorrhagic stroke were age, atrial fibrillation, prior stroke, diabetes, hypertension, systolic blood pressure, cigarette smoking, body mass index, male sex and creatinine clearance. Baseline lipids did not predict non-haemorrhagic stroke. Treatment with pravastatin reduced non-haemorrhagic stroke by 23% (P = 0.016) when considered alone, and 21% (P = 0.024) after adjustment for other risk factors. CONCLUSIONS: The study confirmed the variety of risk factors for non-haemorrhagic stroke. From the risk predictors, a simple prognostic index was created for non-haemorrhagic stroke to identify a group of patients at high risk. Treatment with pravastatin resulted in significant additional benefit after allowance for risk factors.     

Cognitive control and brain resources in major depression: an fMRI study using the n-back task

Several neuroimaging studies have reported 'hypofrontality' in depressed patients performing a cognitive challenge compared to control subjects. Hypofrontality in depression is likely associated with an impaired behavioral performance. It is unclear whether this impaired performance is the consequence or the cause of hypofrontality. Consequently, we proposed to compare the cerebral activity of depressed patients and healthy subjects while controlling for the level of performance. Ten individuals meeting DSM-IV criteria for Major Depression and 10 healthy controls were tested with a verbal version of the n-back task during fMRI scanning. The working memory load was manipulated across the experiment (1,2,3-back) to increase the cognitive demands. fMRI data were acquired on a 1.5-T GE scanner and analyzed using SPM99 software. We did not find any difference between groups in both performance and reaction times for each level of complexity of the n-back task. Depressed patients and control subjects showed bilateral activation of the lateral prefrontal cortex, anterior cingulate and parietal cortex. Activation of these regions was modulated by the complexity of the task. Within this n-back neural network, depressed patients showed greater activation of the lateral prefrontal cortex and the anterior cingulate compared to healthy subjects. This study provides evidence that depressed patients need greater activation within the same neural network to maintain a similar level of performance as controls during a working memory task. Our findings suggest that depression may impair the cognitive capacity of depressed patients by recruiting more brain resources than controls during cognitive control.     

Chediak-Higashi gene in humans. I. Impairment of natural - killer function

Natural-killer (NK)-cell function was profoundly depressed in donors homozygous for the Chediak-Steinbrinck-Higashi syndrome (C-HS) gene when compared with age- and sex-matched normals. This apparent defect was not simply a result of a delayed response because little cytolysis was evident in kinetics experiments even after 24 h of incubation. NK cells from C-HS donors failed to lyse adherent (MDA, CEM, and Alab) or nonadherent (K562 and Molt-4) tumor cell lines or nontransformed human fetal fibroblasts. Therefore, the apparent C-HS defect was not a result of a shift in target selectivities. In addition, the depressed reactivity did not appear to be a result of suppressor cells or factors because: (a) enriched NK populations (nonadherent lymphocytes bearing receptors for the Fc portion of IgG) from C-HS donors were low in NK-cell function, (b) C-HS mononuclear cells did not inhibit the cytotoxicity of normal cells in coculture experiments, and (c) cells from the C-HS donors remained poorly reactive even after culture for up to 7 d. The nature of the defective NK activity in C-HS patients is not clear but may lie within the lytic mechanism rather than at the level of the recognition structure or population size because the frequency of target-binding cells was normal. In vitro NK activity could be partially restored by interferon treatment. Combined with the results presented in the following paper (4), these observations suggest that the C-HS gene causes a selective immunodeficiency disorder, mainly involving NK cells. This finding, in conjunction with the high incidence of spontaneous possibly malignant, lymphoproliferative disorders in these patients, may have important implications regarding the theory of immune surveillance mediated by NK cells.     

Noninvasive imaging of transcriptionally restricted transgene expression following intratumoral injection of an adenovirus in which the COX-2 promoter drives a reporter gene.

PURPOSE: To demonstrate the efficacy of repeated, non-invasive optical imaging of reporter gene expression in monitoring the ability of bi-specific recombinant molecules (i) to "transductionally untarget" adenovirus from Coxsackie and Adenovirus Receptor (CAR)-dependent infection of normal tissue and (ii) to "transductionally retarget" infection to specific target cells. PROCEDURES: sCAR-EGF is a recombinant, bi-specific molecule containing the soluble portion of CAR fused to Epidermal Growth Factor. The sCAR moiety binds to the virus and blocks CAR-dependent adenovirus infection. The EGF moity binds to cellular EGF receptors. We used non-invasive optical imaging of firefly luciferase to repeatedly monitor, in living animals, the ability of sCAR-EGF (i) to "transductionally untarget" systemically administered Ad.CMVfLuc, an adenovirus that constitutively expresses luciferase, from normal tissues and (ii) to "transductionally redirect" adenovirus infection in mice to xenograft tumors that express elevated epidermal growth factor (EGF) receptor levels. RESULTS: Systemic injection of sCAR-EGF "coated" adenovirus expressing firefly luciferase from the CMV early promoter, reduces expression of the reporter gene in the liver and facilitates expression of the reporter gene in tumor xenografts expressing high levels of the EGF-receptor. CONCLUSION: Both liver "untargeting" and tumor "retargeting" of adenovirus by recombinant sCAR-EGF can be imaged non-invasively using a luciferase reporter gene.     

How respect and kindness are experienced at the end of life by nursing home residents

Respect and kindness are core principles of nursing practice, yet little is known about how they are experienced by nursing home (NH) residents at the end of life. The aim of this study was to examine the factors associated with being treated with respect and kindness in the last month of life as an NH resident. A retrospective survey of 208 bereaved family members was conducted in 21 NHs located in a city in central Canada. The majority of participants indicated that the resident had always been treated with respect or kindness. However, significant differences emerged, with not all family members believing that their loved one had always been treated with respect or kindness. The apparent lapses in care practices are troubling and indicate that steps must be taken to address them.