Although comorbidities are identified in routine oncology practice, intervention plans for the coexisting needs of older people receiving chemotherapy are rarely made. This study evaluates the impact ...of geriatrician-delivered comprehensive geriatric assessment (CGA) interventions on chemotherapy toxicity and tolerance for older people with cancer.
Comparative study of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a London Hospital. The observational control group (N=70, October 2010-July 2012) received standard oncology care. The intervention group (N=65, September 2011-February 2013) underwent risk stratification using a patient-completed screening questionnaire and high-risk patients received CGA. Impact of CGA interventions on chemotherapy tolerance outcomes and grade 3+ toxicity rate were evaluated. Outcomes were adjusted for age, comorbidity, metastatic disease and initial dose reductions.
Intervention participants undergoing CGA received mean of 6.2±2.6 (range 0-15) CGA intervention plans each. They were more likely to complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50-11.42), P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16-0.73), P=0.006). Overall grade 3+ toxicity rate was 43.8% in the intervention group and 52.9% in the control (P=0.292).
Geriatrician-led CGA interventions were associated with improved chemotherapy tolerance. Standard oncology care should shift towards modifying coexisting conditions to optimise chemotherapy outcomes for older people.
Background
Increasing numbers of older patients are undergoing vascular surgery. Inadequate preoperative assessment and optimization may contribute to increased postoperative morbidity and mortality.
...Methods
Patients aged at least 65 years scheduled for elective aortic aneurysm repair or lower‐limb arterial surgery were enrolled in an RCT of standard preoperative assessment or preoperative comprehensive geriatric assessment and optimization. Randomization was stratified by sex and surgical site (aorta/lower limb). Primary outcome was length of hospital stay. Secondary outcome measures included new medical co‐morbidities, postoperative medical or surgical complications, discharge to a higher level of dependency and 30‐day readmission rate.
Results
A total of 176 patients were included in the final analysis (control 91, intervention 85). Geometric mean length of stay was 5·53 days in the control group and 3·32 days in the intervention group (ratio of geometric means 0·60, 95 per cent c.i. 0·46 to 0·79; P < 0·001). There was a lower incidence of delirium (11 versus 24 per cent; P = 0·018), cardiac complications (8 versus 27 per cent; P = 0·001) and bladder/bowel complications (33 versus 55 per cent; P = 0·003) in the intervention group compared with the control group. Patients in the intervention group were less likely to require discharge to a higher level of dependency (4 of 85 versus 12 of 91; P = 0·051).
Conclusion
In this study of patients aged 65 years or older undergoing vascular surgery, preoperative comprehensive geriatric assessment was associated with a shorter length of hospital stay. Patients undergoing assessment and optimization had a lower incidence of complications and were less likely to be discharged to a higher level of dependency. Registration number: ISRCTN23142588 (http://www.controlled-trials.com).
Better outcomes
Summary
Comprehensive geriatric assessment is an established clinical approach. It reduces mortality and improves the physical wellbeing of older people in the community or hospitalised for medical ...reasons. Pre‐operative comprehensive geriatric assessment seems a plausible method for reducing adverse postoperative outcomes. The objectives of this systematic review and narrative synthesis are to describe how pre‐operative comprehensive geriatric assessment has been used in surgical patients and to examine the impact of comprehensive geriatric assessment on postoperative outcomes in older patients undergoing scheduled surgery. We searched MEDLINE, EMBASE and Web of Science from 1980 to 2013 (week 26). We included five studies: two randomised controlled trials and three before‐and‐after intervention quasi‐experimental studies. Patient populations, interventions and outcome measures varied between studies. Both the randomised trials showed benefit on postoperative outcomes, including medical complications. Two of the before‐and‐after studies reported a positive impact on postoperative length of stay and other outcomes. The heterogeneity of study methods, populations, interventions and outcomes precluded meta‐analysis. Based on this narrative synthesis, pre‐operative comprehensive geriatric assessment is likely to have a positive impact on postoperative outcomes in older patients undergoing elective surgery, but further definitive research is required. Clinical services providing pre‐operative comprehensive geriatric assessment for older surgical patients should be considered.
Overexpression of ErbB2, a receptor-like tyrosine kinase, is shared by several types of human carcinomas. In breast tumors the extent of overexpression has a prognostic value, thus identifying the ...oncoprotein as a target for therapeutic strategies. Already, antibodies to ErbB2 are used in combination with chemotherapy in the treatment of metastasizing breast cancer. The mechanisms underlying the oncogenic action of ErbB2 involve a complex network in which ErbB2 acts as a ligand-less signaling subunit of three other receptors that directly bind a large repertoire of stroma-derived growth factors. The major partners of ErbB2 in carcinomas are ErbB1 (also called EGFR) and ErbB3, a kinase-defective receptor whose potent mitogenic action is activated in the context of heterodimeric complexes. Why ErbB2-containing heterodimers are relatively oncopotent is a function of a number of processes. Apparently, these heterodimers evade normal inactivation processes, by decreasing the rate of ligand dissociation, internalizing relatively slowly and avoiding the degradative pathway by returning to the cell surface. On the other hand, the heterodimers strongly recruit survival and mitogenic pathways such as the mitogen-activated protein kinases and the phosphatidylinositol 3-kinase. Hyper-activated signaling through the ErbB-signaling network results in dysregulation of the cell cycle homeostatic machinery, with upregulation of active cyclin-D/CDK complexes. Recent data indicate that cell cycle regulators are also linked to chemoresistance in ErbB2-dependent breast carcinoma. Together with D-type cyclins, it seems that the CDK inhibitor p21waf1 plays an important role in evasion from apoptosis. These recent findings herald a preliminary understanding of the output layer which connects elevated ErbB-signaling to oncogenesis and chemoresistance.
Background: older people undergoing elective surgery have significant post-operative problems prolonging hospitalisation. Objective: to design, embed, and evaluate an evidence-based comprehensive ...geriatric assessment (CGA) service for at-risk older patients undergoing elective surgery. Setting: urban teaching hospital. Subjects: elective surgical patients aged 65+. Intervention: multidisciplinary preoperative CGA service with post-operative follow-through (proactive care of older people undergoing surgery ‘POPS’). Methods: observational cohort study and multilevel surveys (development and modelling phase). Prospective ‘before and after’ comparison (exploratory evaluation). Results: findings from the development phase showed high levels of preoperative co-morbidity, no multidisciplinary preoperative input, and multiple potentially preventable post-operative problems delaying discharge in older elective surgery patients. Comparison of 2 cohorts of elective orthopaedic patients (pre-POPS vs POPS, N = 54) showed the POPS group had fewer post-operative medical complications including pneumonia (20% vs 4% p = 0.008) and delirium (19% vs 6% p = 0.036), and significant improvements in areas reflecting multidisciplinary practice including pressure sores (19% vs 4% p = 0.028), poor pain control (30% vs 2% p<0.001), delayed mobilisation (28% vs 9% p = 0.012) and inappropriate catheter use (20% vs 7% p = 0.046). Length of stay was reduced by 4.5 days. There were fewer delayed discharges relating to medical complications (37% vs 13%) or waits for OT assessment or equipment (20% vs 4%). Conclusion: a proactive evidence-based CGA service for at-risk older elective surgical patients was developed according to MRC framework for complex interventions. Pre/post comparison in elective orthopaedic patients showed improved (within methodological limitations) post-operative outcomes indicative of better clinical effectiveness and efficiency, and contributed to the service obtaining mainstream funding. Informed by the present study, a randomised controlled trial is ongoing.
Significant toxicity in chemotherapy trials is usually defined as grade ⩾3. In clinical practice, however, multiple lower grade toxicities are often considered meaningful. The purpose of this ...observational cohort study was to identify which level of toxicity triggers treatment modification and early discontinuation of chemotherapy in older people.
Patients aged 65+ were recruited in a central London hospital. A total of 108 patients were recruited at the start of new chemotherapy treatment between October 2010 and July 2012.
Mean age was 72.1 ± 5 years, median 72 and range 65-86 years. Of the patients, 50.9% (55) were male with gastrointestinal (49), gynaecological (18), lung (15) and other cancers (26). Chemotherapy was palliative in 59.3% (64/108), curative/ neoadjuvant/adjuvant in the others. Mean number of cycles completed was 4.2 ± 3. Treatment modifications due to toxicity occurred in 60 (55.6%) patients, 35% (21/60) of whom had no greater than grade 2 toxicity. Early treatment discontinuation because of toxicity occurred in 23 patients (21.3%), 39.1% (9/23) of whom had no greater than grade 2 toxicity.
Many older patients did not complete treatment as planned. Treatment was modified/discontinued even for one or two low-grade toxicities. Further work is required to clarify whether low-grade toxicity has a greater clinical impact in older people, or whether clinicians have a lower threshold for modifying/discontinuing treatment in older people.
Despite deflections by Galactic and extragalactic magnetic fields, the distribution of ultra-high energy cosmic rays (UHECRs) over the celestial sphere remains a most promising observable for the ...identification of their sources. Thanks to a large number of detected events over the past years, a large-scale anisotropy at energies above 8 EeV has been identified, and there are also indications from the Telescope Array and Pierre Auger Collaborations of deviations from isotropy at intermediate angular scales (about 20 degrees) at the highest energies. In this contribution, we map the flux of UHECRs over the full sky at energies beyond each of two major features in the UHECR spectrum – the ankle and the flux suppression -, and we derive limits for anisotropy on different angular scales in the two energy regimes. In particular, full-sky coverage enables constraints on low-order multipole moments without assumptions about the strength of higher-order multipoles. Following previous efforts from the two Collaborations, we build full-sky maps accounting for the relative exposure of the arrays and differences in the energy normalizations. The procedure relies on cross-calibrating the UHECR fluxes reconstructed in the declination band around the celestial equator covered by both observatories. We present full-sky maps at energies above ~ 10 EeV and ~ 50 EeV, using the largest datasets shared across UHECR collaborations to date. We report on anisotropy searches exploiting full-sky coverage and discuss possible constraints on the distribution of UHECR sources.
Outcomes for older people with cancer are poorer in the United Kingdom compared with that in other countries. Despite this, the UK oncology curricula do not have dedicated geriatric oncology learning ...objectives. This cross-sectional study of UK medical oncology trainees investigates the training, confidence level and attitudes towards treating older people with cancer.
A web-based survey link was sent to the delegates of a national medical oncology trainee meeting. Responses were collected in October 2011.
The response rate was 93% (64 out of 69). The mean age of the respondents was 32.3 years (range 27-42 years) and 64.1% were female. A total of 66.1% of the respondents reported never receiving training on the particular needs of older people with cancer, 19.4% reported to have received this training only once. Only 27.1% of the trainees were confident in assessing risk to make treatment recommendations for older patients compared with 81.4% being confident to treat younger patients. Even fewer were confident with older patients with dementia (10.2%).
This first study of the UK medical oncology trainees highlights the urgent need for change in curricula to address the complex needs of older people with cancer.
Urinary incontinence (UI) is highly prevalent in nursing and residential care homes (CHs) and profoundly impacts on residents' dignity and quality of life. CHs predominantly use absorbent pads to ...contain UI rather than actively treat the condition. Transcutaneous posterior tibial nerve stimulation (TPTNS) is a non-invasive, safe and low-cost intervention with demonstrated effectiveness for reducing UI in adults. However, the effectiveness of TPTNS to treat UI in older adults living in CHs is not known. The ELECTRIC trial aims to establish if a programme of TPTNS is a clinically effective treatment for UI in CH residents and investigate the associated costs and consequences.
This is a pragmatic, multicentre, placebo-controlled, randomised parallel-group trial comparing the effectiveness of TPTNS (target n = 250) with sham stimulation (target n = 250) in reducing volume of UI in CH residents. CH residents (men and women) with self- or staff-reported UI of more than once per week are eligible to take part, including those with cognitive impairment. Outcomes will be measured at 6, 12 and 18 weeks post randomisation using the following measures: 24-h Pad Weight Tests, post void residual urine (bladder scans), Patient Perception of Bladder Condition, Minnesota Toileting Skills Questionnaire and Dementia Quality of Life. Economic evaluation based on a bespoke Resource Use Questionnaire will assess the costs of providing a programme of TPTNS. A concurrent process evaluation will investigate fidelity to the intervention and influencing factors, and qualitative interviews will explore the experiences of TPTNS from the perspective of CH residents, family members, CH staff and managers.
TPTNS is a non-invasive intervention that has demonstrated effectiveness in reducing UI in adults. The ELECTRIC trial will involve CH staff delivering TPTNS to residents and establish whether TPTNS is more effective than sham stimulation for reducing the volume of UI in CH residents. Should TPTNS be shown to be an effective and acceptable treatment for UI in older adults in CHs, it will provide a safe, low-cost and dignified alternative to the current standard approach of containment and medication.
ClinicalTrials.gov, NCT03248362. Registered on 14 August 2017. ISRCTN, ISRCTN98415244. Registered on 25 April 2018. https://www.isrctn.com/.
PDF
