Impairments identified by comprehensive geriatric assessment in potential candidates for left ventricular assist device and heart transplantation.

Background: The aim of this study was to assess the prevalence of frailty and other impairments in potential left ventricular assist device (LVAD) and heart transplantation (HTx) candidates by performing a preoperative comprehensive geriatric assessment (CGA) and reviewing the treatment recommendations resulting from the CGA. Methods and results: This cross-sectional study included 73 patients aged ≥40 years who received a CGA as part of the patient selection procedure for LVAD and HTx. In every patient, a conclusion comprising frailty and other impairments was formulated based on the medical, mental, functional, and social domains and recommendations were made. The mean age was 58 years (range 40-71) and 70 % were male. In 97 % of patients, at least one impairment was identified by the CGA. The most common impairments were polypharmacy, high morbidity burden, reduced renal function, osteopenia, depression, poor quality of life, reduced functionality, (risk of) malnutrition, reduced grip strength and high caregiver burden. A small proportion of the potential LVAD and HTx candidates were frail (7 % according to Fried's frailty criteria, 6 % according to the Edmonton Frail Scale) and 39 % were pre-frail. The domains for which most impairments were found and the domains for which most treatment recommendations were given matched well, with the functional domain as the frontrunner. Conclusion: This study showed that most of the potential candidates for LVAD or HTx have impairments on at least one domain of the CGA. Impairments and associated risks can contribute to the decision making process for candidacy for LVAD and HTx.

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis.

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). INTERPRETATION: In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme.

Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA): rationale and design.

BACKGROUND: The incidence and prevalence of older patients with kidney failure who are dependent on dialysis is increasing. However, observational studies showed limited or no benefit of dialysis on mortality in subgroups of these patients when compared to conservative care. As the focus is shifting towards health-related quality of life (HRQoL), current evidence of effects of conservative care or dialysis on HRQoL in older patients is both limited and biased. Dialysis comes with both high treatment burden for patients and high costs for society; better identification of patients who might not benefit from dialysis could result in significant cost savings. The aim of this prospective study is to compare HRQoL, clinical outcomes, and costs between conservative care and dialysis in older patients. METHODS: The DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study is a prospective, observational cohort study that started in February 2020. It aims to include 1500 patients from 25 Dutch and Belgian centres. Patients aged ≥70 years with an eGFR of 10-15 mL/min/1.73m2 are enrolled in the first stage of the study. When dialysis is initiated or eGFR drops to 10 mL/min/1.73m2 or lower, the second stage of the study commences. In both stages nephrogeriatric assessments will be performed annually, consisting of questionnaires and tests to assess most common geriatric domains, i.e. functional, psychological, somatic, and social status. The primary outcome is HRQoL, measured with the Twelve-item Short-Form Health Survey. Secondary outcomes are clinical outcomes (mortality, hospitalisation, functional status, cognitive functioning, frailty), cost-effectiveness, and decisional regret. All outcomes are (repeated) measures during the first year of the second stage. The total follow-up will be a maximum of 4 years with a minimum of 1 year in the second stage. DISCUSSION: By generating more insight in the effects of conservative care and dialysis on HRQoL, clinical outcomes, and costs, findings of this study will help patients and physicians make a shared decision on the best individual treatment option for kidney failure. TRIAL REGISTRATION: The study was registered in the Netherlands Trial Register ( NL-8352 ) on 5 February 2020.

Clinical judgment versus geriatric assessment for frailty in older patients with cancer.

BACKGROUND: Geriatric assessment (GA) is an appropriate method for identifying frailty in older patients with cancer, but a shorter instrument may be easier to use in clinical practice. Clinical judgment is always available and requires no investments in time or resources. The purpose of this study was to assess correlations between clinical judgment for frailty of the cancer specialist, the general practitioner and patient's self-assessment, and the correlation between clinical judgment and GA. METHODS: This was a dual-center inception cohort study of patients with cancer aged ≥70 years starting curative or first-line palliative chemotherapy. GA included the following domains: (instrumental) activities of daily living, nutrition, mobility, cognition, mood, and polypharmacy. Clinical judgment for frailty was rated on a scale from 0 to 10 (0 = not frail, 10 = frail). Correlation was tested using Kendall's tau-b correlation coefficient. RESULTS: Of all 55 patients, 76% had ≥2 geriatric impairments. Median clinical judgment frailty score was 3 (range 1-10 for cancer specialist and patient and range 0-10 for general practitioner) and did not vary much according to the number of impaired geriatric domains (ranging from 2 for 0-1 impaired domains to 4 for ≥3 impaired domains). Correlations between mutual clinical judgment scores and between clinical judgment and GA were negligible or low. CONCLUSION: Correlations between clinical judgment scores and between clinical judgment and GA were poor. Most patients with multiple geriatric impairments had low 'subjective' frailty scores. Other frailty assessments, such as frailty screening tools or GA, should be considered in addition to clinical judgment when selecting older patients for potential treatment with chemotherapy.

[Assessment instruments in frail older patients; a call for more standardisation]. / Meetinstrumenten bij kwetsbare ouderen: een pleidooi voor meer standaardisatie.

OBJECTIVE: To determine the frequency and background of the use of assessment instruments for the Comprehensive Geriatric Assessment by clinical geriatricians and internists in geriatric medicine; the secondary aim was to make an inventory of the willingness to standardise the assessment instruments used. DESIGN: A descriptive questionnaire study. METHOD: In December 2016, we sent out a digital questionnaire (Survey Monkey) to all the hospitals in the Netherlands. Respondents were asked which instruments they used for specific domains of the Comprehensive Geriatric Assessment, what their choice of instruments was based on, if these instruments had added value, and if they were prepared to change the instruments they used. RESULTS: We received 66 responses (response: 82%). The most frequently-used instruments were: Mini Mental State Examination in combination with the clock drawing test (21%), Geriatric Depression Scale-15 (45%), Katz Index of Independence in Activities of Daily Living-6 (75%), Lawton and Brody (48%), Mini Nutritional Assessment(-short form) (outpatient; 56%) and Short Nutritional Assessment Questionnaire (inpatient: 36%), Experienced Burden Informal Care (46%), Charlson Comorbidity Index (35%), Timed Up and Go (76%), and the Safety Management System (VMS) fall risk question (21%). The most frequently used instruments were used in a large number of hospitals (35-97%).The variation of tests was the greatest in the domains of cognition, malnutrition, and mobility/physical functioning. Many respondents saw the added value of a consensus set of instruments (median: 70%; interquartile range (IQR): 50-86), and most were willing to change the instruments they use (median: 80%; IQR: 65-90). CONCLUSION: This inventory shows that the instruments used in most domains were reasonably uniform. Taking the willingness to change into account, a national set of basis instruments seems to be an achievable aim.

A systematic review on the association of the G8 with geriatric assessment, prognosis and course of treatment in older patients with cancer.

AIM: The aim of this systematic review is to summarise all available data on the use of the G8 screening tool in geriatric oncology, focusing on the diagnostic accuracy of the G8 to predict the presence of impairments on geriatric assessment (GA) and on its association with different clinical outcomes (survival, course of treatment and patient-centred outcomes). METHODS: A systematic search in MEDLINE and EMBASE for studies on the use of the G8 in older patients with cancer. RESULTS: The literature search identified 8987 reports, of which 54 publications from 46 studies were included (including 18 conference abstracts). 19 studies compared the diagnostic characteristics of the G8 with GA. Median sensitivity and specificity of the G8 for frailty on GA were respectively: 85% and 64%. Out of the 24 studies addressing the association of the G8 with survival, 15 (63%) found the G8 was associated with survival. Six out of fourteen studies (43%) reporting on treatment-related complications found an association between G8 scores and risk of complications. Treatment completion, health care utilisation and patient-centred outcomes were investigated less frequently. CONCLUSION: The G8 is a useful diagnostic tool to identify older patients with cancer who require full GA and is associated with survival and treatment-related complications. Future prospective studies should investigate whether the G8 is predictive for other relevant clinical outcomes such as treatment completion and patient-centred outcomes.

Predictive value of each geriatric assessment domain for older patients with cancer: A systematic review.

BACKGROUND: A geriatric assessment (GA) is increasingly used to help guide treatment decisions in older patients with cancer. However, there is no consensus regarding which domains should be included in the GA. In addition, the field of geriatric oncology moves very fast and as a result many new studies have been published since the last review in 2015. Therefore, the objective of this systematic review is to evaluate which domains of the GA could predict patient-related treatment outcomes of older patients with cancer and thereby should be included in a GA. METHODS: A systematic literature search was performed for publications in English or Dutch between September 2006 and July 2017 addressing the association between individual domains of the GA and mortality, postoperative complications, or systemic treatment-related outcomes in older patients with cancer. RESULTS: Eight different domains were evaluated in 46 publications, namely functional status, nutritional status, cognition, mood, physical function, fatigue, social support, and falls. All eight domains were predictive for at least one of the investigated outcomes but the results were quite variable across studies. Physical function and nutritional status were the domains most often associated with mortality and systemic treatment-related outcomes, and the domain physical function was most often associated with postoperative complications. CONCLUSION: Overall, this review demonstrates that the GA should minimally consist of physical function and nutritional status, when the aim is to predict patients-related outcomes of older patients with cancer, although the results are quite heterogeneous. For the other domains, the findings are too inconsistent to draw conclusions about their overall predictive ability.

Geriatric Assessment in Elderly Patients with End-Stage Kidney Disease.

BACKGROUND/AIMS: Decision-making in elderly patients considering dialysis is highly complex. With the increasing number of elderly with end-stage kidney disease (ESKD), it may be important to assess geriatric impairments in this population. The aim of the Geriatric assessment in OLder patients starting Dialysis (GOLD) study was to assess the prevalence of geriatric impairments and frailty in the elderly ESKD population by means of a geriatric assessment (GA), which is a comprehensive tool for overall health assessment. METHODS: This study included 285 patients ≥65 years: 196 patients at the time of dialysis initiation and 89 patients who chose maximal conservative management (MCM). The GA assessed cognition, mood, nutritional status, (instrumental) activities of daily living (ADL), mobility, comorbidity burden, quality of life and overall frailty. RESULTS: The mean age of the participants was 78 years and 36% were women. Of the incident dialysis patients, 77% started haemodialysis and 23% started peritoneal dialysis. Geriatric impairments were highly prevalent in both dialysis and MCM patients. Most frequently impaired geriatric domains in the dialysis group were functional performance (ADL 29%, instrumental ADL (iADL) 79%), cognition (67%) and comorbidity (41%). According to the GA, 77% in the dialysis group and 88% in the MCM group had 2 or more geriatric impairments. In the MCM group, functional impairment (ADL 45%, iADL 85%) was highly prevalent. CONCLUSIONS: Geriatric impairments are highly prevalent in the elderly ESKD population. Since impairments can be missed when not searched for in regular (pre)dialysis care, the first step of improving nephrologic care is awareness of the extensiveness of geriatric impairment.