Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients.

BACKGROUND: In 2019, more than 30 % of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft loss is less frequent compared to younger recipients. Elderly recipients do have increased rates of malignancy and infection-related mortality. Poor kidney transplant function in elderly recipients may be related to both pre-existing (i.e. donor-derived) kidney damage and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors. Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study will test the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney transplant function, a reduced incidence of complications and improved health-related quality of life for kidney transplant recipients aged 65 years and older, compared to standard immunosuppression. METHODS: This open label, randomized, multicenter clinical trial will include 374 elderly kidney transplant recipients (≥ 65 years) and consists of two strata. Stratum A includes elderly recipients of a kidney from an elderly deceased donor and stratum B includes elderly recipients of a kidney from a living donor or from a deceased donor < 65 years. In each stratum, subjects will be randomized to a standard, tacrolimus-based immunosuppressive regimen with mycophenolate mofetil and glucocorticoids or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus and glucocorticoids. The primary endpoint is 'successful transplantation', defined as survival with a functioning graft and an eGFR ≥ 30 ml/min per 1.73 m2 in stratum A and ≥ 45 ml/min per 1.73 m2 in stratum B, after 2 years, respectively. CONCLUSIONS: The OPTIMIZE study will help to determine the optimal immunosuppressive regimen after kidney transplantation for elderly patients and the cost-effectiveness of this regimen. It will also provide deeper insight into immunosenescence and both subjective and objective outcomes after kidney transplantation in elderly recipients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03797196 , registered January 9th, 2019. EudraCT: 2018-003194-10, registered March 19th, 2019.

Recognition of cognitive impairment and depressive symptoms in older patients with heart failure.

INTRODUCTION: Cognitive impairment and depression in patients with heart failure (HF) are common comorbidities and are associated with increased morbidity, readmissions and mortality. Timely recognition of cognitive impairment and depression is important for providing optimal care. The aim of our study was to determine if these disorders were recognised by clinicians and, secondly, if they were associated with hospital admissions and mortality within 6 months' follow-up. METHODS: Patients (aged ≥65 years) diagnosed with HF were included from the cardiology outpatient clinic of Gelre Hospitals. Cognitive status was evaluated with the Montreal Cognitive Assessment test (score ≤22). Depressive symptoms were assessed with the Geriatric Depression Scale (score >5). Patient characteristics were collected from electronic patient files. The clinician was blinded to the tests and asked to assess cognitive status and mood. RESULTS: We included 157 patients. Their median age was 79 years (65-92); 98 (62%) were male. The majority had New York Heart Association functional class II. Cognitive impairment was present in 56 (36%) patients. Depressive symptoms were present in 21 (13%) patients. In 27 of 56 patients (48%) cognitive impairment was not recognised by clinicians. Depressive symptoms were not recognised in 11 of 21 patients (52%). During 6 months' follow-up 24 (15%) patients were readmitted for HF-related reasons and 18 (11%) patients died. There was no difference in readmission and mortality rate between patients with or without cognitive impairment and patients with or without depressive symptoms. CONCLUSION: Cognitive impairment and depressive symptoms were infrequently recognised during outpatient clinic visits.

Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over.

BACKGROUND: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base. METHODS: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure. DISCUSSION: The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date. TRIAL REGISTRATION: Nederlands (Dutch) Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR-41259.058.13 (12-02-2013).

Evaluation and reporting of quality of life outcomes in phase III chemotherapy trials for poor prognosis malignancies.

BACKGROUND: Quality of life (QoL) should be included in trials where treatment is expected to have a limited impact on long-term survival. We set out to determine whether phase III chemotherapy trials addressing solid malignancies with a poor prognosis include QoL as a study objective and to assess the extent to which these data have been published. METHODS: We performed a search of the National Institutes of Health clinical trial registry website to identify phase III chemotherapy trials for poor prognosis solid malignancies. The retrieved protocols were subsequently reviewed, to assess whether QoL was included as an outcome measure. Subsequently, a Medline, Embase and world-wide-web search was performed to identify any full text publication or conference abstract regarding the outcome of trials including QoL, which were then reviewed to determine whether and to what extend quality of life results were included. RESULTS: For the 201 included studies, we found that 57 % of trials did not include QoL as a study objective. Of the remaining trials, 50 % have not reported the QoL results in a full text publication, or presented these only as a single sentence statement. CONCLUSION: Evaluation and publication of QoL results of phase III chemotherapy trials for poor prognosis solid malignancies remains limited. This must be improved in order to provide patients suffering from these malignancies with adequate information regarding the benefits and risks of the treatment in terms of both prolongation and quality of life.

The effects of physical prehabilitation in elderly patients undergoing colorectal surgery: a systematic review.

AIM: Prehabilitation, defined as enhancement of the preoperative condition of a patient, is a possible strategy for improving postoperative outcome. Lack of muscle strength and poor physical condition, increasingly prevalent in older patients, are risk factors for postoperative complications. Eighty-five per cent of patients with colorectal cancer are aged over 60 years. Since surgery is the cornerstone of their treatment, this review systemically examined the literature on the effect of physical prehabilitation in older patients undergoing colorectal surgery. METHOD: Trials and case-control studies investigating the effect of physical prehabilitation in patients over 60 years undergoing colorectal surgery were retrieved from MEDLINE, EMBASE, CINAHL and the Cochrane library. Patient characteristics, the type of intervention and outcome measurements were recorded. The risk of bias and heterogeneity was assessed. RESULTS: Five studies including 353 patients were identified. They were small, containing an average of 77 patients and were of moderate methodological quality. Compliance rates of the prehabilitation programme varied from 16 to 97%. None of the studies could identify a significant reduction of postoperative complications or length of hospital stay. Four studies showed physical improvement (walking distance, respiratory endurance) in the prehabilitation group. Clinical heterogeneity precluded a meta-analysis. CONCLUSION: Prehabilitation is a possible means of enhancing the physical condition of patients preoperatively. The quality of studies in older patients undergoing colorectal surgery is poor, despite the increase in elderly people with colorectal cancer. Defining specific patient groups at risk and standardizing the outcome are essential for improving the results of treatment.

Prevalence of unrecognized benign paroxysmal positional vertigo in older patients.

Dizziness is a relatively common complaint which occurs more often with increasing age. Benign paroxysmal positional vertigo (BPPV) is an important cause which can easily be treated but is frequently not recognized by professionals. The aim of this study was to assess the prevalence of unrecognized BPPV in older patients. Patients ≥70 years of age (n = 989) indicated whether they experienced dizziness, and if so whether the symptoms were typical for BPPV. If affirmed, a diagnostic maneuver was performed. Positive patients were treated at once. All suspected patients completed quality of life questionnaires and were followed for 3 and 6 months. Positive BPPV patients were compared with negative (but suspected) patients. Almost one quarter of the patients (226 patients, 23 %) suffered from dizziness, among whom 101 were suspected of BPPV. Less than half (n = 45) underwent the diagnostic maneuver, of whom 13 (29 %) were positive for BPPV. At follow-up, one patient developed BPPV, leading to a total of 14 positive patients (overall prevalence 1.4 %). BPPV positive patients did not differ from BPPV negative patients. Among a large group of older patients, one quarter experiences dizziness, and 1.4 % has definite BPPV.

Groningen frailty indicator in older patients with end-stage renal disease.

BACKGROUND: Currently over 55% of end-stage renal disease (ESRD) patients are aged ≥60 years and patients >75 years represent the fastest growing segment of the dialysis population. We aimed to assess whether the Groningen frailty indicator (GFI) can be used to distinguish fit older ESRD patients, likely able to tolerate and benefit from dialysis, from frail older patients who need further evaluation with a geriatrician's comprehensive assessment. METHODS: All patients aged ≥65 years visiting the pre-dialysis unit at the Gelre hospital between 2007 and 2013 were included and underwent the GFI (n = 65). Patients with GFI ≥ 4 (frail) were referred for geriatric consultation (n = 13). Results of the GFI and nephrologists' evaluation were compared with geriatrician's assessment. Survival rates and outcomes after one year of follow up were recorded. RESULTS: Twenty patients (32%) were identified as frail. Of the problems identified by the geriatrician in 13 patients, 55% were not reported in the nephrologists' notes. The first year after inclusion, 30% of patients with a GFI ≥ 4 died, compared to 9% of fit patients (p = 0.04). Moreover, 90% of frail patients had been hospitalized one or more times, compared to 53% in the fit group (p = 0.005). CONCLUSION: Although the GFI can be a useful instrument to identify ESRD patients at risk, both the GFI and the nephrologists' assessment failed to identify specific geriatric impairments. Further research is needed to develop a specific frailty indicator for ESRD patients and to determine the value and effect of a comprehensive geriatric assessment in ESRD patients.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?

BACKGROUND: Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. METHOD: The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. RESULTS: In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. CONCLUSION: Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population.

Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment.

With the ongoing ageing of western societies, the proportion of older breast cancer patients will increase. For several years, clinicians and researchers in geriatric oncology have urged for new clinical trials that address patient-related endpoints such as functional decline after treatment of older patients. The aim of this study was to present an overview of trial characteristics and endpoints of all currently running clinical trials in breast cancer, particularly in older patients. The clinical trial register of the United States National Institutes of Health Differences was searched for all current clinical trials on breast cancer treatment. Trial characteristics and endpoints were retrieved from the register and differences in characteristics between studies in older patients specifically (defined as a lower age-limit of 60 years or older) and trials in all patients were assessed using χ(2) tests. We included 463 clinical trials. Nine trials (2 %) specifically investigated breast cancer treatment in older patients. Ninety-one breast cancer trials included any patient-related endpoint (20 %), while five trials specifically addressing older patients included any patient-related endpoint (56 %, P = 0.02). Five of the trials in older patients incorporated a geriatric assessment (56 %). Clinical trials still rarely incorporate patient-related endpoints, even in trials that specifically address older patients. Trials that are specifically designed for older patients do not often incorporate a geriatric assessment in their design. This implicates that current clinical studies are not expected to fill the gap in knowledge concerning treatment of older breast cancer patients in the next decade.

Development of an abbreviated version of the delirium motor subtyping scale (DMSS-4).

BACKGROUND: Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Identification of clinical subtypes can allow for more targeted clinical and research efforts. We sought to develop a brief method for clinical subtyping in clinical and research settings. METHODS: A multi-site database, including motor symptom assessments conducted in 487 patients from palliative care, adult and old age consultation-liaison psychiatry services was used to document motor activity disturbances as per the Delirium Motor Checklist (DMC). Latent class analysis (LCA) was used to identify the class structure underpinning DMC data and also items for a brief subtyping scale. The concordance of the abbreviated scale was then compared with the original Delirium Motor Subtype Scale (DMSS) in 375 patients having delirium as per the American Psychiatric Association's Diagnostic and Statistical Manual (4th edition) criteria. RESULTS: Latent class analysis identified four classes that corresponded closely with the four recognized motor subtypes of delirium. Further, LCA of items (n = 15) that loaded >60% to the model identified four features that reliably identified the classes/subtypes, and these were combined as a brief motor subtyping scale (DMSS-4). There was good concordance for subtype attribution between the original DMSS and the DMSS-4 (κ = 0.63). CONCLUSIONS: The DMSS-4 allows for rapid assessment of clinical subtypes in delirium and has high concordance with the longer and well-validated DMSS. More consistent clinical subtyping in delirium can facilitate better delirium management and more focused research effort.

Oral Health as a Risk Factor for Alzheimer Disease.

In patients with Alzheimer's disease pathophysiological changes of the brain that initiate the onset of Alzheimer's disease include accumulation of amyloid-ß plaques and phosphorylation of tau-tangles. A rather recently considered risk factor for the onset of Alzheimer's disease is poor oral health. The aim of this systematic review of the literature was to assess the potential association(s) of oral health as a risk factor for the onset of Alzheimer's disease. After a systematic search of Pubmed, Embase and Web of Science. A total of 1962 studies were assessed, of which 17 studies demonstrated possible associations between oral health diseases and Alzheimer's disease. 4 theories could be distinguished that describe the possible links between oral health and the development or onset of Alzheimer's disease; 1) role of pathogens, 2) role of inflammatory mediators, 3) role of APOE alleles and 4) role of Aß peptide. The main common denominator of all the theories is the neuroinflammation due to poor oral health. Yet, there is insufficient evidence to prove a link due to the diversity of the designs used and the quality of the study design of the included studies. Therefore, further research is needed to find causal links between oral health and neuroinflammation that possibly can lead to the onset of Alzheimer's disease with the future intention to prevent cognitive decline by better dental care.

The relation between preoperative radiological sarcopenia and postoperative recovery of physical activity in older surgical cancer patients; an explorative study.

To identify older surgical cancer patients at risk of decreased postoperative recovery of physical activity (PA), this study assesses whether preoperative radiological sarcopenia (RS) is associated with a decreased ability to return to baseline PA. RS was defined as decreased psoas muscle mass or -density by gender-specific cut-offs on CT-scans at level of vertebra L3. PA was assessed as steps/day measured with PA tracker and recovery of PA was defined as >90% of preoperative steps/day at 3 months postoperatively. Of 44 included patients aged 65 and over undergoing oncologic surgery, 18 patients (41%) showed RS. Seventeen patients (39%) returned to baseline PA, of which eight patients had RS (47%). RS was not associated with a return to baseline PA (OR: 1.38, 95%CI 0.39-4.92, p = 0.61). In this exploratory study, no association was found between preoperative RS and recovery of PA postoperatively.

Mortality and incident vertebral fractures after 3 years of follow-up among geriatric patients.

UNLABELLED: In a prospective cohort study of 395 geriatric outpatients, mortality after 3 years was associated with prevalent vertebral fractures at baseline. The mortality risk was independently associated with the presence of three or more vertebral fractures at baseline. In the surviving patients, the risk of incident fractures was noteworthy, occurring in 26 % of these patients. INTRODUCTION: The purpose of this study is to determine mortality rate and the incidence of vertebral fractures in a geriatric outpatient group, during a 3-year follow-up period, in a teaching hospital in Amsterdam, The Netherlands. METHODS: This study includes a prospective cohort study of 395 geriatric patients who had their baseline visit at a diagnostic day hospital in 2007 and 2008. They were invited for follow-up 3 years later. Lateral X-rays of the lumbar spine and chest were performed at baseline and after 3 years; vertebral fractures were scored in all patients according to the semi-quantitative method of Genant. RESULTS: After 3 years, mortality was 46 % and associated with prevalent vertebral fractures at baseline (odds ratio (OR), 1.83; 95 % CI, 1.23-2.74). The presence of three or more vertebral fractures at baseline was an independent risk factor for mortality (OR, 3.32; 95 % CI, 1.56-7.07). Other independently associated risk factors were greater age, higher co-morbidity score, and having more prescriptions. Higher cognitive capacity protected against mortality after 3 years. In 72 patients, radiography was repeated. Nineteen patients (26 %) had an incident radiographic vertebral fracture: 16 in those with a prevalent fracture, and 3 in those without a prevalent vertebral fracture at baseline. CONCLUSIONS: In geriatric outpatients, mortality after 3 years was associated with prevalent vertebral fractures at baseline, and the mortality risk was independently associated with 3 or more vertebral fractures at baseline. In survivors, the risk of incident fractures was noteworthy, since these occurred in 26 % of the patients, particularly in those with a prevalent vertebral fracture.

Sleep monitoring by actigraphy in short-stay ICU patients.

Sleep deprivation is common in intensive care unit (ICU) patients. The criterion standard for sleep monitoring, polysomnography, is impractical in ICU. Actigraphy (a wrist watch indicating amount of sleep) proved to be a good alternative in non-ICU patients, but not in prolonged mechanically ventilated patients, probably due to ICU-acquired weakness. Short-stay ICU patients do not suffer from ICU-acquired weakness. However, the accuracy of actigraphy is unknown in these patients. Therefore, we compared actigraphy to polysomnography in short-stay ICU patients. Sleep measurements were conducted in 7 postcardiothoracic surgery patients. The sensitivity (percentage of actigraphy data that agreed with sleep determined using polysomnography) and specificity (percentage of actigraphy data that agreed with awake determined using polysomnography) were calculated. The result showed that actigraphy underestimated the amount of wake time and overestimated the amount of sleep. The median specificity for actigraphy was always less than 19% and sensitivity more than 94%. Therefore, actigraphy is not reliable for sleep monitoring in short-stay ICU patients.

[Development and validation of the Informant Assessment of Geriatric Delirium Scale (I-AGeD). Recognition of delirium in geriatric patients]. / Ontwikkeling en validering van de Informant Assessment of Geriatric Delirium Scale (I-AGeD). Herkenning van delier bij geriatrische patiënten.

OBJECTIVES: Delirium is common in older patients admitted to hospital. Information obtained from patient's relatives or caregivers may contribute to improved detection. Our aim was to develop a caregiver based questionnaire, the Informant Assessment of Geriatric Delirium (I-AGeD), to assist in better recognition of delirium in elderly patients. METHODS: A cross-sectional observational study using a scale construction patient cohort and two validation cohorts was conducted at geriatric departments of two teaching hospitals in The Netherlands. Delirium status, based on DSM-IV criteria, was assessed directly on admission by a geriatric resident and evaluated within the first 48 h of admission. Caregivers filled out a 37-item questionnaire of which 10 items were selected reflecting delirium symptoms, based on their discriminatory abilities, internal consistency and inter-item correlations. RESULTS: A total of 88 patients with complete study protocols in the construction cohort were included. Average age was 86.4 (SD 8.5), and 31/88 patients had delirium on admission. Internal consistency of the 10-item I-AGeD was high (Cronbach's alpha = 0.85). At a cut-off score of >4 sensitivity was 77.4% and specificity 63.2%. In patients without dementia, sensitivity was 100% and specificity 65.2%. Validation occurred by means of two validation cohorts, one consisted of 59 patients and the other of 33 patients. Sensitivity and specificity in these samples ranged from 70.0% to 88.9% and 66.7% to 100%, respectively. CONCLUSION: The newly constructed caregiver based I-AGeD questionnaire is a valid screening instrument for delirium on admission to hospital in geriatric patients.

Competences of internal medicine specialists for the management of patients with multimorbidity. EFIM multimorbidity working group position paper.

Patients with multimorbidity increasingly impact healthcare systems, both in primary care and in hospitals. This is particularly true in Internal Medicine. This population associates with higher mortality rates, polypharmacy, hospital readmissions, post-discharge syndrome, anxiety, depression, accelerated age-related functional decline, and development of geriatric syndromes, amongst others. Internists and Hospitalists, in one of their roles as Generalists, are increasingly asked to attend to these patients, both in their own Departments as well as in surgical areas. The management of polypathology and multimorbidity, however, is often complex, and requires specific clinical skills and corresponding experience. In addition, patients' needs, health-care environment, and routines have changed, so emerging and re-emerging specific competences and approaches are required to offer the best coordinated, continuous, and comprehensive integrated care to these populations, to achieve optimal health outcomes and satisfaction of patients, their relatives, and staff. This position paper proposes a set of emerging and re-emerging competences for internal medicine specialists, which are needed to optimally address multimorbidity now and in the future.

Risk of Four Geriatric Syndromes: A Comparison of Mental Health Care and General Hospital Inpatients.

An observational, cross-sectional study is conducted to compare elevated risk scores of four geriatric syndromes (falls, malnutrition, physical impairment, delirium) in older hospitalized psychiatric patients (n=178) with patients hospitalized in a general hospital (n=687). The median age of all patients was 78 years (IQR 73.3-83.3), 53% were female. After correction for age and gender, we found significantly more often an elevated risk in the mental health care group, compared to the general hospital group of falls (Odds Ratio (OR) = 1.75; 95% Confidence Interval (CI) 1.18-2.57), malnutrition (OR = 4.12; 95% CI 2.67-6.36) and delirium (OR = 6.45; 95% CI 4.23-9.85). The risk on physical impairment was not statistically significantly different in both groups (OR = 1.36; 95% CI .90-2.07). Older mental health care patients have a higher risk to develop geriatric syndromes compared to general hospital patients with the same age and gender, which might be explained by a higher level of frailty.

Preferences about Future Alzheimer's Disease Treatments Elicited through an Online Survey Using the Threshold Technique.

BACKGROUND: Treatments aiming at slowing down the progression of Alzheimer's disease (AD) may soon become available. However, information about the risks that people are willing to accept in order to delay the progression of the disease is limited. OBJECTIVE: To determine the trade-offs that individuals are willing to make between the benefits and risks of hypothetical treatments for AD, and the extent to which these trade-offs depend on individuals' characteristics and beliefs about medicines. DESIGN: Online, cross-sectional survey study. SETTING: Population in the UK. Public link to the survey available at the websites of Alzheimer's Research UK and Join Dementia Research. PARTICIPANTS: Everyone self-reported ≥18 years old was eligible to participate. A total of 4384 people entered the survey and 3658 completed it. MEASUREMENTS: The maximum acceptable risks (MARs) of participants for moderate and severe adverse events in exchange for a 2-year delay in disease progression. The risks were expressed on ordinal scales, from <10% to ≥50%, above a pre-existing risk of 30% for moderate adverse events and 10% for severe adverse events. We obtained the population median MARs using log-normal survival models and quantified the effects of individuals' characteristics and beliefs about medicines in terms of acceleration factors. RESULTS: For the moderate adverse events, 26% of the participants had a MAR ≥50%, followed by 25% of the participants with a MAR of 10 to <20%, giving an estimated median MAR of 25.4% (95% confidence interval [CI] 24.5 to 26.3). For the severe adverse events, 43% of the participants had a MAR <10%, followed by 25% of the participants with a MAR of 10 to <20%, resulting in an estimated median MAR of 12.1% (95%CI 11.6 to 12.5). Factors that were associated with the individuals' MARs for one or both adverse events were age, gender, educational level, living alone, and beliefs about medicines. Whether or not individuals were living with memory problems or had experience as a caregiver had no effect on the MARs for any of the adverse events. CONCLUSION: Trade-offs between benefits and risks of AD treatments are heterogeneous and influenced by individuals' characteristics and beliefs about medicines. This heterogeneity should be acknowledged during the medicinal product decision-making in order to fulfil the needs of the various subpopulations.

Polymorphisms in the melatonin receptor 1B gene and the risk of delirium.

BACKGROUND/AIMS: A disturbed sleep-wake rhythm cycle can be seen in delirium and as melatonin regulates this cycle via melatonin receptors, genetic variations in these receptors may contribute to susceptibility to delirium. The purpose of this study was to investigate whether genetic variants in the melatonin receptor 1B (MTNR1B) gene are associated with delirium. METHODS: Elderly medical and hip surgery patients were included in the study. Five single-nucleotide polymorphisms (SNPs) were determined in the MTNR1B gene, i.e. rs18030962, rs3781638, rs10830963, rs156244 and rs4753426. RESULTS: In total, 53% of 171 hip fracture patients and 33% of 699 medical patients were diagnosed with delirium. None of the polymorphisms were found to be associated with the occurrence of delirium. CONCLUSION: Future research could focus on sequencing this gene to look for other functional SNPs in relation to delirium.

Preoperative physical performance as predictor of postoperative outcomes in patients aged 65 and older scheduled for major abdominal cancer surgery: A systematic review.

BACKGROUND: Abdominal cancer surgery is associated with considerable morbidity in older patients. Assessment of preoperative physical status is therefore essential. The aim of this review was to describe and compare the objective physical tests that are currently used in abdominal cancer surgery in the older patient population with regard to postoperative outcomes. METHODS: Medline, Embase, CINAHL and Web of Science were searched until 31 December 2020. Non-interventional cohort studies were eligible if they included patients ≥65 years undergoing abdominal cancer surgery, reported results on objective preoperative physical assessment such as Cardiopulmonary Exercise Testing (CPET), field walk tests or muscle strength, and on postoperative outcomes. RESULTS: 23 publications were included (10 CPET, 13 non-CPET including Timed Up & Go, grip strength, 6-minute walking test (6MWT) and incremental shuttle walk test (ISWT)). Meta-analysis was precluded due to heterogeneity between study cohorts, different cut-off points, and inconsistent reporting of outcomes. In CPET studies, ventilatory anaerobic threshold and minute ventilation/carbon dioxide production gradient were associated with adverse outcomes. ISWT and 6MWT predicted outcomes in two studies. Tests addressing muscle strength and function were of limited value. No study compared different physical tests. DISCUSSION: CPET has the ability to predict adverse postoperative outcomes, but it is time-consuming and requires expert assessment. ISWT or 6MWT might be a feasible alternative to estimate aerobic capacity. Muscle strength and function tests currently have limited value in risk prediction. Future research should compare the predictive value of different physical instruments with regard to postoperative outcomes in older surgical patients.