Introducing a machine learning algorithm for delirium prediction-the Supporting SURgery with GEriatric Co-Management and AI project (SURGE-Ahead).

INTRODUCTION: Post-operative delirium (POD) is a common complication in older patients, with an incidence of 14-56%. To implement preventative procedures, it is necessary to identify patients at risk for POD. In the present study, we aimed to develop a machine learning (ML) model for POD prediction in older patients, in close cooperation with the PAWEL (patient safety, cost-effectiveness and quality of life in elective surgery) project. METHODS: The model was trained on the PAWEL study's dataset of 878 patients (no intervention, age ≥ 70, 209 with POD). Presence of POD was determined by the Confusion Assessment Method and a chart review. We selected 15 features based on domain knowledge, ethical considerations and a recursive feature elimination. A logistic regression and a linear support vector machine (SVM) were trained, and evaluated using receiver operator characteristics (ROC). RESULTS: The selected features were American Society of Anesthesiologists score, multimorbidity, cut-to-suture time, estimated glomerular filtration rate, polypharmacy, use of cardio-pulmonary bypass, the Montreal cognitive assessment subscores 'memory', 'orientation' and 'verbal fluency', pre-existing dementia, clinical frailty scale, age, recent falls, post-operative isolation and pre-operative benzodiazepines. The linear SVM performed best, with an ROC area under the curve of 0.82 [95% CI 0.78-0.85] in the training set, 0.81 [95% CI 0.71-0.88] in the test set and 0.76 [95% CI 0.71-0.79] in a cross-centre validation. CONCLUSION: We present a clinically useful and explainable ML model for POD prediction. The model will be deployed in the Supporting SURgery with GEriatric Co-Management and AI project.

RSV vaccination strategies for high-risk patients 2023: a collaborative position paper by leading German medical societies and organizations.

Respiratory syncytial virus (RSV) inflicts severe illness and courses of infections not only in neonates, infants, and young children, but also causes significant morbidity and mortality in older adults and in people with immunosuppression, hemato-oncologic disease, chronic lung disease, or cardiovascular disease. In June and August 2023, effective vaccines against RSV were approved for the first time by the European Medicines Agency (EMA) for the EU. The respective pivotal studies showed a very high efficacy of the vaccine in preventing severe RSV-associated respiratory infections. At this point, use of the respective vaccines is restricted to persons aged 60 years or older, according to the registration studies. We therefore recommend use of the vaccination in persons aged 60 years or older. In addition, we recommend use of the vaccination in adults of any age with severe pulmonary or cardiovascular pre-existing conditions, as well as in adults with significant immune compromise, after individual consultation with the treating physician. Cost coverage can be applied for individually with the responsible health insurance company.

Regional outcome disparities in German head and neck cancer patients: Shorter survival in Eastern Germany.

INTRODUCTION: Demographics are important prognostic factors in malignant diseases. A nationwide analysis concerning the prognostic impact of demographics in head and neck cancer (HNC) patients (HNCP) has not been performed previously. METHODS: A retrospective analysis of data from the Center for Cancer Registry Data (ZfKD) and the Federal Statistical Office (Destatis) between 2002 and 2017 was performed. A total of 212'920 HNCP were included. Incidence, tumor stage, age development, sex distribution, age-, residence-, and diagnosis-time-specific survival were examined. RESULTS: Mean age of HNCP increased more rapidly than in the general population (slope coefficient: 0.29 vs. 0.20; p < 0.0001). Higher age and male sex were associated with a worse prognosis. Whereas overall survival (OS) increased from the early to the later observation period for HNCP <70 years, no OS improvement for HNCP >70 years was found. Furthermore, an OS disadvantage was observed for East Germany compared to West Germany (median 47 vs. 60 months; p < 0.0001). This disparity was associated with a disproportionately high ratio of men in East Germany (men/women: 4.4 vs. 3.1; p < 0.0001) and a lower mean age (61 vs. 63 years; p < 0.0001). In addition to stage, age and sex, residence in East Germany were confirmed as an independent factor for OS in a multivariate analysis. CONCLUSION: Finally, three decades after the German reunion, a survival disadvantage for patients in East Germany still exists. This discrepancy may be a result of socioeconomic disparities.

Relationship of the SITLESS intervention on medication use in community-dwelling older adults: an exploratory study.

Background: Sedentary behavior (SB) and physical activity (PA) interventions in older adults can improve health outcomes. Problems related with aging include prevalent comorbidity, multiple non-communicable diseases, complaints, and resulting polypharmacy. This manuscript examines the relationship between an intervention aiming at reducing SB on medication patterns. Method: This manuscript presents a local sub-analysis of the SITLESS trial data on medication use. SITLESS was an exercise referral scheme (ERS) enhanced by self-management strategies (SMS) to reduce SB in community-dwelling older adults. We analyzed data from the ERS + SMS, ERS and usual care (UC) groups. Patient medication records were available at baseline and at the end of the intervention (4-month period) and were analyzed to explore the effect of SITLESS on medication patterns of use. Result: A sample of 75 participants was analyzed, mostly older overweight women with poor body composition scores and mobility limitations. There was a significant reduction of 1.6 medicines (SD = 2.7) in the ERS group (p < 0.01), but not in the UC or ERS + SMS groups. Differences were more evident in medicines used for short periods of time. Conclusion: The findings suggest that an exercise-based program enhanced by SMS to reduce SB might influence medication use for acute conditions but there is a need to further investigate effects on long-term medicine use in older adults.

Optimizing pharmacotherapy and deprescribing strategies in older adults living with multimorbidity and polypharmacy: EuGMS SIG on pharmacology position paper.

Inappropriate polypharmacy is highly prevalent among older adults and presents a significant healthcare concern. Conducting medication reviews and implementing deprescribing strategies in multimorbid older adults with polypharmacy are an inherently complex and challenging task. Recognizing this, the Special Interest Group on Pharmacology of the European Geriatric Medicine Society has compiled evidence on medication review and deprescribing in older adults and has formulated recommendations to enhance appropriate prescribing practices. The current evidence supports the need for a comprehensive and widespread transformation in education, guidelines, research, advocacy, and policy to improve the management of polypharmacy in older individuals. Furthermore, incorporating deprescribing as a routine aspect of care for the ageing population is crucial. We emphasize the importance of involving geriatricians and experts in geriatric pharmacology in driving, and actively participating in this transformative process. By doing so, we can work towards achieving optimal medication use and enhancing the well-being of older adults in the generations to come.

Demographics and access to head and neck cancer care in rural areas compared to urban areas in Germany.

BACKGROUND: Demographic development in rural and urban areas differs substantially. Demographics and access to specialized head and neck cancer centers may affect head and neck cancer patients' (HNCP) outcomes. Here, we compare epidemiological indicators and outcomes of HNCP in rural and urban Germany. PATIENTS AND METHODS: In a retrospective analysis of data from the Center for Cancer Registry Data (ZfKD) between 2002 and 2017, 212,920 HNCP were included. Incidence, demographics, travel distance to specialized centers, and ground values were compared between rural and urban areas with a focus on their association with patient outcomes. RESULTS: The mean age of HNCP was significantly higher in urban areas (mean difference = 1.4 years; p < 0.0001), but increased at a comparable rate (p = 0.26) in rural and urban areas during the observation period. Gender imbalance was higher in rural areas (mean ratio of men/women: 4.1 vs. 3.1; p < 0.0001), but showed a comparable trend toward equilibration in both, rural and urban districts (p = 0.46). The portion of HNCP of the entire HNCP population living in urban areas increased from 55.9% in the year 2002 to 76.4% in the year 2017. There was no significant difference or change in the ratio of advanced to low UICC stage during the observation period (p = 0.26). However, travel distances to medical centers were higher in rural areas, especially (p < 0.0001) in East Germany. Median survival of HNCP in rural areas was significantly lower than in urban areas (42 months [SEM = 0.7; CI: 40.5-43.5] vs. 54 months [SEM = 1.2; CI: 51.7-56.3]; p < 0.0001) in East Germany, whereas in West Germany no significant difference was observed (59 months [SEM = 0.8; CI: 57.4-60.6] vs. 60 months [SEM = 0.5; CI: 59.0-61.0]; p = 0.15). CONCLUSIONS: Place of residence contributes to survival outcome of HNCP. Access to specialized care and socioeconomic factors could be improved in East Germany.

Supporting SURgery with GEriatric Co-Management and AI (SURGE-Ahead): A study protocol for the development of a digital geriatrician.

INTRODUCTION: Geriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge. METHODS: A digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process. DISCUSSION: The outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults. TRIAL REGISTRATION: German clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022.

STOPP/START criteria for potentially inappropriate prescribing in older people: version 3.

PURPOSE: STOPP/START is a physiological systems-based explicit set of criteria that attempts to define the clinically important prescribing problems relating to potentially inappropriate medications (PIMs-STOPP criteria) and potential prescribing omissions (PPOs-START criteria). The previous two versions of STOPP/START criteria were published in 2008 and 2015. The present study describes the revised and updated third version of the criteria. METHODS: A detailed system-by-system review of the published literature from April 2014 to March 2022 was undertaken with the aim of including clinically important new explicit PIM and PPO criteria and removing any criteria considered to be no longer correct or outdated. A panel of 11 academic physicians with recognized expertise in geriatric pharmacotherapy from 8 European countries participated in a Delphi panel with the task of validating the draft criteria. The panel was presented with the draft new criteria using the SurveyMonkey® on-line platform in which panelists were asked to indicate their level of agreement on a five-point Likert scale. RESULTS: Two hundred and four evidence-based draft criteria (one hundred and forty-five STOPP criteria, fifty-nine START criteria) were presented to panelists for assessment using the Delphi validation method. Over the course of four rounds of Delphi validation, the panel achieved consensus on 133 STOPP criteria and 57 START criteria, i.e., 190 STOPP/START criteria in total representing a 66.7% increase in the number of criteria compared to STOPP/START version 2 published in 2015. CONCLUSION: A fully revised and updated version of STOPP/START criteria has been validated by a European expert panel using the Delphi consensus process.

Frailty modifies the effect of polypharmacy and multimorbidity on the risk of death among nursing home residents: Results from the SHELTER study.

Background: Frailty, disability, and polypharmacy are prevalent in nursing home (NH) residents, often co-occurring with multimorbidity. There may be a complex interplay among them in terms of outcomes such as mortality. Aims of the study were to (i) assess whether nursing home residents with polypharmacy (5-9 medications) or hyperpolypharmacy (≥10 drugs), have an increased risk of death and (ii) whether any association is modified by the co-presence of frailty or disability. Methods: Cohort study with longitudinal mortality data including 4,023 residents from 50 European and 7 Israeli NH facilities (mean age = 83.6 years, 73.2% female) in The Services and Health for Elderly in Long Term care (SHELTER) cohort study. Participants were evaluated with the interRAI-LongTerm Care assessment tool. Frailty was evaluated with the FRAIL-NH scale. Hazard ratio (HR) of death over 12 months was assessed with stratified Cox proportional hazards models adjusted for demographics, facilities, and cognitive status. Results: 1,042 (25.9%) participants were not on polypharmacy, 49.8% (n = 2,002) were on polypharmacy, and 24.3% (n = 979) on hyperpolypharmacy. Frailty and disability mostly increased risk of death in the study population (frailty: HR = 1.85, 95%CI 1.49-2.28; disability: HR = 2.10, 95%CI 1.86-2.47). Among non-frail participants, multimorbidity (HR = 1.34, 95%CI = 1.01-1.82) and hyperpolypharmacy (HR = 1.61, 95%CI = 1.09-2.40) were associated with higher risk of death. Among frail participants, no other factors were associated with mortality. Polypharmacy and multimorbidity were not associated with mortality after stratification for disability. Conclusions: Frailty and disability are the strongest predictors of death in NH residents. Multimorbidity and hyperpolypharmacy increase mortality only in people without frailty. These findings may be relevant to identify patients who could benefit from tailored deprescription.

Frailty index and its association with the onset of postoperative delirium in older adults undergoing elective surgery.

BACKGROUND: The association of frailty based on the accumulation of deficits with postoperative delirium (POD) has been poorly examined. We aimed to analyze this association in older patients undergoing elective surgery. METHODS: Preoperative data was used to build a 30-item frailty index (FI) for participants of the PAWEL-study. Delirium was defined by a combination of I-CAM and chart review. Using logistic regressions models we analysed the association between frailty and POD adjusting for age, sex, smoking, alcohol consumption, education and type of surgery. RESULTS: Among 701 participants (mean age 77.1, 52.4% male) median FI was 0.27 (Q1 0.20| Q3 0.34), with 528 (75.3%) frail participants (FI ≥ 0.2). Higher median FI were seen in orthopedic than cardiac surgery patients (0.28 versus 0.23), and in women (0.28 versus 0.25 in men). Frail participants showed a higher POD incidence proportion (25.4% versus 17.9% in non-frail). An increased odds for POD was observed in frail versus non-frail participants (OR 2.14 [95% CI 1.33, 3.44], c-statistic 0.71). A 0.1 increment of FI was associated with OR 1.57 [95% CI 1.30, 1.90] (c-statistic 0.72) for POD. No interaction with sex or type of surgery was detected. Adding timed-up-and-go-test and handgrip strength to the FI did not improve discrimination. CONCLUSION: Our data showed a significant association between frailty defined through a 30-item FI and POD among older adults undergoing elective surgery. Adding functional measures to the FI did not improve discrimination. Hence, our preoperative 30-item FI can help to identify patients with increased odds for POD. TRIAL REGISTRATION: PAWEL and PAWEL-R (sub-) study were registered on the German Clinical Trials Register (number DRKS00013311 and DRKS00012797).

A Systematic Review of the Current Evidence from Randomised Controlled Trials on the Impact of Medication Optimisation or Pharmacological Interventions on Quantitative Measures of Cognitive Function in Geriatric Patients.

BACKGROUND: Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people's cognitive function. Here we aim to systematically review evidence on the impact of medication optimisation and drug interventions on cognitive function in older adults. METHODS: A systematic review was performed using MEDLINE and Web of Science on May 2021. Only randomised controlled trials (RCTs) addressing the impact of medication optimisation or pharmacological interventions on quantitative measures of cognitive function in older adults (aged > 65 years) were included. Single-drug interventions (e.g., on drugs for dementia) were excluded. The quality of the studies was assessed by using the Jadad score. RESULTS: Thirteen studies met the inclusion criteria. In five studies a positive impact of the intervention on metric measures of cognitive function was observed. Only one study showed a significant improvement of cognitive function by medication optimisation. The remaining four positive studies tested methylphenidate, selective oestrogen receptor modulators, folic acid and antipsychotics. The mean Jadad score was low (2.7). CONCLUSION: This systematic review identified a small number of heterogenous RCTs investigating the impact of medication optimisation or pharmacological interventions on cognitive function. Five trials showed a positive impact on at least one aspect of cognitive function, with comprehensive medication optimisation not being more successful than focused drug interventions. More prospective trials are needed to specifically assess ways of limiting the negative impact of certain medication in particular and polypharmacy in general on cognitive function in older patients.

Anticholinergic Drug Exposure Increases the Risk of Delirium in Older Patients Undergoing Elective Surgery.

Introduction: Postoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people. Methods: Between November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD. Results: POD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55-4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15-2.02). Conclusion: Preoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients.

Development of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Community-Dwelling Older Adults: Pooled Analyses of European Cohorts With Special Attention to Medication.

BACKGROUND: Use of fall prevention strategies requires detection of high-risk patients. Our goal was to develop prediction models for falls and recurrent falls in community-dwelling older adults and to improve upon previous models by using a large, pooled sample and by considering a wide range of candidate predictors, including medications. METHODS: Harmonized data from 2 Dutch (LASA, B-PROOF) and 1 German cohort (ActiFE Ulm) of adults aged ≥65 years were used to fit 2 logistic regression models: one for predicting any fall and another for predicting recurrent falls over 1 year. Model generalizability was assessed using internal-external cross-validation. RESULTS: Data of 5 722 participants were included in the analyses, of whom 1 868 (34.7%) endured at least 1 fall and 702 (13.8%) endured a recurrent fall. Positive predictors for any fall were: educational status, depression, verbal fluency, functional limitations, falls history, and use of antiepileptics and drugs for urinary frequency and incontinence; negative predictors were: body mass index (BMI), grip strength, systolic blood pressure, and smoking. Positive predictors for recurrent falls were: educational status, visual impairment, functional limitations, urinary incontinence, falls history, and use of anti-Parkinson drugs, antihistamines, and drugs for urinary frequency and incontinence; BMI was a negative predictor. The average C-statistic value was 0.65 for the model for any fall and 0.70 for the model for recurrent falls. CONCLUSION: Compared with previous models, the model for recurrent falls performed favorably while the model for any fall performed similarly. Validation and optimization of the models in other populations are warranted.

Predictors of resilience in older adults with lower limb osteoarthritis and persistent severe pain.

BACKGROUND: Resilience refers to the process in which people function well despite adversity. Persistent severe pain may be considered an adversity in people with lower limb osteoarthritis (LLOA). The objectives of this study are: (1) to identify what proportion of older adults with LLOA and persistent severe pain show good functioning; and (2) to explore predictors of resilience. METHODS: Data from the European Project on OSteoArthritis (EPOSA) were used involving standardized data from six European population-based cohort studies. LLOA is defined as clinical knee and/or hip osteoarthritis. Persistent severe pain is defined as the highest tertile of the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index both at baseline and follow-up. Resilience is defined as good physical, mental or social functioning at follow-up despite having LLOA with persistent severe pain. RESULTS: In total, 95 (14.9%) out of 638 individuals with LLOA had persistent severe pain. Among these, 10 (11.0%), 54 (57.4%) and 49 (53.8%) had good physical, mental and social functioning, respectively. Only 4 individuals (4.5%) were resilient in all three domains of functioning. Younger age, male sex, higher education, higher mastery, smoking and alcohol use, higher physical activity levels, absence of chronic diseases, and more contacts with friends predicted resilience in one or more domains of functioning. CONCLUSIONS: Few people with LLOA and persistent severe pain showed good physical functioning and about half showed good mental or social functioning. Predictors of resilience differed between domains, and might provide new insights for treatment.

N-terminal pro brain natriuretic peptide reference values in community-dwelling older adults.

AIMS: Available upper reference levels (URLs) in older adults for N-terminal pro brain natriuretic peptide (NT-proBNP), an established biomarker for heart failure, are mainly based on small samples. We aimed to identify NT-proBNP URL in a population-based reference sample of individuals aged ≥65 years. METHODS AND RESULTS: We analysed established NT-proBNP predictors using quantile regression among 2459 participants of two-independent population-based cohorts located in Germany, the Activity and Function in the Elderly Study (ActiFE, n = 1450) and the Study of Health in Pomerania (SHIP-TREND-0, n = 1009). Based on predictors a reference population of 441 subjects (ActiFE, n = 227; SHIP-TREND-0, n = 214) without history of diabetes, cardiovascular, or pulmonary diseases and with systolic blood pressure (BP) <140 mmHg, diastolic BP ≥60 and ≤90 mmHg, haemoglobin in men ≥14 and ≤18 g/dL and in women ≥12 and ≤16 g/dL, GFR ≥60 mL/min/1.73 m2 , CRP <5 mg/L, BMI ≥18 and ≤33 kg/m2 , and hs-cTnI <40 ng/L were built with NT-proBNP median levels and 97.5% quantiles reported stratified by sex and age. In a secondary analysis the URL among 97 SHIP-TREND-0 participants with a left ventricular ejection fraction (LVEF) ≥50 and no diastolic dysfunction were estimated. The median age in the identified reference sample was 70 years, with 41.9% and 40.2% male participants in ActiFE and SHIP-TREND-0, respectively. We observed an age-dependent increment of NT-proBNP levels with higher values in women compared to men. Notably, NT-proBNP levels were >125 ng/L in 165 participants (37.4%), with NT-proBNP URL (97.5% quantiles) equal to 663, 824, 592, and 697 ng/L in men, and 343, 463, 2641, 1276 ng/L in women for ages 65-69, 70-74, 75-79, and 80+ years, respectively. In the secondary analysis with a LVEF ≥50 and no diastolic dysfunction (35 men and 62 women) NT-proBNP levels >125 ng/L were still observed in 38 (39.2%) participants. CONCLUSIONS: This reference sample of apparently healthy asymptomatic older adults showed an age-related increment of NT-proBNP levels with URL markedly higher than the European Society of Cardiology recommended cut-off of 125 ng/L for the diagnosis of heart failure in ambulatory settings. Identifying URL in those ≥80 years remains complex. Our results attempt to provide a frame for the further investigation of age-specific NT-proBNP cut-offs in older adults. Considering the demographic changes, further evaluation of NT-proBNP URL in larger samples of older adults followed by the validation of age-specific cut-off values for the identification of heart failure in those 65 years or older are urgently needed.

Comparison of delirium detection tools in acute care : A rapid review.

BACKGROUND: Delirium is a frequent psychopathological syndrome in geriatric patients. It is sometimes the only symptom of acute illness and bears a high risk for complications. Therefore, feasible assessments are needed for delirium detection. OBJECTIVE AND METHODS: Rapid review of available delirium assessments based on a current Medline search and cross-reference check with a special focus on those implemented in acute care hospital settings. RESULTS: A total of 75 delirium detection tools were identified. Many focused on inattention as well as acute onset and/or fluctuating course of cognitive changes as key features for delirium. A range of assessments are based on the confusion assessment method (CAM) that has been adapted for various clinical settings. The need for a collateral history, time resources and staff training are major challenges in delirium assessment. Latest tests address these through a two-step approach, such as the ultrabrief (UB) CAM or by optional assessment of temporal aspects of cognitive changes (4 As test, 4AT). Most delirium screening assessments are validated for patient interviews, some are suitable for monitoring delirium symptoms over time or diagnosing delirium based on collateral history only. CONCLUSION: Besides the CAM the 4AT has become well-established in acute care because of its good psychometric properties and practicability. There are several other instruments extending and improving the possibilities of delirium detection in different clinical settings.

Systolic Blood Pressure and Mortality in Community-Dwelling Older Adults: Frailty as an Effect Modifier.

Current evidence is insufficient to support different hypertension treatment targets in older adults. We evaluated whether frailty modifies the association between systolic blood pressure (SBP) and 8-year all-cause mortality in community-dwelling older adults. Longitudinal data from the ActiFE Ulm study (Activity and Function in the Elderly in Ulm; Germany) was collected. The association between SBP and mortality was analyzed using Cox proportional hazards models adjusted for age, sex, education, smoking, alcohol consumption, sleep disturbance, diastolic blood pressure, and antihypertensive medications, evaluating the presence of effect modification by frailty according to a frailty index based on the accumulation of deficits. Among 1170 participants (median age 73.9 years, 41.6% women), the prevalence of history of hypertension was 53.8% (median SBP, 144.0 mm Hg [interquartile range, 135.0-149.5], median diastolic blood pressure 78.0 mm Hg [interquartile range, 71.0-86.5]). The median follow-up time was 8.1 years, detecting 268 deaths. We identified 251 (21.5%, 114 deaths) frail participants (frailty index ≥0.2). Effect modification by frailty was detected. Among non-frail a J-shaped association was found with hazard ratio, 4.01 (95% CI, 1.13-14.28) for SBP<110 mm Hg, hazard ratio, 0.92 (95% CI, 0.53-1.59) for SBP 140-150 mm Hg, and hazard ratio, 1.98 (95% CI, 0.75-5.27) for SBP≥160 mm Hg. For frail older adults, a tendency toward lower risk among those with SBP≥130 mm Hg was observed. Our results suggest the presence of effect modification by frailty indicating a possible protective effect for elevated SBP in frail older adults with respect to all-cause mortality even after adjusting for diastolic blood pressure and antihypertensive treatment.

Outcomes of a Delirium Prevention Program in Older Persons After Elective Surgery: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Delirium significantly worsens elective surgery outcomes and costs. Delirium risk is highest in elderly populations, whose surgical health care resource consumption (50%) exceeds their demographic proportion (15% to 18%) in high-resource countries. Effective nonpharmacologic delirium prevention could safely improve care in these vulnerable patients, but data from procedure-specific studies are insufficiently compelling to drive changes in practice. Delirium prevention approaches applicable to different surgical settings remain unexplored. Objective: To examine whether a multifaceted prevention intervention is effective in reducing postoperative delirium incidence and prevalence after various major surgical procedures. Design, Setting, and Participants: This stepped-wedge cluster randomized trial recruited 1470 patients 70 years and older undergoing elective orthopedic, general, or cardiac surgery from November 2017 to April 2019 from 5 German tertiary medical centers. Data were analyzed from December 2019 to July 2021. Interventions: First, structured delirium education was provided to clinical caregivers at each site. Then, the study delirium prevention team assessed patient delirium risk factors and symptoms daily. Prevention was tailored to individual patient needs and could include: cognitive, motor, and sensory stimulation; meal companionship; accompaniment during diagnostic procedures; stress relaxation; and sleep promotion. Main Outcomes and Measures: Postoperative delirium incidence and duration. Results: Of 1470 included patients, 763 (51.9%) were male, and the median (IQR) age was 77 (74-81) years. Overall, the intervention reduced postoperative delirium incidence (odds ratio, 0.87; 95% CI, 0.77-0.98; P = .02) and percentage of days with delirium (intervention, 5.3%; control, 6.9%; P = .03). The effect was significant in patients undergoing orthopedic or abdominal surgery (odds ratio, 0.59; 95% CI, 0.35-0.99; P = .047) but not cardiac surgery (odds ratio, 1.18; 95% CI, 0.70-1.99; P = .54). Conclusions and Relevance: This multifaceted multidisciplinary prevention intervention reduced postoperative delirium occurrence and days with delirium in older patients undergoing different elective surgical procedures but not cardiac procedures. These results suggest implementing this delirium prevention program will improve care and outcomes in older patients undergoing elective general and orthopedic procedures.

Do skeletal muscle composition and gene expression as well as acute exercise-induced serum adaptations in older adults depend on fitness status?

BACKGROUND: Inactive physical behavior among the elderly is one risk factor for cardiovascular disease, immobility and increased all-cause mortality. We aimed to answer the question whether or not circulating and skeletal muscle biomarkers are differentially expressed depending on fitness status in a group of elderly individuals. METHODS: Twenty-eight elderly individuals (73.36 ± 5.46 years) participated in this exploratory study after participating as part of the multinational SITLESS-clinical trial (implementation of self-management and exercise programs over 16 weeks). A cardiopulmonary exercise test (CPX) and resting skeletal muscle biopsy were performed to determine individual physiological performance capacity. Participants were categorized into a high physical fitness group (HPF) and a low physical fitness group (LPF) depending on peak oxygen uptake (VO2peak). Serum blood samples were taken before (pre) and after (post) CPX and were examined regarding serum BDNF, HSP70, Kynurenine, Irisin and Il-6 concentrations. Skeletal muscle tissue was analyzed by silver staining to determine the myosin heavy chain (MyHC) composition and selected genes by qRT-PCR. RESULTS: HPF showed lower body weight and body fat, while skeletal muscle mass and oxygen uptake at the first ventilatory threshold (VO2T1) did not differ between groups. There were positive associations between VO2peak and VO2VT1 in HPF and LPF. MyHC isoform quantification revealed no differences between groups. qRT-PCR showed higher expression of BDNF and BRCA1 in LPF skeletal muscle while there were no differences in other examined genes regarding energy metabolism. Basal serum concentrations of Irisin were higher in HPF compared to LPF with a trend towards higher values in BDNF and HSP70 in HPF. Increases in Il-6 in both groups were observed post. CONCLUSIONS: Although no association between muscle composition/VO2peak with fitness status in older people was detected, higher basal Irisin serum levels in HPF revealed slightly beneficial molecular serum and muscle adaptations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02629666 . Registered 19 November 2015.

Sex-specific differences in DNA double-strand break repair of cycling human lymphocytes during aging.

The gender gap in life expectancy and cancer incidence suggests differences in the aging process between the sexes. Genomic instability has been recognized as a key factor in aging, but little is known about sex-specific differences. Therefore, we analyzed DNA double-strand break (DSB) repair in cycling human peripheral blood lymphocytes (PBL) from male and female donors of different age. Reporter-based DSB repair analyses revealed differential regulation of pathway usage in PBL from male and female donors with age: Non-homologous end joining (NHEJ) was inversely regulated in men and women; the activity of pathways requiring end processing and strand annealing steps such as microhomology-mediated end joining (MMEJ) declined with age in women but not in men. Screening candidate proteins identified the NHEJ protein KU70 as well as the end resection regulatory factors ATM and BLM showing reduced expression during aging in women. Consistently, the regulatory factor BLM contributed to the MMEJ proficiency in young but not in old women as demonstrated by knockdown analysis. In conclusion, we show that DSB repair is subject to changes upon aging and age-related changes in DSB repair are distinct in men and women.