Michael D. Denkinger

What Works to Prevent Falls in Community-Dwelling Older Adults? Umbrella Review of Meta-analyses of Randomized Controlled Trials

Background Preventing falls is an international priority. There is a need to synthesize the highest-quality falls prevention evidence in one place for clinicians. Purpose The aim of this study was to conduct an umbrella review of meta-analyses of randomized controlled trials (RCTs) of falls prevention interventions in community-dwelling older adults. Data Sources The MEDLINE, EMBASE, CINAHL, AMED, BNI, PsycINFO, Cochrane Library, PubMed, and PEDro databases were searched. Study Selection Meta-analyses with one pooled analysis containing ≥3 RCTs that investigated any intervention to prevent falls in community-dwelling older adults aged ≥60 years were eligible. Sixteen meta-analyses, representing 47 pooled analyses, were included. Data Extraction Two authors independently extracted data. Data Synthesis Data were narratively synthesized. The methodological quality of the meta-analyses was moderate. Three meta-analyses defined a fall, and 3 reported adverse events (although minor). There is consistent evidence that exercise reduces falls (including the rate, risk, and odds of falling), with 13/14 pooled analyses (93%) from 7 meta-analyses demonstrating a significant reduction. The methodological quality of meta-analyses investigating exercise were medium/high, and effect sizes ranged from 0.87 (relative risk 95% confidence interval=0.81, 0.94; number of studies=18; number of participants=3,568) to 0.39 (rate ratio 95% confidence interval=0.23, 0.66; number of meta-analyses=6). There is consistent evidence that multifactorial interventions reduce falls (5/6, 83% reported significant reduction). There is conflicting evidence regarding the influence of vitamin D supplementation (7/12, 58.3% reported significant reduction). Limitations Meta-analyses often used different methods of analysis, and reporting of key characteristics (eg, participants, heterogeneity, publication bias) was often lacking. There may be some overlap among included meta-analyses. Conclusions There is consistent evidence that exercise and individually tailored multifactorial interventions are effective in reducing falls in community-dwelling older adults.

Relationship of urinary incontinence and late-life disability: Implications for clinical work and research in geriatrics

The role of urinary incontinence (UI) in the disablement process model has been mainly defined according to its impact on quality of life, global wellbeing, life satisfaction, institutionalization and death, which are global outcomes of disability. Recent research focused on the “active” role of UI in the main pathway of the disablement process model, i.e. actively involved in the causes of disability. The aim of this paper is to review the complex current scientific evidence on this second active role and to define the implications for further research and for clinical work in geriatrics. The relationship between UI and disability can be classified in the following five pathways:1) UI as risk factor for functional decline and reduced physical activity through the increased risk of falls and fractures.2) Functional decline and reduced physical activity as risk factors for the onset of UI.3) Shared risk factors for UI and functional decline: white matter changes, stroke and other neurological conditions.4) UI in a unifying conceptual framework: the multifactorial etiology of geriatric syndromes.5) UI as an indicator of frailty.Understanding these pathways could improve insight into clinical, pharmacological, environmental, behavioral and rehabilitative mechanisms to define measures for the prevention and treatment of the geriatric syndromes cascade. However, research on effective interventions on these overlapping areas is still quite rare. Additionally there is an urgent need to use the standardized terminology of lower urinary tract symptoms (LUTS), established by the International Continence Society (ICS) to find a common language in disability research. To conclude, the relationship of UI and disability is evident in different pathways. Understanding these associations can have substantial implications for both clinical work and research in this area.ZusammenfassungDie Rolle der Harninkontinenz wurde im Modell des „Disablement Process“ bislang hauptsächlich anhand globaler Endpunkte von Behinderung, wie Lebensqualität, allgemeinem Wohlbefinden, Lebenszufriedenheit, Institutionalisierung und Tod untersucht. Aktuelle Forschungsprojekte behandeln stattdessen die aktive Rolle der Harninkontinenz im Hauptpfad des „Disablement Process-Modells“, womit ihr eine direkte Rolle bei der Entstehung von funktioneller Einschränkung und Behinderung zugesprochen wird. Das Ziel dieses Artikels ist es, einen Überblick über die komplexen Zusammenhänge dieser zweiten, „aktiven“ Rolle der Harninkontinenz zu geben und mögliche Auswirkungen für Forschung und klinisch geriatrische Arbeit aufzuzeigen. Der Zusammenhang zwischen Harninkontinenz und Beeinträchtigung kann anhand der folgenden 5 Pfade dargestellt werden:1) Harninkontinenz als Risikofaktor für funktionellen Abbau und reduzierte körperliche Aktivität durch eine Erhöhung des Sturz- und Frakturrisikos.2) Funktionsminderung im Alltag und reduzierte körperliche Aktivität als Risikofaktoren für den Beginn einer Harninkontinenz.3) Gemeinsame Risikofaktoren für das Entstehen von Harninkontinenz und Funktionsminderung im Alltag: Marklagerveränderungen, Schlaganfall und andere neurologische Erkrankungen.4) Harninkontinenz in einem vereinheitlichenden Rahmenkonzept: die multifaktorielle Ätiologie geriatrischer Syndrome.5) Harninkontinenz als Gebrechlichkeits- Indikator.Die Anwendung dieser Pfade könnte zu einem besseren Verständnis klinischer, pharmakologischer, rehabilitativer und verhaltenstherapeutischer Zusammenhänge führen, um Maßnahmen zur Prävention und Behandlung geriatrischer Syndrome zu definieren. Die Zahl von Forschungsprojekten zur weiteren Charakterisierung dieser sich überschneidenden Gebiete ist jedoch weiterhin sehr gering. Zudem besteht dringender Bedarf, die neue und standardisierte Terminologie von Symptomen des unteren Harntrakts (LUTS) der International Continence Society (ICS) zu verwenden, um in zukünftigen Forschungsprojekten mit dem Thema Behinderung im Alter eine gemeinsame Sprache zu finden.Zusammenfassend kommt die Beziehung von Behinderung und Inkontinenz in verschiedenen Pfaden deutlich zum Ausdruck. Das Verständnis dieser Zusammenhänge kann bedeutende Auswirkungen für klinische Arbeit und geriatrische Forschung haben.

Multisite pain, pain frequency and pain severity are associated with depression in older adults: results from the ActiFE Ulm study

BACKGROUND there is ample literature showing pain and depression are related. However, different dimensions of pain have been used in former studies. OBJECTIVE the objective of the study was to compare the strength of the association of different pain dimensions with depression in older adults. METHODS assessments including evaluation of pain (severity, frequency, chronicity, quality, pain medication, painful body sites) and depression (measured by the Hospital Anxiety and Depression Scale) were performed in an observational study in community dwelling older adults (sample mean age 76, n = 1130) in Germany. The associations of different dimension of pain with depression were assessed using descriptive and multivariate methods. RESULTS the number of painful body areas was most significantly associated with self-reported late life depression (OR 1.20, CI 1.11-1.31). Pain severity and frequency (OR 1.12, CI 1.01-1.23 and OR 1.18, CI 1.01-1.37) were also associated with depression; quality and duration were not. Except for severity (OR 1.12, CI 1.02-1.24) associations of pain dimensions were strongly reduced when controlling for relevant confounders and gender was an effect modifier. CONCLUSIONS multisite pain, pain severity and frequency were the best predictors of late life depression. Clinicians should be especially aware of depressive disorders when older patients are complaining of pain in multiple areas across the body.

Pain characteristics and pain control in European nursing homes: cross-sectional and longitudinal results from the Services and Health for Elderly in Long TERm care (SHELTER) study.

OBJECTIVE AND DESIGN Few studies have compared cross-national characteristics of residents with pain in European long term care facilities. The SHELTER project, a cross-national European study on nursing home residents, provides the opportunity to examine this issue. The present study aimed to evaluate key figures about pain and compare them with seven European countries and Israel. SETTING, PARTICIPANTS, AND MEASUREMENTS A total of 3926 nursing home residents were assessed by the interRAI instrument for Long Term Care Facilities (interRAI LTCF). Prevalence of pain, frequency, intensity, consistency, and control were estimated and compared cross-nationally. Correlates between patient-related characteristics and inadequate pain management were tested using bivariate and multivariate logistic regression models. RESULTS Overall, 1900 (48.4%) residents suffered from pain. Pain prevalence varied significantly among countries, ranging from 19.8% in Israel to 73.0% in Finland. Pain was positively associated with female gender, fractures, falls, pressure ulcers, sleeping disorders, unstable health conditions, cancer, depression, and number of drugs. It was negatively associated with dementia. In a multivariate logistic regression model, all associations remained except for sleeping disorders. Clinical correlations varied considerably among countries. Although in 88.1% of cases, pain was self-rated by the residents as sufficiently controlled, in only 56.8% of cases was pain intensity self-rated as absent or mild. Pain control and intensity improved within 1 year. CONCLUSION Pain prevalence is high and varies considerably across Europe. Although most residents considered pain as adequately controlled, a closer look confirmed that many still suffer from high pain intensities. Analyzing the reasons behind these differences may help to improve pain management.

Hematopoietic stem cell aging.

Aging is organized in a hierarchy, in which aging of cells results in aged tissues, ultimately limiting lifespan. For organ systems that also in the adult depend on stem cells for tissue homeostasis like the hematopoietic system that forms immune cells, it is believed that aging of the stem cells strongly contributes to aging-associated dysfunction. In this review, we summarize current aspects on cellular and molecular mechanisms that are associated with aging of hematopoietic stem cells, the role of the stem cell niche for stem cell aging as well as novel and encouraging experimental approaches to attenuate aging of hematopoietic stem cells to target immunosenescence.

Use of Antipsychotic Drugs Among Residents With Dementia in European Long-Term Care Facilities: Results From the SHELTER Study

BACKGROUND Behavioral and psychological symptoms of dementia (BPSD) are common reasons for use of antipsychotic drugs among older individuals with dementia. These drugs are not approved for such use and both the Food and Drug Administration and European Medicines Agency have issued warnings to limit such use. OBJECTIVES This study aimed to describe patterns of antipsychotic drug use in a sample of nursing home residents with dementia in 7 European countries and Israel. DESIGN This cross-sectional, retrospective cohort study used data from the SHELTER study that collected comprehensive resident data using the interRAI Long-Term Care Facility instrument. METHODS Fifty-seven long-term care facilities participated from 8 countries, and the sample included 4156 long-term care residents from these settings. Individuals with dementia, both Alzheimer and non-Alzheimer types, were identified. Potential correlates of any antipsychotic and atypical versus conventional antipsychotic drug use among residents with dementia were identified using generalized estimation equation modeling. RESULTS A total of 2091 individuals with dementia were identified. Antipsychotic drug use among these individuals varied by country, with overall prevalence of use being 32.8% (n = 662). Among antipsychotic users, 7 in 10 were receiving atypical agents. Generalized estimation equation analysis revealed that the strongest correlate of any antipsychotic drug use was severe behavioral symptoms, which increased the likelihood by 2.84. Correlates of atypical versus conventional antipsychotic drug use included psychiatric services, more than 10 medications, moderate behavioral symptoms, and female gender. CONCLUSION Despite recommendations to avoid the use of antipsychotic drugs in patients with dementia, a large proportion of residents in European long-term care facilities continue to receive such agents. Future work should not only establish the appropriateness of such use through outcomes studies, but explore withdrawal strategies as well as alternative treatment modalities.

HSC Aging and Senescent Immune Remodeling

Aging-associated changes in the function of the immune system are referred to as senescent immune remodeling (SIR). Here we review the current understanding on the cellular and molecular mechanisms underlying SIR. We focus on aging-associated changes in T and B cells, and discuss recent evidence supporting the notion that aging of the hematopoietic stem cell (HSC) compartment directly contributes to SIR due to aging-associated alterations in stem cell differentiation. We conclude by outlining strategies to attenuate SIR, including approaches to rejuvenate HSCs, which may open new avenues for targeting SIR in the clinic.

Osteoarthritis and mortality: A prospective cohort study and systematic review with meta-analysis

OBJECTIVES Osteoarthritis (OA) is a leading cause of disability, but the relationship with premature mortality remains uncertain. We aimed to investigate the relationship between OA and mortality from any cause and from cardiovascular disease (CVD). METHODS Electronic literature databases searches were conducted to identify prospective studies comparing mortality in a sample of people with and without OA. Risk of all-cause and CVD mortality were summarized using adjusted hazard ratios (HRs) for joint specific (hand, hip, and knee) and joint non-specific OA. New data from the Progetto Veneto Anziani (PRO.V.A.) study were also included. RESULTS From the PRO.V.A. study (N = 2927), there was no significant increase in mortality risk for participants with any joint OA (N = 1858) compared to non-OA (all-cause, HR = 0.95, 95% CI: 0.77-1.15 and CVD, HR = 1.12, 95% CI: 0.82-1.54). On meta-analysis, seven studies (OA = 10,018/non-OA = 18,541), with a median 12-year follow-up, reported no increased risk of any-cause mortality in those with OA (HR = 1.10, 95% CI: 0.97-1.25). After removing data on hand OA, a significant association between OA and mortality was observed (HR = 1.18, 95% CI: 1.08-1.28). There was a significant higher risk of overall mortality for (1) studies conducted in Europe, (2) patients with multi-joint OA; and (3) a radiological diagnosis of OA. OA was associated with significantly higher CVD mortality (HR = 1.21, 95% CI: 1.10-1.34). CONCLUSIONS People with OA are at increased risk of death due to CVD. The relationship with overall mortality is less clear and may be moderated by the presence of hand OA.

Seasonality of vitamin D status in older people in Southern Germany: implications for assessment

BACKGROUND from a clinical and public health perspective, it is important to understand the influence of seasonality on the serum vitamin D level to adequately assess and interpret an individual measurement. Therefore, the aim of this study was to analyse the effects of seasonal conditions on 25-hydroxyvitamin D (25(OH)D) serum levels in a population-based cohort of older people. METHODS between March 2009 and April 2010 the 25(OH)D serum level was assessed in 1,418 community-dwelling individuals living in Germany aged ≥65 years (56.7% men) with no subscribed vitamin D supplementation. Least-square means of monthly 25(OH)D serum levels with 95% confidence intervals (CI) were estimated, adjusted for gender, age and body mass index. Additionally, the proportion of vitamin deficiency (<20 ng/ml), insufficiency (20-<30 ng/ml) and sufficiency (30 ng/ml or higher) were estimated for each month. Finally, mean values of daily total global solar radiation and daylight were calculated for each month. RESULTS the minimum 25(OH)D serum level was observed in March with 15.4 ng/ml (SD = 6.56 ng/ml) and the maximum in August with 25.6 ng/ml (SD = 6.59 ng/ml). Compared with daylight and global solar radiation the progression over the year was similar but delayed by ∼2 months. The proportion of vitamin D deficiency, insufficiency and sufficiency were 78.8, 19.2 and 1.9% in March and 16.1, 63.4 and 20.5% in August, respectively. CONCLUSION vitamin D insufficiency was very common in this cohort and showed a strong seasonal effect with lowest values in March.

Relationships between physical performance and knee and hip osteoarthritis: findings from the European Project on Osteoarthritis (EPOSA)

BACKGROUND poor physical performance (PP) is known to be associated with disability, lower quality of life and higher mortality rates. Knee and hip osteoarthritis (OA) might be expected to contribute to poor PP, through joint pain and restricted range of movement. Both clinical and self-reported OA are often used for large-scale community and epidemiological studies. OBJECTIVE to examine the relationships between hip and knee OA and PP in a large data set comprising cohorts from six European countries. METHODS a total of 2,942 men and women aged 65-85 years from the Germany, Italy, Netherlands, Spain, Sweden and the UK were recruited. Assessment included an interview and clinical assessment for OA. PP was determined from walking speed, chair rises and balance (range 0-12); low PP was defined as a score of ≤9. RESULTS the mean (SD) age was 74.2 (5.1) years. Rates of self-reported OA were much higher than clinical OA. Advanced age, female gender, lower educational attainment, abstinence from alcohol and higher body mass index were independently associated with low PP. Clinical knee OA, hip OA or both were associated with a higher risk of low PP; OR (95% CI) 2.93 (2.36, 3.64), 3.79 (2.49, 5.76) and 7.22 (3.63, 14.38), respectively, with relationships robust to adjustment for the confounders above as well as pain. CONCLUSION lower limb OA at the hip and knee is associated with low PP, and for clinical diagnosis relationships are robust to adjustment for pain. Those at highest risk have clinical OA at both sites.