Abstract
Background
Frailty was shown to be associated with psychosocial risk factors, but there are few longitudinal data.
Methods
We used data from waves 5 and 6 of the Survey of Health Aging ...Retirement in Europe (SHARE) to study the contribution of loneliness and social isolation to transitions towards frailty defined according to Fried criteria in a sample of 27,468 individuals aged ≥60.
Results
At baseline, there were 13,069 (47.6%) robust individuals, 11,430 (41.6%) pre-frail and 2,969 (10.8%) frail. After 2 years, among robust subjects at baseline, 8,706 (61.8%) were still robust, 4,033 (30.8%) were pre-frail and 330 (2.6%) were frail. Among those who were pre-frail, 1,504 (13.2%) progressed to frail and 3,557 (31.1%) became robust. Among frail people, 182 (6.1%) reversed to robust and 1,271 (42.8%) to pre-frail. Average and high levels of loneliness and social isolation were significantly associated with the risk of robust people becoming frail and pre-frail (except robust with high loneliness to become frail), and of pre-frail people to become frail (except with average loneliness). Reversion to robustness was inversely associated with high levels of loneliness.
Conclusion
Average levels of loneliness and social isolation should not be considered acceptable and should be actively addressed even in the absence of any health conditions through an available evidence-based intervention.
Therapeutic drug and immunogenicity monitoring (TDIM) is increasingly proposed to guide therapy with biologics, characterised by high inter-individual variability of their blood levels, to permit ...objective decisions for the management of non-responders and reduce unnecessary interventions with these expensive treatments. However, TDIM has not yet entered clinical practice partly because of uncertainties regarding the accuracy and precision of enzyme-linked immunosorbent assays (ELISA). Here we report the characterisation of a novel surface plasmon resonance (SPR)-based TDIM, applied to the measurement of serum concentrations of infliximab, an antibody against tumour necrosis factor α (anti-TNFα), and anti-infliximab antibodies. SPR has the obvious advantages of directly detecting and measuring serum antibodies in minutes, avoiding the long incubation/separation/washing/detection steps of the methods proposed so far, reducing complexity and variability. Moreover, drug and anti-drug antibodies can be measured simultaneously. This new method was validated for sensitivity and reproducibility, and showed cost-effectiveness over commercial ELISA kits. This method may be applied to other biotherapeutics. These data pave the way for the development of SPR-based point-of-care devices for rapid on-site analysis.
Background
Delirium is a neuropsychiatric syndrome associated with negative outcomes, including worsening of cognitive and functional status and an increased burden on patients and caregivers. ...Medications with anticholinergic effect have been associated with delirium symptoms, but the relationship is still debated.
Objective
To assess the relation between delirium and anticholinergic load according to the hypothesis that the cumulative anticholinergic burden increases the risk of delirium.
Methods
This retrospective cross-sectional study was conducted in a sample of end-of-life patients in a hospice or living at home between February and August 2019. Delirium was diagnosed on admission using the 4 ‘A’s Test (4AT) and each patient’s anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale.
Results
Of the 461 eligible for analysis, 124 (26.9%) had delirium. Anticholinergic medications were associated with an increased risk of delirium in univariate (OR (95% CI) 1.26 (1.16–1.38),
p
< 0.0001) and multivariate models adjusted for age, sex, dementia, tumors, Karnofsky Performance Status (KPS) score, days of palliative assistance, and setting (OR (95% CI) 1.16 (1.05–1.28),
p
< 0.0001). Patients with delirium had a greater anticholinergic burden than those without, with a dose-effect relationship between total ACB score and delirium. Patients who scored 4 or more had 2 or 3 times the risk of delirium than those not taking anticholinergic drugs. The dose-response relationship was maintained in the multivariate model.
Conclusions
Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity.
Abstract The sustainability of healthcare systems is threatened by the increasing (absolute and relative) number of older persons referring to clinical services. Such global phenomenon is questioning ...the traditional paradigms of medicine, pushing towards the need of new criteria at the basis of clinical decision algorithms. In this context, frailty has been advocated as a geriatric condition potentially capable of overcoming the weakness of chronological age in the identification of individuals requiring adapted care due to their increased vulnerability to stressors. Interestingly, frailty poses itself beyond the concept of nosological conditions due to the difficulties at correctly framing traditional diseases in the complex and heterogeneous scenario of elders. Thus, frailty may play a key role in public health policies for promoting integrated care towards biologically aged individuals, currently presenting multiple unmet clinical needs. At the same time, the term frailty has also been frequently used in the literature for framing a physical condition of risk for (mainly functional) negative endpoints. The combination of such physical impairment with an organ-specific phenotype (e.g., the age-related skeletal muscle decline or sarcopenia) may determine the assumptions for the development of a clinical condition to be used as potential target for ad hoc interventions against physical disability. In the present article, we present the background of frailty and sarcopenia, and discuss their potentialities for reshaping current clinical and research practice in order to promote holistic approach to older patients, solicit personalization of care, and develop new targets for innovative interventions.
Abstract
Measurements of serum concentrations of therapeutic antibodies and anti-drug antibodies (ADA) can support clinical decisions for the management of non-responders, optimizing the therapy. In ...the present study we compared the results obtained by classical ELISA and a recently proposed surface plasmon resonance (SPR)-based immunoassay, in 76 patients receiving infliximab for inflammatory bowel diseases. The two methods indicated very similar serum concentrations of the drug, but there were striking differences as regards ADA. All the sera showing ADA by ELISA (14) also showed ADA by SPR, but the absolute amounts were different, being 7–490 times higher with SPR, with no correlation. Eight patients showed ADA only with SPR, and these ADA had significantly faster dissociation rate constants than those detectable by both SPR and ELISA. The underestimation, or the lack of detection, of ADA by ELISA is likely to reflect the long incubation steps which favor dissociation of the patient’s low-affinity ADA, while the commercial, high-affinity anti-infliximab antibodies used for the calibration curve do not dissociate. This problem is less important with SPR, which monitors binding in real time. The possibility offered by SPR to detect ADA in patients otherwise considered ADA-negative by ELISA could have important implications for clinicians.
Age-related frailty is a multidimensional dynamic condition associated with adverse patient outcomes and high costs for health systems. Several interventions have been proposed to tackle frailty. ...This correspondence article describes the journey through the development of evidence- and consensus-based guidelines on interventions aimed at preventing, delaying or reversing frailty in the context of the FOCUS (Frailty Management Optimisation through EIP-AHA Commitments and Utilisation of Stakeholders Input) project (664367-FOCUS-HP-PJ-2014). The rationale, framework, processes and content of the guidelines are described.
The guidelines were framed into four questions - one general and three on specific groups of interventions - all including frailty as the primary outcome of interest. Quantitative and qualitative studies and reviews conducted in the context of the FOCUS project represented the evidence base. We followed the GRADE Evidence-to-Decision frameworks based on assessment of whether the problem is a priority, the magnitude of the desirable and undesirable effects, the certainty of the evidence, stakeholders' values, the balance between desirable and undesirable effects, the resource use, and other factors like acceptability and feasibility. Experts in the FOCUS consortium acted as panellists in the consensus process. Overall, we eventually recommended interventions intended to affect frailty as well as its course and related outcomes. Specifically, we recommended (1) physical activity programmes or nutritional interventions or a combination of both; (2) interventions based on tailored care and/or geriatric evaluation and management; and (3) interventions based on cognitive training (alone or in combination with exercise and nutritional supplementation). The panel did not support interventions based on hormone treatments or problem-solving therapy. However, all our recommendations were weak (provisional) due to the limited available evidence and based on heterogeneous studies of limited quality. Furthermore, they are conditional to the consideration of participant-, organisational- and contextual/cultural-related facilitators or barriers. There is insufficient evidence in favour of or against other types of interventions.
We provided guidelines based on quantitative and qualitative evidence, adopting methodological standards, and integrating relevant stakeholders' inputs and perspectives. We identified the need for further studies of a higher methodological quality to explore interventions with the potential to affect frailty.
To analyze the relationship between atrial fibrillation (AF) and Charlson comorbidity index (CCI) in a population-based cohort study over a long-term follow-up period, in relation to oral ...anticoagulant (OAC) prescriptions and outcomes.
We used data from the administrative health databases of Lombardy. All patients with AF and age 40 years and older and who were admitted to the hospital in 2002 were considered for analysis and followed up to 2014. AF diagnosis and CCI were established according to codes from the International Classification of Diseases, Ninth Revision.
In 2002, 24,040 patients were admitted with a diagnosis of AF. CCI was higher in patients with AF than in those without AF (1.8±2.1 vs 0.2±0.9; P<.001). Over 12 years of follow-up, AF was associated with an increased risk of higher CCI (beta coefficient, 1.69; 95% CI, 1.67-1.70). In patients with AF, CCI was inversely associated with OAC prescription at baseline (P<.001) and at the end of the follow-up (P=.03). Patients with AF and a high CCI (≥4) had a higher cumulative incidence of stroke, major bleeding, and all-cause death (all P<.001), compared with those with low CCI (range, 0-3). Adjusted Cox regression analysis revealed that time-dependent continuous CCI was associated with an increased risk for stroke, major bleeding, and all-cause death (all P<.001).
In hospitalized patients, AF is associated with an increase in CCI that is inversely associated with OAC prescriptions during follow-up. CCI is independently associated with an increased risk of stroke, major bleeding, and all-cause death.
Purposes
We evaluated the prevalence and factors associated with polypharmacy and investigated the role of polypharmacy as a predictor of length of hospital stay and in-hospital mortality.
Methods
...Thirty-eight internal medicine wards in Italy participated in the
Re
gistro
Po
literapie
SI
MI (REPOSI) study during 2008. One thousand three hundred and thirty-two in-patients aged ≥65 years were enrolled. Polypharmacy was defined as the concomitant use of five or more medications. Linear regression analyses were used to evaluate predictors of length of hospital stay and logistic regression models for predictors of in-hospital mortality. Age, sex, Charlson comorbidity index, polypharmacy, and number of in-hospital clinical adverse events (AEs) were used as possible confounders.
Results
The prevalence of polypharmacy was 51.9% at hospital admission and 67.0% at discharge. Age, number of drugs at admission, hypertension, ischemic heart disease, heart failure, and chronic obstructive pulmonary disease were independently associated with polypharmacy at discharge. In multivariate analysis, the occurrence of at least one AE while in hospital was the only predictor of prolonged hospitalization (each new AE prolonged hospital stay by 3.57 days,
p
< 0.0001). Age odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01–1.08;
p
= 0.02), comorbidities (OR 1.18; 95% CI 1.12–1.24;
p
< 0.0001), and AEs (OR 6.80; 95% CI 3.58–12.9;
p
< 0.0001) were significantly associated with in-hospital mortality.
Conclusions
Although most elderly in-patients receive polypharmacy, in this study, it was not associated with any hospital outcome. However, AEs were strongly correlated with a longer hospital stay and higher mortality risk.
Background
From 20 to 65 % of older adults receiving polypharmacy take at least one potentially inappropriate medication (PIM), leading to a high risk of adverse drug reactions. The term ...deprescribing was coined to describe a process of optimization of drug regimens through the withdrawal of PIMs. There is a paucity of evidence on the attitudes, beliefs and willingness of hospitalized patients towards deprescribing.
Objective
To measure at hospital discharge inpatients’ attitudes and beliefs towards polypharmacy and the potential withdrawal of one or more of their medications using the PATD (Patients’ Attitudes Towards Deprescribing) questionnaire and determine if they are associated with participant characteristics.
Setting
Geriatric and internal medicine wards in an Italian teaching hospital.
Method
Administration of the PATD questionnaire (developed and validated in an Australian outpatient setting, translated and adapted to the Italian setting for this study) to a consecutive sample of 100 older (aged ≥65 years) inpatients with polypharmacy who were interviewed by a nurse or pharmacist at the time of hospital discharge.
Main outcome measure
Older patients’ attitudes and beliefs towards reducing medications and participant characteristics.
Results
Eighty-nine percent of patients surveyed would like to reduce the number of daily medications. The desire for deprescribing was not associated with age, sex or number of medications or medical conditions; older patients were less aware of the reasons for taking medications.
Conclusion
The majority of hospitalized older adults with polypharmacy think they are taking a lot of drugs and would like to reduce this number. Older adults should not be considered a major limitation on deprescribing interventions. Future research should examine this issue with qualitative studies in order to gain a more in-depth understanding and explore how these findings can be translated into a multidisciplinary deprescribing process.
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