Decision-making for long-term tube-feeding in cognitively impaired elderly people

BACKGROUND: The decision to start long-term tube-feeding in elderly people is complex. The process by which such decisions are made is not well understood. The authors examined the factors involved in the decision to start long-term tube-feeding in cognitively impaired older people from the perspective of the substitute decision-maker. METHODS: A telephone survey was administered to the substitute decision-makers of tube-fed patients over 65 years old in chronic care facilities in Ottawa. Subjects were recruited from September 1997 to March 1998. Patients were incapable of making their own decisions about tube-feeding. Data were collected on sociodemographic factors, patients'' health status, advance directives, communication between the substitute decision-maker and the health care team, and the decision-maker''s perceived goals of tube-feeding and satisfaction with the decision regarding tube-feeding. RESULTS: Among the 57 cases in which the patient was eligible for inclusion in the study, 46 substitute decision-makers agreed to participate. Most of the patients had not given advance directives, and only 26 substitute decision-makers (56.5%) were confident that the patient would want to be tube-fed. A physician spoke with the substitute decision-maker about tube-feeding for 15 minutes or less in 17 cases (37.0%) and not at all in 13 cases (28.3%). Most of the substitute decision-makers (39 [84.8%]) felt that they understood the benefits of tube-feeding, but less than half (21 [45.7%]) felt that they understood the risks. The prevention of aspiration and the prolongation of life were the medical benefits most often cited as reasons for tube-feeding. Just over half (24 [52.2%]) of the substitute decision-makers felt that they had received adequate support from the health care team in making the decision. Substitute decision-makers of patients less than 75 years old were more likely than those of older patients to feel supported (odds ratio [OR] 4.2, 95% confidence interval [CI] 1.0-17.9). Compared with the physician''s making the decision independently, substitute decision-makers felt more supported if they primarily made the decision (OR 16.5, 95% CI 2.7-101.4) or if they made the decision together with the physician (OR 5.3, 95% CI 1.0-27.9). Most (20 [43.5%]) of the substitute decision-makers did not feel that tube-feeding improved the patient''s quality of life, and less than half (21 [45.7%]) indicated that they would choose the intervention for themselves. INTERPRETATION: The substitute decision-making process for tube-feeding in cognitively impaired elderly people is limited by a need for advance directives, lack of confidence in substituted judgement and poor communication of information to the substitute decision-maker by the health care team.     

Patient decision-making capacity and risk

Although certain requisites of patient decision-making competency are generally agreed upon, there is no universally recognized standard. Wicclair, of the University of West Virginia Department of Philosophy, offers two reasons why a single standard should not be determined. First, competency is variable according to the decision at hand, i.e., task-related. Second, arguments in support of risk-related criteria fail. Wicclair challenges claims that a risk-related standard is legally the most feasible, is supported by the doctrine of informed consent, is consistent with everyday competence judgments, and achieves the best compromise between patient autonomy and concern for patient well-being. He argues that where risk is high, such a standard threatens unattainable requirements for competency; and where it is low, offers no set minimum, resulting in overly weak competency standards. Wicclair concludes that the standard of decision-making capacity should not vary by risk perceived.     

7,8-dihydroxyflavone rescues spatial memory and synaptic plasticity in cognitively impaired aged rats

7,8-dihydroxyflavone (7,8-DHF) has recently been identified as a potential TrkB agonist that crosses the blood-brain barrier after i.p. administration. We previously demonstrated that 7,8-DHF in vitro rescues long-term synaptic plasticity in the hippocampus of aged rats. This study assessed the rescue effect of 7,8-DHF in vivo on aging-related cognitive impairment in rats, and further determined whether the effect of 7,8-DHF is age dependent. Aged rats at 22 and 30 months of age were pretested for spatial memory in Morris water maze. The aged-impaired rats were retested twice during 7,8-DHF or vehicle treatment, which started 3 weeks after the completion of the pretest. In the 22-month-old rats, daily i.p. administration of 7,8-DHF for 2 weeks improved spatial memory. The improvement in behavioral tests was associated with increases in synapse formation and facilitation of synaptic plasticity in the hippocampus, as well as the activation of several proteins crucial to synaptic plasticity and memory. A more extended treatment paradigm with 7,8-DHF was required to achieve a significant memory improvement in the severely impaired 30-month-old rats. Moreover, 7,8-DHF moderately facilitated the synaptic plasticity, modified the density but not number of spines in the hippocampus of the oldest rats. Taken together, our results suggest that 7,8-DHF can act in vivo to counteract aging-induced declines in spatial memory and synaptic plasticity and morphological changes of hippocampal neurons. The effect of 7,8-DHF is more pronounced in relatively younger impaired rats than in those of more advanced age. These findings demonstrate the reversal of age-dependent memory impairment by in vivo 7,8-DHF application and support the benefit of early treatment for cognitive aging.     

Measuring surgical decision-making with hypothetical cases

Hypothetical clinical cases were used to investigate surgical decision-making in relation to surgical rates across Ontario. Six procedures were studied (cholecystectomy, colectomy, inguinal herniorrhaphy, hysterectomy, cesarean section and tonsillectomy-adenoidectomy), and substantial differences of opinion regarding the choice of surgical or nonsurgical treatment were recorded. The decision to operate, however, was not made more frequently in Ontario counties with high operative rates, and none of the demographic variables studied were correlated with the decision to operate. Other variables that might have affected operative rates were not taken into account. There were also differences of opinion in referral decisions, but generally internists and pediatricians were less likely to refer the hypothetical cases to surgeons than were family physicians.     

Iron-binding antioxidant capacity is impaired in diabetes mellitus

Increased lipid peroxidation contributes to diabetic complications and redox-active iron is known to play an important role in catalyzing peroxidation reactions. We aimed to investigate if diabetes affects the capacity of plasma to protect against iron-driven lipid peroxidation and to identify underlying factors. Glycemic control, serum iron, proteins involved in iron homeostasis, plasma iron-binding antioxidant capacity in a liposomal model, and non-transferrin-bound iron were measured in 40 type 1 and 67 type 2 diabetic patients compared to 100 nondiabetic healthy control subjects. Iron-binding antioxidant capacity was significantly lower in the plasma of diabetic subjects (83 +/- 6 and 84 +/- 5% in type 1 and type 2 diabetes versus 88 +/- 6% in control subjects, p < 0.0005). The contribution of transferrin, ceruloplasmin, and albumin concentrations to the iron-binding antioxidant capacity was lost in diabetes (explaining only 4.2 and 6.3% of the variance in type 1 and type 2 diabetes versus 13.9% in control subjects). This observation could not be explained by differences in Tf glycation, lipid, or inflammatory status and was not associated with higher non-transferrin-bound iron levels. Iron-binding antioxidant capacity is decreased in diabetes mellitus.     

The assessment of competence in cognitively impaired elderly persons: a closer look at the vignette method

This article focuses on the assessment of competence of elderly persons both with and without cognitive impairment. In total 113 patients of a geriatric clinic were interviewed. Competence was assessed by using two clinical vignettes, representing respectively a hypothetical treatment situation with mild consequences (endoscopy) and one with severe consequences (operation for colon cancer). Competence was evaluated using the following standards: the ability to evidence a choice, the ability to understand a situation, the ability to reason about a choice, and the ability to appreciate a situation. In the vignette with mild consequences, elderly persons with cognitive impairment performed significantly worse on understanding, reasoning and appreciation than elderly persons without cognitive impairment. In the vignette with severe consequences, elderly persons with cognitive impairment performed significantly worse only on understanding as compared to elderly persons without cognitive impairment. No differences were found for reasoning and appreciation between the cognitively impaired and non-impaired elderly persons. We conclude that competence is less limited by cognitive impairment when assessed in a treatment situation with severe consequences. Therefore, the use of hypothetical vignettes should be carefully reconsidered.     

Progressively impaired proteasomal capacity during terminal plasma cell differentiation

After few days of intense immunoglobulin (Ig) secretion, most plasma cells undergo apoptosis, thus ending the humoral immune response. We asked whether intrinsic factors link plasma cell lifespan to Ig secretion. Here we show that in the late phases of plasmacytic differentiation, when antibody production becomes maximal, proteasomal activity decreases. The excessive load for the reduced proteolytic capacity correlates with accumulation of polyubiquitinated proteins, stabilization of endogenous proteasomal substrates (including Xbp1s, IkappaBalpha, and Bax), onset of apoptosis, and sensitization to proteasome inhibitors (PI). These events can be reproduced by expressing Ig-mu chain in nonlymphoid cells. Our results suggest that a developmental program links plasma cell death to protein production, and help explaining the peculiar sensitivity of normal and malignant plasma cells to PI.     

Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacity

We have investigated the functional impact of a naturally occurring mutation of the human glutamate transporter GLT1 (EAAT2), which had been detected in a patient with sporadic amyotrophic lateral sclerosis. The mutation involves a substitution of the putative N-linked glycosylation site asparagine 206 by a serine residue (N206S) and results in reduced glycosylation of the transporter and decreased uptake activity. Electrophysiological analysis of N206S revealed a pronounced reduction in transport rate compared with wild-type, but there was no alteration in the apparent affinities for glutamate and sodium. In addition, no change in the sensitivity for the specific transport inhibitor dihydrokainate was observed. However, the decreased rate of transport was associated with a reduction of the N206S transporter in the plasma membrane. Under ionic conditions, which favor the reverse operation mode of the transporter, N206S exhibited an increased reverse transport capacity. Furthermore, if coexpressed in the same cell, N206S manifested a dominant negative effect on the wild-type GLT1 activity, whereas it did not affect wild-type EAAC1. These findings provide evidence for a role of the N-linked glycosylation in both cellular trafficking and transport function. The resulting alteration in glutamate clearance capacity likely contributes to excitotoxicity that participates in motor neuron degeneration in amyotrophic lateral sclerosis.     

Measuring the antioxidant capacity of blood plasma using potentiometry

The use of potentiometry to measure plasma antioxidant capacity to contribute to oxidative stress evaluation is presented. In this assay, plasma (n = 60) diluted (0.3 to 1 ml) in phosphate buffer, pH 7.4, NaCl 9%, was submitted to potentiometry. A platinum wire was the working electrode and saturated calomel the reference. The results are presented as the difference between sample and buffer potential (ΔE). ΔE presented a good inverse correlation with added increasing concentrations of ascorbate (2.5−75 μmol/L; R = −0.99), urate (9.0−150 μmol/L; R = −0.99), and bilirubin (0.78−13 μmol/L; R = −0.99). Increase in the antioxidant capacity decreased ΔE. Depletion of the antioxidant capacity by tert-butylhydroperoxide (6.5−50 μmol/L) presented a direct correlation (0.97) with ΔE. Furthermore, ΔE presented an inverse correlation (R = −0.99) with increased antioxidant capacity of plasma (FRAP) induced by the addition of ascorbate (2.5−75 μmol/L). The response of the potentiometric method proved be adequate for measuring the plasma antioxidant depletion induced by acute exhaustive exercise in rats (control, n = 15; exercised, n = 15). This exercise decreased the concentration of urate (p < 0.05), decreased FRAP (p < 0.5), increased TBARS (p < 0.5), and decreased the potentiometer sensor response (p = 6.5 × 10⁻³). These results demonstrate the adequacy of potentiometry for evaluating the antioxidant capacity of blood plasma samples.     

Muscle synergies reveal impaired trunk muscle coordination strategies in individuals with thoracic spinal cord injury

Spinal cord injury (SCI) can result in paralysis of trunk muscles, which can affect sitting balance. The objective of this study was to analyze trunk muscle coordination of individuals with thoracic SCI and compare it to able-body individuals. A total of 27 individuals were recruited and subdivided into: (a) high thoracic SCI; (b) low thoracic SCI; and (c) able-body groups. Participants were seated and asked to lean their trunk in eight directions while trunk muscle activity was recorded. Muscle coordination was assessed using the non-negative matrix factorization (NMF) method to extract muscle modules, which are the synergistic trunk muscle activations, and their directional activation patterns. Our results showed that individuals with SCI used less muscle modules, more co-contractions, and less directional tuning, compared to able-bodied people. These results suggest impaired and simplified muscle coordination due to the loss of supraspinal input after SCI. Observed variability in muscle coordination within SCI groups also suggests that other mechanisms such as spasticity and muscle stretch reflexes or individual factors such as experience and training contributed to the postural muscle synergies. Overall, muscle coordination deficits revealed impaired neuromuscular strategies which provide implications for rehabilitation of trunk muscles during sitting balance after SCI.     

Aerobic capacity influences the spatial position of individuals within fish schools

The schooling behaviour of fish is of great biological importance, playing a crucial role in the foraging and predator avoidance of numerous species. The extent to which physiological performance traits affect the spatial positioning of individual fish within schools is completely unknown. Schools of juvenile mullet Liza aurata were filmed at three swim speeds in a swim tunnel, with one focal fish from each school then also measured for standard metabolic rate (SMR), maximal metabolic rate (MMR), aerobic scope (AS) and maximum aerobic swim speed. At faster speeds, fish with lower MMR and AS swam near the rear of schools. These trailing fish required fewer tail beats to swim at the same speed as individuals at the front of schools, indicating that posterior positions provide hydrodynamic benefits that reduce swimming costs. Conversely, fish with high aerobic capacity can withstand increased drag at the leading edge of schools, where they could maximize food intake while possibly retaining sufficient AS for other physiological functions. SMR was never related to position, suggesting that high maintenance costs do not necessarily motivate individuals to occupy frontal positions. In the wild, shifting of individuals to optimal spatial positions during changing conditions could influence structure or movement of entire schools.     

Lower than predicted resting metabolic rate is associated with severely impaired cardiorespiratory fitness in obese individuals

Obese individuals have reduced cardiorespiratory fitness as compared with leaner counterparts. Regular exercise maintains or increases fitness and lean body mass. Lean body mass, in turn, has a direct impact on resting metabolic rate (RMR). Given these relationships, we sought to evaluate the association between RMR and cardiorespiratory fitness in obese individuals. We evaluated 64 obese individuals (78% female) with direct assessment of RMR and cardiorespiratory fitness via breath‐by‐breath measurement of oxygen consumption and carbon dioxide production at rest and during exercise. The mean age and BMI were 47.4 ± 12.2 years and 47.2 ± 9.2 kg/m², respectively. The majority of subjects, 69%, had a measured RMR above that predicted by the Harris‐Benedict equation. Compared with the higher RMR group, those with a lower than predicted RMR had increased BMI, with values of 52.9 vs. 44.7 kg/m², P = 0.001, respectively. Analysis of those demonstrating significant effort during cardiopulmonary exercise testing (peak respiratory exchange ratio ≥1.10) revealed a significantly higher peak oxygen uptake (VO₂ peak) in the higher RMR group (17.3 ± 3.5 ml/min/kg) compared with the lower RMR group (13.6 ± 1.9 ml/min/kg), P = 0.003. In summary, a lower than predicted RMR was associated with a severely reduced VO₂ peak and a higher BMI in this cohort. These data suggest that morbid obesity may be a vicious cycle of increasing BMI, reduced cardiorespiratory fitness, muscle deconditioning, and lower RMR. Collectively, these responses may, over time, exacerbate the imbalance between energy intake and expenditure, resulting in progressive increases in body weight and fat stores.     

Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity

Osteoarthritis (OA) is a common joint disease, mainly effecting the elderly population. The cause of OA seems to be an imbalance in catabolic and anabolic factors that develops with age. IL-1 is a catabolic factor known to induce cartilage damage, and transforming growth factor (TGF)-beta is an anabolic factor that can counteract many IL-1-induced effects. In old mice, we observed reduced responsiveness to TGF-beta-induced IL-1 counteraction. We investigated whether expression of TGF-beta and its signaling molecules altered with age. To mimic the TGF-beta deprived conditions in aged mice, we assessed the functional consequence of TGF-beta blocking. We isolated knee joints of mice aged 5 months or 2 years, half of which were exposed to IL-1 by intra-articular injection 24 h prior to knee joint isolation. Immunohistochemistry was performed, staining for TGF-beta1, -2 or -3, TGF-betaRI or -RII, Smad2, -3, -4, -6 and -7 and Smad-2P. The percentage of cells staining positive was determined in tibial cartilage. To mimic the lack of TGF-beta signaling in old mice, young mice were injected with IL-1 and after 2 days Ad-LAP (TGF-beta inhibitor) or a control virus were injected. Proteoglycan (PG) synthesis (³⁵S-sulfate incorporation) and PG content of the cartilage were determined. Our experiments revealed that TGF-beta2 and -3 expression decreased with age, as did the TGF-beta receptors. Although the number of cells positive for the Smad proteins was not altered, the number of cells expressing Smad2P strongly dropped in old mice. IL-1 did not alter the expression patterns. We mimicked the lack of TGF-beta signaling in old mice by TGF-beta inhibition with LAP. This resulted in a reduced level of PG synthesis and aggravation of PG depletion. The limited response of old mice to TGF-beta induced-IL-1 counteraction is not due to a diminished level of intracellular signaling molecules or an upregulation of intracellular inhibitors, but is likely due to an intrinsic absence of sufficient TGF-beta receptor expression. Blocking TGF-beta distorted the natural repair response after IL-1 injection. In conclusion, TGF-beta appears to play an important role in repair of cartilage and a lack of TGF-beta responsiveness in old mice might be at the root of OA development.