Rationale and protocol of the StayFitLonger study: a multicentre trial to measure efficacy and adherence of a home-based computerised multidomain intervention in healthy older adults.

BACKGROUND: In older adults, multidomain training that includes physical and cognitive activities has been associated with improvement of physical and cognitive health. The goal of the multisite StayFitLonger study is to assess a home-based computerised training programme, which combines physical exercises, stimulating cognitive activities and virtual coaching. METHODS: One hundred twenty-eight cognitively healthy older adults will be recruited from the community in Switzerland, Canada and Belgium. The study will comprise (1) a 26-week double-blind randomized controlled efficacy trial and (2) a 22-week pragmatic adherence sub-study. In the efficacy trial, participants will be randomly assigned to an experimental or an active control intervention. In the experimental intervention, participants will use the StayFitLonger programme, which is computerised on a tablet and provides content that combines physical activities with a focus on strength and balance, as well as divided attention, problem solving and memory training. Outcomes will be measured before and after 26 weeks of training. The primary efficacy outcome will be performance on the "Timed-Up & Go" test. Secondary outcomes will include measures of frailty, cognition, mood, fear of falling, quality of life, and activities of daily living. Age, sex, education, baseline cognition, expectation, and adherence will be used as moderators of efficacy. Following the 26-week efficacy trial, all participants will use the experimental programme meaning that participants in the control group will 'cross over' to receive the StayFitLonger programme for 22 weeks. Adherence will be measured in both groups based on dose, volume and frequency of use. In addition, participants' perception of the programme and its functionalities will be characterised through usability, acceptability and user experience. DISCUSSION: This study will determine the efficacy, adherence and participants' perception of a home-based multidomain intervention programme and its functionalities. This will allow for further development and possible commercialization of a scientifically validated training programme. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04237519 Registered on January 22, 2020 - Retrospectively registered.

Pre-frail older adults show improved cognition with StayFitLonger computerized home-based training: a randomized controlled trial.

Multidomain interventions have shown tremendous potential for improving cognition in older adults. It is unclear if multidomain interventions can be delivered remotely and whether remote intervention is beneficial for older adults who are vulnerable or at risk of cognitive decline. In a 26-week multi-site, home-based, double-blind, randomized controlled trial, 120 cognitively healthy older adults (75 robust, 45 pre-frail; age range = 60-94) recruited from Switzerland, Canada, and Belgium were randomized to receive either the StayFitLonger (SFL) computerized multidomain training program or an active control intervention. Delivered on tablets, the SFL intervention combined adapted physical exercises (strength, balance, and mobility), cognitive training (divided attention, problem solving, and memory), opportunities for social and contributive interactions, and psychoeducation. The active control intervention provided basic mobilization exercises and access to video games. Cognitive outcomes were global cognition (Z-scores of attention, verbal fluency, and episodic memory for nondemented older adults; ZAVEN), memory, executive function, and processing speed. Linear mixed model analyses indicated improved performance on the ZAVEN global cognition score in the SFL group but not in the active control group. Stratified analyses by frailty status revealed improved ZAVEN global cognition and processing speed scores following SFL in the pre-frail group but not in the robust group. Overall, the study indicates that a computerized program providing a multidomain intervention at home can improve cognition in older adults. Importantly, pre-frail individuals, who are at higher risk of cognitive decline, seem to benefit more from the intervention. Trial registration: ClinicalTrials.gov, NCT037519 Registered on January 22, 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04237519 .

Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure.

BACKGROUND: Atrial structural remodeling creates a substrate for atrial fibrillation (AF), but the underlying signal transduction mechanisms are unknown. This study assessed the effects of ACE inhibition on arrhythmogenic atrial remodeling and associated mitogen-activated protein kinase (MAPK) changes in a dog model of congestive heart failure (CHF). METHODS AND RESULTS: Dogs were subjected to various durations of ventricular tachypacing (VTP, 220 to 240 bpm) in the presence or absence of oral enalapril 2 mg. kg(-1). d(-1). VTP for 5 weeks induced CHF, local atrial conduction slowing, and interstitial fibrosis and prolonged atrial burst pacing-induced AF. Atrial angiotensin II concentrations and MAPK expression were increased by tachypacing, with substantial changes in phosphorylated forms of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38-kinase. Enalapril significantly reduced tachypacing-induced changes in atrial angiotensin II concentrations and ERK expression. Enalapril also attenuated the effects of CHF on atrial conduction (conduction heterogeneity index reduced from 3.1+/-0.4 to 1.9+/-0.2 ms/mm, P<0.05), atrial fibrosis (from 11.9+/-1.1% to 7.5+/-0.4%, P<0.01), and mean AF duration (from 651+/-164 to 218+/-75 seconds, P<0.05). Vasodilator therapy of a separate group of VTP dogs with hydralazine and isosorbide mononitrate did not alter CHF-induced fibrosis or AF promotion. CONCLUSIONS: CHF-induced increases in angiotensin II content and MAPK activation contribute to arrhythmogenic atrial structural remodeling. ACE inhibition interferes with signal transduction leading to the AF substrate in CHF and may represent a useful new component to AF therapy.

Effect of vagal cooling on the counterregulatory response to hypoglycemia induced by a low dose of insulin in the conscious dog.

We previously demonstrated, using a nerve-cooling technique, that the vagus nerves are not essential for the counterregulatory response to hypoglycemia caused by high levels of insulin. Because high insulin levels per se augment the central nervous system response to hypoglycemia, the question arises whether afferent nerve fibers traveling along the vagus nerves would play a role in the defense of hypoglycemia in the presence of a more moderate insulin level. To address this issue, we studied two groups of conscious 18-h-fasted dogs with cooling coils previously placed on both vagus nerves. Each study consisted of a 100-min equilibration period, a 40-min basal period, and a 150-min hypoglycemic period. Glucose was lowered using a glycogen phosphorylase inhibitor and a low dose of insulin infused into the portal vein (0.7 mU.kg(-1) min(-1)). The arterial plasma insulin level increased to 15 +/- 2 microU/ml and the plasma glucose level fell to a plateau of 57 +/- 3 mg/dl in both groups. The vagal cooling coils were perfused with a 37 degrees C (SHAM COOL; n = 7) or a -20 degrees C (COOL; n = 7) ethanol solution for the last 90 min of the study to block parasympathetic afferent fibers. Vagal cooling caused a marked increase in the heart rate and blocked the hypoglycemia-induced increase in the arterial pancreatic polypeptide level. The average increments in glucagon (pg/ml), epinephrine (pg/ml), norepinephrine (pg/ml), cortisol (microg/dl), glucose production (mg.kg(-1). min(-1)), and glycerol (micromol/l) in the SHAM COOL group were 53 +/- 9, 625 +/- 186, 131 +/- 48, 4.63 +/- 1.05, -0.79 +/- 0.24, and 101 +/- 18, respectively, and in the COOL group, the increments were 39 +/- 7, 837 +/- 235, 93 +/- 39, 6.28 +/- 1.03 (P < 0.05), -0.80 +/- 0.20, and 73 +/- 29, respectively. Based on these data, we conclude that, even in the absence of high insulin concentrations, afferent signaling via the vagus nerves is not required for a normal counterregulatory response to hypoglycemia.

Small increases in insulin inhibit hepatic glucose production solely caused by an effect on glycogen metabolism.

Based on our earlier work, a 2.5-fold increase in insulin secretion should completely inhibit hepatic glucose production through the hormone's direct effect on hepatic glycogen metabolism. The aim of the present study was to test the accuracy of this prediction and to confirm that gluconeogenic flux, as measured by three independent techniques, was unaffected by the increase in insulin. A 40-min basal period was followed by a 180-min experimental period in which an increase in insulin was induced, with euglycemia maintained by peripheral glucose infusion. Arterial and hepatic sinusoidal insulin levels increased from 10 +/- 2 to 19 +/- 3 and 20 +/- 4 to 45 +/- 5 microU/ml, respectively. Net hepatic glucose output decreased rapidly from 1.90 +/- 0.13 to 0.23 +/- 0.16 mg. kg(-1). min(-1). Three methods of measuring gluconeogenesis and glycogenolysis were used: 1) the hepatic arteriovenous difference technique (n = 8), 2) the [(14)C]phosphoenolpyruvate technique (n = 4), and 3) the (2)H(2)O technique (n = 4). The net hepatic glycogenolytic rate decreased from 1.72 +/- 0.20 to -0.28 +/- 0.15 mg. kg(-1). min(-1) (P < 0.05), whereas none of the above methods showed a significant change in hepatic gluconeogenic flux (rate of conversion of phosphoenolpyruvate to glucose-6-phosphate). These results indicate that liver glycogenolysis is acutely sensitive to small changes in plasma insulin, whereas gluconeogenic flux is not.

Pancreatic response to mild non-insulin-induced hypoglycemia does not involve extrinsic neural input.

Mild non-insulin-induced hypoglycemia achieved by administration of a glycogen phosphorylase inhibitor results in increased glucagon and decreased insulin secretion in conscious dogs. Our aim was to determine whether the response of the endocrine pancreas to this mild hypoglycemia can occur in the absence of neural input to the pancreas. Seven dogs underwent surgical pancreatic denervation (PDN [study group]), and seven dogs underwent sham denervation (control [CON] group). Each study consisted of a 100-min equilibration period, a 40-min control period, and a 180-min test period. At the start of the test period, Bay R3401 (10 mg/kg), a glycogen phosphorylase inhibitor, was administered orally. Arterial plasma glucose (mmol/l) fell to a similar minimum in CON (5.0 +/- 0.1) and PDN (4.9 +/- 0.3). Arterial plasma insulin also fell to similar minima in both groups (CON, 20 +/- 6 pmol/l; PDN, 14 +/- 5 pmol/l). Arterial plasma glucagon rose to a similar maximum in CON (73 +/- 8 ng/l) and PDN (72 +/- 9 ng/l). Insulin and glucagon secretion data support these plasma hormone results, and there were no significant differences in the responses in CON and PDN for any parameter. Pancreatic norepinephrine content in PDN was only 4% of that in CON, confirming successful sympathetic denervation. Pancreatic polypeptide levels tended to increase in CON and decrease in PDN in response to mild hypoglycemia, indicative of parasympathetic denervation. It thus can be concluded that the responses of alpha- and beta-cells to mild non-insulin-induced hypoglycemia can occur in the absence of extrinsic neural input.

Sexual concerns and needs of the postcoronary patient's wife.

The sexual concerns and needs of 100 women whose husbands had suffered a myocardial infarction were studied. Thirty-one had considered the impact of myocardial infarction on their sexual life before discharge of their spouse from the hospital and all of them had thereafter. Only 45 of the wives received any sexual information before the spouse's discharge. Seventy-six couples resumed sexual activity after myocardial infarction; 24 (including 14 who tried and failed) did not. Concerns about inadequate sexual instructions, risk of sexual activity, sexual difficulties of the husband, change in sexual patterns, patient's symptoms during intercourse, and emotional relationship of the couples were demonstrated. Fear was not alleviated by information received, but was not important in preventing return to sexual activity; however, fear may have affected the frequency and quality of sexual activity. The need for more comprehensive counseling by physicians and nurses and for the wives to explore their sexual concerns became evident.

Validity of an activities of daily living questionnaire among older patients in the emergency department.

The objective of this study was to determine the validity of French and English versions of the Older American Resources and Services (OARS) activities of daily living (ADL) questionnaire using a premorbid reference period among older emergency department (ED) patients. A sample of 404 ED patients aged 65 and over participating in a study of functional decline was invited to participate in a clinical assessment shortly after their ED visit. The OARS ADL questionnaire was administered either to the patient or a proxy informant at the ED visit. The clinical assessment was conducted by a nurse, blind to the OARS score, using the Functional Autonomy Measurement System (SMAF). Disability scores for the OARS and SMAF were computed, based on the patient's premorbid status. Assessments were conducted in 213 patients (52.7%). The OARS summary scores, a total and an ordinal score, were highly correlated with the SMAF total disability score (Spearman's r of 0.80 and 0.79, respectively). Similar correlations were found for French and English versions. The OARS ADL questionnaire with a premorbid reference period appears to be valid when administered in the ED, both in French and English.

Detection of older people at increased risk of adverse health outcomes after an emergency visit: the ISAR screening tool.

OBJECTIVES: To develop a self-report screening tool to identify older people in the emergency department (ED) of a hospital at increased risk of adverse health outcomes, including: death, admission to a nursing home or long-term hospitalization, or a clinically significant decrease in functional status. DESIGN: Prospective (6-month) follow-up study of a cohort of ED patients aged 65 and older. SETTING: The EDs of four acute-care hospitals in Montreal, Quebec, Canada. PARTICIPANTS: Community-dwelling patients aged 65 and older who came to the EDs during the weekday shift over a 3-month recruitment period. Patients were excluded if they could not be interviewed either because of their medical condition or because of cognitive impairment and no other informant was available. MEASUREMENTS: Measures ascertained at the ED visit included: 27 self-report screening questions on social, physical, and mental risk factors; medical history; use of hospital services, medications, and alcohol; and the Older American Resources and Services (OARS) activities of daily living (ADL) scale. At follow-up, the OARS scale was readministered by telephone, and other adverse health outcomes were ascertained. RESULTS: Among 1673 patients who completed the follow-up measures, 488 (29.2%) had an adverse health outcome. Scale development and selection methods included logistic regression, receiver operating characteristic curves, and expert judgment. The proposed screening tool (ISAR) comprises six self-report questions on functional dependence (premorbid and acute change), recent hospitalization, impaired memory and vision, and polymedication. The tool performed well in the total cohort aged 65 and older, and in sub-groups defined by disposition (admitted or released from ED), language of questionnaire administration (French or English), information source (patient or other), and other characteristics. CONCLUSIONS: The ISAR is a short self-report questionnaire that can quickly identify older patients in the ED at increased risk of several adverse health outcomes and those with current disability.

Effect of physical training on insulin response to intravenous glucose in male peripubertal rats.

This study was undertaken to evaluate the effects of regular endurance-type exercise (i.e., swimming) on glucose tolerance and glucose-stimulated insulin response (GSIR) in 55- and 90-day-old peripubertal male rats. Intravenous glucose tolerance tests (0.5 g/kg) were done in four groups of male Sprague-Dawley rats: two groups of trained (TR; 55- and 90-day-old) and two groups of age- and weight-matched untrained (UNTR) rats. The UNTR rats were subjected to a continuous food restriction to maintain body weights equal to those of the TR rats. Rats were received in our laboratory after weaning at 21 days of age and were evaluated 48 h after the last exercise bout. No significant differences in body weights were found between TR and UNTR rats, at the age of either 55 or 90 days. A significant (P < 0.01) decrease in the mean integrated area under the glucose and insulin curves was observed in TR compared with UNTR groups in 55- as well as 90-day-old rats. These results indicate that exercise training in male rats improves the glucose tolerance and GSIR before and during puberty (21-90 days) independently of a reduction in body weight gain.

Effects of selective hepatic vagotomy on running endurance in rats.

The liver, through the afferent ways of the vagus hepatic nerve, may influence metabolic adaptations during exercise. This study assesses the functional significance of this hepatic innervation by determining the effect of a selective hepatic vagotomy (HV) on running endurance time during submaximal activity in rats subjected to an overnight 50% food restriction. The time to exhaustion was similar for the groups of HV and sham-operated (SHM) rats [66 +/- 15 vs. 64 +/- 21 (SD) min]. The HV group was associated with higher resting levels (P less than 0.05) of hepatic glycogen and plasma glucose. No significant differences were observed between HV and SHM rats at rest and after exercise for muscle glycogen, free fatty acids, insulin, glucagon, and lactate concentrations. These data indicate that if hepatic glucoreceptors do exist and contribute to the metabolic regulation of exercise, their functional significance is secondary to more important regulatory mechanisms.

Increased insulin suppression of plasma free fatty acid concentration in exercise-trained rats.

The effect of exercise training on the insulin suppression of plasma free fatty acid (FFA) concentrations was studied in unanesthetized rats with the hyperinsulinemic-euglycemic clamp technique. Seven rats trained (TR) for 3 h/day by continuous swimming during 8 wk were compared with 6 untrained (UT) body weight-matched rats. Both TR and UT rats were submitted to an exercise swimming session 18 h before the clamp. A smaller mean diameter of adipocytes sampled from the epididymal fat depot was measured in TR animals. The total quantity of glucose infused to maintain euglycemia was 2.2 times higher in TR than in UT animals. No significant differences in plasma insulin concentrations were found between the two groups throughout the experiment. Insulin infusions resulted in a 60% decrease of plasma FFA in TR rats (mean value: from 0.46 to 0.18 mM) compared with 27% in UT animals (mean value: from 0.45 to 0.33 mM). The data indicate a greater ability of insulin to suppress plasma FFA levels with exercise training, which suggests an increased antilipolytic action of insulin in adipocytes under this condition.

Effect of hepatic vagotomy on plasma catecholamines during exercise-induced hypoglycemia.

The existence of a hepatosympathetic reflex active during insulin-induced hypoglycemia has recently been reported. The purpose of the present investigation was to test the hypothesis that the liver, through the afferent innervation of the vagus nerve, contributes to plasma epinephrine and norepinephrine responses during exercise-induced hypoglycemia. Hepatic vagotomized and sham-operated rats were killed at rest or after 30, 60, and 120 min of running exercise (26 m/min, 0% grade). At the end of the 120-min exercise period, liver glycogen, glucose, and insulin levels measured in the portal and peripheral plasma were all significantly reduced (P < 0.05) while epinephrine and norepinephrine concentrations, beta-hydroxybutyrate, lactate, and portal and peripheral glucagon plasma levels were all significantly increased (P < 0.05). However, no significant differences were observed between hepatic vagotomized and sham-operated rats at rest and after exercise for the metabolic and hormonal responses. These results suggest that if a hepatosympathetic reflex is active during an exercise-induced hypoglycemia situation, then this contribution is probably hidden by more important regulatory mechanisms.

Combined effect of 2-deoxy-D-glucose and exercise on plasma catecholamine response.

2-Deoxy-D-glucose (2-DG) is a nonmetabolizable analogue of glucose that, by competitive inhibition of glucose utilization, produces a central neuroglucopenia and a peripheral hyperglycemia. This glucopenic agent was used to gain more insight into the combined effects of central glucopenia and exercise on plasma catecholamine response. This was carried out by comparing one group of exercising (26 m/min, 0% grade) rats injected with 2-DG (2-DG-EX; 250 mg/kg iv) with two control groups: one group of exercising rats injected with a saline solution (SAL-EX) and one group of resting rats injected with 2-DG (2-DG-RE). Significant (P less than 0.05) increases in blood glucose levels were observed 10 min after administration of 2-DG (7.2-13.8 and 7.3-12.4 mmol/l in 2-DG-EX and 2-DG-RE groups, respectively). These elevated blood glucose levels were maintained throughout the experiment in the 2-DG-RE condition but decreased in 2-DG-EX rats to levels observed in the SAL-EX group after 45 min of running (13.8-8.0 mmol/l). The combination of 2-DG-induced neuroglucopenia and exercise resulted in an additive response of norepinephrine (0.59 vs. 0.34 and 0.34 ng/ml; t = 12 min) and an amplified epinephrine response (1.4 vs. 0.37 and 0.31 ng/ml; t = 12 min) compared with the responses to each stimulus alone (2-DG-EX vs. 2-DG-RE and SAL-EX, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Portal glucose infusion increases hepatic glycogen deposition in conscious unrestrained rats.

It has been demonstrated in the conscious dog that portal glucose infusion creates a signal that increases net hepatic glucose uptake and hepatic glycogen deposition. Experiments leading to an understanding of the mechanism by which this change occurs will be facilitated if this finding can be reproduced in the rat. Rats weighing 275-300 g were implanted with four indwelling catheters (one in the portal vein, one in the left carotid artery, and two in the right jugular vein) that were externalized between the scapulae. The rats were studied in a conscious, unrestrained condition 7 days after surgery, following a 24-h fast. Each experiment consisted of a 30- to 60-min equilibration, a 30-min baseline, and a 120-min test period. In the test period, a pancreatic clamp was performed by using somatostatin, insulin, and glucagon. Glucose was given simultaneously either through the jugular vein to clamp the arterial blood level at 220 mg/dl (Pe low group) or at 250 mg/dl (Pe high group), or via the hepatic portal vein (Po group; 6 mg. kg(-1). min(-1)) and the jugular vein to clamp the arterial blood glucose level to 220 mg/dl. In the test period, the arterial plasma glucagon and insulin levels were not significantly different in the three groups (36 +/- 2, 33 +/- 2, and 30 +/- 2 pg/ml and 1.34 +/- 0.08, 1. 37 +/- 0.18, and 1.66 +/- 0.11 ng/ml in Po, Pe low, and Pe high groups, respectively). The arterial blood glucose levels during the test period were 224 +/- 4 mg/dl for Po, 220 +/- 3 for Pe low, and 255 +/- 2 for Pe high group. The liver glycogen content (micromol glucose/g liver) in the two Pe groups was not statistically different (51 +/- 7 and 65 +/- 8, respectively), whereas the glycogen level in the Po group was significantly greater (93 +/- 9, P < 0.05). Because portal glucose delivery also augments hepatic glycogen deposition in the rat, as it does in the dogs, mechanistic studies relating to its function can now be undertaken in this species.

Intracerebroventricular CRF inhibits cold restraint-induced c-fos expression in the dorsal motor nucleus of the vagus and gastric erosions in rats.

Acute exposure to cold-restraint induces vagal-dependent gastric erosions associated with activation of neurons in the dorsal motor nucleus of the vagus (DMN) in rats. The influence of intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF) (10 micrograms) on c-fos expression in the brain and gastric erosions induced by 3 h cold-restraint was investigated in conscious rats. In cold-restraint exposed rats, CRF injected i.c.v. inhibited gastric erosions and the number of Fos positive neurons in the DMN by 93 and 72%, respectively, while Fos labelling in the nucleus tractus solitarius (NTS) was increased by 5-fold compared with vehicle group. c-fos expression was also induced in the central amygdala by i.c.v. CRF, unlike the vehicle-injected group exposed to cold-restraint. c-fos expression induced by cold-restraint in the raphe pallidus (Rpa) and paraventricular nucleus of the hypothalamus was not altered by i.c.v. CRF. These data indicate that central CRF-induced gastric protection results from the inhibition of DMN neuronal activity enhanced by cold-restraint. CRF action on DMN neurons may be related to the increase in the NTS and central amygdala inputs leading to inhibition of DMN neurons rather than to the decrease in the excitatory input from the caudal raphe projections to the DMN.

Hepatic vagotomy does not alter plasma insulin response to a low dose injection of glucose.

It has been reported that insulin concentration is altered by a hepatic vagotomy following intraperitoneal glucose injection (0.3 g/kg) resulting in supraphysiological blood glucose concentrations. On the other hand, neural activity of the hepatic vagus nerve has been shown to be substantially reduced by lower doses (0.05 g/kg intraportal; 0.1 g/kg intravenous). The present study was conducted in order to examine the role of the hepatic vagus nerve in insulin response after intraperitoneal injections of 0.1 and 0.3 g/kg of glucose. Measurements were made 5 days after section of this branch. In a first experiment, arterial glucose and insulin concentrations were not affected by the hepatic vagotomy following injections of either 0.1 or 0.3 g/kg of glucose. The same finding was also found in a second experiment in which portal glucose and insulin levels were measured after injection of 0.1 g/kg of glucose. These results suggest that large changes in neural activity are needed for the hepatic vagus nerve to influence the insulin response.

Effect of hepatic portal injection of ouabain on the hepato-sympathoadrenal reflex.

The purpose of the present investigation was to evaluate the effects of an intraportal injection of ouabain (2 mg/kg), an inhibitor of the sodium-potassium pump, on plasma catecholamine response in unrestrained normally fed rats with and without an intact hepatic vagus nerve. Three groups of rats were submitted to two injection conditions each. Hepatic vagotomized (HV) rats were randomly injected with ouabain or saline (0.9%) in the portal vein. Sham-operated rats were either injected with ouabain or saline in the portal or jugular vein. Ouabain or saline were injected at 0 min and again at 20 min. Plasma catecholamines were measured before the first injection and 15 min after each injection. Blood glucose concentrations were significantly (p < 0.01) increased by the ouabain injection as compared with basal values and saline-injected groups. The hyperglycemic effect of ouabain was not affected by the hepatic vagotomy or the site of infusion. The injection of ouabain, either into the portal or the jugular vein and either after HV or the sham operation, resulted in a significant (p < 0.01) increase in epinephrine levels as compared with saline-infused rats. Plasma norepinephrine levels were significantly (p < 0.05) increased after the second intraportal injection of ouabain in both HV and sham-operated groups. However, the injection of ouabain into the jugular vein did not change the plasma norepinephrine levels. The latter observation indicates a specific action of ouabain in the liver on the sympathetic activity.

Return to the emergency department among elders: patterns and predictors.

OBJECTIVES: 1) To describe the pattern of return visits to the emergency department (ED) among elders over the six months following an index visit; 2) to identify the predictors of early return (within 30 days) and frequent return (three or more return visits in six months); and 3) to evaluate a newly developed screening tool for functional decline, Identification of Seniors At Risk (ISAR), with regard to its ability to predict return visits. METHODS: Subjects were patients aged 65 years or more who visited the EDs of four Canadian hospitals during the weekday shift over a three-month recruitment period. Excluded were patients who: could not be interviewed, due either to their medical conditions or to cognitive impairment, and no other informant was available; refused linkage of study data; or were admitted to hospital at the initial (index) visit. Measures made at the index ED visit included: 27 self-report screening questions on social, physical, and mental risk factors, medical history, use of hospital services, medications, and alcohol. Six of these questions comprised the ISAR scale. Return visits and diagnoses during the six months after the index visit were abstracted from the utilization database. RESULTS: Among 1,122 patients released from the ED, 492 (43.9%) made one or more return visits; 216 (19.3%) returned early and 84 (7.5%) returned frequently. Earlier returns were more likely than later returns to be for the same diagnosis (p = 0.003). Using logistic regression, hospitalization during the previous six months, feeling depressed, and certain diagnoses predicted both early and frequent returns. Also, a history of heart disease, having ever been married, and not drinking alcohol daily predicted early return; a history of diabetes, a recent ED visit, and lack of support predicted frequent use. CONCLUSIONS: In the first month after an ED visit, return rates are highest and are more likely to be for the same diagnosis. Both medical and social factors predict early and frequent returns to the ED; patients at increased risk of return can be quickly identified with a short, self-report questionnaire. The ISAR screening tool, developed to identify patients at increased risk of functional decline, can also identify patients who are more likely to return to the ED.