Determinants of disability in older coronary patients

Background Patient-reported physical function is a major component of disability determinations and an important contributor to health-related quality of life. Prior studies of coronary disability have shown a surprisingly poor correlation between real-life activity profile and exercise capacity measured on the treadmill. The goal of the current investigation was to evaluate the relative importance of medical factors, sex, fitness-related measures, and psychologic factors as determinants of patient-reported physical function score in older persons with established coronary heart disease (CHD). Methods Determinants of disability were studied in 51 community-dwelling patients >65 years old (71 ± 5 years, range 65-83 years) with established chronic CHD. Patient-reported physical function score (scaled 0-100) was measured by the Medical Outcomes Study Short Form physical function section. Independent variables included clinical and demographic data, treadmill testing, rest and exercise echocardiography, measures of body composition, strength, aerobic fitness, and a depression score. Results Patients with a diagnosis of myocardial infarction had a lower physical function score than did patients with other CHD diagnoses (68 ± 19 vs 82 ± 22, P < .05). Univariate predictors of patient-reported physical function score included peak aerobic capacity (R = 0.62), treadmill test duration (R = 0.61), depression score (R = -0.60), handgrip strength (R = 0.42), and comorbidity score (R = -0.39). Peak aerobic capacity (R² = 0.38) and depression score (cumulative R² = 0.60) were the best independent predictors of physical function. Women had lower physical function scores than men (64 ± 22 vs 78 ± 20, P < .05) despite a similar age, diagnostic distribution, depression score, and comorbidity score. Resting left ventricular ejection fraction was not a predictor of physical function score. Conclusions Peak aerobic capacity and depression score were the best independent predictors of patient-reported physical function score in older coronary patients. These data focus on the potential for exercise training and treatment of mental depression to prevent and treat coronary disability in older coronary patients. (Am Heart J 2002;143:151-6.)     

Cost–utility analysis of an advanced pressure ulcer management protocol followed by trained wound,ostomy, and continence nurses

The high prevalence of severe pressure ulcers (PUs) is an important issue that requires to be highlighted in Japan. In a previous study, we devised an advanced PU management protocol to enable early detection of and intervention for deep tissue injury and critical colonization. This protocol was effective for preventing more severe PUs. The present study aimed to compare the cost‐effectiveness of the care provided using an advanced PU management protocol, from a medical provider's perspective, implemented by trained wound, ostomy, and continence nurses (WOCNs), with that of conventional care provided by a control group of WOCNs. A Markov model was constructed for a 1‐year time horizon to determine the incremental cost‐effectiveness ratio of advanced PU management compared with conventional care. The number of quality‐adjusted life‐years gained, and the cost in Japanese yen (¥) ($US1 = ¥120; 2015) was used as the outcome. Model inputs for clinical probabilities and related costs were based on our previous clinical trial results. Univariate sensitivity analyses were performed. Furthermore, a Bayesian multivariate probability sensitivity analysis was performed using Monte Carlo simulations with advanced PU management. Two different models were created for initial cohort distribution. For both models, the expected effectiveness for the intervention group using advanced PU management techniques was high, with a low expected cost value. The sensitivity analyses suggested that the results were robust. Intervention by WOCNs using advanced PU management techniques was more effective and cost‐effective than conventional care.     

What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P: = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: = NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P: values ranging between 0.01-0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P: < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.     

Target-induced death by apoptosis in human lymphokine-activated natural killer cells

Activated human natural killer (NK) cells undergo rapid apoptotic cell death after ligand binding to the Fc receptor (CD16). We examined whether human NK cells die after engagement in cytolytic functions. Peripheral blood NK cells, with and without prior activation in vitro with interleukin-2 (IL-2), were tested for the occurrence of cell death after incubation with K562, the prototype NK-sensitive target cell. A proportion (15.2%) of NK cells that were stimulated for 3 days with IL- 2 and then incubated for 4 hours with K562 cells showed rapid cell death, but NK cells not stimulated with IL-2 did not. This cell death was found to involve nuclear condensation and fragmentation and DNA cleavage, all of which are characteristic of apoptosis. These data indicate that a proportion of activated human NK cells undergo apoptosis as they engage in target cell lysis. Target-induced NK cell death may represent an important mechanism for regulation of inflammatory processes involving NK cells.     

Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.     

Viscoelastic properties of bovine articular cartilage attached to subchondral bone at high frequencies

Background  

Articular cartilage is a viscoelastic material, but its exact behaviour under the full range of physiological loading frequencies is unknown. The objective of this study was to measure the viscoelastic properties of bovine articular cartilage at loading frequencies of up to 92 Hz.     

When "no" might not quite mean "no"; the importance of informed and meaningful non-consent: results from a survey of individuals refusing participation in a health-related research project

Background  

Low participation rates can lead to sampling bias, delays in completion and increased costs. Strategies to improve participation rates should address reasons for non-participation. However, most empirical research has focused on participants' motives rather than the reasons why non-participants refuse to take part. In this study we investigated the reasons why older people choose not to participate in a research project.     

Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?

Following the withdrawal of ephedrine from the dietary supplement marketplace sales of products containing Citrus aurantium (CA) (bitter orange) for weight loss are believed to have increased dramatically. CA contains a number of constituents speculated to lead to weight loss, of which the most frequently cited constituent is synephrine. Concerns have been raised about the safety of products containing synephrine. To develop an adequate basis for clinical and public health recommendations, it is necessary to understand the nature of the synephrine alkaloids in CA. There are six possible isomers of synephrine (para, meta, ortho; and for each a d or l form). Some authors have stated that CA contains only p-synephrine, whereas other authors have stated that CA contains m-synephrine. This is an important distinction because the two molecules have different pharmacologic properties, which may differentially affect safety and efficacy. We are unable to identify published data that explicitly show whether CA contains p-synephrine, m-synephrine, or both. In this brief report, we show that at least one product purportedly containing synephrine alkaloids from CA contains both p-synephrine and m-synephrine. We believe this justifies further investigation into which synephrine alkaloids are present in CA and products purportedly containing synephrine alkaloids from CA and the relative quantities of each of the different isomers.     

Sarcopenia and muscle function during menopause and hormone-replacement therapy

Menopause and the loss of estrogen trigger a deleterious cascade of metabolic and cardiovascular events. Recent data suggest that the menopause transition is associated with changes in body composition that promote a loss of fat-free mass and potentially a decline in skeletal muscle mass that may be related to a decline in energy expenditure, a loss of muscular strength and a decline in physical activity. The mechanisms underlying changes in ovarian function and its influence on skeletal muscle mass, however, are unknown. This brief review examines the impact of the menopause transition on body composition with a particular emphasis on menopause-associated sarcopenia. We also consider the possibility that hormone-replacement may be an effective intervention to offset these changes.