Therapeutic Interventions for Frail Elderly Patients: Part I. Published Randomized Trials

The body of literature for frailty as a prognostic marker continues to grow, yet the evidence for frailty as a therapeutic target is less well defined. In the setting of cardiovascular disease, the prevalence of frailty is elevated and its impact on mortality and major morbidity is substantial. Therapeutic interventions aimed at improving frailty may impart gains in functional status and survival. Randomized clinical trials that tested one or more therapeutic interventions in a population of frail older adults were reviewed. The interventions studied were exercise training in 13 trials, nutritional supplementation in 4 trials, combined exercise plus nutritional supplementation in 7 trials, pharmaceutical agents in 8 trials, multi-dimensional programs in 5 trials, and home-based services in 1 trial. The main findings of these trials are explored along with a discussion of their relative merits and limitations.     

A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO₂), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO₂ (7,319), VE/VCO₂ slope (5,044), EOV (1,617), and OUES (584). Peak VO₂, the VE/VCO₂ slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO₂ and the VE/VCO₂ slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.     

Atypical simple bone cysts of the jaws. II: A possible association with benign fibro-osseous (cemental) lesions of the jaws

Four cases are described of simple bone cysts of the mandible arising concurrently with benign fibro-osseous (cemental) lesions. Previous reports of such findings, and a possible relationship to the so-called 'cementoma' of the long bones, are considered. The relevance of this to the aetiology is addressed, and it is suggested that at least some cases diagnosed as simple bone cysts are closely related to the fibro-osseous lesions.     

Electrically-induced, nerve-mediated relaxation of rabbit urethra involves nitric oxide.

Isolated smooth muscle preparations from the rabbit urethra precontracted with noradrenaline (10(-5) M), endothelin (10(-7) M), or arginine vasopressin (10(-7) M) responded to electrical field stimulation by frequency-dependent non-adrenergic, non-cholinergic relaxations, which could be blocked by tetrodotoxin (10(-6) M). Relaxation was more pronounced in preparations precontracted by endothelin than by noradrenaline or arginine vasopressin. The electrically induced relaxations were reduced in a concentration-dependent manner by pretreatment for 30 minutes with NG-nitro-L-arginine (10(-6) to 10(-4) M) and NG-monomethyl-L-arginine (10(-5) to 10(-4) M). At the highest concentration of NG-nitro-L-arginine used (10(-4) M), relaxation was abolished and/or changed into a contraction. The effect of NG-nitro-L-arginine was reversible. NG-nitro-D-arginine had no effect. Pretreatment for 30 minutes with L-arginine (10(-3) M) slightly, but significantly, enhanced the maximum relaxation to field stimulation in noradrenaline-precontracted preparations. L-arginine pretreatment also prevented the effects of low, but not high, concentrations of NG-nitro-L-arginine. In contrast, D-arginine had no effect. Electrically induced relaxations were not significantly affected by methylene blue (10(-5) M) or superoxide dismutase (20 U/ml). Addition of nitric oxide (present in acidified solution of NaNO2) caused transient and concentration-dependent relaxations in preparations precontracted by noradrenaline. At the maximum concentration used (10(-3) M), the relaxant response averaged 67% of the tension induced by noradrenaline. Nitric-oxide-induced relaxations were not affected by NG-nitro-L-arginine or L-arginine, but were significantly inhibited by methylene blue. In preliminary experiments, effects similar to those found in rabbit urethra were also observed in isolated urethral preparations obtained from three patients. It is suggested that in the urethra, nitric oxide is involved in the mediation of relaxation evoked by electrical stimulation of nerves.     

The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's breast cancer patients.

BACKGROUND: The 1995 Calman-Hine plan outlined radical reform of the UK's cancer services with the aim of improving outcomes and reducing inequalities in National Health Service cancer care. Its main recommendation was to concentrate care into the hands of site-specialist multidisciplinary teams. This study aimed to determine whether these teams improved processes and outcomes of care for breast cancer patients. PATIENTS AND METHODS: All patients diagnosed and treated with breast cancer in the Yorkshire region of the UK from 1995 to 2000 were identified within the Northern and Yorkshire Cancer Registry and Information Service database. Changes in the use of breast-conserving surgery, adjuvant radiotherapy following breast-conserving surgery and 5-year survival were assessed among these patients in relation to their managing breast cancer team's degree of adherence to the manual of cancer service standards (which outlines the specification of the 'ideal' breast cancer team) and the extent of site specialisation of each team's surgeons. RESULTS: Variation was observed in the extent to which the breast cancer teams in Yorkshire had conformed to the Calman-Hine recommendations. Increases in adherence to the recommendations in the manual of cancer service standards were associated with a reduction in the use of breast-conserving surgery [odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.70-0.98, P < 0.01]. Increases in both surgical specialisation (OR = 1.23, 95% CI = 1.00-1.55, P = 0.06) and adherence to the manual of cancer service standards (OR = 1.22, 95% CI = 0.97-1.52, P = 0.05) were associated with the increased use of radiotherapy following breast-conserving surgery. There was a trend towards improved 5-year survival (hazard ratio = 0.93, 95% CI = 0.86-1.01, P = 0.10) in relation to increasing surgical site specialisation. All these effects were present after adjustment for the casemix factors of age, stage of disease, socio-economic background and year of diagnosis. CONCLUSIONS: The extent of implementation of the Calman-Hine report has been variable and, on the basis of limited clinical and organisational information available, its recommendations appear to be associated with improvements in processes and outcomes of care for breast cancer patients.