Elderly patients should receive all forms of medical treatment: a philosophical argument

The use of old age as a criterion for rationing in medicine seems initially appealing. This is because many of the criteria currently being used for deciding the distribution of funds depend on subjective judgements. Age, however, is objective and therefore negates the need for value judgements. It has been suggested that justice and fairness require that limited resources be directed at young patients, who have not had a chance to live their lives, rather than at elderly patients who have already lived most of theirs. It is the purpose of this article to bring forth evidence that elderly patients should be accorded medical treatment on equal basis as younger patients and that policies which deny elderly people treatment on the sole grounds of age, are both unfair and discriminatory and should therefore be resisted.     

The use of empiric clinical data in the evaluation of practice guidelines for unstable angina

OBJECTIVE: To determine the applicability to emergency department (ED) clinical practice of a nationally disseminated practice guideline on the disposition of patients with a diagnosis of unstable angina, and to determine the potential impact of the guideline on hospital admissions and demand for intensive care beds. DESIGN: Application of guideline criteria for ED disposition decisions to a validation sample derived from a prospective clinical trial. SETTING: Five hospitals, including 2 urban general teaching hospitals, 2 urban tertiary care university hospitals, and 1 suburban university-affiliated community hospital. PATIENTS: A consecutive sample of 457 patients who presented with symptoms suggestive of acute cardiac ischemia and who had "unstable angina" or "rule out unstable angina" diagnosed by ED physicians. Greater than 90% of eligible patients were enrolled in the clinical trial; follow-up data sufficient for assignment of a definitive diagnosis were obtained for 99% of subjects. MAIN OUTCOME MEASURES: Acute myocardial infarction and unstable angina, based on blind review of initial and follow-up clinical data, including cardiac enzyme levels and electrocardiograms. After completion of the trial, without knowledge of final diagnosis or outcome, the investigators classified patients into risk groups specified by the unstable angina guideline. RESULTS: Of subjects with an ED diagnosis of unstable angina, only 6% (n=28) met the guideline's criteria corresponding to low risk for adverse events and were therefore suitable for discharge directly to home. Fifty-four percent (n=247) met the intermediate-risk criteria; 40% (n=182) met the high-risk criteria and were identified as requiring admission to an intensive care unit. Actual ED disposition differed from guideline recommendations in 2 major areas: only 4% (1/28) of low-risk patients were discharged to home with outpatient follow-up, and only 40% (72/182) of high-risk patients were admitted to an intensive care unit. CONCLUSIONS: Although the guideline was intended to reduce hospitalization by identifying a low-risk group, the small size of this group among ED patients suggests that little reduction in hospitalization can be expected. Indeed, the guideline may increase demand for the limited number of intensive care beds to accommodate patients with unstable angina considered high-risk but currently placed elsewhere. These results emphasize the need to use empiric data from target clinical settings to assess the likely actual impact of guidelines on clinical care prior to national dissemination.     

Adhesion and aggregation of neutrophils in patients with unstable angina

The adherence and aggregation abilities of neutrophils (PMNs) were evaluated in thirty three patients with unstable angina, who were qualified for PTCA procedure. The control group consisted of forty one clinically healthy persons. The blood for investigations was obtained from coronary sinus and basilic vein just before the procedure, while in the control group from basilic vein only. The adherence of PMNs to plastic surface (rest and stimulated by PMA) was estimated in vitro according to Oez's et al. method by measuring optical density of generated formazan, whereas the aggregation of PMNs was evaluated using the leukergy test according to the method of Fleck in Berliner's and Aronson's modification. In patients with unstable angina statistically significant higher (p < 0.001) adherence of peripheral blood PMNs, compared with control groups was found (patients: rest-0.525 +/- 0.245, stimulated-0.839 +/- 0.419, control group: rest-0.260 +/- 0.129, stimulated-0.522 +/- 0.377). The aggregation of peripheral blood PMNs was significantly higher (p < 0.05) in the sick than in the control group (the sick-10.98 +/- 4.29%, controls-4.65 +/- 3.01%). No differences in investigated parameters of PMNs obtained from peripheral or coronary sinus blood were found.     

Coronary stenosis progression differs in patients with stable angina pectoris with and without a previous history of unstable angina

OBJECTIVES: To compare the evolution of stenoses responsible for acute coronary events with those not associated with acute coronary syndromes. METHODS AND RESULTS: We prospectively studied angiographic stenosis progression in 190 stable angina patients, with single vessel disease, who were awaiting non-urgent coronary angioplasty. Sixty four patients had a previous history of unstable angina (Group 1) and 126 patients had no history of unstable angina (Group 2). Culprit stenoses were classified as "complex' or "smooth'. At restudy, 8 +/- 4 months after the first angiogram, 12 of 63 culprit stenoses in Group 1 had progressed and seven of 125 in Group 2 (19% vs 6%, P = 0.0044). Thirteen of 68 complex culprit stenoses had progressed, compared with only 6 of 120 smooth culprit stenoses (19% vs 5%, P = 0.003). Coronary events occurred in 12 Group 1 patients and nine Group 2 patients (P = 0.02). CONCLUSIONS: In patients with stable angina, stenoses associated with previous episodes of unstable angina are more likely to progress than stenoses not associated with previous unstable angina. Unstable coronary atherosclerotic plaques, even those that have been clinically stable for more than 3 months, may retain the potential for rapid progression to total occlusion.     

Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina

BACKGROUND: We have previously reported aspirin failure in suppressing enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation during the acute phase of unstable angina. The recent discovery of a second prostaglandin H synthase (PGHS-2), inducible in response to inflammatory or mitogenic stimuli, prompted us to reexamine TXA2 biosynthesis in unstable angina as modified by two cyclooxygenase inhibitors differentially affecting PGHS-2 despite a comparable impact on platelet PGHS-1. METHODS AND RESULTS: We randomized 20 patients (15 men and 5 women aged 59+/-10 years) with unstable angina to short-term treatment with aspirin (320 mg/d) or indobufen (200 mg BID) and collected 6 to 18 consecutive urine samples. Urinary 11-dehydro-TXB2 was extracted and measured by a previously validated radioimmunoassay as a reflection of in vivo TXA2 biosynthesis. Metabolite excretion averaged 102 pg/mg creatinine (median value; n=76) in the aspirin group and 55 pg/mg creatinine (median value; n=99) in the indobufen group (P<.001). There were 16 samples (21%) with 11-dehydro-TXB2 excretion >200 pg/mg creatinine among patients treated with aspirin versus 6 such samples (6%) among those treated with indobufen (P<.001). In vitro and ex vivo studies in healthy subjects demonstrated the capacity of indobufen to largely suppress monocyte PGHS-2 activity at therapeutic plasma concentrations. In contrast, aspirin could only inhibit monocyte PGHS-2 transiently at very high concentrations. CONCLUSIONS: We conclude that in unstable angina, episodes of aspirin-insensitive TXA2 biosynthesis may reflect extraplatelet sources, possibly expressing the inducible PGHS in response to a local inflammatory milieu, and a selective PGHS-2 inhibitor would be an ideal tool to test the clinical relevance of this novel pathway of arachidonic acid metabolism in this setting.     

Moderate asthma in adults: diagnosis and management in general medical practice

Moderate asthma is a frequent disorder in general medicine. In 1990, the British Thoracic Society published their first guidelines on the management of asthma. Three years later, we have studied, using a questionnaire, the diagnosis and therapeutic criteria of moderate asthma used by general physicians, and comparing these to the guideline recommendations. Out of 46 physicians questioned in Bordeaux, 40 (87 per cent) agreed to participate in the study. Thirty two physicians (80 per cent) described as moderate an asthma which was mild according to the guidelines; eight physicians (20 per cent) described a moderate asthma according to the guidelines; twenty five (63 per cent) considered as severe a moderate asthma according to the recommendations, although eleven (28 per cent) considered it as moderate and four (10 per cent) did not give an opinion. In total, four (10 per cent) judged asthma severity according to the guidelines (Group R), twenty one (52 per cent) over-estimated the severity of moderate asthma (Group S), and fifteen (37 per cent) gave an inconsistent assessment (Group 1). Twenty six (65 per cent) prescribed an association of beta-2-agonists and inhaled corticosteroids for moderate asthma. Although most of the questioned physicians gave an appropriate treatment for moderate asthma treatment adapted to the severity of the situation, their therapeutic approach did not seem to be based upon the same criteria than that recommended in the guidelines.     

Trauma patients 75 years and older: long-term follow-up results justify aggressive management

BACKGROUND: Long-term survival rate and functional status after trauma for one of the fastest growing segments of the population, patients 75 years and older, is poorly documented. METHODS: Trauma patients 75 years and older who were discharged from our Level I trauma center between June 1988 and July 1992 (n = 279) were contacted by mail or phone. Public death records were used to identify patients who had died. A stepwise logistic regression analysis was performed to determine predictors of poor outcome (death within 6 months). Main outcome measures included mortality and self-assessed functional status. RESULTS: A minimum 4-year follow-up was obtained for 81% of the 279 study patients. The mean follow-up period was 5.4 +/- 1.1 years. Mean age at time of injury was 81 +/- 5 years (range, 75-101 years); mean Injury Severity Score was 9.4 +/- 7.7. At follow-up, 132 patients (47%) had died, 93 patients (33%) were contacted, and 54 patients (19%) could not be located. Twelve percent of patients survived less than 6 months after discharge. Poor survival was predicted by preexisting diseases (dementia, p = 0.001; hypertension, p = 0.02; and chronic obstructive pulmonary disease, p = 0.05) and not by age or severity of injury. The mean age of patients still living was 85 +/- 3.9 years (range, 79-99 years), and 77 of 93 patients were living in an independent setting (33 alone, 44 with spouse or family); of these, 57% reported no difficulties in performing 12 of 14 activities of daily living. CONCLUSION: Despite higher than expected mortality after discharge, aggressive management of trauma patients 75 years and older is justified by the favorable long-term outcome.     

Diagnosis and management of asthma: occupational health nurses'' awareness and use of national consensus practice guidelines

In 7 patients who received liver transplants, 12 plasma proteins were subjected to phenotype analysis in donor and recipient before and after transplantation. The plasma proteins analyzed were haptoglobin, transferrin, glycoprotein GC, alpha-1-antitrypsin, complement factor 3 (C3), orosomucoid 1, properdin factor B, complement factor 6, alpha-2-HS-glycoprotein (A2HS), plasminogen, factor B of coagulation factor XIII, and interalpha-trypsin-inhibitor (ITI). Classification was done with isoelectric focusing or agarose gel electrophoresis (C3). A change from recipient to donor type was observed for all systems with the exception of C3. This is the first time such data have been obtained for the A2HS and ITI systems. The time is indicated at which the recipient type disappeared and the donor type appeared. In addition to the expected phenotype changes from recipient to donor type, unexpected results were found in some systems. For instance, in 2 patients a mixed type was synthesized, or new phenotypes appeared. Possible explanations include blood transfusions, immunosuppressive therapy, extrahepatic sites of synthesis and disturbed transplant function. The usefulness of phenotype determination as a diagnostic criterion for transplant function is discussed.     

Activation of the antibacterial properties and neutrophil myeloperoxidase and acid phosphatase in patients with unstable angina pectoris

Neutrophils are very important in pathogenesis of ischemic disease. They take part in the biomorphology of thrombus and also in the damage of myocardium ischemia in a course of unstable angina pectoris. We evaluated the functional status of neutrophils in peripheral blood, by measurement of bactericidal activity and activity of granulocyte's enzymes: myeloperoxidase (MPO) and acid phosphatase in the patients with unstable angina pectoris. We studied a group of 43 people at the age from 34 to 74 years. The blood for investigation was obtained during the first five hours from the moment of hospitalization. The control group were 40 healthy people. The number of granulocytes was significantly higher in patients with unstable angina pectoris and granulocytes were metabolically activated which was shown in the bigger activity of granulocyte's enzymes like MPO and acid phosphatase than in the control group. The activation of neutrophils is developed by many factors in the course of unstable angina pectoris. They take part in the processes of thrombogenesis and thrombolysis and they are a very important origin for active oxygen metabolites, which are responsible for damage of myocardium ischemia.     

Differences between primary care physicians and cardiologists in management of congestive heart failure: relation to practice guidelines

OBJECTIVES: This study was designed to characterize physician practices in the management of congestive heart failure (CHF) and to determine whether these practices vary by specialty and how they relate to guideline recommendations. BACKGROUND: Congestive heart failure is responsible for considerable mortality, morbidity and health care resource utilization. Although there have been important advances in the diagnostic evaluation and treatment of CHF, little information is available on physician practices in this area. METHODS: We surveyed physicians concerning their management of patients with CHF. The results were analyzed in multivariate models to determine the relation of diagnostic and treatment approaches to physician specialty, time since training, board certification and volume of patients with CHF. Surveys were sent to a sample of 2,250 family and general practitioners (FP/GPs), internists and cardiologists. Responses were examined in relation to guidelines issued by the Agency for Health Care Policy and Research that had been released 9 months previously. RESULTS: Significant differences were found between physician groups with regard to each of the major guideline recommendations. For example, routine evaluation of left ventricular function, a point of emphasis in the guideline, is performed by 87% of cardiologists, but by only 77% of internists and 63% of FP/GPs (p < 0.001 between groups). Angiotensin-converting enzyme inhibitors were used by cardiologists, internists and FP/GPs in 80%, 71% and 60% of patients with mild to moderate CHF, respectively (p < 0.001 between groups). Larger differences were reported in the prescribed dosages of these drugs and their use in patients with renal dysfunction. CONCLUSIONS: Cardiologists report practices more in conformity with published guidelines for CHF than do internists and FP/GPs. Because of the large numbers of patients with CHF and their substantial mortality, morbidity and cost of care, these differences may have a major impact on outcomes and health care costs.     

The use of clinical practice guidelines (CPGs) to evaluate practice and control costs in ventriculoperitoneal shunt management

Radical resection of ductal adenocarcinoma of the pancreas affords the only realistic chance of cure. Despite some reports, in particular from Japan, suggesting an improvement in the long-term prognosis, this is true only in subgroups of selected patients. In actual fact, the overall long-term survival of resected patients is still below 10%. How meaningful is a more extended resection? The lack of randomized prospective trials involving a sufficient number of cases does not enable us to make any final conclusions. The only controlled data, recently reported by an Italian multicenter study, suggested that extended lymphadenectomy improved prognosis not in the whole population of resected patients, but only in a subgroup of patients with lymph node involvement. No definitive judgments can be made without further prospective controlled clinical trials involving a greater number of patients. The suspicion arises that surgery alone, even when extensive, may not be the best treatment for pancreatic ductal cancer.     

General practitioners' management of acute back pain: a survey of reported practice compared with clinical guidelines

OBJECTIVE: To compare general practitioners' reported management of acute back pain with 'evidence based' guidelines for its management. DESIGN: Confidential postal questionnaire. SETTING: One health district in the South and West region. SUBJECTS: 236 general practitioners; 166 (70%) responded. OUTCOME MEASURES: Examination routinely performed, 'danger' symptoms and signs warranting urgent referral, advice given, and satisfaction with management. RESULTS: A minority of general practitioners do not examine reflexes routinely (27%, 95% confidence interval 20% to 34%), and a majority do not examine routinely for muscle weakness or sensation. Although most would refer patients with danger signs, some would not seek urgent advice for saddle anaesthesia (6%, 3% to 11%), extensor plantar response (45%, 37% to 53%), or neurological signs at multiple levels (15%, 10% to 21%). A minority do not give advice about back exercises (42%, 34% to 49%), fitness (34%, 26% to 41%), or everyday activities. A minority performed manipulation (20%) or acupuncture (6%). One third rated their satisfaction with management of back pain as 4 out of 10 or less. CONCLUSIONS: The management of back pain by general practitioners does not match the guidelines, but there is little evidence from general practice for many of the recommendations, including routine examination, activity modification, educational advice, and back exercises. General practitioners need to be more aware of danger symptoms and of the benefits of early mobilisation and possibly of manipulation for persisting symptoms. Guidelines should reference each recommendation and discuss study methodology and the setting of evidence.     

Molecular biology in radiation therapy: the potential impact of recombinant technology on clinical practice

There is good evidence to believe that the most important lesion induced in deoxyribonucleic acid (DNA) by ionizing radiation is a double strand break. Two double strand breaks may interact and rejoin in three different ways. (a) To form a dicentric, which is a lethal event, and will lead to the death of the cell. (b) To form a symmetrical translocation, which may activate an oncogene, and result in, for example, a leukemia or lymphoma. (c) To result in a deletion, which may remove or inactivate a suppressor gene and result in, for example, a solid tumor. Genes identified in mammalian cells may be conveniently grouped into four families. Genes involved in the repair of radiation damage can greatly influence radiosensitivity. Molecular checkpoint genes hold damaged cells in G2 to check for the integrity of their chromosomes before allowing them to proceed into mitosis; consequently, an inactivated checkpoint gene can also result in increased radiosensitivity. Activated oncogenes are associated with only a small proportion of human cancers, and tend to be found more commonly in leukemias and lymphomas and less frequently with solid tumors. A reciprocal translocation is the most likely mechanism by which radiation may activate an oncogene. An inactivated or deleted suppressor gene is commonly associated with a wide range of human cancers. It is becoming increasingly evident that many common cancers do not arise randomly in the population, but that subgroups of individuals are particularly susceptible. The challenge of recombinant technology is that in the near future it may well be possible to determine at birth the susceptibilities of a given individual by identifying mutations in key genes. This is the revolution and challenge we face in the treatment of cancer.     

Comparison of dobutamine electrocardiographic stress test and exercise test in two different groups of patients with unstable angina

DNA vectors expressing an antigen derived from a pathogen or a cancerous cell have been shown, after inoculation into experimental animals, to trigger de novo synthesis of foreign proteins, which induce an immune response. This immune response can be modulated by coinoculation of vectors encoding either cytokines or costimulatory molecules. A variety of cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-2, IL-4, IL-12 and IFN-gamma, as well as the costimulatory molecule B7.1, have been tested to date for their ability to amplify the immune response to genetic vaccines. Although the results obtained thus far clearly show that coadministration of vectors expressing immunomodulatory molecules, such as cytokines, may increase the efficacy of genetic vaccines, this approach is currently considered unsuitable for use in human patients due to the potential side effects of persistent cytokine expression.     

Angioscopic predictors of early adverse outcome after coronary angioplasty in patients with unstable angina and non-Q-wave myocardial infarction

BACKGROUND: Clinical and angiographic criteria have a limited ability to predict adverse outcome in patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA). We investigated whether the use of angioscopy can improve prediction of early adverse outcome after PTCA. METHODS AND RESULTS: Angioscopic characterization of the culprit lesion was performed before PTCA in 32 patients with unstable angina and 10 with non-Q-wave infarction. Seven patients (17%) had an adverse outcome (myocardial infarction, repeat PTCA, or need for coronary artery bypass graft surgery) within 24 hours after PTCA. Six of 18 patients with a yellow culprit lesion had an adverse outcome compared with 1 of 24 in whom the culprit lesion was white (P = .03). Six of 20 patients with plaque disruption suffered an adverse outcome compared with 1 of 22 with nondisrupted plaques (P = .04). Six of 17 patients with intraluminal thrombus had an adverse outcome, whereas only 1 of 25 patients without thrombus suffered an adverse outcome (P = .01). Yellow color, disruption, and thrombus at the culprit lesion site were associated with an eightfold increase in risk of adverse outcome after PTCA. The prediction of PTCA outcome based on characteristics of the plaque that were identifiable by angioscopy was superior to that estimated by the use of angiographic variables. CONCLUSIONS: In patients with unstable angina and non-Q-wave infarction, angioscopic features of disruption, yellow color, or thrombus at the culprit lesion site can identify patients at high risk of early adverse outcome after PTCA. Angioscopy was superior to angiography for prediction of PTCA outcome.     

Mechanisms and medical management of patients with atrial flutter

Type I atrial flutter is due to reentrant excitation, principally in the right atrium. The standard ECG remains the cornerstone for its clinical diagnosis. Acute treatment should be directed at control of the ventricular response rate and, if possible, restoration of sinus rhythm. Radiofrequency catheter ablation therapy provides the best hope of cure, although atrial fibrillation may subsequently occur after an ostensibly successful ablative procedure. Alternatively, antiarrhythmic drug therapy to suppress recurrent atrial flutter episodes may be useful, recognizing that occasional recurrences are common despite therapy. Radiofrequency ablation of the His bundle ablation with placement of an appropriate pacemaker system may be useful in selected patients.     

Improved risk stratification in unstable angina: identification of patients at low risk for in-hospital cardiac events by admission echocardiography

BACKGROUND: Current protocols for risk stratification of patients with acute chest pain syndromes rely on clinical parameters and are oriented toward identification of patients at high risk for adverse cardiac events; however, this paradigm for risk stratification does not adequately address the observation that adverse cardiac events are relatively uncommon in this population. In an era of cost containment, consideration also should be given to identification of patients at low risk for adverse cardiac events, who may be safely discharged without expensive inpatient hospitalization. HYPOTHESIS: The purpose of this study was to develop echocardiographic predictors that identify unstable angina patients at low risk for adverse cardiac events and that discriminate between low- and high-risk patients. METHODS: The predictive accuracy of retrospectively determined echocardiographic predictors were compared in a population-based sample of 66 consecutive unstable angina patients undergoing echocardiography within 24 h of admission. RESULTS: Echocardiographic predictors of adverse events included wall motion score index > or = 0.2, ejection fraction < or = 40%, and mitral regurgitation severity > 2. One or more echocardiographic predictors of adverse events were present in 32 patients (48%). A composite echocardiographic predictor of adverse events was specific, had a high positive predictive value for the identification of high-risk patients, and discriminated between unstable angina patients at high and low risk for adverse cardiac events. CONCLUSION: Echocardiographic predictors of adverse events are specific and discriminate between unstable angina patients at high and low risk for adverse cardiac events.     

Anti-ischemic and anti-anginal effects of thoracic epidural anesthesia versus those of conventional medical therapy in the treatment of severe refractory unstable angina pectoris

BACKGROUND: Cardiac sympathetic blockade by thoracic epidural anesthesia (TEA) dilates stenotic coronary arteries and has been used to control pain in patients with unstable angina. The aim of the present study was to evaluate the potential anti-ischemic effects of cardiac sympathetic blockade by TEA in severe, refractory, unstable angina. METHODS AND RESULTS: Forty patients with unstable angina refractory to standard anti-anginal therapy were randomized to receive either continuous epidural infusion of bupivacaine (TEA, Th1 to Th5) or to standard anti-anginal therapy including beta-blockers, calcium antagonists, aspirin, heparin, and nitroglycerin infusion (control group). The primary end points were number of anginal attacks and severity of myocardial ischemia assessed by 48-hour ambulatory Holter monitoring. The incidence of myocardial ischemia was lower in the TEA group (22% versus 61%; P<.05). The number of ischemic episodes per patient was 1.0+/-0.6 in the TEA group and 3.6+/-0.9 in the control group (P<.05). The episode duration per patient was 4.1+/-2.5 minutes and 19.7+/-6.2 minutes in the TEA and the control groups, respectively (P<.05). The mean area-under-the-ST-time-curve was 6.8+/-4.3 and 32.2+/-14.3 (mm-min) in the TEA and the control groups, respectively (P<.05). Fifteen anginal attacks were recorded in the control group and one attack in the TEA group (0.83+/-0.21 versus 0.06+/-0.06/patient, respectively, P<.01). CONCLUSIONS: The anti-ischemic and anti-anginal effects of continuous TEA are superior to those of conventional therapy in the treatment of refractory unstable angina.