The dynamics of circulation are regulated by numerous mechanisms. One of the many factors that can alter hemeostasis is blood volume, the amount of blood that fills and distends the cardiovascular system. Measuring blood volume serves to establish a possible cause and effect relationship between disorders of circulation and blood volume (persistent hypotension, poor tissue perfusion, hypertension and circulatory overload).1,2
Measuring blood volume has diagnostic applications—to differentiate between relative and true blood disorders (relative anemia due to expansion of plasma volume, relative polycythemia resulting from dehydration and hemoconcentration).
A 29-year-old woman was admitted for removal of a benign thyroid nodule. Her hematocrit level was 32% and hemoglobin value 9.8 gm/100 cc. She related a history of anemia being treated for the past two years. Blood volume measurement showed a normal red blood cell (RBC) volume for her weight and a marked increase in plasma volume.
The information obtained from
Elizabeth Shepard's H can be read and appreciated on many levels. An epistolary novel, it chronicles the mental condition and progress of a 12-year-old boy. The letters that comprise the novel are written by the principal characters, primarily parents, summer camp personnel, peers, the boy's sister, and his psychiatrist. A fascinating correspondence between the child and his imaginary friend (the friend manifest in a stuffed toy shaped like an H) reveals much about the boy's inner life.The author makes compelling use of the epistolary form. That it is somewhat disjointed actually serves to pique the reader's curiosity. I found myself reading faster and more intently as the novel progressed.H would be a very enjoyable read for anyone who likes psychologically based novels and for those with professional training and experience working with disturbed children. I continually found myself formulating a differential diagnosis and then reformulating it with each.
Disease management is an approach to patient care that emphasizes coordinated, comprehensive care along the continuum of disease and across health care delivery systems. Evidence-based medicine is an approach to practice and teaching that integrates pathophysiological rationale, caregiver experience, and patient preferences with valid and current clinical research evidence. Using diabetes mellitus as an example, we describe the importance of evidence-based medicine to the development of disease management programs. We present a method for developing and implementing evidence-based clinical guidelines, clinical pathways, and algorithms and describe the creation of systems to measure and report processes and outcomes that could drive quality improvement in diabetes care. Multidisciplinary teams are ideally suited to develop, lead, and implement evidence-based disease management programs, since they play an essential role in the preventive, diagnostic, and therapeutic decisions for patients with diabetes throughout the course of their disease.
To the Editor.
—Drs Gill and Feinstein1 suggest that studies measuring quality of life should provide an explicit conceptual framework for this measurement and should take the respondent's perspective into account. Both proposals seem constructive. However, these authors fail to apply the sound principles they advocate to their own measurement of the "quality of measurements." For instance, just as health status should not be equated with quality of life, the face validity of an instrument should not be confused with its overall quality. The disregard of psychometric properties2-4 in defining an instrument's quality is particularly worrisome, because an instrument that has excellent face validity can be worthless if it does not satisfy minimum standards of reliability, construct validity, or sensitivity to change.Consider the "quality" of a single-item instrument consisting of the time-honored question "how are you?" to which the response is left open-ended. To fulfill the criteria
Hypertension that goes undetected or untreated is a major cause of mortality and morbidity. However, most patients with hypertension can be effectively treated, their blood pressure lowered, and their risk of death and adverse effects reduced. Hypertension poses a major challenge to the medical profession and offers physicians a unique opportunity to practice preventive medicine. Therefore, all physicians should give careful attention to the report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure (p 255).
Each member of the commission represents a major organization or agency, and the report has the endorsement of these organizations and agencies. Although the report was sponsored by the National Heart and Lung Institute, it is not a government directive on how to practice medicine. The report should be viewed as a useful guide and not as a rigid directive on how to manage high blood pressure. One should
To the Editor.
—The article by Drs Gill and Feinstein1 and the Commentary by Drs Guyatt and Cook2 concerning the relevance of qualitative assessments as appropriate outcome measures are timely. In a metaphorical sense it is like a psychiatrist trying to determine whether a patient is clinically depressed by asking how he or she feels and then deciding whether the answer reflects the patient's affect or mood or, possibly, both.Second, medicine as an art may derive some useful direction in planning the overall medical management of a patient from well-defined quality-of-life measures, but for medicine as a science, such measures are not rigorous enough. Qualitative measures, or functional measures based on subjective situational evaluations, are too variable to be used in comparative efficacy studies. This is not to discount the value of including a patient's outlook on life when determining which treatment is most suitable, given treatment
Several factors are of decisive importance for the individual's capacity to perform physical work: (1) energy output or motor power (aerobic energy yield and anaerobic energy yield); (2) neuromuscular function (strength and technique); and (3) psychological factors (tactics and motivation).
Depending on the nature of the demand of job, sport event, or leisure time activity, one, two, or all factors are of great importance. It is therefore impossible to present one formula that takes into account all aspects of the individual's performance capacity. Natural endowment probably has the dominating influence on the physical work capacity but by training and practice any of the factors may be improved.
Figure 1 presents an analysis of how the energy demand is covered during exhausting exercise; an experiment on a bicycle ergometer with a work load of 350 w is illustrated at left. From a mechanical efficiency of 22% the energy demand can be
I used to struggle with keeping track of all of those multicenter cardiovascular disease trials. With their long titles sprawling across the front pages of high-impact journals, I’ve been admittedly guilty of spending just as much time marveling at their witty acronym aliases as I did their outcomes. Eventually I would get around to the data—usually in an effort to answer some clinical query or to gain confidence in a medical decision. I’d try my best to commit them to memory, searching for applicability to my patient population and hoping that some scientist’s hard work in the garden would be appropriate to be served at my urban hospital table.
To the Editor.—
Poor Dr. Hoffman. He continues to be maligned and misinterpreted. The article by Elveback et al (211:69, 1970) purports to show the total unacceptability of Hoffman's method of estimating maximum limits for the "normal" range. My reading of the data leads me to the opposite conclusion.The authors make much of the difference between their normal range for serum calcium of 8.9 to 10.1 and Hoffman's estimate of 8.7 to 10.3. I cannot accept this very small difference as proof of the invalidity of Hoffman's method. The authors' normal range is based on 576 measurements on a selected population, whereas Hoffman's estimate was based on 4,719 consecutive determinations. Futhermore, the authors mislead the reader when they suggest that the difference between 10.1 and 10.3 or 8.7 and 8.9 is of practical significance. In 1970 (let alone in 1964) laboratories cannot distinguish between a calcium level of
To the Editor.—
I strongly endorse the view of Hoffman et al1 that "orders including terms such as 'amps,' 'pills,' 'vials,' or 'tab' without further specification should neither be written by physicians nor accepted by nurses. More precise doses of a solution of given concentration must be stated." However, the authors do not go quite far enough. Hoffman et al state in case 1 that the patient "was treated with... normal saline." However, "a normal solution is one having a concentration equivalent to a gram-equivalent of solute per liter."2 Thus, a normal solution of sodium chloride contains 58.45 g/L. This is hardly the 9 g/L meant by the author as "normal saline." It would be nice to see the latter term dropped from the medical literature and replaced with "0.9% sodium chloride solution."
When on the morning of the new year a local telecaster smilingly announces the name, the hour, and the place of birth of the year's first newborn, we can be reasonably confident that the information is correct. After all, it is based on data obtained from all the area hospitals. Our certainty, however, is not absolute. Occasionally a birth that occurs in an obscure rooming house, an out-of-the-way cabin, or a taxicab remains unreported. The announced firstborn may not be a first after all.
How much greater must our uncertainty be when a medical author reports a "first"—be it disease, syndrome, or physical sign. The data base for such a claim to priority must of necessity extend to the ends of the globe and the beginnings of medical writing. An appropriately extensive search of the literature is an undertaking that borders on the impossible. The bibliographic sources for such a
To the Editor.
—In the introduction to their Commentary, Drs Guyatt and Cook1 reveal the powerful prejudices that have resulted in centuries of devaluation of the lives of persons with physical disabilities. While giving lip service to "Gill and Feinstein's2 message that people's values differ," Guyatt and Cook identify paraplegia as the epitome of a situation in which quality of life "would be rated low."Under the cloak of platitudes about the person who "transcends" loss to find "new meaning in life," the authors reinforce negative societal stereotypes about the "suffering," "calamity," and "tragedy" that they believe is the lot of the individual who is "paraplegic or even quadriplegic."Thus do they underscore the absolute necessity for critical appraisals of quality-of-life measurements, as advocated by Gill and Feinstein.2 For until the insidious assumption is challenged that the quality of life of an individual with a disability is
Worth the attention of all physicians is the document presented to the United Nations on November 17, 1960, by Sir Julian Huxley, distinguished British biologist, and Mr. Cass Canfield, publisher. They did this on behalf of more than 200 scientists, statesmen, and humanitarians from many countries who urged the United Nations to "take the lead in establishing and implementing a policy designed to limit population growth the world over—in order that human beings everywhere may grow on a qualitative rather than on a merely quantitative level, and in order that they may be assured of the opportunity to develop their highest capacities, and to enjoy individual freedom, the advantages of education and public health, privacy, abundance, security, and the beauty and wonder of the world."
This forthright petition followed reiteration of some ecological facts, glaringly clear to unprejudiced minds. These demonstrate, as the statement puts it, that "unless a favorable balance
To the Editor.—
Dr. Keating met his death in an automobile accident before our paper was published. I have consulted with his colleagues, Dr. Lynwood Smith and others (Sections of Internal Medicine), and Dr. Don Jones and Dr. John McCall (Section of Biochemistry). We would like to make the following points concerning Dr. Gambino's comments.First, it is apparent from our paper that we were not estimating "maximum limits for the normal range" but rather the 2.5 and 97.5 percentage points of the distribution in healthy persons.Next, Dr. Keating's colleagues support his statement concerning the clinical significance of the falsenegative values on serum calcium in the range from 10.1 to 10.3. As reported from here and elsewhere,1-3 borderline hypercalcemia with symptomatic hyperparathyroidism occurs in a small but significant percentage of patients demonstrated to have the disease. Its recognition depends upon an accurately established normal range using the refined
No one was more surprised than the physician himself. The drawing was unmistakable. It showed the artist—a 7-year-old girl—on the examining table. Her older sister was seated nearby in a chair, as was her mother, cradling her baby sister. The doctor sat staring at the computer, his back to the patient—and everyone else. All were smiling. The picture was carefully drawn with beautiful colors and details, and you couldn't miss the message. When he saw the drawing, the physician wrote a caption for it: “The economic stimulus bill has directed $20 billion to health care information technology, largely funding electronic medical record incentives. I wonder how much this technology will really cost?”
To the Editor.—
I should like to comment on the LETTER of McCrae (216:679,1971). It is true that man has certain basic inherited patterns of behavior that have come down to him from his subhuman animal ancestry. Evolutionary theory and the common observations of behavioral science confirm this. These basic behavioral patterns include self preservation, species preservation (sexual behavior), territory formation, and group formation with status-seeking behavior. Another basic pattern, according to Lorenz, is aggressive behavior.Analysis of these behavior patterns shows that the self and species preservation are at the roots of these patterns. In short, man's behavior is aimed at preserving himself and his species; everything else hangs on this. And, indeed, these two are not unrelated, since reproduction by fission can be viewed as a means of self-preservation.Very early in evolutionary history animals began to become diversified on the basis of number of offspring produced
Most physicians tend to think of computers in medicine as having a "far out into the wide blue yonder" aspect. To some this is stimulating; however, many tend to resent things which are hard to understand and the normal reaction is one of conservatism. The purpose of this symposium has been to provide a basic understanding of computers, what they are and how they work. As understanding and experience improve, physicians can move from conservatism to active use of these splendid instruments in the practice of medicine.Computers in Medicine
Computers are not monsters; they have no black magic; they do not "think." It should be apparent that a computer is in fact incredibly stupid, doing only what it has been directed to do. However, when properly directed or programmed, a computer can carry out, in seconds or less and without errors or getting tired, extremely difficult computational tasks which
My lords, the happenings of this case are, to wit: Robert the Surgeon, of Friday Street, rented a house and tavern to one Symon, in St. Martin's parish, there to conduct his trade. Said Symon had a servant, Roger from Westminster, who, in the night following St. Nicholas's Day, December sixth, in the fifth year of King Edward, 1277, did most foully murder his master. And the manner of the murder was thus: Roger cut the throat of the said Symon, asleep in his bed, and did cut off the head entirely from the body, after which he dragged the body to a dark and secret place, a bin between two walls in the house, wherein coals were wont to be kept, such place being long, and not quite two feet wide. The next day, dissembling, the said Roger did put out the bench in front of the tavern and
To the Editor.—
The attempt by Dr. Elveback and her colleagues to exorcise the ghost of Gauss (211:69-75, 1970), calls for some comment.As they state, Gauss was primarily concerned with the theory of errors, but the components in an error distribution are analogous to those in any other type of measurement. If I measure the length of a table with a ruler I should get a single answer; however, the lengths of the table and the ruler vary with temperature and humidity, and there are parallax errors in reading the ruler, so I do not get a constant reading. Since there are three definable sources of variation, the range of measurements should be predictable; unfortunately, the three primary causes of variation, temperature, humidity, and parallax are themselves resultants of more remote causes, so that ultimately there are not three, but an indefinitely large number of determinant factors; as
When Third World nations changed their designation from "underdeveloped" to "developing," they made it clear that there are nuances in the meaning of "development." In a different context, "developing" is proving to be a problem word in medical communications.
Every medical editor is familiar with "the patient developed...," an expression that all too frequently recurs in case reports. Be it a symptom, a syndrome, or a sickness, the patient never tires of "developing" it—and the editor never tires of blue-penciling the transitive "developed." The patient, our stylebooks tell us, may develop an idea, a theme, a project, a skill—anything in which he is an active participant—but he cannot develop a sickness, a syndrome, a symptom, or any other process independent of his volition.
Reluctant to seek substitutes for "developed," the editor frequently attempts to retain it by inverting the sentence so as to have the symptom, syndrome, or sickness "develop"
To the Editor.—
Crosby (219:1212, 1971) wrote, "Had Michelangelo really been with it, he would not have put the spear wound at the traditional location above the liver, but knowing that blood and water came from the wound, he would have placed it close to the symphysis pubis."Under Roman law, the sentence of death by crucifixion was executed on the Tau cross—the horizontal beam (patibulum) rested on the vertical stake (stipes). Most crosses were low (humilis), 6 feet 8 inches.Jesus approached the Agony under terrifying conditions. Scourging at the Pillar, pain, skin-avulsions, bleeding, crowning with a cap of thorns, facial contusions, nasal-bone fracture, climbing the 650 yards of the Via Dolorosa, carrying the patibulum (about 150 lb), producing contusions of the right shoulder and back, and injuries from falling.These traumata plus the exquisite pain of the nails in the wrists (not the palms) and the lacerations
To the Editor.—
If a layman (who thinks of himself as a professional in his own field, but is not an MD) may comment to the physician readers of your journal, I noted with considerable interest the article in MEDICAL NEWS (214:1636, 1970) which stated that men who attend church regularly do not have heart attacks, whereas backsliders and infrequent worshippers drop like flies.Assuming that irrelevant correlations have now been given the weight of scientific fact, I am moved to point out that I have proved the healthiest age for physicians to be between 95 and 99 years.From the obituary pages of the Nov 30 issue of THE JOURNAL, I did some scientifically accurate calculations and determined that the average age of death for 58 randomly selected physicians reported therein was 66.57 years. Following is a breakdown of the number who died in each of several scientifically
To the Editor.—
We have recently read "Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure," (237:255, 1977). The report as a whole is a commendable document, but it contains a number of scientific errors and omissions. The following suggestions are provided to reduce possible hazard to certain patients and to allow greater therapeutic efficacy on many occasions.In Step 1 of the "Stepped-Care Approach" section, the important therapeutic consideration that secondary hyperaldosteronism may lessen efficacy has not been mentioned. A concluding comment could be added to this section in a future edition of the report, to read as follows:The volume depletion produced by thiazide therapy may cause increased secretion of aldosterone, resulting in fluid and sodium retention and a lesser reduction in blood pressure. When secondary hyperaldosteronism is suspected of blunting antihypertensive efficacy in Step 1, the physician should consider adding an
IT IS tempting to begin by stating dramatically: there is no such thing as "group psychotherapy." The only common denominator between therapeutic groups is that the therapist deals with more than one patient during the therapeutic session. The worth of a group method depends on the therapist, the method itself, and the specific composition of a group at the time it begins or when a new member enters. Even more important, it depends on the interaction between these variables and the personality of the individual patient.Types of Groups
There are three basic types of therapy groups. The guidance or didactic group is essentially a class in which the leader teaches patients to deal with conscious attitudes and concrete reality problems. This approach is frequently used to help people with "real" problems they have in common, such as delinquent or retarded children, or a psychiatrically hospitalized spouse.The counseling or
The problem of gene structure and coding was exciting while it lasted. The story of the past two eventful decades, including my own contributions, has been well told,¹⁻³ and need not be repeated here. But molecular genetics, pursued to ever lower levels of organization, inevitably does away with itself: the gap between genetics and biochemistry disappears. More recently, a number of molecular biologists have turned their sights in the opposite direction, ie, up to higher integrative levels, to explore the relatively distant horizons of development, the nervous system, and behavior. When the individual develops from an egg, the one-dimensional information contained in the linear sequence of genes on the chromosomes is somehow translated into a two-dimensional blastula, which later folds to produce a precise three-dimensional array of sense organs, central nervous system, and muscles. Finally, the ensemble interacts to produce behavior, a phenomenon which requires four dimensions, at the
To the Editor.—
An earlier MEDICAL NEWS article1 gave an excellent presentation of problems and confusion surrounding blood and/or breath alcohol concentration (BAC). The article serves as a springboard for physicians to reconsider our role in the treatment of the alcohol-driving problem. Actually, BAC is an accurate measurement and is the cornerstone of prosecution efforts following the adoption of implied consent laws. Physicians, many of whom do not fully understand BAC concepts, may experience confusion in evaluating countermeasures to the alcohol-driving problem. They may be content to console families, patch up the victims, and rehabilitate both victims and offenders. However, our heritage is to be involved in prevention as well as treatment.Fifteen million injuries and 600,000 deaths in this nation during the past 25 years due to the alcohol-impaired driver certainly constitute a major public health problem. Isn't it strange that public health principles have not been used in
To evaluate the efficacy of intravenous immunoglobulin (IVIG) for prevention of viral, opportunistic, and minor bacterial infections in children infected with human immunodeficiency virus (HIV).
Randomized, double-blind, placebo-controlled, outpatient clinical trial comparing subjects treated with 400 mg of IVIG per kilogram of body weight every 28 days with those given albumin placebo.
Twenty-eight clinical centers in mainland United States and Puerto Rico.
Three hundred seventy-six children infected with human immunodeficiency virus with clinical or immunologic evidence of HIV disease, 313 of whom had entry CD4+ counts of at least 0.20 x 10(9)/L (greater than or equal to 200/mm3).
The incidence of laboratory-proven and clinically diagnosed viral, opportunistic, and bacterial infections.
Viral infections and minor bacterial infections contributed more frequently to morbidity in children with entry CD4+ counts of at least 0.20 x 10(9)/L (together over five times as frequent) than did serious bacterial infection, the primary outcome measure of the trial. Opportunistic infections occurred at a similar rate as laboratory-proven serious bacterial infections. In this group of children, IVIG was significantly associated with a decrease in the rate of viral infections and minor bacterial infections per 100 patient-years (36.0 vs 54.0 episodes of viral infection per 100 patient-years, IVIG vs placebo, P = .01; and 115.1 vs 159.7 episodes of minor bacterial infection per 100 patient-years, IVIG vs placebo, P = .02), as well as a decrease in the rate of serious bacterial infections per 100 patient-years (26.4 vs 48.2 episodes per 100 patient-years; P = .002). There was no apparent difference in the rate of opportunistic infections between treatment arms.
Beneficial effect of IVIG was seen across multiple infectious outcome measures, with reductions in serious and minor viral and bacterial infections observed in children with entry CD4+ counts of at least 0.20 x 10(9)/L.
A half decade has elapsed since the Institute of Medicine released 2 landmark reports on health care safety and quality, To Err Is Human1 and Crossing the Quality Chasm.2 Those studies helped articulate a broad agenda for quality improvement in health care, and examples of success on a small scale are numerous. However, the collective impact of improvement work has been far below the potential envisioned by the Institute of Medicine. Health care can benefit now from a new sense of urgency, with levels of discipline and pace akin to those of a political campaign.
The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated.Objective
To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival.Design, Setting, and Patients
CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012.Interventions
After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone.Main Outcomes and Measures
The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up.Results
A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%).Conclusions and Relevance
Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting.Trial Registration
isrctn.org Identifier: ISRCTN34802808
Carcinoma of the esophagus traditionally has been treated by surgery or radiation therapy (RT), but 5-year overall survival rates have been only 5% to 10%. We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy.
To report the long-term outcomes of a previously reported trial designed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma.
Randomized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years, followed by a prospective cohort study conducted between May 1990 and April 1991.
Multi-institution participation, ranging from tertiary academic referral centers to general community practices.
Patients had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a Karnofsky score of at least 50. Interventions Combined modality therapy (n = 134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared with RT only (n = 62): 64 Gy in 32 fractions over 6.4 weeks.
Overall survival, patterns of failure, and toxic effects.
Combined therapy significantly increased overall survival compared with RT alone. In the randomized part of the trial, at 5 years of follow-up the overall survival for combined therapy was 26% (95% confidence interval [CI], 15%-37%) compared with 0% following RT. In the succeeding nonrandomized part, combined therapy produced a 5-year overall survival of 14% (95% CI, 6%-23%). Persistence of disease (despite therapy) was the most common mode of treatment failure; however, it was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%]). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant differences in severe late toxic effects between the groups. However, chemotherapy could be administered as planned in only 89 (68%) of 130 patients (10% had life-threatening toxic effects with combined therapy vs 2% in the RT only group).
Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.
CONTEXT Carcinoma of the esophagus traditionally has been treated by surgery or radiation therapy (RT), but 5-year overall survival rates have been only 5% to 10%. We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy. OBJECTIVE To report the long-term outcomes of a previously reported trial designed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma. DESIGN Randomized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years, followed by a prospective cohort study conducted between May 1990 and April 1991. SETTING Multi-institution participation, ranging from tertiary academic referral centers to general community practices. PATIENTS Patients had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a Karnofsky score of at least 50. INTERVENTIONS Combined modality therapy (n=134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared with RT only (n=62): 64 Gy in 32 fractions over 6.4 weeks. MAIN OUTCOME MEASURES Overall survival, patterns of failure, and toxic effects. RESULTS Combined therapy significantly increased overall survival compared with RT alone. In the randomized part of the trial, at 5 years of follow-up the overall survival for combined therapy was 26% (95% confidence interval [CI], 15%-37%) compared with 0% following RT. In the succeeding nonrandomized part, combined therapy produced a 5-year overall survival of 14% (95% CI, 6%-23%). Persistence of disease (despite therapy) was the most common mode of treatment failure; however, it was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%]). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant differences in severe late toxic effects between the groups. However, chemotherapy could be administered as planned in only 89 (68%) of 130 patients (10% had life-threatening toxic effects with combined therapy vs 2% in the RT only group). CONCLUSION Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.
To test the effect of a novel bradykinin antagonist, deltibant (CP-0127), on survival, organ dysfunction, and other outcomes in patients with the systemic inflammatory response syndrome (SIRS) and presumed sepsis.
Multicenter, randomized, placebo-controlled, double-blind, parallel, dose-ranging trial. Follow-up for 28 days or until death.
A total of 47 US referral hospitals.
A total of 504 patients with SIRS and documented evidence of infection plus either hypotension or dysfunction of 2 organ systems.
Three-day continuous intravenous infusion of either placebo or 1 of 3 doses (0.3, 1.0, or 3.0 microg x kg(-1) x min(-1)) of deltibant. Concurrent therapy at the discretion of the treating physician.
Risk-adjusted, 28-day, log-normal intent-to-treat survival analysis. Risk adjustment was performed using a study-specific risk model derived from the APACHE III database.
Deltibant had no significant effect on risk-adjusted 28-day survival. In a posthoc analysis, risk-adjusted 7-day survival showed a nonsignificant trend toward improvement (P=.09). The 28-day risk-adjusted survival in the prospectively defined subset of patients with gram-negative infections showed a statistically significant improvement (P=.005).
Deltibant may have some effect on survival in patients with SIRS and gram-negative sepsis; however, additional studies would be required to prove this.