Showing papers in "JAMA in 1993"
TL;DR: Dairy therapy remains the first line of treatment of high blood cholesterol, and drug therapy is reserved for patients who are considered to be at high risk for CHD, and the fundamental approach to treatment is comparable.
Abstract: THE SECOND report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II, or ATP II) presents the National Cholesterol Education Program's updated recommendations for cholesterol management. It is similar to the first in general outline, and the fundamental approach to treatment of high blood cholesterol is comparable. This report continues to identify low-density lipoproteins (LDL) as the primary target of cholesterol-lowering therapy. As in the first report, the second report emphasizes the role of the clinical approach in primary prevention of coronary heart disease (CHD). Dietary therapy remains the first line of treatment of high blood cholesterol, and drug therapy is reserved for patients who are considered to be at high risk for CHD. However, the second report contains new features that distinguish it from the first. These include the following: Increased emphasis on See also pp 3002 and 3009.
28,495 citations
TL;DR: The SAPS II, based on a large international sample of patients, provides an estimate of the risk of death without having to specify a primary diagnosis, and is a starting point for future evaluation of the efficiency of intensive care units.
Abstract: Objective. —To develop and validate a new Simplified Acute Physiology Score, the SAPS II, from a large sample of surgical and medical patients, and to provide a method to convert the score to a probability of hospital mortality. Design and Setting. —The SAPS II and the probability of hospital mortality were developed and validated using data from consecutive admissions to 137 adult medical and/or surgical intensive care units in 12 countries. Patients. —The 13 152 patients were randomly divided into developmental (65%) and validation (35%) samples. Patients younger than 18 years, burn patients, coronary care patients, and cardiac surgery patients were excluded. Outcome Measure. —Vital status at hospital discharge. Results. —The SAPS II includes only 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). Goodness-of-fit tests indicated that the model performed well in the developmental sample and validated well in an independent sample of patients (P=.883 andP=.104 in the developmental and validation samples, respectively). The area under the receiver operating characteristic curve was 0.88 in the developmental sample and 0.86 in the validation sample. Conclusion. —The SAPS II, based on a large international sample of patients, provides an estimate of the risk of death without having to specify a primary diagnosis. This is a starting point for future evaluation of the efficiency of intensive care units. (JAMA. 1993;270:2957-2963)
5,836 citations
TL;DR: The most prominent contributors to mortality in the United States in 1990 were tobacco, diet and activity patterns, alcohol, microbial agents, toxic agents, firearms, sexual behavior, motor vehicles, and illicit use of drugs.
Abstract: Objective. —To identify and quantify the major external (nongenetic) factors that contribute to death in the United States. Data Sources. —Articles published between 1977 and 1993 were identified through MEDLINE searches, reference citations, and expert consultation. Government reports and compilations of vital statistics and surveillance data were also obtained. Study Selection. —Sources selected were those that were often cited and those that indicated a quantitative assessment of the relative contributions of various factors to mortality and morbidity. Data Extraction. —Data used were those for which specific methodological assumptions were stated. A table quantifying the contributions of leading factors was constructed using actual counts, generally accepted estimates, and calculated estimates that were developed by summing various individual estimates and correcting to avoid double counting. For the factors of greatest complexity and uncertainty (diet and activity patterns and toxic agents), a conservative approach was taken by choosing the lower boundaries of the various estimates. Data Synthesis. —The most prominent contributors to mortality in the United States in 1990 were tobacco (an estimated 400000 deaths), diet and activity patterns (300 000), alcohol (100 000), microbial agents (90 000), toxic agents (60 000), firearms (35 000), sexual behavior (30 000), motor vehicles (25 000), and illicit use of drugs (20 000). Socioeconomic status and access to medical care are also important contributors, but difficult to quantify independent of the other factors cited. Because the studies reviewed used different approaches to derive estimates, the stated numbers should be viewed as first approximations. Conclusions. —Approximately half of all deaths that occurred in 1990 could be attributed to the factors identified. Although no attempt was made to further quantify the impact of these factors on morbidity and quality of life, the public health burden they impose is considerable and offers guidance for shaping health policy priorities. (JAMA. 1993;270:2207-2212)
5,468 citations
TL;DR: Results presented should prove to be useful to clinicians who wish to compare an individual patient's MMSE scores with a population reference group and to researchers making plans for new studies in which cognitive status is a variable of interest.
Abstract: Objective —To report the distribution of Mini-Mental State Examination (MMSE) scores by age and educational level Design —National Institute of Mental Health Epidemiologic Catchment Area Program surveys conducted between 1980 and 1984 Setting —Community populations in New Haven, Conn; Baltimore, Md; St Louis, Mo; Durham, NC; and Los Angeles, Calif Participants —A total of 18 056 adult participants selected by probability sampling within census tracts and households Main Outcome Measures —Summary scores for the MMSE are given in the form of mean, median, and percentile distributions specific for age and educational level Results —The MMSE scores were related to both age and educational level There was an inverse relationship between MMSE scores and age, ranging from a median of 29 for those 18 to 24 years of age, to 25 for individuals 80 years of age and older The median MMSE score was 29 for individuals with at least 9 years of schooling, 26 for those with 5 to 8 years of schooling, and 22 for those with 0 to 4 years of schooling Conclusions —Cognitive performance as measured by the MMSE varies within the population by age and education The cause of this variation has yet to be determined Mini-Mental State Examination scores should be used to identify current cognitive difficulties and not to make formal diagnoses The results presented should prove to be useful to clinicians who wish to compare an individual patient's MMSE scores with a population reference group and to researchers making plans for new studies in which cognitive status is a variable of interest (JAMA 1993;269:2386-2391)
2,717 citations
TL;DR: A strong association between homocysteine concentration and folate, vitamin B12, and vitamin B6 status, as well as age is indicated, suggesting that a substantial majority of the cases of high homocy steine in this older population can be attributed to vitamin status.
Abstract: Objective. —To describe the distribution of plasma homocysteine concentrations in an elderly population and to analyze the relationship between homocysteine level and intake of vitamins and serum levels of vitamins that serve as coenzymes in homocysteine metabolism. Design. —Cross-sectional analysis of homocysteine levels and vitamin blood levels and intake in elderly participants in the Framingham Study. Setting. —Population-based cohort in Framingham, Mass. Participants. —A total of 1160 adult survivors, aged 67 to 96 years, from the original Framingham Heart Study cohort. Main Outcome Measures. —Plasma homocysteine concentration correlated with plasma folate, vitamin B 12 , pyridoxal-5'-phosphate (PLP), and oral intakes of these vitamins, and the contribution of these vitamins to the prevalence of elevated homocysteine in the population. Results. —Homocysteine levels were positively correlated with age after controlling for vitamin concentrations. After controlling for age, sex, and levels of other vitamins, homocysteine exhibited a strong inverse association with plasma folate. When subjects were grouped by deciles of plasma folate, mean homocysteine was significantly higher in the lowest two folate deciles (15.6 and 13.7 μmol/L, respectively) than in the highest decile (11.0 μmol/L). Homocysteine demonstrated weaker, inverse associations with plasma vitamin B 12 and PLP. Similar inverse associations were demonstrated between homocysteine and intakes of folate and vitamin B 6 , but not vitamin B 12 . Prevalence of high homocysteine (>14 μmol/L) was 29.3% in this cohort, and was greatest among subjects with low folate status. Inadequate plasma concentrations of one or more B vitamins appear to contribute to 67% of the cases of high homocysteine. Conclusions. —These results indicate a strong association between homocysteine concentration and folate, vitamin B 12 , and vitamin B 6 status, as well as age. It is possible that a substantial majority of the cases of high homocysteine in this older population can be attributed to vitamin status. ( JAMA . 1993;270:2693-2698)
1,978 citations
TL;DR: Major depression in patients hospitalized following an MI is an independent risk factor for mortality at 6 months and its impact is at least equivalent to that of left ventricular dysfunction (Killip class) and history of previous MI.
Abstract: Objective. —To determine if the diagnosis of major depression in patients hospitalized following myocardial infarction (Ml) would have an independent impact on cardiac mortality over the first 6 months after discharge. Design. —Prospective evaluation of the impact of depression assessed using a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode. Cox proportional hazards regression was used to evaluate the independent impact of depression after control for significant clinical predictors in the data set. Setting. —A large, university-affiliated hospital specializing in cardiac care, located in Montreal, Quebec. Patients. —All consenting patients (N=222) who met established criteria for Ml between August 1991 and July 1992 and who survived to be discharged from the hospital. Patients were interviewed between 5 and 15 days following the MI and were followed up for 6 months. There were no age limits (range, 24 to 88 years; mean, 60 years). The sample was 78% male. Primary Outcome Measure. —Survival status at 6 months. Results. —By 6 months, 12 patients had died. All deaths were due to cardiac causes. Depression was a significant predictor of mortality (hazard ratio, 5.74; 95% confidence interval, 4.61 to 6.87;P=.0006). The impact of depression remained after control for left ventricular dysfunction (Killip class) and previous Ml, the multivariate significant predictors of mortality in the data set (adjusted hazard ratio, 4.29; 95% confidence interval, 3.14 to 5.44;P=.013). Conclusion. —Major depression in patients hospitalized following an Ml is an independent risk factor for mortality at 6 months. Its impact is at least equivalent to that of left ventricular dysfunction (Killip class) and history of previous Ml. Additional study is needed to determine whether treatment of depression can influence post-MI survival and to assess possible underlying mechanisms. (JAMA. 1993;270:1819-1825)
1,975 citations
TL;DR: The influence of patient age and prostatic size on the serum PSA concentration was assessed in order to use PSA more appropriately to detect clinically significant prostate cancer at an early, potentially curable stage.
Abstract: Objective. —To define the characteristics of serum prostate-specific antigen (PSA) in a population of healthy men without clinically evident prostate cancer, but who are at risk for developing the malignancy. The influence of patient age and prostatic size on the serum PSA concentration was assessed in order to use PSA more appropriately to detect clinically significant prostate cancer at an early, potentially curable stage. Design. —Prospective, community-based study. Participants. —Between December 1989 and March 1991, 2119 healthy men aged 40 to 79 years from Olmsted County, Minnesota, were entered into a prospective study to assess the natural history of benign prostatic hyperplasia. Of these, 537 (25%) were randomly chosen to participate in a detailed clinical examination that included a serum PSA determination (Tandem-R PSA assay), digital rectal examination, and transrectal ultrasonography. Four hundred seventy-one (88%) completed the prostatic evaluation and had no evidence of prostate cancer by any of these three diagnostic tests; these men formed the study population on which all analyses were performed. Main Outcome Measure. —Serum PSA concentration, prostatic volume, and PSA density (serum PSA level/prostatic volume) as a function of patient age. Results. —The serum PSA concentration is correlated with patient age (r=.43;P Conclusions. —The serum PSA concentration is directly correlated with patient age and prostatic volume, the latter of which also is directly related to age. Thus, rather than rely on a single reference range for men of all age groups, it is more appropriate to have age-specific reference ranges. These age-specific reference ranges have the potential to make serum PSA a more discriminating tumor marker for detecting clinically significant cancers in older men (increasing specificity) and to find more potentially curable cancers in younger men (increasing sensitivity). (JAMA. 1993;270:860-864)
1,292 citations
TL;DR: Health insurance coverage alone is not likely to reduce significantly SES differences in health, and attention should be paid both in policy decisions and in clinical practice to other SES-related factors that may influence patterns of health and disease.
Abstract: Objective. —Socioeconomic status (SES) is strongly associated with risk of disease and mortality. Universal health insurance is being debated as one remedy for such health inequalities. This article considers mechanisms through which SES affects health and argues that a broader and more comprehensive approach is needed. Data Sources. —Published articles surveyed using MEDLINE and review articles and bibliographies. Methods and Results. —Research is reviewed on the association of SES with health outcomes in different countries, including those with universal health coverage. Socioeconomic status relates to health at all levels of the SES hierarchy, and access to care accounts for little of this association. Other mechanisms are suggested and implications for policy and clinical practice are discussed. Conclusion. —Health insurance coverage alone is not likely to reduce significantly SES differences in health. Attention should be paid both in policy decisions and in clinical practice to other SES-related factors that may influence patterns of health and disease. (JAMA. 1993;269:3140-3145)
1,056 citations
TL;DR: Among severity systems for intensive care patients, the MPM0 is the only model available for use at ICU admission and bothMPM0 and MPM24 are useful research tools and provide important clinical information when used alone or together.
Abstract: Objective. —To revise and update models in the Mortality Probability Model (MPM II) system to estimate the probability of hospital mortality among 19124 intensive care unit (ICU) patients that can be used for quality assessment within and among ICUs. Design and Setting. —Models developed and validated on consecutive admissions to adult medical and surgical ICUs in 12 countries. Patients. —A total of 12610 patients for model development, 6514 patients for model validation. Patients younger than 18 years and burn, coronary care, and cardiac surgery patients were excluded. Outcome Measure. —Vital status at hospital discharge. Results. —The admission model, MPM0, contains 15 readily obtainable variables. In developmental and validation samples it calibrated well (goodness-of-fit tests:P=.623 andP=.327, respectively, where a highPvalue represents good fit between observed and expected values) and discriminated well (area under the receiver operating characteristic curve=0.837 and 0.824, respectively). The 24-hour model, MPM24(developed on 10357 patients still in the ICU at 24 hours), contains five of the admission variables and eight additional variables easily ascertained at 24 hours. It also calibrated well (P=.764 andP=.231 in the developmental and validation samples, respectively) and discriminated well (area under the receiver operating characteristic curve=0.844 and 0.836 in the developmental and validation samples, respectively). Conclusions. —Among severity systems for intensive care patients, the MPM0is the only model available for use at ICU admission. Both MPM0and MPM24are useful research tools and provide important clinical information when used alone or together. (JAMA. 1993;270:2478-2486)
1,009 citations
TL;DR: Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal digital rectal examination alone.
Abstract: Objective. —To determine whether prostate-specific antigen (PSA)—based screening alters the proportion of organ-confined prostate cancers detected. Design. —A prospective, nonrandomized, serial PSA-based screening trial (follow-up from 6 to 37 months), and a concurrent comparison group. Setting. —Genera community outpatient screening program based at a university center. Patients. —The study group consisted of 10251 men aged 50 years and older (mean and median age, 63 years; mean and median age of patients who underwent biopsies, 66 years) who presented to a prostate cancer screening program and consented to phlebotomy. The comparison group consisted of 266 concurrently studied private patients in the same age range (mean and median age, 68 years) who were referred for prostatic ultrasonography and biopsy because of an abnormal digital rectal examination (DRE). Main Outcome Measure. —Proportion detected with clinically or pathologically advanced prostate cancer. Results. —The men were divided into three groups: the comparison group, the initial PSA-based screening group, and the serial PSA-based screening group. The proportions of prostate cancers detected that were clinically or pathologically advanced were as follows: comparison group, 57% (27/47); initial PSA-based screening group, 37% (91/244); and serial PSA-based screening group, 29% (37/ 129). Screened patients had a lower proportion of advanced cancers than the comparison group (χ 2 [2]=12.3; P =.002); this advantage was observed principally in patients younger than 70 years. Surgical staging revealed that the cancer was microscopically focal and well differentiated (possibly latent cancer) in 2.5% (1/40) of the nonscreened group, 2.9% (7/244) of the initially screened group, and 7.8% (10/129) of the serially screened group (generalized Fisher's Exact Test, P =.08). Conclusion. —Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal DRE alone. ( JAMA . 1993;270:948-954)
999 citations
TL;DR: Findings support the recommendations of the new fifth Joint National Committee report regarding treatment choices for people with stage 1 ("mild") hypertension, as an initial regimen was more effective in preventing cardiovascular and other clinical events than was nutritional-hygienic treatment alone.
Abstract: Objective. —To compare six antihypertensive interventions for the treatment of mild hypertension. Design. —Randomized, double-blind, placebo-controlled clinical trial. Setting. —Four hypertension screening and treatment centers in the United States. Participants. —Hypertensive men and women, aged 45 to 69 years, with diastolic blood pressure less than 100 mm Hg. Intervention. —Sustained nutritional-hygienic advice to all participants to reduce weight, dietary sodium intake, and alcohol intake, and increase physical activity. Participants were randomly allocated to take (1) placebo (n=234); (2) chlorthalidone (n=136); (3) acebutolol (n=132); (4) doxazosin mesylate (n=134); (5) amlodipine maleate (n=131); or (6) enalapril maleate (n=135). Main Outcome Measures. —Blood pressure, quality of life, side effects, blood lipid levels and analysis of other serum components, echocardiographic and electrocardiographic changes, and incidence of cardiovascular events over an average of 4.4 years of follow-up. Results. —Blood pressure reductions were sizable in all six groups, and were significantly greater for participants assigned to drug treatment than placebo ( — 15.9 vs — 9.1 mm Hg for systolic blood pressure and — 12.3 vs —8.6 mm Hg for diastolic blood pressure;p Conclusions. —As an initial regimen, drug treatment in combination with nutritional-hygienic intervention was more effective in preventing cardiovascular and other clinical events than was nutritional-hygienic treatment alone. Drug-treatment group differences were minimal. Pending results from large-scale clinical trials to evaluate drug treatments for their effect on cardiovascular clinical events, these findings support the recommendations of the new fifth Joint National Committee report regarding treatment choices for people with stage 1 ("mild") hypertension. (JAMA. 1993;270:713-724)
TL;DR: Perioperative increase of oxygen delivery with dopexamine hydrochloride significantly reduces mortality and morbidity in high-risk surgical patients.
Abstract: Objective —To assess the effect of deliberate perioperative increase in oxygen delivery on mortality and morbidity in patients who are at high risk of both following surgery Design —Prospective, randomized clinical trial Setting —A teaching hospital general intensive care unit, London, England Patients —A total of 107 surgical patients, who were assessed as high risk from previously identified criteria, were studied during an 18-month period Interventions —Patients were randomly assigned to a control group (n=54) that received best standard perioperative care, or to a protocol group (n=53) that, in addition, had deliberate increase of oxygen delivery index to greater than 600 mL/min per square meter by use of dopexamine hydrochloride infusion Outcome Measures —Mortality and complications were assessed to 28 days postoperatively Results —Groups were similar with respect to demographics, admission criteria, operation type, and admission hemodynamic variables Groups were treated similarly to maintain blood pressure, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure; however, once additional treatment with dopexamine hydrochloride had been given, the protocol group had significantly higher oxygen delivery preoperatively (median, 597 vs 399 mL/min per square meter;P Conclusion —Perioperative increase of oxygen delivery with dopexamine hydrochloride significantly reduces mortality and morbidity in high-risk surgical patients (JAMA 1993;270:2699-2707)
TL;DR: An internal medicine resident in a rheumatology rotation and seeing a 19-year-old woman who has had systemic lupus erythematosus diagnosed on the basis of a characteristic skin rash, arthritis, and renal disease is distressed by the rising creatinine level.
Abstract: CLINICAL SCENARIO You are working as an internal medicine resident in a rheumatology rotation and are seeing a 19-year-old woman who has had systemic lupus erythematosus diagnosed on the basis of a characteristic skin rash, arthritis, and renal disease. A renal biopsy has shown diffuse proliferative nephritis. A year ago her creatinine level was 140 μmol/L, 6 months ago it was 180 μmol/L, and in a blood sample taken a week before this clinic visit, 220 μmol/L. Over the last year she has been taking prednisone, and over the last 6 months, cyclophosphamide, both in appropriate doses. You are distressed by the rising creatinine level and the rheumatology fellow with whom you discuss the problem suggests that you contact the hematology service to consider a trial of plasmapheresis. The fellow states that plasmapheresis is effective in reducing the level of the antibodies responsible for the nephritis and cites a number
TL;DR: Fresh-pressed, unpreserved apple cider can transmit E coli O157:H7 organisms, which cause severe infections, and consumers can reduce their risk by only drinking cider made from apples that have been washed and brushed.
Abstract: Objective. —Esherichia coliO157:H7 causes hemorrhagic colitis and the hemolytic uremic syndrome. In the fall of 1991, an outbreak ofE coliO157:H7 infections in southeastern Massachusetts provided an opportunity to identify transmission by a seemingly unlikely vehicle. Design. —Case-control study to determine the vehicle of infection. New England cider producers were surveyed to assess production practices and determined the survival time ofE coliO157:H7 organisms in apple cider. Results. —Illness was significantly associated with drinking one brand of apple cider. Thirteen (72%) of 18 patients but only 16 (33%) of 49 controls reported drinking apple cider in the week before illness began (odds ratio [OR], 8.3; 95% confidence interval [CI], 1.8 to 39.7). Among those who drank cider, 12 (92%) of 13 patients compared with two (13%) of 16 controls drank cider from cider mill A (lower 95% CI, 2.9;P Conclusions. —Fresh-pressed, unpreserved apple cider can transmitE coliO157:H7 organisms, which cause severe infections. Risk of transmission can be reduced by washing and brushing apples before pressing, and preserving cider with sodium benzoate. Consumers can reduce their risk by only drinking cider made from apples that have been washed and brushed. (JAMA. 1993;269:2217-2220)
TL;DR: The 6-minute walk test is a safe and simple clinical tool that strongly and independently predicts morbidity and mortality in patients with left ventricular dysfunction.
Abstract: Objective. —To study the potential usefulness of the 6-minute walk test, a self-paced submaximal exercise test, as a prognostic indicator in patients with left ventricular dysfunction. Design. —Data were collected during a prospective cohort study, the Studies of Left Ventricular Dysfunction (SOLVD) Registry Substudy. Setting. —Twenty tertiary care hospitals in the United States, Canada, and Belgium. Participants. —A stratified random sample of 898 patients from the SOLVD Registry who had either radiological evidence of congestive heart failure and/or an ejection fraction of 0.45 or less were enrolled in the substudy and underwent a detailed clinical evaluation including a 6-minute walk test. Patients were followed up for a mean of 242 days. Outcome Measures. —Mortality and hospitalization. Results. —During follow-up, 52 walk-test participants (6.2%) died and 252 (30.3%) were hospitalized. Hospitalization for congestive heart failure occurred in 78 participants (9.4%), and the combined endpoint of death or hospitalization for congestive heart failure occurred in 114 walk-test participants (13.7%). Compared with the highest performance level, patients in the lowest performance level had a significantly greater chance of dying (10.23% vs 2.99%;P=.01), of being hospitalized (40.91% vs 19.90%;P=.002), and of being hospitalized for heart failure (22.16% vs 1.99%;P Conclusion. —The 6-minute walk test is a safe and simple clinical tool that strongly and independently predicts morbidity and mortality in patients with left ventricular dysfunction. (JAMA. 1993;270:1702-1707)
TL;DR: This paper found that Hispanics were twice as likely as non-Hispanic whites to receive no ED pain medication (crude relative risk [RR], 2.12; 95% confidence interval [Cl], 1.35 to 3.32;P=.003).
Abstract: Objective. —To determine whether Hispanic patients with isolated long-bone fractures are less likely to receive emergency department (ED) analgesics than similar non-Hispanic white patients. Design. —Retrospective cohort study. Setting. —The UCLA Emergency Medicine Center, a level I trauma center. Participants. —All Hispanic and non-Hispanic white ED patients aged 15 to 55 years, seen between January 1,1990, and December 31,1991, with isolated long-bone fractures, identified byICD-9 codes 812, 813,821, and 823, were eligible for inclusion. Exclusion criteria included injury more than 6 hours prior to presentation, "possible" or chip fractures only, altered mentation, or ethanol intoxication. Main Outcome Measures. —Emergency department administration of analgesic or no analgesic. Results. —The study group consisted of 139 patients meeting inclusion criteria, of whom 31 were Hispanic and 108 non-Hispanic white. Non-Hispanic whites were significantly more likely to speak English, be insured, and suffer nonoccupational injuries. Hispanics were twice as likely as non-Hispanic whites to receive no ED pain medication (crude relative risk [RR], 2.12; 95% confidence interval [Cl], 1.35 to 3.32;P=.003). The RR for ethnicity was similar and significant (P Conclusions. —Hispanics with isolated long-bone fractures are twice as likely as non-Hispanic whites to receive no pain medication in the UCLA Emergency Medicine Center. No covariate measured in this study could account for this effect. An ethnic basis for variability in analgesic practice needs to be further characterized. (JAMA. 1993;269:1537-1539)
TL;DR: It is suggested that women are more prone than men to develop torsades de pointes during administration of cardiovascular drugs that prolong cardiac repolarization and the pathophysiological basis for, and therapeutic implications of, this gender disparity should be further investigated.
Abstract: Objective. —To test the hypothesis that female prevalence is greater than expected among reported cases of torsades de pointes associated with cardiovascular drugs that prolong cardiac repolarization. Data Sources. —A MEDLINE search of the English-language literature for the period of 1980 through 1992, using the termstorsade de pointes, polymorphic ventricular tachycardia, atypical ventricular tachycardia, proarrhythmia, anddrug-induced ventricular tachycardia, supplemented by pertinent references (dating back to 1964) from the reviewed articles and by personal communications with researchers involved in this field. Study Selection. —Ninety-three articles were identified describing at least one case of polymorphic ventricular tachycardia (with gender specified) associated with quinidine, procainamide hydrochloride, disopyramide, amiodarone, sotalol hydrochloride, bepridil hydrochloride, or prenylamine. A total of 332 patients were included in the analysis following application of prospectively defined criteria (eg, corrected QT [QTc] interval of 0.45 second or greater while receiving drug). Data Extraction. —Clinical and electrocardiographic descriptors were extracted for analysis. Expected female prevalence for torsades de pointes associated with quinidine, procainamide, disopyramide, and amiodarone was conservatively estimated from gender-specific data reported for antiarrhythmic drug prescriptions in 1986, as derived from the National Disease and Therapeutic Index, a large pharmaceutical database; expected female prevalence for torsades de pointes associated with sotalol, bepridil, and prenylamine was assumed to be 50% or less since these agents are prescribed for male-predominant cardiovascular conditions. Results. —Women made up 70% (95% confidence interval, 64% to 75%) of the 332 reported cases of cardiovascular-drug—related torsades de pointes, and a female prevalence exceeding 50% was observed in 20 (83%) of 24 studies having at least four included cases. When analyzed according to various descriptors, women still constituted the majority (range, 51% to 94% of torsades de pointes cases), irrespective of the presence or absence of underlying coronary artery or rheumatic heart disease, left ventricular dysfunction, type of underlying arrhythmia, hypokalemia, hypomagnesemia, bradycardia, concomitant digoxin treatment, or level of QTcat baseline or while receiving drug. When cases of torsades de pointes were analyzed by individual drug, observed female prevalence was always greater than expected, representing a statistically significant difference (P Conclustions. —These findings strongly suggest that women are more prone than men to develop torsades de pointes during administration of cardiovascular drugs that prolong cardiac repolarization. The pathophysiological basis for, and therapeutic implications of, this gender disparity should be further investigated. (JAMA. 1993;270:2590-2597)
TL;DR: The addition of basic counseling was associated with major increases in efficacy; and the addition of on-site professional services was even more effective.
Abstract: Objective. To examine whether the addition of counseling, medical care, and psychosocial services improves the efficacy of methadone hydrochloride therapy in the rehabilitation of opiate-dependent ...
TL;DR: It is postulate that the poorly deformable transfused red blood cells cause micro-circulatory occlusion in some organs, which may lead to tissue ischemia inSome organs.
Abstract: Background. —Red blood cell transfusion is commonly used to augment systemic oxygen delivery to supranormal levels in patients with sepsis. However, clinical studies have not consistently demonstrated that this therapeutic maneuver is accompanied by an increase in oxygen utilization at either the whole-body level or within individual organs. Study Objectives. —To determine the effect of red blood cell transfusion on gastrointestinal and whole-body oxygen uptake. Design. —Prospective, controlled, interventional study. Setting. —Multidisciplinary intensive care unit of a tertiary care teaching hospital. Patients. —Twenty-three critically ill patients with sepsis undergoing mechanical ventilation. Measurements and Main Results. —Systemic oxygen uptake was measured by indirect calorimetry and calculated by the Fick method. Gastric intramucosal pH as measured by tonometry was used to assess changes in splanchnic oxygen availability. Measurements were made prior to transfusion of 3 U of packed red blood cells. These were then repeated immediately following transfusion, as well as 3 and 6 hours later. There was no increase in systemic oxygen uptake measured by indirect calorimetry in any of the patients studied for up to 6 hours posttransfusion (including those patients with an elevated arterial lactate concentration). However, the calculated systemic oxygen uptake increased in parallel with the oxygen delivery in all the patients. More importantly, we found an inverse association between the change in gastric intramucosal pH and the age of the transfused blood (r=-.71;P Conclusion. —We failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis. Patients receiving old transfused red blood cells developed evidence of splanchnic ischemia. We postulate that the poorly deformable transfused red blood cells cause microcirculatory occlusion in some organs, which may lead to tissue ischemia in some organs. (JAMA. 1993;269:3024-3029)
TL;DR: Potential interventions that might affect the incidence of VAP or outcome associated with VAP are suggested and indicate that different ICU populations may have different incidences of V AP.
Abstract: Objectives. —To identify factors associated with the development of ventilator-associated pneumonia (VAP) and to examine the incidence of VAP in different intensive care unit (ICU) populations. Design. —An inception cohort study. Setting. —Barnes Hospital, St Louis, Mo, an academic tertiary care center. Patients or Other Participants. —A total of 277 consecutive patients required mechanical ventilation for longer than 24 hours from a medical ICU (75 patients), surgical ICU (100 patients), or cardiothoracic ICU (102 patients). Interventions. —Prospective patient surveillance and data collection. Main Outcome Measures. —Ventilator-associated pneumonia and ICU mortality. Results. —Ventilator-associated pneumonia occurred in 43 patients (15.5%). Stepwise logistic regression analysis identified four factors to be independently associated with VAP (P Conclusions. —These data suggest potential interventions that might affect the incidence of VAP or outcome associated with VAP. Additionally, they indicate that different ICU populations may have different incidences of VAP. (JAMA. 1993;270:1965-1970)
TL;DR: Mediastinal irradiation for Hodgkin's disease increases the risk of subsequent death from heart disease, and risk increased with high mediastinal doses, minimal protective cardiac blocking, young age at irradiation, and increasing duration of follow-up.
Abstract: Objective. —To assess the risk of death from heart disease after Hodgkin's disease therapy. Design. —Retrospective study comparing treated patients with a matched general population. Setting. —Referral center. Patients. —A total of 2232 consecutive Hodgkin's disease patients treated from 1960 through 1991. Follow-up averaged 9.5 years. Main Outcome Measures. —Relative risks (RRs), the ratio of the observed to the expected cases with 95% confidence intervals (Cls), χ tests for trends, and Kaplan-Meier actuarial risks. Results. —Of the 2232 patients, 88 (3.9%) died of heart disease, 55 from acute myocardial infarction and 33 from other cardiac diseases, including congestive heart failure, radiation pericarditis or pancarditis, cardiomyopathy, or valvular heart disease. The RR for cardiac death was 3.1 (Cl, 2.4 to 3.7). Mediastinal radiation of 30 Gy or less (n=385 patients) did not increase risk; above 30 Gy (n=1830), RR was 3.5 (Cl, 2.7 to 4.3). Blocking to limit cardiac exposure reduced the RR for other cardiac diseases from 5.3 (Cl, 3.1 to 7.5) to 1.4 (Cl, 0.6 to 2.9), but not acute myocardial infarction (RR, 3.7 vs 3.4). The RRs increased with duration after treatment (trend in acute myocardial infarction, P =.02; in other cardiac diseases, P =.004). The RR for acute myocardial infarction was highest after irradiation before 20 years of age and decreased with increasing age at treatment ( P Conclusions. —Mediastinal irradiation for Hodgkin's disease increases the risk of subsequent death from heart disease. Risk increased with high mediastinal doses, minimal protective cardiac blocking, young age at irradiation, and increasing duration of follow-up. (JAMA. 1993:270:1949-1955)
TL;DR: The overall mortality risk following renal transplantation was initially increased, but there was a long-term survival benefit compared with similar patients on dialysis.
Abstract: Objective. —To compare mortality risk among cadaveric renal transplant recipients vs transplant candidates on dialysis in the cyclosporine era. Setting. —Patient mortality risk was analyzed by treatment modality for a completed statewide patient population. Patients. —All Michigan residents younger than age 65 years who started end-stage renal disease (ESRD) therapy between January 1,1984, and December 31, 1989, were included. Patients were followed up from ESRD onset (n=5020), to wait-listing for renal transplant (n=1569), to receiving a cadaveric first transplant (n=799), and to December 31, 1989. Main Outcome Measure. —Mortality rates. Results. —Using a time-dependent variable based on the waiting time from date of wait-listing to transplantation and adjusting for age, sex, race, and primary cause of ESRD, the relative risk (RR) of dying was increased early after transplantation and then decreased to a beneficial long-term effect, given survival to 365 days after transplantation (RR, 0.36;P .05). Overall, the estimated times from transplantation to equal mortality risk was 117±28 days and to equal cumulative mortality was 325±91 days. Conclusions. —The overall mortality risk following renal transplantation was initially increased, but there was a long-term survival benefit compared with similar patients on dialysis. These analyses allow improved description of comparative mortality risks for dialysis and transplant patients and allow advising patients regarding comparative survival outcomes. (JAMA. 1993;270:1339-1343)
TL;DR: The data suggest that conjugate vaccines have already had a marked impact on the incidence of Hib disease in the United States, preventing an estimated 10,000 to 16,000 cases of Hib Disease in 1991.
Abstract: Objective. —Effective Haemophilus influenzae type b (Hib) conjugate vaccines were first licensed for use in US children at least 18 months old in December 1987 and for infants at least 2 months old in October 1990. We evaluated trends in Hib disease associated with licensure of Hib conjugate vaccines. Design. —Data from two sources, an intensive laboratory-based active surveillance system and the National Bacterial Meningitis Reporting System (NBMRS), were used separately to evaluate disease incidence. Data from vaccine manufacturers on Hib vaccine doses distributed in the United States were compared with trends in Hib disease incidence. Results. —The age-specific incidence of Hib disease among children less than 5 years old decreased by 71% from 37 per 100 000 persons in 1989 to 11 per 100 000 persons in 1991 (active surveillance data). Haemophilus influenzae meningitis incidence decreased by 82% between 1985 and 1991 (NBMRS data). Increases in doses of Hib vaccine distributed in the United States coincided with steep declines in Hib disease. Both surveillance systems showed decreased rates of Hib disease in infants less than 1 year old before vaccine was licensed for use in this age group. Haemophilus influenzae type b disease incidence in persons at least 12 years old and pneumococcal meningitis incidence in children less than 5 years old did not change substantially during the same period; therefore, decreased Hib disease in children less than 5 years old is not likely to be explained solely by changes in surveillance sensitivity or decreases in bacterial disease due to changes in medical practice. Conclusion. —Our data suggest that conjugate vaccines have already had a marked impact on the incidence of Hib disease in the United States, preventing an estimated 10 000 to 16 000 cases of Hib disease in 1991. The decline of disease in infants less than 1 year old before licensure for this age group warrants further investigation. ( JAMA . 1993;269:221-226)
TL;DR: In vitro cardiac electrophysiologic studies found that terfenadine is equipotent to quinidine as a blocker of the delayed rectifier potassium current in isolated feline myocytes, which indicates that episodes of torsades de pointes are most likely the result of a quinidinelike action of the parent drug and of factors that impair the normally rapid metabolism of terfenADine.
Abstract: Objectives and Methods. —To gain insight into possible mechanisms of and predisposing factors for torsades de pointes during terfenadine therapy, spontaneous reports in the US Food and Drug Administration's Spontaneous Reporting System database were examined. Based on the characteristics of the cases, in vitro cardiac electrophysiologic studies were conducted to test the hypothesis that terfenadine, and not its major metabolite, has actions similar to those of quinidine and is responsible for this form of cardiac toxicity. Design. —Spontaneous reports from the general medical community. Results. —As of April 1,1992,25 cases of torsades de pointes had been reported to the Food and Drug Administration's Spontaneous Reporting System. Predisposing factors in these cases indicated that the parent drug, but not its metabolite, may have actions similar to those of quinidine that are responsible for inducing arrhythmia. In vitro studies found that terfenadine is equipotent to quinidine as a blocker of the delayed rectifier potassium current in isolated feline myocytes. The metabolite, terfenadine carboxylate, did not inhibit this potassium current even at concentrations 30 times higher than the concentration of terfenadine producing a half-maximal effect. Conclusions. —Since blockade of the potassium channel did not occur with the major metabolite of terfenadine, episodes of torsades de pointes are most likely the result of a quinidinelike action of the parent drug and of factors that impair the normally rapid metabolism of terfenadine. Dosage restriction and awareness of the clinical conditions and drug interactions capable of inhibiting the metabolism of terfenadine are essential for prevention of this serious reaction. (JAMA. 1993;269:1532-1536)
TL;DR: Ketoconazole alters the metabolism of terfenadine in normal men and women and results in the accumulation of unmetabolized parent drug, which is associated with significant prolongation of the corrected QT interval and should be avoided.
Abstract: Objective. —To examine prospectively the effects of ketoconazole on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics (corrected QT intervals) of terfenadine in men and women. Design. —Prospective cohort study with each subject serving as his or her own control. Setting. —Outpatient cardiology clinic and inpatient telemetry unit for monitoring period. Participants. —Six healthy volunteers (four men and two women, aged 24 to 35 years) not taking any prescription or over-the-counter medications. Intervention. —After achieving a steady state while taking terfenadine (60 mg every 12 hours for 7 days), daily concomitant oral ketoconazole (200 mg every 12 hours) was added to the subjects' regimen. Pharmacokinetic profiles were obtained while subjects were taking terfenadine alone and after the addition of ketoconazole. Electrocardiograms were obtained at baseline, after 1 week of taking terfenadine alone, and at the time of the second pharmacokinetic profile after the addition of ketoconazole to the regimen. Main Outcome Measures. —Terfenadine and its acid metabolite serum concentrations and corrected QT intervals. Results. —All subjects had detectable levels of unmetabolized terfenadine after the addition of ketoconazole, which was associated with QT prolongation. Only two of the six subjects could complete the entire course of ketoconazole coadministration. Four subjects received a shortened duration of ketoconazole therapy because of significant electrocardiographic repolarization abnormalities. There was a significant change in the area under the curve of the acid metabolite of terfenadine after the addition of ketoconazole administration. Conclusions. —Ketoconazole alters the metabolism of terfenadine in normal men and women and results in the accumulation of unmetabolized parent drug, which is associated with significant prolongation of the corrected QT interval. This drug combination should be avoided. (JAMA. 1993;269:1513-1518)
TL;DR: There was no improvement in outcome associated with initiating treatment before hospital arrival; however, treatment within 70 minutes of symptom onset--whether in the hospital or in the field--minimized the infarct process and its complications.
Abstract: Objective. —To determine the effect of prehospital-initiated vs hospital-initiated treatment of myocardial infarction on clinical outcome. Design. —Randomized, controlled clinical trial. Setting. —Multicenter study involving 19 hospitals and all paramedic systems in the Seattle, Wash, metropolitan area. Patients. —A total of 360 patients with symptoms for 6 hours or less, no risk factors for serious bleeding, and ST-segment elevation were selected by paramedics and a remote physician for inclusion into the trial. They represented 4% of patients with chest pain who were screened and 21% of those with acute infarction. Interventions. —Patients were allocated to have aspirin and alteplase treatment initiated before or after hospital arrival. Intravenous sodium heparin was administered to both groups in the hospital. Main Outcome Measure. —The primary endpoint was a ranked composite score (combining death, stroke, serious bleeding, and infarct size). The relation between time to treatment and outcome (composite score, infarct size, ejection fraction, and mortality) was also assessed. Results. — Initiating treatment before hospital arrival decreased the interval from symptom onset to treatment from 110 to 77 minutes (P Conclusion. —There was no improvement in outcome associated with initiating treatment before hospital arrival; however, treatment within 70 minutes of symptom onset—whether in the hospital or in the field—minimized the infarct process and its complications. (JAMA. 1993;270:1211-1216)
TL;DR: A primary care physician inspired by a recent editorial in JAMA about lifelong learning decides to use some of the time he normally takes for continuing medical education conferences for "practice-based education" tailored to his own practice.
Abstract: CLINICAL SCENARIO You are a primary care physician inspired by a recent editorial in JAMA about lifelong learning. 1 You decide to use some of the time you normally take for continuing medical education conferences for "practice-based education" tailored to your own practice. You begin by setting aside 2 hours every week to read about relevant clinical problems. It is now Friday morning and you have 2 hours to spend in the hospital library. You review a one-page list of questions you have generated from the patients you've seen in the prior week. Your questions include these: What should you tell a 33-year-old woman with migraine headaches who has asked for a prescription for sumatriptan after reading a magazine article about it? Should you be screening older men in your practice for prostate cancer? What should you tell the mother of a 6-month-old boy who had a febrile seizure about
TL;DR: Intensified efforts to improve pneumococcal vaccine coverage among certain populations for whom vaccination is currently recommended is indicated, but universal revaccination is not warranted at this time.
Abstract: Objective. —To determine pneumococcal polysaccharide vaccine efficacy in selected populations at risk for serious pneumococcal infection for whom vaccination is currently recommended and to assess duration of protection after vaccination. Design. —Vaccine efficacy was estimated using indirect cohort analysis to compare the proportion of pneumococcal infections caused by serotypes included in the vaccines of vaccinated and unvaccinated persons who were identified during 14 years of national surveillance. Setting. —Hospital laboratories in the United States that submitted pneumococcal isolates to the Centers for Disease Control and Prevention between May 1978 and April 1992. Participants. —A total of 2837 persons older than 5 years who had pneumococcus isolated from blood or cerebrospinal fluid. Results. —Overall efficacy for preventing infection caused by serotypes included in the vaccine was 57% (95% confidence interval [Cl], 45% to 66%). Efficacy among persons with diabetes mellitus was 84% (95% Cl, 50% to 95%); with coronary vascular disease, 73% (95% Cl, 23% to 90%); with congestive heart failure, 69% (95% Cl, 17% to 88%); with chronic pulmonary diseases, 65% (95% Cl, 26% to 83%); and with anatomic asplenia, 77% (95% CI, 14% to 95%). Efficacy was not documented for patients with alcoholism or cirrhosis, sickle cell disease, chronic renal failure, lymphoma, leukemia, or multiple myeloma, although sample sizes were small for these groups. Efficacy for immunocompetent persons older than 65 years was 75% (95% Cl, 57% to 85%). Efficacy did not decline with increasing interval after vaccination: 5 to 8 years after vaccination it was 71% (95% Cl, 24% to 89%), and 9 years or more after vaccination it was 80% (95% Cl, 16% to 95%). Conclusions. —Intensified efforts to improve pneumococcal vaccine coverage among certain populations for whom vaccination is currently recommended is indicated, but universal revaccination is not warranted at this time. ( JAMA . 1993;270:1826-1831)
TL;DR: Group A streptococcal infections characterized by signs including shock, multi—organ system involvement, and rapidly progressive, destructive soft-tissue infection (necrotizing fasciitis) even though most patients received appropriate antimicrobial therapy, supportive care, and, where necessary, surgical debridement.
Abstract: GROUP A streptococcus (Streptococcus pyogenes) may cause a variety of illnesses ranging from very common, usually clinically mild conditions such as pharyngitis and impetigo to less common severe infections including septicemia and pneumonia. In 1987, Cone et al1described two patients with severe group A streptococcal infections having clinical features similar to the staphylococcal toxic shock syndrome. This syndrome, designated the "streptococcal toxic shock—like syndrome" or the "toxic streptococcal syndrome,"2was further characterized by Stevens et al3in a series of 20 patients. Most patients included in this series were less than 50 years old and otherwise healthy. All had invasive group A streptococcal infections characterized by signs including shock, multi—organ system involvement, and rapidly progressive, destructive soft-tissue infection (necrotizing fasciitis). The case-fatality rate was 30% even though most patients received appropriate antimicrobial therapy, supportive care, and, where necessary, surgical debridement. Ten available isolates were serotyped and