Showing papers in "JAMA in 2000"

Meta-analysis of observational studies in epidemiology - A proposal for reporting

Abstract: ObjectiveBecause of the pressure for timely, informed decisions in public health and clinical practice and the explosion of information in the scientific literature, research results must be synthesized. Meta-analyses are increasingly used to address this problem, and they often evaluate observational studies. A workshop was held in Atlanta, Ga, in April 1997, to examine the reporting of meta-analyses of observational studies and to make recommendations to aid authors, reviewers, editors, and readers.ParticipantsTwenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedical editing. Deliberations of the workshop were open to other interested scientists. Funding for this activity was provided by the Centers for Disease Control and Prevention.EvidenceWe conducted a systematic review of the published literature on the conduct and reporting of meta-analyses in observational studies using MEDLINE, Educational Research Information Center (ERIC), PsycLIT, and the Current Index to Statistics. We also examined reference lists of the 32 studies retrieved and contacted experts in the field. Participants were assigned to small-group discussions on the subjects of bias, searching and abstracting, heterogeneity, study categorization, and statistical methods.Consensus ProcessFrom the material presented at the workshop, the authors developed a checklist summarizing recommendations for reporting meta-analyses of observational studies. The checklist and supporting evidence were circulated to all conference attendees and additional experts. All suggestions for revisions were addressed.ConclusionsThe proposed checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion. Use of the checklist should improve the usefulness of meta-analyses for authors, reviewers, editors, readers, and decision makers. An evaluation plan is suggested and research areas are explored.

World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

Abstract: WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI Ethical Principles for Medical Research Involving Human Subjects 世界医師会ヘルシンキ宣言 ヒトを対象とした医学研究の倫理原則 ---------------------------------------------------------------------------Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the: 29th WMA General Assembly, Tokyo, Japan, October 1975 35th WMA General Assembly, Venice, Italy, October 1983 41st WMA General Assembly, Hong Kong, September 1989 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 52nd WMA General Assembly, Edinburgh, Scotland, October 2000 53rd WMA General Assembly, Washington 2002 (Note of Clarification on paragraph 29 added) 55th WMA General Assembly, Tokyo 2004 (Note of Clarification on Paragraph 30 added) 59th WMA General Assembly, Seoul, October 2008 64th WMA General Assembly, Fortaleza, Brazil, October 2013

Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis: The CLASS Study: A Randomized Controlled Trial

Abstract: ContextConventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2–specific inhibitors are associated with fewer clinical GI toxic effects is unknown.ObjectiveTo determine whether celecoxib, a COX-2–specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs.DesignThe Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000.SettingThree hundred eighty-six clinical sites in the United States and Canada.ParticipantsA total of 8059 patients (≥18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months.InterventionsPatients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis (≤325 mg/d) was permitted.Main Outcome MeasuresIncidence of prospectively defined symptomatic upper GI ulcers and ulcer complications (bleeding, perforation, and obstruction) and other adverse effects during the 6-month treatment period.ResultsFor all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76% vs 1.45% (P = .09) and 2.08% vs 3.54% (P = .02), respectively. For patients not taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44% vs 1.27% (P = .04) and 1.40% vs 2.91% (P = .02). For patients taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01% vs 2.12% (P = .92) and 4.70% vs 6.00% (P = .49). Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity. No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs, irrespective of aspirin use.ConclusionsIn this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly.

The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease.

Abstract: ContextAcute aortic dissection is a life-threatening medical emergency associated with high rates of morbidity and mortality. Data are limited regarding the effect of recent imaging and therapeutic advances on patient care and outcomes in this setting.ObjectiveTo assess the presentation, management, and outcomes of acute aortic dissection.DesignCase series with patients enrolled between January 1996 and December 1998. Data were collected at presentation and by physician review of hospital records.SettingThe International Registry of Acute Aortic Dissection, consisting of 12 international referral centers.ParticipantsA total of 464 patients (mean age, 63 years; 65.3% male), 62.3% of whom had type A dissection.Main Outcome MeasuresPresenting history, physical findings, management, and mortality, as assessed by history and physician review of hospital records.ResultsWhile sudden onset of severe sharp pain was the single most common presenting complaint, the clinical presentation was diverse. Classic physical findings such as aortic regurgitation and pulse deficit were noted in only 31.6% and 15.1% of patients, respectively, and initial chest radiograph and electrocardiogram were frequently not helpful (no abnormalities were noted in 12.4% and 31.3% of patients, respectively). Computed tomography was the initial imaging modality used in 61.1%. Overall in-hospital mortality was 27.4%. Mortality of patients with type A dissection managed surgically was 26%; among those not receiving surgery (typically because of advanced age and comorbidity), mortality was 58%. Mortality of patients with type B dissection treated medically was 10.7%. Surgery was performed in 20% of patients with type B dissection; mortality in this group was 31.4%.ConclusionsAcute aortic dissection presents with a wide range of manifestations, and classic findings are often absent. A high clinical index of suspicion is necessary. Despite recent advances, in-hospital mortality rates remain high. Our data support the need for continued improvement in prevention, diagnosis, and management of acute aortic dissection.

Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community-Based Study

Abstract: ContextSleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both.ObjectiveTo assess the association between SDB and hypertension in a large cohort of middle-aged and older persons.Design and SettingCross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998.ParticipantsA total of 6132 subjects recruited from ongoing population-based studies (aged ≥40 years; 52.8% female).Main Outcome MeasuresApnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a ≥30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a ≥4% drop in oxyhemoglobin saturation), obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication.ResultsMean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (≥30 per hour) with the lowest category (<1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend=.005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (≥12% vs <0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring.ConclusionOur findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

The TIMI Risk Score for Unstable Angina/Non–ST Elevation MI: A Method for Prognostication and Therapeutic Decision Making

Abstract: ContextPatients with unstable angina/non–ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and cardiac ischemic events.ObjectiveTo develop a simple risk score that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different responses to treatments for UA/NSTEMI.Design, Setting, and PatientsTwo phase 3, international, randomized, double-blind trials (the Thrombolysis in Myocardial Infarction [TIMI] 11B trial [August 1996–March 1998] and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial [ESSENCE; October 1994–May 1996]). A total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated heparin (test cohort) and 1953 to receive enoxaparin in TIMI 11B; 1564 and 1607 were assigned respectively in ESSENCE. The 3 validation cohorts were the unfractionated heparin group from ESSENCE and both enoxaparin groups.Main Outcome MeasuresThe TIMI risk score was derived in the test cohort by selection of independent prognostic variables using multivariate logistic regression, assignment of value of 1 when a factor was present and 0 when it was absent, and summing the number of factors present to categorize patients into risk strata. Relative differences in response to therapeutic interventions were determined by comparing the slopes of the rates of events with increasing score in treatment groups and by testing for an interaction between risk score and treatment. Outcomes were TIMI risk score for developing at least 1 component of the primary end point (all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization) through 14 days after randomization.ResultsThe 7 TIMI risk score predictor variables were age 65 years or older, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50% or more, ST-segment deviation on electrocardiogram at presentation, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers. Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B: 4.7% for a score of 0/1; 8.3% for 2; 13.2% for 3; 19.9% for 4; 26.2% for 5; and 40.9% for 6/7 (P<.001 by χ2 for trend). The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups (P<.001). The slope of the increase in event rates with increasing numbers of risk factors was significantly lower in the enoxaparin groups in both TIMI 11B (P = .01) and ESSENCE (P = .03) and there was a significant interaction between TIMI risk score and treatment (P = .02).ConclusionsIn patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient's risk of death and ischemic events and provides a basis for therapeutic decision making.

Smoking and Mental Illness: A Population-Based Prevalence Study

Abstract: ContextStudies of selected groups of persons with mental illness, such as those who are institutionalized or seen in mental health clinics, have reported rates of smoking to be higher than in persons without mental illness. However, recent population-based, nationally representative data are lacking.ObjectiveTo assess rates of smoking and tobacco cessation in adults, with and without mental illness.Design, Setting, and ParticipantsAnalysis of data on 4411 respondents aged 15 to 54 years from the National Comorbidity Survey, a nationally representative multistage probability survey conducted from 1991 to 1992.Main Outcome MeasuresRates of smoking and tobacco cessation according to the number and type of psychiatric diagnoses, assessed by a modified version of the Composite International Diagnostic Interview.ResultsCurrent smoking rates for respondents with no mental illness, lifetime mental illness, and past-month mental illness were 22.5%, 34.8%, and 41.0%, respectively. Lifetime smoking rates were 39.1%, 55.3%, and 59.0%, respectively (P<.001 for all comparisons). Smokers with any history of mental illness had a self-reported quit rate of 37.1% (P = .04), and smokers with past-month mental illness had a self-reported quit rate of 30.5% (P<.001) compared with smokers without mental illness (42.5%). Odds ratios for current and lifetime smoking in respondents with mental illness in the past month vs respondents without mental illness, adjusted for age, sex, and region of the country, were 2.7 (95% confidence interval [CI], 2.3-3.1) and 2.7 (95% CI, 2.4-3.2), respectively. Persons with a mental disorder in the past month consumed approximately 44.3% of cigarettes smoked by this nationally representative sample.ConclusionsPersons with mental illness are about twice as likely to smoke as other persons but have substantial quit rates.

Drug Dependence, a Chronic Medical Illness: Implications for Treatment, Insurance, and Outcomes Evaluation

Abstract: The effects of drug dependence on social systems has helped shape the generally held view that drug dependence is primarily a social problem, not a health problem. In turn, medical approaches to prevention and treatment are lacking. We examined evidence that drug (including alcohol) dependence is a chronic medical illness. A literature review compared the diagnoses, heritability, etiology (genetic and environmental factors), pathophysiology, and response to treatments (adherence and relapse) of drug dependence vs type 2 diabetes mellitus, hypertension, and asthma. Genetic heritability, personal choice, and environmental factors are comparably involved in the etiology and course of all of these disorders. Drug dependence produces significant and lasting changes in brain chemistry and function. Effective medications are available for treating nicotine, alcohol, and opiate dependence but not stimulant or marijuana dependence. Medication adherence and relapse rates are similar across these illnesses. Drug dependence generally has been treated as if it were an acute illness. Review results suggest that long-term care strategies of medication management and continued monitoring produce lasting benefits. Drug dependence should be insured, treated, and evaluated like other chronic illnesses.

Factors Considered Important at the End of Life by Patients, Family, Physicians, and Other Care Providers

Abstract: ContextA clear understanding of what patients, families, and health care practitioners view as important at the end of life is integral to the success of improving care of dying patients. Empirical evidence defining such factors, however, is lacking.ObjectiveTo determine the factors considered important at the end of life by patients, their families, physicians, and other care providers.Design and SettingCross-sectional, stratified random national survey conducted in March-August 1999.ParticipantsSeriously ill patients (n = 340), recently bereaved family (n = 332), physicians (n = 361), and other care providers (nurses, social workers, chaplains, and hospice volunteers; n = 429).Main Outcome MeasuresImportance of 44 attributes of quality at the end of life (5-point scale) and rankings of 9 major attributes, compared in the 4 groups.ResultsTwenty-six items consistently were rated as being important (>70% responding that item is important) across all 4 groups, including pain and symptom management, preparation for death, achieving a sense of completion, decisions about treatment preferences, and being treated as a "whole person." Eight items received strong importance ratings from patients but less from physicians (P<.001), including being mentally aware, having funeral arrangements planned, not being a burden, helping others, and coming to peace with God. Ten items had broad variation within as well as among the 4 groups, including decisions about life-sustaining treatments, dying at home, and talking about the meaning of death. Participants ranked freedom from pain most important and dying at home least important among 9 major attributes.ConclusionsAlthough pain and symptom management, communication with one's physician, preparation for death, and the opportunity to achieve a sense of completion are important to most, other factors important to quality at the end of life differ by role and by individual. Efforts to evaluate and improve patients' and families' experiences at the end of life must account for diverse perceptions of quality.

What Makes Clinical Research Ethical

Abstract: Many believe that informed consent makes clinical research ethical. However, informed consent is neither necessary nor sufficient for ethical clinical research. Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, we propose 7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies: (1) value-enhancements of health or knowledge must be derived from the research; (2) scientific validity-the research must be methodologically rigorous; (3) fair subject selection-scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria for individual subjects; (4) favorable risk-benefit ratio-within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks; (5) independent review-unaffiliated individuals must review the research and approve, amend, or terminate it; (6) informed consent-individuals should be informed about the research and provide their voluntary consent; and (7) respect for enrolled subjects-subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored. Fulfilling all 7 requirements is necessary and sufficient to make clinical research ethical. These requirements are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted. JAMA. 2000;283:2701-2711.

Pituitary-Adrenal and Autonomic Responses to Stress in Women After Sexual and Physical Abuse in Childhood

Abstract: ContextEvidence suggests that early adverse experiences play a preeminent role in development of mood and anxiety disorders and that corticotropin-releasing factor (CRF) systems may mediate this association.ObjectiveTo determine whether early-life stress results in a persistent sensitization of the hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby contributing to vulnerability to psychopathological conditions.Design and SettingProspective controlled study conducted from May 1997 to July 1999 at the General Clinical Research Center of Emory University Hospital, Atlanta, Ga.ParticipantsForty-nine healthy women aged 18 to 45 years with regular menses, with no history of mania or psychosis, with no active substance abuse or eating disorder within 6 months, and who were free of hormonal and psychotropic medications were recruited into 4 study groups (n = 12 with no history of childhood abuse or psychiatric disorder [controls]; n = 13 with diagnosis of current major depression who were sexually or physically abused as children; n = 14 without current major depression who were sexually or physically abused as children; and n = 10 with diagnosis of current major depression and no history of childhood abuse).Main Outcome MeasuresAdrenocorticotropic hormone (ACTH) and cortisol levels and heart rate responses to a standardized psychosocial laboratory stressor compared among the 4 study groups.ResultsWomen with a history of childhood abuse exhibited increased pituitary-adrenal and autonomic responses to stress compared with controls. This effect was particularly robust in women with current symptoms of depression and anxiety. Women with a history of childhood abuse and a current major depression diagnosis exhibited a more than 6-fold greater ACTH response to stress than age-matched controls (net peak of 9.0 pmol/L [41.0 pg/mL]; 95% confidence interval [CI], 4.7-13.3 pmol/L [21.6-60.4 pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL]; 95% CI, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% CI, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001).ConclusionsOur findings suggest that hypothalamic-pituitary-adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF hypersecretion, is a persistent consequence of childhood abuse that may contribute to the diathesis for adulthood psychopathological conditions. Furthermore, these results imply a role for CRF receptor antagonists in the prevention and treatment of psychopathological conditions related to early-life stress.

Longitudinal study of moderate weight change and sleep-disordered breathing.

Abstract: ContextExcess body weight is positively associated with sleep-disordered breathing (SDB), a prevalent condition in the US general population. No large study has been conducted of the longitudinal association between SDB and change in weight.ObjectiveTo measure the independent longitudinal association between weight change and change in SDB severity.DesignPopulation-based, prospective cohort study conducted from July 1989 to January 2000.Setting and ParticipantsSix hundred ninety randomly selected employed Wisconsin residents (mean age at baseline, 46 years; 56% male) who were evaluated twice at 4-year intervals for SDB.Main Outcome MeasuresPercentage change in the apnea-hypopnea index (AHI; apnea events + hypopnea events per hour of sleep) and odds of developing moderate-to-severe SDB (defined by an AHI ≥15 events per hour of sleep), with respect to change in weight.ResultsRelative to stable weight, a 10% weight gain predicted an approximate 32% (95% confidence interval [CI], 20%-45%) increase in the AHI. A 10% weight loss predicted a 26% (95% CI, 18%-34%) decrease in the AHI. A 10% increase in weight predicted a 6-fold (95% CI, 2.2-17.0) increase in the odds of developing moderate-to-severe SDB.ConclusionsOur data indicate that clinical and public health programs that result in even modest weight control are likely to be effective in managing SDB and reducing new occurrence of SDB.

Serum Uric Acid and Cardiovascular Mortality: The NHANES I Epidemiologic Follow-up Study, 1971-1992

Abstract: ContextAlthough many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for cardiovascular mortality, this relationship remains uncertain.ObjectiveTo determine the association of serum uric acid levels with cardiovascular mortality.Design and SettingCross-sectional population-based study of epidemiological follow-up data from the First National Health and Nutrition Examination Survey (NHANES I) from 1971-1975 (baseline) and data from NHANES I Epidemiologic Follow-up Study (NHEFS).ParticipantsA total of 5926 subjects who were aged 25 to 74 years and had serum uric acid level measurements at baseline.Main Outcome MeasuresIschemic heart disease mortality, total cardiovascular mortality, and all-cause mortality, compared by quartiles of serum uric acid level.ResultsIn an average of 16.4 years of follow-up, 1593 deaths occurred, of which 731 (45.9%) were ascribed to cardiovascular disease. Increased serum uric acid levels had a positive relationship to cardiovascular mortality in men and women and in black and white persons. Deaths due to ischemic heart disease in both men and women increased when serum uric acid levels were in the highest quartile compared with the lowest quartile (men, >416 vs <321 µmol/L; risk ratio, 1.77 [95% confidence interval {CI}, 1.08-3.98]; women, >333 vs <238 µmol/L; risk ratio, 3.00 [95% CI, 1.45-6.28]). Cox regression analysis showed that for each 59.48-µmol/L increase in uric acid level, cardiovascular mortality and ischemic heart disease mortality increased. Hazard ratios for men were 1.09 (95% CI, 1.02-1.18) and 1.17 (95% CI, 1.06-1.28), and for women were 1.26 (95% CI, 1.16-1.36) and 1.30 (95% CI, 1.17-1.45), respectively, after adjustment for age, race, body mass index, smoking status, alcohol consumption, cholesterol level, history of hypertension and diabetes, and diuretic use. Further analysis, stratifying by cardiovascular risk status, diuretic use, and menopausal status, confirmed a significant association of uric acid and cardiovascular mortality in all subgroups except among men using diuretics (n=79) and men with 1 or more cardiovascular risk factors (n=1140).ConclusionOur data suggest that increased serum uric acid levels are independently and significantly associated with risk of cardiovascular mortality.

Physicians and the pharmaceutical industry: is a gift ever just a gift?

Abstract: ContextControversy exists over the fact that physicians have regular contact with the pharmaceutical industry and its sales representatives, who spend a large sum of money each year promoting to them by way of gifts, free meals, travel subsidies, sponsored teachings, and symposia.ObjectiveTo identify the extent of and attitudes toward the relationship between physicians and the pharmaceutical industry and its representatives and its impact on the knowledge, attitudes, and behavior of physicians.Data SourcesA MEDLINE search was conducted for English-language articles published from 1994 to present, with review of reference lists from retrieved articles; in addition, an Internet database was searched and 5 key informants were interviewed.Study SelectionA total of 538 studies that provided data on any of the study questions were targeted for retrieval, 29 of which were included in the analysis.Data ExtractionData were extracted by 1 author. Articles using an analytic design were considered to be of higher methodological quality.Data SynthesisPhysician interactions with pharmaceutical representatives were generally endorsed, began in medical school, and continued at a rate of about 4 times per month. Meetings with pharmaceutical representatives were associated with requests by physicians for adding the drugs to the hospital formulary and changes in prescribing practice. Drug company–sponsored continuing medical education (CME) preferentially highlighted the sponsor's drug(s) compared with other CME programs. Attending sponsored CME events and accepting funding for travel or lodging for educational symposia were associated with increased prescription rates of the sponsor's medication. Attending presentations given by pharmaceutical representative speakers was also associated with nonrational prescribing.ConclusionThe present extent of physician-industry interactions appears to affect prescribing and professional behavior and should be further addressed at the level of policy and education.

Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT)

Abstract: CONTEXT Hypertension is associated with a significantly increased risk of morbidity and mortality. Only diuretics and beta-blockers have been shown to reduce this risk in long-term clinical trials. Whether newer antihypertensive agents reduce the incidence of cardiovascular disease (CVD) is unknown. OBJECTIVE To compare the effect of doxazosin, an alpha-blocker, with chlorthalidone, a diuretic, on incidence of CVD in patients with hypertension as part of a study of 4 types of antihypertensive drugs: chlorthalidone, doxazosin, amlodipine, and lisinopril. DESIGN Randomized, double-blind, active-controlled clinical trial, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, initiated in February 1994. In January 2000, after an interim analysis, an independent data review committee recommended discontinuing the doxazosin treatment arm based on comparisons with chlorthalidone. Therefore, outcomes data presented herein reflect follow-up through December 1999. SETTING A total of 625 centers in the United States and Canada. PARTICIPANTS A total of 24,335 patients (aged > or = 55 years) with hypertension and at least 1 other coronary heart disease (CHD) risk factor who received either doxazosin or chlorthalidone. INTERVENTIONS Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n=15,268), or doxazosin, 2 to 8 mg/d (n=9067), for a planned follow-up of 4 to 8 years. MAIN OUTCOME MEASURES The primary outcome measure was fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; secondary outcome measures included all-cause mortality, stroke, and combined CVD (CHD death, nonfatal MI, stroke, angina, coronary revascularization, congestive heart failure [CHF], and peripheral arterial disease); compared by the chlorthalidone group vs the doxazosin group. RESULTS Median follow-up was 3.3 years. A total of 365 patients in the doxazosin group and 608 in the chlorthalidone group had fatal CHD or nonfatal MI, with no difference in risk between the groups (relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.17; P=.71). Total mortality did not differ between the doxazosin and chlorthalidone arms (4-year rates, 9.62% and 9.08%, respectively; RR, 1.03; 95% CI, 0.90-1.15; P=.56.) The doxazosin arm, compared with the chlorthalidone arm, had a higher risk of stroke (RR, 1.19; 95% CI, 1.01-1.40; P=.04) and combined CVD (4-year rates, 25.45% vs 21.76%; RR, 1.25; 95% CI, 1.17-1.33; P<.001). Considered separately, CHF risk was doubled (4-year rates, 8.13% vs 4.45%; RR, 2.04; 95% CI, 1.79-2.32; P<.001); RRs for angina, coronary revascularization, and peripheral arterial disease were 1.16 (P<.001), 1.15 (P=.05), and 1.07 (P=.50), respectively. CONCLUSION Our data indicate that compared with doxazosin, chlorthalidone yields essentially equal risk of CHD death/nonfatal MI but significantly reduces the risk of combined CVD events, particularly CHF, in high-risk hypertensive patients.

Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline

Abstract: ContextAlzheimer disease (AD) is characterized neuropathologically by the presence of amyloid β-peptide (Aβ)–containing plaques and neurofibrillary tangles composed of abnormal tau protein. Considerable controversy exists as to whether the extent of accumulation of Aβ correlates with dementia and whether Aβ alterations precede or follow changes in tau.ObjectivesTo determine whether accumulation of Aβ correlates with the earliest signs of cognitive deterioration and to define the relationship between Aβ accumulation and early tau changes.Design, Setting, and PatientsPostmortem cross-sectional study of 79 nursing home residents with Clinical Dementia Rating (CDR) scale scores of 0.0 to 5.0 who died between 1986 and 1997, comparing the levels of Aβ variants in the cortices of the subjects with no (CDR score, 0.0 [n = 16]), questionable (CDR score, 0.5 [n = 11]), mild (CDR score, 1.0 [n = 22]), moderate (CDR score, 2.0 [n = 15]), or severe (CDR score, 4.0 or 5.0 [n = 15]) dementia.Main Outcome MeasuresLevels of total Aβ peptides with intact or truncated amino termini and ending in either amino acid 40 (Aβx-40) or 42 (Aβx-42) in 5 neocortical brain regions as well as levels of tau protein undergoing early conformational changes in frontal cortex, as a function of CDR score.ResultsThe levels of both Aβx-40 and Aβx-42 were elevated even in cases classified as having questionable dementia (CDR score = 0.5), and increases of both peptides correlated with progression of dementia. Levels of the more fibril-prone Aβx-42 peptide were higher than those of Aβx-40 in nondemented cases and remained higher throughout progression of disease in all regions examined. Finally, increases in Aβx-40 and Aβx-42 precede significant tau pathology at least in the frontal cortex, an area chosen for examination because of the absence of neuritic changes in the absence of disease.ConclusionsIn this study, levels of total Aβx-40 and Aβx-42 were elevated early in dementia and levels of both peptides were strongly correlated with cognitive decline. Of particular interest, in the frontal cortex, Aβ was elevated before the occurrence of significant tau pathology. These results support an important role for Aβ in mediating initial pathogenic events in AD dementia and suggest that treatment strategies targeting the formation, accumulation, or cytotoxic effects of Aβ should be pursued.

Effects of Controlled-Release Metoprolol on Total Mortality, Hospitalizations, and Well-being in Patients With Heart Failure: The Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF)

Abstract: For editorial comment see p 1335. Context Results from recent studies on the effects of b1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of b1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. Objective To examine the effects of the b1-blocker controlled-release/extendedrelease metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure.

Short-term Prognosis After Emergency Department Diagnosis of TIA

Abstract: ContextManagement of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations. Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation.ObjectiveTo determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA.Design and SettingCohort study conducted from March 1997 through February 1998 in 16 hospitals in a health maintenance organization in northern California.PatientsA total of 1707 patients (mean age, 72 years) identified by ED physicians as having presented with TIA.Main Outcome MeasuresRisk of stroke during the 90 days after index TIA; other events, including death, recurrent TIA, and hospitalization for cardiovascular events.ResultsDuring the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days. Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; P = .01), diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9; P<.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2; P = .005), weakness (OR, 1.9; 95% CI, 1.4-2.6; P<.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1; P = .01). Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%).ConclusionsOur results indicate that the short-term risk of stroke and other adverse events among patients who present to an ED with a TIA is substantial. Characteristics of the patient and the TIA may be useful for identifying patients who may benefit from expeditious evaluation and treatment.

Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction.

Abstract: ContextRapid time to treatment with thrombolytic therapy is associated with lower mortality in patients with acute myocardial infarction (MI). However, data on time to primary angioplasty and its relationship to mortality are inconclusive.ObjectiveTo test the hypothesis that more rapid time to reperfusion results in lower mortality in the strategy of primary angioplasty.DesignProspective observational study of data collected from the Second National Registry of Myocardial Infarction between June 1994 and March 1998.SettingA total of 661 community and tertiary care hospitals in the United States.SubjectsA cohort of 27,080 consecutive patients with acute MI associated with ST-segment elevation or left bundle-branch block who were treated with primary angioplasty.Main Outcome MeasureIn-hospital mortality, compared by time from acute MI symptom onset to first balloon inflation and by time from hospital arrival to first balloon inflation (door-to-balloon time).ResultsUsing a multivariate logistic regression model, the adjusted odds of in-hospital mortality did not increase significantly with increasing delay from MI symptom onset to first balloon inflation. However, for door-to-balloon time (median time 1 hour 56 minutes), the adjusted odds of mortality were significantly increased by 41% to 62% for patients with door-to-balloon times longer than 2 hours (for 121-150 minutes: odds ratio [OR], 1.41; 95% confidence interval [CI], 1.08-1.84; P=.01; for 151-180 minutes: OR, 1.62; 95% CI, 1.23-2.14; P 180 minutes: OR, 1.61; 95% CI, 1.25-2.08; P<.001).ConclusionsThe relationship in our study between increased mortality and delay in door-to-balloon time longer than 2 hours (present in nearly 50% of this cohort) suggests that physicians and health care systems should work to minimize door-to-balloon times and that door-to-balloon time should be considered when choosing a reperfusion strategy. Door-to-balloon time also appears to be a valid quality-of-care indicator.

Inequality in quality : Addressing socioeconomic, racial, and ethnic disparities in health care

Abstract: Socioeconomic and racial/ethnic disparities in health care quality have been extensively documented. Recently, the elimination of disparities in health care has become the focus of a national initiative. Yet, there is little effort to monitor and address disparities in health care through organizational quality improvement. After reviewing literature on disparities in health care, we discuss the limitations in existing quality assessment for identifying and addressing these disparities. We propose 5 principles to address these disparities through modifications in quality performance measures: disparities represent a significant quality problem; current data collection efforts are inadequate to identify and address disparities; clinical performance measures should be stratified by race/ethnicity and socioeconomic position for public reporting; population-wide monitoring should incorporate adjustment for race/ethnicity and socioeconomic position; and strategies to adjust payment for race/ethnicity and socioeconomic position should be considered to reflect the known effects of both on morbidity. JAMA. 2000;283:2579-2584

Comparison of vignettes, standardized patients, and chart abstraction: A Prospective validation study of 3 methods for measuring quality

Abstract: ContextBetter health care quality is a universal goal, yet measuring quality has proven to be difficult and problematic. A central problem has been isolating physician practices from other effects of the health care system.ObjectiveTo validate clinical vignettes as a method for measuring the competence of physicians and the quality of their actual practice.DesignProspective trial conducted in 1997 comparing 3 methods for measuring the quality of care for 4 common outpatient conditions: (1) structured reports by standardized patients (SPs), trained actors who presented unannounced to physicians' clinics (the gold standard); (2) abstraction of medical records for those same visits; and (3) physicians' responses to clinical vignettes that exactly corresponded to the SPs' presentations.SettingOutpatient primary care clinics at 2 Veterans Affairs medical centers.ParticipantsNinety-eight (97%) of 101 general internal medicine staff physicians, faculty, and second- and third-year residents consented to be randomized for the study. From this group, 10 physicians at each site were randomly selected for inclusion.Main Outcome MeasuresA total of 160 quality scores (8 cases × 20 physicians) were generated for each method using identical explicit criteria based on national guidelines and local expert panels. Scores were defined as the percentage of process criteria correctly met and were compared among the 3 methods.ResultsThe quality of care, as measured by all 3 methods, ranged from 76.2% (SPs) to 71.0% (vignettes) to 65.6% (chart abstraction). Measuring quality using vignettes consistently produced scores closer to the gold standard of SP scores than using chart abstraction. This pattern was robust when the scores were disaggregated by the 4 conditions (P<.001 to <.05), by case complexity (P<.001), by site (P<.001), and by level of physician training (P values from <.001 to <.05). The pattern persisted, although less dominantly, when we assessed the component domains of the clinical encounter—history, physical examination, diagnosis, and treatment. Vignettes were responsive to expected directions of variation in quality between sites and levels of training. The vignette responses did not appear to be sensitive to physicians' having seen an SP presenting with the same case.ConclusionsOur data indicate that quality of health care can be measured in an outpatient setting by using clinical vignettes. Vignettes appear to be a valid and comprehensive method that directly focuses on the process of care provided in actual clinical practice. Vignettes show promise as an inexpensive case-mix adjusted method for measuring the quality of care provided by a group of physicians.

Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice.

Abstract: Each year, an estimated 590,000 infants acquire human immunodeficiency virus type 1 (HIV) infection from their mothers, mostly in developing countries that are unable to implement interventions now standard in the industrialized world. In resource-poor settings, the HIV pandemic has eroded hard-won gains in infant and child survival. Recent clinical trial results from international settings suggest that short-course antiretroviral regimens could significantly reduce perinatal HIV transmission worldwide if research findings could be translated into practice. This article reviews current knowledge of mother-to-child HIV transmission in developing countries, summarizes key findings from the trials, outlines future research requirements, and describes public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings. Public health efforts must also emphasize primary prevention strategies to reduce incident HIV infections among adolescents and women of childbearing age. Successful implementation of available perinatal HIV interventions could substantially improve global child survival.

Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer : The Prostate Cancer Outcomes Study

Abstract: ContextPatients with prostate cancer and their physicians need knowledge of treatment options and their potential complications, but limited data on complications are available in unselected population-based cohorts of patients.ObjectiveTo measure changes in urinary and sexual function in men who have undergone radical prostatectomy for clinically localized prostate cancer.DesignThe Prostate Cancer Outcomes Study, a population-based longitudinal cohort study with up to 24 months of follow-up.SettingPopulation-based cancer registries in 6 geographic regions of the United States.ParticipantsA total of 1291 black, white, and Hispanic men aged 39 to 79 years who were diagnosed as having primary prostate cancer between October 1, 1994, and October 31, 1995, and who underwent radical prostatectomy within 6 months of diagnosis for clinically localized disease.Main Outcome MeasuresDistribution of and change in urinary and sexual function measures reported by patients at baseline and 6, 12, and 24 months after diagnosis.ResultsAt 18 or more months following radical prostatectomy, 8.4% of men were incontinent and 59.9% were impotent. Among men who were potent before surgery, the proportion of men reporting impotence at 18 or more months after surgery varied according to whether the procedure was nerve sparing (65.6% of non–nerve-sparing, 58.6% of unilateral, and 56.0% of bilateral nerve–sparing). At 18 or more months after surgery, 41.9% reported that their sexual performance was a moderate-to-large problem. Both sexual and urinary function varied by age (39.0% of men aged <60 years vs 15.3%-21.7% of older men were potent at ≥18 months [P<.001]; 13.8% of men aged 75-79 years vs 0.7%-3.6% of younger men experienced the highest level of incontinence at ≥18 months [P = .03]), and sexual function also varied by race (38.4% of black men reported firm erections at ≥18 months vs 25.9% of Hispanic and 21.3% of white men; P = .001).ConclusionsOur study suggests that radical prostatectomy is associated with significant erectile dysfunction and some decline in urinary function. These results may be particularly helpful to community-based physicians and their patients with prostate cancer who face difficult treatment decisions.

The Natural History of Hepatitis C Virus Infection: Host, Viral, and Environmental Factors

Abstract: Context Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood. Objective To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use. Design and setting Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years. Subjects A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up. Main outcome measures Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death. Results Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis. Conclusions Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456

Antiretroviral Therapy in Adults: Updated Recommendations of the International AIDS Society–USA Panel

Abstract: Objective To update recommendations for antiretroviral therapy for adult human immunodeficiency virus type 1 (HIV-1) infection, based on new information and drugs that are available. Participants A 17-member international physician panel with antiretroviral research and HIV patient care experience initially convened by the International AIDS Society–USA in December 1995. Evidence Available clinical and basic science data including phase 3 controlled trials; data on clinical, virologic, and immunologic end points; research conference reports; HIV pathogenesis data; and panel expert opinion. Recommendations were limited to therapies available (US Food and Drug Administration approved) in 1999. Consensus Process The panel assesses new research reports and interim results and regularly meets to consider how the new data affect therapy recommendations. Recommendations are updated via full-panel consensus. Guidelines are presented as recommendations if the supporting evidence warrants routine use in the particular situation and as considerations if data are preliminary or incomplete but suggestive. Conclusions The availability of new antiretroviral drugs has expanded treatment choices. The importance of adherence, emerging long-term complications of therapy, recognition and management of antiretroviral failure, and new monitoring tools are addressed. Optimal care requires individualized management and ongoing attention to relevant scientific and clinical information in the field.

Impact of disseminating quality improvement programs for depression in managed primary care: A randomized controlled trial.

Abstract: ContextCare of patients with depression in managed primary care settings often fails to meet guideline standards, but the long-term impact of quality improvement (QI) programs for depression care in such settings is unknown.ObjectiveTo determine if QI programs in managed care practices for depressed primary care patients improve quality of care, health outcomes, and employment.DesignRandomized controlled trial initiated from June 1996 to March 1997.SettingForty-six primary care clinics in 6 US managed care organizations.ParticipantsOf 27,332 consecutively screened patients, 1356 with current depressive symptoms and either 12-month, lifetime, or no depressive disorder were enrolled.InterventionsMatched clinics were randomized to usual care (mailing of practice guidelines) or to 1 of 2 QI programs that involved institutional commitment to QI, training local experts and nurse specialists to provide clinician and patient education, identification of a pool of potentially depressed patients, and either nurses for medication follow-up or access to trained psychotherapists.Main Outcome MeasuresProcess of care (use of antidepressant medication, mental health specialty counseling visits, medical visits for mental health problems, any medical visits), health outcomes (probable depression and health-related quality of life [HRQOL]), and employment at baseline and at 6- and 12-month follow-up.ResultsPatients in QI (n = 913) and control (n = 443) clinics did not differ significantly at baseline in service use, HRQOL, or employment after nonresponse weighting. At 6 months, 50.9% of QI patients and 39.7% of controls had counseling or used antidepressant medication at an appropriate dosage (P<.001), with a similar pattern at 12 months (59.2% vs 50.1%; P = .006). There were no differences in probability of having any medical visit at any point (each P≥.21). At 6 months, 47.5% of QI patients and 36.6% of controls had a medical visit for mental health problems (P = .001), and QI patients were more likely to see a mental health specialist at 6 months (39.8% vs 27.2%; P<.001) and at 12 months (29.1% vs 22.7%; P = .03). At 6 months, 39.9% of QI patients and 49.9% of controls still met criteria for probable depressive disorder (P = .001), with a similar pattern at 12 months (41.6% vs 51.2%; P = .005). Initially employed QI patients were more likely to be working at 12 months relative to controls (P = .05).ConclusionsWhen these managed primary care practices implemented QI programs that improve opportunities for depression treatment without mandating it, quality of care, mental health outcomes, and retention of employment of depressed patients improved over a year, while medical visits did not increase overall.

Users' Guides to the Medical Literature: XXII: How to Use Articles About Clinical Decision Rules

Abstract: Clinical experience provides clinicians with an intuitive sense of which findings on history, physical examination, and investigation are critical in making an accurate diagnosis, or an accurate assessment of a patient’s fate. A clinical decision rule (CDR) is a clinical tool that quantifies the individual contributions that various components of the history, physical examination, and basic laboratory results make toward the diagnosis, prognosis, or likely response to treatment in a patient. Clinical decision rules attempt to formally test, simplify, and increase the accuracy of clinicians’ diagnostic and prognostic assessments. Existing CDRs guide clinicians, establish pretest probability, provide screening tests for common problems, and estimate risk. Three steps are involved in the development and testing of a CDR: creation of the rule, testing or validating the rule, and assessing the impact of the rule on clinical behavior. Clinicians evaluating CDRs for possible clinical use should assess the following components: the method of derivation; the validation of the CDR to ensure that its repeated use leads to the same results; and its predictive power. We consider CDRs that have been validated in a new clinical setting to be level 1 CDRs and most appropriate for implementation. Level 1 CDRs have the potential to inform clinical judgment, to change clinical behavior, and to reduce unnecessary costs, while maintaining quality of care and patient satisfaction. JAMA. 2000;284:79-84 www.jama.com

Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk.

Abstract: N A RECENT COLLABORATIVE REanalysis of more than 90% of the world’s epidemiological data on the relationship between menopausal hormone replacement therapy (HRT) and breast cancer risk, it was found that longer durations of recent, but not past, use of HRT increased breast cancer risk, particularly among leaner women and for tumors that were less clinically advanced. 1 Unresolved issues include the extent to which the findings were due to a biological effect of hormones rather than issues of screening and ascertainment. The data were also insufficient to determine whether a combined estrogen-progestin regimen increased risk beyond that associated with estrogen alone. In 1994, we published data on HRT

Regional brain volume abnormalities and long-term cognitive outcome in preterm infants.

Abstract: ContextPreterm infants have a high prevalence of long-term cognitive and behavioral disturbances. However, it is not known whether the stresses associated with premature birth disrupt regionally specific brain maturation or whether abnormalities in brain structure contribute to cognitive deficits.ObjectiveTo determine whether regional brain volumes differ between term and preterm children and to examine the association of regional brain volumes in prematurely born children with long-term cognitive outcomes.Design and SettingCase-control study conducted in 1998 and 1999 at 2 US university medical schools.ParticipantsA consecutive sample of 25 eight-year-old preterm children recruited from a longitudinal follow-up study of preterm infants and 39 term control children who were recruited from the community and who were comparable with the preterm children in age, sex, maternal education, and minority status.Main Outcome MeasuresVolumes of cortical subdivisions, ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala, and hippocampus, derived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cognitive measures (at age 8 years) and perinatal variables among preterm children.ResultsRegional cortical volumes were significantly smaller in the preterm children, most prominently in sensorimotor regions (difference: left, 14.6%; right, 14.3% [P<.001 for both]) but also in premotor (left, 11.2%; right, 12.6% [P<.001 for both]), midtemporal (left, 7.4% [P = .01]; right, 10.2% [P<.001]), parieto-occipital (left, 7.9% [P = .01]; right, 7.4% [P = .005]), and subgenual (left, 8.9% [P = .03]; right, 11.7% [P = .01]) cortices. Preterm children's brain volumes were significantly larger (by 105.7%-271.6%) in the occipital and temporal horns of the ventricles (P<.001 for all) and smaller in the cerebellum (6.7%; P = .02), basal ganglia (11.4%-13.8%; P≤.005), amygdala (left, 20.2% [P = .001]; right, 30.0% [P<.001]), hippocampus (left, 16.0% [P = .001]; right, 12.0% [P = .007]), and corpus callosum (13.1%-35.2%; P≤.01 for all). Volumes of sensorimotor and midtemporal cortices were associated positively with full-scale, verbal, and performance IQ scores (P<.01 for all).ConclusionsOur data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome.