Showing papers in "JAMA Internal Medicine in 2002"
TL;DR: Better primary care, especially coordination of care, could reduce avoidable hospitalization rates, especially for individuals with multiple chronic conditions.
Abstract: Methods: A cross-sectional analysis was conducted on a nationally random sample of 1217103 Medicare feefor-service beneficiaries aged 65 and older living in the United States and enrolled in both Medicare Part A and Medicare Part B during 1999. Multiple logistic regression was used to analyze the influence of age, sex, and number of types of chronic conditions on the risk of incurring inpatient hospitalizations for ambulatory care sensitive conditions and hospitalizations with preventable complications among aged Medicare beneficiaries. Results: In 1999, 82% of aged Medicare beneficiaries had 1 or more chronic conditions, and 65% had multiple chronic conditions. Inpatient admissions for ambulatory care sensitive conditions and hospitalizations with preventable complications increased with the number of chronic conditions. For example, Medicare beneficiaries with 4 or more chronic conditions were 99 times more likely than a beneficiary without any chronic conditions to have an admission for an ambulatory care sensitive condition (95% confidence interval, 86-113). Per capita Medicare expenditures increased with the number of types of chronic conditions from $211 among beneficiaries without a chronic condition to $13973 among beneficiaries with 4 or more types of chronic conditions. Conclusions: The risk of an avoidable inpatient admission or a preventable complication in an inpatient setting increases dramatically with the number of chronic conditions. Better primary care, especially coordination of care, could reduce avoidable hospitalization rates, especially for individuals with multiple chronic conditions.
2,063 citations
TL;DR: The overweight category is associated with increased relative and population attributable risk for hypertension and cardiovascular sequelae and interventions to reduce adiposity and avoid excess weight may have large effects on the development of risk factors and cardiovascular disease at an individual and population level.
Abstract: Background To our knowledge, no single investigation concerning the long-term effects of overweight status on the risk for hypertension, hypercholesterolemia, diabetes mellitus, and cardiovascular sequelae has been reported. Methods Relations between categories of body mass index (BMI), cardiovascular disease risk factors, and vascular disease end points were examined prospectively in Framingham Heart Study participants aged 35 to 75 years, who were followed up to 44 years. The primary outcome was new cardiovascular disease, which included angina pectoris, myocardial infarction, coronary heart disease, or stroke. Analyses compared overweight (BMI [calculated as weight in kilograms divided by the square of height in meters], 25.0-29.9) and obese persons (BMI ≥30) to a referent group of normal-weight persons (BMI, 18.5-24.9). Results The age-adjusted relative risk (RR) for new hypertension was highly associated with overweight status (men: RR, 1.46; women: RR, 1.75). New hypercholesterolemia and diabetes mellitus were less highly associated with excess adiposity. The age-adjusted RR (confidence interval [CI]) for cardiovascular disease was increased among those who were overweight (men: 1.21 [1.05-1.40]; women: 1.20 [1.03-1.41]) and the obese (men: 1.46 [1.20-1.77]; women: 1.64 [1.37-1.98]). High population attributable risks were related to excess weight (BMI ≥25) for the outcomes hypertension (26% men; 28% women), angina pectoris (26% men; 22% women), and coronary heart disease (23% men; 15% women). Conclusions The overweight category is associated with increased relative and population attributable risk for hypertension and cardiovascular sequelae. Interventions to reduce adiposity and avoid excess weight may have large effects on the development of risk factors and cardiovascular disease at an individual and population level.
1,859 citations
TL;DR: A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex, particularly in older adults.
Abstract: Background Sleep-disordered breathing (SDB) is common, but largely undiagnosed in the general population. Information on demographic patterns of SDB occurrence and its predictive factors in the general population is needed to target high-risk groups that may benefit from diagnosis. Methods The sample comprised 5615 community-dwelling men and women aged between 40 and 98 years who were enrolled in the Sleep Heart Health Study. Data were collected by questionnaire, clinical examinations, and in-home polysomnography. Sleep-disordered breathing status was based on the average number of apnea and hypopnea episodes per hour of sleep (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to estimate cross-sectional associations of selected participant characteristics with SDB defined by an AHI of 15 or greater. Results Male sex, age, body mass index, neck girth, snoring, and repeated breathing pause frequency were independent, significant correlates of an AHI of 15 or greater. People reporting habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times more likely to have an AHI of 15 or greater vs an AHI less than 15, but there were weaker associations for other factors with an AHI of 15 or greater. The odds ratios (95% confidence interval) for an AHI of 15 or greater vs an AHI less than 15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and neck girth. As age increased, the magnitude of associations for SDB and body habitus, snoring, and breathing pauses decreased. Conclusions A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex. Breathing pauses and obesity may be particularly insensitive for identifying SDB in older people. A better understanding of predictive factors for SDB, particularly in older adults, is needed.
1,255 citations
TL;DR: Routine universal screening and sensitive in-depth assessment of women presenting with frequent gynecological, chronic stress-related, or central nervous system complaints are needed to support disclosure of domestic violence.
Abstract: Background: Domestic violence results in long-term and immediate health problems. This study compared selected physical health problems of abused and never abused women with similar access to health care. Methods: A case-control study of enrollees in a multisite metropolitan health maintenance organization sampled 2535 women enrollees aged 21 to 55 years who responded to an invitation to participate; 447 (18%) could not be contacted, 7 (0.3%) were ineligible, and 76 (3%) refused, yielding a sample of 2005. The Abuse Assessment Screen identified women physically and/or sexually abused between January 1, 1989, and December 31, 1997, resulting in 201 cases. The 240 controls were a random sample of never abused women. The general health perceptions subscale of the Medical Outcomes Study 36Item Short-Form Health Survey measured general health. The Miller Abuse Physical Symptom and Injury Scale measured abuse-specific health problems. tal status, educational level, and income. Direct weights were used to standardize for comparisons. Significance was tested using logistic and negative binomial regressions. Abused women had more (P.05) headaches, back pain, sexually transmitted diseases, vaginal bleeding, vaginal infections, pelvic pain, painful intercourse, urinary tract infections, appetite loss, abdominal pain, and digestive problems. Abused women also had more (P.001) gynecological, chronic stress–related, central nervous system, and total health problems. Conclusions: Abused women have a 50% to 70% increase in gynecological, central nervous system, and stressrelated problems, with women sexually and physically abused most likely to report problems. Routine universal screening and sensitive in-depth assessment of women presenting with frequent gynecological, chronic stress– related, or central nervous system complaints are needed to support disclosure of domestic violence. Arch Intern Med. 2002;162:1157-1163
1,055 citations
TL;DR: With few exceptions, within the 3 BMI categories, those with high WC values were increasingly likely to have hypertension, diabetes, dyslipidemia, and the metabolic syndrome compared with those with normal WC values.
Abstract: Background No evidence supports the waist circumference (WC) cutoff points recommended by the National Institutes of Health to identify subjects at increased health risk within the various body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) categories. Objective To examine whether the prevalence of hypertension, type 2 diabetes mellitus, dyslipidemia, and the metabolic syndrome is greater in individuals with high compared with normal WC values within the same BMI category. Methods The subjects consisted of 14 924 adult participants of the Third National Health and Nutrition Examination Survey, which is a nationally representative cross-sectional survey. Subjects were grouped by BMI and WC in accordance with the National Institutes of Health cutoff points. Within the normal-weight (18.5-24.9), overweight (25.0-29.9), and class I obese (30.0-34.9) BMI categories, we computed odds ratios for hypertension, diabetes, dyslipidemia, and the metabolic syndrome and compared subjects in the high-risk (men, >102 cm; women, >88 cm) and normal-risk (men, ≤102 cm; women, ≤88 cm) WC categories. Results With few exceptions, within the 3 BMI categories, those with high WC values were increasingly likely to have hypertension, diabetes, dyslipidemia, and the metabolic syndrome compared with those with normal WC values. Many of these associations remained significant after adjusting for the confounding variables (age, race, poverty-income ratio, physical activity, smoking, and alcohol intake) in normal-weight, overweight, and class I obese women and overweight men. Conclusions The National Institutes of Health cutoff points for WC help to identify those at increased health risk within the normal-weight, overweight, and class I obese BMI categories.
1,025 citations
TL;DR: Estimating the population attributable risk (defined as the percentage of all cases of a disease in a population that can be "attributed" to a risk factor) for deep vein thrombosis and pulmonary embolism associated with venous thromboembolism risk factors suggests greater emphasis should be placed on prophylaxis for hospitalized medical patients.
Abstract: Objective To assess the potential impact of controlling risk factors on the incidence of venous thromboembolism by estimating the population attributable risk (defined as the percentage of all cases of a disease in a population that can be "attributed" to a risk factor) for deep vein thrombosis and pulmonary embolism associated with venous thromboembolism risk factors. Methods Using data from a population-based, nested, case-control study of the 625 Olmsted County, Minnesota, residents with a definite first lifetime deep vein thrombosis or pulmonary embolism diagnosed during the 15-year period 1976 to 1990 and 625 unaffected Olmsted County residents matched for age and sex, we developed a conditional logistic regression model appropriate to the matched case-control study design and then estimated attributable risk for the risk factors individually and collectively. Results Fifty-nine percent of the cases of venous thromboembolism in the community could be attributed to institutionalization (current or recent hospitalization or nursing home residence). Hospitalization for surgery (24%) and for medical illness (22%) accounted for a similar proportion of the cases, while nursing home residence accounted for 13%. The individual attributable risk estimates for malignant neoplasm, trauma, congestive heart failure, central venous catheter or pacemaker placement, neurological disease with extremity paresis, and superficial vein thrombosis were 18%, 12%, 10%, 9%, 7%, and 5%, respectively. Together, the 8 risk factors accounted for 74% of disease occurrence. Conclusions Factors associated with institutionalization independently account for more than 50% of all cases of venous thromboembolism in the community. Greater emphasis should be placed on prophylaxis for hospitalized medical patients. Other recognized risk factors account for about 25% of all cases of venous thromboembolism, while the remaining 25% of cases are idiopathic.
1,014 citations
TL;DR: Race remained strongly associated with a higher distrust score and even after controlling for markers of social class, African Americans were less trusting than white Americans.
Abstract: Background: Investigators have voiced concerns that distrust of research and the medical community inpedes successful recruitment of African Americans into clinical research. Objective: To examine possible differences in distrust by race and to determine to what extent other sociodemographic factors explain any racial differences in distrust. Methods: We analyzed data from 527 African American and 382 white respondents of a national telephone survey on participation in clinical research. Our main outcome was a 7-item index of distrust. Results: African American respondents were more likely that white respondents not to trust that their physicians would fully explain research participation (41.7% vs 23.4%,P<.01)and to state that they believed their physicians exposed them to unnecessary risks (45.5% vs 34.8%,P<.01). African American respondents had a significantly higher mean distrust index score than white respondents(3.1 vs 1.8,P<.01). After controlling for other sociodemographic variables in a logistic regression model, race remained strongly associated with a highter distrust score (prevalence odds ratio, 4.7;95% confidence interval,2.9-7.7). Conclusions: Even after controlling for markers of social class, African Americans were less trusting than white Americans. Racial differences in disturst have important implications for investigation as they engage African Americans in research.
935 citations
TL;DR: The hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting is supported and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.
Abstract: Background The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness. Objective To establish the biological correlates of frailty in the presence and absence of concurrent cardiovascular disease and diabetes mellitus. Methods Participants were 4735 community-dwelling adults 65 years and older. Frail, intermediate, and nonfrail subjects were identified by a validated screening tool and exclusion criteria. Bivariate relationships between frailty level and physiological measures were evaluated by Pearson χ 2 tests for categorical variables and analysis of variance F tests for continuous variables. Multinomial logistic regression was performed to evaluate multivariable relationships between frailty status and physiological measures. Results Of 4735 Cardiovascular Health Study participants, 299 (6.3%) were identified as frail, 2147 (45.3%) as intermediate, and 2289 (48.3%) as not frail. Frail vs nonfrail participants had increased mean ± SD levels of C-reactive protein (5.5 ± 9.8 vs 2.7 ± 4.0 mg/L), factor VIII (13 790 ± 4480 vs 11 860 ± 3460 mg/dL), and, in a smaller subset, D dimer (647 ± 1033 vs 224 ± 258 ng/mL) ( P ≤.001 for all, χ 2 test for trend). These differences persisted when individuals with cardiovascular disease and diabetes were excluded and after adjustment for age, sex, and race. Conclusions These findings support the hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.
891 citations
TL;DR: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure–lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.
Abstract: Background After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. Objective To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. Methods Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. Results Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P P Conclusion The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure–lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.
810 citations
TL;DR: Medication errors were common (nearly 1 of every 5 doses in the typical hospital and skilled nursing facility) and the percentage of errors rated potentially harmful was 7%, or more than 40 per day in a typical 300-patient facility.
Abstract: Background Medication errors are a national concern. Objective To identify the prevalence of medication errors (doses administered differently than ordered). Design A prospective cohort study. Setting Hospitals accredited by the Joint Commission on Accreditation of Healthcare Organizations, nonaccredited hospitals, and skilled nursing facilities in Georgia and Colorado. Participants A stratified random sample of 36 institutions. Twenty-six declined, with random replacement. Medication doses given (or omitted) during at least 1 medication pass during a 1- to 4-day period by nurses on high medication–volume nursing units. The target sample was 50 day-shift doses per nursing unit or until all doses for that medication pass were administered. Methods Medication errors were witnessed by observation, and verified by a research pharmacist (E.A.F.). Clinical significance was judged by an expert panel of physicians. Main Outcome Measure Medication errors reaching patients. Results In the 36 institutions, 19% of the doses (605/3216) were in error. The most frequent errors by category were wrong time (43%), omission (30%), wrong dose (17%), and unauthorized drug (4%). Seven percent of the errors were judged potential adverse drug events. There was no significant difference between error rates in the 3 settings (P= .82) or by size (P= .39). Error rates were higher in Colorado than in Georgia (P= .04) Conclusions Medication errors were common (nearly 1 of every 5 doses in the typical hospital and skilled nursing facility). The percentage of errors rated potentially harmful was 7%, or more than 40 per day in a typical 300-patient facility. The problem of defective medication administration systems, although varied, is widespread.
781 citations
TL;DR: Patients with septic shock with the TLR4 Asp299Gly/Thr399Ile alleles had a higher prevalence of gram-negative infections and mutations in theTLR4 receptor may predispose people to develop septicshock with gram- negative microorganisms.
Abstract: Background Septic shock remains a significant health concern worldwide, and despite progress in understanding the physiological and molecular basis of septic shock, the high mortality rate of patients with septic shock remains unchanged. We recently identified a common polymorphism in toll-like receptor 4 (TLR4) that is associated with hyporesponsiveness to inhaled endotoxin or lipopolysaccharide in humans. Methods Since TLR4 is a major receptor for lipopolysaccharide in mammals and gram-negative bacteria are the prevalent pathogen associated with septic shock, we investigated whether these specific TLR4 alleles are associated with a predisposition to a more severe disease outcome for patients with septic shock. We genotyped 91 patients with septic shock as well as 73 healthy blood donor controls for the presence of the TLR4 Asp299Gly and TLR4 Thr399Ile mutations. Results We found the TLR4 Asp299Gly allele exclusively in patients with septic shock ( P = .05). Furthermore, patients with septic shock with the TLR4 Asp299Gly/Thr399Ile alleles had a higher prevalence of gram-negative infections. Conclusion Mutations in the TLR4 receptor may predispose people to develop septic shock with gram-negative microorganisms.
TL;DR: In this article, a randomized, open-label multicenter trial performed between April 1995 and March 1999, compared subcutaneous enoxaparin sodium (1.5 mg/kg once a day) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer.
Abstract: Background The use of warfarin sodium for treating venous thromboembolism in patients with cancer is associated with a significant risk of recurrence and bleeding. The use of low-molecular-weight heparin sodium for secondary prevention of venous thromboembolism in cancer patients may reduce the complication rate. Objective To determine whether a fixed dose of subcutaneous low-molecular-weight heparin is superior to oral warfarin for the secondary prophylaxis of venous thromboembolism in patients with cancer and venous thromboembolism. Methods In a randomized, open-label multicenter trial performed between April 1995 and March 1999, we compared subcutaneous enoxaparin sodium (1.5 mg/kg once a day) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer. Main Outcome Measure A combined outcome event defined as major bleeding or recurrent venous thromboembolism within 3 months. Results Of the 71 evaluable patients assigned to receive warfarin, 15 (21.1%; 95% confidence interval [CI], 12.3%-32.4%) experienced one major outcome event compared with 7 (10.5%) of the 67 evaluable patients assigned to receive enoxaparin (95% CI, 4.3%-20.3%; P = .09). There were 6 deaths owing to hemorrhage in the warfarin group compared with none in the enoxaparin group. In the warfarin group, 17 patients (22.7%) died (95% CI, 13.8%-33.8%) compared with 8 (11.3%) in the enoxaparin group (95% CI, 5.0%-21.0%; P = .07). No difference was observed regarding the progression of the underlying cancer or cancer-related death. Conclusions These results confirm that warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer. Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients.
TL;DR: In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.
Abstract: Background Orthopedic surgery remains a condition at high risk of venous thromboembolism (VTE). Fondaparinux, the first of a new class of synthetic selective factor Xa inhibitors, may further reduce this risk compared with currently available thromboprophylactic treatments. Methods A meta-analysis of 4 multicenter, randomized, double-blind trials in patients undergoing elective hip replacement, elective major knee surgery, and surgery for hip fracture (N = 7344) was performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of fondaparinux sodium starting 6 hours after surgery was more effective and as safe as approved enoxaparin regimens in preventing VTE. The primary efficacy outcome was VTE up to day 11, defined as deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism. The primary safety outcome was major bleeding. Results Fondaparinux significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682 patients) compared with enoxaparin (371 [13.7%] of 2703 patients), with a common odds reduction of 55.2% (95% confidence interval, 45.8% to 63.1%; P P = .008), the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups. Conclusion In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.
TL;DR: Lower kidney function was associated with a lower hemoglobin level and a higher prevalence and severity of anemia below, but not above, an estimated glomerular filtration rate (GFR) of 60 mL/min per 1.73 m(2).
Abstract: Background Kidney failure is known to cause anemia, which is associated with a higher risk of cardiac failure and mortality. The impact of milder decreases in kidney function on hemoglobin levels and anemia in the US population, however, is unknown. Methods We analyzed a population-based sample of 15419 participants 20 years and older in the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994. Results Lower kidney function was associated with a lower hemoglobin level and a higher prevalence and severity of anemia below, but not above, an estimated glomerular filtration rate (GFR) of 60 mL/min per 1.73 m2. Adjusted to the age of 60 years, the predicted median hemoglobin level among men (women) decreased from 14.9 (13.5) g/dL at an estimated GFR of 60 mL/min per 1.73 m2to 13.8 (12.2) g/dL at an estimated GFR of 30 mL/min per 1.73 m2and to 12.0 (10.3) g/dL at an estimated GFR of 15 mL/min per 1.73 m2. The prevalence of anemia (hemoglobin level Conclusion Below an estimated GFR of 60 mL/min per 1.73 m2, lower kidney function is strongly associated with a higher prevalence of anemia among the US adult population.
TL;DR: The data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease and suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.
Abstract: Background The association between traditional cardiovascular risk factors and risk of venous thromboembolism (VTE) has not been extensively examined in prospective studies. Methods To determine whether atherosclerotic risk factors are also associated with increased incidence of VTE, we conducted a prospective study of 19 293 men and women without previous VTE in 6 US communities between 1987 and 1998. Results There were 215 validated VTE events (1.45 per 1000 person-years) during a median of 8 years of follow-up. The age-adjusted hazard ratio was 1.4 (95% confidence interval [CI], 1.1-1.9) for men vs women, 1.6 (95% CI, 1.2-2.2) for blacks vs whites, and 1.7 (95% CI, 1.5-2.0) per decade of age. Cigarette smoking, hypertension, dyslipidemia, physical inactivity, and alcohol consumption were not associated with risk of VTE. Age-, race-, and sex-adjusted hazard ratios for body mass index categories (calculated as the weight in kilograms divided by the height in meters squared) of less than 25, 25 to less than 30, 30 to less than 35, 35 to less than 40, and 40 or more were 1.0, 1.5, 2.2, 1.5, and 2.7, respectively (P Conclusions Our data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease. In addition, the findings suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.
TL;DR: Comparing the characteristics of patients in heart failure (HF) RCTs with those of patients with HF in the community, and to document these trends over time, did not find a significant improvement in the representation of the trials.
Abstract: Background Appropriate representation of specific groups of patients in randomized controlled trials (RCTs) and generalizability of evidence obtained have been questioned. We sought to compare the characteristics of patients in heart failure (HF) RCTs with those of patients with HF in the community, and to document these trends over time. Methods MEDLINE was searched from 1985 through December 1999 for all HF RCTs. Additional trials were obtained through bibliographies of the reviewed articles, previous meta-analyses, and overviews of the HF trials. Original reports of RCTs of interventions for chronic HF were selected if they were published in the English language and included 50 or more participants. Publication year, sources of support, location of principal investigator, sample size, type of intervention, inclusion and exclusion criteria, characteristics of participants, and the use of invasive diagnostic tests were extracted. Results Participants in the 59 HF RCTs we reviewed were markedly different from the patients with HF in the community. Patients in RCTs were younger, more often male, more likely to have subnormal systolic ejection fraction, and were most commonly white. We did not find a significant improvement in the representation of the trials, with respect to these characteristics, among those published recently compared with those from the late 1980s and early 1990s. Conclusions Clinical trials are focusing on a relatively small segment of the HF population. The consequences of underrepresenting minorities, women, and elderly are unknown but may be particularly important for HF. Future clinical trials should adequately include populations that carry the burden of the disease.
TL;DR: Isotonic hydration is superior to half-isotonicHydration in the prevention of contrast media–associated nephropathy and three predefined subgroups benefited in particular from isotonic hydrations: women, persons with diabetes, and patients receiving 250 mL or more of contrast.
Abstract: Background The administration of radiographic contrast agents remains an important cause of acute renal failure. The optimal infusion for hydration has not been evaluated. Objective To compare the incidence of contrast media–associated nephrotoxicity with isotonic or half-isotonic hydration. Design Prospective, randomized, controlled, open-label study. Methods Patients scheduled for elective or emergency coronary angioplasty were randomly assigned to receive isotonic (0.9% saline) or half-isotonic (0.45% sodium chloride plus 5% glucose) hydration beginning the morning of the procedure for elective interventions and immediately before emergency interventions. An increase in serum creatinine of at least 0.5 mg/dL (44 µmol/L) within 48 hours was defined as contrast media–associated nephrotoxicity. Secondary end points were cardiac and peripheral vascular complications. Results A total of 1620 patients were assigned to receive isotonic (n = 809) or half-isotonic (n = 811) hydration. Primary end point analysis was possible in 1383 patients. Baseline characteristics were well matched. Contrast media–associated nephropathy was significantly reduced with isotonic (0.7%, 95% confidence interval, 0.1%-1.4%) vs half-isotonic (2.0%, 95% confidence interval, 1.0%-3.1%) hydration (P= .04). Three predefined subgroups benefited in particular from isotonic hydration: women, persons with diabetes, and patients receiving 250 mL or more of contrast. The incidence of cardiac (isotonic, 5.3% vs half-isotonic, 6.4%;P= .59) and peripheral vascular (isotonic, 1.6% vs half-isotonic, 1.5%,P= .93) complications was similar between the 2 hydration groups. Conclusion Isotonic hydration is superior to half-isotonic hydration in the prevention of contrast media–associated nephropathy.
TL;DR: Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification.
Abstract: less than 4 mm and a Lequesne index score of less than 9 points. Progressive joint space narrowing with placebo use was �0.19 mm (95% confidence interval, �0.29 to �0.09 mm) after 3 years. Conversely, there was no average change with glucosamine sulfate use (0.04 mm; 95% confidence interval, �0.06 to 0.14 mm), with a significant difference between groups (P=.001). Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings (0.5 mm): 5% vs 14% (P = .05). Symptoms improved modestly with placebo use but as much as 20% to 25% with glucosamine sulfate use, with significant final differences on the Lequesne index and the WOMAC total index and pain, function, and stiffness subscales. Safety was good and without differences between groups. Conclusion: Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification. Arch Intern Med. 2002;162:2113-2123
TL;DR: Delirium is an independent marker for increased mortality among older medical inpatients during the 12 months after hospital admission and is a particularly important prognostic marker among patients without dementia.
Abstract: Background Delirium has not been found to be a significant predictor of postdischarge mortality, but previous research has methodologic limitations including small sample sizes and inadequate control of confounding. This study aimed to determine the independent effects of presence of delirium, type of delirium (incident vs prevalent), and severity of delirium symptoms on 12-month mortality among older medical inpatients. Methods A prospective, observational study of 2 cohorts of medical inpatients was conducted with patients 65 years or older: 243 patients had prevalent or incident delirium, and 118 controls had no delirium. Baseline measures included presence of delirium and/or dementia, severity of delirium symptoms, physical function, comorbidity, and physiological and clinical severity of illness. Mortality during the 12 months after enrollment was analyzed with the Cox proportional hazards model with adjustment for covariates. Results The unadjusted hazard ratio of delirium with mortality was 3.44 (95% confidence interval, 2.05-5.75); the adjusted hazard ratio was 2.11 (95% confidence interval, 1.18-3.77). The effect of delirium was sustained over the entire 12-month period after adjustment for covariates and was stronger among patients without dementia. Among patients with dementia, there was a weak, nonsignificant effect of delirium on survival. After adjustment for covariates, mortality did not differ between patients with incident and prevalent delirium, but among patients with delirium without dementia, greater severity of delirium symptoms was associated with higher mortality. Conclusions Delirium is an independent marker for increased mortality among older medical inpatients during the 12 months after hospital admission. It is a particularly important prognostic marker among patients without dementia.
TL;DR: In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.
Abstract: Background Diabetes mellitus, impaired fasting glucose level, or insulin resistance are associated with increased risk of cardiovascular disease. Objectives To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes. Methods Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized controlled trial that enrolled 2531 men with coronary heart disease (CHD), a high-density lipoprotein cholesterol level of 40 mg/dL or less (≤1.04 mmol/L), and a low-density lipoprotein cholesterol level of 140 mg/dL or less (≤3.63 mmol/L). Subjects received either gemfibrozil (1200 mg/d) or matching placebo and were followed up for an average of 5.1 years. In this article, we report the composite end point (CHD death, stroke, or myocardial infarction). Results Compared with those with a normal fasting glucose level, risk was increased in subjects with known diabetes (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.44-2.43; P = .001) and those with newly diagnosed diabetes (HR, 1.72; 95% CI, 1.10-2.68; P = .02). In persons without diabetes, a fasting plasma insulin level of 39 µU/mL or greater (≥271 pmol/L) was associated with a 31% increased risk of events ( P = .03). Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P = .004). The reduction in CHD death was 41% (HR, 0.59; 95% CI, 0.39-0.91; P = .02). Among individuals without diabetes, gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile (risk reduction, 35%; P = .04). Conclusion In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.
TL;DR: Low doses of ER niacin (1000 or 1500 mg/d) are a treatment option for dyslipidemia in patients with type 2 diabetes and no hepatotoxic effects or myopathy were observed.
Abstract: Background: Diabetic dyslipidemia is characterized by high triglyceride levels; low high-density lipoprotein cholesterol levels; small, dense low-density lipoprotein particles; and high free fatty acid levels. Niacin reduces concentrations of triglyceride-rich and small low-density lipoprotein particles while increasing high-density lipoprotein cholesterol levels. It also lowers levels of free fatty acids and lipoprotein(a). However, the use of niacin in patients with diabetes has been discouraged because high doses can worsen glycemic control. We evaluated the efficacy and safety of once-daily extended-release (ER) niacin in patients with diabetic dyslipidemia. Methods: During a 16-week, double-blind, placebocontrolled trial, 148 patients were randomized to placebo (n=49) or 1000 (n=45) or 1500 mg/d (n=52) of ER niacin. Sixty-nine patients (47%) were also receiving concomitant therapy with statins. Results: Dose-dependent increases in high-density lipoprotein cholesterol levels (+19% to +24% [P.05] vs placebo for both niacin dosages) and reductions in triglyceride levels (–13% to –28% [P.05] vs placebo for the 1500-mg ER niacin) were observed. Baseline and week 16 values for glycosylated hemoglobin levels were 7.13% and 7.11%, respectively, in the placebo group; 7.28% and 7.35%, respectively, in the 1000-mg ER niacin group (P=.16 vs placebo); and 7.2% and 7.5%, respectively, in the 1500-mg ER niacin group (P=.048 vs placebo). Four patients discontinued participation because of inadequate glucose control. Rates of adverse event rates other than flushing were similar for the niacin and placebo groups. Four patients discontinued participation owing to flushing (including 1 receiving placebo). No hepatotoxic effects or myopathy were observed. Conclusion: Low doses of ER niacin (1000 or 1500 mg/d) are a treatment option for dyslipidemia in patients with type 2 diabetes.
TL;DR: This study describes racial or ethnic patterns of cancer-specific survival and relative risks of cancer death for all cancers combined and for cancers of the colon and rectum, lung and bronchus, prostate, and female breast for the 6 major USracial or ethnic groups.
Abstract: Background: Available cancer statistics pertain primarily to white and African American populations. This study describes racial or ethnic patterns of cancer-specific survival and relative risks (RRs) of cancer death for all cancers combined and for cancers of the colon and rectum, lung and bronchus, prostate, and female breast for the 6 major US racial or ethnic groups. Methods: Cancer-specific survival rates were analyzed for more than 1.78 million patients who resided in the 9 SEER (Surveillance, Epidemiology, and End Results) Program geographic areas and were diagnosed between 1975 and 1997 as having an incident invasive cancer, by 6 racial or ethnic groups (non-Hispanic whites, Hispanic whites, African Americans, Asian Americans, Hawaiian natives, and American Indians and Alaskan natives). Results: Survival rates improved between 1988 to 1997 for virtually all racial or ethnic groups. However, racial or ethnic differences in RRs of cancer death persisted after controlling for age for all cancers combined and for age and stage for specific cancer sites (P.01). African American, American Indian and Alaskan native, and Hawaiian native patients tended to have higher RRs of cancer death than the other groups. American Indians and Alaskan natives generally exhibited the highest RRs of cancer death, except for colorectal cancer in males. Conclusions: Survival rates in patients with cancer have improved in recent years, but racial or ethnic differences in survival rates and in RRs of cancer death persist. Additional studies are needed to clarify the socioeconomic, medical, biological, cultural, and other determinants of these findings.
TL;DR: The results suggest that the association between physical activity and reduced coronary heart disease risk may be mediated by anti-inflammatory effects of regular physical activity.
Abstract: Background: Physical activity has been associated with a reduced risk of coronary heart disease, but the mechanism underlying this association is unclear. Because coronary heart disease is increasingly seen as an inflammatory process, it might be reasonable to hypothesize that physical activity reduces risk of coronary heart disease by reducing or preventing inflammation. Methods: The study examined the relationship between physical activity and elevated inflammation as indicated by a high C-reactive protein level, white blood cell count, or fibrinogen level. Study subjects were 3638 apparently healthy US men and women 40 years and older who participated in the Third National Health and Nutrition Examination Survey. Results: More frequent physical activity was independently associated with a lower odds of having an elevated C-reactive protein level. Compared with those engaging in physical activity 0 to 3 times per month, the odds of having an elevated C-reactive protein level was reduced among those engaging in physical activity 4 to 21 times per month (odds ratio, 0.77; 95% confidence interval, 0.58-1.02) and 22 or more times per month (odds ratio, 0.63; 95% confidence interval, 0.43-0.93) (P for trend, .02). Similar associations were seen for white blood cell count and fibrinogen levels. Conclusions: More frequent physical activity is independently associated with a lower odds of having elevated inflammation levels among apparently healthy US adults 40 years and older, independent of several confounding factors. The results suggest that the association between physical activity and reduced coronary heart disease risk may be mediated by anti-inflammatory effects of regular physical activity. Arch Intern Med. 2002;162:1286-1292
TL;DR: It is suggested that an important reason why physicians do not treat hypertension more aggressively is that they are willing to accept an elevated systolic BP in their patients.
Abstract: Background Primary care physicians may not be aggressive enough with the management of hypertension. The purpose of this study was to identify barriers to primary care physicians' willingness to increase the intensity of treatment among patients with uncontrolled hypertension. Methods Descriptive survey study. We sampled patient visits in a large midwestern health system to identify patients with uncontrolled hypertension. The treating primary care physicians were asked to complete a survey about the patient visit with a copy of the office notes attached to the survey (patient visits, n = 270; response rate, 86%). Results Pharmacologic therapy was initiated or changed at only 38% of visits, despite documented hypertension for at least 6 months before the patients' most recent visit. The most frequently cited reason for no initiation or change in therapy was related to the primary care physicians being satisfied with the blood pressure (BP) value (satisfactory BP response, 30%; satisfactory diastolic BP response, 16%; only borderline hypertension, 10%). At 93% of these visits, systolic BP values were 140 mm Hg or higher, which is above the cut point recommended by Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines, and 35% were 150 mm Hg or higher. On average, physicians reported that 150 mm Hg was the lowest systolic BP at which they would recommend pharmacologic treatment to patients, compared with 91 mm Hg for diastolic BP. Conclusions Our findings suggest that an important reason why physicians do not treat hypertension more aggressively is that they are willing to accept an elevated systolic BP in their patients. This has an important impact on public health because of the positive association between systolic BP and cardiovascular disease.
TL;DR: Staphylococcus aureus has emerged as a dominant cause of IE, and is an independent predictor of mortality, in patients with definite or possible IE at Duke University Medical Center from 1993 to 1999.
Abstract: Background: Limited data exist on recent demographic and microbiological changes in infective endocarditis (IE) and the impact of these changes on patient survival. Methods: Data were collected from all patients with definite or possible IE at Duke University Medical Center, Durham, NC, from 1993 to 1999. Logistic regression analysis was used to identify demographic and microbiological changes that occurred in patients with IE over the study period. The impact of these changes on survival was evaluated using Cox proportional hazards modeling. Results: Among the 329 study patients, rates of hemodialysis dependence, immunosuppression, and Staphylococcus aureus infection increased during the study period (P=.04, P=.008, and P.001, respectively), while rates of infection due to viridans group streptococci decreased (P=.007). Hemodialysis was independently associated with S aureus infection (odds ratio, 3.1; 95% confidence interval, 1.6-5.9). Patients with S aureus IE had a higher 1-year mortality rate (43.9% vs 32.5%; P=.04) that persisted after adjustment for other illness severity characteristics (hazard ratio, 1.5; 95% confidence interval, 1.03-2.3). Conclusions: The demographic and microbiological characteristics of IE at our institution have changed over the past decade in ways that suggest a link between medical practice and IE characteristics. Staphylococcus aureus has emerged as a dominant cause of IE, and is an independent predictor of mortality. These findings identify clinical settings that may warrant closer surveillance and more aggressive measures in the identification and prevention of endocarditis. Arch Intern Med. 2002;162:90-94
TL;DR: These prospective data indicate a significant increase in the relative risk of total stroke and its 2 major subtypes with each unit increase of BMI that is independent of the effects of hypertension, diabetes, and cholesterol.
Abstract: Background Although obesity is an established risk factor for coronary heart disease, its role as a risk factor for stroke remains controversial. Methods Prospective cohort study among 21 414 US male physicians participating in the Physicians' Health Study. Incidence of total, ischemic, and hemorrhagic stroke was measured by self-report and confirmed by medical record review. We used Cox proportional hazards models to evaluate the association of body mass index (BMI), calculated as self-reported weight in kilograms divided by the square of the height in meters, with risk of total, ischemic, and hemorrhagic stroke. Results During 12.5 years of follow-up, 747 strokes (631 ischemic, 104 hemorrhagic, and 12 undefined) occurred. Compared with participants with BMIs less than 23, those with BMIs of 30 or greater had an adjusted relative risk of 2.00 (95% confidence interval [CI], 1.48-2.71) for total stroke, 1.95 (95% CI, 1.39-2.72) for ischemic stroke, and 2.25 (95% CI, 1.01-5.01) for hemorrhagic stroke. When BMI was evaluated as a continuous variable, each unit increase of BMI was associated with a significant 6% increase in the adjusted relative risks of total (95% CI, 4%-8%), ischemic (95% CI, 3%-8%), and hemorrhagic stroke (95% CI, 1%-12%). Additional adjustment for hypertension, diabetes mellitus, and hypercholesterolemia slightly attenuated the risks for total and ischemic (relative risk, 4%; 95% CI, 2%-7%), but not hemorrhagic, stroke. Conclusions These prospective data indicate a significant increase in the relative risk of total stroke and its 2 major subtypes with each unit increase of BMI that is independent of the effects of hypertension, diabetes, and cholesterol. Because BMI is a modifiable risk factor, the prevention of stroke may be another benefit associated with preventing obesity in adults.
TL;DR: The reduction in hospitalizations, costs, and other resource use achieved using standardized telephonic case management in the early months after a heart failure admission is greater than that usually achieved with pharmaceutical therapy and comparable with other disease management approaches.
Abstract: Background Case management is believed to promote continuity of care and decrease hospitalization rates, although few controlled trials have tested this approach. Objective To assess the effectiveness of a standardized telephonic case-management intervention in decreasing resource use in patients with chronic heart failure. Methods A randomized controlled clinical trial was used to assess the effect of telephonic case management on resource use. Patients were identified at hospitalization and assigned to receive 6 months of intervention (n = 130) or usual care (n = 228) based on the group to which their physician was randomized. Hospitalization rates, readmission rates, hospital days, days to first rehospitalization, multiple readmissions, emergency department visits, inpatient costs, outpatient resource use, and patient satisfaction were measured at 3 and 6 months. Results The heart failure hospitalization rate was 45.7% lower in the intervention group at 3 months ( P = .03) and 47.8% lower at 6 months ( P = .01). Heart failure hospital days ( P = .03) and multiple readmissions ( P = .03) were significantly lower in the intervention group at 6 months. Inpatient heart failure costs were 45.5% lower at 6 months ( P = .04). A cost saving was realized even after intervention costs were deducted. There was no evidence of cost shifting to the outpatient setting. Patient satisfaction with care was higher in the intervention group. Conclusions The reduction in hospitalizations, costs, and other resource use achieved using standardized telephonic case management in the early months after a heart failure admission is greater than that usually achieved with pharmaceutical therapy and comparable with other disease management approaches.
TL;DR: In critically ill patients, after accurate adjustment for disease severity and acute illness, it is found MRSA bacteremia to have a higher attributable mortality than MSSA b acteremia.
Abstract: Background: Staphylococcus aureus bacteremia carries high mortality rates The clinical impact of methicillin resistance remains controversial: outcome comparisons between patients with bacteremia involving methicillin-susceptible (MSSA) and methicillinresistant (MRSA) S aureus are difficult to perform because of important differences in severity of illness Methods: A retrospective cohort analysis and 2 independent case-control analyses were performed to determine and compare outcomes and attributable mortality rates of MSSA (n=38) and MRSA bacteremia (n=47) in critically ill patients For the case-control studies, matching (1:2 ratio) was based on the APACHE (Acute Physiology and Chronic Health Evaluation) II classification: APACHE II score (±1 point) and diagnostic category Results: Patients with MRSA bacteremia had more acute renal failure and hemodynamic instability than patients with MSSA bacteremia They had a longer intensive care unit stay and ventilator dependency Patients with MRSA bacteremia had a higher 30-day mortality rate (532% vs 184%) and in-hospital mortality rate (638% vs 237%) (P05) Multivariate survival analysis demonstrated acute renal failure, length of mechanical ventilation, age, and methicillin resistance to be independently associated with mortality (P05) The attributable mortality rate for MSSA bacteremia was 13%: mortality rates for cases and controls were respectively 237% and 224% (P=94) The attributable mortality rate for MRSA bacteremia was 234%: mortality rates for cases and controls were respectively 638% and 404% (P = 02) The difference (221%) between both attributable mortality rates was significant (95% confidence interval, 88%-353%) Conclusion: In critically ill patients, after accurate adjustment for disease severity and acute illness, we found MRSA bacteremia to have a higher attributable mortality than MSSA bacteremia Arch Intern Med 2002;162:2229-2235
TL;DR: While obesity is a risk factor for self-reported asthma, obese participants are at a lower risk for (objective) airflow obstruction, suggesting asthma might be overdiagnosed in the obese population.
Abstract: Background Previous research suggests that obesity is an important risk factor for asthma. However, since obesity can cause dyspnea through mechanisms other than airflow obstruction, diagnostic misclassification of asthma could partially account for this association. Objective To determine whether there is a relationship between obesity and airflow obstruction. Methods A total of 16 171 participants (17 years or older) from the Third National Health and Nutrition Examination Survey (NHANES III) were divided into 5 quintiles based on their body mass index (BMI) to determine the association between BMI quintile and risk of self-reported asthma, bronchodilator use, exercise performance, and airflow obstruction. Significant airflow obstruction was defined as a ratio less than 80% the predicted value of forced expiratory volume in 1 second to forced vital capacity adjusted for age, sex, and race. Results The highest BMI quintile (ie, the most obese participants) had the greatest risk of self-reported asthma (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.24-1.81), bronchodilator use (OR, 1.94; 95% CI, 1.38-2.72), and dyspnea with exertion (OR, 2.66; 95% CI, 2.35-3.00). Paradoxically, the highest BMI quintile had the lowest risk for significant airflow obstruction ( P = .001). Conclusions This study demonstrates that while obesity is a risk factor for self-reported asthma, obese participants are at a lower risk for (objective) airflow obstruction. Many more obese than nonobese participants were using bronchodilators despite a lack of objective evidence for airflow obstruction. These data suggest that mechanisms other than airflow obstruction are responsible for dyspnea genesis in obesity and that asthma might be overdiagnosed in the obese population.
TL;DR: These prospective data in US male physicians suggest that the inverse association between nut consumption and total coronary heart disease death is primarily due to a reduction in the risk of sudden cardiac death.
Abstract: Background Dietary nut intake has been associated with a reduced risk of coronary heart disease mortality; however, the mechanism is unclear. Since components of nuts may have antiarrhythmic properties, part of the benefit may be due to a reduction in sudden cardiac death. Methods We prospectively assessed whether increasing frequency of nut consumption, as ascertained by an abbreviated food frequency questionnaire at 12 months of follow-up, was associated with a lower risk of sudden cardiac death and other coronary heart disease end points among 21 454 male participants enrolled in the US Physicians' Health Study. Participants were followed up for an average of 17 years. Results Dietary nut intake was associated with a significantly reduced risk of sudden cardiac death after controlling for known cardiac risk factors and other dietary habits ( P for trend, .01). Compared with men who rarely or never consumed nuts, those who consumed nuts 2 or more times per week had reduced risks of sudden cardiac death (relative risk, 0.53; 95% confidence interval, 0.30-0.92) and total coronary heart disease death (relative risk, 0.70; 95% confidence interval, 0.50-0.98). In contrast, nut intake was not associated with significantly reduced risks of nonsudden coronary heart disease death or nonfatal myocardial infarction. Conclusion These prospective data in US male physicians suggest that the inverse association between nut consumption and total coronary heart disease death is primarily due to a reduction in the risk of sudden cardiac death.