Herpes simplex virus type 2 and HIV infection among US military personnel: implications for health prevention programmes.

US military personnel are routinely screened for HIV infection. Herpes simplex virus type 2 (HSV-2) is a risk factor for HIV acquisition. To determine the association between HSV-2 and HIV, a matched case-control study was conducted among US Army and Air Force service members with incident HIV infections (cases) randomly matched with two HIV-uninfected service members (controls) between 2000 and 2004. HSV-2 prevalence was significantly higher among cases (30.3%, 138/456) than among controls (9.7%, 88/912, P < 0.001). HSV-2 was strongly associated with HIV in univariate (odds ratio [OR] = 4.2, 95% confidence interval [CI] = 3.1-5.8) and multiple analyses (adjusted [OR] = 3.9, 95% CI = 2.8-5.6). The population attributable risk percentage of HIV infection due to HSV-2 was 23%. Identifying HSV-2 infections may afford the opportunity to provide targeted behavioural interventions that could decrease the incidence of HIV infections in the US military population; further studies are needed.

High prevalence of HIV infection among rural tea plantation residents in Kericho, Kenya.

Human immunodeficiency virus type 1 (HIV-1) epidemiology among residents of a rural agricultural plantation in Kericho, Kenya was studied. HIV-1 prevalence was 14.3%, and was higher among women (19.1%) than men (11.3%). Risk factors associated with HIV-1 for men were age (>or=25 years), marital history (one or more marriages), age difference from current spouse (>or=5 years), Luo ethnicity, sexually transmitted infection (STI) symptoms in the past 6 months, circumcision (protective), and sexual activity (>or=7 years). Among women, risk factors associated with HIV-1 were age (25-29 years, >or=35 years), marital history (one or more marriages), age difference from current spouse (>or=10 years), Luo ethnicity, STI symptoms in the past 6 months, and a STI history in the past 5 years. Most participants (96%) expressed a willingness to participate in a future HIV vaccine study. These findings will facilitate targeted intervention and prevention measures for HIV-1 infection in Kericho.

Clinical inertia in the management of Type 2 diabetes metabolic risk factors.

AIMS: Delays in the initiation and intensification of medical therapy may be one reason patients with diabetes do not reach evidence-based goals for metabolic control. We assessed intensification of medical therapy over time, comparing the management of hyperglycaemia, hypertension, and hyperlipidaemia. METHODS: Prospective cohort study of 598 adults with Type 2 diabetes receiving primary care in an academic medical centre from May 1997 to April 1999. We assessed whether patients failing to achieve standard treatment goals for haemoglobin A1c (HbA1c), systolic blood pressure (SBP), or low density lipoprotein (LDL) cholesterol when last measured during 12 months (Year 1, 5/97-4/98) had increases in their corresponding medical regimen during the following 12 months (Year 2, 5/98-4/99). RESULTS: Among untreated patients in Year 1, seven of 12 (58%) of those above goal for HbA1c were initiated on medical therapy in Year 2, compared with 16 of 48 (34%) above SBP goal (P=0.02) and 26 of 115 (23%) above LDL cholesterol goal (P=0.02). Among patients on therapy and above goal, 124 of 244 (51%) patients with elevated HbA1c had their regimen increased in Year 2, compared with 85 of 282 (30%) with elevated SBP (P<0.001) and 22 of 79 (30%) with elevated LDL cholesterol (P<0.001). From Year 1 to Year 2 there was a decline in the overall proportion of patients above goal for LDL cholesterol (from 58% to 45%, P=0.002) but not for HbA1c or blood pressure. CONCLUSIONS: Greater initiation and intensification of pharmaceutical therapy, particularly for elevated blood pressure or cholesterol, may represent a specific opportunity to improve metabolic control in Type 2 diabetes.

Processes of care, illness severity, and outcomes in the management of community-acquired pneumonia at academic hospitals.

BACKGROUND: Prompt antibiotic administration, oxygenation measurement, and blood cultures are generally considered markers of high-quality care in the inpatient management of community-acquired pneumonia (CAP). However, few studies have examined the relationship between prompt achievement of process-of-care markers and outcomes for patients with CAP. We examined whether antibiotic administration within 8 hours of hospital arrival, a blood culture within 24 hours, an oxygenation measurement within 24 hours, or performing blood cultures before giving antibiotics was associated with the following: (1) reaching clinical stability within 48 hours of hospital admission, (2) a decreased length of hospital stay, or (3) fewer inpatient deaths. METHODS: A retrospective medical record review identified 1062 eligible patients discharged from the hospital with a diagnosis of CAP between December 1, 1997, and February 28, 1998, among 38 US academic hospitals. We assessed the independent relationship between each process marker and the 3 clinical outcomes, controlling for the Pneumonia Severity Index on admission. We also examined the relationship of pneumonia severity on admission to process marker achievement and clinical outcomes. RESULTS: Overall, there was no consistent or statistically significant relationship between achieving process markers and better clinical outcomes (P>.40 for all). We did observe that performing blood cultures within 24 hours was related to not achieving clinical stability within 48 hours (odds ratio, 1.62; 95% confidence interval, 1.13-2.33). However, this finding likely reflects residual confounding by severity of illness, since increasing pneumonia severity on admission was associated with blood culture performance (P =.009) and with shorter times to antibiotic administration (P =.04). CONCLUSIONS: Achieving process-of-care markers was not associated with improved outcomes, but was related to the severity of pneumonia as assessed on admission. Our results highlight the difficulty in demonstrating a link between process-of-care markers and outcomes in observational studies of CAP. Randomized studies are needed to objectively evaluate the impact of process-of-care markers on CAP outcomes.

Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin.

BACKGROUND: An elevated international normalized ratio (INR) increases the risk for major hemorrhage during warfarin therapy. Optimal management of patients with asymptomatic elevations in INR is hampered by the lack of understanding of the time course of INR decay after cessation of warfarin therapy. OBJECTIVE: To identify predictors of the rate of INR normalization after excessive anticoagulation. DESIGN: Retrospective cohort study. SETTING: Outpatient anticoagulant therapy unit. PATIENTS: Outpatients with an INR greater than 6.0 were identified from August 1993 to September 1998. Patients in whom two doses of warfarin were withheld and a follow-up INR was obtained on the second calendar day were enrolled. No patient received vitamin K(1). MEASUREMENTS: The INR was measured 2 days after an INR greater than 6.0 was recorded. RESULTS: Of 633 study patients with an initial INR greater than 6.0, 232 (37%) still had an INR of 4.0 or greater after two doses of warfarin were withheld. Patients who required larger weekly maintenance doses of warfarin were less likely to have an INR of 4.0 or greater on day 2 (adjusted odds ratio per 10 mg of warfarin, 0.87 [95% CI, 0.79 to 0.97]). Other risk factors for having an INR of 4.0 or greater on day 2 included age (odds ratio per decade of life, 1.18 [CI, 1.01 to 1.38]), index INR (odds ratio per unit, 1.25 [CI, 1.14 to 1.37]), decompensated congestive heart failure (odds ratio, 2.79 [CI, 1.30 to 5.98]), and active cancer (odds ratio, 2.48 [CI, 1.11 to 5.57]). CONCLUSIONS: Steady-state warfarin dose, advanced age, and extreme elevation in INR are risk factors for prolonged delay in return of the INR to within the therapeutic range. Decompensated congestive heart failure and active cancer greatly increase this risk.

Arterial blood gas and pulse oximetry in initial management of patients with community-acquired pneumonia.

OBJECTIVE: To identify the factors associated with the use of arterial blood gas (ABG) and pulse oximetry (PO) in the initial management of patients with community-acquired pneumonia (CAP) and arterial hypoxemia at presentation. PARTICIPANTS: A total of 944 outpatients and 1,332 inpatients with clinical and radiographic evidence of CAP prospectively enrolled from 5 study sites in the United States and Canada. ANALYSES: Separate multivariate logistic regression analyses were used to 1) compare measurement of ABG and PO within 48 hours of presentation across sites while controlling for patient differences, and 2) identify factors associated with arterial hypoxemia (PaO2 <60 mm Hg or SaO2 <90% for non-African Americans and <92% for African Americans) while breathing room air. RESULTS: Range of ABG use by site was from 0% to 6.4% (P =.06) for outpatients and from 49.2% to 77.3% for inpatients (P <.001), while PO use ranged from 9.4% to 57.8% for outpatients (P <.001) and from 47.9% to 85.1% for inpatients (P <.001). Differences among sites remained after controlling for patient demographic characteristics, comorbidity, and illness severity. In patients with 1 or more measurements of oxygenation at presentation, hypoxemia was independently associated with 6 risk factors: age >30 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.7 to 5.9), chronic obstructive pulmonary disease (OR, 1.9; 95% CI, 1.4 to 2.6), congestive heart failure (OR, 1.5; 95% CI, 1.0 to 2.1), respiratory rate >24 per minute (OR, 2.3; 95% CI, 1.8 to 3.0), altered mental status (OR, 1.6; 95% CI, 1.1 to 2.3), and chest radiographic infiltrate involving >1 lobe (OR, 2.2; 95% CI, 1.7 to 2.9). The prevalence of hypoxemia among those tested ranged from 13% for inpatients with no risk factors to 54.6% for inpatients with > or =3 risk factors. Of the 210 outpatients who had > or =2 of these risk factors, only 64 (30.5%) had either an ABG or PO performed. In the 48 outpatients tested without supplemental O2 with > or =2 risk factors 8.3% were hypoxemic. CONCLUSIONS: In the initial management of CAP, use of ABG and PO varied widely across sites. Increasing the assessment of arterial oxygenation among patients with CAP is likely to increase the detection of arterial hypoxemia, particularly among outpatients.

Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study.

OBJECTIVE: Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS). RESEARCH DESIGN AND METHODS: We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models. RESULTS: The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007). CONCLUSIONS: Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

Surgical and nonsurgical management of sciatica secondary to a lumbar disc herniation: five-year outcomes from the Maine Lumbar Spine Study.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: To assess 5-year outcomes for patients with sciatica caused by a lumbar disc herniation treated surgically or nonsurgically. SUMMARY OF BACKGROUND DATA: There is limited knowledge about long-term treatment outcomes of sciatica caused by a lumbar disc herniation, particularly the relative benefits of surgical and conservative therapy in contemporary clinical practice. METHODS: Eligible, consenting patients recruited from the practices of orthopedic surgeons, neurosurgeons, and occupational medicine physicians throughout Maine had baseline interviews with mailed follow-up questionnaires at 3, 6, and 12 months and annually thereafter. Clinical data were obtained at baseline from a physician questionnaire. Outcomes included patient-reported symptoms of leg and back pain, functional status, satisfaction, and employment and compensation status. RESULTS: Of 507 patients initially enrolled, 5-year outcomes were available for 402 (79.3%) patients: 220 (80%) treated surgically and 182 (78.4%) treated nonsurgically. Surgically treated patients had worse baseline symptoms and functional status than those initially treated nonsurgically. By 5 years 19% of surgical patients had undergone at least one additional lumbar spine operation, and 16% of nonsurgical patients had opted for at least one lumbar spine operation. Overall, patients treated initially with surgery reported better outcomes. At the 5-year follow-up, 70% of patients initially treated surgically reported improvement in their predominant symptom (back or leg pain) versus 56% of those initially treated nonsurgically (P < 0.001). Similarly, a larger proportion of surgical patients reported satisfaction with their current status (63% vs. 46%, P < 0.001). These differences persisted after adjustment for other determinants of outcome. The relative advantage of surgery was greatest early in follow-up and narrowed over 5 years. There was no difference in the proportion of patients receiving disability compensation at the 5-year follow-up. The least symptomatic patients at baseline did well regardless of initial treatment, although function improved more in the surgical group. CONCLUSIONS: For patients with moderate or severe sciatica, surgical treatment was associated with greater improvement than nonsurgical treatment at 5 years. However, patients treated surgically were as likely to be receiving disability compensation, and the relative benefit of surgery decreased over time.

Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.

CONTEXT: Atrial fibrillation is the most common arrhythmia in elderly persons and a potent risk factor for stroke. However, recent prevalence and projected future numbers of persons with atrial fibrillation are not well described. OBJECTIVE: To estimate prevalence of atrial fibrillation and US national projections of the numbers of persons with atrial fibrillation through the year 2050. DESIGN, SETTING, AND PATIENTS: Cross-sectional study of adults aged 20 years or older who were enrolled in a large health maintenance organization in California and who had atrial fibrillation diagnosed between July 1, 1996, and December 31, 1997. MAIN OUTCOME MEASURES: Prevalence of atrial fibrillation in the study population of 1.89 million; projected number of persons in the United States with atrial fibrillation between 1995-2050. RESULTS: A total of 17 974 adults with diagnosed atrial fibrillation were identified during the study period; 45% were aged 75 years or older. The prevalence of atrial fibrillation was 0.95% (95% confidence interval, 0.94%-0.96%). Atrial fibrillation was more common in men than in women (1.1% vs 0.8%; P<.001). Prevalence increased from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older. Among persons aged 50 years or older, prevalence of atrial fibrillation was higher in whites than in blacks (2.2% vs 1.5%; P<.001). We estimate approximately 2.3 million US adults currently have atrial fibrillation. We project that this will increase to more than 5.6 million (lower bound, 5.0; upper bound, 6.3) by the year 2050, with more than 50% of affected individuals aged 80 years or older. CONCLUSIONS: Our study confirms that atrial fibrillation is common among older adults and provides a contemporary basis for estimates of prevalence in the United States. The number of patients with atrial fibrillation is likely to increase 2.5-fold during the next 50 years, reflecting the growing proportion of elderly individuals. Coordinated efforts are needed to face the increasing challenge of optimal stroke prevention and rhythm management in patients with atrial fibrillation.

Corneal sensation after topical anesthesia.

PURPOSE: To compare the topical effects of tetracaine, lidocaine, and bupivacaine on corneal sensitivity in normal eyes. METHODS: Corneal touch sensitivity was measured with a Cochet-Bonnet anesthesiometer before and at 2.5-minute intervals after instillation of the anesthetic agent, until baseline levels had been reestablished. Seventeen healthy volunteers were randomized into five groups. Group 1 included 0.5% tetracaine (n = 6); group 2, 4% lidocaine (n = 8); group 3, 0.75% bupivacaine (n = 8); group 4, 0.5% tetracaine + 4% lidocaine (n = 5); and group 5, 0.5% tetracaine + 0.75% bupivacaine (n = 7). RESULTS: The duration of anesthesia showed no differences between groups 1, 3, and 5. Although there was no difference between groups 2 and 4, both groups demonstrated significantly longer effects than groups 1, 3, and 5 (p < 0.005). CONCLUSION: The application of 4% lidocaine results in a significantly prolonged topical anesthetic effect when compared with tetracaine and bupivacaine.

Antithrombotic therapy in atrial fibrillation.

Atrial fibrillation is a common condition affecting elderly individuals; as many as 10% of people older than age 80 years have AF. AF is also a potent risk factor for ischemic stroke, raising the risk of stroke fivefold. A set of consistent randomized controlled trials has demonstrated that long-term anticoagulation can largely reverse the risk of stroke attributable to AF. In these trials, anticoagulation generally proved quite safe, raising the risk of intracranial hemorrhage by less than 0.5% per year. The anticoagulation target for AF is INR 2 to 3 with INR 2.5 as the specific goal. The trials were much less consistent about the efficacy of aspirin, although it seems that aspirin has a small stroke-preventive effect. The recommended dose of aspirin is 325 mg per day. Because it raises the risk of hemorrhage and adds the burden of frequent monitoring of INR values, anticoagulation is recommended for those patients with AF at higher risk of stroke. Such higher risk is conferred by the following risk factors: (1) a history of a prior stroke, TIA, or other systemic embolic event; (2) a history of hypertension; (3) diabetes mellitus; (4) left ventricular dysfunction; (5) mitral stenosis; and (6) older age. The exact age threshold conferring sufficiently increased risk is uncertain, with some research indicating the threshold should be age 65 years, and other research indicating the threshold should be age 75 years. For lower-risk patients, aspirin is recommended. Future research should focus on the oldest patients with AF. These individuals face the highest risk of ischemic stroke without anticoagulation and the highest risk of major hemorrhage with anticoagulation. Only small numbers of such elderly patients were included in the randomized trials. Future research should also focus on improved risk stratification, allowing better targeting of anticoagulation. Discoveries of new antithrombotic agents and new drugs and devices for preservation of sinus rhythm could radically improve stroke-preventive strategies for AF.

The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus.

PURPOSE: Cardiovascular complications account for over 50% of mortality among patients with type 2 diabetes mellitus. We quantify the cardiovascular benefit of lowering cholesterol, blood pressure, and glucose levels in these patients. METHODS: We conducted a meta-analysis of randomized controlled trials in type 2 diabetes or diabetes subgroups, comparing the cardiovascular effects of intensive medication control of risk factor levels in standard therapy or placebo. We identified trials by searching MEDLINE (1966 to 2000) and review articles. Treatment details, patient characteristics, and outcome events were obtained using a specified protocol. Data were pooled using fixed-effects models. RESULTS: Seven serum cholesterol-lowering trials, six blood pressure-lowering trials, and five blood glucose-lowering trials met eligibility criteria. For aggregate cardiac events (coronary heart disease death and nonfatal myocardial infarction), cholesterol lowering [rate ratio (RR) = 0.75; 95% confidence interval (CI): 0.61 to 0.93) and blood pressure lowering (RR = 0.73; 95% CI: 0.57 to 0.94) produced large, significant effects, whereas intensive glucose lowering reduced events without reaching statistical significance (RR = 0.87; 95% CI: 0.74 to 1.01). We observed this pattern for all individual cardiovascular outcomes. For cholesterol-lowering and blood pressure-lowering therapy, 69 to 300 person-years of treatment were needed to prevent one cardiovascular event. CONCLUSION: The evidence from these clinical trials demonstrates that lipid and blood pressure lowering in patients with type 2 diabetes is associated with substantial cardiovascular benefits. Intensive glucose lowering is essential for the prevention of microvascular disease, but improvements in cholesterol and blood pressure levels are central to reducing cardiovascular disease in these patients.

Relation between length of hospital stay and costs of care for patients with community-acquired pneumonia.

PURPOSE: Patients with pneumonia often remain hospitalized after becoming clinically stable, without demonstrated benefits on outcome. The purposes of this study were to assess the relation between length of hospital stay and daily medical care costs and to estimate the potential cost savings associated with a reduced length of stay for patients with pneumonia. SUBJECTS AND METHODS: As part of a prospective study of adults hospitalized with community-acquired pneumonia at a community hospital and two university teaching hospitals, daily medical care costs were estimated by multiplying individual charges by department-specific cost-to-charge ratios obtained from each hospital's Medicare cost reports. RESULTS: The median total cost of hospitalization for all 982 inpatients was $5, 942, with a median daily cost of $836, including $491 (59%) for room and $345 (41%) for non-room costs. Average daily non-room costs were 282% greater on the first hospital day, 59% greater on the second day, and 19% greater on the third day than the average daily cost throughout the hospitalization (all P <0.05), and were 14% to 72% lower on the last 3 days of hospitalization. Average daily room costs remained relatively constant throughout the hospital stay, with the exception of the day of discharge. A projected mean savings of $680 was associated with a 1-day reduction in length of stay. CONCLUSIONS: Despite institutional differences in total costs, patterns of daily resource use throughout hospitalization were similar at all institutions. A 1-day reduction in length of stay might yield substantial cost-savings.

Clinical presentation, processes and outcomes of care for patients with pneumococcal pneumonia.

OBJECTIVE: To describe the presentation, resolution of symptoms, processes of care, and outcomes of pneumococcal pneumonia, and to compare features of the bacteremic and nonbacteremic forms of this illness. DESIGN: A prospective cohort study. SETTING: Five medical institutions in 3 geographic locations. PARTICIPANTS: Inpatients and outpatients with community-acquired pneumonia (CAP). MEASUREMENTS: Sociodemographic characteristics, respiratory and nonrespiratory symptoms, and physical examination findings were obtained from interviews or chart review. Severity of illness was assessed using a validated prediction rule for short-term mortality in CAP. Pneumococcal pneumonia was categorized as bacteremic; nonbacteremic, pure etiology; or nonbacteremic, mixed etiology. MAIN RESULTS: One hundred fifty-eight (6.9%) of 2,287 patients (944 outpatients, 1,343 inpatients) with CAP had pneumococcal pneumonia. Sixty-five (41%) of the 158 with pneumococcal pneumonia were bacteremic; 74 (47%) were nonbacteremic with S. pneumoniae as sole pathogen; and 19 (12%) were nonbacteremic with S. pneumoniae as one of multiple pathogens. The pneumococcal bacteremia rate for outpatients was 2.6% and for inpatients it was 6.6%. Cough, dyspnea, and pleuritic pain were common respiratory symptoms. Hemoptysis occurred in 16% to 22% of the patients. A large number of nonrespiratory symptoms were noted. Bacteremic patients were less likely than nonbacteremic patients to have sputum production and myalgias (60% vs 82% and 33% vs 57%, respectively; P <.01 for both), more likely to have elevated blood urea nitrogen and serum creatinine levels, and more likely to receive penicillin therapy. Half of bacteremic patients were in the low risk category for short-term mortality (groups I to III), similar to the nonbacteremic patients. None of the 32 bacteremic patients in risk groups I to III died, while 7 of 23 (30%) in risk group V died. Intensive care unit admissions and pneumonia-related mortality were similar between bacteremic and nonbacteremic groups, although 46% of the bacteremic group had respiratory failure compared with 32% and 37% for the other groups. The nonbacteremic pure etiology patients returned to household activities faster than bacteremic patients. Symptoms frequently persisted at 30 days: cough (50%); dyspnea (53%); sputum production (48%); pleuritic pain (13%); and fatigue (63%). CONCLUSIONS: There were few differences in the presentation of bacteremic and nonbacteremic pneumococcal pneumonia. About half of bacteremic pneumococcal pneumonia patients were at low risk for mortality. Symptom resolution frequently was slow.

Smoking by patients in a smoke-free hospital: prevalence, predictors, and implications.

BACKGROUND: No-smoking policies are now mandated in all U.S. hospitals. They require hospitalized smokers to abstain temporarily from tobacco. Little is known about patients' compliance with these policies or about their effects on patients' comfort and subsequent smoking behavior. Hospitalization in a smoke-free hospital might precipitate nicotine withdrawal in smokers, but it might also offer smokers an opportunity to stop smoking. METHODS: To assess the prevalence, predictors, and implications of smoking during hospitalization, we analyzed data from a cohort of 650 adult smokers who were admitted to an urban teaching hospital and participating in a smoking intervention trial. We measured nicotine withdrawal symptoms at study entry (24-48 h after admission) and patients' self-reports of smoking while hospitalized, compliance with the hospital no-smoking policy (smoking prohibited indoors but permitted outdoors), and smoking status 1 and 6 months after discharge. RESULTS: One-quarter of smokers admitted to a smoke-free hospital reported smoking during their hospital stay, although only 4% of smokers admitted violating policy by smoking indoors. Within 48 h of admission, 55% of smokers reported cigarette cravings and 29% of smokers reported difficulty refraining from smoking. Smokers with cigarette cravings were more likely to smoke while hospitalized (OR 3.6; 95% CI: 1.9-6.7). Those with nicotine withdrawal symptoms were more likely to violate the hospital no-smoking policy (OR 6.8; 95% CI: 5.3-8.3). Abstaining from tobacco use while hospitalized was a strong independent predictor of continued abstinence after discharge (OR 3.8; 95% CI: 1.4-10.3). CONCLUSIONS: Smoking by patients in a smoke-free hospital was common. Craving for cigarettes and symptoms consistent with nicotine withdrawal occurred frequently in hospitalized smokers and were associated with smoking during hospitalization, which was itself strongly linked with continuing to smoke after discharge. Pharmacologic treatment of cigarette cravings in hospitalized smokers could potentially improve patient comfort, increase compliance with hospital no-smoking policies, and promote smoking cessation after hospital discharge. This approach deserves further study.

Implications of stroke risk criteria on the anticoagulation decision in nonvalvular atrial fibrillation: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study.

BACKGROUND: Warfarin dramatically reduces the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) but increases the likelihood of bleeding. Accurately identifying patients who need anticoagulation is critical. We assessed the potential impact of prominent stroke risk classification schemes on this decision in a large sample of patients with NVAF. METHODS AND RESULTS: We used clinical and electrocardiographic databases to identify 13 559 ambulatory patients with NVAF from July 1996 through December 1997. We compared the proportion of patients classified as having a low enough stroke risk to receive aspirin using published criteria from the Atrial Fibrillation Investigators (AFI), American College of Chest Physicians (ACCP), and the Stroke Prevention in Atrial Fibrillation Investigators (SPAF). In this cohort, AFI criteria classified 11% as having a low stroke risk, compared with 23% for ACCP and 29% for SPAF (kappa range, 0.44 to 0.85). This 2- to-3-fold increase in low stroke risk patients by ACCP and SPAF criteria primarily resulted from the inclusion of many older subjects (65 to 75 years+/-men >75 years) with no additional clinical stroke risk factors. CONCLUSIONS: The age threshold for assigning an increased stroke risk has a dramatic impact on whether to recommend warfarin in populations of patients with NVAF. Large, prospective studies with many stroke events are needed to precisely determine the relationship of age to stroke risk in AF and to identify which AF subgroups are at a sufficiently low stroke risk to forego anticoagulation.

Apolipoprotein E isoform polymorphisms are not associated with insulin resistance: the Framingham Offspring Study.

OBJECTIVE: Insulin resistance and the apolipoprotein (apo) allele e4 have both been associated with coronary heart disease (CHD). We examined the relationship between insulin resistance and apo(e) polymorphisms among participants in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS: During 1991-1995, subjects underwent a clinical examination and an oral glucose tolerance test with measurement of fasting and 2-h glucose, insulin levels, and fasting lipid levels. We measured insulin resistance using the homeostasis model, in which insulin resistance (HOMA-IR) = fasting insulin x glucose/22.5. Apo(e) isoforms and phenotypes were determined in 1983-1987 using isoelectric focusing of plasma VLDL. Of the 2,120 subjects with complete HOMA-IR and apo(e) data, 204 with type 2 diabetes were excluded. The remainder were classified with features of the insulin resistance syndrome including impaired glucose tolerance (1997 American Diabetes Association criteria), hypertension (criteria from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [6th report]), obesity (BMI >85th percentile), high waist-to-hip ratio (>85th percentile), and high triglyceride and low HDL levels (NCEP-2 criteria). We analyzed data with contingency tables and age- and sex-adjusted logistic regression models. RESULTS: Among the 1,916 subjects, the mean age was 55 (range 28-83 years) and 51% were women. Median HOMA-IR was 6.4 (interquartile range 5.2-8.2), and allele frequencies were 7.8, 79.9, and 12.4% for apo(e) alleles e2, e3, and e4, respectively There were no differences in proportions of apo(e) isoforms or alleles across increasing quintiles of HOMA-IR. A less dramatic increase in proportions occurred with elevated triglycerides associated with increasing HOMA-IR among those with apo(e) isoforms 2/2 and 2/3 compared with the others (P < or = 0.01 for interaction). Otherwise, apo(e) did not substantially modify associations between insulin resistance and features of the insulin resistance syndrome. CONCLUSIONS: There is no association between apo(e) polymorphisms and insulin resistance. These appear to represent 2 completely independent risk factors for CHD.

Prospective study of the outcomes of ambulatory patients with excessive warfarin anticoagulation.

BACKGROUND: Warfarin sodium therapy is highly effective in preventing thromboembolism. Its major toxic effect is hemorrhage, the risk of which increases with the international normalized ratio (INR). Data on the rate of major hemorrhage and the rate of INR decay after an episode of excessive anticoagulation therapy would help guide management of elevated INRs in the outpatient setting. METHODS: We prospectively followed up outpatients in an anticoagulant therapy unit from April 24, 1995, through March 1, 1996. Study patients had to be taking warfarin for longer than 1 month and have an INR target range of 2.0 to 3.0. Consecutive outpatients with an INR greater than 6.0 were identified and compared with a randomly selected concurrent set of patients whose INR was in the target range. Major hemorrhage was defined as fatal, intracranial, or requiring hospitalization and transfusion of at least 2 U of blood. RESULTS: One hundred fourteen patients with INRs greater than 6.0 were identified and compared with 268 patients with INRs in the target range. None of the patients had clinically apparent bleeding at the time of the INR measurement, and none received phytonadione (vitamin K1). Patients did not differ significantly in age, sex, indication, or duration of warfarin therapy. Ten patients with an INR greater than 6.0 (8.8%; 95% confidence interval, 4.3%-15.5%) sought medical attention for abnormal bleeding, and 5 of these experienced a major hemorrhage during 14-day follow-up (4.4%; 95% confidence interval, 1.4%-9.9%) compared with none of the patients with an in-range INR (P<.001). Thirty-three percent of patients with INRs greater than 6.0 had INRs less than 4.0 within 24 hours, 55% within 48 hours, 73% within 72 hours, and nearly 90% within 96 hours of temporary discontinuation of warfarin therapy. CONCLUSIONS: Outpatients with INRs greater than 6.0 face a significant short-term risk of major hemorrhage. Randomized trials are needed to determine the net benefit of preventive treatment with phytonadione.