Unadjusted Risk Ratio Research Articles

National Impact of the Troponin Diagnostic Standard on the Prevalence and Prognosis of Acute Myocardial Infarction in Older Persons

Consensus guidelines from the American College of Cardiology, the American Heart Association, and the European Society of Cardiology have made cardiac troponin central to the diagnosis of acute myocardial infarction (AMI). Although multiple studies have shown that the troponin diagnostic standard facilitates the identification of new AMI cases in the general population, and that elevations of troponin are associated with poor prognosis, questions remain regarding the impact of the troponin diagnostic standard on the prevalence and prognosis of AMI in older persons. Nationwide samples of eligible Medicare beneficiaries aged > or =65 years who were hospitalized (n = 71,120) with a primary discharge diagnosis of AMI between April 1998 and March 1999 (baseline cohort) or July 2000 and June 2001 (remeasurement cohort) were evaluated. The analysis was restricted to patients with clinically confirmed AMI who underwent testing for both CK-MB and troponin. The majority of these patients (71.0%) were both CK-MB- and troponin-positive, but 17.8% were diagnosed with AMI based solely on positive troponin levels. Combining the CK-MB or both groups as a reference and troponin as a design variable to fit Cox proportional hazards models, troponin-only-positive patients had an unadjusted risk ratio (RR) of 1.14 (95% confidence interval [CI], 1.07-1.22) for the 30-day mortality and RR of 1.09 (95% CI, 1.03-1.15) for the 3-year mortality. However, after adjusting for patient demographics, clinical characteristics, physician specialties, and hospitals characteristics, troponin-only-positive patients had similar risk for early- and long-term mortality as the other 2 groups; the risk-adjusted RR for 30-day mortality was 0.96 (95% CI, 0.89-1.02) and for 3-year mortality was 0.95 (95% CI, 0.90-1.00). The widespread application of cardiac troponins results in a substantial increase in AMI diagnoses in older patients. Contrary to the prevailing wisdom that troponin-only-positive AMIs are smaller "infarctlets" and likely to have better prognosis, older persons with troponin-only AMIs are at similar risk for early and long-term mortality compared with those with CK-MB-positive AMIs. Therefore, nationwide efforts should focus on the unique characteristics of this emerging patient population so as to improve quality of care provided to this high-risk cohort of patients with AMI.

Nurse staffing levels and hospital mortality in critical care settings: literature review and meta‐analysis

This paper reports a review of the literature on the association between critical care nurse staffing levels and patient mortality. Statistically significant inverse associations between levels of nurse staffing and hospital mortality have not been consistently found in the literature. Critical care settings are ideal to address this relationship due to high patient acuity and mortality, high intensity of the nursing care required, and availability of individual risk adjustment methods. Major electronic databases were searched, including MEDLINE, EMBASE, and the Cumulative Index of Nursing and Allied Health Literature. The search terms included critical/intensive care, quality of health care, mortality/hospital mortality, personnel staffing and scheduling, and nursing staff (hospital). Only papers published in English were included. The original search was conducted in 2002 and updated in 2005. Nine studies were selected from 251 references screened. All nine were observational. Six were conducted in the United States of America, one in Austria, one in Brazil, and one in Scotland. The unadjusted risk ratio of nurse staffing (high vs. low) on hospital mortality were combined meta-analytically (five studies). The pooled estimate was 0.65 (95% confidence interval 0.47-0.91). However, after adjusting for various covariates within each study, the individually reported associations between high nurse staffing and low hospital mortality became non-significant in all but one study. The impact of nurse staffing levels on patients' hospital mortality in critical care settings was not evident in the reviewed studies. Methodological challenges that might have impeded correct assessment of the association include measurement problems in exposure status and confounding factors, often uncontrolled. The lack of association also indicates that hospital mortality may not be sensitive enough to detect the consequences of low nurse staffing levels in critical care settings.

Is There Cross-Reactivity Between Penicillins and Cephalosporins?

Background We sought to determine the risk of an allergic reaction to a cephalosporin exposure in those with prior penicillin reactions. Methods We conducted a retrospective cohort study using the United Kingdom General Practice Research Database. We selected all patients receiving a prescription for penicillin followed by a prescription for a cephalosporin and identified allergic-like events within 30 days after each prescription. Allergic events were defined by 2 sets of codes: 1 more restrictive, 1 more inclusive. Comparison was made with a population of patients receiving a prescription for a penicillin followed by a prescription for a sulfonamide antibiotic. Results A total of 3 375 162 patients received a penicillin; 506 679 (15%) received a subsequent cephalosporin. Among patients receiving a penicillin followed by a cephalosporin, the unadjusted risk ratio of an allergic-like event for those who had a prior event, compared with those who had no such prior event, narrowly defined, was 10.1 (confidence interval 7.4-13.8). The absolute risk of anaphylaxis after a cephalosporin was less than 0.001%. The unadjusted risk ratio for sulfonamide antibiotic, rather than cephalosporin after penicillin allergic-like events was 7.2 (confidence interval 3.8-13.5). Conclusion Patients with allergic-like events after penicillin had a markedly increased risk of events after either subsequent cephalosporins or sulfonamide antibiotics. Cross-reactivity is not an adequate explanation for this increased risk, and the risk of anaphylaxis is very low. Thus, our data indicate that cephalosporins can be considered for patients with penicillin allergy.

Maternal Pre-pregnancy Overweight and Obesity and the Risk of Cesarean Delivery in Nulliparous Women

To examine the effect of maternal pre-pregnancy overweight and obesity on the risk of term cesarean delivery in nulliparous women. The authors examined data from 641 nulliparous women with a term pregnancy that participated in the Pregnancy, Infection, and Nutrition Study from 1995 to 2002. Unadjusted and adjusted risk ratios and 95% confidence intervals (CI) were computed for normal weight (BMI 19.8-26.0 kg/m(2)), overweight (BMI 26.1-29.0 kg/m(2)), and obese (BMI>29.0 kg/m(2)) women. Normal weight women served as the referent population. The unadjusted risk ratio for cesarean delivery for overweight women compared with normal weight women was 1.4 (95% CI, 0.97, 2.1) and for obese women compared with normal weight women was 1.4 (95% CI, 1.03, 2.0). After controlling for maternal height, education, weight gain during pregnancy, and labor induction, the adjusted risk ratio for cesarean delivery among overweight women was 1.2 (95% CI, 0.8, 1.8). The adjusted risk ratio for obese women was 1.5 (95% CI, 1.05, 2.0). Our analysis confirms that there is a moderate association between maternal pre-pregnancy obesity and an unplanned term cesarean delivery. However, the risk is not as large as previously reported.

Fracture risk in patients with prostate cancer on androgen deprivation therapy

Although a decrease in bone mass is a well-known side effect of hormone therapy for prostate carcinoma, its clinical significance is unclear, as there is only scanty information about the incidence of fractures. Therefore, the aim of this study was to determine the risk of non-metastatic fractures in patients with prostate cancer undergoing androgen deprivation therapy. We performed a retrospective cohort study that comprised 288 patients with cancer who were subjected to androgen deprivation therapy (ADT). All were given LHRH agonists, and most of them also received peripheral androgen receptor blockers. The results were compared with a control group of 300 men that were not receiving ADT. The incidence rates of peripheral and vertebral fractures in the group of men on ADT were 1.9 and 0.8 per 100 patient-years, respectively. Incidence rates in the control group were 0.5 and 0.2, respectively. In the whole study group, 35 patients had at least one fracture during follow-up (25 on ADT, ten controls). Thus, the number of patients with at least one fracture was significantly higher in the group on ADT (P = 0.001 by the log-rank test). The unadjusted risk ratio was 4.2 (CI 2.0-8.9). A similar value (risk ratio 3.6; CI 1.6-7.7, P = 0.001) was found after it was adjusted for other factors, such as age or prior fractures. Therefore, ADT is associated with a fourfold increase in the incidence rate of both peripheral and vertebral fractures. Although the absolute incidence remains relatively small, preventive measures should be considered for high-risk patients.

N-Terminal Pro-B-Type Natriuretic Peptide as a Prognostic Marker in Acute Coronary Syndrome

Background and Objectives:Biochemical markers are useful for the prediction of cardiac events in patients with acute coronary syndrome (ACS). The N-terminal fragment of the BNP prohormone (NT-proBNP), which is synthesized by cardiac ventricles in response to increased wall stress, may be a prognostic marker in ACS. The relation between the NT-pro BNP levels on admission and major adverse cardiovascular events (MACEs) were assessed in a cohort of patients with ACS. Subjects and Methods:Between October 2002 and April 2004, blood samples for the determination of NT-proBNP level were obtained on admission from 78 patients with ST-elevation myocardial infarction (STEMI), 32 with non-ST elevation MI (NSTEMI) and 66 with unstable angina (UA). Patients were followed concerning MACEs (death, MI, heart failure, stroke and revascularization) for a median of 7 months in median. Results:22 patients (13%) had events. The mean NTproBNP level was significantly lower in the event-free survivors than in those with events (1342±1598 versus 6129±6522 pg/mL, p<0.0001). The optimal cut-off value of the NT-proBNP level using a receiver-operating-characteristic curve was 1445 pg/mL. The unadjusted risk ratio of patients with an NT-proBNP level greater than the threshold was 7.0 (95% confidence interval, 2.6 to 19.0). In a multivariate Cox regression model, including clinical background factors and other biochemical markers, the NT-proBNP level was the most powerful indicator of MACEs (risk ratio, 8.0 [95% confidence interval, 1.7 to 37.1]). The coronary angiographic Gensini score was also a predictor of prognosis in ACS (risk ratio, 3.8 [95% confidence interval, 1.0 to 14.0]). Conclusion:A single measurement of the NT-proBNP level on admission appears to be useful as a prognostic factor in the prediction of MACEs in patients after ACS. (Korean Circulation J 2004;34(11):1070-1081)

Explaining the association of maternal age with cesarean delivery for nulliparous and parous women

Method We used data on 6,805 live births from the National Maternal and Infant Health Survey to examine the positive association between maternal age and Cesarean delivery. Results For parous women, the unadjusted risk ratio [RR] for Cesarean, comparing 35 year olds with 20 year olds, was estimated to be 1.40 [95% confidence limits (CL) = 1.18, 1.65]; this association disappeared upon adjustment for obstetrical predictors and other factors (adjusted RR = 1.04; 95% CL = 0.80, 1.35). In contrast, for nulliparous women, the unadjusted risk ratio was 2.16 (95% CL = 1.78, 2.63) and remained substantial upon adjustment (RR = 1.74; 95% CL = 1.25, 2.43). Conclusion These results, along with baseline risk information, suggest that older nulliparous women and their obstetricians should be the target of future efforts to control Cesarean rates.

Silent Myocardial Ischemia

Silent myocardial ischemia is defined as objective documentation of myocardial ischemia in the absence of angina or anginal equivalents. Since its original description in the 1970s, it has undergone intensive investigation, and its clinical significance is now well established. This review will serve as an update on the pathophysiology, detection, prevalence, prognosis, and treatment of silent ischemia in both asymptomatic patients and those with angina, whether stable or unstable. ### Pain Studies No discussion of silent ischemia is complete without consideration of the cardiac pain mechanism. Although much has been learned about this subject, much is still uncertain. The afferent fibers that run in the cardiac sympathetic nerves are usually thought of as the essential pathway for the transmission of cardiac pain (Figure 1). The atria and ventricles are abundantly supplied with sympathetic sensory innervation; from the heart, the sensory nerve endings connect to afferent fibers in cardiac nerve bundles, which in turn connect to the upper 5 thoracic sympathetic ganglia and the upper 5 thoracic dorsal roots of the spinal cord. Within the spinal cord, impulses mediated by this sympathetic afferent route probably converge with impulses from somatic thoracic structures onto the same ascending spinal neurons. This would be the basis for cardiac pain referred to the chest, wall, arm, back etc. In addition to this “convergence-projection theory,” the contribution of vagal afferent fibers must be acknowledged for an explanation of cardiac pain referred to the jaw and neck. How these vagal fibers are activated remains unclear. Furthermore, somatic localization of ischemic pain cannot predict the site of myocardial ischemia (anterior, inferior, or lateral) from one patient to the next. Figure 1. Mechanisms of cardiac pain. From Droste and Roskamm (used with permission).4 The actual “trigger” that stimulates the sensory nerve endings remains elusive. If a chemical pain stimulus is involved, …

N-Terminal Pro-B-Type natriuretic peptide and long-term mortality in acute coronary syndromes

Background— B-type natriuretic peptide (BNP) is a predictor of short- and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS. Methods and Results— Blood samples for N-BNP determination were obtained in the subacute phase in 204 patients with ST-elevation myocardial infarction (MI): 220 with non-ST segment elevation MI and 185 with unstable angina in the subacute phase. After a median follow-up of 51 months, 86 patients (14%) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 versus 1306 pmol/L; P<0.0001). The unadjusted risk ratio of patients with supramedian N-BNP levels was 3.9 (95% confidence interval, 2.4 to 6.5). In a multivariate Cox regression model, N-BNP (risk ratio 2.1 [95%...

N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes.

B-type natriuretic peptide (BNP) is a predictor of short- and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS. Blood samples for N-BNP determination were obtained in the subacute phase in 204 patients with ST-elevation myocardial infarction (MI): 220 with non-ST segment elevation MI and 185 with unstable angina in the subacute phase. After a median follow-up of 51 months, 86 patients (14%) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 versus 1306 pmol/L; P<0.0001). The unadjusted risk ratio of patients with supramedian N-BNP levels was 3.9 (95% confidence interval, 2.4 to 6.5). In a multivariate Cox regression model, N-BNP (risk ratio 2.1 [95% confidence interval, 1.1 to 3.9]) added prognostic information above and beyond Killip class, patient age, and left ventricular ejection fraction. Adjustment for peak troponin T levels did not markedly alter the relation between N-BNP and mortality. In patients with no evidence of clinical heart failure, N-BNP remained a significant predictor of mortality after adjustment for age and ejection fraction (risk ratio, 2.4 [95% confidence interval, 1.1 to 5.4]). N-BNP is a powerful indicator of long-term mortality in patients with ACS and provides prognostic information above and beyond conventional risk markers.

Silent acute rejection during prolonged delayed graft function reduces kidney allograft survival.

The relationship between the effects of early, silent, acute rejection (AR) and delayed graft function (DGF) on kidney allograft survival remain controversial, and the role of protocol biopsies during DGF is unclear. We hypothesized that protocol biopsies during DGF would reveal a high incidence of silent AR that may adversely affect long-term allograft survival. We routinely carried out protocol biopsies in patients requiring dialysis 7 to 10 days posttransplant. We retrospectively examined the extent to which silent AR, diagnosed by protocol biopsies during prolonged DGF, may mediate the adverse effects of DGF on graft survival in 410 consecutive transplants using Cox proportional hazards analysis. By 40 days posttransplant, the cumulative incidence of AR was 57.2% among 65 patients who had a protocol biopsies during DGF, while it was only 15.1% among the 345 who did not need a protocol biopsy. Mild DGF (n=30) requiring one or two dialysis treatments had no effect on graft survival, but the unadjusted risk ratio (and 95% confidence interval) associated with more prolonged DGF (n=104) was 3.08 (2.09-4.52, P<0.0001). The risk for graft failure from AR detected on protocol biopsy was 2.91 (1.60-5.27, P=0.0004) and was similar to the risk from early AR in patients without DGF, 2.95 (1.72-5.07, P<0.0001). After taking the effects of AR into account, the risk of graft failure attributable to prolonged DGF was reduced to 1.76 (1.06-2.94, P=0.0294), suggesting that much of the risk of DGF was because of the risk of AR. Silent AR is common during DGF. Prolonged DGF is associated with reduced graft survival after kidney transplantation, and much of this association can be explained by silent AR. In the absence of data from randomized trials, protocol biopsies and treatment of silent AR during prolonged DGF appear to be warranted.

Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.

The role of C-reactive protein (CRP) as a novel plasma marker of atherothrombotic disease is currently under investigation. Previous studies have mostly related CRP to coronary heart disease, were often restricted to a case-control design, and failed to include pertinent risk factors to evaluate the joint and net effect of CRP on the outcome. We related plasma CRP levels to incidence of first ischemic stroke or transient ischemic attack (TIA) in the Framingham Study original cohort. There were 591 men and 871 women free of stroke/TIA during their 1980 to 1982 clinic examinations, when their mean age was 69.7 years. CRP levels were measured by using an enzyme immunoassay on previously frozen serum samples. Analyses were based on sex-specific CRP quartiles. Risk ratios (RRs) were derived, and series of trend analyses were performed. During 12 to 14 years of follow-up, 196 ischemic strokes and TIAs occurred. Independent of age, men in the highest CRP quartile had 2 times the risk of ischemic stroke/TIA (RR=2.0, P=0.027), and women had almost 3 times the risk (RR=2.7, P=0.0003) compared with those in the lowest quartile. Assessment of the trend in risk across quartiles showed unadjusted risk increase for men (RR=1.347, P=0.0025) and women (RR=1.441, P=0.0001). After adjustment for smoking, total/HDL cholesterol, systolic blood pressure, and diabetes, the increase in risk across CRP quartiles remained statistically significant for both men (P=0.0365) and women (P=0.0084). Independent of other cardiovascular risk factors, elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly.

Plasma C-Reactive Protein, Systolic Hypertension and Risk of Ischemic Stroke and TIA: The Framingham Study

83 Background: The role of plasma C-reactive protein (CRP) as marker of cerebrovascular risk is currently under investigation. We evaluated relative risk of developing first ischemic stroke and TIA among the patients with elevated systolic blood pressure (SBP) and/or elevated plasma CRP levels versus those patients with unelevated SBP and unelevated CRP. Methods: We studied 591 men and 868 women of the original Framingham Study cohort who were free of stroke and TIA at the time of their 1980–1982 clinic exam. Sex-specific Cox proportional hazards regressions were used to quantify the risk of 14-year incidence of ischemic stroke/TIA associated with elevated SBP and CRP. Unadjusted models and models adjusted for age, smoking, total & HDL cholesterol, and diabetes were used. SBP and CRP were included in the Cox models as sex-specific quartiles. Risk ratios of first ischemic stroke/TIA for individuals with elevated (in the upper quartile) SBP (SBP+) and CRP (CRP+) were determined using the SBP-/CRP- individuals as a reference group. Similarly, simultaneous evaluation of the risk of first ischemic stroke/TIA was done for SBP+/CRP- and SBP-/CRP+ using the individuals in SBP-/CRP- as a reference group. Results: Relative to SBP-/CRP- men (incidence of first ischemic stroke/TIA of 36/328, or 11.0%), SBP+/CRP+ men (where incidence was 8/32, or 25.0%) had unadjusted risk ratio of 3.56 (p=0.001). This ratio was nearly twice that for SBP+/CRP- men (incidence=20/115, or 17.4%; RR=1.89, p=0.023). Relative to SBP-/CRP- women (incidence= 45/485, or 9.3%), the unadjusted risk ratio increased from 2.03 in SBP+/CRP- women (incidence=27/166, or 16.3%; p=0.001) to 3.44 in SBP+/CRP+ women (incidence=15/58, or 25.9%; p Conclusion: Having both CRP levels and systolic BP above the 75 th percentile for each of these parameters significantly increased risk of developing first ischemic stroke/TIA in both sexes.

Plasma C-Reactive Protein, Systolic Hypertension and Risk of Ischemic Stroke and TIA: The Framingham Study

83 Background: The role of plasma C-reactive protein (CRP) as marker of cerebrovascular risk is currently under investigation. We evaluated relative risk of developing first ischemic stroke and TIA among the patients with elevated systolic blood pressure (SBP) and/or elevated plasma CRP levels versus those patients with unelevated SBP and unelevated CRP. Methods: We studied 591 men and 868 women of the original Framingham Study cohort who were free of stroke and TIA at the time of their 1980–1982 clinic exam. Sex-specific Cox proportional hazards regressions were used to quantify the risk of 14-year incidence of ischemic stroke/TIA associated with elevated SBP and CRP. Unadjusted models and models adjusted for age, smoking, total &amp; HDL cholesterol, and diabetes were used. SBP and CRP were included in the Cox models as sex-specific quartiles. Risk ratios of first ischemic stroke/TIA for individuals with elevated (in the upper quartile) SBP (SBP+) and CRP (CRP+) were determined using the SBP-/CRP- individuals as a reference group. Similarly, simultaneous evaluation of the risk of first ischemic stroke/TIA was done for SBP+/CRP- and SBP-/CRP+ using the individuals in SBP-/CRP- as a reference group. Results: Relative to SBP-/CRP- men (incidence of first ischemic stroke/TIA of 36/328, or 11.0%), SBP+/CRP+ men (where incidence was 8/32, or 25.0%) had unadjusted risk ratio of 3.56 (p=0.001). This ratio was nearly twice that for SBP+/CRP- men (incidence=20/115, or 17.4%; RR=1.89, p=0.023). Relative to SBP-/CRP- women (incidence= 45/485, or 9.3%), the unadjusted risk ratio increased from 2.03 in SBP+/CRP- women (incidence=27/166, or 16.3%; p=0.001) to 3.44 in SBP+/CRP+ women (incidence=15/58, or 25.9%; p&lt;0.001). Adjustment for age did not significantly alter this relationship. Following multivariate adjustment, risk of developing first ischemic stroke/TIA remained significantly elevated in SBP+/CRP+ men (RR=2.7; p=0.018) and women (RR=2.06; p=0.027). Conclusion: Having both CRP levels and systolic BP above the 75 th percentile for each of these parameters significantly increased risk of developing first ischemic stroke/TIA in both sexes.

Differences in mortality and morbidity in African Caribbean and European people with non-insulin dependent diabetes mellitus: results of 20 year follow up of a London cohort of a multinational study.

To examine differences in morbidity and mortality due to non-insulin dependent diabetes in African Caribbeans and Europeans. Cohort study of patients with non-insulin dependent diabetes drawn from diabetes clinics in London. Baseline investigations were performed in 1975-7; follow up continued until 1995. 150 Europeans and 77 African Caribbeans with non-insulin dependent diabetes. All cause and cardiovascular mortality; prevalence of microvascular and macrovascular complications. Duration of diabetes was shorter in African Caribbeans, particularly women. African Caribbeans were more likely than the Europeans to have been given a diagnosis after the onset of symptoms and less likely to be taking insulin. Mean cholesterol concentration was lower in African Caribbeans, but blood pressure and body mass index were not different in the two ethnic groups. Prevalence of microvascular and macrovascular complications was insignificantly lower in African Caribbens than in Europeans. 59 Europeans and 16 African Caribbeans had died by the end of follow up. The risk ratio for all cause mortality was 0.41 (95% confidence interval 0.23 to 0.73) (P = 0.002) for African Caribbeans v Europeans. This was attenuated to 0.59 (0.32 to 1.10) (P = 0.1) after adjustment for sex, smoking, proteinuria, and body mass index. Further adjustment for systolic blood pressure, cholesterol concentration, age, duration of diabetes, and treatment made little difference to the risk ratio. Unadjusted risk ratio for cardiovascular and ischaemic heart disease were 0.33 (0.15 to 0.70) (P = 0.004) and 0.37 (0.16 to 0.85) (P = 0.02) respectively. African Caribbeans with non-insulin dependent diabetes maintain a low risk of heart disease. Management priorities for diabetes developed in one ethnic group may not necessarily be applicable to other groups.

Influence of gender on short- and long-term mortality after acute myocardial infarction

The aim of this study was to assess differences in short- and long-term mortality between male and female patients with acute myocardial infarction (AMI). The study population consisted of 6,676 consecutive patients admitted alive with an enzyme-confirmed AMI to 27 Danish hospitals from 1990 to 1992. Five patients were excluded because of missing information. Female patients (n = 2,170) were on average 5 years older than male patients (n = 4,501, p < 0.001), had lower body mass index, and more often had diabetes, hypertension, and congestive heart failure. Left ventricular systolic function was the same for men and women. Women received thrombolytic therapy less often. The 1-year mortality for female patients was 28 ± 1% and for men 21 ± 1% (p < 0.001). The unadjusted risk ratio associated with male gender in a proportional-hazards model was 0.76 (95% confidence intervals [CI] 0.70 to 0.83). Adjustment for age removed the importance of gender, and the risk ratio associated with male gender was 1.06 (95% CI 0.97 to 1.2, p = 0.2). An introduction of further variables in the model did not change this. Subdividing mortality into 6-day, 30-day, and late mortality demonstrated a significantly increased mortality in women in the short-term (6 and 30 days), with a risk ratio in men of 0.58 (95% CI 0.42 to 0.81) and 0.80 (95% CI 0.65 to 0.99), respectively. From day 30 onward there was an increased mortality in men with a risk ratio of 1.16 (95% CI 1.03 to 1.31, p = 0.01). Thus, women admitted alive to the hospital with an AMI have an increased long-term mortality that is explained by their older age. However, short-term mortality in women seems to increase independently of other risk factors, but is later followed by an increase in mortality in men.

Screening for cutaneous melanoma by skin self-examination.

Although some evidence indicates that early detection protects against the development of lethal melanoma, no randomized clinical trials have been conducted to measure the efficacy of early detection (or screening) in preventing death from this disease. Since melanoma incidence in the United States is relatively rare, a randomized clinical trial to test the efficacy of screening would be extremely expensive. As an alternative to a randomized clinical trial, we conducted a population-based, case-control study to investigate whether early detection through skin self-examination (SSE) is associated with a decreased risk of lethal melanoma (includes the presence of advanced disease with distant metastases in addition to death from melanoma). SSE (conducting a careful, deliberate, and purposeful examination of the skin) was assessed in all subjects by use of a structured questionnaire and personal interviews. The major exposure variable, SSE, was defined following focus-group interviews with melanoma patients and healthy control subjects. The final study population consisted of 1199 Caucasian residents of the state of Connecticut enrolled from January 15, 1987, through May 15, 1989; 650 individuals were newly diagnosed with cutaneous melanoma, and the remaining 549 individuals were age- and sex-frequency matched control subjects from the general population. During the study interviews, nevi on the arms and backs of subjects were counted. In 5 years of follow-up (through March 1994), 110 lethal cases of melanoma were identified. The study design allowed separate estimation of the impact of SSE on reduced melanoma incidence (primary prevention) and survival among incident cases (secondary prevention). Odds ratios (ORs) were used to measure the associations between SSE and melanoma and between SSE and lethal melanoma. SSE, practiced by only 15% of all subjects, was associated with a reduced risk of melanoma incidence (adjusted OR = 0.66; 95% confidence interval [CI] = 0.44-0.99; comparing case patients with control subjects). The data indicated further that SSE may reduce the risk of advanced disease among melanoma patients (unadjusted risk ratio = 0.58; 95% CI = 0.31-1.11); however, longer follow-up is required to confirm this latter estimate. If both estimates are correct, they suggest, in combination, that SSE may reduce mortality from melanoma by 63% (adjusted OR = 0.37; 95% CI = 0.16-0.84; comparing lethal cases with general population controls). SSE may provide a useful and inexpensive screening method to reduce the incidence of melanoma. SSE may also reduce the development of advanced disease. The results of this study need to be replicated before strategies to increase the practice of SSE are further developed and promoted.

The rostral part of the trigeminal sensory complex is involved in orofacial nociception : R. Dallel, P. Raboisson, P. Auroy and A. Woda, Brain Res., 448 (1988) 7–19

This study estimated the cumulative incidence and risk ratio for osteonecrosis of the jaw (ONJ) after tooth extraction in patients with and without administration of bisphosphonates (BP) and identified potential risk factors for bisphosphonate-induced osteonecrosis of the jaw (BIONJ). A cohort study was conducted in all patients undergoing tooth extraction at a university hospital in Japan from April 2006 to June 2009. Of 3216 patients, 126 had BP administration, of whom 5 (3.9%, 95% confidence interval (CI): 1.2–9.2) developed ONJ, versus 1 (0.032%, 95% CI: 0.00081–0.18) among 3090 patients without BP administration. BP administration was associated with the development of ONJ after tooth extraction, with an unadjusted risk ratio of 122.6 (95% CI: 14.4–1041.8). When stratified by age and route of BP administration, the risk ratio for ONJ patients aged 65 years or older with intravenous BP administration compared to those without was 200.2 (95% CI: 23.8–1679.4, P < 0.001). Patients receiving BP showed a significant association between the incidence of BIONJ and alveolar bone loss score. The risk of ONJ is higher in patients with than without BP administration, particularly intravenous administration. Severe periodontitis might be a risk factor for BIONJ.