Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study

To assess the effect of postmenopausal use of estrogens on the subsequent risk of hip fracture, we performed a retrospective cohort study of 2873 women in the Framingham Heart Study. Information obtained at routine biennial examinations about the use of estrogens, body weight, age at menopause, smoking, and alcohol consumption was used to evaluate the risk of hip fracture among postmenopausal women who received estrogens. Hip fractures occurred in 179 postmenopausal women, at a rate that increased exponentially after the age of 50. The risk of fracture was inversely related to weight at all ages. The relative risk of hip fracture in subjects who had taken estrogens at any time was 0.65 after adjustment for age and weight (95 percent confidence interval, 0.44 to 0.98). The adjusted relative risk in women who had taken estrogens within the previous two years was further reduced, to 0.34 (95 percent confidence interval, 0.12 to 0.98). Taking estrogens within four years of menopause also protected against fracture. The number of women in each age group who took estrogens was insufficient for a definitive evaluation of risk, but recent use of estrogens appeared to be protective in women under the age of 65 (no fractures among those who took estrogens) and those 65 to 74. We cannot exclude some degree of selection bias among the women who received estrogen-replacement therapy. Nevertheless, this large cohort study supports the hypothesis that postmenopausal use of estrogens protects against subsequent hip fracture in women.     

Risk factors for falls as a cause of hip fracture in women. The Northeast Hip Fracture Study Group

BACKGROUND. Although even in the elderly most falls are not associated with fractures, over 90 percent of hip fractures are the result of a fall. Few studies have assessed whether the risk factors for falls are also important risk factors for hip fracture. METHODS. To examine the importance of risk factors for falls in the epidemiology of hip fracture, we performed a case-control study of 174 women (median age, 80 years) admitted with a first hip fracture to 1 of 30 hospitals in New York and Philadelphia. Controls, matched to the case patients according to age and hospital, were selected from general surgical and orthopedic surgical hospital services. Information was obtained by direct interview. RESULTS. As measured by the odds ratio, increased risks for hip fracture were associated with lower-limb dysfunction (odds ratio = 1.7; 95 percent confidence interval, 1.1 to 2.8), visual impairment (odds ratio = 5.1; 95 percent confidence interval, 1.9 to 13.9), previous stroke (odds ratio = 2.0; 95 percent confidence interval, 1.0 to 4.0), Parkinson's disease (odds ratio = 9.4; 95 percent confidence interval, 1.2 to 76.1), and use of long-acting barbiturates (odds ratio = 5.2; 95 percent confidence interval, 0.6 to 45.0). Of the controls, 44 (25 percent) had had a recent fall. The case patients were more likely than these controls to have fallen from a standing height or higher (odds ratio = 2.4; 95 percent confidence interval, 1.0 to 5.7). Of those with hip fracture the younger patients (less than 75 years old) were more likely than the older ones (greater than or equal to 75 years old) to have fallen on a hard surface (odds ratio = 1.9; 95 percent confidence interval, 1.04 to 3.7). CONCLUSIONS. A number of factors that have been identified as risk factors for falls are also associated with hip fracture, including lower-limb dysfunction, neurologic conditions, barbiturate use, and visual impairment. Given the prevalence of these problems among the elderly, who are at highest risk, programs to prevent hip fracture should include measures to prevent falls in addition to measures to slow bone loss.     

Smoking and mortality among older men and women in three communities

BACKGROUND. Although cigarette smoking is the leading avoidable cause of premature death in middle age, some have claimed that no association is present among older persons. METHODS. We prospectively examined the relation of cigarette-smoking habits with mortality from all causes, cardiovascular causes, and cancer among 7178 persons 65 years of age or older without a history of myocardial infarction, stroke, or cancer who lived in one of three communities: East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. At the time of the initial interview, prevalence rates of smoking in the three communities ranged from 5.2 to 17.8 percent among women and from 14.2 to 25.8 percent among men. During five years of follow-up there were 1442 deaths, 729 due to cardiovascular disease and 316 due to cancer. RESULTS. In both sexes, rates of total mortality among current smokers were twice what they were among participants who had never smoked. Relative risks, as adjusted for age and community, were 2.1 among the men (95 percent confidence interval, 1.7 to 2.7) and 1.8 among the women (95 percent confidence interval, 1.4 to 2.4). Current smokers had higher rates of cardiovascular mortality than those who had never smoked (as adjusted for age and community, the relative risk was 2.0 [95 percent confidence interval, 1.4 to 2.9] among the men and 1.6 [95 percent confidence interval, 1.1 to 2.3] among the women), as well as increased rates of cancer mortality (relative risk, 2.4 [95 percent confidence interval, 1.4 to 4.1] among the men and 2.4 [95 percent confidence interval, 1.4 to 3.9] among the women). In both sexes, former smokers had rates of cardiovascular mortality similar to those of the participants who had never smoked, regardless of age at cessation, whereas the rates for all cancers, as well as smoking-related cancers, remained elevated among men who had once smoked. CONCLUSIONS. Our prospective findings indicate that the mortality hazards of smoking extend well into later life, and suggest that cessation will continue to improve life expectancy in older people.     

Prevention of hip fracture in elderly people with use of a hip protector

BACKGROUND: Hip fractures are common in frail elderly adults worldwide. We investigated the effect of an anatomically designed external hip protector on the risk of these age-related fractures. METHODS: We randomly assigned 1801 ambulatory but frail elderly adults (1409 women and 392 men; mean age, 82 years), in a 1:2 ratio, either to a group that wore a hip protector or to a control group. Fractures of the hip and all other fractures were recorded until the end of the first full month after 62 hip fractures had occurred in the control group. The risk of fracture in the two groups was compared, and in the hip-protector group the risk of fracture was also analyzed according to whether the protector had been in use at the time of a fall. RESULTS: During follow-up, 13 subjects in the hip-protector group had a hip fracture, as compared with 67 subjects in the control group. The respective rates of hip fracture were 21.3 and 46.0 per 1000 person-years (relative hazard in the hip-protector group, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.008). The risk of pelvic fracture was slightly but not significantly lower in the hip-protector group than in the control group (2 subjects and 12 subjects, respectively, had pelvic fracture) (relative hazard, 0.4; 95 percent confidence interval, 0.1 to 1.8; P > or = 0.05). The risk of other fractures was similar in the two groups. In the hip-protector group, four subjects had a hip fracture (among 1034 falls) while wearing the protector, and nine subjects had a hip fracture (among 370 falls) while not wearing the protector (relative hazard, 0.2; 95 percent confidence interval, 0.05 to 0.5; P=0.002). CONCLUSIONS: The risk of hip fracture can be reduced in frail elderly adults by the use of an anatomically designed external hip protector.     

Siblings, day-care attendance, and the risk of asthma and wheezing during childhood

BACKGROUND: Young children with older siblings and those who attend day care are at increased risk for infections, which in turn may protect against the development of allergic diseases, including asthma. However, the results of studies examining the relation between exposure to other children and the subsequent development of asthma have been conflicting. METHODS: In a study involving 1035 children followed since birth as part of the Tucson Children's Respiratory Study, we determined the incidence of asthma (defined as at least one episode of asthma diagnosed by a physician when the child was 6 to 13 years old) and the prevalence of frequent wheezing (more than three wheezing episodes during the preceding year) in relation to the number of siblings at home and in relation to attendance at day care during infancy. RESULTS: The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interval, 0.7 to 1.0; P=0.04), as did attendance at day care during the first six months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2 to 1.0; P=0.04). Children with more exposure to other children at home or at day care were more likely to have frequent wheezing at the age of 2 years than children with little or no exposure (adjusted relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.8; P=0.01) but were less likely to have frequent wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0; P=0.03) through the age of 13 (adjusted relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). CONCLUSIONS: Exposure of young children to older children at home or to other children at day care protects against the development of asthma and frequent wheezing later in childhood.     

Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group

BACKGROUND: Risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known. METHODS: We studied 5445 women 70 to 79 years old who had osteoporosis (indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [-4] or lower than -3 plus a nonskeletal risk factor for hip fracture, such as poor gait or a propensity to fall) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck (T score, lower than -4 or lower than -3 plus a hip-axis length of 11.1 cm or greater). The women were randomly assigned to receive treatment with oral risedronate (2.5 or 5.0 mg daily) or placebo for three years. The primary end point was the occurrence of hip fracture. RESULTS: Overall, the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent, as compared with 3.9 percent among those assigned to placebo (relative risk, 0.7; 95 percent confidence interval, 0.6 to 0.9; P=0.02). In the group of women with osteoporosis (those 70 to 79 years old), the incidence of hip fracture among those assigned to risedronate was 1.9 percent, as compared with 3.2 percent among those assigned to placebo (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.9; P=0.009). In the group of women selected primarily on the basis of nonskeletal risk factors (those at least 80 years of age), the incidence of hip fracture was 4.2 percent among those assigned to risedronate and 5.1 percent among those assigned to placebo (P=0.35). CONCLUSIONS: Risedronate significantly reduces the risk of hip fracture among elderly women with confirmed osteoporosis but not among elderly women selected primarily on the basis of risk factors other than low bone mineral density.     

Phenylpropanolamine and the risk of hemorrhagic stroke

BACKGROUND: Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study. METHODS: Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient. RESULTS: There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants. CONCLUSIONS: The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.     

Psychotropic drug use and the risk of hip fracture

To assess the risk of hip fracture associated with the use of four classes of psychotropic drugs, we performed a case-control study of 1021 patients with hip fractures and 5606 controls among elderly Medicaid enrollees. Persons treated with hypnotics-anxiolytics having short (less than or equal to 24 hours) elimination half-lives had no increased risk of hip fracture. By contrast, a significantly increased risk was associated with current use of hypnotics-anxiolytics having long (greater than 24 hours) elimination half-lives (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.4), tricyclic antidepressants (odds ratio, 1.9; 95 percent confidence interval, 1.3 to 2.8), and antipsychotics (odds ratio, 2.0; 95 percent confidence interval, 1.6 to 2.6). The risk increased in relation to the doses of drugs in these three classes. An analysis for possible confounding by dementia did not alter the results. Previous but noncurrent use of drugs in these classes conferred no increase in risk. Although a cause-and-effect relation was not proved, these data support the hypothesis that the sedative and autonomic effects of psychotropic drugs increase the risk of falling and fractures in elderly persons. The results suggest the need for studies of this association in other populations and for evaluation of newer psychotropic drugs with fewer undesirable sedative and autonomic effects.     

A prospective study of past use of oral contraceptive agents and risk of cardiovascular diseases

We evaluated the effects of past use of oral contraceptive agents on the risk of various cardiovascular diseases among women in the Nurses' Health Study cohort. We studied 119,061 women who were 30 to 55 years of age in 1976, who provided information on their use of oral contraceptives, and who at entry had had no previous coronary disease or stroke. End points were documented by medical records. During eight years of follow-up (484,096 person-years among those who had never used oral contraceptives, 415,488 among past users, and 22,376 among current users), there were 485 new cases of major coronary disease (380 nonfatal myocardial infarctions and 105 deaths from coronary disease), 282 strokes (205 nonfatal and 77 fatal), and 48 other deaths from cardiovascular causes. We found no evidence to suggest an increase in the risk of cardiovascular diseases among past users of oral contraceptives, even with prolonged previous use. After adjustment for a variety of risk factors, the relative risk of major coronary disease for women who had used oral contraceptives in the past, as compared with those who had never used such agents, was 0.8 (95 percent confidence interval, 0.6 to 1.0); of stroke, 1.0 (95 percent confidence interval, 0.7 to 1.3); and of death from all cardiovascular causes, 0.9 (95 percent confidence interval, 0.7 to 1.2). We found neither evidence of increased risk with longer use nor any trend with the amount of time since the last use. According to these prospective data, the use of oral contraceptive agents in the past does not materially raise a woman's risk of subsequent cardiovascular disease.     

Risk factors for injury to women from domestic violence against women

BACKGROUND: Domestic violence is the most common cause of nonfatal injury to women in the United States. To identify risk factors for such injuries, we examined the socioeconomic and behavioral characteristics of women who were victims of domestic violence and the men who injured them. METHODS: We conducted a case-control study at eight large, university-affiliated emergency departments. The 256 intentionally injured women had acute injuries resulting from a physical assault by a male partner. The 659 controls were women treated for other conditions in the emergency department. Information was collected with a standardized questionnaire; no information was obtained directly from the male partners. RESULTS: The 256 intentionally injured women had a total of 434 contusions and abrasions, 89 lacerations, and 41 fractures and dislocations. In a multivariate analysis, the characteristics of the partners that were most closely associated with an increased risk of inflicting injury as a result of domestic violence were alcohol abuse (adjusted relative risk, 3.6; 95 percent confidence interval, 2.2 to 5.9); drug use (adjusted relative risk, 3.5; 95 percent confidence interval, 2.0 to 6.4); intermittent employment (adjusted relative risk, 3.1; 95 percent confidence interval, 1.1 to 8.8); recent unemployment (adjusted relative risk, 2.7; 95 percent confidence interval, 1.2 to 6.5); having less than a high-school-graduate's education (adjusted relative risk, 2.5; 95 percent confidence interval, 1.4 to 4.4); and being a former husband, estranged husband, or former boyfriend (adjusted relative risk, 3.5; 95 percent confidence interval, 1.5 to 8.3). CONCLUSIONS: Women at greatest risk for injury from domestic violence include those with male partners who abuse alcohol or use drugs, are unemployed or intermittently employed, have less than a high-school-graduate's education, and are former husbands, estranged husbands, or former boyfriends of the women.     

Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study

A pattern of left ventricular hypertrophy evident on the electrocardiogram is a harbinger of morbidity and mortality from cardiovascular disease. Echocardiography permits the noninvasive determination of left ventricular mass and the examination of its role as a precursor of morbidity and mortality. We examined the relation of left ventricular mass to the incidence of cardiovascular disease, mortality from cardiovascular disease, and mortality from all causes in 3220 subjects enrolled in the Framingham Heart Study who were 40 years of age or older and free of clinically apparent cardiovascular disease, in whom left ventricular mass was determined echocardiographically. During a four-year follow-up period, there were 208 incident cardiovascular events, 37 deaths from cardiovascular disease, and 124 deaths from all causes. Left ventricular mass, determined echocardiographically, was associated with all outcome events. This relation persisted after we adjusted for age, diastolic blood pressure, pulse pressure, treatment for hypertension, cigarette smoking, diabetes, obesity, the ratio of total cholesterol to high-density lipoprotein cholesterol, and electrocardiographic evidence of left ventricular hypertrophy. In men, the risk factor-adjusted relative risk of cardiovascular disease was 1.49 for each increment of 50 g per meter in left ventricular mass corrected for the subject's height (95 percent confidence interval, 1.20 to 1.85); in women, it was 1.57 (95 percent confidence interval, 1.20 to 2.04). Left ventricular mass (corrected for height) was also associated with the incidence of death from cardiovascular disease (relative risk, 1.73 [95 percent confidence interval, 1.19 to 2.52] in men and 2.12 [95 percent confidence interval, 1.28 to 3.49] in women). Left ventricular mass (corrected for height) was associated with death from all causes (relative risk, 1.49 [95 percent confidence interval, 1.14 to 1.94] in men and 2.01 [95 percent confidence interval, 1.44 to 2.81] in women). We conclude that the estimation of left ventricular mass by echocardiography offers prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors. An increase in left ventricular mass predicts a higher incidence of clinical events, including death, attributable to cardiovascular disease.     

Stomach cancer after partial gastrectomy for benign ulcer disease

We followed for 25 to 33 years 6459 patients who had undergone partial gastrectomy for benign ulcer disease to determine the incidence of stomach cancer. The overall risk was no different from that among sex- and age-matched controls from the Swedish Cancer Registry (standardized incidence ratio = 0.96; 95 percent confidence limits, 0.78 and 1.16). However, when the patients were classified according to the duration of follow-up after operation, sex, surgical procedure, diagnosis at the time of operation, and age at operation, differences in risk were observed between the subgroups. After adjustment for potential confounding variables, the average adjusted risk increased 28 percent (adjusted standardized incidence ratio = 1.28; 95 percent confidence limits, 1.11 and 1.49) for each successive five-year interval after operation. The adjusted risk was greater among women than men (adjusted standardized incidence ratio = 1.96; 95 percent confidence limits, 1.18 and 3.24). Patients who had undergone a Billroth I anastomosis had a lower crude risk, both overall (standardized incidence ratio = 0.40; 95 percent confidence limits, 0.20 and 0.71) and after we controlled for other confounding variables (adjusted standardized incidence ratio = 0.27; 95 percent confidence limits, 0.12 and 0.62), than did those who had undergone a Billroth II procedure. The adjusted risk of stomach cancer was greater among patients operated on for gastric ulcer than among those operated on for duodenal ulcer (adjusted standardized incidence ratio = 2.21; 95 percent confidence limits, 1.45 and 3.35). Risk decreased with increased age at operation. Between successive strata of age at operation (less than 39, 40 to 49, 50 to 59, and greater than or equal to 60 years of age), the adjusted risk decreased on the average by about half (adjusted standardized incidence ratio = 0.52; 95 percent confidence limits, 0.41 and 0.66).     

Risk factors for human immunodeficiency virus infection in intravenous drug users

To identify risk factors for human immunodeficiency virus (HIV) infection in intravenous drug users, we undertook a study of the seroprevalence of HIV antibody in 452 persons enrolled in a methadone-treatment program in the Bronx, New York. The seroprevalence of HIV was 39.4 percent overall, 49.1 percent in blacks, 41.8 percent in Hispanics, and 17.2 percent in non-Hispanic whites (P less than 0.001 for all comparisons). The presence of HIV antibody was associated with the number of injections per month (P less than 0.001), the percentage of injections with used needles (P less than 0.001), the average number of injections with cocaine per month (P less than 0.001), and the percentage of injections with needles that were shared with strangers or acquaintances (P less than 0.001), a practice that was more common among blacks and Hispanics than among whites. The number of heterosexual sex partners who used intravenous drugs was associated with HIV infection in women (P less than 0.004) and was the only risk factor found for users who had not injected drugs after 1982 (P less than 0.05). The presence of HIV antibody was independently associated with being black or Hispanic (adjusted odds ratio, 4.56; 95 percent confidence interval, 2.65 to 8.14), a more recent year of the last injection of drugs (adjusted odds ratio, 1.24; 95 percent confidence interval, 1.13 to 1.35), the percentage of injections of drugs that took place in "shooting galleries" (adjusted odds ratio, 1.49; 95 percent confidence interval, 1.19 to 1.88), having sex partners who used intravenous drugs (adjusted odds ratio 1.24; 95 percent confidence interval, 1.06 to 1.45), and low income (adjusted odds ratio, 1.55; 95 percent confidence interval, 1.10 to 2.17). We conclude that differences in both the social setting of drug use and behavior related to injection carry different risks for infection with HIV and may explain, in part, the higher seroprevalence of HIV among blacks and Hispanics. In addition, we found that heterosexual activity was an independent risk factor for drug users.     

Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty

BACKGROUND: Recent studies have shown that symptomatic venous thromboembolism after total hip arthroplasty most commonly develops after the patient is discharged from the hospital. Risk factors associated with these symptomatic thromboembolic events are not well defined. METHODS: Using administrative data from the California Medicare records for 1993 through 1996, we identified 297 patients 65 years of age or older who were rehospitalized for thromboembolism within three months after total hip arthroplasty. We compared demographic, surgical, and medical variables potentially associated with the development of thromboembolism in these patients and 592 unmatched controls. RESULTS: A total of 89.6 percent of patients with thromboembolism and 93.8 percent of control patients were treated with pneumatic compression, warfarin, enoxaparin, or unfractionated heparin, alone or in combination. In addition, 22.2 percent and 29.7 percent, respectively, received warfarin after discharge. A body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or greater was associated with rehospitalization for thromboembolism, with an odds ratio of 2.5 (95 percent confidence interval, 1.8 to 3.4). In a multivariate model, the only prophylactic regimens associated with a reduced risk of thromboembolism were pneumatic compression in patients with body-mass indexes of less than 25 (odds ratio, 0.3; 95 percent confidence interval, 0.2 to 0.6) and warfarin treatment after discharge (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 1.0). CONCLUSIONS: In patients who underwent total hip arthroplasty, a body-mass index of 25 or greater was associated with subsequent hospitalization for thromboembolism. Pneumatic compression in patients with a body-mass index of less than 25 and prophylaxis with warfarin after discharge were independently protective against thromboembolism.     

Appendectomy and protection against ulcerative colitis

BACKGROUND: A history of appendectomy is rare in patients with ulcerative colitis. This suggests a protective effect of appendectomy or that appendicitis and ulcerative colitis are alternative inflammatory responses. We sought to characterize this inverse relation further. METHODS: We studied a cohort of 212,963 patients who underwent appendectomy before the age of 50 years between 1964 and 1993 and a cohort of matched controls who were identified from the Swedish Inpatient Register and the nationwide census. The cohort was followed until 1995 for any subsequent diagnosis of ulcerative colitis. RESULTS: Patients who underwent appendectomy for appendicitis and mesenteric lymphadenitis had a low risk of ulcerative colitis (for patients with perforated appendicitis, the adjusted hazard ratio was 0.58 [95 percent confidence interval, 0.38 to 0.87]; for those with nonperforated appendicitis it was 0.76 [95 percent confidence interval, 0.65 to 0.90]; and for those with mesenteric lymphadenitis it was 0.57 [95 percent confidence interval, 0.36 to 0.89]). In contrast, patients who underwent appendectomy for nonspecific abdominal pain had the same risk of ulcerative colitis as the controls (adjusted hazard ratio, 1.06; 95 percent confidence interval, 0.74 to 1.52). For the patients who had appendicitis, an inverse relation with the risk of ulcerative colitis was found only for those who underwent surgery before the age of 20 years (P<0.001). CONCLUSIONS: Appendectomy for an inflammatory condition (appendicitis or lymphadenitis) but not for nonspecific abdominal pain is associated with a low risk of subsequent ulcerative colitis. This inverse relation is limited to patients who undergo surgery before the age of 20 years.     

Effect of Opioids on All-cause Mortality and Sustained Opioid Use in Elderly Patients with Hip Fracture: a Korea Nationwide Cohort Study

BackgroundThe purpose of our study was to assess the use of opioids before and after hip fracture in elderly patients in order to determine the effect of opioid use on all-cause mortality, and to analyze how the history of opioid use before fracture increases the risk of sustained use following hip fracture using a Korea nationwide cohort.MethodsOur study identified hip fracture patients from the Korean National Health Insurance Service-Senior cohort. The index date was defined as 90-days after admission to the acute care hospital that fulfilled the eligibility criteria of elderly hip fracture. Patients were classified into past user, current user, and sustained user according to the use of opioid at each period based on the time of admission and index date. The opioids were classified into strong opioids and tramadol. A generalized estimating equation model with a Poisson distribution and logarithmic link function was performed to estimate the adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) to assess the association between past use and sustained use. A multivariable-adjusted Cox proportional hazard model was used to investigate the effects of strong opioid and tramadol use on all-cause mortality.ResultsA total of 12,927 patients were included in our study. There were 7,384 (57.12%) opioid past-users, 11,467 (88.71%) opioid current-users, and 7,172 (55.48%) sustained users. In comparison of the death risk according to current use or the defined daily dose of the opioids or past opioid use, there were no significant differences in the adjusted hazard ratio for death in all groups, compared to the current non-users (P > 0.05). Among survivors 1 year after hip fracture, opioid past-use increased the risk of opioid sustained use by 1.52-fold (aRR; 95% CI, 1.45–1.8; P < 0.001).ConclusionCurrent use and past use of opioid did not increase all-cause mortality after hip fracture in elderly patients over 65 years of age. Past use of opioid before hip fracture increased risk of sustained use of opioid compared to the current opioid used without past use.     

Impact of high-normal blood pressure on the risk of cardiovascular disease.

BACKGROUND: Information is limited regarding the absolute and relative risk of cardiovascular disease in persons with high-normal blood pressure (systolic pressure of 130 to 139 mm Hg, diastolic pressure of 85 to 89 mm Hg, or both). METHODS: We investigated the association between blood-pressure category at base line and the incidence of cardiovascular disease on follow-up among 6859 participants in the Framingham Heart Study who were initially free of hypertension and cardiovascular disease. RESULTS: A stepwise increase in cardiovascular event rates was noted in persons with higher baseline blood-pressure categories. The 10-year cumulative incidence of cardiovascular disease in subjects 35 to 64 years of age who had high-normal blood pressure was 4 percent (95 percent confidence interval, 2 to 5 percent) for women and 8 percent (95 percent confidence interval, 6 to 10 percent) for men; in older subjects (those 65 to 90 years old), the incidence was 18 percent (95 percent confidence interval, 12 to 23 percent) for women and 25 percent (95 percent confidence interval, 17 to 34 percent) for men. As compared with optimal blood pressure, high-normal blood pressure was associated with a risk-factor-adjusted hazard ratio for cardiovascular disease of 2.5 (95 percent confidence interval, 1.6 to 4.1) in women and 1.6 (95 percent confidence interval, 1.1 to 2.2) in men. CONCLUSIONS: High-normal blood pressure is associated with an increased risk of cardiovascular disease. Our findings emphasize the need to determine whether lowering high-normal blood pressure can reduce the risk of cardiovascular disease.     

Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study

BACKGROUND: Previous research has suggested that thiazide diuretics and beta-blockers may promote the development of type 2 diabetes mellitus. However, the results of previous studies have been inconsistent, and many studies have been limited by inadequate data on outcomes and by potential confounding. METHODS: We conducted a prospective study of 12,550 adults 45 to 64 years old who did not have diabetes. An extensive health evaluation conducted at base line included assessment of medication use and measurement of blood pressure with a random-zero sphygmomanometer. The incidence of new cases of diabetes was assessed after three years and after six years by measurement of serum glucose concentrations while the subjects were fasting. RESULTS: After simultaneous adjustment for age, sex, race, education, adiposity, family history with respect to diabetes, physical-activity level, other health-related behavior, and coexisting illnesses, subjects with hypertension who were taking thiazide diuretics were not at greater risk for the subsequent development of diabetes than were subjects with hypertension who were not receiving any antihypertensive therapy (relative hazard, 0.91; 95 percent confidence interval, 0.73 to 1.13). Likewise, subjects who were taking angiotensin-converting-enzyme inhibitors and calcium-channel antagonists were not at greater risk than those not taking any medication. In contrast, subjects with hypertension who were taking beta-blockers had a 28 percent higher risk of subsequent diabetes (relative hazard, 1.28; 95 percent confidence interval, 1.04 to 1.57). CONCLUSIONS: Concern about the risk of diabetes should not discourage physicians from prescribing thiazide diuretics to nondiabetic adults who have hypertension. The use of beta-blockers appears to increase the risk of diabetes, but this adverse effect must be weighed against the proven benefits of beta-blockers in reducing the risk of cardiovascular events.     

Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study

BACKGROUND. The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. Our 1985 report in the Journal, based on four years of follow-up, suggested that estrogen therapy reduced the risk of coronary heart disease, but a report published simultaneously from the Framingham Study suggested that the risk was increased. In addition, studies of the effect of estrogens on stroke have yielded conflicting results. METHODS. We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study, and who did not have a history of cancer or cardiovascular disease at base line. During up to 10 years of follow-up (337,854 person-years), we documented 224 strokes, 405 cases of major coronary disease (nonfatal myocardial infarctions or deaths from coronary causes), and 1263 deaths from all causes. RESULTS. After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taking estrogen was 0.56 (95 percent confidence interval, 0.40 to 0.80); the risk was significantly reduced among women with either natural or surgical menopause. We observed no effect of the duration of estrogen use independent of age. The findings were similar in analyses limited to women who had recently visited their physicians (relative risk, 0.45; 95 percent confidence interval, 0.31 to 0.66) and in a low-risk group that excluded women reporting current cigarette smoking, diabetes, hypertension, hypercholesterolemia, or a Quetelet index above the 90th percentile (relative risk, 0.53; 95 percent confidence interval, 0.31 to 0.91). The relative risk for current and former users of estrogen as compared with those who had never used it was 0.89 (95 percent confidence interval, 0.78 to 1.00) for total mortality and 0.72 (95 percent confidence interval, 0.55 to 0.95) for mortality from cardiovascular disease. The relative risk of stroke when current users were compared with those who had never used estrogen was 0.97 (95 percent confidence interval, 0.65 to 1.45), with no marked differences according to type of stroke. CONCLUSIONS. Current estrogen use is associated with a reduction in the incidence of coronary heart disease as well as in mortality from cardiovascular disease, but it is not associated with any change in the risk of stroke.     

Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 Participants.

BACKGROUND: There is conflicting information about whether short-term mortality after myocardial infarction is higher among women than among men after adjustment for age and other prognostic factors. We hypothesized that younger, but not older, women have higher mortality rates during hospitalization than their male peers. METHODS: We analyzed data on 384,878 patients (155,565 women and 229,313 men) who were 30 to 89 years of age and who had been enrolled in the National Registry of Myocardial Infarction 2 between June 1994 and January 1998. Patients who had been transferred from or to other hospitals were excluded. RESULTS: The overall mortality rate during hospitalization was 16.7 percent among the women and 11.5 percent among the men. Sex-based differences in the rates varied according to age. Among patients less than 50 years of age, the mortality rate for the women was more than twice that for the men. The difference in the rates decreased with increasing age and was no longer significant after the age of 74 (P< 0.001 for the interaction between sex and age). Logistic-regression analysis showed that the odds of death were 11.1 percent greater for women than for men with every five-year decrease in age (95 percent confidence interval, 10.1 to 12.1 percent). Differences in medical history, the clinical severity of the infarction, and early management accounted for only about one third of the difference in the risk. After adjustment for these factors, women still had a higher risk of death for every five years of decreasing age (increase in the odds of death, 7.0 percent; 95 percent confidence interval, 5.9 to 8.1 percent). CONCLUSIONS: After myocardial infarction, younger women, but not older women, have higher rates of death during hospitalization than men of the same age. The younger the age of the patients, the higher the risk of death among women relative to men. Younger women with myocardial infarction represent a high-risk group deserving of special study.