Recent metformin adherence and the risk of hypoglycaemia in the year following intensification with a sulfonylurea.

AIM: To evaluate whether recent low adherence to metformin monotherapy is associated with hypoglycaemia after addition of a sulfonylurea. METHODS: We assembled a retrospective cohort of veterans who filled a new prescription for metformin between 2001 and 2011 and intensified treatment with a sulfonylurea after ≥1 year of metformin use. We calculated metformin adherence from pharmacy data using the proportion of days covered in the 180-day period before intensification. The primary outcome was hypoglycaemia, defined as a hospitalization or emergency department visit for hypoglycaemia or an outpatient blood glucose measurement <3.3 mmol/l in the year following intensification. Cox proportional hazards models were used to compare the risk of hypoglycaemia between participants with low (<80%) and high (≥80%) adherence. Adherence was also modelled as a continuous variable using restricted cubic splines. RESULTS: Of 187 267 participants who initiated metformin monotherapy, 49 424 added a sulfonylurea after ≥1 year. The median (interquartile range) rate of treatment adherence was 87 (50-100)% and 43% had adherence <80%. Hypoglycaemia rates per 1000 person-years were 23.1 (95% CI 21.1-25.4) and 24.5 (95% CI 22.7-26.4) in participants with low and high adherence, respectively (adjusted hazard ratio 0.95, 95% CI 0.84-1.08). The risk of hypoglycaemia was similar across all levels of adherence when adherence was modelled as a continuous variable. CONCLUSIONS: We found no evidence that past low adherence to metformin monotherapy was associated with hypoglycaemia after intensification with a sulfonylurea.

Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy.

BACKGROUND: The Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Study 403) demonstrated that zoster vaccine was efficacious through 4 years after vaccination. The Short-Term Persistence Substudy (STPS) was initiated after the SPS to further assess the persistence of vaccine efficacy. METHODS: The STPS re-enrolled 7320 vaccine and 6950 placebo recipients from the 38 546-subject SPS population. Methods of surveillance, case determination, and follow-up were analogous to those in the SPS. Vaccine efficacy for herpes zoster (HZ) burden of illness, incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, for the combined SPS and STPS populations, and for each year through year 7 after vaccination. RESULTS: In the STPS as compared to the SPS, vaccine efficacy for HZ burden of illness decreased from 61.1% to 50.1%, vaccine efficacy for the incidence of PHN decreased from 66.5% to 60.1%, and vaccine efficacy for the incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of vaccine efficacy in each year after vaccination for all 3 outcomes showed a decrease in vaccine efficacy after year 1, with a further decline thereafter. Vaccine efficacy was statistically significant for the incidence of HZ and the HZ burden of illness through year 5. CONCLUSIONS: Vaccine efficacy for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of vaccine efficacy through year 5 after vaccination but, vaccine efficacy is uncertain beyond that point.

Blood pressure control among patients with hypertension and newly diagnosed diabetes.

AIMS: To determine the proportion of patients who achieved blood pressure control during the 2 years following new diabetes diagnosis. METHODS: A retrospective cohort of veterans ≥ 18 years with hypertension who initiated a diabetes medication from 2000 to 2007 in the Veterans Administration Mid-South Network was assembled. Blood pressure control at diabetes treatment initiation (baseline) was compared with blood pressure control 6, 12, 18 and 24 months later. The Veterans Affairs and American Diabetes Association definitions of control, ≤ 140/90 and ≤ 130/80 mmHg, respectively, were primary and secondary outcomes. RESULTS: At baseline, 59.5% of 16,182 patients had controlled blood pressure according to the Veterans Affairs guideline (31.5% using American Diabetes Association definition). Six months following initiation of diabetes treatment, 65.7% had their blood pressure controlled (P < 0.001). Blood pressure control was sustained but not further improved between 6 months and 2 years, with 66.5% controlled at 2 years following baseline. Higher initial systolic blood pressure, black race and hospitalization in the previous year were associated with higher likelihood of uncontrolled blood pressure at 6 months; whereas baseline cardiovascular disease, baseline dementia and later year of cohort entry were associated with lower likelihood of uncontrolled blood pressure. CONCLUSION: We found an increase in blood pressure control in the 6 months following initiation of diabetes treatment. However, overall blood pressure control remained suboptimal and with no further improvement over the next 18 months.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Changing patterns of medication use in patients with rheumatoid arthritis in a Medicaid population.

OBJECTIVE: To examine changes in patterns of medication utilization in patients with RA. METHODS: Data from Tennessee Medicaid (TennCare) databases (1995-2004) were used to identify adults with both a diagnosis of RA and at least one DMARD prescription each year. Annual age-specific utilization of DMARDs, glucocorticoids, NSAIDs and narcotics was measured on the last day of each year to determine the point prevalence of use of these agents. RESULTS: Records from 23 342 patients with treated RA were analysed. Most patients were females (78%) and white (74%). The median age was 57 yrs (interquartile range: 48-65). The proportion of patients who had a current DMARD prescription on the index date increased from 62% in 1995 to 71% in 2004 (P < 0.001). MTX was the most commonly used DMARD. By the end of 2004, 22% of patients had a current prescription for a biologic, and etanercept represented 51% of all biologic therapies. During the study period, the overall utilization of glucocorticoids decreased from 46% to 38% (P < 0.001), whereas NSAID utilization increased from 33% to 38% (P < 0.001), and use of narcotics increased from 38% to 55% (P < 0.001). A secondary analysis that identified RA patients based on diagnosis codes alone, showed similar patterns, but lower DMARD utilization which increased from 33% to 52% overall and from 0% to 16% for biologics. CONCLUSIONS: The utilization of DMARDs increased in TennCare patients with RA, and by 2004, use of biologics was substantial. Although glucocorticoid utilization decreased, use of both NSAIDs and narcotics increased.

Cyclic antidepressants and the risk of hip fracture.

To determine whether cyclic antidepressants increase the risk of hip fracture, we conducted a population-based case-control study in the Canadian province of Saskatchewan. We identified 4501 persons 65 years of age or older with a first hospitalization for hip fracture between 1977 and 1985 and 24,041 comparable controls. Current antidepressant users had a relative risk of hip fracture of 1.6 (95% confidence interval, 1.3 to 1.9). Medical record review for a sample of 164 cases suggested this finding was not due to confounding by body mass, impaired ambulation, functional status, or dementia.

Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study.

BACKGROUND: Previous observational studies have provided limited information on the effect of specific nonsteroidal anti-inflammatory drugs (NSAIDs) and different patterns of use (duration and dose) on the incidence of colorectal cancer. OBJECTIVE: To determine how patterns of use (duration, dose, and specific drug) of NSAIDs affect incidence of colorectal cancer. DESIGN: Population-based retrospective cohort study. SETTING: Tennessee Medicaid Program, 1985-1992. SUBJECTS: Enrollees (n = 104217) aged 65 years or older with at least 5 years of enrollment. MAIN OUTCOME MEASURES: Incident histologically confirmed colorectal cancer. RESULTS: Users of nonaspirin NSAIDs for at least 48 months of the previous 5 years had a relative risk (RR) of 0.49 (95% confidence interval [CI], 0.24-1.00) for colon cancer when compared with those with no use of NSAIDs. Among those with more than 12 months of cumulative use, those using NSAIDs in the past year (recent users) had an RR of 0.61 (95% CI, 0.48-0.77), whereas those with no recent use had an RR of 0.76 (95% CI, 0.50-1.15). No specific NSAID offered a unique protective effect and low doses of NSAIDs appeared to be at least as effective as higher doses. Protection was most pronounced for right-sided lesions. The RR among recent users with more than 12 months of cumulative use was 0.81 (95% CI, 0.49-1.32) for rectal cancer, 0.77 (95% CI, 0.55-1.08) for left-sided colon cancer, and 0.48 (95% CI, 0.34-0.68) for right-sided colon cancer. CONCLUSIONS: In this elderly population, long-term use of nonaspirin NSAIDs nearly halved the risk of colon cancer. This study was consistent with previous studies that suggest that duration of use but not daily dose of NSAIDs is an important factor for chemoprevention. Our data also suggest that the protective effect is shared by most NSAIDs, and not confined to a small number of these drugs.

Mortality following hip fracture before and after implementation of the prospective payment system.

Recent studies of patients with hip fractures from two hospitals have suggested that the marked reduction in length of stay that occurred following implementation of the Medicare prospective payment system (PPS) resulted in decreased quality of care for these patients. To assess whether this change influenced mortality, we studied patients with hip fractures aged 65 years or older from a 20% sample of Michigan Medicare enrollees. There were 2130 such patients in the 2 years preceding (October 1981 through September 1983) and 2238 in the 2 years following (October 1984 through September 1986) implementation of PPS. Although the demographic characteristics of patients with hip fractures did not change after PPS, the mean length of stay (95% confidence interval) decreased by 4.4 (4.1 to 4.7) days. However, mortality in the year following the fracture did not change: 23.2% before PPS, 23.7% after PPS; rate difference of 0.5% (-2.0 to 3.0). This finding was consistently present within subgroups defined by patient demographic characteristics. Furthermore, when the analysis was restricted to patients treated in those hospitals with the greatest reduction in average length of stay following PPS (7.5 days, or 35%), there was no significant change in 1-year mortality. For those patients who were enrolled in Medicaid and not in a nursing home at the time of the fracture, there was no increase in the rate of nursing home residence 1 year after the fracture. Thus, the findings of this population-based study suggest that the key outcomes of postfracture mortality and nursing home residence were not affected by the implementation of PPS.

Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease.

BACKGROUND: Although joint use of nonsteroidal anti-inflammatory drugs (NSAIDs) and oral anticoagulants may increase the risk of gastrointestinal tract hemorrhage in elderly persons, no epidemiologic studies have been performed to quantify this risk. METHODS: We performed a retrospective cohort study of Tennessee Medicaid enrollees aged 65 years or older from 1984 through 1986. A total of 103,954 individuals contributed 209,066 person-years of follow-up, including 2203 person-years of current oral anticoagulant use, to the study. RESULTS: Of the cohort members, 1371 had confirmed hospitalizations for peptic ulcer disease. Of these, 661 (48%) presented with frank hematemesis or melena and thus met the definition for hemorrhagic peptic ulcer disease. Among current users of oral anticoagulants, the adjusted incidence of hospitalization for peptic ulcer disease was 14.3 per 1000 person-years, and the adjusted incidence of hospitalization for hemorrhagic peptic ulcer disease was 10.2 per 1000 person-years. Compared with nonusers, current anticoagulant users were at increased risk for hospitalization for ulcer disease (relative risk, 2.2; 95% confidence interval, 1.6 to 3.1), primarily due to the increased risk of hospitalization for hemorrhagic ulcers (relative risk, 3.3; 95% confidence interval, 2.3 to 4.9). Compared with nonusers of either drug, the relative risk of hemorrhagic peptic ulcer disease among current users of both anticoagulants and NSAIDs was 12.7 (95% confidence interval, 6.3 to 25.7). However, the prevalence of NSAID use among anticoagulant users was 13.5%, the same as in those who were not using anticoagulants. CONCLUSIONS: The nearly 13-fold increase in the risk of developing hemorrhagic peptic ulcer disease in concurrent users of oral anticoagulants and NSAIDs suggests that NSAIDs should be prescribed with extreme caution in patients undergoing anticoagulation therapy.

Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas.

BACKGROUND: Our knowledge about the risk of hypoglycemia associated with diabetes treatment is derived from studies that often exclude frail, elderly persons. OBJECTIVE: To determine the incidence and risk factors for developing serious hypoglycemia among older persons using sulfonylureas or insulin. METHODS: We conducted a population-based, retrospective cohort study of 19932 Tennessee Medicaid enrollees, aged 65 years or older, who used insulin or sulfonylureas from 1985 through 1989. The main end point was serious hypoglycemia defined as a hospitalization, emergency department admission, or death associated with hypoglycemic symptoms and a concomitant blood glucose determination of less than 2.8 mmol/L (< 50 mg/dL). RESULTS: We identified 586 persons with a first episode of serious hypoglycemia during 33,048 person-years of insulin or sulfonylurea use. The crude rates (per 100 person-years) of serious hypoglycemia were 1.23 (95% confidence interval [CI], 1.08-1.38) in users of sulfonylureas and 2.76 (95% CI, 2.47-3.06) among insulin users. Recent hospital discharge was the strongest predictor of subsequent hypoglycemia in older persons with diabetes. The adjusted relative risk of serious hypoglycemia occurring in days 1 through 30 after hospital discharge was 4.5 (95% CI, 3.5-5.7) compared with the risk associated with a hypoglycemic event occurring 366 or more days after hospital discharge. Other independent risk factors included advanced age (relative risk, 1.8; 95% CI, 1.4-2.3), black race (relative risk, 2.0; 95% CI, 1.7-2.4), and use of 5 or more concomitant medications (relative risk, 1.3; 95% CI, 1.1-1.5). CONCLUSIONS: In this population, the incidence of serious hypoglycemia is approximately 2 per 100 person-years, suggesting that many older adults can be safely treated with hypoglycemic drugs. Frail, elderly persons--the oldest-old, those using multiple medications, and those who are frequently hospitalized--are at a higher risk for drug-associated hypoglycemia. Such individuals may benefit from intensive education about the symptoms of hypoglycemia and close monitoring for adverse events related to diabetes treatment.

Reducing antipsychotic drug use in nursing homes. A controlled trial of provider education.

OBJECTIVE: In the United States, 20% or more of nursing home residents receive antipsychotic drugs, primarily for the behavioral manifestations of dementia. This high level of use of drugs with substantial toxicity has engendered a strong and persistent controversy and recently has led to explicit regulatory measures to curtail use (Omnibus Budget Reconciliation Act of 1987). We developed and tested a comprehensive program to reduce antipsychotic use through education of physicians, nurses, and other nursing home staff. The primary elements of the program were instruction in use of behavioral techniques to manage behavior problems and encouragement of a trial of gradual antipsychotic withdrawal. DESIGN: In a nonrandomized controlled trial, the program was implemented (beginning in August 1990) in two rural Tennessee community nursing homes with elevated antipsychotic use; two other comparable homes were selected as concurrent controls. PATIENTS: Throughout the study 194 residents were in the education homes and 184 were in the control homes. Residents in both groups of homes had comparable demographic characteristics and functional status, and each group had a baseline rate of 29 days of antipsychotic use per 100 days of nursing home residence. MAIN OUTCOME MEASURES: The primary end points were postintervention changes in administration of antipsychotics and other psychotropic drugs, use of physical restraints, and frequency of behavior problems. RESULTS: Days of antipsychotic use decreased by 72% in the education homes vs 13% in the control homes (P < .001). No significant changes were noted in the use of other psychotropic drugs in either group. Days of physical restraint use decreased 36% in the education homes vs 5% in the control homes (P < .001). Behavior problem frequency did not increase in either group, even among the 48% of baseline antipsychotic users in the education homes who had antipsychotic drug regimens discontinued for 3 or more months. CONCLUSIONS: The educational program led to a substantial reduction in antipsychotic use with no increase in the frequency of behavior problems. This suggests that for many antipsychotic drug users benefits may be marginal and that programs to reduce such drug use among the 250,000 US nursing home residents receiving these drugs should have high priority.

Deep venous thrombosis and pulmonary embolism. Risk of subsequent malignant neoplasms.

We conducted a noncurrent prospective study of all Olmsted County, Minnesota, residents who had had a lower-extremity venogram, pulmonary angiogram, or lung scan performed because of suspicion of deep venous thrombosis or pulmonary emboli. One hundred thirteen cancer-free patients were followed for 386 person-years from the date of procedure. Nine subsequent cancers were observed compared with 4.5 expected (relative risk, 2.0; 95% confidence interval, 0.9 to 3.8), using total cancer incidence rates for the Rochester, Minn, population. Five hundred seventeen cancer-free controls were followed for 2072 person-years. Twenty subsequent cancers were observed compared with 11.6 expected, yielding a relative risk of 1.7 (95% confidence interval, 1.1 to 2.7). When cases and controls were compared directly, no statistically significant difference in cancer-free survival was found.

Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema.

OBJECTIVE: To study the association of race and other patient characteristics associated with angiotensin converting enzyme (ACE) inhibitor-associated angioedema. METHODS: This was a retrospective cohort study of participants in the Tennessee Medicaid Program ( >or= 15 years of age) to whom ACE inhibitors had been prescribed from 1986 through 1992. RESULTS: We identified 82 patients with confirmed angioedema during 51,752 person-years of ACE inhibitor use, giving an overall rate of angioedema of 1.6 per 1000 person-years of ACE inhibitor use. After potential confounding factors were controlled for, the adjusted relative risk (RR) of angioedema among black American users of ACE inhibitors was 4.5 (95% confidence interval [CI] 2.9 to 6.8) compared with white subjects. In addition to race, other factors associated with a significantly increased relative risk in the entire population were the first 30 days of ACE inhibitor use (RR, 4.6; 95% CI, 2.5 to 8.5) compared to > 1 year of use, use of either lisinopril (RR, 2.2; 95% CI, 1.2 to 3.9) or enalapril (RR, 2.2; 95% CI, 1.4 to 3.5) compared to captopril, and previous hospitalization for any diagnosis within 30 days (RR, 2.0; 95% CI, 1.1 to 3.6). Neither ACE inhibitor dose nor concurrent diuretic use was associated with the risk of angioedema. CONCLUSIONS: These data suggest that black Americans have a substantially increased risk of ACE inhibitor-associated angioedema compared with white subjects and that this increased risk cannot be attributed to an effect of dose, specific ACE inhibitor, or concurrent medications.

Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury.

Nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs in many countries. Use of the majority of NSAIDs increases with age, primarily for symptoms associated with osteoarthritis and other chronic musculoskeletal conditions. Population-based studies have shown that, on any given day, 10-20% of elderly people (> or = 65 years old) have a current or recent NSAID prescription. Over a 6-month period in Alberta, Canada, 27% of elderly people were prescribed NSAIDs. Furthermore, in Tennessee (USA), 40% of elderly people received at least one NSAID prescription annually, and 6% had NSAID prescriptions for > 75% of the year. NSAIDs cause a wide variety of side-effects. The most clinically important side-effects are upper gastrointestinal tract dyspepsia, peptic ulceration, hemorrhage, and perforation, leading to death in some patients. Gastrointestinal side-effects are common; the most common NSAID-associated side-effect is epigastric pain/indigestion. Gastrointestinal side-effects are also a frequent reason both for withdrawal of NSAIDs and for co-treatment with another drug. Indeed, in two population-based studies of people aged > or = 65 years, the use of agents to prevent peptic ulcers or relieve dyspepsia was nearly twice as common in regular NSAID users (20-26%) than in non-NSAID users (11%). In Alberta, Canada, it has been estimated that NSAID use accounts for 28% of all prescriptions for anti-ulcer drugs in people aged at least 65 years. Many studies have now shown that NSAIDs increase the risk of peptic ulcer complications by 3-5-fold, and in several different populations it has been estimated that 15-35% of all peptic ulcer complications are due to NSAIDs. In the United States alone, there are an estimated 41,000 hospitalizations and 3,300 deaths each year among the elderly that are associated with NSAIDs. Factors that increase the risk of serious peptic ulcer disease include older age, history of peptic ulcer disease, gastrointestinal hemorrhage, dyspepsia, and/or previous NSAID intolerance, as well as several measures of poor health.

Prospects for changing the burden of nonsteroidal anti-inflammatory drug toxicity.

Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of clinically important upper gastrointestinal ulcers and bleeds about fourfold. Other risk factors for these events include advanced age, higher NSAID dose, prior ulcer or bleed, use of anticoagulants, use of corticosteroids, and poor general health. Among NSAID users with more than one risk factor, the incidence of serious ulcer complications may be as high as 4% to 8% per year. NSAIDs may also increase blood pressure and have adverse effects on renal function. NSAID-associated toxicity may be decreased by (1) trying less toxic alternative drugs; (2) using NSAIDs less frequently or at a lower dose; (3) use of cotherapy, such as misoprostol or proton pump inhibitors, to prevent complications; (4) or use of the more selective cyclooxygenase-2 inhibitors. More research is needed to determine which of these strategies or combination of strategies is optimal in terms of patient safety and cost.

Risk of seizures after measles-mumps-rubella immunization.

To evaluate the risks of seizures and other neurologic events following measles-mumps-rubella (MMR) or measles-rubella (MR) immunization, a retrospective cohort study was conducted among 18,364 Tennessee children enrolled in Medicaid who received MMR or MR immunizations in their first 3 years of life. One hundred children had seizures at some time between immunization and 36 months; there were no encephalopathies during this period. Four children had febrile seizures in the 7 through 14 days following MMR or MR immunization compared with 72 in the interval 30 or more days following MMR or MR immunization yielding a relative risk (95% confidence interval) of 2.1 (0.7 to 6.4). Although not statistically significant, this increase in febrile seizures in the 7- through 14-day interval following MMR immunization is coincident with the occurrence of fever following MMR immunization and is consistent with reports of other investigators.

No increased risk for invasive bacterial infection found following diphtheria-tetanus-pertussis immunization.

During the acellular pertussis vaccine trial in Sweden, 4 children who were randomly assigned to receive the vaccine died of suspected or confirmed bacterial infections compared to 1 expected. There were no deaths in the placebo arm. This raised concern about the role of pertussis immunization in the development of serious infections. Through linking computerized immunization records with an active surveillance system for serious bacterial infections in children, the authors studied a cohort of 64,591 children immunized through Tennessee county health clinics who had a total of 158 episodes of invasive bacterial infections after a diphtheria and tetanus toxoids and pertussis (DTP) immunization. There were 8 invasive bacterial infections that occurred within the first 7 days following DTP immunization, yielding an age-adjusted relative risk (95% confidence interval) of 1.0 (0.5 to 2.0), compared to the interval 29 or more days following immunization. There were 7 and 20 infections in the 8- through 14- and 15- through 28-day intervals following DTP immunization, giving relative risks of 0.8 (0.4 to 1.7) and 1.2 (0.7 to 1.9), respectively. These data provide reassurance that the use of DTP vaccine is not followed by a large increased risk of serious bacterial infections.

Incidence of malignant bone and joint tumors in Olmsted County, Minnesota, 1935 through 1981.

During the 47-year period 1935 through 1981, 30 cases of malignant bone and joint tumors (in 20 male and 10 female patients) were identified among Olmsted County, Minnesota, residents. The incidence rates per 100,000 population, age-adjusted to the 1970 US total white population, were 1.0 overall, 1.4 for male subjects, and 0.7 for female subjects. Mortality rates, likewise age-adjusted, were 0.7 overall and 1.1 and 0.3 for male and female subjects, respectively. These rates are similar to those from tumor registries, a finding that suggests that reporting of these tumors is relatively complete. The similarity of the incidence and the mortality rates is consistent with the high case-fatality rate. A comparison of the Olmsted County cases with Mayo Clinic referral cases provides some evidence for referral bias, as the referral patients were significantly younger and had significantly more high-grade tumors.

Breast cancer in residents of Rochester, Minnesota: incidence and survival, 1935 to 1982.

The incidence and survival rates for breast cancer among residents of Rochester, Minnesota, from 1975 to 1982 were compared with rates from 1935 to 1974. The age-adjusted incidence rates of breast cancer, after exclusion of patients with carcinoma in situ, increased 14% between the periods 1965 to 1974 and 1975 to 1982 (from 87.2 to 99.5 per 100,000 person-years). Much of this increase was due to the greater number of patients with less advanced disease: the frequency of both regional lymph node involvement and distant metastatic disease at initial diagnosis decreased. In addition, the incidence of carcinoma in situ more than doubled between the periods 1935 to 1944 and 1975 to 1982. These increased proportions of less advanced disease coincide with increased public and physician awareness of the importance of early detection. No change was demonstrated in overall survival during the study period, perhaps because the follow-up for the final study period was shorter than that for the previous periods. When divided into subsets by staging characteristics, only patients with distant metastatic disease had statistically significant improvement in survival over time (P less than or equal to 0.01)--from a median survival of 21 months in the period 1955 to 1974 to 28 months in the period 1975 to 1982. This increased survival is probably related to advances in therapy (such as combination chemotherapy). In addition, earlier detection of distant metastatic disease in the later study periods might have produced the apparent improvement in survival in this subgroup.

Risk factors for sudden unexpected cardiac death in young women in Rochester, Minnesota, 1960 through 1974.

A case-control study of sudden unexpected death (SUD) as the initial manifestation of coronary heart disease in women younger than 60 years of age was conducted in Rochester, Minnesota. Risk factors among the 15 SUD cases identified during the years 1960 through 1974 were compared with those in two control groups--a population group of 60 (4 age-matched controls per case) and the 59 cases of myocardial infarction diagnosed in women younger than 60 years of age in Rochester during the same period. By using Miettinen's matched analysis for comparison of SUD cases and matched controls, the relative risks for the accepted coronary heart disease risk factors of ever smoking and hypertension were 8.6 (95% confidence interval [CI], 1.3 to 57.3) and 5.7 (95% CI, 1.2 to 26.9), respectively. In a comparison of SUD cases and myocardial infarction cases by using the Mantel-Haenszel procedure and stratifying by five age groups, the odds ratios were 1.2 for ever smoking and 0.8 for hypertension. Six of the 15 SUD cases had a diagnosis of alcoholism compared with 2 of the 60 controls and 4 of the 59 myocardial infarction cases; thus, the relative risks were 12.0 (95% CI, 3.4 to 41.9) and 4.8 (95% CI, 1.3 to 18.2), respectively. Ever married SUD cases were nulliparous or had fewer children more often than the controls or the myocardial infarction cases. The combination of major psychiatric diagnosis and major tranquilizer use occurred with greater frequency among SUD cases than among controls (relative risk, 2.9; 95% CI, 0.6 to 14.1), whereas comparison of SUD cases and myocardial infarction cases for this variable resulted in a relative risk of 0.7 (95% CI, 0.3 to 1.9).