Marie R. Griffin

Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus: A Cohort Study

BACKGROUND The effects of sulfonylureas and metformin on outcomes of cardiovascular disease (CVD) in type 2 diabetes are not well-characterized. OBJECTIVE To compare the effects of sulfonylureas and metformin on CVD outcomes (acute myocardial infarction and stroke) or death. DESIGN Retrospective cohort study. SETTING National Veterans Health Administration databases linked to Medicare files. PATIENTS Veterans who initiated metformin or sulfonylurea therapy for diabetes. Patients with chronic kidney disease or serious medical illness were excluded. MEASUREMENTS Composite outcome of hospitalization for acute myocardial infarction or stroke, or death, adjusted for baseline demographic characteristics; medications; cholesterol, hemoglobin A1c, and serum creatinine levels; blood pressure; body mass index; health care utilization; and comorbid conditions. RESULTS Among 253 690 patients initiating treatment (98 665 with sulfonylurea therapy and 155 025 with metformin therapy), crude rates of the composite outcome were 18.2 per 1000 person-years in sulfonylurea users and 10.4 per 1000 person-years in metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0] more CVD events with sulfonylureas per 1000 person-years; adjusted hazard ratio [aHR], 1.21 [CI, 1.13 to 1.30]). Results were consistent for both glyburide (aHR, 1.26 [CI, 1.16 to 1.37]) and glipizide (aHR, 1.15 [CI, 1.06 to 1.26]) in subgroups by CVD history, age, body mass index, and albuminuria; in a propensity score-matched cohort analysis; and in sensitivity analyses. LIMITATION Most of the veterans in the study population were white men; data on women and minority groups were limited but reflective of the Veterans Health Administration population. CONCLUSION Use of sulfonylureas compared with metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality and the U.S. Department of Health and Human Services.

The burden of respiratory syncytial virus infection in young children.

BACKGROUND The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined. METHODS We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties. We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric offices from 2002 through 2004. RSV was detected by culture and reverse-transcriptase polymerase chain reaction. Clinical information was obtained from parents and medical records. We calculated population-based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits. RESULTS Among 5067 children enrolled in the study, 919 (18%) had RSV infections. Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most of the children had no coexisting illnesses. Only prematurity and a young age were independent risk factors for hospitalization. Estimated rates of RSV-associated office visits among children under 5 years of age were three times those in emergency departments. Outpatients had moderately severe RSV-associated illness, but few of the illnesses (3%) were diagnosed as being caused by RSV. CONCLUSIONS RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection.

THE EFFECT OF INFLUENZA ON HOSPITALIZATIONS, OUTPATIENT VISITS, AND COURSES OF ANTIBIOTICS IN CHILDREN

BACKGROUND Despite high annual rates of influenza in children, influenza vaccines are given to children infrequently. We measured the disease burden of influenza in a large cohort of healthy children in the Tennessee Medicaid program who were younger than 15 years of age. METHODS We determined the rates of hospitalization for acute cardiopulmonary conditions, outpatient visits, and courses of antibiotics over a period of 19 consecutive years. Using the differences in the rates of these events when influenzavirus was circulating and the rates from November through April when there was no influenza in the community, we calculated morbidity attributable to influenza. There was a total of 2,035,143 person-years of observation. RESULTS During periods when influenzavirus was circulating, the average number of hospitalizations for cardiopulmonary conditions in excess of the expected number was 104 per 10,000 children per year for children younger than 6 months of age, 50 per 10,000 per year for those 6 months to less than 12 months, 19 per 10,000 per year for those 1 year to less than 3 years, 9 per 10,000 per year for those 3 years to less than 5 years, and 4 per 10,000 per year for those 5 years to less than 15 years. For every 100 children, an annual average of 6 to 15 outpatient visits and 3 to 9 courses of antibiotics were attributable to influenza. In winter, 10 to 30 percent of the excess number of courses of antibiotics occurred during periods when influenzavirus was circulating. CONCLUSIONS Healthy children younger than one year of age are hospitalized for illness attributable to influenza at rates similar to those for adults at high risk for influenza. The rate of hospitalization decreases markedly with age. Influenza accounts for a substantial number of outpatient visits and courses of antibiotics in children of all ages.

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.

Nonsteroidal Anti-inflammatory Drug Use and Increased Risk for Peptic Ulcer Disease in Elderly Persons

OBJECTIVE To evaluate the relative risk for peptic ulcer disease that is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. DESIGN Nested case-control study. SETTING Tennessee Medicaid program. PARTICIPANTS Medicaid enrollees 65 years of age or older were included in the study. The 1415 case patients had been hospitalized for confirmed peptic ulcer disease at some point from 1984 through 1986. The 7063 control persons represented a stratified random sample of other Medicaid enrollees. MEASUREMENTS AND MAIN RESULTS The estimated relative risk for the development of peptic ulcer disease among current users of nonaspirin nonsteroidal anti-inflammatory drugs, compared with that among nonusers, was 4.1 (95% CI, 3.5 to 4.7). For current users, the risk increased with increasing dose, from a relative risk of 2.8 (CI, 1.8 to 4.3) for the lowest to a relative risk of 8.0 (CI, 4.4 to 14.8) for the highest dose category. The risk was greatest in the first month of use (relative risk, 7.2; CI, 4.9 to 10.5). If the association is fully causal, 29% of peptic ulcers in the study sample resulted from the use of these drugs, and the excess risk associated with such use was 17.4 hospitalizations for ulcer disease per 1000 person-years of exposure. CONCLUSIONS These data support other findings indicating that a clinically significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. The data show that this risk increases with dose and recency of use and that use of these drugs may be responsible for a large proportion of peptic ulcer disease among elderly persons.

Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis

BACKGROUND Routine infant immunisation with seven-valent pneumococcal conjugate vaccine (PCV7) began in the USA in 2000. Although invasive pneumococcal disease has declined substantially, the programmes effect on hospital admissions for pneumonia is unknown. We therefore assessed the effect of the programme on rates of all-cause and pneumococcal pneumonia admissions. METHODS Data from the Nationwide Inpatient Sample, the largest inpatient database available in the USA, were analysed with an interrupted time-series analysis that used pneumonia (all-cause and pneumococcal) admission rates as the main outcomes. Monthly admission rates estimated for years after the introduction of PCV7 vaccination (2001-2004) were compared with expected rates calculated from pre-PCV7 years (1997-1999). The year of vaccine introduction (2000) was excluded, and rates of admission for dehydration were assessed for comparison. FINDINGS At the end of 2004, all-cause pneumonia admission rates had declined by 39% (95% CI 22-52) for children younger than 2 years, who were the target population of the vaccination programme. This annual decline in all-cause pneumonia admissions of 506 (291-675) per 100,000 children younger than 2 years represented about 41,000 pneumonia admissions prevented in 2004. During the 8 study years, 10,659 (2%) children younger than 2 years admitted with pneumonia were coded as having pneumococcal disease; these rates declined by 65% (47-77). This decline represented about 17 fewer admissions per 100,000 children in 2004. Admission rates for dehydration for children younger than 2 years remained stable over the study period. INTERPRETATION The reduction in all-cause pneumonia admissions in children younger than 2 years provides an estimate of the proportion of childhood pneumonias attributable to Streptococcus pneumoniae in the USA that are vaccine preventable. Our results contribute to the growing body of evidence supporting the beneficial effects of the pneumococcal conjugate vaccines in children.

corticosteroid Use and Peptic Ulcer Disease: Role of Nonsteroidal Anti-inflammatory Drugs

OBJECTIVE To estimate the relative risk for peptic ulcer disease that is associated with the use of oral corticosteroids. DESIGN A nested case-control study. SETTING Tennessee Medicaid program. PARTICIPANTS The case patients (n = 1415) were hospitalized between 1984 and 1986 for gastric or duodenal ulcer or for upper gastrointestinal hemorrhage of unknown cause. The controls (n = 7063) were randomly selected from Medicaid enrollees not meeting the study criteria for inclusion as case patients. MEASUREMENTS AND MAIN RESULTS The estimated relative risk for the development of peptic ulcer disease among current users of oral corticosteroids was 2.0 (95% CI, 1.3 to 3.0). However, the risk was increased only in those who concurrently received nonsteroidal anti-inflammatory drugs (NSAIDs); these persons had an estimated relative risk associated with current corticosteroid use of 4.4 (CI, 2.0 to 9.7). In contrast, the estimated relative risk for those corticosteroid users not receiving NSAIDs was 1.1 (CI, 0.5 to 2.1). Persons concurrently receiving corticosteroids and NSAIDs had a risk for peptic ulcer disease that was 15 times greater than that of nonusers of either drug. CONCLUSION Discrepant findings among earlier studies regarding steroids and the risk for peptic ulcer disease could in part be due to differences in the use of NSAIDs among study participants. The high risk for peptic ulcer disease associated with combined use of NSAIDs and corticosteroids indicates the need to prescribe this drug combination cautiously.

COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease.

Results of premarketing and postmarketing trials have raised doubts about the cardiovascular safety of the non-steroidal anti-inflammatory drug (NSAID) rofecoxib, especially at doses greater than 25 mg. Between Jan 1, 1999, and June 30, 2001, we did a retrospective cohort study of individuals on the expanded Tennessee Medicaid programme (TennCare), in which we assessed occurrence of serious coronary heart disease (CHD) in non-users (n=202916) and in users of rofecoxib and other NSAIDs (rofecoxib n=24 132, other n=151 728). Participants were aged 50-84 years, lived in the community, and had no life-threatening non-cardiovascular illness. Users of high-dose rofecoxib were 1.70 (95% CI 0.98-2.95, p=0.058) times more likely than non-users to have CHD; among new users this rate increased to 1.93 (1.09-3.42, p=0.024). By contrast, there was no evidence of raised risk of CHD among users of rofecoxib at doses of 25 mg or less or among users of other NSAIDs.

Burden of Interpandemic Influenza in Children Younger than 5 Years: A 25-Year Prospective Study

Many respiratory viruses cause morbidity in young children, but a licensed vaccine and effective oral therapy are available only for influenzavirus. To determine the incidence of laboratory-confirmed influenza illness, we prospectively followed up 1665 healthy children aged <5 years who were enrolled in the Vanderbilt Vaccine Clinic at some point from 1974 through 1999. Viral cultures were obtained when the children presented with clinical illness. The isolation of influenzavirus was associated with an estimated 95 health care visits for children with symptoms of influenza, 46 episodes of acute otitis media, and 8 episodes of lower respiratory tract disease per 1000 children yearly. Rates of acute otitis media and lower respiratory tract disease were highest among children aged <2 years. Hospitalizations associated with culture-positive influenza occurred at an annual rate of 3-4 per 1000 children aged <2 years. Influenza is associated with substantial morbidity in otherwise healthy children aged <5 years.

Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings.

CONTEXT During the 1990s, antibiotic prescriptions for acute respiratory tract infection (ARTI) decreased in the United States. The sustainability of those changes is unknown. OBJECTIVE To assess trends in antibiotic prescriptions for ARTI. DESIGN, SETTING, AND PARTICIPANTS The National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data (1995-2006) were used to examine trends in antibiotic prescription rates by antibiotic indication and class. Annual survey data and census denominators were combined in 2-year intervals for rate calculations. MAIN OUTCOME MEASURES National annual visit rates and antibiotic prescription rates for ARTI, including otitis media (OM) and non-ARTI. RESULTS Among children younger than 5 years, annual ARTI visit rates decreased by 17% (95% confidence interval [CI], 9%-24%), from 1883 per 1000 population in 1995-1996 to 1560 per 1000 population in 2005-2006, primarily due to a 33% (95% CI, 22%-43%) decrease in OM visit rates (950 to 634 per 1000 population, respectively). This decrease was accompanied by a 36% (95% CI, 26%-45%) decrease in ARTI-associated antibiotic prescriptions (1216 to 779 per 1000 population). Among persons aged 5 years or older, ARTI visit rates remained stable but associated antibiotic prescription rates decreased by 18% (95% CI, 6%-29%), from 178 to 146 per 1000 population. Antibiotic prescription rates for non-OM ARTI for which antibiotics are rarely indicated decreased by 41% (95% CI, 22%-55%) and 24% (95% CI, 10%-37%) among persons younger than 5 years and 5 years or older, respectively. Overall, ARTI-associated prescription rates for penicillin, cephalosporin, and sulfonamide/tetracycline decreased. Prescription rates for azithromycin increased and it became the most commonly prescribed macrolide for ARTI and OM (10% of OM visits). Among adults, quinolone prescriptions increased. CONCLUSIONS Overall antibiotic prescription rates for ARTI decreased, associated with fewer OM visits in children younger than 5 years and with fewer prescriptions for ARTI for which antibiotics are rarely indicated. However, prescription rates for broad-spectrum antibiotics increased significantly.