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Key Points: Question: Can a coordinated, multifaceted intervention increase the prescription of 3 evidence-based therapies among adults with type 2 diabetes and atherosclerotic cardiovascular disease? Findings: In a cluster randomized clinical trial of cardiology clinics across the US, participants in the intervention group were more likely to be prescribed all 3 therapies (high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and sodium-glucose cotransporter 2 inhibitors and/or glucagon-like peptide 1 receptor agonists) after an intervention of assessment, education, and feedback vs those in the usual care group (173/457 [37.9%] vs 85/588 [14.5%], respectively, which is a difference of 23.4%). Meaning: A coordinated, multifaceted intervention increased prescription of 3 groups of evidence-based therapies in adults with type 2 diabetes and atherosclerotic cardiovascular disease. Importance: Evidence-based therapies to reduce atherosclerotic cardiovascular disease risk in adults with type 2 diabetes are underused in clinical practice. Objective: To assess the effect of a coordinated, multifaceted intervention of assessment, education, and feedback vs usual care on the proportion of adults with type 2 diabetes and atherosclerotic cardiovascular disease prescribed all 3 groups of recommended, evidence-based therapies (high-intensity statins, angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs], and sodium-glucose cotransporter 2 [SGLT2] inhibitors and/or glucagon-like peptide 1 receptor agonists [GLP-1RAs]). Design, Setting, and Participants: Cluster randomized clinical trial with 43 US cardiology clinics recruiting participants from July 2019 through May 2022 and follow-up through December 2022. The participants were adults with type 2 diabetes and atherosclerotic cardiovascular disease not already taking all 3 groups of evidence-based therapies. Interventions: Assessing local barriers, developing care pathways, coordinating care, educating clinicians, reporting data back to the clinics, and providing tools for participants (n = 459) vs usual care per practice guidelines (n = 590). Main Outcomes and Measures: The primary outcome was the proportion of participants prescribed all 3 groups of recommended therapies at 6 to 12 months after enrollment. The secondary outcomes included changes in atherosclerotic cardiovascular disease risk factors and a composite outcome of all-cause death or hospitalization for myocardial infarction, stroke, decompensated heart failure, or urgent revascularization (the trial was not powered to show these differences). Results: Of 1049 participants enrolled (459 at 20 intervention clinics and 590 at 23 usual care clinics), the median age was 70 years and there were 338 women (32.2%), 173 Black participants (16.5%), and 90 Hispanic participants (8.6%). At the last follow-up visit (12 months for 97.3% of participants), those in the intervention group were more likely to be prescribed all 3 therapies (173/457 [37.9%]) vs the usual care group (85/588 [14.5%]), which is a difference of 23.4% (adjusted odds ratio [OR], 4.38 [95% CI, 2.49 to 7.71]; P <.001) and were more likely to be prescribed each of the 3 therapies (change from baseline in high-intensity statins from 66.5% to 70.7% for intervention vs from 58.2% to 56.8% for usual care [adjusted OR, 1.73; 95% CI, 1.06-2.83]; ACEIs or ARBs: from 75.1% to 81.4% for intervention vs from 69.6% to 68.4% for usual care [adjusted OR, 1.82; 95% CI, 1.14-2.91]; SGLT2 inhibitors and/or GLP-1RAs: from 12.3% to 60.4% for intervention vs from 14.5% to 35.5% for usual care [adjusted OR, 3.11; 95% CI, 2.08-4.64]). The intervention was not associated with changes in atherosclerotic cardiovascular disease risk factors. The composite secondary outcome occurred in 23 of 457 participants (5%) in the intervention group vs 40 of 588 participants (6.8%) in the usual care group (adjusted hazard ratio, 0.79 [95% CI, 0.46 to 1.33]). Conclusions and Relevance: A coordinated, multifaceted intervention increased prescription of 3 groups of evidence-based therapies in adults with type 2 diabetes and atherosclerotic cardiovascular disease. Trial Registration: ClinicalTrials.gov Identifier: NCT03936660 This cluster randomized clinical trial assesses the effect of a coordinated, multifaceted intervention of assessment, education, and feedback vs usual care on the prescribing of all 3 groups of recommended therapies (high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and sodium-glucose cotransporter 2 inhibitors and/or glucagon-like peptide 1 receptor agonists) for adults with type 2 diabetes and atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Importance: Adoption of guideline-directed medical therapy for patients with heart failure is variable. Interventions to improve guideline-directed medical therapy have failed to consistently achieve target metrics, and limited data exist to inform efforts to improve heart failure quality of care.Objective: To evaluate the effect of a hospital and postdischarge quality improvement intervention compared with usual care on heart failure outcomes and care.Design, Setting, and Participants: This cluster randomized clinical trial was conducted at 161 US hospitals and included 5647 patients (2675 intervention vs 2972 usual care) followed up after a hospital discharge for acute heart failure with reduced ejection fraction (HFrEF). The trial was performed from 2017 to 2020, and the date of final follow-up was August 31, 2020.Interventions: Hospitals (n = 82) randomized to a hospital and postdischarge quality improvement intervention received regular education of clinicians by a trained group of heart failure and quality improvement experts and audit and feedback on heart failure process measures (eg, use of guideline-directed medical therapy for HFrEF) and outcomes. Hospitals (n = 79) randomized to usual care received access to a generalized heart failure education website.Main Outcomes and Measures: The coprimary outcomes were a composite of first heart failure rehospitalization or all-cause mortality and change in an opportunity-based composite score for heart failure quality (percentage of recommendations followed).Results: Among 5647 patients (mean age, 63 years; 33% women; 38% Black; 87% chronic heart failure; 49% recent heart failure hospitalization), vital status was known for 5636 (99.8%). Heart failure rehospitalization or all-cause mortality occurred in 38.6% in the intervention group vs 39.2% in usual care (adjusted hazard ratio, 0.92 [95% CI, 0.81 to 1.05). The baseline quality-of-care score was 42.1% vs 45.5%, respectively, and the change from baseline to follow-up was 2.3% vs -1.0% (difference, 3.3% [95% CI, -0.8% to 7.3%]), with no significant difference between the 2 groups in the odds of achieving a higher composite quality score at last follow-up (adjusted odds ratio, 1.06 [95% CI, 0.93 to 1.21]).Conclusions and Relevance: Among patients with HFrEF in hospitals randomized to a hospital and postdischarge quality improvement intervention vs usual care, there was no significant difference in time to first heart failure rehospitalization or death, or in change in a composite heart failure quality-of-care score.Trial Registration: ClinicalTrials.gov Identifier: NCT03035474. [ABSTRACT FROM AUTHOR]

Importance: Despite guideline recommendations, many patients discontinue P2Y12 inhibitor therapy earlier than the recommended 1 year after myocardial infarction (MI), and higher-potency P2Y12 inhibitors are underutilized. Cost is frequently cited as an explanation for both of these observations.Objective: To determine whether removing co-payment barriers increases P2Y12 inhibitor persistence and lowers risk of major adverse cardiovascular events (MACE).Design, Setting, and Participants: Cluster randomized clinical trial among 301 hospitals enrolling adult patients with acute MI (June 5, 2015, through September 30, 2016); patients were followed up for 1 year after discharge (final date of follow-up was October 23, 2017), with blinded adjudication of MACE; choice of P2Y12 inhibitor was per clinician discretion.Interventions: Hospitals randomized to the intervention (n = 131 [6436 patients]) provided patients with co-payment vouchers for clopidogrel or ticagrelor for 1 year (median voucher value for a 30-day supply, $137 [25th-75th percentile, $20-$339]). Hospitals randomized to usual care (n = 156 [4565 patients]) did not provide study vouchers.Main Outcomes and Measures: Independent coprimary outcomes were patient-reported persistence with P2Y12 inhibitor (defined as continued treatment without gap in use ≥30 days) and MACE (death, recurrent MI, or stroke) at 1 year among patients discharged with a prescription for clopidogrel or ticagrelor.Results: Among 11 001 enrolled patients (median age, 62 years; 3459 [31%] women), 10 102 patients were discharged with prescriptions for clopidogrel or ticagrelor (clopidogrel prescribed to 2317 [36.0%] in the intervention group and 2497 [54.7%] in the usual care group), 4393 of 6135 patients (72%) in the intervention group used the voucher, and follow-up data at 1 year were available for 10 802 patients (98.2%). Patient-reported persistence with P2Y12 inhibitors at 1 year was higher in the intervention group than in the control group (unadjusted rates, 5340/6135 [87.0%] vs 3324/3967 [83.8%], respectively; P < .001; adjusted difference, 2.3% [95% CI, 0.4% to 4.1%]; adjusted odds ratio, 1.19 [95% CI, 1.02 to 1.40]). There was no significant difference in MACE at 1 year between intervention and usual care groups (unadjusted cumulative incidence, 10.2% vs 10.6%; P = .65; adjusted difference, 0.66% [95% CI, -0.73% to 2.06%]; adjusted hazard ratio, 1.07 [95% CI, 0.93 to 1.25]).Conclusions and Relevance: Among patients with MI, provision of vouchers to offset medication co-payments for P2Y12 inhibitors, compared with no vouchers, resulted in a 3.3% absolute increase in patient-reported persistence with P2Y12 inhibitors and no significant reduction in 1-year MACE outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT02406677. [ABSTRACT FROM AUTHOR]

Single-site, intensive, community-based blood pressure (BP) intervention programs have led to BP improvements. The authors examined the American Heart Association's Check. Change.Control: (CCC) program (4069 patients/18 cities) to determine whether BP interventions can effectively be scaled to multiple communities, using a simplified template and local customization. Effectiveness was evaluated at each site via site percent enrollment goals, participant engagement, and BP change from first to last measurement. High-enrolling sites frequently recruited at senior residential institutions and service organizations held hypertension management classes and utilized established and new community partners. High-engagement sites regularly held hypertension education classes and followed up with participants. Top-performing sites commonly distributed BP cuffs, checked BP at engagement activities, and trained volunteers. CCC demonstrated that simplified community-based hypertension intervention programs may lead to BP improvements, but there was high outcomes variability among programs. Several factors were associated with BP improvement that may guide future program development. [ABSTRACT FROM AUTHOR]

BACKGROUND: An increase in endogenous cat-echolamine levels after traumatic brain injury (TBI) is well described. Animal studies suggest that postinjury anemia is exacerbated by a persistent hyperadrenergic state. This study aims to determine if beta-blocker (BB) exposure affects anemia after TBI. STUDY DESIGN AND METHODS: We reviewed a Level I trauma registry for patients with TBI, examining markers of anemia between patients who received BB with those who did not. RESULTS: A total of 174 patients were exposed to BB (BB+) and 245 were not exposed (BB-). The mean age in the BB+ group was 50 years (vs. 36 years in BB-group, p < 0.001). The mean injury severity score was 33.6 for the BB+ group (vs. 30.8 for BB- group, p = 0.01). While BB+ patients were more likely to receive a transfusion (60.9% vs. 35.1%, p < 0.001), BB+ patients reached their nadir hemoglobin (Hb) at a later day of hospitalization and their rate of decrease in Hb was significantly slower (both p < 0.001). Choosing Hb cutoffs for anemia of both 7 and 10 g/dL, Kaplan-Meier demonstrated a significant delay in time to anemia. CONCLUSION: This study suggests beta-blockade delays anemia after TBI. Elaboration of this effect may demonstrate an additional benefit of beta-blockade after head injury. [ABSTRACT FROM AUTHOR]

The article discusses a study of the prevalence and outcomes of same-day discharge among older patients undergoing elective percutaneous coronary intervention (PCI) in the U.S. between November 2004 and December 2008. The Duke University Medical Center institutional review board in North Carolina has approved the study. Death and rehospitalization were included in the primary end points assessed for the analysis. Results stress the variability of same-day discharge among older patients undergoing elective PCI across PCI facilities. Also noted is the lack of association between a same-day discharge strategy and increased risk for death or readmission.

There is increasing evidence that patient centered care, including communication skills, is an essential component to chronic illness care. Our aim was to evaluate patient centered primary care as a determinant of medication adherence. We mailed 1,341 veterans with hypertension the Short Form Primary Care Assessment Survey (PCAS) which measures elements of patient centered primary care. We prospectively collected each patient's antihypertensive medication adherence for 6 months. Patients were characterized as adherent if they had medication for >80%. 654 surveys were returned (50.7%); and 499 patients with complete data were analyzed. Antihypertensive adherence increased as scores in patient centered care increased [RR 3.18 (95% CI 1.44, 16.23) bootstrap 5000 resamples] for PCAS score of 4.5 (highest quartile) versus 1.5 (lowest quartile). Future research is needed to determine if improving patient centered care, particularly communication skills, could lead to improvements in health related behaviors such as medication adherence and health outcomes. [ABSTRACT FROM AUTHOR]

The article discusses a study of the use of optimal medical therapy (OMT) in patients with stable angina undergoing percutaneous coronary intervention (PCI) before and after publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study. The study involved patients in the National Cardiovascular Data Registry in the U.S. between September 1, 2005 and June 30, 2009. Majority of the patients who were receiving OMT before their PCI had more comorbidities. It cites the similarities in demographic and clinical characteristics of patients in the before and after COURAGE trial periods. Results show that almost a third of patients failed to receive OMT.

Background: Proton-pump inhibitors (PPIs) and clopidogrel are frequently coprescribed, although the benefits and harms of their concurrent use are unclear.Objective: To examine the association between concurrent use of PPIs and clopidogrel and the risks for hospitalizations for gastroduodenal bleeding and serious cardiovascular disease.Design: Retrospective cohort study using automated data to identify patients who received clopidogrel between 1999 through 2005 after hospitalization for coronary heart disease.Setting: Tennessee Medicaid program.Patients: 20,596 patients (including 7593 concurrent users of clopidogrel and PPIs) hospitalized for myocardial infarction, coronary artery revascularization, or unstable angina pectoris.Measurements: Baseline and follow-up drug use was assessed from automated records of dispensed prescriptions. Primary outcomes were hospitalizations for gastroduodenal bleeding and serious cardiovascular disease (fatal or nonfatal myocardial infarction or sudden cardiac death, stroke, or other cardiovascular death).Results: Pantoprazole and omeprazole accounted for 62% and 9% of concurrent PPI use, respectively. Adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50% lower than that in nonusers (hazard ratio, 0.50 [95% CI, 0.39 to 0.65]). For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 (CI, 11.7 to 36.9) hospitalizations for gastroduodenal bleeding per 1000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 (CI, 0.82 to 1.19) for the entire cohort and 1.01 (CI, 0.76 to 1.34) for the subgroup of patients who had percutaneous coronary interventions with stenting during the qualifying hospitalization.Limitations: Unmeasured confounding and misclassification of exposure (no information on adherence or over-the-counter use of drugs) and end points (not confirmed by medical record review) were possible. Because many patients entered the cohort from hospitals with relatively few cohort members, the analysis relied on the assumption that after adjustment for observed covariates, PPI users from one such hospital could be compared with nonusers from a different hospital.Conclusion: In patients with serious coronary heart disease treated with clopidogrel, concurrent PPI use was associated with reduced incidence of hospitalizations for gastroduodenal bleeding. The corresponding point estimate for serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk.Primary Funding Source: Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Background: Proton-pump inhibitors (PPIs) and clopidogrel are frequently coprescribed, although the benefits and harms of their concurrent use are unclear. Objective: To examine the association between concurrent use of PPIs and clopidogrel and the risks for hospitalizations for gastroduodenal bleeding and serious cardiovascular disease. Design: Retrospective cohort study using automated data to identify patients who received clopidogrel between 1999 through 2005 after hospitalization for coronary heart disease. Setting: Tennessee Medicaid program. Patients: 20 596 patients (including 7593 concurrent users of clopidogrel and PPIs) hospitalized for myocardial infarction, coronary artery revascularization, or unstable angina pectoris. Measurements: Baseline and follow-up drug use was assessed from automated records of dispensed prescriptions. Primary outcomes were hospitalizations for gastroduodenal bleeding and serious cardiovascular disease (fatal or nonfatal myocardial infarction or sudden cardiac death, stroke, or other cardiovascular death). Results: Pantoprazole and omeprazole accounted for 62% and 9% of concurrent PPI use, respectively. Adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50% lower than that in nonusers (hazard ratio, 0.50 [95% CI, 0.39 to 0.65]). For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 (CI, 11.7 to 36.9) hospitalizations for gastroduodenal bleeding per 1000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 (CI, 0.82 to 1.19) for the entire cohort and 1.01 (CI, 0.76 to 1.34) for the subgroup of patients who had percutaneous coronary interventions with stenting during the qualifying hospitalization. Limitations: Unmeasured confounding and misclassification of exposure (no information on adherence or over-the-counter use of drugs) and end points (not confirmed by medical record review) were possible. Because many patients entered the cohort from hospitals with relatively few cohort members, the analysis relied on the assumption that after adjustment for observed covariates, PPI users from one such hospital could be compared with nonusers from a different hospital. Conclusion: In patients with serious coronary heart disease treated with clopidogrel, concurrent PPI use was associated with reduced incidence of hospitalizations for gastroduodenal bleeding. The corresponding point estimate for serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk. Primary Funding Source: Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Objective. In clinical trials of RA patients on traditional DMARDs, the addition of TNF-α antagonists increased infections compared with addition of placebo. Our objective was to compare serious infections following initiation of different RA regimens. Prior comparative studies of DMARD initiation have yielded conflicting results. Methods. We estimated hospitalization rates for infections following initiation of TNF-α antagonists, other DMARDs and oral glucocorticoids in Tennessee Medicaid-enrolled RA patients (1995-2005). Exposure time was measured using pharmacy information and infections were identified using validated definitions. Initiation of RA regimens was compared using Cox regression models with MTX as the reference. Sensitivity analyses excluded glucocorticoid users, applied a first exposure carried forward approach, restricted observations to 2002-05 and first episodes of use and explored effects of unmeasured confounders. Results. We identified 28 906 new episodes of medication use, including TNF-α antagonists (8%), MTX alone (15%) and glucocorticoids alone (57%). Compared with MTX initiation, TNF-α antagonist initiation did not significantly increase the risk of hospitalizations for pneumonia [adjusted hazard ratio (aHR) 1.61; 95% CI 0.85, 3.03] or any infection (aHR 1.31; 95% CI 0.78, 2.19). Initiation of LEF, SSZ or HCQ did not increase serious infections, compared with MTX. Both initiation and concurrent glucocorticoid use were associated with a dose-dependent increase in serious infections. Sensitivity analyses showed consistent results. Conclusions. Compared with initiation of MTX alone, initiation of TNF-α antagonists was not associated with a large increase in the risk of serious infections. Glucocorticoid use was associated with a dosedependent increase in the risk of these infections. [ABSTRACT FROM AUTHOR]

Purpose Studies of non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular events using administrative data require identification of incident acute myocardial infarctions (AMIs) and information on whether confounders differ by NSAID status. Methods We identified patients with a first AMI hospitalization from Tennessee Medicaid files as those with primary ICD-9 discharge diagnosis 410.x and hospitalization stay of > 2 calendar days. Eligible persons were non-institutionalized, aged 50-84 years between 1999-2004, had continuous enrollment and no AMI, stroke, or non-cardiovascular serious medical illness in the prior year. Of 5524 patients with a potential first AMI, a systematic sample ( n = 350) was selected for review. Using defined criteria, we classified events using chest pain history, EKG, and cardiac enzymes, and calculated the positive predictive value (PPV) for definite or probable AMI. Results 337 of 350 (96.3%) charts were abstracted and 307 (91.1%), 6 (1.8%), and 24 (7.1%) events were categorized as definite, probable, and no AMI, respectively. PPV for any definite or probable AMI was 92.8% (95% CI 89.6-95.2); for an AMI without an event in the past year 91.7% (95% CI 88.3-94.2), and for an incident AMI was 72.7% (95% CI 67.7-77.2). Age-adjusted prevalence of current smoking (46.4% vs. 39.1%, p = 0.35) and aspirin use (36.9% vs. 35.9%, p = 0.90) was similar among NSAID users and non-users Conclusions ICD-9 code 410.x had high predictive value for identifying AMI. Among those with AMI, smoking and aspirin use was similar in NSAID exposure groups, suggesting these factors will not confound the relationship between NSAIDs and cardiovascular outcomes. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose To determine if certain non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of cardiovascular events: acute myocardial infarction (AMI), stroke, and death from coronary heart disease (CHD). Methods We conducted a retrospective cohort study of Tennessee Medicaid enrollees aged 35-94 years between 1 January 1999 and 31 December 2005. Eligible persons were non-institutionalized, had continuous enrollment, and had no serious illness prior to cohort entry. Exposure to celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin was studied. The outcome was hospitalization for AMI, stroke, or death from CHD among those with and without a history of cardiovascular disease (CVD). Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) are reported. Results There were 610 001 persons in the final cohort and 14% had a baseline history of CVD. In those without CVD ( N = 525 249) there were 1 566 678 person-years of follow-up and 12 184 events. In this group, non-users had 7.90 events/1000 person-years. Events/1000 person-years were 10.41 for current use of celecoxib (aHR 1.00, 95% CI 0.89-1.13), 10.91 for rofecoxib (aHR 1.21, 95% CI 1.07-1.37), 12.46 for valdecoxib (aHR 1.30 95% CI 1.04-1.61), and 13.25 for indomethacin (aHR 1.36, 95% CI 1.11-1.66) compared to non-users. Among patients with a past history of CVD ( N = 84 752) there were 397 977 person-years of follow-up and 10 248 events. Non-users had 28.30 events/1000 person-years. Among those with CVD, rofecoxib use was associated with increased event rate (30.28 events/1000 person-years [aHR 1.21, 95% CI 1.08-1.37]) and naproxen was associated with a decreased event rate (22.66 events/1000 person-years [aHR 0.88, 95% CI 0.79-0.99]). Among new users, the results were similar except risk among naproxen users was no longer different than non-users. Conclusions We found an increased risk of cardiovascular events among all and new current users of rofecoxib, valdecoxib, and indomethacin in patients with no history of CVD. Among patients with CVD, all and new current rofecoxib use was associated with an increased risk of a cardiovascular event. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study assessed the relationship between community characteristics and alcohol use among 6,636 youth, aged from 14 to 20, in 2004. After adjusting for individual-level characteristics, youth from communities with a greater proportion of grandparents as caregivers, larger numbers of married couple families, and higher employment rates were significantly less likely to report past 30-day alcohol use. Youth from communities with higher median household income were significantly more likely to report past 30-day alcohol use. Adolescents in communities with a greater percentage of whites were significantly more likely to report binge drinking. The results indicate that the community context is an important predictor of alcohol use. [ABSTRACT FROM AUTHOR]

This study was designed to assess the association between pregnancy-related exposures to antibiotics recommended for use in the event of a bioterrorism attack and major congenital malformations. A retrospective cohort study included 30 049 infants from Tennessee Medicaid born between 1985 and 2000 identified from computerised state databases. Infants with fetal exposures to ciprofloxacin, azithromycin, doxycycline and amoxicillin (antibiotics recommended for potential bioterrorism attacks) (n = 24 521) and erythromycin (included as a positive control) (n = 2128) were compared with infants with no fetal exposure to any antibiotics (n = 3400). Major congenital malformations identified from computerised records were confirmed through medical record review. Overall, 869 (2.9%) of infants in the cohort had a confirmed major congenital malformation, with major malformations ranging from 2.5% to 3.0% among the antibiotic-specific exposure groups. No increased risk was present in multivariable analyses for any malformations and for malformations of specific organ systems. In conclusion, these data suggest that ciprofloxacin, azithromycin, doxycycline or amoxicillin use by pregnant women should not result in a greater incidence of overall major congenital malformations in infants whose mothers take these medications, though a large increase in risk cannot be ruled out. [ABSTRACT FROM AUTHOR]