Pediatric gastroesophageal reflux disease and acid-related conditions: trends in incidence of diagnosis and acid suppression therapy.

OBJECTIVE: To describe the incidence of diagnosis of gastroesophageal reflux disease and acid-related conditions (GERD/ARC) throughout childhood and characterize patterns of diagnosis and treatment with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H(2)RAs). METHODS: Cohorts of GERD/ARC children (age 0-18 years) were identified from a large US administrative claims database covering 1999-2005 using ICD-9 codes. Incidence, healthcare utilization (HCU), costs, therapy discontinuation and switching rates were compared between various age and patient groups. RESULTS: Between 2000 and 2005 annual incidence of GERD/ARC diagnosis among infants (age ≤1 year) more than tripled (from 3.4 to 12.3%) and increased by 30% to 50% in other age groups. Patients diagnosed by GI specialists (9.2%) were more likely to be treated with PPIs compared to patients diagnosed by primary care physician (PCP). PPI-initiated patients doubled (from 31.5% in 1999 to 62.6% in 2005) and, when compared with H(2)RA-initiated patients, were associated with 30% less discontinuation and 90% less therapy switching in the first month, and with higher comorbidity burden and pre-treatment total HCU and costs when diagnosed by GI specialists. LIMITATIONS: The use of an exploratory definition for GERD/ARC, administrative claims data and potential coding errors in diagnosis codes used in selection process may limit the generalizability of the results. CONCLUSIONS: GERD/ARC incidence increased for children of all ages between 2000 and 2005. PCPs made the majority of diagnoses. PPI initiations have now surpassed H(2)RA initiations.

Healthcare costs of GERD and acid-related conditions in pediatric patients, with comparison between histamine-2 receptor antagonists and proton pump inhibitors.

BACKGROUND: Gastroesophageal reflux disease and acid-related conditions (GERD/ARC) are common in pediatric practice but their costs have not been well characterized. AIM: To compare healthcare costs (HCC) and healthcare utilization (HCU) of pediatric GERD/ARC between groups of GERD/ARC patients initiated on histamine-2 receptor antagonists (H(2)RAs) or proton pump inhibitors (PPIs) and matched controls. PATIENTS AND METHODS: Children (age < 18 years) diagnosed with GERD or ARC (exploratory category) were identified from a large US claims database (1999-2005) using ICD-9 codes. Costs of pediatric GERD/ARC were estimated by comparing 6-month post-diagnosis HCC between cases and matched controls. GERD/ARC-related HCC and HCU for the year 2005 were further compared between GERD/ARC patients initiated with PPIs vs. H(2)RAs in terms of the cost differences relative to pre-initiation (difference-in-difference) and using multivariate regression to adjust for demographics, pre-treatment health status and pre-treatment costs. RESULTS: A total of 27 865 matched pairs were identified. GERD/ARC patients incurred on average more 6-month total HCC than controls ($2386). In 2005, 1010 pediatric patients were initiated on H(2)RAs or PPIs. About 61% were initiated on PPIs and incurred 1.8 times higher 6-month post-initiation GERD/ARC-related HCC than H(2)RA-initiated patients ($661 vs. $372, p < 0.001). Although total 6-month GERD/ARC-related HCC increased for both PPI- and H(2)RA-treated patients, the increase was 30% less for PPI-treated patients ($173 vs. $246, p = 0.521) in the difference-in-difference analysis and 69% less in the multivariate analysis ($109 vs. $347, p = 0.040). LIMITATIONS: The use of an exploratory definition for GERD/ARC, administrative claims data and potential coding errors in diagnosis codes used in selection process may limit the generalizability of the results. CONCLUSION: Pediatric GERD/ARC patients incurred significantly higher healthcare costs compared to similar children without GERD/ARC. Compared to patients initiated with H(2)RAs, patients initiated with PPIs had more baseline comorbidities, and lower GERD/ARC-related HCC after beginning treatment.

Outcomes with the use of glycoprotein IIb/IIIa inhibitors in non-ST-segment elevation acute coronary syndromes.

OBJECTIVE: To compare the characteristics, management, and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) who would have been eligible for inclusion in clinical trials of glycoprotein (GP) IIb/IIIa inhibitors with those of ineligible patients. DESIGN: Multinational, prospective, observational study (GRACE, Global Registry of Acute Coronary Events). SETTING: Patients hospitalised for a suspected acute coronary syndrome and enrolled in GRACE between April 1999 and December 2004. PATIENTS: 29 039 patients with NSTE ACS. MAIN OUTCOME MEASURES: Characteristics and outcomes were compared for trial-eligible (75.0%) and trial-ineligible (25.0%) patients. RESULTS: GP IIb/IIIa inhibitors were administered to 20.0% of eligible and 15.3% of ineligible patients. Compared with eligible patients, ineligible patients who received GP IIb/IIIa inhibitors had significantly higher rates of hospital death (6.8% vs 3.7%) and major bleeding (4.9% vs 2.2%). After adjustment for their higher baseline risk, ineligible patients still experienced higher hospital death rates (adjusted odds ratio (OR) 1.60; 95% confidence interval (CI) 1.01 to 2.39), but not higher bleeding rates, than the eligible group. Use of GP IIb/IIIa inhibitors was associated with a trend towards lower 6-month mortality in eligible (OR 0.86, 95% CI 0.72 to 1.02) and ineligible (OR 0.82, 95% CI 0.65 to 1.05) patients compared with those in whom this therapy was not used. CONCLUSIONS: GP IIb/IIIa inhibitors were markedly underused in the real-world population, irrespective of whether patients were trial-eligible or not. Despite the higher risk of ineligible patients, the benefits of GP IIb/IIIa inhibitors appear to be no less than in eligible patients.

Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention. The Global Registry of Acute Coronary Events.

OBJECTIVE: Treatment delays may result in different clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy vs primary percutaneous coronary intervention (PCI). The aim of this analysis was to examine how treatment delays relate to 6-month mortality in reperfusion-treated patients enrolled in the Global Registry of Acute Coronary Events (GRACE). DESIGN: Prospective, observational cohort study. SETTING: 106 hospitals in 14 countries. PATIENTS: 3959 patients who presented with STEMI within 6 h of symptom onset and received reperfusion with either a fibrin-specific fibrinolytic drug or primary PCI. MAIN OUTCOME MEASURES: 6-month mortality. METHODS: Multivariable logistic regression was used to assess the relationship between outcomes and treatment delay separately in each cohort, with time modelled with a quadratic term after adjusting for covariates from the GRACE risk score. RESULTS: A total of 1786 (45.1%) patients received fibrinolytic therapy, and 2173 (54.9%) underwent primary PCI. After multivariable adjustment, longer treatment delays were associated with a higher 6-month mortality in both fibrinolytic therapy and primary PCI patients (p<0.001 for both cohorts). For patients who received fibrinolytic therapy, 6-month mortality increased by 0.30% per 10-min delay in door-to-needle time between 30 and 60 min compared with 0.18% per 10-min delay in door-to-balloon time between 90 and 150 min for patients undergoing primary PCI. CONCLUSIONS: Treatment delays in reperfusion therapy are associated with higher 6-month mortality, but this relationship may be even more critical in patients receiving fibrinolytic therapy.

Intervention in acute coronary syndromes: do patients undergo intervention on the basis of their risk characteristics? The Global Registry of Acute Coronary Events (GRACE).

OBJECTIVE: To determine whether revascularisation is more likely to be performed in higher-risk patients and whether the findings are influenced by hospitals adopting more or less aggressive revascularisation strategies. METHODS: GRACE (Global Registry of Acute Coronary Events) is a multinational, observational cohort study. This study involved 24,189 patients enrolled at 73 hospitals with on-site angiographic facilities. RESULTS: Overall, 32.5% of patients with a non-ST elevation acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI; 53.7% in ST segment elevation myocardial infarction (STEMI)) and 7.2% underwent coronary artery bypass grafting (CABG; 4.0% in STEMI). The cumulative rate of in-hospital death rose correspondingly with the GRACE risk score (variables: age, Killip class, systolic blood pressure, ST segment deviation, cardiac arrest at admission, serum creatinine, raised cardiac markers, heart rate), from 1.2% in low-risk to 3.3% in medium-risk and 13.0% in high-risk patients (c statistic = 0.83). PCI procedures were more likely to be performed in low- (40% non-STEMI, 60% STEMI) than medium- (35%, 54%) or high-risk patients (25%, 41%). No such gradient was apparent for patients undergoing CABG. These findings were seen in STEMI and non-ST elevation ACS, in all geographical regions and irrespective of whether hospitals adopted low (4.2-33.7%, n = 7210 observations), medium (35.7-51.4%, n = 7913 observations) or high rates (52.6-77.0%, n = 8942 observations) of intervention. CONCLUSIONS: A risk-averse strategy to angiography appears to be widely adopted. Proceeding to PCI relates to referral practice and angiographic findings rather than the patient's risk status. Systematic and accurate risk stratification may allow higher-risk patients to be selected for revascularisation procedures, in contrast to current international practice.

Management and outcomes of lower risk patients presenting with acute coronary syndromes in a multinational observational registry.

OBJECTIVE: To document patterns of risk stratification, management practices, and outcomes among patients with acute coronary syndromes (ACS) presenting without high risk features. PATIENTS: The study was based on 11,885 consecutive patients presenting with non-ST segment elevation ACS enrolled in GRACE (global registry of acute coronary events). Patients without dynamic ST segment changes, positive troponin (or other cardiac markers), or haemodynamic or arrhythmic instability were defined as being at lower risk. MAIN OUTCOME MEASURES: Management and outcomes were compared with high risk presentations. RESULTS: Of 11,885 patients presenting with unstable angina or non-ST segment elevation myocardial infarction, 4252 (36%) were regarded as being at lower risk. Functional testing for risk stratification was performed in 1163 of 4207 (28%) lower risk and 1531 of 7521 (20%) high risk patients (p < 0.0001). Coronary angiography was performed in 1930 of 4190 (46%) and 3860 of 7544 (51%), and echocardiography in 1692 of 4190 (40%) and 4348 of 7533 (58%) of lower risk and high risk patients, respectively (p < 0.0001 for both). Over one third of patients did not undergo further risk assessment with angiography or functional testing (2746 of 7437 (37%) high risk, 1499 of 4148 (36%) lower risk, not significant). Death occurring in hospital was more likely in the high risk cohort (41 of 4227 (1.0%) lower risk v 215 of 7586 (2.8%) high risk, p < 0.0001), whereas rates of recurrent angina during admission and readmission were similar in both groups (1354 of 4231 (32%) high risk, 2313 of 7587 (31%) lower risk, not significant). In the six months after discharge, death or myocardial infarction occurred in 79 of 3223 (2.5%) lower risk patients and 302 of 5451 (5.5%) high risk patients (p < 0.0001). CONCLUSIONS: Globally, further risk stratification after ACS presentation is suboptimal, regardless of presenting characteristics. Although in-hospital death and myocardial infarction are uncommon, recurrent ischaemia is encountered often in both groups. It remains to be seen whether better outcomes may be achieved with wider application of risk stratification and appropriately directed management strategies.

Contemporary management of acute coronary syndromes: does the practice match the evidence? The global registry of acute coronary events (GRACE).

OBJECTIVE: To determine to what extent evidence based guidelines are followed in the management of acute coronary syndromes (ACS) in the UK, elsewhere in Europe, and multinationally, and what the outcomes are. DESIGN: Multinational, prospective, observational registry (GRACE, global registry of acute coronary events) with six months' follow up. SETTING: Patients presenting to a cluster of hospitals. The study was designed to collect data representative of the full spectrum of ACS in specific geographic populations. PATIENTS: Patients admitted with a working diagnosis of unstable angina or suspected myocardial infarction (MI). MAIN OUTCOME MEASURES: Death during hospitalisation and at six months' follow up (adjusted for baseline risks). RESULTS: In ST elevation MI, reperfusion was applied more often in the UK (71%) than in Europe (65%) and multinationally (59%) (p < 0.01). However, this was almost entirely by lytic treatment, in contrast with elsewhere (primary percutaneous coronary intervention 1%, 29%, 16%, respectively). Statins were applied more frequently in the UK for all classes of patients with ACS (p < 0.0001). In contrast there was lower use of revascularisation procedures in non-ST MI (20% v 37% v 28%, respectively) and glycoprotein IIb/IIIa antagonists (6% v 25% v 26%, respectively). In-hospital death rates, adjusted for baseline risk, were not significantly different but six month death rates were higher in the UK for ST elevation MI (7.2% UK, 4.3% Europe, 5.3% multinationally; p < 0.0001) and non-ST elevation MI (7.5%, 6.2%, and 6.7%, respectively; p = 0.012, UK v Europe). CONCLUSIONS: Current management of ACS in the UK more closely follows the recommendations of the National Service Framework than British or European guidelines. Differences in practice may account for the observed higher event rates in the UK after hospital discharge.

T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation.

In a trial of prophylactic implantation of a defibrillator, a mortality benefit was seen among patients with previous myocardial infarction and a left-ventricular ejection fraction of 0.30 or less. We identified 129 similar patients from two previously published clinical trials in which microvolt T-wave alternans testing was prospectively assessed. At 24 months of follow-up, no sudden cardiac death or cardiac arrest was seen among patients who tested T-wave alternans negative, compared with an event rate of 15.6% among the remaining patients. Testing of T-wave alternans seems to identify patients who are at low risk of ventricular tachyarrhythmic event and who may not benefit from defibrillator therapy.