Contraindicated use of cisapride: impact of food and drug administration regulatory action

Context  Cisapride, a gastrointestinal tract promotility agent, can cause life-threatening cardiac arrhythmias in patients susceptible either because of concurrent use of medications that interfere with cisapride metabolism or prolong the QT interval or because of the presence of other diseases that predispose to such arrhythmias. In June 1998, the US Food and Drug Administration (FDA) determined that use of cisapride was contraindicated in such patients and informed practitioners through additions to the boxed warning in the label and a "Dear Health Care Professional" letter sent by the drug's manufacturer. Objective  To evaluate the impact of the FDA's 1998 regulatory action regarding contraindicated use of cisapride. Design and Setting  Analysis of data for the 1-year periods before (July 1997-June 1998) and after (July 1998-June 1999) the regulatory action from the population-based, pharmacoepidemiology research databases of 2 managed care organizations (sites A and B) and a state Medicaid program (site C). Participants  Patients with at least 180 days of prior enrollment in 1 of the 3 sites who were prescribed cisapride at least once in the period before (n = 24 840) or after (n = 22 459) regulatory action. Patients could be included in both cohorts. Main Outcome Measures  Proportion of cisapride users in each period for whom cisapride use was contraindicated by the product label, based on computerized patient medical encounter records. Results  In the year prior to regulatory action, cisapride use was contraindicated for 26%, 30%, and 60% of users in study sites A, B, and C, respectively. In the year after regulatory action, use was contraindicated for 24%, 28%, and 58% of users, a reduction in contraindicated use of approximately 2 per 100 cisapride users at each site. When the analysis was restricted to new users of cisapride after regulatory action, only minor reductions in contraindicated use were found. Conclusion  The FDA's 1998 regulatory action regarding cisapride use had no material effect on contraindicated cisapride use. More effective ways to communicate new information about drug safety are needed.      

Infection control practices to reduce airborne bacteria during total knee replacement: a hospital survey in four states.

OBJECTIVE: To describe the use of laminar airflow, body exhaust, and ultraviolet lights during total knee replacement (TKR) in four U.S. states. DESIGN: Survey of healthcare facilities. SETTING: Hospitals in Illinois, North Carolina, Ohio, and Tennessee that performed TKR during 2000 as identified by Medicare claims data. PARTICIPANTS: Hospitals responding to a mailed questionnaire. RESULTS: Two hundred ninety-five (73%) of 405 eligible hospitals that performed 18,374 primary and revision TKR procedures responded to the questionnaire. Among responding hospitals, 30% reported regular use (for > 75% of procedures) of laminar airflow, 42% reported regular use of body exhaust, and 5% reported regular use of ultraviolet lights. Among hospitals providing complete data, 150 (58%) performing 66% of procedures reported regular use of at least one of these techniques. On regression analyses, laminar airflow was used more often by hospitals with a TKR volume greater than 25 procedures per year (odds ratio [OR], 2.0; 95% confidence interval [CI95], 1.1-3.7) and orthopedic residency programs (OR, 2.8; CI95, 1.3-6.3), but its use was not significantly related to hospital setting or ownership status. CONCLUSIONS: Although these clean air practices are not recommended by any U.S. governmental or professional organization, they are used in nearly two-thirds of TKR procedures. Better information about their impact on current practice and more explicit guidelines may aid decisions about the use of these resource-intensive infection control practices.     

Fetal echocardiography. VII. Doppler color flow mapping: a new technique for the diagnosis of congenital heart disease

One of the difficulties for the fetal sonographer is the complete elucidation of structural defects of the cardiovascular system that are associated with intracardiac or great vessel flow disturbances. With the recent introduction of Doppler color flow mapping, in which blood flow is displayed in color superimposed on a real-time image, it has been impossible to identify flow disturbances in the pediatric and adult patient. This study was undertaken to determine whether Doppler color flow mapping could be used in the fetus to identify normal and abnormal cardiovascular anatomy. Thirty-five normal and high-risk fetuses were examined between 16 and 40 weeks of gestation. Doppler color flow mapping identified normal and abnormal anatomy (ventricular septal defect, atrial septal defect, endocardial fibroelastosis, dysplastic pulmonary valve, and tricuspid regurgitation). It appears that Doppler color flow mapping will add a new dimension to fetal cardiovascular imaging.     

IL-24 intrinsically regulates Th17 cell pathogenicity in mice

In certain instances, Th17 responses are associated with severe immunopathology. T cell–intrinsic mechanisms that restrict pathogenic effector functions have been described for type 1 and 2 responses but are less well studied for Th17 cells. Here, we report a cell-intrinsic feedback mechanism that controls the pathogenicity of Th17 cells. Th17 cells produce IL-24, which prompts them to secrete IL-10. The IL-10–inducing function of IL-24 is independent of the cell surface receptor of IL-24 on Th17 cells. Rather, IL-24 is recruited to the inner mitochondrial membrane, where it interacts with the NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 13 (also known as Grim19), a constituent of complex I of the respiratory chain. Together, Grim19 and IL-24 promote the accumulation of STAT3 in the mitochondrial compartment. We propose that IL-24–guided mitochondrial STAT3 constitutes a rheostat to blunt extensive STAT3 deflections in the nucleus, which might then contribute to a robust IL-10 response in Th17 cells and a restriction of immunopathology in experimental autoimmune encephalomyelitis.     

Cerebrovascular responses to somatomotor stimulation in Parkinson’s disease: A multivariate analysis

Parkinson’s disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients.55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO₂ (EtCO₂; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO₂ and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation.Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.     

Low-risk gestational trophoblastic neoplasia: evaluating the need for initial inpatient treatment during low-dose methotrexate chemotherapy

OBJECTIVE: To evaluate the need for initial inpatient treatment for patients being treated with low-dose intramuscular methotrexate for low-risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Clinical notes of all patients treated with low-dose intramuscular methotrexate for low-risk GTN were analyzed and side effects noted. RESULTS: There were no episodes of increased uterine bleeding requiring extra medical intervention. There were 7 cases of chest pain; none required a change from methotrexate chemotherapy. CONCLUSION: Patients being treated with low-dose intramuscular methotrexate for low-risk GTN do not need to be treated routinely in the hospital for their first treatment cycle.     

Algorithms for identification of Guillain–Barré Syndrome among adolescents in claims databases

Background

Health insurance claims databases can provide data for studies of vaccine-related Guillain–Barre’ Syndrome (GBS), but not all patients with a diagnostic ICD-9-CM code for GBS have the disease. The objective of this study was to evaluate the positive predictive values (PPVs) of claims-based algorithms for identifying GBS cases in 4 claims database environments.

Methods

Potential cases were adolescents ages 11–21 with at least one claim for GBS (ICD-9-CM code 357.0). Medical record reviews by a panel of 3 neurologists were conducted for case confirmation. Claims data considered for inclusion in the case-ascertainment algorithm included coding position, physician specialty, visit type, diagnostic tests. PPVs were used to assess the contribution of study factors in predicting case status.

Results

Among 361 individuals with a GBS diagnosis code, 106 were confirmed overall (PPV = 0.29), varying from 0.24 to 0.56 across the 4 sites. Requiring the GBS code to be associated with a neurologist visit (PPV = 0.53) or to be in a primary position on an inpatient claim (0.56) improved the performance. A composite algorithm including a primary inpatient GBS code and a neurologist visit associated with any GBS code gave the highest PPV (0.70). Incorporating claims for diagnostic testing had little impact on the PPV. Findings were generally similar across study sites.

Conclusions

Algorithms were able to identify GBS cases better than the single occurrence of the diagnostic code for GBS, and these algorithms may perform similarly in different claims environments.