The incidence and management of infusion reactions to infliximab: a large center experience

OBJECTIVE: To assess the incidence and management of infusion reactions to infliximab, a chimeric monoclonal antibody that targets human tumor necrosis factor-alpha, in patients with Crohn's disease treated at a large infusion center. METHODS: A total of 165 consecutive patients who received 479 infliximab infusions in the Division of Clinical Immunology Infusion Center at Mount Sinai Medical Center from July, 1998 to January, 2001 were evaluated. Specific treatment protocols for initial and subsequent acute infusion reactions were followed and the outcomes documented. RESULTS: The overall incidence of infusion reactions to infliximab was 6.1% (29 of 479) of infusions, affecting 9.7% (16 of 165) of patients. Mild, moderate, or severe acute reactions occurred in 3.1% (15 of 479), 1.2% (six of 479), and 1.0% (five of 479) of infliximab infusions, respectively. Use of treatment protocols resulted in rapid resolution of all acute reactions to infliximab. With the prophylaxis protocol, all patients who experienced an initial mild or moderate acute reaction were able to receive additional infusions. Four patients experienced a total of five severe acute reactions. Three patients were retreated: two patients had no further problems, whereas one patient had a second severe acute reaction that rapidly resolved with treatment. Suggesting that acute infusion reactions are not type I hypersensitivity reactions, in 11 patients who experienced 14 acute infusion reactions, serum tryptase levels were normal. Delayed infusion reactions occurred in 0.6% (three of 479) of infusions. CONCLUSIONS: Infliximab infusions were accompanied by acute reactions in approximately 5% of infusions. These reactions did not seem to be true IgE-mediated type I hypersensitivity events. Using appropriate treatment protocols, these reactions were effectively treated and prevented upon retreatment in nearly all patients. Delayed reactions were rare, occurring in <1% of infusions.     

Targeted Physician Education and Standardizing Documentation Improves Documented Reporting with Inflammatory Bowel Disease Quality Measures in a Large Academic and Private Practice

Background

Prior studies have shown poor compliance with quality measures for IBD at academic and private practices. We sought to provide focused interventions to improve compliance and documentation with the IBD measures.

Methods

Two centers, academic practice (AP) and private practice (PP), initially reviewed their compliance with eight established IBD quality measures in consecutive charts. A multi-faceted intervention was developed to improve awareness and documentation of these measures. The initial data and the quality measures were reviewed at a group meeting. Following this, a handout summarizing the measures was placed in each exam room. The AP added a new screen to the EHR that summarized the relevant IBD history, while the PP added a new template that was filled out and imported into the charts. Three months after this intervention, charts were reviewed for compliance with the measures.

Results

The intervention cohort consisted of 768 patients (AP = 569/PP = 199) compared to the initial cohort of 566 patients (AP = 367/PP = 199). Improvement was seen throughout all measures compared to the initial cohort. The AP reported compliance with all relevant measures in 21% and the PP in 60% compared to 7 and 10% in the initial cohort. PP had ≥ 75% compliance with every measure, of which only assessment for bone loss and pneumococcal vaccination was under 80%. In contrast, the AP compliance ranged from 35 to 100% with assessment for bone loss, influenza, and pneumococcal vaccination scoring lowest.

Conclusion

Our study demonstrates that focused low-cost interventions can significantly improve compliance with IBD quality measures in different practice settings.

     

Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation

Molecular genetic and phenotypic analyses were performed in a highly unusual case of combined protein S and protein C deficiency manifesting in a family in which a child had died perinatally from renal vein thrombosis. Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency. Am umbilical vein blood sample at 22 weeks gestation showed isolated protein C deficiency. This pregnancy proceeded to a full-term delivery without thrombotic complications. Molecular genetic analysis of the PROC and PROS gene segregating in the family then yielded one PROC gene lesion in the father and two PROS gene lesions, one in each parent. These lesions were shown to segregate with the respective deficiency states through the family pedigree. Analysis of DNA from paraffin-embedded liver tissue taken from the deceased child showed the presence of both PROS mutations, as well as the PROC mutation. Genotypic analysis of the second child showed a PROC mutation, but neither PROS mutation consistent with its possession of normal protein S levels and a low/borderline protein C level. Antenatal diagnosis was then performed in a third pregnancy by direct mutation detection. However, although the fetus carried only the paternal PROS and PROC gene lesions, the child developed renal thrombosis in utero. It may be that a further genetic lesion at a third locus still remains to be defined. Alternatively, the intrauterine development of thrombosis in this infant could have been caused, at least in part by a transplacental thrombotic stimulus arising in the protein S-deficient maternal circulation. This analysis may, therefore, serve as a warning against extrapolating too readily from genotype to phenotype in families with a complex thrombotic disorder.     

需要体外生命支持的新生儿甲状腺毒症并持续肺动脉高压

作者报道1例新生儿Graves病引起与新生儿甲状腺毒症有关的严重持续性肺动脉高压(PPH N)以至于接受体外循环膜氧合治疗。虽然甲状腺功能亢进在新生儿阶段很少见,但其与成人肺动脉高压相关。甲状腺功能亢进影响肺血管压力的确切机制目前尚不清楚。最近研究证明甲状腺功能亢进直接     

Studies of the affective state in bereaved children

The process of bereavement in children ranges from the absence of grief to symptoms of anxiety and conduct disturbances. Some psychoanalytic opinion holds that the absence of grief, associated with lack of cognitive maturity, leads to the development of psychopathology later in life. Other writers describe a mourning response, taking the form of ambivalence, anxiety, and care giving, which may protect against subsequent depression. This paper describes the affective response in 16 children ages four to 17 years, two to three years following the death of a parent, in order to further characterize developmental aspects of the emotional repertoire of bereavement. Only children aged 12 and over were depressed according to the Poznansky Children's Depression Rating Scale and criteria in the DSM-III. Conduct disturbances were observed in the younger children and some of the older children and were correlated with depression in the group as a whole. This suggests that the expression of depressive affect depends on maturation and that the young child may register grief only through anxiety and negativism. Examples of this spectrum of responses are offered in two case vignettes.     

Evaluating learning and knowledge retention after a continuing medical education course on total mesorectal excision for surgeons

The purpose of this study was to determine whether knowledge gained (as determined by a formal course test) by surgeons in a continuing education course on total mesorectal excision and rectal cancer management is retained 1 year later. A formal course test had been previously developed and validated. The test evaluated course content including pelvic anatomy, surgical techniques, imaging, pathology, adjuvant therapies, and cancer and functional outcomes. Validation was determined by the absence of change in pre- and posttest scores of the "expert" course instructors (n = 8, P = .6) and by a linear correlation in test scores with increasing level of general-surgery resident training (n = 16, P = .001). Significant learning by the 58 surgeons taking the course had been shown by improvement in test scores from before the course (mean score 19) to after the course (mean score 25.3, P = .001, out of a possible 33 total mark). At 1 year after the course, those course participants (n = 44, 76%) who had provided postcourse contact information were asked to complete the course test again. Responses were received from 18 surgeons (41% of those surveyed, 31% of the original course participants). The mean score on the test after 1 year was 23.8. Compared with the immediate posttest scores, there was no significant knowledge loss over the year (P = .09). We conclude that knowledge acquired during a continuing education course for surgeons on total mesorectal excision and rectal-cancer management is retained 1 year later.     

Is permissive hypoxemia a beneficial strategy for pediatric acute lung injury?

The adverse effects of high oxygen levels have been widely reported, and clinicians have struggled for many years to find the ideal balance between inspired oxygen levels and acceptable arterial oxygen saturation. However, when asked "what is an acceptable oxygen saturation," one is hard pressed to find a definitive answer. Permissive hypoxemia is a concept similar to the well-described strategy of permissive hypercapnia. It is a strategy that allows the arterial oxygen saturation to be less than normal in an attempt to minimize the amount of artificial support provided to the lungs by mechanical ventilation. It must be noted that this concept is predominantly based on physiology, as data in the medical literature are very limited. Permissive hypoxemia as an approach to acute lung injury remains controversial in the clinical setting.