The nocebo effect challenges the non-medical infliximab switch in practice.

BACKGROUND: In clinical practice, non-medical switching of biological medication may provoke nocebo effects due to unexplained deterioration of therapeutic benefits. Indication extrapolation, idiosyncratic reactions, and interchangeability remain challenged in clinical practice after biosimilar approval by the European Medicines Agency. The principle of "first do no harm" may be challenged in a patient when switching from originator to biosimilar biological. AIM: To describe the 1-year results of a pragmatic study on infliximab biosimilar implementation in immune-mediated inflammatory disease patients on the basis of shared decision-making under effectiveness and safety monitoring. METHODS: Inflammatory bowel disease and rheumatology patients on infliximab originator were converted to infliximab biosimilar after providing informed consent. Nocebo response patients were monitored after switch back to originator. Linear mixed models were used to analyze continuous endpoints on effectiveness and laboratory outcomes to determine significance (P ≤ 0.05) of change over time after switching. RESULTS: After inviting 146 patients, a group of 125 patients enrolled in the project over time, respectively, 73 Crohn's disease, 28 ulcerative colitis, nine rheumatoid arthritis, ten psoriatic arthritis, and five ankylosing spondylitis patients. No statistically significant changes in effectiveness and safety were observed in any of the indications after a median of 4 infusions in 9 months of study. An overall nocebo response of 12.8% was found among the patients during a minimal observation period of 6 months after the transition to biosimilar infliximab. The overall nocebo response rate did not differ between the studied indications. CONCLUSIONS: In inflammatory bowel disease and rheumatological patients, similar effectiveness and safety were demonstrated on the transition into infliximab biosimilar. In our series, patient empowerment and registration of treatment outcomes delineated biosimilar transition, an approach that hypothetically could reduce nocebo response rates which are relevant to account for regarding biosimilar implementation.

Evaluation of an interdisciplinary re-isolation policy for patients with previous Clostridium difficile diarrhea.

BACKGROUND: Diarrhea caused by Clostridium difficile is increasingly recognized as a nosocomial problem. The effectiveness and cost of a new program to decrease nosocomial spread by identifying patients scheduled for readmission who were previously positive for toxin was evaluated. METHODS: The Memorial Sloan-Kettering Cancer Center is a 410-bed comprehensive cancer center in New York City. Many patients are readmitted during their course of cancer therapy. In 1995 as a result of concern about the nosocomial spread of C difficile, we implemented a policy that all patients who were positive for C difficile toxin in the previous 6 months with no subsequent toxin-negative stool as an outpatient would be placed into contact isolation on readmission pending evaluation of stool specimens. Patients who were previously positive for C difficile toxin were identified to infection control and admitting office databases via computer. Admitting personnel contacted infection control with all readmissions to determine whether a private room was required. RESULTS: Between July 1, 1995, and June 30, 1996, 47 patients who were previously positive for C difficile toxin were readmitted. Before their first scheduled readmission, the specimens for 15 (32%) of these patients were negative for C difficile toxin. They were subsequently cleared as outpatients and were readmitted without isolation. Workup of the remaining 32 patients revealed that the specimens for 7 patients were positive for C difficile toxin and 86 isolation days were used. An additional 25 patients used 107 isolation days and were either cleared after a negative specimen was obtained in-house or discharged without having an appropriate specimen sent. Four patients (9%) had reoccurring C difficile after having toxin-negative stools. We estimate (because outpatient specimens were not collected) the cost incurred at $48,500 annually, including the incremental cost of hospital isolation and equipment. CONCLUSION: Our policy to control the spread of nosocomial C difficile required interdisciplinary cooperation between infection control and the admitting department. By identifying patients who were positive for toxin through admitting, we were able to place all potentially infected patients into isolation. Our positivity rate of 15% on readmission demonstrates the importance of this policy. The cost of controlling C difficile can be significantly lowered by clearing patients who were previously positive for toxin before hospital readmission.

Vancomycin-resistant Enterococcus faecium on a pediatric oncology ward: duration of stool shedding and incidence of clinical infection.

OBJECTIVE: To determine the duration of stool shedding and incidence of clinical infection among pediatric oncology patients colonized with vancomycin-resistant Enterococcus faecium (VRE) in our institution. METHODS: Stool cultures were obtained from all patients admitted from May 15 to August 2, 1994. Patients were followed for evidence of clinical VRE infection and surveillance stool results through August 15, 1995. Genetic relatedness of stool-clinical isolate pairs and serial stool samples was evaluated using pulsed field gel electrophoresis. RESULTS: Twenty-three (32%) of 73 screened patients were colonized with VRE. Eight (35%) of the colonized patients cleared VRE from stool; 10 (43%) were persistent carriers, excreting organisms for 19 to 331 days (median, 112 days); and 5 patients had an insufficient number of stools to determine length of carriage. Persistent carriers had a median of 6 hospital readmissions; 8 of 10 were positive at first or second readmission Clinical VRE infection developed in 6 of 73 patients (annual incidence, 8.2%). Clinical cases had more days of neutropenia between colonization and infection than colonized patients during a comparable follow-up (49 vs. 16 days, P = 0.04). Five of 6 stool-clinical isolate pairs were identical by pulsed field gel electrophoresis. Serial stools from 6 of 7 patients (collected 20 to 343 days apart) were identical by pulsed field gel electrophoresis. CONCLUSION: Persistent gastrointestinal colonization with VRE is common among pediatric oncology patients. Carriage of the same VRE clone for up to 1 year was demonstrated. In the majority of cases invasive and colonizing isolates were identical by DNA fingerprinting techniques, suggesting that the colonizing VRE was the source of infection. Intermittent excretion of organisms in stool makes vigilant tracking and immediate isolation of such patients crucial to control efforts. Prolonged neutropenia may increase the risk of developing clinical infection among VRE-colonized patients.

Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an emerging pathogen in immunocompromised patients.

OBJECTIVE: To describe 13 infections caused by Mycobacterium haemophilum. DESIGN: Identification of patients by microbiologic record review, followed by medical record review and a case-control study. SETTING: Seven metropolitan hospitals in New York. PATIENTS: All patients with M. haemophilum infections diagnosed between January 1989 and September 1991 and followed through September 1992. Surviving patients were enrolled in the case-control study. RESULTS: Infection with M. haemophilum causes disseminated cutaneous lesions, bacteremia, and diseases of the bones, joints, lymphatics, and the lungs. Improper culture techniques may delay laboratory diagnosis, and isolates may be identified incorrectly as other mycobacterial species. Persons with profound deficits in cell-mediated immunity have an increased risk for infection. These include persons with human immunodeficiency virus infection or lymphoma and those receiving medication to treat immunosuppression after organ transplant. Various antimycobacterial regimens have been used with apparent success to treat M. haemophilum infection. However, standards for defining antimicrobial susceptibility to the organism do not exist. CONCLUSIONS: Clinicians should consider this pathogen when evaluating an immunocompromised patient with cutaneous ulcerating lesions, joint effusions, or osteomyelitis. Microbiologists must be familiar with the fastidious growth requirements of this organism and screen appropriate specimens for mycobacteria using an acid-fast stain. If acid-fast bacilli are seen, M. haemophilum should be considered as the infecting organism as well as other mycobacteria, and appropriate media and incubation conditions should be used.

A cluster of four cases of Mycobacterium haemophilum infection.

Four cases of infection with Mycobacterium haemophilum occurred at a single hospital in a seven-month period. Only 22 cases have been reported since 1976. All four patients were immunocompromised; two had AIDS and two were the first known recipients of allogeneic bone marrow transplants (BMT) to develop the infection. One BMT recipient died of Mycobacterium haemophilum pneumonia. The organism requires hemin or ferric ammonium citrate and incubation of media at 30 degrees C for optimum growth. Clinicians and microbiologists should consider infection with Mycobacterium haemophilum, particularly when specimens are from immunocompromised patients with unexplained illness and/or when acid-fast bacilli are seen on smear.

A harness for 24-hour pH-monitoring in the dog.

Twenty-four hour pH monitoring is used widely in the field of upper gastrointestinal disease. This technique allows the study of pH profiles in normal subjects and those with esophageal, gastric, or duodenal disease. However, it has not been possible to study ambulatory pH in animals. We have designed and developed a harness to carry a pH recorder that enables 24-hour pH studies to be performed in the dog. We studied pH profiles in 10 dogs. The harness is adaptable and could be used for other long-term physiological measurements.