Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases.

BACKGROUND: Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. AIM: To develop evidence-based consensus statements for TDM-guided anti-TNF therapy in IBD. METHODS: A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. RESULTS: 22/24 statements met criteria for consensus. For anti-TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3-8 and 5-12 µg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints-such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision-making. In stable clinical response, TDM-guided dosing may avoid future relapse. Data indicate drug-tolerant anti-drug antibody assays do not offer an advantage over drug-sensitive assays. Further data are required prior to recommending TDM for non-anti-TNF biological agents. CONCLUSION: Consensus statements support the role of TDM in optimising anti-TNF agents to treat IBD, especially in situations of treatment failure.

Functionalized Multi-Walled Carbon Nanotube Paper for Monitoring Chemical Vapors.

The multi-walled carbon nanotube paper is prepared by vacuum filtration of pure nanotubes and their functionalized forms prepared by KMnO4 and H2O2 oxidation or by grafting with Poly(methyl methacrylate) (PMMA) and polypyrrole to form sensory nanotubes layer for detection of volatile organic compounds in air. The selected compounds for experimentation (acetone, diethyl ether, isopentane, methanol, tetrahydrofuran) have different polarities and volume fractions of saturated vapors. The sensing is measured by electrical resistance of the paper, which increases when exposed to vapors. A reversible reaction is observed when the paper is removed from the vapors. The functionalized nanotubes differ in their sensitivity to selected organics solvents. For example, KMnO4 oxidized paper has differentiated response to all used vapors, so the measured data may indicate clearly the type of the vapor. On the other hand, the MWCNT/PMMA composite has nearly the same response to acetone, diethyl ether and tetrahydrofuran and different response to isopentane and methanol. The investigation can lead to construction of sensory unit which could be capable of detecting and identifying different vapors in the air.

Payment by salary or fee-for-service. Effect on health care resource use in the last year of life.

OBJECTIVE: To investigate the effect of physician payment method on use of health care resources. DESIGN: Retrospective analysis of patient health care data collected for 3 years (1994 to 1996) from the Vital Statistics Department of the British Columbia Ministry of Health. Billing numbers identified physician payment method. SETTING: Salaried and fee-for-service primary care practices in the Capital Region District of Victoria, BC. PARTICIPANTS: A total of 582 patients in their last year of life: 106 were attended by salaried family physicians at a community health clinic; 476 were attended by fee-for-service practitioners. Groups were comparable in age, sex, and geographical location. MAIN OUTCOME MEASURES: Number and cost of specialist and diagnostic services and medications, number of days in hospital (acute and extended care), and main causes of death. RESULTS: None of the dependent measures showed any statistically significant differences based on comparisons between many variables for patients in the two groups. Costs of pharmaceutical, specialist, and diagnostic services were not significantly different for the two groups. There were three main causes of death, according to codes on death certificates: heart disease, malignant neoplasms, and cerebrovascular disease. CONCLUSION: Whether physicians were paid by salary or fee-for-service had no empirical effect on health care resource use.

The processing of T-lymphocytes by the but of the suckling neonate.

The suggestion that intact effector lymphocytes can pass from maternal milk through the gut wall of the suckling neonate has been tested directly by labelling alloantigen-stimulated T cells in vitro with [125I]iododeoxyuridine and following their fate after intraoral administration to newborn mice by whole body gamma counting. The cells were rapidly lost from the animal when compared to cells injected intraperitoneally, and at a rate indistinguishable from cells deliberately killed and given intraorally. If the alloantigen used to stimulate the T cells in vitro was shared by the neonate, the T cells were lost even faster. It was also found that highly lethal labelled leukemia cells behaved in a similar fashion and did not cause excess mortality if given intraorally. These results suggest that few, if any, lymphocytes traverse the neonatal gut wall and indicate that subcellular fractions may be responsible for maternal to neonatal transfer of immunological effector functions.