Summary 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.

No abstract

This study was conducted to compare the suppressive effects of calcium carbonate and calcium citrate on bone resorption in early postmenopause. Calcium citrate is thought to be better absorbed. We therefore tested the hypothesis that calcium as citrate is more effective than calcium as carbonate in suppressing parathyroid hormone (PTH) and C-terminal telopeptide. Twenty-five healthy postmenopausal women were recruited in this double blind crossover study. The subjects were randomly allocated to receive either 1,000 mg of elemental calcium as carbonate or 500 mg of calcium as citrate. They were given the alternate calcium dose 1 week later. Serum measurements of total and ionized calcium, phosphate, PTH, and CrossLaps were repeated 12 hours after each dose. Analysis of variance found no significant difference between measures for the two salts. Tests for equivalence indicated that 500 mg of calcium citrate may be superior to 1,000 mg of calcium carbonate in raising serum total and ionized calcium (P = 0.04 and 0.05, respectively). For all parameters measured, 500 mg of calcium citrate was at least as beneficial as 1,000 mg of calcium carbonate. Calcium citrate is at least as effective as calcium carbonate in suppressing PTH and C-terminal telopeptide cross-links, at half the dose. This may be because calcium as citrate is better absorbed than calcium as carbonate. If calcium citrate can be used in lower doses, it may be better tolerated than calcium carbonate.

Objective: To assess the feasibility of administering an inexpensive preparation of vitamin D3 100 000 IU orally 3 monthly to aged‐care residents. Design: Prospective, controlled open‐label implementation trial. Setting: Residential aged care, November 2003 to May 2004 (primary study). Participants: 137 ambulant residents: 107 treated (mean age, 85 years; 79 were women), 30 untreated controls (mean age, 87 years; 22 were women). Interventions: Lactose microencapsulated vitamin D3 100 000 IU orally at baseline, then 3 monthly (three or more doses); untreated subjects were observed contemporaneously. Main outcome measures: Serum levels of 25‐hydroxyvitamin D [25(OH)D] at 6 months compared with baseline; acceptability of the program to residents and staff. Results: At baseline, 95% of residents assessed (n = 137) had serum 25(OH)D levels below the desirable range of 60–160 nmol/L. At 6 months, all treated residents (n = 98) achieved desired levels, with the mean (± SD) 25(OH)D level increasing from 36.4 ± 12.6 nmol/L (range, 12–75 nmol/L) at baseline to 124.0 ± 27.9 nmol/L (range, 68–244 nmol/L). In no resident did 25(OH)D approach toxic levels. The mean serum 25(OH)D level remained low in the control group (n = 27): 42.8 ± 18.3 nmol/L (range, 18–98 nmol/L). The difference between the mean 25(OH)D levels of treatment and control groups at 6 months was 81.2 nmol/L (95% CI, 69.7–92.0 nmol/L). The cost of the supplement was $4 per resident per annum. Substudies showed mean trough serum 25(OH)D levels in the desired range at 3 months (n = 31), but below the desired range at 6 months (n = 50). Subjects given 3‐monthly doses for up to 2 years maintained serum 25(OH)D levels within the desired range, with no trend toward undesirable accumulation (n = 11). Conclusions: Vitamin D3 100 000 IU given orally 3 monthly is a practical, safe, effective and inexpensive way to meet the vitamin D3 requirements of aged‐care residents.

IMPORTANCEThe use of perioperative, prophylactic, intravenous antibiotics is standard practice to reduce the risk of surgical site infection after oncologic resection and complex endoprosthetic reconstruction for lower extremity bone tumors. However, evidence guiding the duration of prophylactic treatment remains limited.OBJECTIVE To assess the effect of a 5-day regimen of postoperative, prophylactic, intravenous antibiotics compared with a 1-day regimen on the rate of surgical site infections within 1 year after surgery.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical superiority trial was performed at 48 clinical sites in 12 countries from January 1, 2013, to October 29, 2019. The trial included patients with a primary bone tumor or a soft tissue sarcoma that had invaded the femur or tibia or oligometastatic bone disease of the femur or tibia with expected survival of at least 1 year who required surgical management by excision and endoprosthetic reconstruction. A total of 611 patients were enrolled, and 7 were excluded for ineligibility.INTERVENTIONS A 1-or 5-day regimen of postoperative prophylactic intravenous cephalosporin (cefazolin or cefuroxime) that began within 8 hours after skin closure and was administered every 8 hours thereafter. Those randomized to the 1-day regimen received identical saline doses every 8 hours for the remaining 4 days; patients, care providers, and outcomes assessors were blinded to treatment regimen. MAIN OUTCOMES AND MEASURESThe primary outcome in this superiority trial was a surgical site infection (superficial incisional, deep incisional, or organ space) classified according to the criteria established by the Centers for Disease Control and Prevention within 1 year after surgery. Secondary outcomes included antibiotic-related complications, unplanned additional operations, oncologic and functional outcomes, and mortality. RESULTSOf the 604 patients included in the final analysis (mean [SD] age, 41.2 [21.9] years; 361 [59.8%] male; 114 [18.9%] Asian, 43 [7.1%] Black, 34 [5.6%] Hispanic, 15 [2.5%] Indigenous, 384 [63.8%] White, and 12 [2.0%] other), 293 were randomized to a 5-day regimen and 311 to a 1-day regimen. A surgical site infection occurred in 44 patients (15.0%) allocated to the 5-day regimen and in 52 patients (16.7%) allocated to the 1-day regimen (hazard ratio, 0.93; 95% CI, 0.62-1.40; P = .73). Antibiotic-related complications occurred in 15 patients (5.1%) in the 5-day regimen and in 5 patients (1.6%) allocated to the 1-day regimen (hazard ratio, 3.24; 95% CI, 1.17-8.98; P = .02). Other secondary outcomes did not differ significantly between treatment groups.CONCLUSIONS AND RELEVANCE This randomized clinical trial did not confirm the superiority of a 5-day regimen of postoperative intravenous antibiotics over a 1-day regimen in preventing surgical site infections after surgery for lower extremity bone tumors that required an endoprosthesis. The 5-day regimen group had significantly more antibiotic-related complications.