Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Coercive Pressures and Anti-corruption Reporting: The Case of ASEAN Countries

This paper aims to investigate the extent of anti-corruption reporting by ASEAN companies and examine whether coercive factors influence the level of disclosure. The authors adopt indicators from the Global Reporting Initiative version 4.0 to measure the extent of anti-corruption disclosures in 117 companies’ reports. Informed by a coercive isomorphism tenet drawn from the institutional theory, the authors propose that several institutional factors influence the extent of their voluntary disclosures. The findings reveal that a large degree of variability difference between the average levels of anti-corruption disclosure in Thailand (434 words) and the Philippines (149 words). The dependence on government tenders and foreign ownership are associated with the level of disclosure. Surprisingly, the United Nation Global Compact membership is not a significant determinant of anti-corruption reporting. This signifies that the membership in the international initiative does not correspond to individual company’s commitment to disclose anti-corruption information. In spite of significant efforts undertaken by global organizations to combat corruption, the level of anti-corruption disclosure is significantly different among the four countries under study. The disclosure of sensitive information such as the confirmed incidences of corruption cases requires careful consideration by the top management as it is subjected to legal implications and reputational risks. Thus, impression management can complement the coercive pressure in explaining the level of anti-corruption reporting. This study is among the first studies which explores the association between coercive factors and the level of anti-corruption disclosure in ASEAN region

Analgesia in Major Abdominal Surgery

Successful enhanced recovery after surgery relies on early mobilisation and nutrition. The former relies on effective analgesia, which also indirectly affects the latter. Effective analgesia is a primary technique which when combined with maximal multimodal analgesia, provides adequate pain relief without motor blockade, urinary retention and hypotension whilst avoiding high dose systemic opiate, and its antecedent side effects. Other attributes required for widespread application of a technique are safety, lack of cumbersome attachments, minimal contraindications and ease of deployment and training. The resurgence of the forgotten technique of rectus sheath blockade, improved by the recent ability to prolong the block by bilateral catheter insertion in the rectus sheath space, may satisfy all the requirements of effective analgesia for patients undergoing open midline abdominal surgery. These catheters can be placed prior to surgery under ultrasound guidance or directly by the surgeon. Furthermore, they may also be placed postoperatively under ultrasound guidance on the intensive care unit prior to waking patients who have been ventilated following emergency surgery