Pharmacokinetics, Safety, and Tolerability of Anti-SARS-CoV-2 Monoclonal Antibody, Sotrovimab, Delivered Intravenously or Intramuscularly in Japanese and Caucasian Healthy Volunteers.

BACKGROUND AND OBJECTIVE: Sotrovimab 500 mg administered by a single intravenous (IV) infusion has been granted special approval for emergency use in Japan for treatment of SARS-CoV-2 infection in adults and children aged ≥ 12 years weighing ≥ 40 kg. This Phase 1, single-dose study investigated the pharmacokinetics, safety, and tolerability of IV or intramuscular (IM) sotrovimab 500 mg doses versus placebo in healthy Japanese and Caucasian volunteers. METHODS: This was a two-part, Phase 1, randomized, placebo-controlled, single-blind study. In Part 1, participants received a single sotrovimab 500 mg IV infusion or matching placebo on Day 1. In Part 2, participants received a single sotrovimab 500 mg IM dose or matching placebo on Day 1, administered as two 4 mL injections. RESULTS: There was no effect of ethnicity on the peak or total serum exposure of IV sotrovimab through Week 18; after adjusting for body weight, the point estimate and 90 % confidence interval for the ratio of total exposure between Japanese and Caucasian participants fell within conventional bioavailability bounds (80-125%). Geometric mean Cmax and AUClast following a single IM administration of sotrovimab were higher in Japanese participants compared with Caucasian participants, even after adjustment for body weight. Overall, a single IV or IM dose of sotrovimab was well tolerated by both Japanese and Caucasian participants. CONCLUSIONS: After adjusting for body weight, exposures following a single IV dose of sotrovimab 500 mg were similar between Japanese and Caucasian participants, and higher in Japanese participants following IM administration. Higher exposures were not associated with any safety signals. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04988152.

Counselling by primary care physicians may help patients with heartburn-predominant uninvestigated dyspepsia.

OBJECTIVE: To determine whether strategies to counsel and empower patients with heartburn-predominant dyspepsia could improve health-related quality of life. METHODS: Using a cluster randomized, parallel group, multicentre design, nine centres were assigned to provide either basic or comprehensive counselling to patients (age range 18 to 50 years) presenting with heartburn-predominant upper gastrointestinal symptoms, who would be considered for drug therapy without further investigation. Patients were treated for four weeks with esomeprazole 40 mg once daily, followed by six months of treatment that was at the physician's discretion. The primary end point was the baseline change in Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire score. RESULTS: A total of 135 patients from nine centres were included in the intention-to-treat analysis. There was a statistically significant baseline improvement in all domains of the QOLRAD questionnaire in both study arms at four and seven months (P<0.0001). After four months, the overall mean change in QOLRAD score appeared greater in the comprehensive counselling group than in the basic counselling group (1.77 versus 1.47, respectively); however, this difference was not statistically significant (P=0.07). After seven months, the overall mean baseline change in QOLRAD score between the comprehensive and basic counselling groups was not statistically significant (1.69 versus 1.56, respectively; P=0.63). CONCLUSIONS: A standardized, comprehensive counselling intervention showed a positive initial trend in improving quality of life in patients with heartburn-predominant uninvestigated dyspepsia. Further investigation is needed to confirm the potential benefits of providing patients with comprehensive counselling regarding disease management.

Barriers to the implementation of practice guidelines in managing patients with nonvariceal upper gastrointestinal bleeding: A qualitative approach.

BACKGROUND/OBJECTIVE: Guidelines for the management of patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) are inconsistently applied by health care providers, potentially resulting in suboptimal care and patient outcomes. A needs assessment was performed to assess health care providers' barriers to the implementation of these guidelines in Canada. METHODS: Semistructured telephone interviews were conducted by trained research personnel with 22 selectively sampled health care professionals actively treating and managing NVUGIB patients, including emergency room physicians (ER), intensivists (ICU), gastroenterologists (GI), gastroenterology nurses and hospital administrators. Participants were chosen from a representative sample of six Canadian community- and academic-based hospitals that participated in a national Canadian audit on the management of NVUGIB. RESULTS: Participants reported substantive gaps in the implementation of NVUGIB guidelines that included the following: lack of knowledge of the specifics of the NVUGIB guidelines (ER, ICU, nurses); limited belief in the value of guidelines, especially in areas where evidence is lacking (ER, ICU); limited belief in the value of available tools to support implementation of guidelines (GI); lack of knowledge of the roles and responsibilities of health care professions and disciplines, and lack of effective collaboration skills (ER, ICU and GI); variability of knowledge and skills of health care professionals within professions (eg, variability of nurses' knowledge and skills in endoscopic procedures); and perceived overuse of intravenous proton pump inhibitor treatment, with limited concern regarding cost or side effect implications (all participants). CONCLUSIONS: In the present study population, ER, ICU and nurses did not adhere to NVUGIB guidelines because they were neither aware of nor familiar with them, whereas the GI lack of adherence to NVUGIB guidelines was influenced more by attitudinal and contextual barriers. These findings can guide the design of multifaceted educational and behavioural interventions when attempting to effectively disseminate existing guidelines, and for guideline implementation into practice.