Objective: This study assessed feasibility of using quality improvement (QI) tools to improve management of perioperative pain in hospitals in multiple developing countries.
Methods: The International Pain Registry and Developing Countries working groups, from the International Association for the Study of Pain (IASP), sponsored the project and PAIN OUT, a QI and research network, coordinated it, and provided the research tools. The IASP published a call about the project on its website. Principal investigators (PIs) were responsible for implementing a preintervention and postintervention study in 1 to 2 surgical wards in their hospitals, and they were free to choose the QI intervention. Trained surveyors used standardized and validated web-based tools for collecting findings about perioperative pain management and patient reported outcomes (PROs). Four processes and PROs, independent of surgery type, assessed effectiveness of the interventions.
Results: Forty-three providers responded to the call; 13 applications were selected; and PIs from 8 hospitals, in 14 wards, in 7 countries, completed the study. Interventions focused on teaching providers about pain management. Processes improved in 35% and PROs in 37.5% of wards.
Conclusions: The project proved useful on multiple levels. It offered PIs a framework and tools to perform QI work and findings to present to colleagues and administration. Management practices and PROs improved on some wards. Interpretation of change proved complex, site-dependent, and related to multiple factors. PAIN OUT gained experience coordinating a multicentre, international QI project. The IASP promoted research, education, and QI work.
APPROACH AND RESULTS: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p
APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings.
CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.
METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P