Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency.

PURPOSE: Pyruvate kinase deficiency (PKD) is a rare disease and understanding of its epidemiology and associated burden remains limited. With no current curative therapy, clinical manifestations can be life threatening, clinically managed by maintaining adequate hemoglobin levels through transfusion and subsequent support, but with frequent complications. Treatment goals are to maintain/improve the patient's quality of life. With new therapies, reliable, valid, and relevant patient-reported outcome (PRO) tools are required for use in clinical trials. METHODS: Systematic literature search identified no current PRO tools for capturing/measuring the impact of PKD and treatments in clinical trials. Therefore, the search strategy was revised to consider conditions analogous to PKD in terms of symptoms and impacts that might serve as parallels to the experience in PKD; this included sickle cell anemia, thalassemia, and hemolytic anemia. Psychometric properties, strengths, and weakness of selected appropriate PRO instruments were compared, and recommendations made for choice of PRO tools. RESULTS: In adult populations, EORTC QLQ C30 and SF-36v2 are recommended, the former being a basic minimum, covering generic HRQoL, and core symptoms such as fatigue. In pediatric populations, PedsQL Generic Core Scale to measure HRQoL and PedsQL MFS scale to measure fatigue are recommended. CONCLUSIONS: Some symptoms/life impacts may be unique to PKD and not observable in analogous conditions. A 'Physico-Psychosocial Model' derived from the 'Medical Model' is proposed to form the basis for a hypothesized conceptual framework to address the development of PKD-specific PRO instruments.

The evolution and long-term results of laparoscopic antireflux surgery for the treatment of gastroesophageal reflux disease.

BACKGROUND: For nearly 2 decades, the laparoscopic correction of gastroesophageal reflux disease (GERD) has demonstrated its utility. However, the surgical technique has evolved over time, with mixed long-term results. We briefly review the evolution of antireflux surgery for the treatment of GERD, provide an update specific to the long-term efficacy of laparoscopic antireflux surgery (LARS), and analyze the factors predictive of a desirable outcome. MATERIALS AND METHODS: PubMed and Medline database searches were performed to identify articles regarding the laparoscopic treatment of GERD. Emphasis was placed on randomized control trials (RCTs) and reports with follow-up >1 year. Specific parameters addressed included operative technique, resolution of symptoms, complications, quality of life, division of short gastric vessels (SGVs), mesh repair, and approximation of the crura. Those studies specifically addressing follow-up of <1 year, the pediatric or elderly population, redo fundoplication, and repair of paraesophageal hernia and short esophagus were excluded. RESULTS: LARS has varied in technical approach through the years. Not until recently have more long-term, objective studies become available to allow for evidenced-based appraisals. Our review of the literature found no long-term difference in the rates of heartburn, gas-bloat, antacid use, or patient satisfaction between laparoscopic Nissen and Toupet fundoplication. In addition, several studies have shown that more patients had an abnormal pH profile following laparoscopic partial as opposed to total fundoplication. Conversely, dysphagia was more common following laparoscopic total versus partial fundoplication in 50% of RCTs at 12-month follow-up, though this resolved over time, being present in only 20% with follow-up >24 months. We confirmed that preoperative factors, such as hiatal hernia, atypical symptoms, poor antacid response, body mass index (BMI), and postoperative vomiting, are potential predictors of an unsatisfactory long-term outcome. Last, no trial disfavored division of the short gastric vessels (SGVs), closure of the crura, or mesh repair for hiatal defects. CONCLUSION: LARS has significantly evolved over time. The laparoscopic total fundoplication appears to provide more durable long-term results than the partial approach, as long as the technical elements of the operation are respected. Division of the SGVs, closure of the crura, and the use of mesh for large hiatal defects positively impacts long-term outcome. Hiatal hernia, atypical symptoms, poor antacid response, body mass index (BMI), and postoperative vomiting are potential predictors of failure in LARS.