Deprescribing proton pump inhibitors: evidence-based clinical practice guideline

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper or stop proton pump inhibitors (PPIs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. METHODS: Five health professionals (1 family physician, 3 pharmacists, and 1 gastroenterologist) and 5 nonvoting members comprised the overall team; members disclosed conflicts of interest. The guideline process included the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, with a detailed evidence review in in-person, telephone, and online meetings. Uniquely, the guideline development process included a systematic review of PPI deprescribing trials and examination of reviews of the harm of continued PPI use. Narrative syntheses of patient preferences and resource-implication literature informed recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and then to health care professional associations for review and revisions made at each stage. A decision-support algorithm was developed in conjunction with the guideline. RECOMMENDATIONS: This guideline recommends deprescribing PPIs (reducing dose, stopping, or using "on-demand" dosing) in adults who have completed a minimum of 4 weeks of PPI treatment for heartburn or mild to moderate gastroesophageal reflux disease or esophagitis, and whose symptoms are resolved. The recommendations do not apply to those who have or have had Barrett esophagus, severe esophagitis grade C or D, or documented history of bleeding gastrointestinal ulcers. CONCLUSION: This guideline provides practical recommendations for making decisions about when and how to reduce the dose of or stop PPIs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Outcome of laparoscopic redo fundoplication.

BACKGROUND: To date, there has been no objective evidence for the effectiveness of laparoscopic redo fundoplication. We therefore reviewed our experience and based our analysis on a number of objective parameters. METHODS: We prospectively followed 28 consecutive patients (five men and 23 women; mean age, 48.64 +/- 2.57 years) who required redo fundoplication. These patients were part of a series of laparoscopic Nissen fundoplications done between 1992 and 2001. The indications were recurrent symptoms of gastroesophageal reflux disease (GERD) (21 patients), acute herniation of the wrap (three patients), and chronic paraesophageal hernia (four patients). A diagnosis of recurrent GERD was based on endoscopy, 24-h pH study, manometry, and symptom score evaluation. A diagnosis of paraesophageal and acute herniation was based on contrast swallow studies and/or gastroscopy. RESULTS: Twenty-six redo fundoplications were completed laparoscopically; two were converted to open. The mean operative time was 55.43 +/- 3.81 min. There were no intraoperative complications. The mean hospital stay was 3.0 +/- 0.35 days. Postoperative complications included postoperative pneumonia in one patient. Two patients from the laparoscopic group required a third operation-one for acute herniation of the redo wrap, which was fixed laparoscopically, and the other for acute recurrent paraesophageal hernia, which was fixed via an open transthoracic approach. The mean follow-up after revision is 25.14 +/- 3.48 months, with a significant decrease in acid reflux from 5.01% +/- 0.99 to 0.48% +/- 0.23 ( p < 0.0001), a significant decrease in symptom score from 28.96 +/- 2.93 to 10.75 +/- 2.61 ( p < 0.0001), and a small but significant increase in lower esophageal sphincter (LES) pressure from 13.71 +/- 1.79 to 16.69 +/- 1.50 ( p = 0.04). CONCLUSIONS: Laparoscopic redo fundoplication is technically feasible and clinically effective over a 2-year objective follow-up. Conversion and complication rates are low.

The T cell receptor V beta repertoire in HIV-1 infection and disease.

Viral superantigens (SAg) were shown in mice to induce anergy and deletion of T cells bearing specific T cell receptor V beta subsets, these perturbations being mainly restricted to CD4+ T cells. In accordance with this model, a putative HIV-associated SAg could contribute to the pathogenesis of HIV-1 infection and AIDS. To reveal the presence of this putative molecule, three study protocols were designed that relied on the fact that similarity of the expressed V beta repertoire of a given pair of individuals is proportional to the relative likeness of their MHC background: (1) by using a quantitative PCR technique that allows simultaneous typing of 24 V beta families, the V beta repertoires of HIV-discordant monozygotic twins were compared; (2) the V beta repertoire found in lymph nodes of HIV-infected subjects was contrasted to that found in peripheral blood of the same individuals; (3) the V beta repertoire of a cohort of HIV-infected mothers was compared with that of their HIV-infected and uninfected children. Results from these approaches revealed that significant perturbations of the TCR V beta repertoire were taking place in HIV-infected subjects, and that these alterations were restricted to T cells expressing specific V beta s. These results are consistent with the presence of an HIV-associated SAg in HIV-1 infection.