Prediction Models of Mortality in Acute Pancreatitis in Adults: A Systematic Review.

BACKGROUND: Acute pancreatitis (AP) varies in severity, prompting development of systems aimed at predicting prognosis to help guide therapy. Although several prediction approaches are available, their test characteristics and clinical utility are not completely understood. PURPOSE: To evaluate the test characteristics (prognostic accuracy, incremental predictive value) and clinical utility (effect on patient outcomes) of severity scores for predicting mortality in AP. DATA SOURCES: Ovid MEDLINE and EMBASE (inception to 3 May 2016). STUDY SELECTION: Longitudinal studies, in any language, that evaluated the prognostic value of at least 1 clinical severity score in AP. DATA EXTRACTION: Dual data extraction and quality assessment. DATA SYNTHESIS: Of 4039 citations screened, 94 unique studies evaluating 18 scores in 53 547 patients met the inclusion criteria. All studies provided data on prognostic accuracy, whereas 6 provided data on incremental predictive values. Most scores demonstrated low prognostic accuracy. The Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson criteria were studied most extensively. The median sensitivity and specificity of APACHE II at a threshold of 7 were 100% (range, 68% to 100%) and 63% (range, 21% to 96%), respectively, and those of the Ranson criteria at a threshold of 2 were 90% (range, 0% to 100%) and 67% (range, 14% to 97%), respectively. Estimates of sensitivity were based on relatively few patients. Evidence was limited regarding the incremental predictive value of the scoring systems or their effect on patient outcomes. LIMITATION: Substantial clinical heterogeneity and inadequate methodological and reporting quality precluded a meta-analysis. CONCLUSION: The test characteristics and clinical utility of AP severity scores remain uncertain. Additional studies with improved methodological rigor are needed, and the development of new scoring systems may be justified. PRIMARY FUNDING SOURCE: Global Scholarship Programme for Research Excellence for 2014 to 2015, The Chinese University of Hong Kong.

Methotrexate in patients with primary biliary cirrhosis who respond incompletely to treatment with ursodeoxycholic acid.

BACKGROUND: Approximately 35% of PBC patients have progressive disease despite treatment with UDCA. AIMS: We offered treatment with methotrexate and colchicine to PBC patients who had not responded fully to UDCA, after at least 1 year of treatment. METHODS: A total of 91 PBC patients failed to respond adequately to UDCA, defined as patients whose liver biopsies showed persistent interface hepatitis and whose serum alkaline phosphatase levels remained more than 50% above normal after at least 12 months on UDCA. We added colchicine (0.6 mg orally twice daily) for 6 months. If there was no decrease in alkaline phosphatase, methotrexate (0.25 mg/kg lean body weight orally per week) was added. Liver biopsies were performed at least three times: at diagnosis, after a patient had been on UDCA for at least 1 year (mean 3.4 years), and after a patient had been on methotrexate for at least 6 months (mean 2.2 years). A fourth liver biopsy was performed in 51 patients after they had been on methotrexate for at least another year (mean 3.5 years). RESULTS: From the time that methotrexate was begun until the final visit, there were significant decreases in the mean levels of alkaline phosphatase, 323 to 151, ALT, 73 to 39, fibrosis, 2.5 to 2.0, and inflammation scores, 2.0 to 1.0, (p < 0.0001 for all). Based on pre-specified definitions, 73 patients (80%) responded to methotrexate while 18 (20%) did not. CONCLUSIONS: In 91 PBC patients who responded incompletely to UDCA, colchicine and methotrexate significantly improved liver enzyme tests and liver histology.

Putting the puzzle together: epidemiological and clinical clues in the etiology of eosinophilic esophagitis.

The cause of eosinophilic esophagitis remains unknown, but its epidemiology and clinical features provide pieces to the puzzle. Eosinophilic esophagitis probably emerged in the 1950s or early 1960s, has an increasing incidence, occurs in most developed countries, is related to food allergies, affects adults and children, has a strong male predominance, clusters in families, and is commonly associated with other allergic and atopic disorders. Several theories have been proposed to explain its evolution, but none has been convincingly demonstrated.

Quality incentive payment systems: promise and problems.

Public and corporate pressure to improve the quality of healthcare in the United States has never been greater. Rising costs, recent discouraging appraisals of patient safety, accelerating malpractice litigation, and an increasing burden of chronic disease have intensified the demand for a change in current policies. Central to these efforts are payers who are increasingly creating financial incentives for providers to deliver high-quality healthcare. It is hoped that these programs (sometimes referred to as "quality incentive payment systems") will stimulate the adoption of systems that will reduce variability and assure that high-quality care is being delivered. Whether these programs will achieve their objectives remains to be determined. There are many unanswered questions about their effectiveness.

A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results.

Primary biliary cirrhosis frequently progresses despite treatment with ursodeoxycholic acid (UDCA), the only approved therapy. Previous studies suggested that colchicine and methotrexate may improve biochemical tests of liver function, symptoms, and liver histology. The aim of the present study was to determine if the addition of colchicine or methotrexate to UDCA would improve survival free of liver transplantation. Eighty-five patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase levels were at least twice the normal level and who were not yet candidates for liver transplantation were randomly assigned to receive colchicine or methotrexate in a double-blind study. UDCA was administered to all patients after 2 years. The primary end point was survival free of liver transplantation. Patients were followed up for a total of up to 10 years or until treatment failure. Data were analyzed on an intention-to-treat basis. Transplant-free survival was similar in both groups: 0.57 for colchicine plus UDCA and 0.44 for methotrexate plus UDCA, results that are similar to those predicted by the Mayo prognostic model. Significant improvement in liver biochemical tests and liver histology was observed in a subset of patients in both treatment groups who remained in the study for all 10 years. In conclusion, neither colchcine plus UDCA nor methotrexate plus UDCA improved survival beyond that predicted by the Mayo prognostic model. However, clinical, histologic, and biochemical improvement observed among those who remained in the study for 10 years suggests a possible benefit of these drugs in a subset of patients.

Development and prospective validation of a model for predicting weaning in chronic ventilator dependent patients.

BACKGROUND: Approximately ten percent of patients placed on mechanical ventilation during acute illness will require long-term ventilator support. Unfortunately, despite rehabilitation, some will never be liberated from the ventilator. A method of predicting weaning outcomes for these patients could help conserve resources and minimize frustrating failed weaning attempts for this population. The objective of this investigation was to identify predictors of weaning outcome for patients admitted to a chronic ventilator unit (CVU). METHODS: This was a retrospective analysis with prospective validation. The study setting was a 25 bed CVU within a rehabilitation hospital. The training group consisted of 43 patients referred to our facility for weaning after > 3 weeks of mechanical ventilation. A multivariate model to predict weaning outcome was constructed in this group and applied to a prospective group of 31 patients followed during an 18-month period. RESULTS: A modified Glasgow Coma Scale (GCS) and the presence of sustained spontaneous respirations (SSR), defined as the presence of 2 breaths recorded above the ventilator settings on four occasions, were highly predictive of weaning success within six months of CVU admission. Patients with a modified GCS > or = 8 were 6.5 times more likely to wean than those with a modified GCS < 8 (95% confidence interval 1.6-26.3) and those with SSR were 25.5 times more likely to wean than those without SSR (95% confidence interval 4.3-51.9). CONCLUSIONS: In our population of CVU patients, simple parameters that were available on admission and did not directly reflect cardiopulmonary function were useful predictors of weaning outcome.

Short-term treatment of gastroesophageal reflux disease.

OBJECTIVE: To investigate the efficacy of acid suppressant drugs in the empirical treatment of gastroesophageal reflux disease (GERD) and in the treatment of endoscopy-negative reflux disease (ENRD). DESIGN: medline, embase, and the Cochrane Controlled Trials Register were searched. Bibliographies were reviewed. SETTING: Studies were eligible that compared the short-term use of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) with each other or with placebo in adults with GERD who were enrolled irrespective of endoscopic findings (empirical cases) or in whom endoscopy showed no signs of esophagitis (endoscopy-negative cases). MEASUREMENTS: Of 1,408 studies, only 13 could be included for meta-analysis. Data on 3,433 patients empirically treated for GERD and 2,520 patients treated for ENRD were extracted. The primary endpoint was relief of heartburn. MAIN RESULTS: In the empirical treatment of GERD, the summary relative risk (sRR) for symptom relief from H2RAs versus placebo was 0.77 (95% confidence interval [95% CI], 0.60 to 0.99). RR in the only placebo-controlled PPI trial was 0.35 (95% CI, 0.26 to 0.46). The sRR for standard dose PPIs versus H2RAs was 0.55 (95% CI, 0.44 to 0.68). In treatment of ENRD, both PPIs (sRR, 0.64; 95% CI, 0.52 to 0.79) and H2RAs (sRR, 0.78; 95% CI, 0.62 to 0.97) were superior to placebo, and PPIs were superior to H2RAs (sRR, 0.81; 95% CI, 0.70 to 0.95). CONCLUSIONS: Acid suppressant therapy (with a PPI or an H2RA) is more effective than placebo for short-term relief of heartburn in patients with persistent symptoms who are treated empirically for GERD and in those in whom esophagitis was excluded after endoscopy. The benefit of PPIs compared with H2RAs is more pronounced in patients treated empirically.

Correlation of quality measures with estimates of treatment effect in meta-analyses of randomized controlled trials.

CONTEXT: Specific features of trial quality may be associated with exaggeration or shrinking of the observed treatment effect in randomized studies. Therefore, assessment of trial quality is often used in meta-analysis. However, the degree to which specific quality measures are associated with treatment effects has not been well established across a broad range of clinical areas. OBJECTIVE: To determine if quality measures are associated with treatment effect size in randomized controlled trials (RCTs). DESIGN: Quality measures from published quality assessment scales were evaluated in RCTs included in meta-analyses from 4 medical areas (cardiovascular disease, infectious disease, pediatrics, and surgery). Included meta-analyses incorporated at least 6 RCTs, examined dichotomous outcomes, and demonstrated significant between-study heterogeneity in the odds ratio (OR) scale. MAIN OUTCOME MEASURES: Relative ORs comparing overall treatment effect (summary OR) of high vs low-quality studies, as determined by each quality measure, with relative ORs less than 1 indicating larger treatment effect in low-quality studies. RESULTS: Twenty-four quality measures were analyzed for 276 RCTs from 26 meta-analyses. Relative ORs of high vs low-quality studies for these quality measures ranged from 0.83 to 1.26; none was statistically significantly associated with treatment effect. The proportion of studies fulfilling specific quality measures varied widely in the 4 medical areas. In analyses limited to specific medical areas, placebo control, multicenter studies, study country, caregiver blinding, and statistical methods were significantly associated with treatment effect on 7 occasions. These relative ORs ranged from 0.40 to 1.74. However, the directions of these associations were not consistent. CONCLUSIONS: Individual quality measures are not reliably associated with the strength of treatment effect across studies and medical areas. Although use of specific quality measures may be appropriate in specific well-defined areas in which there is pertinent evidence, findings of associations with treatment effect cannot be generalized to all clinical areas or meta-analyses.