Summaries

The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH): a systematic review.

NAFLD global prevalence is 30% and increasing which requires urgent and comprehensive strategies to raise awareness and address al aspects of NAFLD on local, regional, and global levels.

Pubmed Journal ReadQx

1. What is the overall global prevalence of NAFLD?

• The overall global prevalence of NAFLD is 30.1% across the entire study period (1990-2019).

2. Has the prevalence of NAFLD increased over time?

• Yes, the trend analysis showed NAFLD prevalence has increased from 25.3% (1990-2006) to 38.2% (2016-2019).

3. What are the regional NAFLD prevalence rates?

• The highest NAFLD prevalence rate was observed in Latin America (44.4%), followed by North Africa and Middle East (MENA) (36.5%), South Asia (33.8%), South-East Asia (33.1%), North America (31.2%), East Asia (29.7%), Asia Pacific (28.0%), and Western Europe (25.1%).

4. How do these findings differ from another meta-analysis?

• The findings differ from another meta-analysis which provided prevalence data only for four regions [Africa 56.8%, North America 47.8%, Europe 32.6% and Asia 31.6%]. The differences could be explained by the methodologic differences and lack of control for important biases.

5. How do age and obesity affect the NAFLD prevalence?

• Age and obesity are highly associated with NAFLD prevalence.

6. How was the potential for over-coverage bias addressed in the meta-analysis?

• The potential for over-coverage bias was addressed by making adjustments using the country-specific population size to estimate population size-adjusted global prevalence and strictly applying the exclusion criteria.

7. How did the researchers estimate the incidence and mortality rates for NAFLD?

• The researchers estimated the incidence and mortality rates for NAFLD by determining the global and regional prevalence rates for NAFLD, and then performing adjustments to overcome biases that are inherent in the administrative and annual medical check-up datasets.

8. What is the pooled mortality rate for NAFLD?

• The pooled mortality rate for NAFLD was 12.60 per 1,000 PY for all-cause mortality, 4.20 per 1,000 PY for cardiac-specific mortality, 2.83 per 1,000 PY for extra-hepatic cancer-specific mortality, and 0.92 per 1,000 PY for liver-specific mortality.

9. How did the researchers adjust for selection bias in the study?

• The researchers adjusted for selection bias by using population all-cause mortality data and then creating proportionate cause-specific death rates.

10. How does the study align with the Global Burden of Disease (GBD) regional classification system?

• The study aligns with the GBD regional classification system by providing more detail to the regional prevalence rates for NAFLD.

11. Is there a significant increase in the incidence of NAFLD over time?

• Yes, the estimates suggest a 58.0% increase in the incidence of NAFLD from 1994-2006 to 2010-2014.

12. Does the study show a significant increase in the incidence of NAFLD in specific age groups?

• The study shows numerical increases in age groups of <40 and >50 but none of these differences were statistically significant.

13. How were the pooled mortality rates for NAFLD calculated?

• The pooled mortality rates for NAFLD were calculated by taking into account the all-cause mortality, cardiac-specific mortality, extra-hepatic cancer-specific mortality, and liver-specific mortality.

14. What is the potential impact of selection bias on the mortality rates for NAFLD?

• Selection bias could potentially lead to a higher mortality rate for NAFLD subjects with a liver biopsy, as they may suffer from more severe disease.

15. How was the potential for bias in administrative and annual medical check-up datasets addressed in the study?

• The potential for bias in administrative and annual medical check-up datasets was addressed by performing adjustments and using population all-cause mortality data to create proportionate cause-specific death rates.

Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH.

Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Pubmed Journal ReadQx

1. What was the hypothesis of the study?

• The hypothesis was that the HMII-pH technique would be capable of diagnosing PAR episodes with good interobserver reproducibility.

2. What criteria were used to identify candidate PAR episodes?

• The criteria used were a rapid pharyngeal pH decrease of at least 2 units, reaching a nadir pH of less than 5 within 30 seconds during esophageal acidification.

3. What percentage of candidate PAR episodes were HMII-pH-proven PAR episodes?

• 80.0% (71.0-87.0%) of candidate PAR episodes were HMII-pH-proven PAR episodes.

4. Was there good interobserver reproducibility of the HMII-pH technique?

• Yes, there was good interobserver reproducibility of the HMII-pH technique based on the proposed criteria.

5. Were equipment-related or swallow-induced episodes found to be HMII-pH-proven PAR episodes?

• No, none of the equipment-related or swallow-induced episodes were found to be HMII-pH-proven PAR episodes.

6. How do the study's findings of PAR episodes in healthy controls compare to previous studies?

• The study's findings of rare PAR episodes in healthy controls are in line with those reported by Hoppo et al but were lower than that by Zerbib et al.

7. What factors contribute to inconsistent results among studies of PAR episodes?

• Factors contributing to inconsistent results among studies include pharyngeal pH sensor locations, number of impedance sensors in the pharynx, definition of pharyngeal reflux (acid or nonacid, gaseous, or liquid), artifacts, and poor interobserver reproducibility.

8. What is the feasibility of HMII-pH tracing in differentiating refluxes from swallows?

• The high concordance of 95.4% (83/87) for interpreting retrograde pharyngeal impedance changes between observers in the study suggests the feasibility of HMII-pH tracing in differentiating refluxes from swallows.

9. How could artificial intelligence be applied to facilitate the interpretation of PAR episodes?

• Artificial intelligence could be applied to facilitate the interpretation of PAR episodes based on the findings of the current study.

10. What limitations does the study have?

• The study has limitations such as not considering pharyngeal refluxate with pH above 5, esophageal refluxate with pH above 4, and pure gas refluxes, which may have underestimated pharyngeal reflux episodes, small sample size of the study resulting in lower precision and not considering pure gas refluxes.

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**Beta-blockers in the era of precision medicine in patients with cirrhosis.**

Lifestyle factors for the prevention of inflammatory bowel disease .

Across six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification.

Pubmed Journal ReadQx

1. What is the focus of the study described in the text?

• The study focuses on the contribution of modifiable lifestyle and dietary factors to the risk of Crohn's disease (CD) and ulcerative colitis (UC).

2. How many cases of CD and UC could have been prevented by adhering to low-risk modifiable lifestyle factors in the US cohorts?

• 43% of CD cases and 44% of UC cases could have been prevented by adhering to low-risk modifiable lifestyle factors in the US cohorts.

3. How many CD and UC cases could have been prevented by adherence to American healthy lifestyle recommendations in the US cohorts?

• 61% of CD cases and 42% of UC cases could have been prevented by adherence to American healthy lifestyle recommendations in the US cohorts.

4. What proportion of CD and UC cases could be attributed to family history in the primary cohorts?

• Family history accounted for a modest population-attributable risk (PAR) of 12% for CD and 9% for UC in the primary cohorts.

5. What proportion of IBD cases has been attributed to lifestyle factors in previous studies?

• In an Italian cohort, smoking, oral contraceptive use and lack of breastfeeding accounted for roughly 30% of the attributable risk for IBD, while in a study by Brant et al, current tobacco use conferred a 47% attributable risk for CD.

6. How do the estimates of the contribution of modifiable lifestyle and dietary factors to the risk of CD and UC in this study compare to those published for other immune-mediated diseases?

• The estimates of the contribution of modifiable lifestyle and dietary factors to the risk of CD and UC in this study are similar to those published for other immune-mediated diseases such as rheumatoid arthritis (RA) and psoriasis.

7. What is the key assumption of the findings in this study?

• The key assumption of the findings in this study is that the relationship between lifestyle factors and IBD development is causal.

8. What lines of evidence support the role of environmental and lifestyle factors in the development of IBD?

• Lines of evidence supporting the role of environmental and lifestyle factors in the development of IBD include the low contribution of genetic factors to the variance of IBD, the high incidence of IBD in industrialised societies and the sharp rise of IBD in developing countries, the increased risk of IBD in second-generation immigrants, and the link between the dietary and lifestyle factors considered in the study and systemic inflammation, microbial dysbiosis and gut permeability.

9. What strategies have been applied in other immune-mediated diseases for primary prevention?

• Strategies for primary prevention in other immune-mediated diseases have included dietary and lifestyle modifications, as well as vaccination and pharmacological therapies.

10. What are the implications of the findings of this study for IBD prevention?

• The findings of this study suggest that adherence to an overall healthy lifestyle may prevent a modest proportion of cases of CD and UC, and that current guidelines for healthy living, which are primarily recommended to reduce cardiovascular disease (CVD) risk, may have additional benefits for the prevention of other immune-mediated diseases such as IBD.

Meta-analysis: Use of proton pump inhibitors and risk of gastric cancer in patients requiring gastric acid suppression.

1. What is the purpose of this systematic review with meta-analysis? The purpose of this systematic review with meta-analysis was to investigate the association between proton pump inhibitors (PPIs) and the risk of gastric cancer.

2. What were the main findings of this study? The main findings of this study were that there was no statistical evidence of an association between PPIs and gastric cancer when considering studies that addressed confounding in a comprehensive manner. The certainty in the summary effect estimate was low.

3. Why did the authors focus on studies using H2 receptor agonists (H2RAs) as the comparator group? The authors focused on studies using H2RAs as the comparator group because they may be at similar risk of developing gastric cancer with respect to those exposed to PPIs. This choice was motivated by epidemiological considerations, as exposure to PPIs may be associated with several known and unknown prognostic factors for gastric cancer, making it difficult to comprehensively handle confounding when using unexposed individuals as the comparator group.

4. What were the limitations of this study? The limitations of this study included the fact that the evidence was of low certainty, as non-randomized studies are prone to residual and unmeasured confounding. Additionally, the rarity of the event made it difficult to perform exceptionally large and lengthy randomized trials that would be needed to provide reliable estimates.

5. What are the implications of these findings for clinical practice? These findings suggest that PPIs may result in trivial to no difference in the risk of gastric cancer. However, due to the low certainty of the evidence, further research is needed to confirm these findings.

Efficacy and Safety of Drugs for Gastroparesis: Systematic Review and Network Meta-analysis.

In a network meta-analysis, oral dopamine antagonists and tachkinin-1 antagonists were more efficacious than placebo for gastroparesis, but confidence in the evidence was low to moderate for most comparisons. There is an unmet need for efficacious therapies for gastroparesis.

Pubmed Journal ReadQx

1. What is the focus of the systematic review and network meta-analysis described in the text?

   • The focus of the analysis is drugs used to treat gastroparesis.

2. How many RCTs and patients were included in the analysis?

   • The analysis included data from 29 RCTs containing almost 4000 patients.

3. What drugs were found to be significantly more effective than placebo in improving global gastroparesis symptoms?

   • Clebopride and domperidone were found to be significantly more effective than placebo in improving global gastroparesis symptoms.

4. Which drug classes were found to be superior to placebo in the analysis by drug class?

   • Oral dopamine antagonists and tachykinin-1 antagonists were found to be superior to placebo in the analysis by drug class.

5. Which drugs were found to be the most effective for individual symptoms of gastroparesis?

   • Oral metoclopramide was found to be the most effective for nausea, fullness, and bloating, based on only one small trial. Tradipitant and TZP-102 were more effective than placebo for nausea and TZP-102 was superior to placebo for fullness. None of the drugs studied were more effective than placebo for vomiting or abdominal pain.

6. What was the primary endpoint of interest in the analysis?

   • The primary endpoint of interest was global gastroparesis symptoms.

7. How was heterogeneity between studies evaluated in the analysis?

   • Heterogeneity between studies was evaluated by examining the level of confidence in most comparisons across the network.

8. Were any drugs found to be more effective than placebo in patients with diabetic gastroparesis?

   • No drugs were found to be more effective than placebo in patients with diabetic gastroparesis.

9. Which drug was found to be the least likely to be associated with adverse events or withdrawals?

   • Camicinal was the drug found to be the least likely to be associated with adverse events or withdrawals.

10. Which drug was found to be significantly more likely to be associated with adverse events than placebo?

    • Prucalopride was found to be significantly more likely to be associated with adverse events than placebo.

6. Was there evidence of publication bias or other small study effects in the primary analysis?

   • There was no evidence of publication bias or other small study effects in the primary analysis.

7. How was the assumption of transitivity addressed in the analysis?

   • The assumption of transitivity, which refers to the idea that indirect comparisons between drugs assume that any patient included in the network could have been recruited to any of the trials and assigned to any of the drugs, was addressed by considering factors such as differences in patient population, criteria for response, and method of diagnosis of gastroparesis that could affect transitivity.

8. How was the intention-to-treat analysis conducted in the study?

   • The intention-to-treat analysis in the study assumed that all dropouts were treatment failures.

9. What statistical model was used in the analysis?

   • A random effects model was used in the analysis in order to avoid overestimating the efficacy of therapies.

10. How was the literature search conducted for the systematic review?

• The literature search for the systematic review was conducted rigorously and reproducibly, with the eligibility judging and data extraction performed independently by two investigators. The search also included clinicaltrials.gov for unpublished RCTs and contact with trial authors to obtain supplementary data, and imputed dichotomous responder data to maximize the number of eligible studies.