Impact of Gender on Gastroesophageal Reflux Disease Complications: Analysis of 27 Million Hospitalizations.

BACKGROUND AND AIMS: Previous studies have reported gender differences in patients with gastroesophageal reflux disease (GERD). These studies have also reported differences based on gender in the rates of complications. In this study, we aim to identify gender disparities in the rates of GERD complications in the United States. METHODS: We queried the 2016-2020 National Inpatient Sample database to identify patients with GERD. Patients with eosinophilic esophagitis or missing demographics were excluded. We compared patient demographics, comorbidities and complications based on gender. Multivariate logistic regression analysis was used to identify the impact of gender on complications of GERD. RESULTS: 27.2 million patients were included in the analysis. Out of them, 58.4% of the hospitalized patients with GERD were female. Majority of the women were White (75%), aged>65 years (57.5%) and were in the Medicare group (64%). After adjusting for confounders, females were noted to have lower odds of esophagitis (aOR=0.85, 95%CI: 0.84-0.86, p<0.001), esophageal stricture (aOR=0.95, 95%CI: 0.93-0.97, p<0.001), Barrett's esophagus (aOR=0.58, 95%CI: 0.57-0.59, p<0.001) and esophageal cancer (aOR=0.22, 95%CI: 0.21-0.23, p<0.001). CONCLUSIONS: Our study confirms the findings of previous literature that females, despite comprising the majority of the study population, had a lower incidence of GERD related complications. Further studies identifying the underlying reason for these differences are required.

Prescribing trends of proton pump inhibitors and histamine blockers among children in the United Kingdom (1998-2019): A population-based assessment.

PURPOSE: To describe the prescribing trends of proton pump inhibitors (PPIs) and H2 receptor antagonists (H2 RAs) among children with gastroesophageal reflux in the United Kingdom between 1998 and 2019. METHODS: We conducted a population-based retrospective cohort study using data from the Clinical Practice Research Datalink that included all children aged ≤18 years with a first ever diagnosis of gastroesophageal reflux between 1998 and 2019. Using negative binomial regression, we estimated crude and adjusted annual prescription rates per 1000 person-years and corresponding 95% confidence intervals (CIs) for PPIs and H2 RAs. We also assessed rate ratios of PPIs and H2 RAs prescription rates to examine changes in prescribing over time. RESULTS: Our cohort included 177 477 children with a first ever diagnosis of gastroesophageal reflux during the study period. The median age was 13 years (IQR: 1, 17) among children prescribed PPIs and 0.2 years (IQR: 0.1, 0.6) among those prescribed H2 RAs. The total prescription rate of all GERD drugs was 1468 prescriptions per 1000 person-years (PYs) (95% CI 1463-1472). Overall, PPIs had a higher prescription rate (815 per 1000 PYs, 95% CI 812-818) than H2 RAs (653 per 1000 PYs 95% CI 650-655). Sex- and age-adjusted rate ratios of 2019 versus 1998 demonstrated a 10% increase and a 76% decrease in the prescription rates of PPIs and H2 RAs, respectively. CONCLUSIONS: Prescription rates for PPIs increased, especially during the first half of the study period, while prescription rates for H2 RA decreased over time.

Assessment of Gastroesophageal Reflux Symptoms and Sleep Quality Among Women in the Nurses' Health Study II.

Importance: Limited data exist on the association of gastroesophageal reflux (GER) symptoms with sleep quality. Objective: To prospectively investigate the association between GER symptoms and sleep quality. Design, Setting, and Participants: This prospective cohort study included data from the Nurses' Health Study II of female nurses in the US. Participants self-reported the frequency and duration of GER symptoms beginning June 2005, with updates every 4 years through June 2015. Follow-up was completed June 2019, and data were analyzed from November 15, 2022, to June 4, 2023. Exposures: Frequency and duration of GER symptoms. Main Outcomes and Measures: Poor sleep quality was assessed in 2017 through a modified Pittsburgh Sleep Quality Index, which included difficulty in falling asleep, restlessness of sleep, daytime sleepiness, sleep disturbance, and sleep duration. Relative risk (RR) for poor sleep quality and individual components of poor sleep quality was estimated according to the frequency and duration of GER symptoms. Results: Among 48 536 women (median age, 59 years [range, 48-69 years]), 7929 (16.3%) developed poor sleep quality during 4 years of follow-up. Compared with those with GER symptoms less than once a month, the multivariable RR for poor sleep quality among women with GER symptoms more than once a week was 1.53 (95% CI, 1.45-1.62). Women who had GER symptoms once or more a week for more than 7 years had an RR of 1.36 (95% CI, 1.30-1.43) compared with women who had not had GER symptoms once or more a week. The frequency and duration of GER symptoms were significantly associated with each individual component of poor sleep quality; for example, the multivariable RRs for GER symptoms 2 or more times per week compared with no GER symptoms were 1.49 (95% CI, 1.39-1.58) for difficulty in falling asleep, 1.47 (95% CI, 1.39-1.56) for excessive daytime sleepiness, and 1.44 (95% CI, 1.36-1.53) for restlessness of sleep. Conclusions and Relevance: In this prospective cohort study of female nurses in the Nurses' Health Study II, the frequency and duration of GER symptoms were associated with subsequent risk of poor sleep quality. The findings suggest that effective treatment of GER disease may be important not only for improvement of symptoms but also for the reduction of comorbidities associated with poor sleep quality.

Burden of gastroesophageal reflux disease in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of disease study 2019.

INTRODUCTION: For effective preventive strategies against GORD (gastro-esophageal reflux disease), we assessed the GORD burden from 1990 to 2019. METHODS: The burden of GORD between 1990 and 2019 was evaluated globally, regionally, and nationally. Using ASIR (age-standardized incidence), ASYLDs (age-standardized years lived with disabilitys), we compared them to the GBD world population per 100,000. The estimates were based on 95% uncertainty intervals (UIs). The AAPC (average annual percent change) in incidence, YLDs, along with prevalence rates with associated 95% CIs were estimated. RESULTS: Data to estimate the burden of GORD are scarce till now. The global ASIR of GORD in 2019 was 3792.79 per 100,000, an increase AAPC of 0.112% from 1990. The prevalence of GORD increased with a AAPC of 0.096% to 9574.45 per 100,000. Global ASYLDs in 2019 was 73.63, an increase AAPC of 0.105% from 1990. The GORD burden varies greatly depending on the development level and geographical location. USA demonstrated the most obvious decreasing trend in burden of GORD, while Sweden had an increasing trend. That the increase in GORD YLDs was mediated primarily by the growth and aging of population, was revealed by decomposition analyses. There was an inverse relationship between SDI (socio-demographic index) and GORD-burden. Frontier analyses revealed significant scope of improvement in the status of development at all levels. CONCLUSION: GORD is a public health challenge, especially in Latin America. Some SDI quintiles had declining rates, while some countries experienced increased rates. Thus, resources should be allocated for preventative measures based on country-specific estimates.

GERD after Peroral Endoscopic Myotomy: Assessment of Incidence and Predisposing Factors.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an effective intervention for achalasia, but GERD is a major postoperative adverse event. This study aimed to characterize post-POEM GERD and identify preoperative or technical factors impacting development or severity of GERD. STUDY DESIGN: This is a retrospective review of patients who underwent POEM at our institution. Favorable outcome was defined as postoperative Eckardt score of 3 or less. Subjective GERD was defined as symptoms consistent with reflux. Objective GERD was based on a DeMeester score greater than 14.7 or Los Angeles grade C or D esophagitis. Severe GERD was defined as a DeMeester score greater than 50.0 or Los Angeles grade D esophagitis Preoperative clinical and objective data and technical surgical elements were compared between those with and without GERD. Multivariate logistic analysis was performed to identify factors associated with each GERD definition. RESULTS: A total of 183 patients underwent POEM. At a mean ± SD follow-up of 21.7 ± 20.7 months, 93.4% achieved favorable outcome. Subjective, objective, and severe objective GERD were found in 38.8%, 50.5%, and 19.2% of patients, respectively. Of those with objective GERD, 24.0% had no reflux symptoms. Women were more likely to report GERD symptoms (p = 0.007), but objective GERD rates were similar between sexes (p = 0.606). The independent predictors for objective GERD were normal preoperative diameter of esophagus (odds ratio [OR] 3.4; p = 0.008) and lower esophageal sphincter (LES) pressure less than 45 mmHg (OR 1.86; p = 0.027). The independent predictors for severe objective GERD were LES pressure less than 45 mmHg (OR 6.57; p = 0.007) and obesity (OR 5.03; p = 0.005). The length of esophageal or gastric myotomy or indication of procedure had no impact on the incidence or severity of GERD. CONCLUSION: The rate of pathologic GERD after POEM is higher than symptomatic GERD. A nonhypertensive preoperative LES is a predictor for post-POEM GERD. No modifiable factors impact GERD after POEM.

Prevalence, Predictors, and Management of Gastroesophageal Reflux Disease After Laparoscopic Sleeve Gastrectomy: a Multicenter Cohort Study.

BACKGROUND: One of the most popular bariatric procedures is laparoscopic sleeve gastrectomy (LSG), which can either cause or worsen gastroesophageal reflux disease (GERD). Therefore, the goal of this study was to examine the prevalence, predictors, and management of GERD symptoms after LSG. MATERIALS AND METHODS: From January 2017 to January 2022, we looked at patients who had a primary LSG and developed GERD. Before LSG, all patients underwent a barium meal and upper endoscopy. After LSG, barium meal, endoscopy, esophageal manometry, and 24-h pH measurements were performed for selected patients. The diagnosis of GERD is based on the GERD-HRQL questionnaire and upper endoscopy. RESULTS: The study included 1537 patients (62.5% women and 37.5% men) with a mean age of 34.4 years. The mean % TWL was 40.7% during a mean follow-up period of 15.9 months. A total of 379 patients (24.7%) experienced postoperative GERD, of whom 328 (21.3%) had postoperative de novo GERD symptoms, 25 (1.6%) had worsened preoperative GERD, and 26 (1.7%) had the same preoperative GERD symptoms. Antral preservation and gastropexy were protective factors against the development of GERD after LSG. LSG was converted to LRYGB in 15.8% of the patients with GERD. The response to medical treatment was observed in 300 (79.2%) patients with GERD. CONCLUSION: Post-LSG GERD presented in 379 patients (24.7%). Antral preservation and gastropexy were protective factors for the development of postoperative GERD after LSG. Medical treatment was the main line of treatment for GERD. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05416645.

Global, regional and national burden of gastroesophageal reflux disease, 1990-2019: update from the GBD 2019 study.

BACKGROUND: Because trends in the epidemiology and burden of gastroesophageal reflux disease (GERD) are changing, reinvestigating the geographical differences and trend changes is essential. Here we evaluated the latest epidemiologic patterns and trends for GERD, using data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: Annual case numbers, age-standardized rates of prevalence, incidence, and years of life lived with disability (YLDs), and their estimated annual percentage changes (EAPCs) for GERD between 1990 and 2019 were derived from the GBD 2019 study. Association between GERD burden and socio-demographic index (SDI) was also investigated. RESULTS: In 2019, there were 783.95 million cases of GERD globally. Between 1990 and 2019, the total number of prevalent cases, incident cases, and YLDs increased by 77.53%, 74.79%, and 77.19%, respectively. The global age-standardized incidence rate (ASIR) and age-standardized YLD rate (ASYR) increased during this period (EAPC = 0.06 and 0.05, respectively). Tropical Latin America and East Asia had the highest and lowest age-standardiZed prevalence rate (ASPR), ASIR, and ASYR in 2019, respectively. From 1990 to 2019, prevalent cases, incident cases, YLDs, and their corresponding age-standardized rates of GERD were higher in females than males in all years. Higher SDI was associated with lower ASPR, ASIR, and ASYR of GERD in 2019. CONCLUSIONS: GERD will continue to be a major public health burden due to increasing numbers of prevalent cases, incident cases, and YLDs. In order to tackle this troublesome disease, it is crucial to understand the changes in both global and regional trends in epidemiology and the burden for policymakers and other stakeholders. Key messagesThis is the most updated estimate on GERD epidemiology globally, including 204 countries, some of which were not assessed before.The overall burden of GERD continued to worsen with the prevalent cases increasing by 77.53% from 441.57 million in 1990 to 783.95 million in 2019.GERD is likely to remain a common reason for consultation in primary care, and our data may allow for health service provision planning.

Quality of life assessment before and after laparoscopic sleeve gastrectomy: a prospective study.

OBJECTIVE: Obesity has a negative effect on the quality of life (QoL), and therefore, the goal of bariatric surgery is not only to decrease excess weight but also to improve QoL and obesity-related comorbidities. Laparoscopic sleeve gastrectomy (LSG) has become the most commonly applied bariatric procedure worldwide, although there is a lack of prospective data on QoL in patients undergoing this procedure. Therefore, this prospective study aimed to compare QoL of obese patients before, and one year after LSG, and also to analyze the weight loss process and resolution of obesity-related comorbidities. PATIENTS AND METHODS: Patients undergoing LSG between January 2019 and December 2019 were included. They completed the Bariatric Quality of Life index (BQL) before surgery and one year after. Anthropometric data and obesity-related comorbidities were recorded. RESULTS: Thirty-eight patients were included in the study. The mean age was 37.9 ± 11.2 years, and the majority were women (68.4%). One year after the surgery, the mean body mass index (BMI) decreased from 45.5 ± 8.2 kg/m2 to 29.3 ± 6.1 kg/m2 (p<0.0001), and the mean percentage excess weight loss (%EWL) was 85.1 ± 22.3%. The preoperative total score of BQL was 46.05 ± 7.01 points and postoperatively it increased to 66.52 ± 5.53 points (p<0.0001). BQL total score and %EWL was positively and significantly correlated (r=0.479, p=0.002). Postoperatively, all obesity-related comorbidities were improved, although de novo gastroesophageal reflux disease (GERD) appeared in 7.8% of the cases. CONCLUSIONS: LSG improves QoL and allows resolution of obesity-related comorbidities, but a small proportion of patients may develop troublesome GERD postoperatively.

Clusters of comorbidities in idiopathic pulmonary fibrosis.

INTRODUCTION: Comorbidities are common in patients with idiopathic pulmonary fibrosis (IPF) and negatively impact health-related quality of life, health-care costs and mortality. Retrospective studies have focused on individual comorbidities, but clusters of multiple comorbidities have rarely been analysed. This study aimed to comprehensively and prospectively assess comorbidities in a multicentre, real-world cohort of patients with IPF, including prespecified conditions of special interest and to analyse clusters of comorbidities and examine characteristics, disease course and mortality of the clusters. METHODS: Several measurements, questionnaires, medications and medical history were combined to assess comorbidities. Using self-organizing maps, clusters of comorbidities were identified and phenotypes characterized. Disease course was assessed using mixed effects models and mortality using Cox regression. RESULTS: One-hundred and fifty IPF patients were included prospectively. All except one patient suffered from at least one comorbidity and multimorbidity was common. Arterial hypertension, gastro-oesophageal reflux disease, hypercholesterolemia, emphysema and obstructive sleep apnea were most prevalent. Four comorbidity clusters were identified. Each cluster had distinct comorbidity profiles, patient characteristics, symptom burden and disease severity. Patients with fewer comorbidities had better exercise capacity and less dyspnea at baseline, but a trend towards faster deterioration was observed. Mortality analyses showed no significant differences between clusters. CONCLUSIONS: Multimorbidity is prevalent in patients with IPF. Four specific clusters of comorbidities may represent phenotypes in IPF. A trend towards faster decline in exercise capacity and dyspnea was observed in patients with fewer comorbidities. Increased knowledge of comorbidities facilitates prevention and treatment of comorbidities in patients with IPF.

Peroral endoscopic myotomy: 10-year outcomes from a large, single-center U.S. series with high follow-up completion and comprehensive analysis of long-term efficacy, safety, objective GERD, and endoscopic functional luminal assessment.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is becoming the treatment of choice for achalasia. Data beyond 3 years are emerging but are limited. We herein report our 10-year experience, focusing on long-term efficacy and safety including the prevalence, management, and sequelae of postoperative reflux. METHODS: This was a single-center prospective cohort study. RESULTS: Six hundred ten consecutive patients received POEM from October 2009 to October 2019, 160 for type 1 achalasia (26.2%), 307 for type II (50.3%), 93 for type III (15.6%), 25 for untyped achalasia (4.1%), and 23 for nonachalasia disorders (3.8%). Two hundred ninety-two patients (47.9%) had prior treatment(s). There was no aborted POEM. Median operation time was 54 minutes. Accidental mucosotomies occurred in 64 patients (10.5%) and clinically significant adverse events in 21 patients (3.4%). No adverse events led to death, surgery, interventional radiology interventions/drains, or altered functional status. At a median follow-up of 30 months, 29 failures occurred, defined as postoperative Eckardt score >3 or need for additional treatment. The Kaplan-Meier clinical success estimates at years 1, 2, 3, 4, 5, 6, and 7 were 98%, 96%, 96%, 94%, 92%, 91%, and 91%, respectively. These are highly accurate estimates because only 13 patients (2%) were missing follow-up assessments. One hundred twenty-five patients (20.5%) had reflux symptoms more than once per week. At a median of 4 months, the pH study was completed in 406 patients (66.6%) and was positive in 232 (57.1%), and endoscopy was completed in 438 patients (71.8%) and showed reflux esophagitis in 218 (49.8%), mostly mild. CONCLUSIONS: POEM is exceptionally safe and highly effective on long-term follow-up, with >90% clinical success at ≥5 years.

Differential features of chronic cough according to etiology and the simple decision tree for predicting causes.

Finding etiology of chronic cough is an essential part of treatment. Although guidelines include many laboratory tests for diagnosis, these are not possible in many primary care centers. We aimed to identify the characteristics and the differences associated with its cause to develop a clinical prediction model. Adult subjects with chronic cough who completed both Korean version of the Leicester Cough Questionnaire (K-LCQ) and COugh Assessment Test (COAT) were enrolled. Clinical characteristics of each etiology were compared using features included in questionnaires. Decision tree models were built to classify the causes. A total of 246 subjects were included for analysis. Subjects with asthma including cough variant asthma (CVA) suffered from more severe cough in physical and psychological domains. Subjects with eosinophilic bronchitis (EB) presented less severe cough in physical domain. Those with gastro-esophageal reflux disease (GERD) displayed less severe cough in all 3 domains. In logistic regression, voice hoarseness was an independent feature of upper airway cough syndrome (UACS), whereas female sex, tiredness, and hypersensitivity to irritants were predictors of asthma/CVA; less hoarseness was a significant feature of EB, and feeling fed-up and hoarseness were less common characteristics of GERD. The decision tree was built to classify the causes and the accuracy was relatively high for both K-LCQ and COAT, except for UACS. Voice hoarseness, degree of tiredness, hypersensitivity to irritants and feeling fed-up are important features in determining the etiologies. The decision tree may further assists classifying the causes of chronic cough.

Estimate of Refractory Reflux Disease in the United States: Economic Burden and Associated Clinical Characteristics.

GOALS: To update the estimate of the prevalence of refractory gastroesophageal reflux disease (GERD) in the United States, and to assess the clinical and economic differences between patients with and without refractory GERD. BACKGROUND: GERD affects 18% to 28% of the US population, with nearly 40% of GERD patients presenting with refractory symptoms despite ongoing therapy. STUDY: Retrospective analysis of the IBM MarketScan databases between January 2011 and June 2018. Inclusion criteria were prescription fill and subsequent refill of a proton pump inhibitor or H2-receptor antagonist (earliest claim=index date), diagnosis of GERD 60 days preceding and/or following index, continuous insurance enrolment for 12 months preceding/following index, and absence of prior GERD diagnosis or GERD medication. We derived refractory GERD symptom scores for all patients on the basis of a previously published algorithm. Health care costs and comorbidities were assessed for all patients and compared between those with and without refractory GERD. RESULTS: In total, 399,017 GERD patients qualified for the study; 103,654 (26%) met our definition of having indications of refractory GERD symptoms. Patients with refractory GERD symptoms reported significantly higher rates of hiatal hernia (25.1% vs. 5.9%), esophagitis (37.3% vs. 11.8%), esophageal stricture (11.3% vs. 1.5%), and dysphagia (26.8% vs. 7.1%; P<0.01 for each). The refractory GERD symptoms cohort incurred ~$10,000 greater health care costs per patient per year compared with patients without refractory GERD symptoms ($26,057±$58,948 vs. $15,285±$39,307; P<0.01). CONCLUSIONS: Refractory GERD symptoms were associated with a substantial increase in health care costs. Treatments aimed at improving refractory GERD symptoms may mitigate symptom burden, potentially reducing health care expenditure.

Gastroesophageal reflux disease: A risk factor for laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma in the NIH-AARP Diet and Health Study cohort.

BACKGROUND: Prior studies have suggested that gastroesophageal reflux disease (GERD) may be associated with risk of squamous cancers of the larynx and esophagus; however, most of these studies have had methodological limitations or insufficient control for potential confounders. METHODS: We prospectively examined the association between GERD and esophageal adenocarcinoma (EADC), esophageal squamous cell carcinoma (ESCC), and laryngeal squamous cell carcinoma (LSCC) in 490,605 participants of the NIH-AARP Diet and Health Study cohort who were 50-71 years of age at baseline. Exposure to risk factors were obtained from the baseline questionnaire. GERD diagnosis was extracted among eligible participants via linkage to Medicare diagnoses codes and then multiply imputed for non-Medicare-eligible participants. Hazard ratios (HRs) and 95% CIs of GERD were computed using Cox regression. RESULTS: From 1995 to 2011, we accrued 931 cases of EADC, 876 cases of LSCC, and 301 cases of ESCC in this cohort and estimated multivariable-adjusted HRs of 2.23 (95% CI, 1.72-2.90), 1.91 (95% CI, 1.24-2.94), and 1.99 (95% CI, 1.39-2.84) for EADC, LSCC, and ESCC, respectively. The associations were independent of sex, smoking status, alcohol intake, and follow-up time periods. We estimated that among the general population in the United States, 22.04% of people aged 50-71 years suffered from GERD. Using risk factor distributions for the United States from national survey data, 16.92% of LSCC cases and 17.32% of ESCC cases among individuals aged 50-71 years were estimated to be associated with GERD. CONCLUSION: GERD is a common gastrointestinal disorder, but future prospective studies are needed to replicate our findings. If replicated, they may inform clinical surveillance of GERD patients and suggest new avenues for prevention of these malignancies.

Asthma, long-term asthma control medication and tooth wear in American adolescents and young adults.

OBJECTIVE: This study explored the associations of asthma and long-term asthma control medication with tooth wear among American adolescents and young adults. METHODS: Data from 2186 participants of the National Health and Nutrition Examination Survey (NHANES) were used. Asthma and prescribed long-term medication were collected through questionnaires. The number of surfaces with tooth wear was determined during clinical examinations. Associations were tested in Hurdle regression models adjusting for confounders. RESULTS: The prevalence of tooth wear was 58%, with an average of 6.1 (SD: 4.0) surfaces affected among those with the condition. The prevalence of asthma was 10.3%, with 2.9% of participants using long-term medication for asthma control. In the adjusted regression model, asthma was not associated with tooth wear. However, long-term control medication was associated with greater odds of having tooth wear (odds ratio: 3.33; 95%CI: 1.24-8.97), but it was not associated with the number of surfaces with tooth wear among those with the condition (rate ratio: 1.01; 95% CI: 0.58-1.75). CONCLUSION: This cross-sectional analysis of national data shows that taking long-term asthma medication was positively associated with having tooth wear.

Lack of Correlation Between Subjective and Objective Measures of Gastroesophageal Reflux Disease: Call for a Novel Validated Assessment Tool.

Background. Objective measures including the DeMeester score, lower esophageal sphincter (LES) pressure, acid exposure time, and body mass index (BMI) are used to determine gastroesophageal reflux disease (GERD) severity and eligibility for various antireflux surgical procedures. The GERD Health-Related Quality of Life (GERD-HRQL) survey is widely used to evaluate patients' subjective severity of symptoms and GERD-related quality of life. The purpose of this project was to identify whether or not the subjective measure (GERD-HRQL) correlated with objective measures (DeMeester score, LES, acid exposure time, and BMI) of GERD severity. Methods. A retrospective review of the medical records of patients who underwent antireflux surgery from 2013-2018 was completed. Patients' GERD severity was measured preoperatively and postoperatively using the GERD-HRQL. Statistical analysis included the calculation of Spearman correlation coefficients, Wilcoxon rank sum, sign, and chi-square tests. Results. 151 patients were included in the study; 64% were female. The mean age and BMI were 54.6 ± 14.6 years and 30.1 ± 4.1 kg/m2, respectively. The mean preoperative DeMeester score was 43.1 ± 36.1, LES pressure was 19.9 ± 18.4 mmHg, and acid exposure time was 11.4 ± 9.6. Mean GERD-HRQL scores decreased from 27.3 ± 9.2 preoperative to 5.3 ± 4.5 postoperative; P < .0001. Preoperative GERD-HRQL scores were not correlated with the DeMeester score (r = .11; P = .389), LES pressure (r = -.20; P = .089), acid exposure time (r = .05; P = .755), BMI (r = .10; P = .329), or age (r = -.16; P = .118). Conclusions. Total GERD-HRQL scores significantly decreased from pre- to postoperative. There was no correlation between subjective and objective GERD scoring. These data indicate the need for both physiologic evaluation and subjective assessment of patient symptoms during preoperative workup. There is a need for a contemporary, validated GERD questionnaire that correlates with objective pH testing.

Gastroesophageal reflux and asthma: when, how, and why.

PURPOSE OF REVIEW: Gastro-esophageal reflux is a possible cause of uncontrolled symptoms of asthma and should be actively investigated and treated before severe asthma is diagnosed and biological therapy started. RECENT FINDINGS: Recent investigations on esophageal function and tissue biomarkers in patients with asthma and associated GERD have established a relevant role for esophageal motility and neuronal sensory abnormalities in linking the two diseases. Characterization of the underpinning inflammatory substrate has showed mixed results as both neutrophilic and eosinophilic type 2 inflammatory changes have been described. SUMMARY: New findings regarding inflammatory mechanisms in GERD-associated asthma as well as new diagnostic tools to investigate functional esophageal abnormalities and characterize asthma endotype have identified potential treatable traits that may improve the clinical management and outcome of asthmatic patients with GERD.

Optimal Timing for Cancer Screening and Adaptive Surveillance Using Mathematical Modeling.

Cancer screening and early detection efforts have been partially successful in reducing incidence and mortality, but many improvements are needed. Although current medical practice is informed by epidemiologic studies and experts, the decisions for guidelines are ultimately ad hoc. We propose here that quantitative optimization of protocols can potentially increase screening success and reduce overdiagnosis. Mathematical modeling of the stochastic process of cancer evolution can be used to derive and optimize the timing of clinical screens so that the probability is maximal that a patient is screened within a certain "window of opportunity" for intervention when early cancer development may be observable. Alternative to a strictly empirical approach or microsimulations of a multitude of possible scenarios, biologically based mechanistic modeling can be used for predicting when best to screen and begin adaptive surveillance. We introduce a methodology for optimizing screening, assessing potential risks, and quantifying associated costs to healthcare using multiscale models. As a case study in Barrett's esophagus, these methods were applied for a model of esophageal adenocarcinoma that was previously calibrated to U.S. cancer registry data. Optimal screening ages for patients with symptomatic gastroesophageal reflux disease were older (58 for men and 64 for women) than what is currently recommended (age > 50 years). These ages are in a cost-effective range to start screening and were independently validated by data used in current guidelines. Collectively, our framework captures critical aspects of cancer evolution within patients with Barrett's esophagus for a more personalized screening design. SIGNIFICANCE: This study demonstrates how mathematical modeling of cancer evolution can be used to optimize screening regimes, with the added potential to improve surveillance regimes. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/4/1123/F1.large.jpg.

A comparison of the efficacy and safety of complementary and alternative therapies for gastroesophageal reflux disease: A protocol for network meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases in the world and is showing increasing prevalence in some countries. The disease has a chronic course that leads to a significant decline in the quality of life of patients and is associated with a high economic burden worldwide. And complementary and alternative medicine is used to treat the disease. Over the past few decades, a number of randomized controlled trials and systematic evaluations have been conducted to evaluate the effectiveness and safety of different types of complementary and alternative medicine methods, so there is an urgent need to summarize and further evaluate these studies. METHODS: We will search the following sources without restrictions for date, language, or publication status: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Library, and EMBASE, China National Knowledge Infrastructure, Chinese Bio-medicine Database, VIP Chinese Periodical Database, Wan Fang Database. We will apply a combination of Medical Subject Heading and free-text terms incorporating database-specific controlled vocabularies and text words to implement search strategies. We will also search the ongoing trials registered in the World Health Organization's International Clinical Trials Registry Platform. Besides, the previous relevant reviews conducted on complementary and alternative therapies for GERD and reference lists of included studies will also be searched. RESULTS: This study will provide a reliable basis for the treatment of GERD with complementary and alternative therapies. CONCLUSIONS: The findings will be an available reference to evaluate the efficacy and safety of complementary and alternative therapies on GERD and may provide decision-making reference on which method to choose for clinicians. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020169332.

The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Oesophageal cancer is a common and often fatal cancer that has two main histological subtypes: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Updated statistics on the incidence and mortality of oesophageal cancer, and on the disability-adjusted life-years (DALYs) caused by the disease, can assist policy makers in allocating resources for prevention, treatment, and care of oesophageal cancer. We report the latest estimates of these statistics for 195 countries and territories between 1990 and 2017, by age, sex, and Socio-demographic Index (SDI), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD). METHODS: We used data from vital registration systems, vital registration-samples, verbal autopsy records, and cancer registries, combined with relevant modelling, to estimate the mortality, incidence, and burden of oesophageal cancer from 1990 to 2017. Mortality-to-incidence ratios (MIRs) were estimated and fed into a Cause of Death Ensemble model (CODEm) including risk factors. MIRs were used for mortality and non-fatal modelling. Estimates of DALYs attributable to the main risk factors of oesophageal cancer available in GBD were also calculated. The proportion of oesophageal squamous cell carcinoma to all oesophageal cancers was extracted by use of publicly available data, and its variation was examined against SDI, the Healthcare Access and Quality (HAQ) Index, and available risk factors in GBD that are specific for oesophageal squamous cell carcinoma (eg, unimproved water source and indoor air pollution) and for oesophageal adenocarcinoma (gastro-oesophageal reflux disease). FINDINGS: There were 473 000 (95% uncertainty interval [95% UI] 459 000-485 000) new cases of oesophageal cancer and 436 000 (425 000-448 000) deaths due to oesophageal cancer in 2017. Age-standardised incidence was 5·9 (5·7-6·1) per 100 000 population and age-standardised mortality was 5·5 (5·3-5·6) per 100 000. Oesophageal cancer caused 9·78 million (9·53-10·03) DALYs, with an age-standardised rate of 120 (117-123) per 100 000 population. Between 1990 and 2017, age-standardised incidence decreased by 22·0% (18·6-25·2), mortality decreased by 29·0% (25·8-32·0), and DALYs decreased by 33·4% (30·4-36·1) globally. However, as a result of population growth and ageing, the total number of new cases increased by 52·3% (45·9-58·9), from 310 000 (300 000-322 000) to 473 000 (459 000-485 000); the number of deaths increased by 40·0% (34·1-46·3), from 311 000 (301 000-323 000) to 436 000 (425 000-448 000); and total DALYs increased by 27·4% (22·1-33·1), from 7·68 million (7·42-7·97) to 9·78 million (9·53-10·03). At the national level, China had the highest number of incident cases (235 000 [223 000-246 000]), deaths (213 000 [203 000-223 000]), and DALYs (4·46 million [4·25-4·69]) in 2017. The highest national-level age-standardised incidence rates in 2017 were observed in Malawi (23·0 [19·4-26·5] per 100 000 population) and Mongolia (18·5 [16·4-20·8] per 100 000). In 2017, age-standardised incidence was 2·7 times higher, mortality 2·9 times higher, and DALYs 3·0 times higher in males than in females. In 2017, a substantial proportion of oesophageal cancer DALYs were attributable to known risk factors: tobacco smoking (39·0% [35·5-42·2]), alcohol consumption (33·8% [27·3-39·9]), high BMI (19·5% [6·3-36·0]), a diet low in fruits (19·1% [4·2-34·6]), and use of chewing tobacco (7·5% [5·2-9·6]). Countries with a low SDI and HAQ Index and high levels of indoor air pollution had a higher proportion of oesophageal squamous cell carcinoma to all oesophageal cancer cases than did countries with a high SDI and HAQ Index and with low levels of indoor air pollution. INTERPRETATION: Despite reductions in age-standardised incidence and mortality rates, oesophageal cancer remains a major cause of cancer mortality and burden across the world. Oesophageal cancer is a highly fatal disease, requiring increased primary prevention efforts and, possibly, screening in some high-risk areas. Substantial variation exists in age-standardised incidence rates across regions and countries, for reasons that are unclear. FUNDING: Bill & Melinda Gates Foundation.