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1.
Spat Spatiotemporal Epidemiol ; 49: 100650, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38876563

ABSTRACT

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that was first detected in captive cervids in Colorado, United States (US) in 1967, but has since spread into free-ranging white-tailed deer (Odocoileus virginianus) across the US and Canada as well as to Scandinavia and South Korea. In some areas, the disease is considered endemic in wild deer populations, and governmental wildlife agencies have employed epidemiological models to understand long-term environmental risk. However, continued rapid spread of CWD into new regions of the continent has underscored the need for extension of these models into broader tools applicable for wide use by wildlife agencies. Additionally, efforts to semi-automate models will facilitate access of technical scientific methods to broader users. We introduce software (Habitat Risk) designed to link a previously published epidemiological model with spatially referenced environmental and disease testing data to enable agency personnel to make up-to-date, localized, data-driven predictions regarding the odds of CWD detection in surrounding areas after an outbreak is discovered. Habitat Risk requires pre-processing publicly available environmental datasets and standardization of disease testing (surveillance) data, after which an autonomous computational workflow terminates in a user interface that displays an interactive map of disease risk. We demonstrated the use of the Habitat Risk software with surveillance data of white-tailed deer from Tennessee, USA.


Subject(s)
Deer , Ecosystem , Software , Wasting Disease, Chronic , Wasting Disease, Chronic/epidemiology , Animals , Animals, Wild , Risk Assessment/methods
2.
Ecol Evol ; 14(5): e11347, 2024 May.
Article in English | MEDLINE | ID: mdl-38774134

ABSTRACT

Chronic wasting disease (CWD) can spread among cervids by direct and indirect transmission, the former being more likely in emerging areas. Identifying subpopulations allows the delineation of focal areas to target for intervention. We aimed to assess the population structure of white-tailed deer (Odocoileus virginianus) in the northeastern United States at a regional scale to inform managers regarding gene flow throughout the region. We genotyped 10 microsatellites in 5701 wild deer samples from Maryland, New York, Ohio, Pennsylvania, and Virginia. We evaluated the distribution of genetic variability through spatial principal component analysis and inferred genetic structure using non-spatial and spatial Bayesian clustering algorithms (BCAs). We simulated populations representing each inferred wild cluster, wild deer in each state and each physiographic province, total wild population, and a captive population. We conducted genetic assignment tests using these potential sources, calculating the probability of samples being correctly assigned to their origin. Non-spatial BCA identified two clusters across the region, while spatial BCA suggested a maximum of nine clusters. Assignment tests correctly placed deer into captive or wild origin in most cases (94%), as previously reported, but performance varied when assigning wild deer to more specific origins. Assignments to clusters inferred via non-spatial BCA performed well, but efficiency was greatly reduced when assigning samples to clusters inferred via spatial BCA. Differences between spatial BCA clusters are not strong enough to make assignment tests a reliable method for inferring the geographic origin of deer using 10 microsatellites. However, the genetic distinction between clusters may indicate natural and anthropogenic barriers of interest for management.

3.
Am J Gastroenterol ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38775971

ABSTRACT

INTRODUCTION: Increased intra-abdominal pressure in patients with elevated body mass index (BMI) may affect measurements of esophagogastric junction (EGJ) opening. METHODS: Findings from adult patients who underwent both impedance planimetry with functional luminal imaging probe (FLIP) and high-resolution manometry (HRM) were compared by BMI. RESULTS: Among patients with no EGJ outflow obstruction on HRM, abnormal EGJ classifications on FLIP were more common among those with elevated than normal BMI (61.1% vs 31.6%, P = 0.037). DISCUSSION: Discordant results between FLIP and HRM on EGJ opening are more common in patients with elevated BMI. Body composition may impact EGJ function and measures on current testing modalities.

4.
Sci Rep ; 14(1): 11340, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760358

ABSTRACT

Genetics studies are used by wildlife managers and researchers to gain inference into a population of a species of interest. To gain these insights, microsatellites have been the primary method; however, there currently is a shift from microsatellites to single nucleotide polymorphisms (SNPs). With the different DNA requirements between microsatellites and SNPs, an investigation into which samples can provide adequate DNA yield is warranted. Using samples that were collected from previous genetic projects from regions in the USA from 2014 to 2021, we investigated the DNA yield of eight sample categories to gain insights into which provided adequate DNA to be used in ddRADseq or already developed high- or medium-density SNP panels. We found seven sample categories that met the DNA requirements for use in all three panels, and one sample category that did not meet any of the three panels requirements; however, DNA integrity was highly variable and not all sample categories that met panel DNA requirements could be considered high quality DNA. Additionally, we used linear random-effects models to determine which covariates would have the greatest influence on DNA yield. We determined that all covariates (tissue type, storage method, preservative, DNA quality, time until DNA extraction and time after DNA extraction) could influence DNA yield.


Subject(s)
DNA , Polymorphism, Single Nucleotide , DNA/genetics , DNA/analysis , Animals , Microsatellite Repeats/genetics , Specimen Handling/methods
5.
Proc Natl Acad Sci U S A ; 121(23): e2403557121, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38809709

ABSTRACT

The Asian water tower (AWT) serves as the source of 10 major Asian river systems and supports the lives of ~2 billion people. Obtaining reliable precipitation data over the AWT is a prerequisite for understanding the water cycle within this pivotal region. Here, we quantitatively reveal that the "observed" precipitation over the AWT is considerably underestimated in view of observational evidence from three water cycle components, namely, evapotranspiration, runoff, and accumulated snow. We found that three paradoxes appear if the so-called observed precipitation is corrected, namely, actual evapotranspiration exceeding precipitation, unrealistically high runoff coefficients, and accumulated snow water equivalent exceeding contemporaneous precipitation. We then explain the cause of precipitation underestimation from instrumental error caused by wind-induced gauge undercatch and the representativeness error caused by sparse-uneven gauge density and the complexity of local surface conditions. These findings require us to rethink previous results concerning the water cycle, prompting the study to discuss potential solutions.

7.
Clin Transl Gastroenterol ; 15(6): e00717, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38752627

ABSTRACT

INTRODUCTION: Gastroesophageal reflux disease (GERD) has been associated with increased incidence/recurrence of atrial fibrillation (AF). However, the impact of GERD and proton pump inhibitor (PPI) therapy on outcomes of AF catheter ablation remains unclear. We aimed to assess the association between the presence of GERD and risk of repeat AF ablation, stratified by PPI therapy. METHODS: A retrospective cohort study was conducted on patients with paroxysmal/persistent AF undergoing initial ablation in January 2011-September 2015. GERD was defined by endoscopic findings, objective reflux testing, or clinical symptoms. The association between GERD/PPI use and time to repeat ablation was evaluated by time-to-event analysis with censoring at the last clinic follow-up within 1 year. RESULTS: Three hundred eighty-one subjects were included. Patients with GERD (n = 80) had a higher 1-year repeat ablation rate compared with those with no GERD (25% vs 11.3%, P = 0.0034). Stratifying by PPI use, patients with untreated GERD (37.5%) more likely needed repeat ablation compared with reflux-free (11.3%, P = 0.0003) and treated GERD (16.7%, P = 0.035) subjects. On multivariable Cox regression analyses, GERD was an independent risk factor of repeat ablation (hazard ratio [HR] 3.30, confidence interval [CI] 1.79-6.08, P = 0.0001). Specifically, untreated GERD was associated with earlier repeat ablation compared with no GERD (HR 4.02, CI 1.62-12.05, P = 0.0013). However, no significant difference in repeat ablation risk was noted between reflux-free and PPI-treated GERD groups. DISCUSSION: GERD was an independent predictor for risk of repeat AF ablation within 1 year, even after controlling for major cardiovascular comorbidities and confounders. PPI therapy modulated this risk, as repeat ablation-free survival for PPI-treated GERD was noninferior to reflux-free patients.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Gastroesophageal Reflux , Proton Pump Inhibitors , Recurrence , Humans , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/surgery , Gastroesophageal Reflux/complications , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/adverse effects , Atrial Fibrillation/surgery , Atrial Fibrillation/drug therapy , Male , Female , Retrospective Studies , Middle Aged , Catheter Ablation/adverse effects , Aged , Risk Factors , Reoperation/statistics & numerical data , Treatment Outcome
8.
Article in English | MEDLINE | ID: mdl-38657883

ABSTRACT

BACKGROUND AND AIMS: Fecal incontinence (FI) is highly prevalent with substantial impacts on quality of life and health care utilization. The impact of obesity on FI remains unclear, with differing conclusions using body mass index (BMI) as a risk factor. We aimed to determine the association between obesity and FI, and whether this relationship is dependent on the distribution of adiposity (waist circumference-to-height ratio [WHtR]). METHODS: This was a population-based analysis of the National Health and Nutrition Examination Survey, including participants who responded to the bowel health survey in 2005 to 2010. FI was defined by the accidental bowel leakage of solid stool, liquid, or mucus at least once in the past month. Stepwise multivariable logistic regression models were constructed to assess risk factors for FI. RESULTS: A total of 7606 participants were included, with an overall FI prevalence of 9.2%. When stratified by quartiles of body measurements, FI was increasingly prevalent from the 1st to the 4th quartile for both WHtR (range, 5.3%-12.5%) and BMI (range, 7.1%-10.5%). WHtR was associated with FI and was a stronger predictor than BMI in all quartiles of body measurement. On multivariable analysis, WHtR remained a significant predictor of FI comparing the 4th with the 1st quartile of body measurements (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.11-2.80; P = .017), whereas BMI was not. A WHtR cutoff of >0.592 optimized the Youden index in prediction of FI in the overall sample. CONCLUSION: WHtR was independently associated with increased odds of FI in this nationally representative sample of United States adults, whereas BMI was not consistently correlated. This suggests bowel continence may depend more on how body mass is distributed.

10.
Prion ; 18(1): 72-86, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38676289

ABSTRACT

Infectious prions are resistant to degradation and remain infectious in the environment for several years. Chronic wasting disease (CWD) has been detected in cervids inhabiting North America, the Nordic countries, and South Korea. CWD-prion spread is partially attributed to carcass transport and disposal. We employed a forensic approach to investigate an illegal carcass dump site connected with a CWD-positive herd. We integrated anatomic, genetic, and prion amplification methods to discover CWD-positive remains from six white-tailed deer (Odocoileus virginianus) and, using microsatellite markers, confirmed a portion originated from the CWD-infected herd. This approach provides a foundation for future studies of carcass prion transmission risk.


Subject(s)
Deer , Prions , Wasting Disease, Chronic , Animals , Wasting Disease, Chronic/transmission , Prions/genetics , Prions/metabolism , Microsatellite Repeats/genetics
11.
Am J Gastroenterol ; 119(6): 1126-1140, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38634551

ABSTRACT

INTRODUCTION: Divergent recommendations for periprocedural management of glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA) medications rely on limited evidence. We performed a systematic review and meta-analysis to provide quantitative measures of gastric emptying relevant to mechanisms of weight loss and to periprocedural management of GLP-1 RA. We hypothesized that the magnitude of gastric emptying delay would be low and of limited clinical significance to procedural sedation risks. METHODS: A protocolized search identified studies on GLP-1 RA that quantified gastric emptying measures. Pooled estimates using random effects were presented as a weighted mean difference with 95% confidence intervals (CIs). Univariate meta-regression was performed to assess the influence of GLP-1 RA type, short-acting vs long-acting mechanism of action, and duration of treatment on gastric emptying. RESULTS: Fifteen studies met the inclusion criteria. Five studies (n = 247) utilized gastric emptying scintigraphy. Mean T 1/2 was 138.4 minutes (95% CI 74.5-202.3) for GLP-1 RA vs 95.0 minutes (95% CI 54.9-135.0) for placebo, with a pooled mean difference of 36.0 minutes (95% CI 17.0-55.0, P < 0.01, I2 = 79.4%). Ten studies (n = 411) utilized the acetaminophen absorption test, with no significant delay in gastric emptying measured by T max , area under the curve (AUC) 4hr , and AUC 5hr with GLP-1 RA ( P > 0.05). On meta-regression, the type of GLP-1 RA, mechanism of action, and treatment duration did not impact gastric emptying ( P > 0.05). DISCUSSION: While a gastric emptying delay of ∼36 minutes is quantifiable on GLP-1 RA medications, it is of limited magnitude relative to standard periprocedural fasting periods. There were no substantial differences in gastric emptying on modalities reflective of liquid emptying (acetaminophen absorption test), particularly at time points relevant to periprocedural care.


Subject(s)
Gastric Emptying , Glucagon-Like Peptide 1 , Humans , Gastric Emptying/drug effects , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Weight Loss/drug effects , Perioperative Care/methods
12.
Curr Opin Gastroenterol ; 40(4): 305-313, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38662405

ABSTRACT

PURPOSE OF REVIEW: Symptoms/complications related to extraesophageal reflux (EER) are increasingly prevalent presentations and pose significant challenges for clinicians. We summarize and discuss clinical advances and developments in pathophysiology, testing and treatment algorithms of upper/lower airway manifestations of EER. RECENT FINDINGS: Growing evidence supports likely multifactorial causes of laryngeal symptoms, including EER, oropharyngeal pathologies, allergic conditions, and cognitive-affective processes (brain-larynx interaction). Diagnostic paradigm for laryngopharyngeal reflux (LPR) is shifting towards a personalized approach with noninvasive strategies/prediction tools to risk-stratify patients for upfront reflux testing over empiric acid suppression trials. Management should be multipronged to include antireflux therapies and treatments targeting other causes. Lower airway complications of EER may result in lung dysfunction and poor transplant outcomes. Esophageal symptoms are often absent and routine esophageal/reflux testing to guide timely antireflux therapies may lead to improved outcomes. Modalities that leverage impedance technology may be important, given the potential role of nonacidic reflux. Novel impedance-based metrics such as mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index may provide adjunctive diagnostic values. SUMMARY: Standardized approach to diagnosis/management of EER should include multidisciplinary care teams and consider different phenotypes, nonreflux contributors, and the complex gut-airway relationships. Prompt antireflux therapies after careful candidate selection may improve outcomes of these airway complications.


Subject(s)
Gastroesophageal Reflux , Humans , Esophageal pH Monitoring , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/physiopathology , Gastroesophageal Reflux/therapy , Laryngopharyngeal Reflux/therapy , Laryngopharyngeal Reflux/diagnosis , Laryngopharyngeal Reflux/physiopathology , Laryngopharyngeal Reflux/etiology
13.
Phys Rev E ; 109(2-1): 024501, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38491709

ABSTRACT

We use molecular dynamics (MD) simulation and nanofluidic experiments to probe the non-equilibrium transient physics of two nanochannel-confined polymers driven against a permeable barrier in a flow field. For chains with a persistence length P smaller than the channel diameter D, both simulation and experiment with dsDNA reveal nonuniform mixing of the two chains, with one chain dominating locally in what we term "aggregates." Aggregates undergo stochastic dynamics, persisting for a limited time, then disappearing and reforming. Whereas aggregate-prone mixing occurs immediately at sufficiently high flow speeds, chains stay segregated at intermediate flow for some time, often attempting to mix multiple times, before suddenly successfully mixing. Observation of successful mixing nucleation events in nanofluidic experiments reveal that they arise through a peculiar "back-propagation" mechanism whereby the upstream chain, closest to the barrier, penetrates and passes through the downstream chain (farthest from the barrier) moving against the flow direction. Simulations suggest that the observed back-propagation nucleation mechanism is favored at intermediate flow speeds and arises from a special configuration where the upstream chain exhibits one or more folds facing the downstream chain, while the downstream chain has an unfolded chain end facing upstream.

14.
Article in English | MEDLINE | ID: mdl-38529209

ABSTRACT

Background: Hip resurfacing arthroplasty (HRA) provides an attractive alternative to total hip arthroplasty (THA) for the management of osteoarthritis in younger, more active patients; however, concerns persist over complications specific to HRA. The aims of this systematic review were to assess the documented long-term survival rates of the metal-on-metal BIRMINGHAM HIP Resurfacing System at a follow-up of at least 10 years and to analyze the functional outcomes and cause of failures. Methods: A systematic review was undertaken of all published cohort studies available in the MEDLINE, Cochrane, Embase, and PubMed research databases up to December 2021, as recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction was focused on survival rates, causes of failure, and functional outcomes. Survival estimates at 10 years were pooled in a meta-analysis, with each series weighted by its variance. Causes of failure were presented as a percentage of the pooled revisions. Results: A total of 11 studies were identified, encompassing 3,129 cases. Across the 9 studies that had reported a mean follow-up, the mean follow-up was 11.7 years (range, 9.55 to 13.7 years). We found a pooled 10-year survival rate of 95.5% (95% confidence interval, 93.4% to 97.1%). There were 149 revisions among the studies (range, 4 to 38 revisions per study), a rate of 4.8% of the total procedures performed. The 2 main causes of revision were aseptic loosening (20.1% of revisions) and adverse reactions to metal debris (20.1%). There were no revisions for dislocation. Of the studies that reported preoperative functional scores, all reported significant improvement in mean scores postoperatively except for 1 study in which the mean Tegner activity score did not significantly improve. Conclusions: When performed for appropriate indications, patients undergoing an HRA with use of the BIRMINGHAM HIP Resurfacing System can expect good implant survivorship at 10 years with acceptable functional results and low rates of dislocation and infection. This systematic review, however, confirms concerns regarding adverse reactions to metal debris as a leading cause of revision. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

15.
Transl Psychiatry ; 14(1): 132, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38431658

ABSTRACT

Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = -0.32, p = 0.0023, n = 88) and remission (r = -0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression.


Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/genetics , Venlafaxine Hydrochloride/therapeutic use , Depression , Genetic Risk Score , Genome-Wide Association Study , Antidepressive Agents/therapeutic use , Treatment Outcome
16.
Dis Esophagus ; 37(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38521967

ABSTRACT

Acid reflux has been associated with allograft injury and rejection in lung transplant patients; however, the pathogenic role of non-acid reflux remains debated. We aimed to evaluate the impact of concurrent abnormal non-acid reflux with acid reflux on chronic rejection in lung transplant patients with acid reflux. This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined impedance-pH study off acid suppression. Only subjects with acid exposure >4% were included. Non-acid reflux (pH > 4) episodes >27 was considered abnormal per prior normative studies. Chronic rejection was defined as chronic lung allograft dysfunction (CLAD) per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods, with censoring at death, anti-reflux surgery, or last follow-up. In total, 68 subjects (28 abnormal/40 normal non-acid reflux) met inclusion criteria for the study. Baseline demographic/clinical characteristics were similar between groups. Among this cohort of patients with increased acid exposure, subjects with concurrent abnormal non-acid reflux had significantly higher risk of CLAD than those without on Kaplan-Meier analysis (log-ranked P = 0.0269). On Cox multivariable regression analysis controlling for body mass index, age at transplantation, and proton pump inhibitor use, concurrent abnormal non-acid reflux remained independently predictive of increased CLAD risk (hazard ratio 2.31, confidence interval: 1.03-5.19, P = 0.04). Presence of concurrent abnormal non-acid reflux in lung transplant subjects with increased acid exposure is associated with additional risk of chronic rejection. Non-acid reflux may also contribute to pathogenicity in lung allograft injury/rejection, supporting a potential role for impedance-based testing in this population.


Subject(s)
Gastroesophageal Reflux , Graft Rejection , Lung Transplantation , Proportional Hazards Models , Humans , Lung Transplantation/adverse effects , Female , Male , Retrospective Studies , Graft Rejection/etiology , Middle Aged , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/complications , Adult , Risk Factors , Kaplan-Meier Estimate , Esophageal pH Monitoring , Chronic Disease
17.
Article in English | MEDLINE | ID: mdl-38367746

ABSTRACT

BACKGROUND AND AIMS: Heartburn symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCABs) are under development as a new class of therapy. We performed economic analyses to align GERD drug development with the needs of gastroenterologists, insurers and patients in a value-based environment. METHODS: A decision-analytic model was constructed to compare vonoprazan 20 mg daily (an example of a PCAB), common over-the-counter or prescription proton pump inhibitor regimens, and no treatment over a 1-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared with healthy control subjects. Costs and quality-adjusted life years were reported. RESULTS: Without insurance coverage for appropriate therapy, patients spend $4443 and insurers spend $3784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3000 in annual costs to patients and insurers, could generate quality-adjusted life year gains (+0.06 per year), and could be cost-saving to insurers as a covered option at a price up to $8.57 per pill, if these drugs are able to demonstrate similar effectiveness to proton pump inhibitors in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts. DISCUSSION: We demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.

18.
Clin Gastroenterol Hepatol ; 22(6): 1200-1209.e1, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38309491

ABSTRACT

BACKGROUND & AIMS: Discerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict the likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms. METHODS: This multicenter international study collected data from adults with chronic laryngeal symptoms who underwent objective testing (upper gastrointestinal endoscopy and/or ambulatory reflux monitoring) between March 2018 and May 2023. The training phase identified a model with optimal receiver operating characteristic curves, and ß coefficients informed a weighted model. The validation phase assessed performance characteristics of the weighted model. RESULTS: A total of 856 adults, 304 in the training cohort and 552 in the validation cohort, were included. In the training phase, the optimal predictive model (area under the curve, 0.68; 95% CI, 0.62-0.74), was the Cough, Overweight/obesity, Globus, Hiatal Hernia, Regurgitation, and male seX (COuGH RefluX) score, with a lower threshold of 2.5 and an upper threshold of 5.0 to predict proven GERD. In the validation phase, the COuGH RefluX score had an area under the curve of 0.67 (95% CI, 0.62-0.71), with 79% sensitivity and 81% specificity for proven GERD. CONCLUSIONS: The externally validated COuGH RefluX score is a clinically practical model to predict the likelihood of proven GERD. The score classifies most patients with chronic laryngeal symptoms as low/high likelihood of proven GERD, with only 38% remaining as indeterminate. Thus, the COuGH RefluX score can guide diagnostic strategies and reduce inappropriate proton pump inhibitor use or testing for patients referred for evaluation of chronic laryngeal symptoms.


Subject(s)
Cough , Gastroesophageal Reflux , Humans , Male , Female , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/complications , Middle Aged , Cough/etiology , Adult , Chronic Disease , Aged , ROC Curve , Laryngeal Diseases/diagnosis , Laryngeal Diseases/complications
19.
Am J Gastroenterol ; 119(5): 991-995, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38314789

ABSTRACT

INTRODUCTION: The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. METHODS: A total of 305 patients with newly diagnosed EoE received standard (omeprazole 20 mg daily), once-daily moderate (40 mg daily), twice-daily moderate (20 mg twice daily), or high (40 mg twice daily) dose PPI for ≥8 weeks. RESULTS: Approximately 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate 52.8%/high 54.3%) than once-daily (standard 11.8%/moderate 10%) dosing ( P < 0.0001). On multivariable analysis, twice-daily moderate (adjusted odds ratio 6.75, confidence interval 2.53-18.0, P = 0.0008) and high (adjusted odds ratio 12.8, confidence interval 4.69-34.8, P < 0.0001) doses independently predicted histologic response. DISCUSSION: Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.


Subject(s)
Drug Administration Schedule , Eosinophilic Esophagitis , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/administration & dosage , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/pathology , Male , Female , Adult , Middle Aged , Omeprazole/administration & dosage , Treatment Outcome , Remission Induction , Young Adult , Dose-Response Relationship, Drug
20.
Nephrology (Carlton) ; 29(6): 311-324, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38403867

ABSTRACT

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.


Subject(s)
Consensus , Hyperkalemia , Humans , Hyperkalemia/epidemiology , Hyperkalemia/therapy , Hyperkalemia/diagnosis , Asia/epidemiology , Risk Factors , Potassium/blood , Silicates/therapeutic use , Silicates/adverse effects
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