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Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease.

ABSTRACT: We aimed to determine the potential value of panel-based pharmacogenetic (PGx) testing in patients with chronic pain or gastroesophageal reflux disease (GERD) who underwent single-gene PGx testing to guide opioid or proton pump inhibitor (PPI) therapy, respectively. Of 448 patients included (chronic pain, n = 337; GERD, n = 111), mean age was 57 years, 68% were female, and 73% were white. Excluding opiates for the pain cohort and PPIs for the GERD cohort, 76.6% of patients with pain and 71.2% with GERD were prescribed at least one additional medication with a high level of PGx evidence, most commonly ondansetron or selective serotonin reuptake inhibitors. The most common genes that could inform PGx drug prescribing were CYP2C19, CYP2D6, CYP2C9, and SLCO1B1. Our findings suggest that patients with chronic pain or GERD are commonly prescribed drugs with a high level of evidence for a PGx-guided approach, supporting panel-based testing in these populations.

SUBMITTER: Elchynski AL

PROVIDER: S-EPMC8605985 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease.

Elchynski Amanda L AL Cicali Emily J EJ Ferrer Del Busto Maria C MC Hamilton Alessandra A Chang Ku-Lang KL Schmidt Siegfried O SO Weiner Brian B Davis Richard R Estores David D Max Smith D D Wiisanen Kristin K Johnson Julie A JA Cavallari Larisa H LH

The pharmacogenomics journal 20210601 6

We aimed to determine the potential value of panel-based pharmacogenetic (PGx) testing in patients with chronic pain or gastroesophageal reflux disease (GERD) who underwent single-gene PGx testing to guide opioid or proton pump inhibitor (PPI) therapy, respectively. Of 448 patients included (chronic pain, n = 337; GERD, n = 111), mean age was 57 years, 68% were female, and 73% were white. Excluding opiates for the pain cohort and PPIs for the GERD cohort, 76.6% of patients with pain and 71.2% wi ...[more]

PMID: 34075203

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Project description:BackgroundNot all gastroesophageal reflux-induced cough (GERC) patients respond to anti-reflux treatment. It is not certain whether reflux-related symptoms or other clinical characteristics could indicate a successful response to anti-reflux treatment. In this study, we aimed to investigate the relationship between clinical features and anti-reflux response.MethodsWe retrospectively analyzed the clinical characteristics of suspected GERC who had reflux-related symptoms or reflux evidence based on abnormal 24-hour esophageal pH value monitoring, or who had no evidence of other common causes of chronic cough in our chronic cough database with a standard case report form. All patients experienced anti-reflux treatment with proton pump inhibitors (PPIs) plus prokinetic agents for at least 2 weeks and were divided into responders and non-responders based on the treatment response.ResultsAmong 241 patients with suspected GERC, 146 (60.6%) showed a successful response. There was no significant difference in regard to the proportion of reflux-related symptoms, and results of 24-hour esophageal pH value monitoring between responders and non-responders. Compared with non-responders, responders had higher proportions of nasal itching (21.2% vs. 8.4%; P=0.014), tickle in the throat (51.4% vs. 35.8%; P=0.025) and lower proportion of pharyngeal foreign body sensation (32.9% vs. 54.7%; P=0.001). Multivariate analysis showed that nasal itching [hazard ratio (HR): 1.593, 95% confidence interval (CI): 1.025-2.476, P=0.039], tickle in the throat (HR: 1.605, 95% CI: 1.152-2.238, P=0.005), pharyngeal foreign body sensation (HR: 0.499, 95% CI: 0.346-0.720, P<0.001) and sensitivity to at least one cough trigger (HR: 0.480, 95% CI: 0.237-0.973, P=0.042) were associated with the therapeutic response.ConclusionsOver half of suspected GERC patients benefited from anti-reflux therapy. A few clinical features rather than reflux-related symptoms might indicate a response to anti-reflux treatment. Further study is needed for the predictive value.

Project description:BackgroundGastroesophageal reflux disease (GERD) is a common comorbidity in patients with interstitial lung disease (ILD). We built and validated a model using the national inpatient sample (NIS) database to assess the contributory role of GERD in ILD-related hospitalizations mortality.MethodsIn this retrospective analysis, we extracted ILD-related hospitalizations data between 2007 and 2019 from the NIS database. Univariable logistic regression was used for predictor selection. Data were split into the training and validation cohorts (0.6 and 0.4, respectively). We used decision tree analysis (classification and regression tree, CART) to create a predictive model to explore the role of GERD in ILD-related hospitalizations mortality. Different metrics were used to evaluate our model. A bootstrap-based technique was implemented to balance our training data outcome to improve our model metrics in the validation cohort. We conducted a variance-based sensitivity analysis to evaluate GERD's importance in our model.FindingsThe model had a sensitivity of 73.43%, specificity of 66.15%, precision of 0.27, negative predictive value (NPV) of 93.62%, accuracy of 67.2%, Matthews Correlation Coefficient (MCC) of 0.3, F1 score of 0.4, and area under the curve (AUC) for the receiver operating characteristic (ROC) curve of 0.76. GERD did not predict survival in our cohort. GERD contribution to the model was ranked the eleventh among twenty-nine variables included in this analysis (importance of 0.003, normalized importance of 5%). GERD was the best predictor in ILD-related hospitalizations who didn't receive mechanical ventilation.InterpretationsGERD is associated with mild ILD-related hospitalization. Our model-performance measures suggest overall an acceptable discrimination. Our model showed that GERD does not have a prognostic value in ILD-related hospitalization, indicating that GERD per se might not have any impact on mortality in hospitalized ILD patients.

Project description:BackgroundEmpiric therapy with multichannel intraluminal impedance-pH monitoring (MII-pH) has been used for the initial treatment of gastroesophageal reflux-induced chronic cough (GERC). However, an algorithm based on the gastroesophageal reflux disease questionnaire (GerdQ) has the potential to achieve a simple, structured, and effective treatment approach for patients with GERC.ObjectivesThis study compared the efficacy of anti-reflux therapy based on GerdQ (new structured pathway, NSP) with medical treatment after MII-pH examination (ordinary clinical pathway, OCP) in the management of GERC.DesignFor the NSP, we adapted the GerdQ score to establish the basis for a treatment algorithm. For the OCP, treatment was determined using the MII-pH examination results.MethodsThe non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP.ResultsOverall, the NSP and OCP-based therapeutic algorithms have similar efficacy for GERC [NI analysis: 95% confidence interval (CI), -4.97 to 17.73, p = 0.009; superiority analysis: p = 0.420]. Moreover, the cough symptom scores and cough threshold improved faster in the NSP group than in the OCP group at week 8 (p < 0.05). In the subgroup analyses using the GerdQ and GerdQ impact scale (GIS) scores, patients with low-likelihood GERC (GerdQ < 8) were more likely to benefit from OCP (NI analysis: 95% CI, -19.73 to 18.02, p = 0.213). On the other hand, in patients with high-likelihood and low-reflux impact GERC patients (GerdQ > 8 and GIS < 4), the NSP arm was not inferior to the standard treatment of OCP (NI analysis: 95% CI, -8.85 to 28.21%, p = 0.04; superiority analysis: p = 0.339), indicating that GerdQ- and GIS-guided diagnosis and management of patients with GERC could be an alternative to MII-pH management, especially in settings with reduced medical resources.ConclusionsThe use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting.Trial registrationThis research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).

Dataset Information

Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease.

Publications

Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease.

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