Abstract
Restlessness is a core symptom underlying restless legs syndrome (RLS), neuroleptic-induced akathisia, and opioid withdrawal. These three conditions also share other clinical components ...suggesting some overlap in their pathophysiology. Recent prospective studies demonstrate the frequent incidence of RLS-like symptoms during opioid withdrawal and supervised prescription opioid tapering. Based on the therapeutic role of µ-opioid receptor (MOR) agonists in the three clinical conditions and recent preclinical experimental data in rodents, we provide a coherent and unifying neurobiological basis for the restlessness observed in these three clinical syndromes and propose a heuristic hypothesis of a key role of the specific striatal neurons that express MORs in akathisia/restlessness.
Graphical Abstract
Graphical Abstract
Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease of the oesophagus and is clinically characterized by upper gastrointestinal (GI) symptoms including dysphagia and esophageal ...food impaction. Histopathologic manifestations, which include intraepithelial eosinophilic inflammation and alterations of the esophageal squamous epithelium, such as basal zone hyperplasia (BZH) and dilated intercellular spaces (DIS), are thought to contribute to esophageal dysfunction and disease symptoms. Corroborative clinical and discovery science‐based studies have established that EoE is characterized by an underlying allergic inflammatory response, in part, related to the IL‐13/CCL26/eosinophil axis driving dysregulation of several key epithelial barrier and proliferative regulatory genes including kallikrein (KLK) serine proteases, calpain 14 (CAPN14) and anoctamin 1 (ANO1). The contribution of these inflammatory and proliferative processes to the clinical and histological manifestations of disease are not fully elucidated. Herein, we discuss the immune molecules and cells that are thought to underlie the clinical and pathologic manifestations of EoE and the emerging therapeutics targeting these processes for the treatment of EoE.
Routine HIV viral load testing is not widely accessible in most resource-limited settings, including Kenya. To increase access to viral load testing, alternative sample types like dried blood spots ...(DBS), which overcome the logistic barriers associated with plasma separation and cold chain shipment need to be considered and evaluated. The current study evaluated matched dried blood spots (DBS) and dried plasma spots (DPS) against plasma using the Abbott M 2000 (Abbott) and Roche Cobas Ampliprep/Cobas TaqMan (CAP/CTM) quantitative viral load assays in western Kenya.
Matched plasma DBS and DPS were obtained from 200 HIV-1 infected antiretroviral treatment (ART)-experienced patients attending patient support centers in Western Kenya. Standard quantitative assay performance parameters with accompanying 95% confidence intervals (CI) were assessed at the assays lower detection limit (400cps/ml for CAP/CTM and 550cps/ml for Abbott) using SAS version 9.2. Receiver operating curves (ROC) were further used to assess viral-load thresholds with best assay performance (reference assay CAP/CTM plasma).
Using the Abbott test, the sensitivity and specificity, respectively, for DPS were (97.3%, 95%CI: 93.2-99.2 and 98.1% 95%CI: 89.7-100) and those for DBS (93.9% 95%CI: 88.8-97.2 and 88.0% 95%CI: 82.2-92.4). The correlation and agreement using paired plasma and DPS/DBS were strong, with r2 = 90.5 and rc = 68.1. The Bland-Altman relative percent change was 95.3 for DPS, (95%CI: 90.4-97.7) and 73.6 (95%CI: 51.6-86.5) for DBS. Using the CAP/CTM assay, the sensitivity for DBS was significantly higher compared to DPS (100.0% 95% CI: 97.6-100.0 vs. 94.7% 95%CI: 89.8-97.7), while the specificity for DBS was lower: 4%, 95% CI: 0.4-13.7 compared to DPS: 94.0%, 95% CI: 83.5-98.7. When compared under different clinical relevant thresholds, the accuracy for the Abbott assay was 95% at the 1000cps/ml cut-off with a sensitivity and specificity of 96.6% 95% CI 91.8-98.7 and 90.4% 95% CI 78.2-96.4 respectively. The optimum threshold was at 3000 cps/ml with an accuracy of 95.5%, sensitivity and specificity of 94.6% 95%CI 89.3-97.5 and 98.1% 95%CI 88.4-99.9) respectively. The best threshold for CAP/CTM was at 4000 copies /mL, with 92.5% accuracy (sensitivity of 96.0% 95%CI 91.0-98.3 and specificity of 82.7% 95%CI 69.2-91.3).
There was similar performance between matched DBS, DPS and plasma using the Abbott test, and good correlation for matched DPS and plasma using the CAPCTM test. The findings suggest that DBS and DPS may be reliably used as alternative specimens to plasma to measure HIV-1 VL using Abbott, and DPS may be reliably used with CAP/CTM in resource-limited settings.
Despite effective dietary treatments, physicians prefer medications for eosinophilic esophagitis (EoE).
We conducted a web-based survey of providers to assess the perceived effectiveness, practice ...patterns, and barriers to EoE dietary therapy.
Providers view diet as the least effective treatment. The greatest barrier was the belief that patients are disinterested and unlikely to adhere (58%). With less access to dietitians (56%), nonacademic providers often manage diets without dietitian guidance (41%).
Given high patient acceptance for diets and multiple treatment options for EoE, clinicians need evidence-based knowledge on EoE diets, access to dietitians, and awareness of patient preferences.
In recent years, social media has transformed how we as gastroenterologists communicate with each other and has grown into an arena of knowledge and peer support for patients. Gastroenterologists ...commonly use social media for education networking, patient populations use social media for peer support and advocacy, but little is known about how gastroenterologists can use social media to conduct thoughtful and rigorous patient-centered research. Therefore, we aim to introduce the scope of social media research, highlight prominent examples in gastroenterology, and review innovative opportunities and unique challenges to using and studying social media for research.
Despite the rising prevalence and incidence of eosinophilic esophagitis (EoE), the etiology and pathophysiology remain unknown. Studies to date suggest that complex interactions between genetic and ...environmental risk factors result in the development and presentation of disease. Examining environmental factors both in the early life and later life exposures offers potential clues for the development of EoE, although challenges exist in making causal inferences due to diagnostic delay and access, ascertainment biases, and misclassification of cases. The authors review studies supporting early life factors as etiologic factors in the development of EoE.
Objective
Viral load suppression (VLS) is critical in reducing morbidity and mortality associated with HIV as well as minimizing the likelihood of HIV transmission to uninfected persons. The ...objective of this study was to identify factors associated with VLS among people living with HIV (PLWH) on antiretroviral (ARV) therapy to inform HIV programme strategies in Nigeria.
Methods
Adult participants, aged 15–64 years, from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS), who self‐reported to be a PLWH or had detectable ARVs, were analysed to examine factors associated with VLS defined as HIV RNA <1000 copies/mL. NAIIS measured HIV prevalence, viral load, ARV and hepatitis B in PLWH. Logistic regression models were used and reported weighted prevalence.
Results
Of 1322 participants, 949 (68.25%) were women and 1287 (96.82%) had detectable ARVs. The median age was 39.31 interquartile range (IQR): 31.47–47.63 years. Prevalence of VLS was 80.88%. Compared with participants with detectable ARVs, those with undetectable ARVs in their blood specimens had lower odds of VLS adjusted odds ratio (aOR) = 0.24, 95% confidence interval (CI): 0.08–0.64). Coinfection with hepatitis B and nonnucleoside reverse transcriptase inhibitor metabolites were also associated with lower odds of VLS. Older people (45–54 vs 15–24 years) had increased odds of VLS (aOR = 2.81, 95% CI: 1.14–6.90).
Conclusion
Young people and those with undetectable ARVs had lower odds of virological suppression. Targeted interventions focusing on young people and adherence to medication are needed to achieve the UNAIDS 95–95‐95 goals for HIV epidemic control.
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