The role of a contrast study in the investigation of Paediatric Gastroesophageal Reflux Disease.

Masters Degree in the Department of Pediatric Surgery. University of Kwazulu-Natal, Durban.Background: Gastroesophageal reflux (GER) is a common finding in the pediatric population. This can either be physiological re flux or established disease that may require surgical intervention. There is currently no consensus on a gold standard in the diagnosis of gastroesophageal reflux disease (GERD). The purpose of this article is to describe the role of contrast radiography in this process, looking in particular at the subset of neurologically impaired (NI) children. Methods: A retrospective chart review of children admitted for the work-up of GER or for gastronomy insertion, to the Department of Paediatric Surgery at Inkosi Albert Luthuli Central Hospital (IALCH) from January 2014-December 2015. Results: 42 patients (25 male, 17 female) were admitted during this period. 27(64%) were neurologically impaired. All patients had a contrast study performed. Twenty (48%) contrast studies showed GER. Twenty-two (52%) studies were negative for GER and these children subsequently had oesophageal pH monitoring studies performed. Twelve (55%) pH monitoring studies were positive for GER. Ten (45%) pH studies were negative for GER. The sensitivity of a contrast study to show GER was 62.5%. Anatomical anomalies diagnosed on contrast radiography were hiatal hernias (3), oesophageal strictures (2), situs inversus (1) and pylorospasm (1). Conclusions: Contrast radiography has a low sensitivity in diagnosing GER and adjuvant studies are sometimes necessary. However, it is useful in recognising anatomical anomalies that either predispose to GER or is a consequence of GER. It is a particularly helpful diagnostic tool in the management of neurologically impaired children who require feeding gastrostomy tubes

Verification and Validation of Numerical Modelling Approaches Pertinent to Stomach Modelling

The digestive system is vital to the human body. Over many decades, scientists have been investigating the food breakdown mechanisms inside the stomach through in vivo human and animal studies and in vitro experiments. Due to recent improvements in computing speed and algorithm development, computational modelling has become a viable option to investigate in-body processes. Such in silico models are more easily controlled to investigate individual variables, do not require invasive physical experiments, and can provide valuable insights into the local physics of gastric flow. There is a huge potential for numerical approaches in stomach modelling as they can provide a comprehensive understanding of the complex flow and chemistry in the stomach. However, to make sure the numerical methods are accurate and reliable, rigorous verification and validation are essential as part of model development. A significant focus of this thesis was on verifying and validating the numerical modelling approaches pertinent to stomach modellin

Treating an intervention level 1 patient: futile or brave?

An ethical dilemma describes conflicting opinions by different members of the care team. This article focuses on AJ, a five-year-old child with cerebral palsy, who was born deaf and blind as a result of having contracted rubella in utero. The case is examined against Sokol’s four-quadrant analysis of ethical issues, giving a framework designed to facilitate the systematic identification and analysis of clinical ethical problems. The issue is whether the medical team should have palliated AJ, or continued with invasive therapy and feeding. The conclusion is that paediatric palliative care is often difficult, but that the dietitian has a duty to contribute his or her knowledge to benefit the patient.Department of HE and Training approved lis

Treating an intervention level 1 patient: futile or brave?

An ethical dilemma describes conflicting opinions by different members of the care team. This article focuses on AJ, a five-year-old child with cerebral palsy, who was born deaf and blind as a result of having contracted rubella in utero. The case is examined against Sokol’s four-quadrant analysis of ethical issues, giving a framework designed to facilitate the systematic identification and analysis of clinical ethical problems. The issue is whether the medical team should have palliated AJ, or continued with invasive therapy and feeding. The conclusion is that paediatric palliative care is often difficult, but that the dietitian has a duty to contribute his or her knowledge to benefit the patient.Keywords: futile treatment, cerebral palsy, gastro-oesophageal reflux disease, palliative care, nasogastric feeding, nasojejunal feedin

Gastric Alimetry® test interpretation in gastroduodenal disorders : review and recommendations

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut–brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising > 2000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this paper presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid and is expected to continue to evolve with further development

Integration of advanced methods and models to study drug absorption and related processes : An UNGAP perspective

Funding Information: AI acknowledges the support of projects icp009 (ALKOOL) of PRACE-ICEI (grant agreement 800858) for awarding access to Piz Daint, at the Swiss National Supercomputing Centre (CSCS), Switzerland and BG05M2OP001–1.001–0004 (UNITe) of the Bulgarian Ministry of Education and Science. For further details on points raised in this article, please contact [email protected]. Funding Information: Acknowledgements. JAGH is supported by the Biocenter Finland, the Helsinki Institute of Life Sciences, and the Faculty of Pharmacy, University of Helsinki. Publisher Copyright: © 2021 The AuthorsThis collection of contributions from the European Network on Understanding Gastrointestinal Absorption-related Processes (UNGAP) community assembly aims to provide information on some of the current and newer methods employed to study the behaviour of medicines. It is the product of interactions in the immediate pre-Covid period when UNGAP members were able to meet and set up workshops and to discuss progress across the disciplines. UNGAP activities are divided into work packages that cover special treatment populations, absorption processes in different regions of the gut, the development of advanced formulations and the integration of food and pharmaceutical scientists in the food-drug interface. This involves both new and established technical approaches in which we have attempted to define best practice and highlight areas where further research is needed. Over the last months we have been able to reflect on some of the key innovative approaches which we were tasked with mapping, including theoretical, in silico, in vitro, in vivo and ex vivo, preclinical and clinical approaches. This is the product of some of us in a snapshot of where UNGAP has travelled and what aspects of innovative technologies are important. It is not a comprehensive review of all methods used in research to study drug dissolution and absorption, but provides an ample panorama of current and advanced methods generally and potentially useful in this area. This collection starts from a consideration of advances in a priori approaches: an understanding of the molecular properties of the compound to predict biological characteristics relevant to absorption. The next four sections discuss a major activity in the UNGAP initiative, the pursuit of more representative conditions to study lumenal dissolution of drug formulations developed independently by academic teams. They are important because they illustrate examples of in vitro simulation systems that have begun to provide a useful understanding of formulation behaviour in the upper GI tract for industry. The Leuven team highlights the importance of the physiology of the digestive tract, as they describe the relevance of gastric and intestinal fluids on the behaviour of drugs along the tract. This provides the introduction to microdosing as an early tool to study drug disposition. Microdosing in oncology is starting to use gamma-emitting tracers, which provides a link through SPECT to the next section on nuclear medicine. The last two papers link the modelling approaches used by the pharmaceutical industry, in silico to Pop-PK linking to Darwich and Aarons, who provide discussion on pharmacometric modelling, completing the loop of molecule to man.Peer reviewe

Nerve localization techniques for peripheral nerve block and possible future directions

Ultrasound guidance is now a standard nerve localization technique for peripheral nerve block (PNB). Ultrasonography allows simultaneous visualization of the target nerve, needle, local anesthetic injectate and surrounding anatomical structures. Accurate deposition of local anesthetic next to the nerve is essential to the success of the nerve block procedure. Unfortunately, due to limitations in the visibility of both needle tip and nerve surface, the precise relationship between needle tip and target nerve is unknown at the moment of injection. Importantly, nerve injury may result both from an inappropriately placed needle tip and inappropriately placed local anesthetic. The relationship between the block needle tip and target nerve is of paramount importance to the safe conduct of peripheral nerve block. This review summarizes the evolution of nerve localization in regional anesthesia, characterizes a problem faced by clinicians in performing ultrasound guided nerve block and explores the potential technological solutions to this problem

Establishing virtual bioequivalence and clinically relevant specifications using in vitro biorelevant dissolution testing and physiologically-based population pharmacokinetic modeling. Case example:Naproxen

Background Physiologically-based population pharmacokinetic modeling (popPBPK) coupled with in vitro biopharmaceutics tools such as biorelevant dissolution testing can serve as a powerful tool to establish virtual bioequivalence and set clinically relevant specifications. One of several applications of popPBPK modeling is in the emerging field of virtual bioequivalence (VBE), where it can be used to streamline drug development by implementing model-informed formulation design and to inform regulatory decision-making e.g., with respect to evaluating the possibility of extending BCS-based biowaivers beyond BCS Class I and III compounds in certain cases. Methods In this study, Naproxen, a BCS class II weak acid was chosen as the model compound. In vitro biorelevant solubility and dissolution experiments were performed and the resulting data were used as an input to the PBPK model, following a stepwise workflow for the confirmation of the biopharmaceutical parameters. The naproxen PBPK model was developed by implementing a middle-out approach and verified against clinical data obtained from the literature. Once confidence in the performance of the model was achieved, several in vivo dissolution scenarios, based on model-based analysis of the in vitro data, were used to simulate clinical trials in healthy adults. Inter-occasion variability (IOV) was also added to critical physiological parameters and mechanistically propagated through the simulations. The various trials were simulated on a “worst/best case” dissolution scenario and average bioequivalence was assessed according to Cmax, AUC and Tmax. Results VBE results demonstrated that naproxen products with in vitro dissolution reaching 85% dissolved within 90 min would lie comfortably within the bioequivalence limits for Cmax and AUC. Based on the establishment of VBE, a dissolution “safe space” was designed and a clinically relevant specification for naproxen products was proposed. The interplay between formulation-related and drug-specific PK parameters (e.g., t1/2) to predict the in vivo performance was also investigated. Conclusion Over a wide range of values, the in vitro dissolution rate is not critical for the clinical performance of naproxen products and therefore naproxen could be eligible for BCS-based biowaivers based on in vitro dissolution under intestinal conditions. This approach may also be applicable to other poorly soluble acidic compounds with long half-lives, providing an opportunity to streamline drug development and regulatory decision-making without putting the patient at a risk