ADVANCING CAPSULE ENDOSCOPY IN THE EXAMINATION OF THE UPPER GASTROINTESTINAL TRACT

Advancements in capsule endoscopy technology allow it to image the upper gastrointestinal tract. Oesophagogastroduodenoscopy (OGD) is the gold standard examination, but it is often poorly tolerated and requires sedative premedication. This thesis examines how capsule endoscopy can improve the quality of an upper GI endoscopic examination. The first study examines the rate of, and factors affecting missed cancer occurrence after conventional OGD. In this retrospective study, a total of 48 (7.7%) of 627 patients with oesophagogastric cancer had OGDs up to three years prior, which are considered missed opportunities to diagnose early neoplasia. Endoscopy sessions with missed cancer occurrence had at least one procedure more when compared to sessions where cancer was subsequently diagnosed or sessions where benign focal lesions were diagnosed. In the next two studies, we examine the patients experience in a comparative study of tolerance and acceptability between magnet controlled capsule endoscopy (MACE) and conventional OGD (n=44) and transnasal endoscopy (TNE; n=16). By comparison to OGD in Chapter 4 and TNE in Chapter 5, patients were more accepting of and preferred MACE. Patients experienced significantly more distress (greater distress with higher median score) due to gagging (6 vs 1), choking (5 vs 1), abdominal bloating (2 vs 1), instrumentation (4 vs 1), discomfort during (5 vs 1) and after (2 vs 1) OGD when compared to MACE (all p<0.0001). Patients undergoing TNE were more distressed by gagging (1.5 vs 1, p=0.03), choking (3 vs 1, p=0.001), instrumentation (4.5 vs 1, p=0.001), discomfort during (5 vs 1, p=0.001) and after TNE (2 vs 1, p=0.01) by comparison to MACE. A small bowel examination can be performed immediately after an upper GI MACE. It is hypothesised that laxative pre-procedure preparation may benefit small bowel mucosal visualisation, although likely to impact on tolerability and acceptance. The fourth study examines how to optimise an upper GI MACE examination to investigate iii the small bowel. In advance of a small bowel capsule endoscopy, 186 patients were randomised to three pre-procedure preparation groups: clear fluids only or a single or split dose of polyethylene glycol (PEG) the examine the need for laxative pre-procedure medication. Split dose PEG improved distal small bowel mucosal views and overall adequacy of examination compared to clear fluids alone, although patients tolerated better and were more accepting of the later. Acceptance of novel technology may be prohibited by cost. In the final study, we perform a cost minimisation analysis to examine how the cost of MACE compares to TNE and OGD, and examine in scenario analyses the potential effects of the COVID-19 pandemic and need for endoscopic biopsies on cost. We found that per procedure, MACE was most expensive, followed by OGD and TNE. As a result of the COVID-19 pandemic, the costs of OGD and TNE would rise by between 27% to 112% depending on changes in endoscopy capacity. In scenario analyses, cost parity between MACE and OGD could be reached if the price of single use capsule endoscopes fell by two thirds. If endoscopy capacity fell to 40%, cost parity could be reached if the price of capsule endoscopes fell by a third. This thesis supports the use of MACE in the upper GI tract from the perspective of a superior patient experience compared to conventional OGD. Further improvements in imaging technology and reduction in cost of MACE will advance capsule endoscopy in the examination of the upper GI tract

Functional gastrointestinal disorders are increased in joint hypermobility-related disorders with concomitant postural orthostatic tachycardia syndrome.

Background Individuals with hypermobility spectrum disorders/hypermobile Ehlers‐Danlos syndrome (HSD/hEDS) frequently fulfill criteria for Rome IV functional gastrointestinal disorders (FGIDs). Postural orthostatic tachycardia syndrome (POTS) is also commonly reported in HSD/hEDS and may impact on co‐morbidity with and severity of FGIDs, although this remains to be studied. We determined the impact of concomitant POTS and HSD/hEDS on their association with Rome IV FGIDs. Methods With the help of the charity organization Ehlers‐Danlos Support UK, an online cross‐sectional health survey was completed by individuals with HSD/hEDS. The survey enquired for (a) self‐reported doctor diagnosis of POTS, chronic fatigue syndrome, and fibromyalgia, (b) the presence and symptom frequency of Rome IV FGIDs, and (c) anxiety and depression scores. Key Results Of 616 subjects with HSD/hEDS, 37.5% reported a doctor diagnosis of POTS. POTS‐positive individuals were significantly younger than POTS‐negative subjects (37 vs 40 years, P = 0.002), more likely to report chronic fatigue syndrome (44% vs 31%, P < 0.0001), and showed a trend toward increased prevalence of fibromyalgia (44% vs 37%, P = 0.06) and higher depression score (P = 0.07). POTS‐positive subjects were also more likely to fulfill criteria for Rome IV FGIDs across various organ domains and experienced both upper and lower gastrointestinal symptoms significantly more frequently. The increased associations for FGIDs and GI symptom frequency remained unchanged in HSD/hEDS subjects with POTS following adjustments for age, chronic fatigue syndrome, fibromyalgia, and depression scores. Conclusions and Inferences The high FGID burden in HSD/hEDS is further amplified in the presence of POTS. Future studies should elucidate the mechanism by which POTS arises in HSD/hEDS and is associated with increased GI symptoms