Pop-up COVID-19 vaccination clinics for vulnerable groups in the Midlands.

INTRODUCTION: Roma, travellers and the homeless suffer from a higher risk of both COVID-19 infection and severe disease relative to the general population. The purpose of this project was to ensure as many members as possible from vulnerable groups in the Midlands availed of COVID-19 vaccines. METHODS: Following on from successful testing of vulnerable populations in the Midlands of Ireland in March/April 2021, a collaboration of HSE Midland's Department of Public Health, Safetynet Primary Care and the HSE Midlands Traveller Health Unit (MTHU) operated pop-up vaccination clinics in June/July 2021, targeting the same populations. Clinics delivered the first dose of the Pfizer/BioNTech COVID-19 vaccine, registering clients for second doses in Community Vaccination Centres (CVCs). RESULTS: Thirteen clinics were hosted between 8 June 2021 and 20 July 2021, resulting in 890 first-dose Pfizer vaccinations delivered to vulnerable populations. DISCUSSION: Trust established months prior with our grassroots testing service resulted in strong vaccine uptake, with the quality service provided seeding further demand over time. This service integrated into the national system and allowed individuals to receive their second doses within the community.

Three-dimensional structure of cyclic antibiotic teicoplanin aglycone using NMR distance and dihedral angle restraints in a DMSO solvation model.

The three-dimensional solution conformation of teicoplanin aglycone was determined using NMR spectroscopy. A combination of NOE and dihedral angle restraints in a DMSO solvation model was used to calculate an ensemble of structures having a root mean square deviation of 0.17 Å. The structures were generated using systematic searches of conformational space for optimal satisfaction of distance and dihedral angle restraints. Comparison of the NMR-derived structure of teicoplanin aglycone with the X-ray structure of a teicoplanin aglycone analog revealed a common backbone conformation with deviation of two aromatic side chain substituents. Experimentally determined backbone (13)C chemical shifts showed good agreement with those computed at the density functional level of theory, providing a cross validation of the backbone conformation. The flexible portion of the molecule was consistent with the region that changes conformation to accommodate protein binding. The results showed that a hydrogen-bonded DMSO molecule in combination with NMR-derived restraints together enabled calculation of structures that satisfied experimental data.

Impact of tumour epithelial subtype on circulating microRNAs in breast cancer patients.

While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45). Three miRNAs of interest were then quantified in the circulation(n = 166) and tissue (n = 100) of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes >2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of miRNAs, and highlights divergent miRNA profiles between tissue and blood samples from breast cancer patients.

Retrospective analysis of radiation exposure during endoscopic retrograde cholagiopancreatography: critical determinants.

BACKGROUND: Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) has a logarithmic relationship with radiation exposure, and carries a known risk of radiation exposure to patients and staff. Factors associated with prolonged fluoroscopy duration have not been well delineated. OBJECTIVES: To determine the specific patient, physician and procedural factors that affect fluoroscopy duration. METHODS: A retrospective analysis of 1071 ERCPs performed at two tertiary care referral hospitals over an 18-month period was conducted. Patient, physician and procedural variables were recorded at the time of the procedure. RESULTS: The mean duration of 969 fluoroscopy procedures was 4.66 min (95% CI 4.38 to 4.93). Multivariable analysis showed that the specific patient factors associated with prolonged fluoroscopy duration included age and diagnosis (both P<0.0001). The endoscopist was found to play an important role in the duration of fluoroscopy (ie, all endoscopists studied had a mean fluoroscopy duration significantly different from the reference endoscopist). In addition, the following procedural variables were found to be significant: number of procedures, basket use, biopsies, papillotomy (all P<0.0001) and use of a tritome (P=0.004). Mean fluoroscopy duration (in minutes) with 95% CIs for different diagnoses were as follows: common bile duct stones (n=443) 5.12 (3.05 to 4.07); benign biliary strictures (n=135) 3.94 (3.26 to 4.63); malignant biliary strictures (n=124) 5.82 (4.80 to 6.85); chronic pancreatitis (n=49) 4.53 (3.44 to 5.63); bile leak (n=26) 3.67 (2.23 to 5.09); and ampullary mass (n=11) 3.88 (1.28 to 6.48). When no pathology was found (n=195), the mean fluoroscopy time was 3.56 min (95% CI 3.05 to 4.07). Comparison using t tests determined that the only two diagnoses for which fluoroscopy duration was significantly different from the reference diagnosis of 'no pathology found' were common bile duct stones (P<0.0001) and malignant strictures (P<0.0001). CONCLUSIONS: Factors that significantly affected fluoroscopy duration included age, diagnosis, endoscopist, and the number and nature of procedures performed. Elderly patients with biliary stones or a malignant stricture were likely to require the longest duration of fluoroscopy. These identified variables may help endoscopists predict which procedures are associated with prolonged fluoroscopy duration so that appropriate precautions can be undertaken.

Prospective analysis of fluoroscopy duration during ERCP: critical determinants.

BACKGROUND: Fluoroscopy during ERCP has a linear relationship with radiation, carrying risk of exposure. OBJECTIVE: To determine patient, physician, and procedural factors affecting fluoroscopy duration. DESIGN: Prospective analysis of ERCPs with evaluation of patient, physician, and procedural variables. SETTING: Two tertiary-care hospitals. PATIENTS: Consecutive patients undergoing ERCP. INTERVENTIONS: ERCP. MAIN OUTCOME MEASUREMENTS: Variables associated with prolonged fluoroscopy duration. RESULTS: Mean fluoroscopy time (388 ERCPs) was 6.77 minutes (95% CI, 6.15-7.39). No patient factors were found to significantly affect fluoroscopy duration. Fluoroscopy duration was significantly lower for 2 endoscopists compared with the reference endoscopist (average of 4.16 minutes less; 95% CI, -5.48 to -2.48). Multivariable analysis identified variables associated with longer fluoroscopy duration; stent insertion (+3.11 minutes; 95% CI, 1.91-4.30), lithotripsy (+5.74 minutes; 95% CI, 0.931-10.5), needle-knife sphincterotomy (+4.44 minutes; 95% CI, 2.20-6.67), biopsies (+2.11 minutes; 95% CI, 0.025-4.18), use of a guidewire (+1.55 minutes; 95% CI, 0.025-3.07), additional guidewires (+5.61 minutes; 95% CI, 2.69-8.51), and balloon catheter (+4.27 minutes; 95% CI, 3.00-5.53). Mean fluoroscopy duration when a gastroenterology fellow was involved (n = 318) was 7.05 minutes (95% CI, 6.35-7.76) compared with 5.44 minutes (95% CI, 4.26-6.63) when no fellow present (n = 70) (P < .0451). LIMITATIONS: Only 2 centers; others may have different results. Not blinded; investigators may change their practice because fluoroscopy was duration studied. Irrelevance of measuring fluoroscopy duration because endoscopists using protection may not have increased radiation exposure. CONCLUSIONS: In this prospective analysis, factors associated with fluoroscopy duration included endoscopists; stent insertion; lithotripsy; biopsies; use of a needle-knife, guidewire, and balloon catheter; and involvement of a gastroenterology fellow. These identified variables may help endoscopists predict which procedures are associated with prolonged fluoroscopy duration and may lead to appropriate precautions.

Long-term follow-up of patients with iron deficiency anaemia after a negative gastrointestinal evaluation.

OBJECTIVES: Our aim was to determine whether patients who have had a negative gastrointestinal evaluation (i.e. oesophagogastroduodenoscopy and a colonic examination) for iron deficiency anaemia are subsequently found to have recurrent anaemia or significant pathology. METHODS: From a prospectively entered endoscopy database, we identified a cohort of patients who had negative upper and lower gastrointestinal (GI) investigations for iron deficiency anaemia. We carried out a retrospective chart review of these patients to determine their outcome after a GI evaluation. In particular, we wished to determine the proportion of patients who had recurrent anaemia, became transfusion dependent or were found to have significant pathology. RESULTS: Sixty-nine patients, with an average age of 65.8 years (range 29-87), were followed up for a median of 5 years and 10 months (range 7-109). In 57 patients (83%), the anaemia resolved after the initial treatment period. Fifteen patients (22%) died during the follow-up period, two from a GI cancer and 13 from non-GI-related causes. Six patients (9%) developed persistent anaemia severe enough to require recurrent blood or iron transfusions. Seventeen patients (25%) had a transient recurrent anaemia and four (6%) were diagnosed with GI malignancies during the follow-up. CONCLUSION: For the majority of patients with the iron deficiency anaemia and a negative GI evaluation the outcome is favourable, although a proportion (6%) may subsequently be found to have significant GI pathology. We believe that this number could be minimized by the use of colonoscopy rather than barium enema. In addition, small bowel investigations should not be limited to those who are transfusion dependent, as is currently recommended.

For patients with predicted low risk for choledocholithiasis undergoing laparoscopic cholecystectomy, selective intraoperative cholangiography and postoperative endoscopic retrograde cholangiopancreatography is an effective strategy to limit unnecessary procedures.

BACKGROUND: There is debate about whether intraoperative cholangiography (IOC) should be performed routinely or selectively during laparoscopic cholecystectomy (LC) in patients with suspected choledocholithiasis. The timing of endoscopic retrograde cholangiopancreatography (ERCP) in these patients also is an issue. We reviewed the experience in our center, where a management algorithm limiting ERCP in relation to LC was adopted. METHODS: We retrospectively reviewed every LC performed by one surgeon during 6 years and the related ERCPs. RESULTS: A total of 264 LCs were performed. In 30 patients, stones were cleared or excluded by preoperative ERCP. In the remaining 234 LCs, 31 of 34 IOCs were successfully performed. Two of 31 IOCs were positive for bile duct stones; stone removal was successful in each patient at subsequent ERCP. Only 10 of 201 patients who did not have IOC required postsurgical ERCP within 10 weeks of LC, 3 of whom had common bile duct stones at ERCP. CONCLUSIONS: For patients who underwent LC, we performed selective IOC with postoperative ERCP for positive studies. Review of our experience using this algorithm showed it to be a powerful tool in limiting unnecessary ERCPs. Our data suggest that routine preoperative ERCP cannot be justified. Selective IOC during LC misses relatively few cases of biliary stones; these can be managed quickly by experienced endoscopists.

Endoscopic stenting: where are we now and where can we go?

Self expanding metal stents (SEMS) play an important role in the management of malignant obstructing lesions in the gastrointestinal tract. Traditionally, they have been used for palliation in malignant gastric outlet and colonic obstruction and esophageal malignancy. The development of the polyflex stent, which is a removable self expanding plastic stent, allows temporary stent insertion for benign esophageal disease and possibly for patients undergoing neoadjuvant chemotherapy prior to esophagectomy. Potential complications of SEMS insertion include perforation, tumour overgrowth or ingrowth, and stent migration. Newer stents are being developed with the aim of increasing technical and clinical success rates, while reducing complication rates. Other areas of development include biodegradable stents for benign disease and radioactive or drug-eluting stents for malignant disease. It is hoped that, in the future, newer stents will improve our management of these difficult conditions and, possibly, provide prognostic as well as symptomatic benefit in the setting of malignant obstruction.

Endoscopic retrograde cholangiopancreatography in the management of benign biliary strictures.

Several conditions may cause benign biliary stricture formation. Intraoperative bile duct injury, most often sustained during laparoscopic cholecystectomy, is the leading cause. Although surgical bypass procedure was the traditional treatment of choice for benign extrahepatic biliary strictures, therapeutic endoscopic retrograde cholangiopancreatography has recently come into favor; however, success rates have been variable and largely dependent on the underlying etiology. Because endoscopic therapy may be unsuccessful, a multidisciplinary approach to management, with surgical or radiological intervention if necessary, should be considered.

Endoscopy in the management of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver condition characterized by progressive fibrosis and destruction of the intra- and extrahepatic biliary tree. PSC has a clear association with inflammatory bowel disease and is often progressive, leading to cirrhosis and end-stage liver failure. For many patients, liver transplantation offers the only hope of long-term survival. No effective medical treatment exists, and therapy is often aimed at treating complications of the disorder, including dominant biliary strictures, which may cause symptomatic jaundice, cholangitis, and pruritus. Studies on endoscopic therapy (eg, biliary dilation and/or stent insertion) have shown favorable results, although most studies have been small, retrospective, and uncontrolled. Up to 20% of patients with PSC develop cholangiocarcinoma; however, distinguishing between cholangiocarcinoma and benign strictures can be difficult. Ideally, randomized trials are required to determine the safest and most effective endoscopic management for symptomatic dominant strictures.