Background: Local audits of Helicobacter pylori (H. pylori) prescriptions and outcomes are necessary to assess guideline awareness among clinicians and treatment effectiveness. Aims: The aims were to investigate first-line prescriptions and effectiveness over a 10-year period in Ireland and evaluate the influence of the 2017 Irish consensus guidelines on these trends. Methods: Data were collected at e-CRF AEG-REDCap from the European Registry on H. pylori management (Hp-EuReg) and quality reviewed from 2013 to 2022. All treatment-naïve cases were assessed for effectiveness by modified intention-to-treat (mITT) analysis. Multivariate analysis was also performed. Results: Data from 1000 patients (mean age 50 ± 15 years; 54% female) were analyzed. Clarithromycin (C) and amoxicillin (A) triple therapy represented 88% of treatments, followed by sequential C, A, and metronidazole (M) therapy (4.3%) and triple C + M (2.7%). Bismuth quadruple therapy was prescribed in 1.7% of cases. Treatment durations of 14, 10, and 7 days accounted for 87%, 4.5%, and 8.5% of prescriptions, respectively. High-, standard-, and low-dose proton pump inhibitors (PPIs; 80 mg, 40 mg, and 20 mg omeprazole equivalent b.i.d.) were used in 86%, 0.9%, and 13% of cases, respectively. The overall eradication rate was 80%, while it was 81% for triple C + A. Good compliance and high-dose PPI were associated with higher overall mITT eradication rates (OR 4.5 and OR 1.9, respectively) and triple C + A eradication rates (OR 4.2 and OR 1.9, respectively). Overall eradication rates increased from 74% pre-2017 to 82% (p < 0.05) by the end of 2022. Similarly, the triple C + A eradication rates increased from 76% to 83% (p < 0.05). Conclusions: While first-line treatment effectiveness improved in clinical practice over time, cure rates remain below 90%. Alternative first-line strategies are required in Ireland.

A series of lysine-based vinyl sulfone peptidomimetics were synthesised and evaluated for anti-trypanosomal activity against bloodstream forms of T. brucei. This focused set of compounds, varying in the P₃ position, were accessed in a divergent manner from a common intermediate (ammonium salt 8). Several P₃ analogues exhibited sub-micromolar EC₅₀ values, with thiourea 14, urea 15 and amide 21 representing the most potent anti-trypanosomal derivatives of the series. In order to establish an in vitro selectivity index the most active anti-trypanosomal compounds were also assessed for their impact on cell viability and cytotoxity effects in mammalian cells. Encouragingly, all compounds only reduced cellular metabolic activity in mammalian cells to a modest level and little, or no cytotoxicity, was observed with the series.

Background: There has been a reduction in successful H. pylori eradication rates recently, which is largely attributed to increasing antibiotic resistance. In areas of high dual clarithromycin and metronidazole resistance such as ours, Maastricht VI/Florence guidelines recommend bismuth quadruple therapy (BQT) as first line of therapy; however, the availability of bismuth was poor in Ireland until recently. Similarly, tetracycline, a component of BQT, is restricted locally, with doxycycline (D) being approved and reimbursed for most indications. Aims: To assess the efficacy of BQT-D therapy for H. pylori eradication in an Irish cohort. Methods: All patients testing positive for H. pylori in three Irish referral centres by urea breath test, stool antigen, or histology were treated prospectively with BQT-D (bismuth subcitrate 120 mg QDS, metronidazole 400 mg TDS, doxycycline 100 mg BD and esomeprazole 40 mg BD) for 14 days. Eradication was evaluated with a urea breath test (UBT) >4 weeks after therapy cessation or by stool antigen testing, as available. Outcomes were recorded and analysed according to demographics and H. pylori treatment history of the patients. Results: 217 patients completed post-eradication testing. Of which, 124 (57%) were female, with a mean age 52 years. 180 patients (83%) were treatment-naïve. A total of 165/180 (92%) of the treatment-naïve patients had successful eradication. There was no association between eradication and gender or age in this cohort (p = 0.3091, p = 0.962 respectively). A total of 29 patients received this therapy as second-line therapy, of which 22 (76%) had successful eradication. Eight patients received the regimen as rescue therapy, with seven (88%) having successful eradication. No serious adverse events were reported. Eleven individuals (6.5%) commented on the complicated nature of the regimen, with 11 tablets being taken at five intervals daily. Conclusions: BQT-D as first-line therapy for H. pylori infection is highly effective in a high dual-resistance population, achieving >90% eradication. BQT-D as a second-line treatment performed less well. Our data support BQT-D as a first-line treatment.

Resistance surveillance programmes are essential for choosing the most appropriate eradication therapy for the stomach pathogen Helicobacter pylori. This study aimed to determine H. pylori antimicrobial resistance rates in Ireland. H. pylori was cultured from patients attending four gastroenterology clinics from 2018 to 2023. Antimicrobial susceptibility testing (AST) was performed using Etests for metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline and rifampicin and resistance classified using EUCAST guidelines. Resistance rates were compared between H. pylori treatment-naïve and previously treated patients (primary and secondary resistance, respectively). Samples from 138 culture-positive patients (mean age 49.4 ± 15.7 years, 47.1% female) were analysed. A total of 28.7% of isolates from treatment-naïve patients were susceptible to all antimicrobials tested. Primary resistance rates to metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline and rifampicin were 44.3%, 36.5%, 18.3%, 14.6%, 9.6% and 9.6%, respectively. Primary dual resistance to clarithromycin and metronidazole was 22.6% and primary multidrug resistance was 13.0%. Secondary resistance rates were significantly higher than primary resistance rates for clarithromycin, metronidazole, dual resistance to clarithromycin and either amoxicillin, metronidazole or levofloxacin, and multidrug resistance. Female sex and older age were associated with increased risk of resistance. H. pylori resistance rates were high in our cohort. Clarithromycin-based triple therapy should no longer be used in Ireland in the absence of pre-treatment AST. Resistance to amoxicillin, tetracycline and rifampicin should be monitored closely.

Background: Long COVID syndrome (LCS) affects at least 10% of COVID-19 survivors. Dysautonomia and orthostatic intolerance (OI) are recognised manifestations of long COVID syndrome (LCS). Postural orthostatic syndrome of hypocapnia (POSH) is among the most frequently identified physiological markers of orthostatic intolerance in this patient population. This study aims to evaluate the prevalence of OI and POSH in a cohort of patients with LCS and then treat patients with LCS and evidence of dysfunctional breathing and hypocapnia with targeted respiratory rehabilitation to evaluate the response in physiology and symptoms. Methods: Adults (>18 years) with a diagnosis of long COVID syndrome (LCS) underwent a NASA lean test (NLT) in our dedicated long COVID clinic. The NLT consists of measurements of respiratory rate, heart rate, blood pressure, oxygen saturation, end-tidal carbon dioxide (ETCO₂), and symptoms taken over a 10 min period in the supine position, followed by repeated measurements in the leaning position. Patients with evidence of LCS, dysfunctional breathing and hypocapnia from the lean test were referred for targeted respiratory rehabilitation using the Papworth method. Results: A representative sample of patients with LCS (N = 50) underwent the NLT. Orthostatic symptoms were elicited in 50.0% of patients (n = 25) during the NASA Lean Test. Supine or orthostatic hypocapnia was identified in 64.0% of patients (n = 32), while postural orthostatic tachycardia and postural orthostatic hypotension were each observed in 32.0% of patients (n = 16). A total of 62.0% (n = 31) of patients with LCS who had persistent dyspnoea or evidence of OI as supported by supine or orthostatic hypocapnia were referred for targeted respiratory rehabilitation. Of the group referred, 41.9% (13 of the 31) completed respiratory rehabilitation. Comparing mean pre- and post-physiotherapy respiratory rehabilitation values, there was a significant improvement in the Malmö POTS score and the breathing pattern assessment tool (BPAT) (5.7 ± 1.9 vs. 2.1 ± 1.0, p < 0.0001) without a corresponding improvement in end-tidal CO₂. Conclusions: These findings provide additional evidence supporting the presence of dysautonomia and OI in patients with long COVID syndrome (LCS). The NLT is a test for OI that can be easily performed in the clinic. Respiratory rehabilitation can improve symptoms related to dysfunctional breathing and OI in LCS. Although hypocapnia has been implicated in orthostatic cerebral vasoconstriction and was postulated as a treatable target in LCS, improvement in the symptoms that we observed were independent of changes in end-tidal CO₂ on lean testing.