Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Post-Covid-19 Irritable Bowel Syndrome

Objectives The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. Design GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p < 0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. Conclusion Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls

Psychological and Clinical Factors Mediate Post-COVID-19 Irritable Bowel Syndrome

Background: Exposure to COVID-19 has been shown previously to be associated with a higher risk for irritable bowel syndrome (IBS). This study aimed to better explain this relationship using mediation analysis. Methods: This post hoc analysis of a multicenter cohort study includes 623 patients with and without COVID-19 infection. All participants completed the ROME IV criteria, gastrointestinal symptom rating scale (GSRS), and hospital anxiety and depression scale (HADS) over 1 year. Mediation analysis utilized the PROCESS macro and Baron and Kenny's method for parametric and nonparametric mediating variables, respectively. Key results: The impact of COVID-19 on the development of post-COVID-19 IBS is completely mediated by dyspnea at baseline (adjusted OR = 3.561, p = 0.012), severity of acid regurgitation at 1 month [indirect effect, log-odds metric = 0.090, 95% CI (0.006-0.180)], hunger pains at 1 [indirect effect, log-odds metric = 0.094, 95% CI (0.024-0.178)], and 6 months [indirect effect, log-odds metric = 0.074, 95% CI (0.003-0.150)], depression at 6 [indirect effect, log-odds metric = 0.106, 95% CI (0.009-0.225)] and 12 months [indirect effect, log-odds metric = 0.146, 95% CI (0.016-0.311)] as well as borborygmus [indirect effect, log-odds metric = 0.095, 95% CI (0.009-0.203)], abdominal distention [indirect effect, log-odds metric = 0.162, 95% CI (0.047-0.303)], and increased flatus [indirect effect, log-odds metric = 0.110, 95% CI (0.005-0.234)] at 12 months. Conclusions and inferences: Our findings provide evidence for psychological and clinical mediators between COVID-19 and post-COVID-19 IBS, which may be promising targets for interventions tailored for treating or preventing depression. The presence of specific GI symptoms at COVID-19 onset and their persistence should increase awareness of a potential new onset of IBS diagnosis.

Long-Term Impact of COVID-19 on Disorders of Gut–Brain Interaction: Incidence, Symptom Burden, and Psychological Comorbidities

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the potential exacerbation of gastrointestinal symptoms in patients with disorders of gut-brain interaction (DGBIs). However, the distinct symptom trajectories and psychological burden in patients with post-COVID-19 DGBIs compared with patients with pre-existing irritable bowel syndrome (IBS)/functional dyspepsia (FD) and non-DGBI controls remain poorly understood. Objectives: To examine the long-term gastrointestinal symptom progression and psychological comorbidities in patients with post-COVID-19 DGBI, patients with pre-existing IBS/FD and non-DGBI controls. Methods: This post hoc analysis of a prospective multicenter cohort study reviewed patient charts for demographic data and medical history. Participants completed the Gastrointestinal Symptom Rating Scale at four time points: baseline, 1, 6, and 12&nbsp;months, and the Hospital Anxiety and Depression Scale at 6 and 12&nbsp;months. The cohort was divided into three groups: (1) post-COVID-19 DGBIs (2) non-DGBI, and (3) pre-existing IBS/FD, with the post-COVID-19 DGBIs group compared to the latter two control groups. Results: Among 599 eligible patients, 27 (4.5%) were identified as post-COVID-19 DGBI. This group experienced worsening abdominal pain, hunger pain, heartburn, and acid regurgitation, unlike symptom improvement or stability in non-DGBI controls (p&nbsp;&lt;&nbsp;0.001 for all symptoms, except hunger pain, p&nbsp;=&nbsp;0.001). While patients with pre-existing IBS/FD improved in most gastrointestinal symptoms but worsened in constipation and incomplete evacuation, patients with post-COVID-19 DGBI exhibited consistent symptom deterioration across multiple gastrointestinal domains. Anxiety and depression remained unchanged in patients with post-COVID-19 DGBI, contrasting with significant reductions in controls (non-DGBI: p&nbsp;=&nbsp;0.003 and p&nbsp;=&nbsp;0.057; pre-existing IBS/FD: p&nbsp;=&nbsp;0.019 and p&nbsp;=&nbsp;0.007, respectively). Conclusions: COVID-19 infection is associated with the development of newly diagnosed DGBIs and distinct symptom trajectories when compared with patients with pre-existing IBS/FD. Patients with post-COVID-19 DGBI experience progressive gastrointestinal symptom deterioration and persistent psychological distress, underscoring the need for tailored management strategies for this unique subgroup

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

STREPTOCOCCAL PHARYNGITIS – AN ACTUAL POINT OF VIEW

The infection with Streptococcus pyogenes causes acute illness and also poststreptococcal syndromes of acute glomerulonephritis and acute rheumatic fever. Material and method: Retrospective study of the cases with acute pharyngitis admitted in the Hospital of Infectious Diseases from Iassy in 2010 with a bacteriological and therapeutically analysis. Results: It registered 1562 patients. 128 patients were diagnosticated with streptococcal pharyngitis (by throat culture) and 1434 cases had negative throat. 43 cases of streptococcal pharyngitis and 423 cases of the others had severe clinical form. ASLO titer had high value in 35,3% from tests. In 1394 cases, Penicillin G was preferred; 113 patients were treated with Clarithromycine, 20 with Erythromycine and 35 with Clindamycine. Conclusions: In patients with symptomatology suggestive for the streptococcal pharyngitis, an etiologically diagnosis should be determined by performing a throat culture or a rapid antigen-detection test before the administration of therapy. The empirical antibiotic treatment on the basis of symptoms alone results in overuse of antibiotics, increased costs, and an increased rate of side effects from antibiotics. Penicillin is the preferred treatment