Abstract
Background
New therapeutic options are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). Repurposing existing pharmaceuticals provides an immediate treatment ...opportunity. We assessed the efficacy of sofosbuvir and daclatasvir with ribavirin for treating patients with COVID-19.
Methods
This was a single-centre, randomized controlled trial in adults with moderate COVID-19 admitted to the Ghaem Shahr Razi Hospital in Mazandaran Province, Iran. Patients were randomly assigned to 400 mg sofosbuvir, 60 mg daclatasvir and 1200 mg ribavirin (intervention group) or to standard care (control group). The primary endpoint of this study was length of hospital stay. This study is registered by IRCT.ir under the ID: IRCT20200328046886N1.
Results
Between 20 March 2020 and 8 April 2020, 48 patients were recruited; 24 patients were randomly assigned to the intervention group and 24 to the control group. The median duration of hospital stay was 6 days in both groups (P = 0.398). The number of ICU admissions in the sofosbuvir/daclatasvir/ribavirin group was not significantly lower than the control group (0 versus 4, P = 0.109). There was no difference in the number of deaths between the groups (0 versus 3, P = 0.234). The cumulative incidence of recovery was higher in the sofosbuvir/daclatasvir/ribavirin arm (Gray’s P = 0.033).
Conclusions
This randomized trial was too small to make definitive conclusions. There were trends in favour of the sofosbuvir/daclatasvir/ribavirin arm for recovery and lower death rates. However, there was an imbalance in the baseline characteristics between the arms. Larger randomized trials should be conducted to investigate this treatment further.
Abstract
Intestinal epithelial cell damage caused by SARS-CoV-2 infection was thought to be associated with gastrointestinal symptoms and decreased fecal consistency. The association of the ...gastrointestinal symptoms with the COVID-19-mediated inflammatory response triggered by the gastrointestinal immune system was investigated in this paper. Intestinal inflammation marker fecal calprotectin along with serum calprotectin and other inflammatory markers were measured in COVID-19 cases with and without GI manifestations as well as healthy individuals. Analyses were performed to compare COVID-19 patient subgroups and healthy controls and examine the relationship between fecal and serum calprotectin levels with gastrointestinal symptoms and disease severity. COVID-19 patients (
n
= 70) were found to have markedly elevated median levels of fecal (124.3 vs. 25.0 µg/g;
P
< 0/0001) and serum calprotectin (3500 vs. 1060 ng/mL;
P
< 0/0001) compared with uninfected controls. Fecal and serum calprotectin levels were not significantly different between COVID-19 patients who displayed GI symptoms and those who did not. Compared with other acute phase markers, both fecal and serum calprotectin were superior in identifying COVID-19 patients who progressed to severe illness. Although the progression of COVID-19 disease is marked by an elevation of fecal and serum calprotectin, gastrointestinal symptoms or diarrhea were not correlated with calprotectin increase level.
Abstract
Background
The combination of sofosbuvir and daclatasvir has a well-established safety profile and improves clinical outcomes in HCV patients. In silico and in vitro studies suggest that ...sofosbuvir/daclatasvir may show antiviral activity against SARS-CoV-2.
Methods
Three clinical trials comparing sofosbuvir/daclatasvir-based regimens with a comparator in hospitalized COVID-19 patients were combined in a meta-analysis. The primary outcomes measured were clinical recovery within 14 days of randomization, time to clinical recovery and all-cause mortality. A two-step approach was used to analyse individual-level patient data. The individual trial statistics were pooled using the random-effects inverse-variance model.
Results
Our search identified eight studies of which three met the inclusion criteria (n = 176 patients); two studies were randomized and one was non-randomized. Baseline characteristics were similar across treatment arms. Clinical recovery within 14 days of randomization was higher in the sofosbuvir/daclatasvir arms compared with control arms risk ratio = 1.34 (95% CI = 1.05–1.71), P = 0.020. Sofosbuvir/daclatasvir improves time to clinical recovery HR = 2.04 (95% CI = 1.25–3.32), P = 0.004. The pooled risk of all-cause mortality was significantly lower in the sofosbuvir/daclatasvir arms compared with control arms risk ratio = 0.31 (95% CI = 0.12–0.78), P = 0.013.
Conclusions
Available evidence suggests that sofosbuvir/daclatasvir improves survival and clinical recovery in patients with moderate to severe COVID-19. However, the sample size for analysis was relatively small, one of the trials was not randomized and the designs were not standardized. These results need to be confirmed in larger randomized controlled trials.
Celiac disease (CD) is an immune-mediated disorder with various manifestations. The aim of this study was to evaluate the prevalence of gastrointestinal (GI) and extra-intestinal symptoms of celiac ...patients, especially migraine, and compare it with healthy individuals.
We compared 1000 celiac subjects (CS) registered at our celiac center with the control group for headache-based on International Classification of Headache Disorders, third edition criteria and their GI symptoms. Besides, CS with migraine and non-migrainous headache were compared in terms of GI symptoms and accompanied conditions.
Headache was more common in CS than controls (34% vs 27% respectively, P value<0.001) and more prevalent in females (71.9% in females vs 28% in males, P value = 0.004). Moreover, the prevalence of migraine in CS was higher than controls (20.7 vs 11.9% respectively, P value<0.001). Furthermore, migraine was more prevalent in females with CD (80% in females vs 19% in males, P value = 0.033), and often without aura (76%). Abdominal pain (76.9%, P value = 0.025), diarrhea (54.9%, P value = 0.002), and constipation (42.9%, P value = 0.011) were the most common GI symptoms in CS with headache and more prevalent in CS with migraine. Conversely, type 1 diabetes mellitus was less common in CS with migraine than in CS with non-migrainous headache. (P value = 0.001). On multivariate logistic regression analysis, female sex (OR 1.50, 95%CI 1.22-1.83, P value < 0.001), and CD (OR 1.36, 95%CI 1.12-1.65, P value = 0.002) were independent predictors of headache, whereas age more than 60 years (OR 0.70, 95%CI 0.50-0.97, P value = 0.032) had a protective effect.
Headache especially migraine is more prevalent in CS than healthy controls. In addition, abdominal pain, diarrhea, and constipation are more common in CS with migraine than in CS with non-migrainous headaches. Therefore, evaluation of CD in patients with migraine and these simultaneous GI symptoms seems reasonable.
Despite the rising prevalence of Inflammatory Bowel Disease (IBD), age and sex differences in its outcomes remain understudied. We investigated age and sex differences in IBD patients using a ...nationwide study in Iran, the Iranian Registry of Crohn's and Colitis (IRCC). The IRCC is a national registry that gathered information on adult IBD patients since 2017. The collected data included demographic information, medication history, disease activity, comorbidities, diagnosis age, prognosis, the extent of ulcerative colitis (UC), Crohn's disease (CD) location, and extraintestinal manifestations. The statistical methods included the independent Student's t-test, Chi-square test, and binary logistic regression, using R version 4.2.2. Among the 9,392 IBD patients, 7,496 (3,600 females) and 1,896 (808 females) had UC and CD, respectively. Sex difference showed higher odds of active disease in the past six months in male CD patients (OR 1.24 95%CI 1.03, 1.49) vs. females, but in male UC patients, the OR was 0.85 0.78, 0.93. Severe disease was less likely in CD patients aged 19-59 and >60 vs. <18. Similarly, UC patients 60. This study emphasizes the importance of understanding age and sex differences in IBD outcomes. These findings contribute to the ongoing global discussion on IBD management and facilitate the development of targeted interventions and personalized care.
Appendiceal mucocele (AM) is a rare disease, manifested by accumulation of mucus in appendiceal lumen. The role of ulcerative colitis (UC) in the occurrence of appendiceal mucocele is not known. ...However, it is suggested that AM may be a presentation of colorectal cancer in IBD patients.
Here, we presented 3 cases of concomitant AM and ulcerative colitis. The first patient was a 55-year-old woman with 2-year history of left sided UC; the second person was a 52-year-old woman with 12-year history of pan-UC; and the third patient was a 60-year-old man with 11-year history of pan-colitis. They were all referred due to indolent right lower quadrant abdominal pain. Imaging evaluations suggested the presence of appendiceal mucocele and therefore, they all went under operation. Pathologic evaluation reported AM of mucinous cyst adenoma type; low-grade appendiceal mucinous neoplasm of appendix with intact serosa; and cyst-adenoma type AM for the three above-mentioned patients, respectively.
Although concomitant occurrence of AM and ulcerative colitis is rare, regarding the potential of neoplastic changes in AM, physicians must keep in mind the diagnosis of AM in UC patients with non-specific abdominal RLQ pain or bulged appendiceal orifice during colonoscopy.
The efficacy of first-and second-line Helicobacter pylori(H.pylori)eradication regimens varies considerably in West Asian countries,mainly due to the variable prevalence of resistant ...organisms.However,no review article has yet evaluated and compared the efficacy of different regimens among different countries of this region.Therefore,we conducted a review to select the best options and provide recommendations for H.pylori treatment in this geographic region.A search through PubMed was carried out to obtain relevant randomized clinical trials published in English language up to June2013.According to the results,among different therapeutic regimens used as the first-line protocols,10-d Bismuth-Furazolidone/Metronidazole quadruple therapy,14-d Clarithromycin-containing hybrid therapy and 14-d quadruple therapy including a proton pump inhibitor +Bismuth+Tetracycline(500 mg QID)+Metronidazole(500 mg TDS)seemed to be appropriate options.Among second-line therapeutic regimens,Bismuthbased quadruple therapies containing Tetracycline and Furazolidone/Metronidazole,triple therapy containing Amoxicillin and Gatifloxacin and Quadruple therapy including Bismuth+Azithromycin and Ofloxacin seemed to be effective options.Third-line therapies were not evaluated in West Asia;most guidelines,however,recommend choosing optimal eradication regimen according to the pattern of antibiotic susceptibility of H.pylori.Although we limited our investigation to H.pylori eradication regimens in West Asia,the clinical significance of the results goes beyond the countries situated in this geographic region.In fact,the results are transferrable to any region as long as the patterns of resistance are the same.
Background
The eradication of Helicobacter pylori has been always a concern. In the present study, we aimed to compare two novel treatments in Iran.
Method
Four hundred and twenty patients with ...peptic ulcer and naïve H. pylori infection were randomized in the study. Two hundred and ten patients received hybrid therapy: pantoprazole 40 mg/b.i.d. and amoxicillin 1 g/b.i.d. for 14 days plus 500 mg clarithromycin and 500 mg tinidazole, both twice daily for the last 7 days. The other 210 patients received sequential therapy: 40 mg pantoprazole/b.i.d. for 10 days and 1 g amoxicillin/b.i.d. for the first 5 days, followed by 500 mg clarithromycin/b.i.d. and 500 mg tinidazole/b.i.d. for the last 5 days. C¹⁴‐urea breath test was performed 8 weeks after the treatment.
Results
Three hundred and ninety‐six patients (197 patients in the hybrid group and 199 patients in the sequential group) completed the study. The compliance rates were 96.7 and 98.6% for the two groups, respectively. The intention‐to‐treat eradication rate was 89.5% (95% CI = 85.4–93.6) for the hybrid group and 76.7% (95% CI = 71–82.4) for the sequential group (p = .001), and the per‐protocol eradication rates were 92.9% (95% CI = 89.2–96.5) and 79.9% (95% CI = 74.1–85.4) for the hybrid and sequential groups (p = .001), respectively. Severe adverse effects were observed in 2.4% of patients in the hybrid group and 3.8% of those in the sequential group.
Conclusion
According to our results, sequential regimen does not seem to be an appropriate therapy for H. pylori eradication in the Iranian population, whereas hybrid therapy showed to be more effective. However, considering the high cost of clarithromycin in Iran, we recommend further studies to compare hybrid therapy with bismuth‐containing regimens or to assess the effects of hybrid therapies with periods shorter than 14 days.
Background and purpose: About half of the world’s population is infected with Helicobacter pylori (H. pylori). But, the efficacy of therapeutic regimens decreases over time due to increasing ...resistance of H. pylori to antibiotics. This research aimed at evaluating the efficacy of two triple therapy regimens. Materials and methods: This tudy was performed in Sari Imam Khomeini Hospital, 2016-2017. One hundred forty patients with peptic ulcer disease and naïve H. pylori infection were randomly divided into two groups to receive either 10-day standard triple therapy (Pantoprazole 40 mg, Amoxicillin 1 gr, and Clarithromycin 500mg, all twice daily) or 10-day Levofloxacin-containing triple therapy (Pantoprazole 40 mg BD, Amoxicillin 1000mg BD, and Levofloxacin 500 mg/daily). Eight weeks after the treatment, H. pylori eradication was assessed by 14C- urea breath test. Results: A total of 133 patients completed the study. According to intention to treat analysis (ITT), H. pylori eradication rates were 75.7% (95% CI: 65.7%-85.7%) and 58.8% (95% CI= 47.1%-70%) in standard and Levofloxacin-containing therapies, respectively. Also, per-protocol eradication rates were 83% (95% CI: 74%-92%) and 61% (95% CI= 49%-73%), respectively. The rates of severe adverse effects of therapy were 7.1% and 2.9% in the aforementioned groups, respectively. Conclusion: Both Clarithromycin- and Levofloxacin-containing triple therapies do not seem to be suitable options for first-line H. pylori eradication in Iran. We suggest using Clarithromycin in quadruple regimens and reserve Levofloxacin to be used in second-line eradication regimens, as recommended by Maastricht V Consensus Report. (Clinical Trials Registry Number: IRCT2015110224825NI)
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