Background Currently no effective antiviral therapy has been found to treat COVID-19. The aim of this trial was to assess if the addition of sofosbuvir and daclatasvir improved clinical outcomes in patients with moderate or severe COVID-19. Methods This was an open-label, multicentre, randomized controlled clinical trial in adults with moderate or severe COVID-19 admitted to four university hospitals in Iran. Patients were randomized into a treatment arm receiving sofosbuvir and daclatasvir plus standard care, or a control arm receiving standard care alone. The primary endpoint was clinical recovery within 14 days of treatment. The study is registered with IRCT.ir under registration number IRCT20200128046294N2. Results Between 26 March and 26 April 2020, 66 patients were recruited and allocated to either the treatment arm (n = 33) or the control arm (n = 33). Clinical recovery within 14 days was achieved by 29/33 (88%) in the treatment arm and 22/33 (67%) in the control arm (P = 0.076). The treatment arm had a significantly shorter median duration of hospitalization [6 days (IQR 4–8)] than the control group [8 days (IQR 5–13)]; P = 0.029. Cumulative incidence of hospital discharge was significantly higher in the treatment arm versus the control (Gray’s P = 0.041). Three patients died in the treatment arm and five in the control arm. No serious adverse events were reported. Conclusions The addition of sofosbuvir and daclatasvir to standard care significantly reduced the duration of hospital stay compared with standard care alone. Although fewer deaths were observed in the treatment arm, this was not statistically significant. Conducting larger scale trials seems prudent.

Eosinophilic esophagitis should be considered in the differential diagnosis of any cases with refractory reflux who complain of chronic unexplained dysphagia, with history of recurrent food impaction, and atopy or abnormal endoscopic features.

Background:Oesophageal squamous cell carcinoma (ESCC) is a fatal disease with 5-year survival rates of <5% in Northern Iran. Oesophageal squamous dysplasia (ESD) is the precursor histologic lesion of ESCC. This pilot study was conducted to assess the feasibility, safety, and acceptability of non-endoscopic cytological examination of the oesophagus and to provide initial data on the accuracy of cytological atypia for identifying patients with ESD in this very-high-risk area.Methods:Randomly selected asymptomatic participants of the Golestan Cohort Study were recruited. A cytological specimen was taken using a capsule sponge device and evaluated for atypical cells. Sections of the cytological specimen were also stained for p53 protein. Patient acceptability was assessed using a visual analogue scale. The cytological diagnosis was compared with a chromoendoscopic examination using Lugol's solution.Results:Three hundred and forty-four subjects (43% male, mean (s.d.) age 55.6 (7.9) years) were referred to the study clinic. Three hundred and twelve met eligibility criteria and consented, of which 301 subjects (96.5%) completed both cytological and endoscopic examinations. There were no complications. Most of the participants (279; 92.7%) were satisfied with the examination. The sensitivity and specificity of the cytological examination for identifying subjects with high-grade ESD were 100 and 97%, respectively. We found an accuracy of 100% (95% CI=99–100%) for a combination of cytological examination and p53 staining to detect high-grade ESD.Conclusions:The capsule sponge methodology seems to be a feasible, safe, and acceptable method for diagnosing precancerous lesions of the oesophagus in this population, with promising initial accuracy data for the detection of high-grade ESD.

Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of the COVID-19 pandemic and is the cause of increased mortality, especially among elderly patients and those who have severe complications, such as chronic pulmonary obstruction, hypertension, diabetes, and cancer. Nutrition, especially micronutrients, plays an important role in reducing mortality and complications from COVID-19 because micronutrients strengthen our immune system and nutritional status is an important factor that affects the outcome of patients with COVID-19. Among micronutrients, selenium has an important effect on both intrinsic and acquired immunity. Host selenium deficiency affects the viral genome and increases the virulence of viruses. We have investigated the serum selenium levels in COVID-19 patients and healthy control individuals. Methods A total of 50 patients with COVID-19 infection were included in this study. During hospitalization, 13 patients died (non-survivor group) and 37 patients recovered (survivor group). We assessed the serum selenium levels in 50 COVID-19 patients and 50 healthy individuals by Agilent SpectrAA-240 Z atomic absorption spectrometer. Results The serum selenium level was significantly lower in COVID-19 patients (77. 8 ± 13.9 μg/L) as compared to healthy control individuals (91.7 ± 16.7 μg/L), but there was no significant difference between the survivor and non-survivor groups. Also, there was no significant relationship between serum selenium levels and laboratory findings of COVID-19 patients. Conclusions These results suggest that decreased serum selenium levels may be a risk factor for the COVID-19 infection, but there was no significant relationship between selenium and severity and mortality of COVID-19 disease.

Tooth loss and periodontal disease have been associated with several cancers, and poor oral health may be an important risk factor for upper gastrointestinal (UGI, i.e., esophageal and gastric) cancers. We assessed the relationship between oral health and UGI cancers using a large prospective study of over 50,000 adults living in Golestan Province, Iran, a high-incidence area for these cancers. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for the association between three different measures of oral health [frequency of tooth brushing; number of missing teeth; and the sum of decayed, missing, and filled teeth (DMFT)] and UGI cancers. During a median follow-up duration of 13 years, there were 794 incident UGI cancers (396 esophageal and 398 gastric cancers). Daily tooth brushing was associated with a decreased risk of developing both esophageal (HR = 0.670; 95% CI: 0.486–0.924) and gastric (HR = 0.741; 95% CI: 0.544–1.01) cancers (combined UGI cancer HR = 0.697; 95% CI: 0.558–0.871) compared with never brushing. Tooth loss in excess of the loess smoothed, age- and sex-specific median number of teeth lost was significantly associated with esophageal (HR = 1.64; 95% CI: 1.08–2.47) and gastric cancers (HR = 1.58; 95% CI: 1.05–2.38). There were some adverse associations between DMFT and UGI cancers but most were not statistically significant. These results suggest increased risk of developing UGI cancers among individuals with poor oral health, and those who do not perform regular oral hygiene. Prevention Relevance: Poor oral health is associated with the risk of upper gastrointestinal cancers, and oral hygiene practices may help prevent these cancers.

Background The combination of sofosbuvir and daclatasvir is a potent, pangenotypic regimen suitable for mass-scale hepatitis C treatment, especially in resource-limited countries where newer, expensive combinations are not available. This combination has been widely tested on genotype 4. However, Phase III trials of this combination in other genotypes have been cost prohibitive. With the introduction of generic, low-cost sofosbuvir and daclatasvir, large-scale studies in resource-limited countries are now possible. Methods Sofosbuvir at 400 mg and daclatasvir at 60 mg were coformulated into a fixed-dose combination (FDC) tablet (Sovodak, Rojan Pharma, Tehran, Iran). Patients from 46 centers were dosed for 12 or 24 weeks with or without ribavirin, in line with existing guidelines. Responses to treatment were evaluated 12 weeks after the end of treatment (for a sustained virological response at Week 12; SVR12). Results There were 1361 patients recruited. Overall, the patients were 21% female, with a mean age of 50 years; 39% were cirrhotic; 22% were treatment-experienced; 47% were genotype 1, 41% were genotype 3, and 2% were other genotypes. The genotype was not known in 10% of the patients. The intention-to-treat and per-protocol SVR12 rates were 94.7% and 98.8%, respectively. The safety profile was unremarkable, treatment was well tolerated, and compliance with the single-tablet regimen was excellent. Conclusions The treatment with FDC of sofosbuvir and daclatasvir achieved high SVR12 rates, equivalent to those seen in Phase III trials of other pangenotypic options, and has been conducted at a similar scale in a representative, real-world population at a cost of under $100 per patient, which makes this combination suitable for elimination protocols in resource-limited countries. Clinical Trials Registration NCT03200184.

We evaluated the immune response to neonatal HBV immunization in children of infected parents 10-18 years after primary vaccination. Healthy individuals immunized with an infantile course of three doses of HBV vaccine were tested for persistence of anti-HB surface antibody (HBsAb). Those with an HBsAb level of <10 IU/mL received a booster dose of the vaccine with subsequent doses to those without protective titres. HBsAb concentrations were determined 4 weeks after each dose of the booster vaccine. The data were analysed separately for three age groups: 10-11, 12-14 and 15-18 years old. A total of 541 healthy individuals were studied. The highest seroprotection rate of 48% was observed in the youngest vaccinees (10-11 years old). This declined to 26.5% in the oldest (15-18 years old) group (P = 0.008). The youngest vaccinees showed the highest rate of anamnestic immune responses (96%). However, 25% of oldest individuals failed to mount an anamnestic immune response in challenge with a booster dose of the vaccine (P = 0.005), suggesting waning immunity with increasing age. Age (OR: 0.80; P = 0.01) and prebooster HBsAb levels (OR: 0.37; P = 0.01) identified responders to first booster doses of the vaccine by logistic regression analysis. The majority of high-risk vaccinees showed anamnestic immune response 10-11 years after primary immunization. However, we found a significant proportion (25%) of older individuals with no anamnetic response, which suggests a waning of immune memory. Detailed long-term follow-up studies are necessary to determine the risk of natural infection among these individuals before a booster schedule can be recommended.

Background: Various observational studies have examined a potential relationship between Helicobacter pylori colonization and inflammatory bowel diseases (IBDs); however, results are inconclusive. This systematic review evaluates articles reporting an association between human H. pylori colonization and IBD. Methods: A systematic search of studies was conducted to evaluate a possible relationship between H. pylori colonization and IBD. Seven databases and different types of gray literature were searched. After screening for relevant articles, selection and data extraction were done. After that, the data were analyzed, and pooled odds ratios (ORs) were calculated, using meta-analysis. Heterogeneity, sensitivity, and subgroups analyses were conducted. Funnel plots followed by Begg and Egger tests were done to assess the publication bias. Results: Among 58 studies, including 13,549 patients with IBD and 506,554 controls, the prevalence of H. pylori colonization was 22.74% and 36.30%, respectively. A significant negative association was observed between H. pylori colonization and IBD (pooled OR: 0.45, 95% confidence interval 0.39-0.53, P≤0.001). The random-effect model showed significant statistical heterogeneity in the included studies (I 2=79%). No publication bias was observed. Among subgroups, ORs were notably different when the data were stratified by the age difference between patient and control group, and by study regions and/or continent. Finally, the meta-regression analysis showed significant results, in terms of the age difference and region variables. Conclusions: In this meta-analysis, all statistical data support the theory that H. pylori has a protective role in IBD. However, more primary studies using proper methodology are needed to confirm this association.