Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Anemia prevalence, severity, types, and correlates among adult women and men in a multiethnic Iranian population: the Khuzestan Comprehensive Health Study (KCHS).

BACKGROUND: Despite all recent health-related improvements, anemia remains an extensive global public health issue affecting the lives of about one-fourth of the world population in a geographically heterogeneous pattern. We, therefore, aimed to illustrate the prevalence, severity, most common types, and major determinants of anemia among adults in Khuzestan, Iran, from 2016 to 2019. METHODS: In a large population-based cross-sectional study comprising of a diverse population, each participant underwent a questionnaire-based interview and laboratory testing for hematological analysis. A hemoglobin (HGB) concentration of < 12 g/dL in non-pregnant women and < 13 g/dL in men were defined anemic. The multivariate logistic regression analysis was performed to explore the association between anemia and its potential determinants. RESULTS: Data on 29,550 (96.87%) males and non-pregnant females between 20-65 years of age (mean age: 41.90 ± 11.88 years; female sex: 63.58%; Arab ethnicity: 48.65%), whose HGB level was available, were included in the study. The mean ± SD HGB concentration was 13.75 ± 1.65 g/dL. The age- and sex-standardized prevalence rate of anemia was 10.86% (95% CI: 10.51-11.23%). The most prevalent degree was mild anemia (7.71%, 95% CI: 7.40-8.03%) and only 0.17% were severely anemic. Of those considered anemic, the highest proportion was related to normochromic/microcytic (50.65%), followed by hypochromic/microcytic (30.29%). In the multiple logistic regression, the parameters of female gender (OR: 3.17, 95% CI: 2.68-3.76), age group of 35-49 years (OR: 1.66, 95% CI: 1.52-1.82), being underweight (OR: 1.58, 95% CI: 1.29-1.93), being unemployed or retired (OR: 1.55, 95% CI: 1.33-1.81), and living in urban areas (OR: 1.18, 95% CI: 1.09-1.29) were major determinants of anemia. Additionally, we observed a minor but significant positive association between anemia status and CKD, older ages, increased night sleep duration, being a housewife and married, as well as a negative association between anemia and factors including hookah smoking, presence of metabolic syndrome, and overweight and obesity. CONCLUSIONS: Taken together, the anemia prevalence in this study population was of mild public health significance. The major suspected causes might be iron deficiency and chronic disease anemias. Comparably higher rates of anemia were observed amongst women, individuals aged 35-49 years, underweights, unemployed or retired subjects, and urban residents.

Changes in liver fibrosis in patients with chronic hepatitis C after successful direct-acting antiviral therapy.

INTRODUCTION AND OBJECTIVES: After successful treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs), the stage of liver fibrosis decreases over time. Here, we aimed to assess the changes in the liver fibrosis stage using transient elastography (TE) after successful DAA therapy in HCV-infected cirrhotic patients who were referred to Shariati hospital from 2016 to 2017. MATERIAL AND METHODS: In this observational cohort, all HCV-infected cirrhotic patients who were treated with a combination of sofosbuvir/daclatasvir, had sustained virologic response (SVR), and had undergone pre- and post-treatment TE, were enrolled. The primary outcome was the changes in TE parameters six months after the end of treatment compared with baseline. RESULTS: A total of 442 eligible subjects received DAA therapy. Overall, the SVR rate was 96.6%. Of these, 149 patients had completed the protocol and were enrolled. The mean age of patients was 56.1 ± 10.3 years and the predominant sex was male (77.9%). The median (Q1 -Q3 ) liver stiffness (LS) value at baseline was 26.3 kPa (18.1-38 kPa), which significantly decreased to 20.9 kPa (12-29.7 kPa) [z = -8.45, P-value < .001]. Also, the liver steatosis of patients with baseline CAP ≥ 220 dB/m had a significant response to treatment [z = -2.3, P-value = .023]. Based on multivariate analysis, a higher baseline liver fibrosis stage was the only determinant of LS values improvement in our study. CONCLUSION: Successful HCV eradication in patients with liver fibrosis results in significant improvement in LS, even in cirrhotic patients.

Sofosbuvir and daclatasvir compared with standard of care in the treatment of patients admitted to hospital with moderate or severe coronavirus infection (COVID-19): a randomized controlled trial.

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.

Dyssynergic Defecation: A Comprehensive Review on Diagnosis and Management.

About one-third of chronically constipated patients have an evacuation disorder, and dyssynergic defecation is a common cause of the evacuation disorder. In dyssynergic defecation, the coordination between abdominal and pelvic floor muscles during defecation is disrupted and patients cannot produce a normal bowel movement. The etiology of dyssynergic defecation is still unknown. Although a detailed history taking and a careful examination including digital rectal examination could be useful, other modalities such as anorectal manometry and balloon expulsion test are necessary for the diagnosis. Biofeedback therapy is one of the most effective and safe treatments. Here, we provide an overview of dyssynergic defecation as well as how to diagnose and manage this condition.

A Population-Based Cross-sectional Study on the Prevalence and Associated Risk Factors of Helicobacter pylori Infection in Rafsanjan, a Low Gastric Cancer Area in Southeast Iran.

Background: Despite all improvements in sanitation and exposure to antibiotics over time, Helicobacter pylori (HP) prevalence remains high, affecting the lives of about half of the world population, which can gradually lead to serious upper gastrointestinal disorders. Understanding HP's epidemiologic patterns help us to better manage the burden of this infection and to plan more effectively regarding potential screening or eradication strategies. We, therefore, aimed to report the crude and age- and sex-standardized prevalence rate of HP infection, its trend, and possible associated factors among asymptomatic healthy individuals in Rafsanjan city, a low-incidence area of gastric cancer (GC) in the southeast of Iran, from July 2018 to December 2021. Methods: This population-based cross-sectional descriptive study included 2,046 male and female subjects between 3 to 72 years who were in good health condition. Study participants were randomly selected from the Health Houses and each underwent a questionnaire-based interview and provided blood and feces samples. The presence of HP infection was detected by serum IgG antibodies and stool antigen test. Results: The overall and age- and sex-standardized prevalence rates of HP infection were 50.9% and 43%, respectively. The prevalence rate has notably decreased in all age groups compared with 2007. Also, it was significantly higher among men (P=0.033) and increased with advancing age (P<0.001). A higher population density living in a specific room area (P=0.012) increased the likelihood of HP infection. Conclusion: To conclude, the prevalence of HP infection is decreasing over time in Rafsanjan city, which may be due to improvements in living standards in this area. A healthy lifestyle and adherence to hygienic principles, especially during childhood, may be required for a reduction in the prevalence of HP infection.

Gastric Cancer in Iran: An Overview of Risk Factors and Preventive Measures.

Despite all recent treatment advances and the worldwide decline in the incidence rate, gastric cancer (GC) remains an ongoing global health challenge and one of the major leading causes of cancer-specific deaths, particularly in high-incidence regions including Iran. Since GC is often diagnosed in advanced stages, the best action may be to enable early diagnosis of the disease or even prevent it in the first place through identification and control of the underlying risk factors. Endoscopy, as the gold standard method, is both expensive and invasive, making it an unfavorable device in this regard. Therefore, it is crucial to implement a reliable region-specific screening and surveillance program to identify high-risk individuals with more efficient screening modalities. Here, in addition to a review of current GC knowledge, we presented the data of newly-established Population-based Cancer Registries (PBCRs) in Iran. Our assessment confirmed earlier reports of a very high GC incidence rate in the northwestern and northern provinces of Iran, most notably Ardabil. Along with the important role of conventional risk factors such as Helicobacter pylori (HP) infection and high dietary intake of salt, of more interest, we highlighted new region-specific risk factors, namely hookah, and opium. In conclusion, it seems the best results in reducing GC incidence and mortality rates on larger scales arise from modifying behavioral and environmental risk factors and advancing genetic and molecular biomarkers in order to supersede endoscopy. Regular endoscopic screening and antibiotic chemoprophylaxis against HP are still more appropriate in high-risk groups with specified criteria.