Effects of 14-days bismuth- and tetracycline-containing quadruple therapy with concomitant regimen for the first line Helicobacterpylori eradication.

Background: Helicobacter pylori (H. pylori) has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma. Methods: This study was performed in Mazandaran, Sari, situated in North of Iran. Three-hundred and twenty-eight adult patients with endoscopically approved gastric or duodenal ulcers or erosions and H. pylori infection were randomly divided into 2 groups to receive either 14 days PABT (Pantoprazole 40 mg, Amoxicillin 1 g, Bismuth 425 mg (all twice daily) and Tetracycline 500 mg four times a day) and PACM (Pantoprazole 40 mg, Amoxicillin 1g, Clarithromycin 500 mg, and Metronidazole 500 mg, all twice daily). To evaluate H. pylori eradication, fecal H. pylori antigen test was performed 8 weeks after treatment. Results: The eradication rates were 94.51% in the PABT and 91.46% in PACM group based on the intention to treat analysis. Moreover, the eradication rates were 95.58% and 92.72% according to per-protocol analysis, respectively. Also, both groups had very low rates of severe side effects. Conclusion: Regarding the ideal eradication rates achieved by both treatment groups and the low rates of severe side effects, both treatment protocols can be prescribed for H. pylori eradication in North of Iran.

Sofosbuvir/daclatasvir regimens for the treatment of COVID-19: an individual patient data meta-analysis.

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.

Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial.

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.

Efficacy and tolerability of fourteen-day sequential quadruple regimen: pantoprazole, bismuth, amoxicillin, metronidazole and or furazolidone as first-line therapy for eradication of Helicobacter pylori: a randomized, double-blind clinical trial.

The optimal pharmacological regimen for eradication of Helicobacter pylori (H. pylori) has been investigated for many years. This study aimed to evaluate the efficacy and tolerability of bismuth-based quadruple therapy (B-QT) and a modified sequential therapy (ST) regimens in eradication of H. pylori. A randomized, double-blind trial was conducted on 344 patients. Patients with H. pylori infection and without a history of previous treatment were randomized to receive 14-day B-QT (bismuth subcitrate 240 mg, pantoprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily) or 14-day ST (bismuth subcitrate 240 mg, pantoprazole 40 mg, amoxicillin 1000 mg, and metronidazole 500 mg twice a day for seven days followed by bismuth subcitrate 240 mg, pantoprazole 40 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice a day for additional seven days). Drug adverse effects were assessed during the study. H. pylori eradication was determined eight weeks after the end of treatment using 14C-urea breath test. Based on per-protocol and intention-to-treat, the eradication rate was significantly higher (p<0.05) in the B-QT regimen 91.9 % (95 % CI; 88.1-94.0) and 90.2 % (95 % CI; 86.3-92.9), respectively compared to the ST regimen 80.8 % (95 % CI; 76.6-84.9) and 78.1 % (95 % CI; 73.7-82.4), respectively. The severity of vomiting and loss of appetite were significantly higher in ST regimen (p<0.05). The B-QT regimen was more effective and safer than the ST regimen. Conclusively, it is suggested to assess the efficacy and safety of this regimen in longer studies, larger population, and in other communities.

Tabari Cohort Profile and Preliminary Results in Urban Areas and Mountainous Regions of Mazandaran, Iran.

BACKGROUND: The Tabari cohort study (TCS), part of the Prospective Epidemiological Research Studies in IrAN (PERSIAN), is a large longitudinal prospective cohort designed to better understand the risk factors associated with major non-communicable diseases (NCDs) across two urban and mountainous regions in north of Iran. METHODS: The enrollment phase of TCS started in June 2015 and ended in November 2017. During this phase, individuals aged 35-70 years from urban and mountainous regions of Sari township (Mazandaran province) were invited to the cohort center by health volunteers (urban regions) and Behvarz (mountainous areas) using census information. Data was collected based on the PERSIAN cohort study protocols. Hypertension was defind as systolic blood pressure ≥140 mm Hg or a diastolic blood pressure ≥90 mm Hg or history of diagnosis with hypertension or taking antihypertensive medications among participants free from cardiovascular diseases. Diabetes was defined as fasting blood sugar ≥126 mg/dL or a history of diagnosis or taking glucoselowering medications among all participants. RESULTS: A total of 10,255 participants were enrolled in TCS, 59.5% of whom were female. Among the total population, 7,012 participants were urban residents (68.4%). The prevalence of daily smoking in the total population was 9.1%. Body mass index in 75.9% of participants was ≥25 kg/m2. The prevalence of hypertension, diabetes, and thyroid disorders were 22.2%, 17.2%, and 10.5%, respectively. CONCLUSION: The Tabari cohort is different from other cohorts in terms of levels of risk factors associated with NCDs. This study has certain important strengths including its population-based design and large sample size that provides a valid platform for conducting future investigations and trials. A biobank that has been designed to store blood, nail, hair and urine samples for future research is another strength of this study. Researchers who are interested in using the information can refer to the following web page: http://persiancohort.com.

Evaluation of the Additive Effect of Domperidone on Patients with Refractory Gastroesophageal Reflux Disease; A Randomized Double Blind Clinical Trial.

BACKGROUND Gastroesophageal reflux disease (GERD) is a common problem with annoying symptoms. It is associated with negative impact on quality of life. Prokinetic agents may be used in combination with acid suppression agents as an adjunctive in patients with GERD refractory to proton pump inhibitors (PPI) therapy, rather than as sole treatment. This study aimed to evaluate the efficacy of combination of PPI with domperidone (a prokinetic agent) compared with PPI alone in the treatment of patients with refractory GERD. METHODS This study was a double blind clinical trial on 29 patients with GERD refractory to PPI during the period of one month. By randomization, the patients were divided into two groups. Group A was treated by pantoprazole 40 mg twice daily and domperidone three times a day for a month, while group B was treated by pantoprazole 40 mg twice daily and placebo three times a day. In this study endoscopy was performed to evaluate the prevalence of erosive esophagitis, non-erosive reflux, and hiatal hernia. Manometry was conducted to study the prevalence of dysmotility. GERD symptom questionnaires including the Gastrointestinal Symptom Rating Scale (GSRS), Carlson Dennett, and the Medical Outcomes Study Short Form-36 health survey (SF36) were used before and after treatment for screening GERD and assessing treatment response. RESULTS There were 17 (58.62%) women and 12 (41.37%) men. The prevalence of erosive esophagitis and non-erosive reflux, was 10.34% and 89.66%, respectively. There was a significant difference comparing reflux symptoms before and after treatment between the two groups according to reflux and Carlson Dennett questionnaires. At the end of the study, symptoms of reflux significantly improved by treatment. Although, the quality of life questionnaire scores improved by treatment, there was no statistically significant difference in response to treatment between the two groups. CONCLUSION In this research, we showed that adding domperidone to PPI could not make any improvement in patients with refractory reflux regarding the quality of life and improving the symptoms.

A Comparison between Hybrid and Concomitant Regimens for Helicobacter Pylori Eradication: A Randomized Clinical Trial.

BACKGROUND Helicobacter pylori (H. pylori) is one of the most common bacterial infections worldwide. We designed a study to compare the efficacy of 14-day hybrid regimen with 10-day concomitant therapy for H. pylori eradication in Iran. METHODS 252 patients with naïve H. pylori infection were randomly divided to receive either hybrid regimen (pantoprazole 40 mg, and amoxicillin 1 gr twice daily for 14 days, accompanied by clarithromycin 500 mg, and metronidazole 500 mg, twice daily just during the last 7 days) or concomitant regimen (pantoprazole 40 mg, amoxicillin 1 gr, clarithromycin 500 mg, and metronidazole 500 mg, all twice daily for 10 days). 8 weeks after therapy, 14C- urease breath test was performed to confirm eradication. RESULTS According to intention to treat analysis, the eradication rates were 87.3% (95% CI: 81.4-93.1) and 80.9% (95% CI: 74-87.8) in hybrid and concomitant groups, respectively (p=0.38). Per-protocol eradication rates were 89.3% (95% CI: 83.8-94.7) and 83.1% (95% CI: 76.3-89.8), respectively (p=0.19). The rates of severe side effects were not statistically different between the two groups (4% vs. 8.7%). CONCLUSION 14-day hybrid therapy can be considered as a nearly acceptable regimen with few severe side effects in Iran. However, it seems that the efficacy of this therapy is decreasing as the resistance rates to antibiotics are increasing. We suggest further studies to assess the efficacy of a more prolonged concomitant therapy for H. pylori eradication in Iran.

Comparison of quadruple and triple Furazolidone containing regimens on eradication of helicobacter pylori.

BACKGROUND: The effectiveness of classic standard triple therapy regimen of helicobacter pylori (H. pylori) eradication has decreased to unacceptably low levels, largely related to development of resistance to metronidazole and clarithromycin. Thus successful eradication of H. pylori infections remains challenging. Therefore alternative treatments with superior effectiveness and safety should be designed and appropriately tested in all areas depending on the native resistance patterns. Furazolidone has been used successfully in eradication regimens previously and regimens containing furazolidone may be an ideal regimen. METHODS: H. pylori infected patients with proven gastric or duodenal ulcers and /or gastric or duodenal erosions at Imam Khomeini Hospital in Sari/Northern Iran, were randomly allocated into three groups: group A (OABF) with furazolidone (F) (200 mg bid.), group B (OABM-F) metronidazole (M) (500 mg bid.) for the first five days, followed by furazolidone (F) (200 mg bid.) for the second five days and group C (OAF) with furazolidone (F) (200 mg tid.). Omeprazole (O) (20 mg bid.) and amoxicillin (A) (1000 mg bid.) were given in all groups; bismuth (B) (240 mg bid.) was prescribed in groups A & B. Duration of all eradication regimens were ten days. Eight weeks after treatment, a 14C-urea breath test was performed for evaluation of H. pylori eradication. RESULTS: A total of 372 patients were enrolled in three groups randomly (124 patients in each group); 120 (97%) patients in group A (OABF), 120 (97%) in group B (OABM-F) and 116 (93%) in group C (OAF) completed the study. The intention-to-treat eradication rates were 83.7% (95% CI= 77.3-90.4), 79.8% (95% CI= 72.6-87), and 84.6% (95% CI= 78.2-91.1) and per-protocol eradication rates were 86.6% (95% CI= 80.5-92.8), 82.5% (95% CI= 75.6-89.4), and 90.5% (95% CI= 85.1-95.9) for groups OABF, OABM-F, and OAF, respectively. No statistical significant differences were found in case of severe drug adverse effects between the above mentioned three groups (p> 0.05). The most common side effects, namely nausea and fever, occurred in all groups, but more frequently in group C (OAF) (p< 0.05). CONCLUSION: In developing countries such as Iran, furazolidone-based regimens can substitute clarithromycinbased regimens for H. pylori eradication because of a very low level of resistance, low cost and high effectiveness. Considering per-protocol eradication rate of ten days OAF regimen, and the acceptable limit of ninety percent, we recommend this regimen in developing countries such as Iran to be substituted of classic standard triple therapy. In order to minimize rare serious adverse effects, one week high dose OAF regimen should be taken into consideration in other studies.

Acute bleeding in duodenal gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. The biological pattern of these tumors ranges from benign-appearing small lesions to malignant sarcomas. Only 3%-5% of GISTs are found in the duodenum. A duodenal GIST is a rare source of upper gastrointestinal bleeding. A remarkable percentage of duodenal GISTs are localized in the third and fourth part of the duodenum and may not be noticed on standard upper endoscopy. Push enteroscopy is sometimes advisable to find these lesions. Surgical resection either limited or pancreaticoduodenectomy can be the treatment of choice. In general, adjuvant therapy with imatinib has been proved to extend survival in patients with GIST.The current case, a 24-year-old male, presented with acute upper gastrointestinal bleeding from a submucosal ulcerated tumor located in the distal third part of the duodenum, 3 cm distal from the papilla of Vater. After primary care and blood transfusion in a local hospital, partial resection of the duodenum was performed as a definitive surgical therapy. Histopathology showed a GIST with a diameter of 3 cm and moderately malignant according to tumor grade, and <5 mitoses/10 high power field (HPF).