The efficacy of Elbasvir/Grazoprevir fixed-dose combination for 8 weeks in HCV treatment and health-related quality of life (HRQoL) in treatment-naïve, non-cirrhotic, genotype 4-infected patients (ELEGANT-4): A single-center, single-arm, open-label, phase 3 trial.

Background: Cost, adverse events, and long treatment duration can be significant obstacles in treating hepatitis C virus (HCV)-infected individuals. Shortening the treatment regimen can minimize these barriers, thereby enhancing adherence and increasing medication availability to more patients. Methods: This is a single-centre, single-arm, open-label, phase 3 clinical trial on treatment naïve, non-cirrhotic, HCV genotype 4 patients. The study aimed to evaluate an 8-week course of Elbasvir (ELB)/Grazoprevir (GZR) in this population. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR-12). The secondary endpoints were SVR-4, adverse events, and changes in health- and hepatitis-related quality of life (HRQoL). Results: Of the 30 patients who were enrolled, 29 (97%) achieved SVR-12 and SVR-4 (95% CI: 90-100%). No patients experienced serious or life-threatening adverse events (AEs), but mild/moderate AEs were reported by 16 (53%). The most commonly reported AEs were itching/skin rash (20%), headache (16.7%), abdominal/epigastric pain and decreased appetite (13.3% each), and nausea/vomiting (10%). Marked improvements in HRQoL were reported between the first (baseline) and third (SVR-12) timepoints. HRQoL score improvements involved the physical, mental, and hepatitis-specific indices, and ranged between 6 and 42 points (out of 100, P ≤0.003). Conclusion: The trial provides empirical evidence that HCV genotype 4-infected patients can achieve viral eradication with an 8-week-regimen of ELB/GZR. Further, this course of treatment is associated with a minimal adverse event profile and potentially significant improvements in quality of life. (ClinicalTrials.gov number, NCT03578640).

Peroral endoscopic myotomy (POEM) for the treatment of achalasia: A multicenter Middle Eastern experience.

BACKGROUND: Peroral endoscopic myotomy (POEM) was proposed in 2010 as a minimally invasive procedure for the treatment of achalasia. In this article, we describe the Middle Eastern experience with the procedure in terms of efficacy, length of admission, and short- and long-term complications. METHODS: A retrospective analysis of our prospectively collected data on patients who underwent a POEM procedure was conducted between March 2019 and May 2020. The primary outcome was clinical success rate, defined as a postprocedure Eckardt score ≤3 at ≥3 months. Secondary outcomes included the length of hospital stay, presence of reflux symptoms or need for proton pump inhibitors (PPIs) ≥3 months, and adverse events. RESULTS: During the study period, 67 patients (35 females) underwent the procedure for achalasia. The participants' ages ranged from 11 to 80 years (mean 41 ± 18 years). Eckardt scores before the treatment ranged between 4 and 12 (mean 8.85 ± 1.75). Sixty-four patients (95.5%) achieved Eckardt scores of ≤3 at ≥3 months after the procedure (95% confidence interval [CI]: 91%-100%). The difference between pre- and post-procedural Eckardt scores averaged around -8 points (95% CI: -7.5 to -8.5 P < 0.0001). Adverse events were reported in 24 patients (35.8%) and included pneumoperitoneum (32.8%), reflux symptoms at 3 months (29.9%), and surgical emphysema (3%). Six patients had adverse events that led to prolongation of admission; 3% of whom had aspiration pneumonia, 3% had pneumoperitoneum, 1.5% had both, and 1.5% had an esophageal tear. CONCLUSIONS: POEM is a promising procedure for the treatment of achalasia with a high clinical success rate, short hospital admission, and a reassuring safety profile.

Revealing Hepatitis B Virus as a Silent Killer: A Call-to-Action for Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) was the first country in the Middle East to adopt the hepatitis B virus (HBV) vaccine. Despite an expanded HBV immunization program and significant progress in HBV prevention in the country, HBV infection is a significant public health burden. This review lists coordinated solutions for healthcare stakeholders, patients, and health authorities to curb HBV and its impact in KSA. It further aims to draw policymakers' attention to key priorities to bridge HBV care gaps in the country. METHODS: As part of the pre-engagement activity, medical experts across KSA were interviewed to gain a preliminary understanding of the current unmet needs in HBV management in the country. Top-recommended action points derived from the pre-engagement activity were discussed. Key priority action points to curb the impact of HBV in KSA were identified. RESULTS: The priority action points together with the challenges and unmet needs in the management and care of HBV in KSA were: (a) establish a national-level registry, (b) implement screening campaigns, (c) improve linkage of care between primary care physicians (PCPs) and specialists, and (d) increase PCP education and awareness. CONCLUSION: This work is an endeavor to set the stage for a strategic policy framework aimed at eliminating HBV in KSA. The action points/steps for the identified priorities must run parallelly across various regions in KSA, to successfully manage and further eliminate the threat of HBV.

Peripancreatic fluid collections, plastic stents, and different sub-types of metal stents: Where does the evidence land?

BACKGROUND: Peripancreatic fluid collections (PFCs) are a frequent complication of acute pancreatitis. Symptomatic PFCs may need to be drained, and there are multiple endoscopic accessories that can facilitate the procedure. This paper aims to compare the success rate, number of procedures required for resolution and adverse events rate for PFCs EUS-guided drainage with plastic stents and lumen-apposing metal stents (LAMS). METHODS: This is a retrospective analysis of a consecutive sample of patients that was collected from 2013 - 2019. The medical records of these patients were reviewed, and the outcomes for each type of stent (plastic vs LAMS, and different subtypes of LAMS) were compared in terms of clinical success, number of re-interventions needed, and adverse events. RESULTS: A total of 33 patients (23 males) were treated for PFCs with EUS-guided drainage and stenting. The patients' ages ranged between 14 and 85 years (mean ± SD: 43.5 ± 19 years). Overall, there was no difference between plastic stents and LAMS in terms of symptomatic recovery (P = 0. 24), but metal stents had better results with regards to radiological resolution (P = 0.03), and were associated with a higher number of necrosectomies (P = 0.029). Adverse events occurred more frequently in patients who had plastic stents, but direct comparison between the two groups showed that the difference was not statistically significant (P = 0.2). Stratification for different LAMS subtypes showed no difference in terms of symptomatic or radiological resolution (P =0.49), number of rescue procedures (P = 0.41), and adverse events (P = 0.81). CONCLUSION: Our study, along with the current available evidence, suggests a slight advantage of metal stents over plastic stents in terms of clinical success, need for rescue procedures, and incidence of adverse events. Furthermore, it provides empirical evidence that the different sub-types of LAMS perform similarly when compared against each other.

The utility of digital cholangioscopy (SpyGlass DS) in biliary and pancreatic diseases: A clinical feasibility study at two tertiary care centers in Saudi Arabia (with Videos).

BACKGROUND AND STUDY AIM: Since its inception in 2007, single-operator cholangioscopy (SOC) has gained popularity for many diagnostically and therapeutically challenging biliary and pancreatic conditions. Many studies have been published to evaluate the feasibility, usefulness, cost-effectiveness, and safety profile of the first generation. This paper is a descriptive study in which we aim to share the experience of two tertiary care centers with the novel version of SOC, SpyGlass DS. PATIENTS AND METHODS: We retrospectively reviewed the records of all the patients who went through the procedure from October 2015 - July 2019 to explore the scope of biliary and pancreatic conditions in which SOC was utilized. Technical success was defined as the ability to visualize the lesion and complete the procedure as planned, whereas clinical success was determined by the ability to achieve the desired diagnostic/therapeutic outcome. RESULTS: During the period of interest, 66 patients (34 males) went through 84 cholangioscopy procedures. Forty-four patients failed the conventional extraction methods and needed the intervention for the treatment of difficult stones, 24 patients needed a diagnostic evaluation of biliary strictures, and 3 needed an intervention to remove migrated stents. Technical success was achieved in 98.8% (83/84) of the procedures (95% CI: 96-100%). Regarding clinical success, stone breakdown and removal was achieved in 92% of the procedures (49/53; 95% CI: 85-100%). Tissue samples were successfully obtained in 95.8% (23/24) of patients with strictures (95% CI: 88-100%). The biopsy was appropriate to make a histological diagnosis in 83.3% of cases (20/24; 95% CI: 68-98%). The median number of sessions needed to achieve the deisred outcome was one (ranging between 1 and 6 sessions). CONCLUSION: The new version of SOC, SpyGlass DS, provides a feasible and an effective option for the management of difficult cholelithiasis, as well as visually evaluating and obtaining histological samples for indeterminate biliary strictures. However, data from more extensive studies are needed to establish its non-inferiority to the fiberoptic version in terms of short- and long-term outcomes, cost-effectiveness, and complications.

Streamlining and cycle time reduction of the startup phase of clinical trials.

OBJECTIVE: The startup phase of a clinical trial (CT) plays a vital role in the execution of new drug development. Hence, the aim of this study is to identify the factors responsible for delaying the CT startup phase. Further, it focuses on streamlining and reducing the cycle time of the startup phase of newly sponsored CTs. METHODS: Thirteen sponsored CTs conducted between 2016 and 2017 at the Clinical Research Department of King Fahad Medical City, Riyadh, Saudi Arabia, were considered for this study. Eight trials were analyzed to identify the data specific to startup metrics using the FOCUS-PDCA cycle (Find an improvement area-Organize a team-Clarify current practices-Understand the source of variation/problem-Select a Strategy-Plan-Do-Check-Act). Six measures incorporated in the metrics were (1) date of initial contact with site to the signing of confidentiality agreement, (2) date of receiving questionnaire from sponsor to date of its completion, (4) time taken to review protocol and approve investigational drug service form, and (5) time taken to study protocol and approve pharmacy and pathology and clinical laboratory medicine form and date of receipt of institutional review board (IRB) submission package to final IRB approval. Fishbone analysis was used to understand the potential causes of process variation. Mean (SD) time was calculated for each metric before and after implementation of the intervention protocol to analyze and compare percentage reduction in the mean cycle time of CTs. Data were represented as mean (SD), and the P value was calculated for each metric. The significance level was set at P < 0.05. RESULTS: Of the various potential factors of delay identified through fishbone analysis, the two major ones were lack of a well-defined timeline for approval and review of the study protocol and inconsistent IRB meetings. After introduction of the new intervention protocol, the entire CT life cycle was reduced by 45.6% (mean [SD], 24.8 [8.2] weeks vs. 13.5 [11.6] weeks before and after the intervention, respectively). CONCLUSION: Various factors are responsible for the delay of the startup phase of CTs, and understanding the impact of each element allows for optimization and faster execution of the startup phase of CTs.

The utility of esophagogastroduodenoscopy and Helicobacter pylori screening in the preoperative assessment of patients undergoing bariatric surgery: A cross-sectional, single-center study in Saudi Arabia.

BACKGROUND/AIM: Esophagogastroduodenoscopy (EGD) and Helicobacter pylori screening are routine parts of the preoperative assessment of patients undergoing bariatric surgery at many centers around the world. The reason for this step is to identify abnormalities that may change the surgical approach. In this study, we aim to evaluate the extent to which endoscopic findings and H. pylori testing affect the plan of care in bariatric patients. PATIENTS AND METHODS: We retrospectively reviewed the investigational processes of 356 patients planned for bariatric surgery (2014-2016) at our center. Patients were categorized into two main groups (4 subgroups) from endoscopic findings. One group included patients with normal EGD and patients who had abnormal findings that did not change the surgical approach, whereas the other included patients who had findings that changed or canceled the surgical plan. A logistic regression analysis was used to evaluate how strongly can factors such as patient demographics, BMI, comorbidities, symptomatology, and H. pylori status predict the risk of having plan-changing endoscopic abnormalities. RESULTS: The ages ranged between 15 and 66 years with a mean ± SD of 37 ± 11 years, and 56% were females. The majority of patients (75%; 95% CI: 73 - 82%) had either no findings (41%) or had abnormalities that did not change the surgical approach (34%). Only 25% (95% CI: 21-29%) were found to have pathologies that altered the surgical approach, and 0.6% of them had findings that were considered contraindications for surgery. In spite the relatively high prevalence of H. pylori in our cohort (41%; 95% CI 36-46%), the proportion of patients who had plan-changing abnormalities did not differ markedly from other studies. Gastroesophageal reflux disease (GERD) and obstructive sleep apnea symptoms were the only significant predictors of EGD findings (P = 0.009). CONCLUSIONS: GERD and sleep apnea symptoms can be strong predictors of EGD abnormalities. However, this evidence is still not enough to safely recommend changing the current practice. Therefore, until a sensitive clinical prediction score is derived and validated according to the symptoms, we suggest that EGD should continue as the standard of care in all patients undergoing bariatric surgery.

Acute Pancreatitis: An Exploratory, Cross-sectional, Single-center Study of the Epidemiological Features of the Disease in a Sample of Saudi Patients.

Epidemiological studies on Acute Pancreatitis (AP) are significantly scarce in the Saudi Arabian Literature. In this paper, we aim to explore the current trends of AP in a sample of Saudi patients. This is a cross-sectional study in which we reviewed AP-related admissions from 2014 to 2017. Data collected included demographics, clinical presentation, investigations, severity, complications, and the outcome at the end of hospitalization. During the study period, 107 patients were admitted due to AP. Fifty-seven (53%) were males. Biliary pancreatitis was the most common etiology found among our patients (39.3%; 95% CI: 30.5-48.7), followed by alcoholic pancreatitis (11.2%; 95% CI: 6.5-18.6) and hypertriglyceridemia (8%; 95% CI: 4.5-15.2). Pancreatic pseudocysts were the most common complication we found in this series (15%; 95% CI: 9.4-23). Of all the hospitalized patients in this study, eight patients (7.9%) died (95% CI: 3.8-14.1). The number of AP-related admissions and mortality rate appear to have increased as compared with the numbers in earlier national studies. The etiological groups have also changed. As compared with Western/Asian studies, however, there was almost no difference in the epidemiological patterns except for the mortality rate.

Microbial dysbiosis in inflammatory bowel diseases: results of a metagenomic study in Saudi Arabia.

BACKGROUND: The intestinal microbiota plays an essential role in the pathogenesis of ulcerative colitis (UC)and Crohn disease (CD). METHODS: Metagenomic studies were used to study microbiota in the diagnosed cases of UC and CD at King Fahad Medical City, Riyadh, Saudi Arabia. Each segment of the colon was flushed with distilled water during colonoscopy, and the material was aspirated, immediately frozen for the study. The patients attending for screening colonoscopies were taken as age-matched healthy controls. The UC patients were followed clinically for any signs of exacerbation relapse, and CD patients were followed for any complications. RESULTS: The metagenomic data on 46 (24 females) patients with CD were analyzed along with a group of age and gender-matched controls. Their age ranged from 14 to 65 years, mean age 25.19±10.67 years. There were 50 UC patient (28 females) mean age of 34.42±12.58, and their age ranged from 13-58 years. This study identified enrichment of 19 genera in the control group (Abiotrophia, Anaerofustis, Butyrivibrio, Campylobacter, Catenibacterium, Coprococcus, Dorea, Eubacterium, Facklamia, Klebsiella, Lactococcus, Oscillibacter, Paenibacillus, Parabacteroides, Parasutterella, Porphyromonas, Prevotella, Ruminococcus, Treponema). There was a significant enrichment of 14 genera in our CD cohort (Beggiatoa, Burkholderia, Cyanothece, Enterococcus, Escherichia, Fusobacterium, Jonquetella, Mitsuokella, Parvimonas, Peptostreptococcus, Shigella, Succinatimonas, ThermoanaerobacterVerrucomicrobiales, Vibrio). There was a significant enrichment of 7 genera in UC cohort (Beggiatoa, Burkholderia, Parascardovia, Parvimonas, Pseudoflavonifractor, Thermoanaerobacter, Verrucomicrobiales). CONCLUSIONS: A significant dysbiosis was found in UC and CD patients compared to controls.

Position statement on the diagnosis and management of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common cause of abnormal liver enzymes in many developed countries. Non-alcoholic fatty liver disease is also known as an important cause of cryptogenic cirrhosis and second leading cause for liver transplantation. It is commonly associated with metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of NAFLD. In spite of promising performance of non-invasive tools, liver biopsy remains the gold standard test for NASH diagnosis. Over decades, many drugs have been investigated in phase 2 and 3; however, no approved therapy to date. Despite the alarming global rates of NAFLD, there are no local community-based studies on the prevalence of NAFLD or local practice guidelines on its management; this expert review aims to fill this gap.

ERCP quality indicators: The experience of a high-volume tertiary care center in Saudi Arabia.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most technically demanding and high-risk procedures performed by GI endoscopists. Therefore, guidelines or position statements on various aspects of quality indicators, safety indicators and credentialing for ERCP have been developed by gastroenterology associations. In this paper, we evaluate the ERCP quality in a single, high-volume, tertiary care center in Saudi Arabia using a number of measures commonly stated by these organizations, and compare the experience of that center to the previously-published standards in this regard. PATIENTS AND METHODS: This is a descriptive, retrospective chart review of a consecutive sample taken over 12 continuous months (July 2016-June 2017). Data collected included demographic characteristics, and technical/clinical details from three time periods: preprocedure, intraprocedure, and postprocedure. Measurement parameters were all taken from the ASGE/ACG guidelines. Data was represented by the percentage of which each indicator was achieved, and the 95% proportion confidence intervals (CIs) when needed. RESULTS: From July 2016 to June 2017, 281 ERCP procedures were performed. An outstanding majority of them (95.7%) was done for therapeutic purposes, whereas 4.3% were diagnostic procedures. The sample included 206 patients, of whom 83 (40.3%) were males. The age of the participants ranged between 11 and 101 years (mean age ±â€¯SD; 51 ±â€¯19). The quality of ERCP at the center in which the study was done met the performance targets stated by the ASGE/ACG for almost all indicators. Adverse events reported in our series were lower than previous studies for pancreatitis and perforation, and slightly higher in the incidence of bleeding, cholangitis, and death. CONCLUSION: In a single, high-volume, tertiary care center in Saudi Arabia, the quality of ERCP met the performance targets stated by the ASGE/ACG for almost all indicators.

Colonic Mucosal Microbiota in Colorectal Cancer: A Single-Center Metagenomic Study in Saudi Arabia.

BACKGROUND AND AIM: Because genetic and geographic variations in intestinal microbiota are known to exist, the focus of this study was to establish an estimation of microbiota in colorectal cancer (CRC) patients in Saudi Arabia by means of metagenomic studies. METHODS: From July 2010 to November 2012, colorectal cancer patients attending our hospital were enrolled for the metagenomic studies. All underwent clinical, endoscopic, and histological assessment. Mucosal microbiota samples were collected from each patient by jet-flushing colonic mucosa with distilled water at unified segments of the colon, followed by aspiration, during colonoscopy. Total purified dsDNA was extracted and quantified prior to metagenomic sequencing using an Illumina platform. Satisfactory DNA samples (n = 29) were subjected to metagenomics studies, followed by comprehensive comparative phylogenetic analysis. An equal number of healthy age-matched controls were also examined for colonic mucosal microbiota. RESULTS: Metagenomics data on 29 patients (14 females) in the age range 38-77 years were analyzed. The majority 11 (37%) of our patients were overweight (BMI = 25-30). Rectal bleeding was the presenting symptom in 18/29 (62%), while symptomatic anemia was the presenting symptom in 11/29 (37%). The location of colon cancer was rectal in 14 (48%), while cecal growth was observed in 8 (27%). Hepatic flexure growth was found in 1 (3%), descending colonic growth was found in 2 (6%), and 4 (13%) patients had transverse colon growth. The metagenomics analysis was carried out, and a total of 3.58G reads were sequenced, and about 321.91G data were used in the analysis. This study identified 11 genera specific to colorectal cancer patients when compared to genera in the control group. Bacteroides fragilis and Fusobacterium were found to be significantly prevalent in the carcinoma group when compared to the control group. CONCLUSION: The current study has given an insight into the microbiota of colorectal cancer patients in Saudi Arabia and has identified various genera significantly present in these patients when compared to those of the control group.