Drivers of tidal flow variability in the Pussur fluvial estuary: A numerical study by HEC-RAS.

This paper aims at characterizing the longitudinal and temporal variability of tidal flows in the Gorai-Pussur River system of Bangladesh, which spans about 158 km, starting from Bordia upstream to Akram Point downstream. Considering the upstream fresh water discharge and the downstream tide level as the drivers of tidal flow variability, the spatiotemporal change in hydrodynamics of the Pussur Fluvial Estuary was simulated using HEC-RAS software at the neap-spring and seasonal scales. The model was calibrated by comparing the simulated discharge and water levels with available measured data at an intermediate station. During the dry season, the tidal effect from the sea reaches Bordia, while in the monsoon season, the tide reaches about 15 km less (up to Kalia) due to the increased flow of freshwater. The Pussur river experiences tidal amplification up to Chalna, located approximately 90 km from its mouth. Beyond Chalna, tidal dumping covers a distance of 100-170 km upto Bordia. The tidal range ratio between Akram Point and Mongla is 1.28. The phase shift of the high water is found approximately 1.0 h over a distance of 50 km. It is found that due to 50% increase of discharge in Bordia, the increase of discharges at Kalia and Chalna were found as 43% and 7%, respectively. For a 0.5 m increase in water level at downstream (Akram Point), the high and low water levels at Chalna are increased by 0.15 and 0.69 m, while for 1.0 m increase in water level at downstream, the high and low water levels at Chalna are increased by 0.67 and 1.20 m, respectively.

Comparison of two assessments of real-world data and real-world evidence for regulatory decision-making.

Real-world data (RWD) and real-world evidence (RWE) are increasingly used to support regulatory decision making, but regulatory agencies and stakeholders may apply different definitions for RWD and use different criteria to determine when analysis of such data are considered RWE in decisions on drug approvals. To explore this issue, we reviewed two prominent publications that operationalized the definitions of RWD and RWE when describing the use of RWE in drug approvals by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Both publications considered noninterventional (observational) studies, RWD as a comparator arm for a single-arm trial, product-related literature reviews, and RWD to support clinical trial implementation (e.g., to identify potential participants) as generating RWE. In contrast, inconsistencies were identified regarding types of data sources and study designs that were considered as not generating RWE. For example, a lack of agreement existed regarding whether RWE is generated when RWD describe therapeutic contexts or are used in phase I/II interventional trials, open-label extension studies, or pharmacovigilance activities. These discrepancies highlight opportunities to develop a consistent understanding of the role of RWE in regulatory decision making for drug approvals among regulatory agencies and stakeholders.

Public healthcare system utilization for chronic hepatitis C infection in Vietnam.

BACKGROUND: Healthcare utilization is typically adversely affected when the treatment is expensive and requires multiple visits. We examined the determinants of healthcare-seeking for Hepatitis C virus (HCV) infection which is asymptomatic, chronic, and requires costly treatment in an urban tertiary care referral hospital in Vietnam. METHODS: We conducted a secondary analysis of hospital data for patients attending the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam between 2017 and 2020 specifically for HCV infection treatment. Poisson regression was used to determine the effect of personal factors (age, sex, comorbidities) and structural factors (health insurance, proximity to the facility, seasonality, year of visit) on the number of hospital visits. RESULTS: From 2017 to 2020 a total of 22,052 eligible patients sought treatment in the hospital. Among the patients, 50.4% were males and 58.7% were > 50 years of age. The mean number of visits per person was 2.17. In the multivariate analysis compared to 2017, the number of hospital visits increased by 4% in 2018 and then significantly decreased in 2019 and 2020. Visit numbers were significantly lower (6%) among South East region residents compared to those from Central Highlands and for those who lived further away from the hospital. The visit numbers were significantly higher among older age groups (5-11%), those with health insurance (6%), and those with comorbidities (5%) compared to others. Although the number of hospital visits by females was higher (7%) than males in 2017, it significantly decreased in subsequent years. CONCLUSIONS: Our study indicated that there are both structural and individual factors affecting the number of visits for HCV treatment. To meet the global strategy for elimination of HCV, Vietnam Government needs to address the structural and personal barriers to healthcare seeking, with a special focus on women.

Clinical manifestations and outcomes of COVID-19 in maintenance hemodialysis patients of a high infectious epidemic country: a prospective cross-sectional study.

Introduction: The outbreak of COVID-19 poses great challenges for patients on maintenance haemodialysis. Here, we reported the clinical characteristics and laboratory features of maintenance haemodialysis (MHD) patients with COVID-19 in Bangladesh. Methods: Altogether, 67 MHD patients were enroled in the study from two dedicated tertiary-level hospitals for COVID-19 after the prospective cross-sectional execution of selection criteria. Data were collected from medical records and interviews. Different statistical analysis was carried out in the data analysis. Results: The mean age was 55.0±9.9 years, with 40 males (59.7%). The mean dialysis duration was 23.4±11.5 months. The most common symptoms were fever (82.1%), cough (53.7%), and shortness of breath (55.2%), while the common comorbid condition was hypertension (98.5%), followed by diabetes (56.7%). Among MHD patients, 52.2% to 79.1% suffered from severe to critical COVID-19, 48 patients (71.6%) had 26-75% lung involvement on high resolution computed tomography of the chest, 23 patients (34.3%) did not survive, 20 patients (29.9%) were admitted to ICU, and nine patients (13.4%) needed mechanical ventilation. Patients who did not survive were significantly older (mean age: 63.0 vs. 50.86 years, P=0.0001), had significantly higher cardiovascular risk factors (69.6% vs. 43.2%, P=0.04), severe shortness of breath (82.6% vs. 40.9%, P=0.0001), and longer hospital stays (mean days: 17.9 vs. 13.0, P=0,0001) compared to the survivor group. The white blood cell count, C-reactive protein, lactate dehydrogenase, pro-calcitonin, and thrombocytopenia were significantly (P<0.0001) higher, while the albumin level was significantly lower (P=0.0001) in non-survivor compared to patients who survived. Conclusion: Maintenance haemodialysis patients had severe to critical COVID-19 and had a higher risk of non-survival if they were older and had comorbidities such as hypertension and diabetes. Therefore, MHD patients with COVID-19 need close monitoring to improve their outcomes.

Use of Real-World Evidence in Neuroscience-Related New Drug and Biologics License Applications for Novel Therapeutics.

The US Food and Drug Administration (FDA) is evaluating the potential use of real-world evidence (RWE) in regulatory decision making. Some groups have evaluated the use of RWE in regulatory submissions in the United States and abroad, reporting that reliance on RWE to support new product approvals is relatively common. Confusion regarding the use of RWE in drug-approval decisions may arise, however, based on different application of the terms real-world data (RWD) and RWE. We evaluated RWE in new drug applications (NDAs) and biologics license applications (BLAs) from January 2019 to June 2021 for novel drugs and biologics approved by the FDA with indications related to psychiatry, neurology, pain, or sedation (here, termed neuroscience-related). We sought to determine whether the submissions included RWE and to describe the types of data and study designs used. Thirty neuroscience-related NDAs or BLAs were identified for novel drugs and biologics approved during the time-period of interest. Among these approvals, three applications (10%) were adjudicated as containing RWE, one of which included RWE as primary evidence of effectiveness. Our findings highlight how different operational definitions of the terms RWD and RWE can result in demonstrably different reporting of the use of RWE in regulatory decision making for neuroscience-related novel drugs and biologics. A better understanding of this topic, along with awareness of regulatory definitions of RWE, are important factors to promote accurate tracking and reporting of regulatory submissions involving RWE. These factors can also improve awareness among the stakeholder community regarding the role of RWD and RWE in regulatory decision making.

Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure.

Nucleic acid testing to confirm sustained virological response (SVR) after HCV therapy is technical, often expensive, and frequently unavailable where disease prevalence is highest. Alternative surrogate biomarkers merit evaluation. In a short-treatment trial in Vietnam (SEARCH-1; n = 52) we analysed how changes in alanine transaminase (ΔALT) and aspartate transaminase (ΔAST), from end of treatment (EOT) to EOT + 12 weeks, related to SVR, defined as HCV RNA < lower limit of quantification 12 weeks after EOT. In a separate UK trial (STOPHCV1; n = 202), we then tested the hypothesis that any elevation in ALT or AST between EOT and EOT12 is a sensitive screen for treatment failure. In SEARCH-1, among 48 individuals with data, 13 failed to achieve SVR. Median ΔALT and ΔAST were negative in cured patients but elevated when treatment failed [median ΔALT (IQR): -2 IU/L (-6, +2)] versus +17 IU/L (+7.5, +38) (p< 0.001). Amongst treatment failures, 12/13 had increase in ALT and 13/13 had increase in AST after EOT, compared with 12/35 in those cured. In STOPHCV1, 196/202 patients had evaluable data, of which 57 did not achieve SVR. A rise in ALT after EOT was 100% sensitive (95% C.I. [93.7 - 100%]) and 51% specific (42.4 - 59.7%) for detecting treatment failure. ΔAST >0 IU/L was 98.1% (89.9 - 99.9%) sensitive and 35.8% (27.3 - 45.1%) specific. A rise in ALT or AST after HCV therapy is a highly sensitive screen for treatment failure in mild liver disease. This finding could reduce costs and complexity of managing HCV.

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study.

Background: World Health Organization has called for research into predictive factors for selecting persons who could be successfully treated with shorter durations of direct-acting antiviral (DAA) therapy for hepatitis C. We evaluated early virological response as a means of shortening treatment and explored host, viral and pharmacokinetic contributors to treatment outcome. Methods: Duration of sofosbuvir and daclatasvir (SOF/DCV) was determined according to day 2 (D2) virologic response for HCV genotype (gt) 1- or 6-infected adults in Vietnam with mild liver disease. Participants received 4- or 8-week treatment according to whether D2 HCV RNA was above or below 500 IU/ml (standard duration is 12 weeks). Primary endpoint was sustained virological response (SVR12). Those failing therapy were retreated with 12 weeks SOF/DCV. Host IFNL4 genotype and viral sequencing was performed at baseline, with repeat viral sequencing if virological rebound was observed. Levels of SOF, its inactive metabolite GS-331007 and DCV were measured on days 0 and 28. Results: Of 52 adults enrolled, 34 received 4 weeks SOF/DCV, 17 got 8 weeks and 1 withdrew. SVR12 was achieved in 21/34 (62%) treated for 4 weeks, and 17/17 (100%) treated for 8 weeks. Overall, 38/51 (75%) were cured with first-line treatment (mean duration 37 days). Despite a high prevalence of putative NS5A-inhibitor resistance-associated substitutions (RASs), all first-line treatment failures cured after retreatment (13/13). We found no evidence treatment failure was associated with host IFNL4 genotype, viral subtype, baseline RAS, SOF or DCV levels. Conclusions: Shortened SOF/DCV therapy, with retreatment if needed, reduces DAA use in patients with mild liver disease, while maintaining high cure rates. D2 virologic response alone does not adequately predict SVR12 with 4-week treatment. Funding: Funded by the Medical Research Council (Grant MR/P025064/1) and The Global Challenges Research 70 Fund (Wellcome Trust Grant 206/296/Z/17/Z).

Hepatitis C is a blood-borne virus that causes thousands of deaths from liver cirrhosis and liver cancer each year. Antiviral therapies can cure most cases of infection in 12 weeks. Unfortunately, treatment is expensive, and sticking with the regimen for 12 weeks can be difficult. It may be especially challenging for unhoused people or those who use injection drugs and who have high rates of hepatitis C infection. Shorter durations of therapy may make it more accessible, especially for high-risk populations. But studies of shorter antiviral treatment durations have yet to produce high enough cure rates. Finding ways to identify patients who would benefit from shorter therapy is a key goal of the World Health Organization. Potential characteristics that may predict a faster treatment response include low virus levels before initiating treatment, patient genetics, drug resistance mutations in the virus, and higher drug levels in the patient's blood during treatment. For example, previous research showed that a rapid decrease in virus levels in a patient's blood two days after starting antiviral therapy with three drugs predicted patient cures after three weeks of treatment. To test if high cure rates could be achieved in just four weeks of treatment, Flower et al. enrolled 52 patients with hepatitis C in a study to receive the most widely accessible dual antiviral treatment (sofosbuvir and daclatasvir). Participants received four or eight weeks of treatment, depending on the amount of viral RNA in their blood after two days of treatment. The results indicate that a rapid decrease in virus levels in the blood does not adequately predict cure rates with four weeks of two-drug combination therapy. However, eight weeks may be highly effective, regardless of viral levels early in treatment. Thirty-four individuals with low virus levels on the second day of treatment received four weeks of therapy, which cured 21 or 62% of them. All seventeen individuals with higher viral levels on day two were cured after eight weeks of treatment. Twelve weeks of retreatment was sufficient to cure the 13 individuals who did not achieve cure with four weeks of therapy. Even patients with drug resistance genes after the first round of therapy responded to a longer second round. Flower et al. show that patient genetics, virus subtype, drug levels in the patient's blood, and viral drug resistance genes before therapy, were not associated with patient cures after four weeks of treatment. Given that retreatment is safe and effective, larger studies are now needed to determine whether eight weeks of therapy with sofosbuvir and daclatasvir may be enough to cure patients with mild liver disease. More studies are also necessary to identify patients that may benefit from shorter therapy durations. Finding ways to shorten antiviral therapy for hepatitis C could help make treatment more accessible and reduce therapy costs for both individuals and governments.

Real-world assessment of the treatment patterns and outcomes among patients with multiple myeloma across different risk stratification criteria in the United States: a retrospective cohort study.

This study evaluated prognostic performance of International Staging System (ISS), revised ISS, and chromosomal abnormalities (CA) in newly diagnosed multiple myeloma patients to describe treatment patterns (cohort 1; n = 1979) and survival outcomes (cohort 2; n = 1382). In both cohorts, ∼18%, 41%, and 37% of patients were high-risk according to the R-ISS, ISS, and high-risk CA criteria, respectively. Across all risk stratification criteria, 60% of patients received triplets. In cohort 2, the median modified progression-free survival decreased with each increasing risk stage (23.5, 12.1, and 8.8 months in R-ISS I, II, and III, respectively, and 16.0, 12.7, and 10.4 months in ISS I, II, and III). Similar trends were observed in the proportions of two-year overall survival. In conclusion, R-ISS has greater discriminatory power than ISS or high-risk CA alone and can be implemented in a real-world setting. Accordingly, a more risk-adapted approach can be feasible, with a greater population-level impact.

The endemic Helicobacter pylori population in Southern Vietnam has both South East Asian and European origins.

BACKGROUND: The burden of Helicobacter pylori-induced gastric cancer varies based on predominant H. pylori population in various geographical regions. Vietnam is a high H. pylori burden country with the highest age-standardized incidence rate of gastric cancer (16.3 cases/100,000 for both sexes) in Southeast Asia, despite this data on the H. pylori population is scanty. We examined the global context of the endemic H. pylori population in Vietnam and present a contextual and comparative genomics analysis of 83 H. pylori isolates from patients in Vietnam. RESULTS: There are at least two major H. pylori populations are circulating in symptomatic Vietnamese patients. The majority of the isolates (~ 80%, 66/83) belong to the hspEastAsia and the remaining belong to hpEurope population (~ 20%, 17/83). In total, 66 isolates (66/83) were cagA positive, 64 were hspEastAsia isolates and two were hpEurope isolates. Examination of the second repeat region revealed that most of the cagA genes were ABD type (63/66; 61 were hspEastAsia isolates and two were hpEurope isolates). The remaining three isolates (all from hspEastAsia isolates) were ABC or ABCC types. We also detected that 4.5% (3/66) cagA gene from hspEastAsia isolates contained EPIYA-like sequences, ESIYA at EPIYA-B segments. Analysis of the vacA allelic type revealed 98.8% (82/83) and 41% (34/83) of the strains harboured the s1 and m1 allelic variant, respectively; 34/83 carried both s1m1 alleles. The most frequent genotypes among the cagA positive isolates were vacA s1m1/cagA + and vacA s1m2/cagA + , accounting for 51.5% (34/66) and 48.5% (32/66) of the isolates, respectively. CONCLUSIONS: There are two predominant lineages of H. pylori circulating in Vietnam; most of the isolates belong to the hspEastAsia population. The hpEurope population is further divided into two smaller clusters.

High Cure Rates for Hepatitis C Virus Genotype 6 in Advanced Liver Fibrosis With 12 Weeks Sofosbuvir and Daclatasvir: The Vietnam SEARCH Study.

BACKGROUND: Genotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis. METHODS: In this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load <500 IU/mL at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/mL received 24 weeks. Primary endpoint was sustained virological response (SVR). RESULTS: Of 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load <500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline. CONCLUSIONS: Prescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is <5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.

A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.

BACKGROUND: Hepatitis E virus (HEV) infection is endemic in Bangladesh and there are occasional outbreaks. The molecular characteristics and pathogenesis of endemic and outbreak HEV strains are poorly understood. We compared the genetic relatedness and virulence associated mutations of endemic HEV strains with outbreak strains. METHODS: We analyzed systematically collected serum samples from HEV immunoglobulin M (IgM) positive patients attended at Bangabandhu Sheikh Mujib Medical University, Dhaka from August 2013 to June 2015. HEV RNA positive samples were subjected to whole genome sequencing. Genotype and subtype of the strains were determined by phylogenetic analysis. Virulence associated mutations e.g. acute viral hepatitis (AVH), fulminant hepatic failure (FHF), chronic hepatitis, ribavirin treatment failure (RTF), B and T cell neutralization epitopes were determined. RESULTS: 92 HEV immunoglobulin M (IgM) antibody positive plasma samples (43 in 2013-2014 and 49 in 2014-2015) were studied. 77.1% (70/92) of the samples were HEV RNA positive. A 279 bp open reading frame (ORF) 2 and ORF 3 sequence was obtained from 54.2% (38/70) of the strains. Of these 38 strains, whole genome sequence (WGS) was obtained from 21 strains. In phylogenetic analysis of 38 (279 bp) sequence all HEV sequences belonged to genotype 1 and subtype 1a. Further phylogenetic analysis of 21 HEV WGS, Bangladeshi HEV sequences clustered with genotype 1a sequences from neighboring countries. Within genotype 1a cluster, Bangladesh HEV strains formed a separate cluster with the 2010 HEV outbreak strains from northern Bangladesh. 80.9 to 100% of the strains had A317T, T735I, L1120I, L1110F, P259S, V1479I, G1634K mutations associates AVH, FHF and RTF. Mutations in T cell recognition epitope T3, T5, T7 was observed in 76.1%, 100% and 100% of the strains respectively. CONCLUSION: Strains of HEV genotype 1a are dominant in Bangladesh and are associated with endemic and outbreak of HEV infection. HEV isolates in Bangladesh have high prevalence of virulence associated mutations and mutation which alters antigenicity to B and T cell epitopes.

Catheter ablation and healthcare utilization and cost among patients with paroxysmal versus persistent atrial fibrillation.

BACKGROUND: Ablation reduces atrial fibrillation (AF) burden and improves health-related quality of life. The relationship between ablation, healthcare utilization, and AF type (paroxysmal AF [PAF] vs persistent AF [PsAF]) remains unclear. OBJECTIVE: To compare changes in AF-related healthcare utilization and costs from preablation to postablation among patients with PAF and PsAF. METHODS: Patients (2794 PAF, 1909 PsAF) undergoing ablation (2016-2018) were identified using the Optum database. Outcomes included inpatient admissions, emergency department (ED) visits, office visits, cardioversion, and antiarrhythmic drug (AAD) use. Costs (2018 US$) and outcomes were compared for the year before/after ablation using the McNemar test and Wilcoxon signed rank test. RESULTS: Compared to PAF patients, PsAF patients were older (68.6 ± 9.0 years vs 67.4 ± 9.9 years, P < .0001), were less commonly female (36.3% vs 44.1%, P < .0001), and more commonly had a CHA2DS2-VASc ≥ 3(71.2% vs 62.7%, P < .0001). The 12-month postablation costs were lower for AF-specific inpatient admissions (PAF -28%, PsAF -33%), ED visits (PAF -76%, PsAF -70%), AAD prescription fills (PAF -25%, PsAF -7%), and cardioversions (PAF -59%, PsAF -55%) as compared to 12 months before ablation. Although these reductions were observed for both PAF and PsAF patients, absolute costs remained higher for PsAF. Total AF costs were higher during the 1 year after ablation vs before ablation (PAF: 11%, P < .0001; PsAF: 10%, P < .0001) owing to repeat ablation. However, in the 18-month follow-up analysis, postablation costs were overall reduced (PAF: 35%, P < .0001; PsAF: 34%, P < .0001), despite including costs from repeat ablation. CONCLUSION: Significant reductions in healthcare utilization and costs were observed among PAF and PsAF patients undergoing ablation. These data suggest a strategy of earlier ablation may reduce long-term healthcare utilization and costs.

Limited duration of antiarrhythmic drug use for newly diagnosed atrial fibrillation in a nationwide population under age 65.

INTRODUCTION: Antiarrhythmic drugs (AADs) are commonly used for the treatment of newly diagnosed symptomatic atrial fibrillation (AF), however initial AAD choice, duration of therapy, rates of discontinuation, and factors associated with a durable response to therapy are poorly understood. This study assesses the initial choice and duration of antiarrhythmic drug therapy in the first 2 years after diagnosis of AF in a younger, commercially insured population. METHODS: A large nationally representative sample of patients age 20-64 was studied using the IBM MarketScan Database. Patients who started an AAD within 90 days of AF diagnosis with continuous enrollment for 1-year pre-index diagnosis and 2 years post-index were included. A Cox proportional hazards model was used to determine factors associated with AAD discontinuation. RESULTS: Flecainide was used most frequently (26.8%), followed by amiodarone (22.5%), dronedarone (18.3%), sotalol (15.8%), and propafenone (14.0%), with other AADs used less frequently. Twenty-two percent of patients who started on an AAD underwent ablation within 2 years, with 79% discontinuing the AAD after ablation. Ablation was the strongest predictor of AAD discontinuation (hazard ratio [HR], 1.70; 95% confidence interval [CI]: 1.61-1.80), followed by the male gender (HR, 1.10; CI: 1.02-1.19). Older patients (HR, 0.76; CI: 0.72-0.80; reference age 18-49) and those with comorbidities, including cardiomyopathy (HR, 075; CI: 0.61-0.91), diabetes (HR, 0.83; CI: 0.75-0.91), and hypertension (HR, 0.87; CI: 0.81-0.94) were less likely to discontinue AADs. CONCLUSION: Only 31% of patients remained on the initial AAD at 2 years, with a mean duration of initial therapy 7.6 months before discontinuation.

A comparative whole genome analysis of Helicobacter pylori from a human dense South Asian setting.

Helicobacter pylori, a Gram-negative bacterium, is associated with a wide range of gastric diseases such as gastritis, duodenal ulcer, and gastric cancer. The prevalence of H pylori and risk of disease vary in different parts of the world based on the prevailing bacterial lineage. Here, we present a contextual and comparative genomics analysis of 20 clinical isolates of H pylori from patients in Bangladesh. Despite a uniform host ethnicity (Bengali), isolates were classified as being part of the HpAsia2 (50%) or HpEurope (50%) population. Out of twenty isolates, eighteen isolates were cagA positive, with two HpEurope isolates being cagA negative, three EPIYA motif patterns (AB, AB-C, and ABC-C) were observed among the cagA-positive isolates. Three vacA genotypes were observed with the s1m1i1dic1 genotype observed in 75% of isolates; the s1m2i1d1c2 and s2m2i2d2c2 genotypes were found to be 15% and 10% of isolates, respectively. The non-virulent genotypes s2m2i2d2c2 was only observed in HpEurope population isolates. Genotypic analysis of oipA gene, present in all isolates, revealed five different patterns of the CT repeat; all HpAsia2 isolates were in "ON" while 20% of HpEurope isolates were genotypically "OFF." The three blood group antigen binding adhesins encoded genes (bab genes) examined and we observed that the most common genotype was (babA/babB/-) found in eight isolates, notably six were HpAsia2 isolates. The babA gene was found in all HpAsia2 isolates but present in only half of the HpEurope isolates. In silico antibiotic susceptibility analysis revealed that 40% of the strains were multi-drug resistant. Mutations associated with resistance to metronidazole, fluoroquinolone, and clarithromycin were detected 90%, 45%, and 5%, respectively, in H pylori strain. In conclusion, it is evident that two populations of H pylori with similar antibiotic profiles are predominant in Bangladesh, and it appears that genotypically the HpAisa2 isolates are potentially more virulent than the HpEurope isolates.

Microbial Resistance Movements: An Overview of Global Public Health Threats Posed by Antimicrobial Resistance, and How Best to Counter.

Antibiotics changed medical practice by significantly decreasing the morbidity and mortality associated with bacterial infection. However, infectious diseases remain the leading cause of death in the world. There is global concern about the rise in antimicrobial resistance (AMR), which affects both developed and developing countries. AMR is a public health challenge with extensive health, economic, and societal implications. This paper sets AMR in context, starting with the history of antibiotics, including the discovery of penicillin and the golden era of antibiotics, before exploring the problems and challenges we now face due to AMR. Among the factors discussed is the low level of development of new antimicrobials and the irrational prescribing of antibiotics in developed and developing countries. A fundamental problem is the knowledge, attitude, and practice (KAP) regarding antibiotics among medical practitioners, and we explore this aspect in some depth, including a discussion on the KAP among medical students. We conclude with suggestions on how to address this public health threat, including recommendations on training medical students about antibiotics, and strategies to overcome the problems of irrational antibiotic prescribing and AMR.

Healthcare utilization and cost in patients with atrial fibrillation and heart failure undergoing catheter ablation.

BACKGROUND: Catheter ablation is an effective treatment for patients with atrial fibrillation (AF) and heart failure (HF). However, little is known about how healthcare utilization and cost change after ablation in this population. We sought to determine healthcare utilization and cost patterns among patients with AF and HF undergoing ablation. METHODS: Using a large United States administrative database, we identified (n = 1568) treated with ablation with a primary and secondary diagnosis of AF and HF, respectively, were evaluated 1-year pre- and postablation for outcomes including inpatient admissions (AF or HF), emergency department (ED) visits, cardioversions, length of stay (LOS), and cost. A secondary analysis was extended to 3-years postablation. RESULTS: Reductions were observed in AF-related admissions (64%), LOS (65%), cardioversions (52%), ED visits (51%, all values, p < .0001), and HF-related admissions (22%, p = .01). There was a 40% reduction in inpatient admission cost ($4165 preablation to $2510 postablation, p < .0001). In a sensitivity analysis excluding repeat-ablation patients, a greater reduction in overall AF management cost was observed compared to the full cohort (-43% vs. -2%). Comparing 1-year pre- to 3-years postablation, both total mean AF-management cost ($850 per-patient per-month 1-year pre- to $546 3-years postablation, p < .0001) and AF-related healthcare utilization was reduced. CONCLUSIONS: Catheter ablation in patients with AF and HF resulted in significant reductions in healthcare utilization and cost through 3-years of follow-up. This reduction was observed regardless of whether repeat ablation was performed, reflecting the positive impact of ablation on longer term cost reduction.

Real-world characteristics and readmissions among patients undergoing ablation for ventricular tachycardia: a retrospective database analysis of commercially insured patients in the USA.

BACKGROUND: Radiofrequency catheter ablation is an effective treatment to alleviate symptoms and reduce recurrent implantable cardioverter-defibrillator (ICD/CRT-D) shocks in patients with ventricular tachycardia (VT). OBJECTIVE: To assess the characteristics and outcomes (complications, inpatient readmissions) of commercially insured patients in the USA undergoing ablation for ischaemic or non-ischaemic VT. METHODS: Patients aged 18-64 years with a primary diagnosis of VT who underwent ablation between 2006 and 2015 were identified using the IBM MarketScan Commercial Database. The rate of complications including vascular complications, pericarditis, pulmonary embolism and pericardial tamponade over a 30-day post-ablation period (including index admission) was examined. Inpatient readmissions (VT-related, heart failure (HF)-related and non-VT arrhythmia-related) over the 12-month post-ablation period were examined. A Cox regression model was used to determine factors associated with inpatient readmissions. RESULTS: 5242 patients (488 with ischaemic and 4754 with non-ischaemic VT) met the study criteria. The majority of VT ablations occurred in an outpatient setting (57% for ischaemic and 66% for non-ischaemic VT). Among complications, vascular complications were most frequent (2.05% among ischaemic and 1.6% among non-ischaemic VT patients) over the 30-day post-ablation period. Among ischaemic VT patients, 17%, 7.6% and 4.7% had VT-related, HF-related and non-VT arrhythmia-related inpatient readmissions, respectively in the 12-month post-ablation period. For non-ischaemic VT patients, these numbers were 7.5%, 1.7% and 3.1%, respectively. Inpatient setting (vs outpatient), baseline ICD/CRT-D implantation, HF comorbidity and ≥2 prior hospitalisations were associated with a higher risk of post-ablation VT-related inpatient readmissions among ischaemic VT patients. Similar factors also were associated with a higher risk of post-ablation VT-related inpatient readmission among non-ischaemic VT patients. CONCLUSION: Setting of ablation and comorbidity status were found to influence readmission rates. Complication and readmission rates following VT ablation were low indicating towards the favourable safety profile of VT ablation.

A deep learning approach based on convolutional LSTM for detecting diabetes.

Diabetes is a chronic disease that occurs when the pancreas does not generate sufficient insulin or the body cannot effectively utilize the produced insulin. If it remains unidentified and untreated, then it could be very deadliest. One can lead a healthy life with proper treatment if the presence of diabetes can be detected at an early stage. When the conventional process of detecting diabetes is tedious, there is a need of an automated system for identifying diabetes from the clinical and physical data. In this study, we developed a novel diabetes classifying model based on Convolutional Long Short-term Memory (Conv-LSTM) that was not applied yet in this regard. We applied another three popular models such as Convolutional Neural Network (CNN), Traditional LSTM (T-LSTM), and CNN-LSTM and compared the performance with our developed model over the Pima Indians Diabetes Database (PIDD). Significant features were extracted from the dataset using Boruta algorithm that returned glucose, BMI, insulin, blood pressure, and age as important features for classifying diabetes patients more accurately. We performed hyperparameter optimization using Grid Search algorithm in order to find the optimal parameters for the applied models. Initial experiment by splitting the dataset into separate training and testing sets, the Conv-LSTM-based model classified the diabetes patients with the highest accuracy of 91.38 %. In later, using cross-validation technique the Conv-LSTM model achieved the highest accuracy of 97.26 % and outperformed the other three models along with the state-of-the-art models.

Effectiveness of sofosbuvir based direct-acting antiviral regimens for chronic hepatitis C virus genotype 6 patients: Real-world experience in Vietnam.

BACKGROUND: Hepatitis C virus (HCV) genotype 6 is the commonest cause of chronic hepatitis C infection in much of southeast Asia, but data on the effectiveness of direct-acting antiviral agents (DAAs) against this genotype are limited. We conducted a retrospective cohort study of patients attending the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam, to define the effectiveness of DAAs in the treatment of chronic HCV genotype 6 in actual practice. METHODS: We included all patients with genotype 6 infections attending our hospital between March 2016 and October 2017 who received treatment with sofosbuvir-based DAA treatment regimens, and compared their responses with those with genotype 1 infections. RESULTS: 1758 patients (1148 genotype 6, 65.4%; 610 genotype 1, 34.6%) were analyzed. The majority of patients (1480, 84.2%) received sofosbuvir/ledipasvir (SOF/LDV) ± ribavirin (RBV); 278 (15.8%) received sofosbuvir/Daclatasvir (SOF/DCV) ± RBV. The median age of the patients was 57 years, (interquartile range (IQR) 46-64 years) The baseline HCV viral load (log IU/ml) was significantly higher in patients infected with genotype 6 compared with those infected with genotype 1 (6.8, 5.3-6.6 versus 6.3, 5.3-6.5 log10 IU/ml, p = <0.001, Mann Whitney U test). A sustained virological response (SVR), defined as an undetectable viral load measured between 12 and 24 weeks after completing treatment, and indicating cure, was seen in 97.3% (1711/1758) of patients. Treatment failure, defined as HCV viral load ≥15 IU/ml ≥12 weeks after completing treatment appeared to be more frequent in patients infected with genotype 6 virus (3.2%, 37/1148) than in those infected with genotype 1 (1.7%, 10/610), p = 0.050 chi-squared test). We found no evidence that patient's age, gender, liver cirrhosis, diabetes, HBV or HIV coinfection, prior treatment failure with pegylated interferon therapy, body mass index (BMI), aspartate aminotransferase to platelet ratio index (APRI), or fibrosis 4 (FIB-4) index were associated with treatment failure. CONCLUSIONS: Our study suggests that patients with HCV genotype 6 infection in Vietnam may respond less well to treatment with sofosbuvir based DAAs than patients with genotype 1 infections. Further studies are needed to confirm this observation and to define whether it is driven by genotype-specific mutations.