Policy Stringency,Handwashing and COVID-19 cases: Evidence from Global dataset

Objective: Since the COVID-19 pandemic, many governments globally have introduced policy measures to contain the spread of the virus. Popular COVID-19 containment measures include lockdowns of various forms (aggregated into government response stringency index [GRSI]) and handwashing (HWF). The effectiveness of these policy measures remains unclear in the academic literature. This study, therefore, examines the effect of government policy stringency and handwashing on total daily reported COVID-19 cases.Method: We use a comprehensive dataset of 176 countries to investigate the effect of government policy stringency and handwashing on daily reported COVID-19 cases. In this study, we apply the Lewbel (2012) two-stage least squares technique to control endogeneity.Results: Our results indicated that GRSI significantly contributes to the increase in the total and new confirmed cases of COVI-19. Sensitivity analyses revealed that the 1st, 4th, and 5th quintiles of GRIS significantly reduce total confirmed cases of COVID-19. Also, the result indicated that while the 1st quintile of GRIS contributes significantly to reducing the new confirmed cases of COVID-19, the 3rd, 4th, and 5th quintiles of GRSI contribute significantly to increasing the new confirmed cases of COVID-19. The results indicated that HWF reduces total and new confirmed cases of COVID-19; however, such effect is not robust to income and regional effects. Nonlinear analysis revealed that while GRSI has an inverted U-shaped relationship with total and new confirmed cases of COVID-19, HWF has a U-shaped relationship.Conclusion: We suggest that policymakers should focus on raising awareness and full engagement of all members of society in implementing public health policies rather than using stringent lockdown measures.     

Prevention of alloimmune rejection using XBP1-deleted bone marrow-derived dendritic cells in heart transplantation

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Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan

PurposeEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both recommended as first-line treatments for patients with chronic hepatitis B virus (CHB) infection according to international HBV treatment guidelines. However, recent studies reported conflicting results regarding the preferred antiviral in the prevention of hepatocellular carcinoma (HCC). This cohort study aimed to investigate this issue by using Taiwan's National Health Insurance Research Database, wherein a “finite” but not life-long treatment policy was applied.MethodsFrom January 2008 to December 2013, a total of 12,388 consecutive adult patients with CHB who received a finite course of TDF treatment (n = 1250) or ETV treatment (n = 11,138) were analyzed through screening for study eligibility followed by the 1:4 propensity score matching method.FindingsIn the entire cohort, the annual incidence and survival between the ETV and TDF groups were not significantly different regarding HCC occurrence (2.05 vs 2.74 per 100 patient-years [PY]; P = 0.055; hazard ratio [HR], 0.975; log-rank, P = 0.966), cirrhosis-related complications (1.9 vs 2.4 per 100 PY; P = 0.149; HR, 0.869; log-rank, P = 0.388), or all-cause mortality (2.16 vs 1.6 per 100 PY; P = 0.119; HR, 0.831; log-rank, P = 0.342), respectively. Propensity score matching analyses yielded similar results regarding HCC occurrence, cirrhosis-related complications, and all-cause mortality. In addition, these findings were consistently reproduced in the subgroups of patients with chronic hepatitis and cirrhosis that developed before antiviral treatment.ImplicationsETV and TDF did not significantly differ in prevention of HCC occurrence or reduction of cirrhosis-related complications and all-cause mortality in patients with CHB receiving a finite period of treatment.     

An Artificial Gut/Absorption Simulator: Simultaneous Evaluation of Desupersaturation and Absorption from Ketoconazole Supersaturated Solutions

For supersaturating formulations of BCS-II compounds, which by definition have high intestinal permeability, a closed USP apparatus does not provide the necessary absorptive conditions during dissolution. To address this, an artificial gut simulator (AGS) has been constructed consisting of a 2.5 mL donor compartment in which a hollow fiber-based absorption module is suspended. Drug from donor diffuses across the hollow fiber membrane to be absorbed by the continuously flowing intraluminal receiver fluid. The membrane surface area and intraluminal fluid flow rate are tuned to obtain the physiologically observed absorption rate constant for a weakly basic, poorly water-soluble model compound, ketoconazole (KTZ). Supersaturated solutions of KTZ were generated in the donor in pH 6.5 phosphate buffer by the pH-shift method in the absence (closed system, control) and presence (open system, biorelevant) of an optimally or suboptimally tuned absorption module. Drug concentrations in the donor and intraluminal fluids were determined by in-line UV spectroscopy. The presence of an absorptive sink reduced the supersaturated solution's crystallization propensity, more so in the case of the optimally tuned AGS. This study demonstrates the significance of simulating absorption of drug at a physiological rate during dissolution studies, especially to predict the performance of formulations of BCS-II drugs.     

Ventricular Tachycardia Burden and Mortality: Association or Causality?

Ventricular tachycardia (VT) is a potentially fatal cardiac rhythm disorder. Implantable cardioverter defibrillators (ICDs) are the primary management strategy for VT and have been shown to reduce the incidence of death but, ICDs do not reduce VT recurrences. Further, mounting evidence indicates that high VT burden, defined as the cumulative number of recurrent VTs or ICD shocks, is associated with an elevated risk of death; however, it is unclear if high VT burden is a cause of death or a marker of severe heart disease. Proposed mechanisms for a causal pathway suggest that multiple VT episodes or potential deleterious effects from ICDs might alter the myocardium of the ventricles to induce worsening heart disease, which might translate to an increased risk of mortality. In this review, we present the evidence to support association and causation hypotheses for the relationship between VT burden and risk of mortality and indicate potential gaps in evidence. Overall, there is insufficient evidence to prove causal hypotheses for the relationship between VT burden and mortality. Consistent definitions for VT burden, randomized controlled trials that assess the relationship between VT burden and mortality, and observational studies that capture VT burden are warranted to investigate if a potential causal relationship exists.