ABSTRACT
In November 2018, the U.S. food and drug administration (FDA) issued guidance for the development of drugs for chronic hepatitis B virus infection (draft for comments) (hereinafter referred to as draft for comments), and in April 2022, the FDA issued Chronic Hepatitis B Virus Infection: Developing Drugs for Treatment, which has been updated with some details based on the Draft for Comments. This guidance further emphasizes the importance of HBsAg clearance in clinical trials, and classifies chronic suppressive therapy into two categories, namely noninferiority (NI) (or superiority) test with nucleos(t)ide analogues as control and add-on superiority trial with nucleos(t)ide analogues as control, and as for the latter, HBV DNA is no longer recommended as a primary endpoint of the trial, which poses a huge challenge to the development of innovative drugs targeting HBV DNA. The new finite duration therapy should aim to eliminate HBsAg and reduce virologic relapse and the risk of liver disease progression during treatment cessation. Reduction in HBsAg from baseline is not recommended as a primary endpoint for phase Ⅲ clinical trials, since the correlation between such reduction and clinical response remains unclear. In addition, this guidance also specifies the duration of treatment cessation and treatment consolidation period and the criteria for withdrawal of nucleos(t)ide analogues.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinical effect of one stage anterior and posterior fusion and posterior fixation for the treatment of thoracic and lumbar spinal tuberculosis.</p><p><b>METHODS</b>From March 2003 to December 2006, one stage anterior and posterior fusion and posterior fixation were performed to treat 23 patients who suffered thoracic and lumbar spinal tuberculosis. There were 15 males and 8 females with an average of 37.6 years (17-61 years). 4 cases' tuberculose focus were in thoracic vertebra, 8 cases in thoracolumbar, 11 cases in lumbar.</p><p><b>RESULTS</b>The average follow up period was 28.7 months (9-40 months). The symptoms of all patients had primarily relieved and the patients can ambulate at 2-3 weeks after treatment. At the 6th after operation, the X-ray showed interbody fusion. Frankel grading of 16 patients with incomplete paraplegia were improved averagely 1.62 grades. The major complications including 2 cases of temporary sinus formation, 1 case of fixtor breaking and 1 case of recurring (owing to an inadequate postoperative chemotherapy).</p><p><b>CONCLUSION</b>One stage anterior and posterior fusion and posterior fixation can effectually resect focus, rebuild stability of spine, promote interbody fusion and recovery of incomplete paraplegia in treating thoracic and lumbar spinal tuberculosis.</p>