Selecting an appropriate all-oral short-course regimen for patients with multidrug-resistant or pre-extensive drug-resistant tuberculosis in China: A multicenter prospective cohort study.

OBJECTIVES: Long, ineffective, and toxic regimens hinder the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant tuberculosis (pre-XDR-TB). METHODS: We conducted a multicenter cohort study to prospectively evaluate the safety and efficacy of three 9-month, all-oral, 5-drug regimens. Regimen A (bedaquiline [Bdq]+linezolid [Lzd]+moxifloxacin [Mfx]+cycloserine [Cs]+pyrazinamide [Pza]) and Regimen B (Lzd+Mfx+Cs+clofazimine [Cfz]+Pza) were used to treat MDR-TB patients (Groups A and B, respectively, assigned according to the patient's treatment preference), while Regimen C (Bdq+Lzd+Cs+Cfz+Pza) was used to treat pre-XDR-TB patients (Group C). The primary endpoint was the occurrence of an unfavorable outcome within 12 months of treatment completion, regardless of regimen. RESULTS: A total of 104 patients (34 in Group A, 46 in Group B, and 24 in Group C), with a median age of 35.5 (29.0-54.0) years, were included in the analysis population. At 12 months after treatment completion, five patients were deemed non-assessable. Of the remaining 99 participants, seven (7.1%) had an unfavorable outcome (including two deaths from any cause, four with treatment failure, and one loss to follow-up) and 92 (92.9%) had a favorable outcome. Culture conversion was achieved in 82.5% (80/97) of participants at month 2 and in 97.9% (94/97) of participants at month 6. Adverse events (AEs) resulting in drug adjustment occurred in 69.2% (72/104) of participants, mainly due to Lzd and Pza use. A QT interval prolongation of ≥ 500 ms occurred in 5.8% (6/104) of participants. CONCLUSION: The primary outcome of the three tailored, 9-month, all-oral, 5-drug regimens was satisfactory in the vast majority of MDR-TB and pre-XDR-TB patients, with manageable and reversible AEs.

Effect of Electro-Thermo-Mechanical Coupling Stress on Top-Cooled E-Mode AlGaN/GaN HEMT.

This work investigated the effects of single stress and electro-thermo-mechanical coupling stress on the electrical properties of top-cooled enhancement mode (E-mode) Aluminium Gallium Nitride/Gallium Nitride (AlGaN/GaN) high electron mobility transistor (HEMT) (GS66508T). Planar pressure, linear deformation, punctate deformation, environmental temperature, electro-thermal coupling, thermo-mechanical coupling, and electro-thermo-mechanical coupling stresses were applied to the device. It was found that different kinds of stress had different influence mechanisms on the device. Namely, excessive mechanical pressure/deformation stress caused serious, irrecoverable degradation of the device's leakage current, with the gate leakage current (Ig) increasing by ~107 times and the drain-to-source leakage current (Idss) increasing by ~106 times after mechanical punctate deformation of 0.5 mm. The device characteristics were not restored after the mechanical stress was removed. Compared with three mechanical stresses, environmental thermal stress had a greater influence on the device's transfer characteristic and on-resistance (Ron) but far less influence on Ig and Idss. As was expected, multiple stress coupled to the device promoted invalidation of the device. For more in-depth investigation, finite element simulation carried out with COMSOL was used to analyze the effect of electro-thermo-mechanical coupling stress on top-cooled E-mode AlGaN/GaN HEMT. The results of the experiments and simulation demonstrated that single and coupled stresses, especially mechanical stress coupled with other stresses, degraded the electrical properties or even caused irreversible damage to top-cooled E-mode AlGaN/GaN HEMT. Mechanical stress should be reduced as much as possible in the packaging design, transportation, storage, and application of top-cooled E-mode AlGaN/GaN HEMT.

The Electrical and Thermal Characteristics of Stacked GaN MISHEMT.

To study the working performance of 3D stacked chips, a double-layer stacked GaN MISHEMTs structure was designed to study the electro-thermal characteristics and heat transfer process of stacked chips. Firstly, the electrical characteristics of double-layer and single-layer GaN MISHEMTs are compared at room temperature. Under the same conditions, the output current of double-layer GaN MISHEMTs is twice that of single-layer GaN MISHEMTs, but its off-state current is much higher than that of a single-layer device. Meanwhile, there is no significant difference between the threshold voltages of the double-layer and single-layer GaN MISHEMTs. Then, the effect of temperature on the electrical characteristics of double-layer GaN MISHEMTs is also investigated. When the temperature increased from room temperature to 150 °C, the device's threshold voltage gradually shifted negatively, the output current of the device decreased, and the off-state current of the device increased. Furthermore, a thermal resistance network model has been established to analyze the thermal characteristics of the stacked GaN MISHEMTs. The relative error between the results calculated according to the model and the experimental results does not exceed 4.26%, which verified the correctness and accuracy of the presented model to predict the temperature distribution of the stacked GaN MISHEMTs.