Chinese expert consensus on the combined use of antiviral drugs for novel coronavirus infection.

Expert consensus on the use of human serum albumin in critically ill patients.

Biopsy has been used to diagnose thoracic diseases for more than a century. Percutaneous needle biopsy plays a crucial role in the diagnosis, staging, and treatment planning for tumors in the lungs, thoracic wall, hilum, and mediastinum. With the continuous improvement in imaging techniques, the range of clinical applications for percutaneous needle biopsy is also expanding. It has become important to improve Chinese professionals’ and technicians’ understanding of percutaneous transthoracic needle biopsy (PTNB) in order to standardize operating procedures and to strengthen perioperative management. However, there is currently no Chinese expert consensus that provides systematic standardization and guidance for PTNB in clinical practice. The Committee of Chinese Society of Interventional Oncology (CSIO) of the Chinese Anti‐Cancer Association (CACA) initiated a Chinese multidisciplinary expert consensus on PTNB. The consensus includes image‐guided methods, indications, contraindications, multidisciplinary team recommendations, biopsy procedures, daytime/outpatient biopsy, complications, pathological examination, and management of negative results.

Antiviral combination therapies for persistent COVID-19 in immunocompromised patients

In recent years, the emergence of newly detected pathogens and the increase of drug resistant bacterial bring serious challenges for the diagnosis and treatment of infectious diseases. Tetracycline drugs are widely used in clinical practice, and the varieties of these drugs are constantly being updated. However, there is still a lack of guidance documents for the rational clinical application of tetracycline drugs in China. Meanwhile, some healthcare workers have doubts about their pharmaceutical characteristics, timing and methods of clinical application. In order to further standardize the clinical application of tetracycline drugs and provide professional evidence-based medicine suggestions for medical personnel in medical institutions, under the leadership of Hospital Infection Control Branch of Chinese Preventive Medicine Association and Clinical Pharmacology Branch of Chinese Pharmacological Society, experts from areas of infection, respiratory medicine, critical care medicine, emergency, infection control, pharmacy and other disciplines organized a consensus meeting and formulated multidisciplinary expert consensus on the rational use of tetracyclines commonly used in clinical practice. This expert consensus is based on the pharmaceutical characteristics of tetracyclines commonly used in China, the mechanism of action and drug resistance status of tetracyclines, combined with the infection site, pathogen characteristics and bacterial drug resistance. This expert consensus also pays attention to special populations and off-label drug use, and integrates domestic and foreign recommendations and the latest evidence-based medicine evidence, and 17 expert consensus opinions for clinical physicians, pharmacists, and other professionals in medical institutions to refer to were formed. In view of the particularity and complexity of infectious diseases and the individual differences of patients, in order to benefit patients, individualized anti-infection strategies should be implemented.

Literature-based review of the drugs used for the treatment of COVID-19

Several novel therapeutic approaches are currently in the pipeline for HCV treatment. They include new target host immune system as novel interferon, toll-like receptor agonists, therapeutic vaccines or interleukins, new target cell replication drug as ribavirin analogues, cyclophilin inhibitors, alpha glucosidase inhibitors, dephosphorylationinhibitors of eukaryotic initiation factors 2alpha, antisense molecule, entry inhibitors and specifically targeted antiviral therapy (STAT-C) such as viral enzyme inhibitor ( protease and polymerase). Several STAT-C molecules are currently in development and will soon be at hand and will offer new treatment opportunities to patients infected with hepatitis C. Promising results leading to more than 70% of sustained virological response in genotype 1 naive patients have been reported with two proteases inhibitors (telaprevir and boceprevir) in combination with pegylated interferon and ribavirin that are currently in phase III. These studies also demonstrated the potential to shorten treatment duration in those with a rapid viral response and the realistic hope for retreatment (40 and 75%) in previous non responders or relapsers to interferon based therapies. In addition there is indication that STAT-C drugs may help to overcome negative host factors that have historically been associated with poor response rates (such as ethnicity, insulin resistance, steatosis and cirrhosis). However these trials also emphasize the limitations of protease inhibitors and viral resistance data have provided important new lessons for small molecule drug development. In the near feature, it is likely that IFN-based therapy plus ribavirin will remain the backbone of the treatment of chronic hepatitis C. PEG-IFN and ribavirin are needed in order to prevent HCV resistance to STAT-C drugs and subsequently increase SVR. Genotypic and phenotypic resistance tests will also enter the therapeutic arena. Once several STAT-C agents without cross resistance become available, treatment strategies will include a combination of several drugs with different mechanisms of action (protease inhibitors and polymerase inhibitors) that could hopefully results in IFN and/or ribavirin sparing regimen. The first dual -- combination clinical trial with oral antiviral is still ongoing. Patients receiving this combination for 14 days had undetectable HCV RNA in 63% of naive genotype1 patients. This early success has moved IFN-free regimen a step closer to reality for patients. In the future, there might be combinations of antivirals having additive potency, lacking cross resistance and with a good safety profile.

Critical Care During the Coronavirus Crisis: Challenges and Considerations for the Cardiothoracic and Vascular Anesthesia Community

Effect of pre-hospitalization use of oral antiviral agents on reducing critical illness and mortality for patients with COVID-19 pneumonia

Percutaneous balloon compression (PBC) is recognized as a simple, safe, and effective intervention for trigeminal neuralgia (TN) and has been widely adopted in clinical practice across China. However, variations in its application exist among different regions. To standardize procedural protocols and enhance clinical outcomes, a multidisciplinary panel of Chinese experts from pain medicine and neurosurgery collaboratively developed this clinical expert consensus. The consensus formulation involved a systematic literature review of major databases, including Wanfang and PubMed, among others, and focusing on high-quality evidence such as systematic reviews, meta-analyses, randomized controlled trials, expert consensus statements, and clinical guidelines. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and structured consensus conference methods, the panel held iterative discussions and conducted voting sessions to finalize the recommendations. This document summarizes key aspects of PBC, including relevant anatomy, mechanisms of action, indications, contraindications, detailed operative techniques, and efficacy evaluation. It aims to serve as a practical reference for clinicians to standardize and optimize the use of PBC in the treatment of trigeminal neuralgia.

Novel and repurposed antiviral drugs are available for the treatment of coronavirus disease 2019 (COVID-19). However, antiviral combinations may be more potent and lead to faster viral clearance, but the methods for screening antiviral combinations against respiratory viruses are not well established and labor-intensive. Here, we describe a time-efficient (72-96 h) and simple in vitro drug-sensitivity assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using standard 96-well plates. We employ different synergy models (zero interaction potency, highest single agent, Loewe, Bliss) to determine the efficacy of antiviral therapies and synergistic combinations against ancestral and emerging clinical SARS-CoV-2 strains. We found that monotherapy of remdesivir, nirmatrelvir, and active metabolite of molnupiravir (EIDD-1931) demonstrated baseline EC50s within clinically achievable levels of 4.34 mg/L (CI: 3.74-4.94 mg/L), 1.25 mg/L (CI: 1.10-1.45 mg/L), and 0.25 mg/L (CI: 0.20-0.30 mg/L), respectively, against the ancestral SARS-CoV-2 strain. However, their efficacy varied against newer Omicron variants BA.1.1.15 and BA.2, particularly with the protease inhibitor nirmatrelvir. We also found that remdesivir and nirmatrelvir have a consistent, strong synergistic effect (Bliss synergy score >10) at clinically relevant drug concentrations (nirmatrelvir 0.25-1 mg/L with remdesivir 1-4 mg/L) across all SARS-CoV-2 strains tested. This method offers a practical tool that streamlines the identification of effective combination therapies and the detection of antiviral resistance. Our findings support the use of antiviral drug combinations targeting multiple viral components to enhance COVID-19 treatment efficacy, particularly in the context of emerging viral strains.

Background After failure to a first aTNF agent in Crohn’s disease (CD), a second aTNF shows higher rates of failure and discontinuation. Initiating a therapy with a different mechanism of action (MoA) such as ustekinumab (UST) or vedolizumab (VDZ) could lead to a greater durability of second-line biological treatment with a higher safety profile. Methods A retrospective and multicenter study (10 hospitals in Andalusia). We included patients with active CD (Harvey-Bradsaw index >4) who had failed a first aTNF agent and started a second-line biological with other aTNF or other MoA (UST or VDZ) between July 2017 and February 2020. The aim was to evaluate the long-term durability and safety of aTNF agents compared with other MoA as a second-line biological treatment. Results 249 CD patients were included; There were no significant differences between both groups in age, sex, disease duration, location, CD behavior, perianal disease, smoking habit or concomitant corticosteroid use. Whereas there were significant differences in the proportion of patients with abdominal surgery (29.5% aTNF group vs 42.5% othermMoA, p=0.032), and concomitant immunomodulators (41.9% aTNF vs 25.8% other MoA, p=0.008). Second-line biological treatment was aTNF in 129 patients (57 IFX and 72 ADA) and other MoA in 120 (97 UST and 23 VDZ). Second aTNF was discontinued in 81/129 patients (62.8%) after a median follow-up of 21 months (mo). Whereas 24/120 patients (20%) discontinued other MoA after a median follow-up of 41mo (p< 0.001). The rate of discontinuation per patient-year of follow-up was 20.9% for aTNF and 6.7% for other MoA. The probability of maintaining aTNF or other MoA was 64.4% vs 88.3% at 12mo, 46.5% vs 81.7% at 24mo and 31% vs 80% at 36mo (p<0.001). Discontinuation rates during follow-up were 68.4% for IFX, 58.3% for ADA, 39.1% for VDZ and 15.5% for UST (p<0.001). Reasons for discontinuation were 32.4% primary non-response (63.6% aTNF and 36.4% other MoA), 51% loss of response (82.7% aTNF and 17.3% other MoA) and 16.7% intolerance or adverse events (82.3% aTNF and 17.7% other MoA). Adverse events were reported in 31/249 patients (12%), 25/31 with aTNF and 6/31 with other MoA (5 vs 0 infusion reactions, 4 vs 1 mild infections, 1 vs 0 severe infections, 10 vs 2 cutaneous injury, 2 vs 1 arthralgias and 3 vs 2 other event). Conclusion In our clinical practice, a second-line aTNF associated with significantly lower long-term drug survival compared to changing to a different MoA. Lower rates of discontinuation were observed with change to a different MoA, especially to ustekinumab. Ustekinumab and vedolizumab showed a better safety profile than infliximab or adalimumab as second-line biologic in CD.

To evaluate the performance of chat generative pretrained transformer (ChatGPT) in key domains of clinical pharmacy practice, including prescription review, patient medication education, adverse drug reaction (ADR) recognition, ADR causality assessment and drug counselling. Questions and clinical pharmacist's answers were collected from real clinical cases and clinical pharmacist competency assessment. ChatGPT's responses were generated by inputting the same question into the 'New Chat' box of ChatGPT Mar 23 Version. Five licensed clinical pharmacists independently rated these answers on a scale of 0 (Completely incorrect) to 10 (Completely correct). The mean scores of ChatGPT and clinical pharmacists were compared using a paired 2-tailed Student's t-test. The text content of the answers was also descriptively summarized together. The quantitative results indicated that ChatGPT was excellent in drug counselling (ChatGPT: 8.77 vs. clinical pharmacist: 9.50, P = .0791) and weak in prescription review (5.23 vs. 9.90, P = .0089), patient medication education (6.20 vs. 9.07, P = .0032), ADR recognition (5.07 vs. 9.70, P = .0483) and ADR causality assessment (4.03 vs. 9.73, P = .023). The capabilities and limitations of ChatGPT in clinical pharmacy practice were summarized based on the completeness and accuracy of the answers. ChatGPT revealed robust retrieval, information integration and dialogue capabilities. It lacked medicine-specific datasets as well as the ability for handling advanced reasoning and complex instructions. While ChatGPT holds promise in clinical pharmacy practice as a supplementary tool, the ability of ChatGPT to handle complex problems needs further improvement and refinement.

Plasma exchange and COVID 19

With the significant increase in the use of extracorporeal membrane oxygenation in patients with severe respiratory failure, cardiogenic shock, and cardiopulmonary resuscitation, complications related to extracorporeal membrane oxygenation are increasingly being taken seriously. Cerebral injury is one of the most serious complications during extracorporeal membrane oxygenation treatment, and is an important factor affecting the hospital mortality rate and long-term quality of life. Due to the use of analgesics, sedatives, and muscle relaxants interfering with neurological physical examination results, cerebral injury that occurs during extracorporeal membrane oxygenation therapy is not easily detected in a timely manner. Therefore, bedside cerebral monitoring has important value in quickly detecting cerebral injury in patients with extracorporeal membrane oxygenation and providing early intervention guidance. Therefore, Extracorporeal Life Support Professional Committee of Chinese Medical Doctor Association organized relevant experts across the country to develop the"Chinese expert consensus on cerebral monitoring in patients with extracorporeal membrane oxygenation", this expert consensus is based on the pathological and physiological mechanisms of cerebral injury in patients with extracorporeal membrane oxygenation. It is based on the current application status of cerebral monitoring technologies such as neurological physical examination, plasma brain injury biomarkers, brain imaging, intracranial pressure, cerebral blood flow, brain oxygen, electroencephalogram, and somatosensory evoked potential. Combining the special clinical application scenarios of extracorporeal membrane oxygenation and integrating the latest evidence-based medical evidence, we have formed 15 consensus recommendations which can be referenced by professionals in critical care medicine, neurology, cardiovascular disease, respiratory and critical care, emergency medicine, and other fields. Given the particularity, complexity, and individual differences of critically ill patients, the recommendations formed by this expert consensus need to implement personalized strategies.

Background Adverse drug reactions (ADRs) monitoring in cancer patients is important to ensure early detection, effective management and possible prevention subsequently. Objectives This study was conducted to detect and monitor ADRs to anti-cancer agents, and to assess impact of clinical pharmacists (CPs)' interventions in minimizing ADRs to anti-cancer agents. Setting Private, specialty oncology care hospital in South India. Methods CPs prospectively followed cancer patients admitted to inpatient wards and treated at ambulatory care in order to identify ADRs, for a period of 3years. Identified/reported ADRs were discussed with concerned oncologists and/or nurses, documented electronically and assessed further for their causality, severity, preventability and grading. Based on study findings during year 1, interventions (educational, therapeutic and system based) were developed by CPs and implemented in order to minimize preventable ADRs. Impact of CPs' interventions was studied during year 2 and year 3. Main outcome measure(s) Preventable factors contributing to ADRs and percentage of preventable ADRs before and after CPs' interventions. Results A total of 1279 ADRs were reported in 1133 patients from a cohort of 1328 patients. Vomiting (23.22%), alopecia (9.53%), diarrhoea (8.67%) and myelosuppression (7.42%) were the common ADRs reported. Inappropriate administration frequency and regimen of anti-emetics (22%), lack of/suboptimal supportive care (18%) and administration errors (16%) were identified as common contributing (preventable) factors for ADRs in year 1. Percentage of preventable ADRs was 81% during year 1 (pre-intervention), and 45% and 34% in year 2 and year 3 respectively (post-interventions). Conclusion Interventions by CPs helped to minimize preventable ADRs to anti-cancer agents.