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Precision radiotherapy, which accurately delivers the dose on a tumor and confers little or no irradiation to the surrounding normal tissue and organs, results in maximum tumor control and decreases the toxicity to the utmost extent. Proton beam therapy (PBT) provides superior dose distributions and has a dosimetric advantage over photon beam therapy. Initially, the clinical practice and study of proton beam therapy focused on ocular tumor, skull base, paraspinal tumors (chondrosarcoma and chordoma), and unresectable sarcomas, which responded poorly when treated with photon radiotherapy. Then, it is widely regarded as an ideal mode for reirradiation and pediatrics due to reducing unwanted side effects by lessening the dose to normal tissue. During the past decade, the application of PBT has been rapidly increasing worldwide and gradually expanding for the treatment of various malignancies. However, to date, the role of PBT in clinical settings is still controversial, and there are considerable challenges in its application. We systematically review the latest advances of PBT and the challenges for patient treatment in the era of precision medicine.

Objective To evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhotic PVT, and compare differences in efficacy and safety among different anticoagulants. Methods We comprehensively searched Pubmed, Cochrane Library, EMBASE, and ClinicalTrials.gov from inception to April 2022 for studies using anticoagulants for cirrhotic PVT. Meta-analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results 3 RCTs and 14 cohort studies involving 1270 patients were included. Anticoagulant therapy can increase the recanalization rate compared with non-anticoagulation therapy (OR 4.44, 95% CI 3.11-6.32, I2 = 2.5%) and can decrease the extension rate of cirrhotic PVT (OR 0.33, 95% CI 0.18-0.62, I2 = 41.0%), without increasing the incidence of total bleeding (OR 1.21, 95% CI 0.75-1.97, I2 = 9.8%), major bleeding (OR 0.98, 95% CI 0.49-1.95, I2 = 19.7%), and variceal bleeding (OR 0.35, 95% CI 0.12-1.01, I2 = 39.9%). Subgroup analysis showed that VKA, LMWH, and DOACs could increase the recanalization rate of PVT and were not associated with the risk of bleeding. Studies that compared direct oral anticoagulants (DOACs) with warfarin directly showed that the recanalization rate of PVT in the DOACs group might be higher than that in the warfarin group (OR 30.99, 95% CI 7.39-129.87, I2 = 0.0%), and there was no difference in the rate of total bleeding (OR 0.30, 95% CI 0.01-8.65, I2 = 79.6%). Conclusions Anticoagulants are safe and effective in patients with cirrhotic PVT. The rate of PVT recanalization associated with DOACs may be higher than warfarin.

Background Combining immune checkpoint and proton pump inhibitors is widely used in cancer treatment. However, the drug-drug interactions of these substances are currently unknown. This study aimed to explore drug-drug interactions associated with concomitant immune checkpoint and proton pump inhibitors. Methods Data were obtained from the US Food and Drug Administration Adverse Event Reporting System from 2014 to 2023. Disproportionality analysis was used for data mining by calculating the reporting odds ratios (RORs) with 95% confidence intervals (95%Cls). The adjusted RORs (RORadj) were then analysed using logistic regression analysis, considering age, sex, and reporting year. Drug-drug interactions occur when a combination treatment enhances the frequency of an event. Further confirmation of the robustness of the findings was achieved using additive and multiplicative models, which are the two statistical methodologies for signal detection of DDIs using spontaneous reporting system. Results The total number of reports on immune checkpoint combined with proton pump inhibitors was 4,276. Median patient age was 66 years (interquartile range [IQR]: 60–74 years). Significant interaction signals were observed for congenital, familial and genetic disorders (RORadj = 2.66, 95%CI, 1.38–5.14, additive models = 0.7322, multiplicative models = 3.5142), hepatobiliary disorders (RORcrude = 6.64, 95%CI, 5.82–7.58, RORadj = 7.10, 95%CI, 6.16–8.18, additive models = 2.0525, multiplicative models = 1.1622), metabolism and nutrition disorders (RORcrude = 3.27, 95%CI, 2.90–3.69, RORadj = 2.66, 95%CI, 2.30–3.08, additive models = 0.6194), and skin and subcutaneous tissue disorders (RORcrude = 1.41, 95%CI, 1.26–1.58, RORadj = 1.53, 95%CI, 1.34–1.75, additive models = 0.6927, multiplicative models = 5.3599). Subset data analysis showed that programmed death-1 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders; hepatobiliary disorders; and skin and subcutaneous tissue disorders. Programmed death ligand-1 combined with proton pump inhibitors was associated with adverse reactions of metabolism and nutrition disorders. Cytotoxic T-lymphocyte antigen-4 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders, and skin and subcutaneous tissue disorders. Conclusions Based on real-world data, four Standardized MedDRA Query System Organ Class toxicities were identified as drug-drug interactions associated with combining immune checkpoint and proton pump inhibitors. Clinicians should be cautious when administering these drugs concomitantly. Preclinical trials and robust clinical studies are required to explore the mechanisms and relationships underlying interactions, thus improving understanding of drug-drug interactions associated with this combination therapy.

Data on the impact of morbid obesity (body mass index [BMI] ≥ 40 kg/m2) on the pharmacokinetics (PK), pharmacodynamics (PD) of direct oral anticoagulants (DOACs) are relatively limited, making it difficult to design optimal dosing regimens in morbidly obese patients. To review literature on PK/PD profile, efficacy, and safety of DOACs in venous thromboembolism (VTE) and nonvalvular atrial fibrillation (AF) patients with morbid obesity and make recommendations regarding optimal dosing regimens in these patient populations. A detailed literature search was conducted (from inception to June 22, 2022) for relevant articles involving PK/PD and clinical data on DOACs use in morbidly obese patients with VTE or AF, or healthy volunteers. A total of 28 studies were identified. DOAC-specific PK variations and clinical outcomes have been observed. Obesity may have a modest effect on PK/PD of dabigatran, apixaban, or rivaroxaban. Dabigatran was effective in AF patients with morbid obesity but might increase the risk of gastrointestinal bleeding. Standard dosing of apixaban or rivaroxaban is effective and safe for VTE and AF patients with morbid obesity. Trough edoxaban concentration and anti-Xa activity were similar in different BMI groups (18.5 to >40 kg/m2), and standard dosing of edoxaban may be effective and safe for AF patients. Current evidence suggests dabigatran should be used with caution in patients with AF as it might increase the risk of gastrointestinal bleeding; Standard dosing of apixaban or rivaroxaban can be used in VTE or AF patients; Standard dosing of edoxaban may be considered in AF patients.

Background and objective To evaluate the cost-effectiveness of new anticoagulants and warfarin in the prevention of stroke in Chinese patients with atrial fibrillation (AF). Methods The Markov model was constructed to compare patients’ quality-adjusted life-years (QALYs) using drug cost, the cost of the examination after taking a drug, and the incremental cost of other treatments. Both dabigatran (110 and 150 mg, twice a day) and rivaroxaban (20 mg, once a day) were compared with warfarin (3–6 mg, once a day). Willingness to pay, three times the 2018 China GDP per capita (9481.88 $), was the cost-effect threshold in our study. Results The total cost were was 5317.31$, 29673.33$, 23615.49$, and 34324.91$ for warfarin, rivaroxaban, dabigatran 110 mg bid, and dabigatran 150 mg bid, respectively. The QALYs for each of the four interventions were 11.07 years, 15.46 years, 12.4 years, and 15 years, respectively. The cost-effectiveness analysis of the three new oral anticoagulants and warfarin showed that the incremental cost-effectiveness ratio (ICER) was 5548.07$/QALY when rivaroxaban was compared with warfarin. Rivaroxaban was the most cost-effective choice and warfarin was the least. Conclusions In Chinese patients with AF, although warfarin is cheaper, rivaroxaban has a better cost-effectiveness advantage from an economic point of view.

Objectives‘National Special Stewardship in the Clinical Use of Antibiotics’ was put forward in July 2011 in China. We aimed to retrospectively evaluate the impact of antimicrobial stewardship (AMS) managed by clinical pharmacists on antibiotic utilisation, prophylaxis and antimicrobial resistance (AMR).DesignThis was a retrospective observational study of trends in antibiotic use and AMR in the context of AMS.SettingBeijing Chaoyang Hospital, a 1400-bed tertiary hospital, in China.Data and participantsAntibiotic prescriptions from 820 doctors included all outpatients (n=17 766 637) and inpatients (n=376 627) during 2010–2016. Bacterial resistance data were from all inpatients (n=350 699) during 2011–2016.InterventionsMultiaspect intervention measures were implemented by clinical pharmacists (13 persons), for example, formulating the activity programme and performance management, advising on antibacterial prescriptions and training.Outcome measuresThe proportion of antibiotic prescriptions among outpatients and inpatients, intensity of consumption in defined daily dose (DDD)/100 bed-days, antibiotic prophylaxis in type I incision operations and resistance rates of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were retrospectively analysed.ResultsThe proportion of antibiotic prescriptions decreased in outpatients (from 19.38% to 13.21%) and in inpatients (from 64.34% to 34.65%), the intensity of consumption dropped from 102.46 to 37.38 DDD/100 bed-days. The proportion of antibiotic prophylaxis decreased from 98.94% to 18.93%. The proportion of rational timing of initial dose increased from 71.11% to 96.74%, the proportion of rational duration rose from 2.84% to 42.63%. Time series analysis demonstrated the resistance rates of E. coli and P. aeruginosa to fluoroquinolones decreased, the incidence rate of methicillin-resistant Staphylococcus aureus also decreased, whereas the resistance rates of E. coli and K. pneumoniae to carbapenems increased. The antibiotic use was partly positively correlated with AMR.ConclusionsAMS had an important role in reducing antibiotic use and surgical antibiotic prophylaxis. The AMR was positively correlated with antibiotic consumption to some extent.

Background Tigecycline has broad-spectrum anti-bacterial activity and often used for critically ill patients with complicated infections. Only a few clinical studies have reported the coagulation disorder induced by tigecycline. The aim of this study was to investigate the association between tigecycline and coagulation dysfunction using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Method Data from January 2005 to December 2020 in FAERS were retrieved. We investigated the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare tigecycline with the full database and other antibiotics. Results The total number of reports of coagulation dysfunction related to tigecycline as the primary suspect drug was 223. The median time to event of the coagulation dysfunction events was 10 (interquartile range [IQR] 6.75–13) days. 80.72% coagulation-related adverse events appeared within the first 14 days since the initiation of tigecycline administration. The overall ROR (95% CI) for coagulation-related adverse events was 3.55 (3.08, 4.09). The RORs (95% CI) for thrombocytopenia, hypofibrinogenaemia, coagulopathy, activated partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time prolonged were 8.21 (6.34, 10.62), 705.41 (526.81, 944.54), 30.67 (21.92, 42.92), 42.98 (24.85, 74.31), 4.67 (2.51, 8.71), and 27.99 (15.01, 52.19), respectively. In analyses stratified on comparing tigecycline to vancomycin and daptomycin, significant coagulation dysfunction signals were found with the RORs (95% CI) 2.74 (2.34, 3.22) and 3.08 (2.57, 3.70). Conclusions We found a strong signal of high frequency of reporting coagulation dysfunction in tigecycline. Health professionals should be aware of the potential coagulation disorders risk and monitor coagulation parameters during anti-bacterial therapy with tigecycline, particularly the need to monitor fibrinogen levels.

This study aims to assess the efficacy and safety of pharmacoprophylaxis regimens for venous thromboembolism (VTE) in patients undergoing bariatric surgery. A total of 15 studies were included. Low molecular-weight heparins (LMWH) and fondaparinux may be equally effective in reducing VTE risk (OR 1.02, 95% confidence interval [CI] 0.14–7.39). Pooled estimate suggested uncertain effects of augmented LMWH dosing on VTE prophylaxis compared with standard dosing (OR 0.57, 95% CI 0.07–4.39), but may increase major bleeding (OR 3.03, 95% CI 0.38–23.96). Very low-quality evidence showed an inconclusive effect of extended prophylaxis on VTE (OR 0.54, 95% CI 0.15–1.90) and major bleeding (OR 1.24, 95% CI 0.92–1.68) compared with restricted prophylaxis. Standard LMWH dosing may be effective and safe. Current evidences are insufficient to support extended prophylaxis.

Objective The haematopoietic cytopenia (HC) of the cyclin-dependent kinase (CDK)4/6 inhibitors was evaluated using the Food and Drug Administration Adverse Event Reporting System (FAERS). Method Data from 1 January 2015 to 31 December 2021 has been retrieved from the FAERS database. Disproportionality analysis and Bayesian analysis were utilized in the data mining. The reporting odds ratio (ROR) with 95% confidence interval (CI) for HC was calculated for each CDK 4/6 inhibitor agent. Clinical features of the patients were collected and compared between death outcome and non-death outcome groups. Time to onset (TTO), proportion of deaths, life-threatening and hospitalizations of CDK 4/6 inhibitors-associated HC were also studied. Results A total of 17,235 cases of HC associated with CDK 4/6 inhibitors were identified with a median age of 65 years (interquartile range [IQR] 57–73). Palbociclib appeared the strongest signal, with the highest (ROR 9.64, 95% CI 9.46–9.83), followed by ribociclib (ROR 6.38, 95% CI 6.04–6.73) and then abemaciclib (ROR 2.72, 95% CI 2.49–2.97). Patients aged 18–64 had a higher proportion of deaths than those aged 65–84 (12.21% vs. 9.91%, p = 0.001). In Africa and Asia, the proportions of deaths were higher (31.65% and 26.13%, respectively). The median TTO was 26 days (IQR 14–65) for abemaciclib, 33 days (IQR 15–134) for palbociclib and 23 days (IQR 14–69) for ribociclib, respectively. The highest proportion of deaths, life-threatening and hospitalizations all occurred in abemaciclib (13.00%, 5.42% and 44.04%, respectively). Conclusions Greater proportions of deaths occurred in Africa and Asia. HC may occur early in any CDK 4/6 inhibitor regimen. Abemaciclib had the highest proportion of deaths, life-threatening and hospitalizations. Health care workers should be more concerned about CDK 4/6 inhibitors. The higher proportions of serious events, including deaths, from Africa and Asia, as well as for abemaciclib, deserve further investigations through additional pharmacoepidemiological approaches.

This study aimed to compare the prevalence of potentially inappropriate medications (PIMs) among Chinese aged patients using the Beers criteria of 2015, the Screening Tool of Older Persons' Prescriptions (STOPP) of 2014 and the criteria of PIMs for older adults in China (Chinese criteria), and to identify the correlates of the PIMs' use. A retrospective, cross-sectional study was conducted among geriatric patients at Beijing Chao-Yang Hospital between January 2018 and March 2018. Three criteria (the Beers criteria of 2015, the STOPP criteria of 2014 and the Chinese criteria) were used to detect PIMs. A multivariate logistic regression analysis was carried out to determine factors associated with the use of PIMs. Leading PIMs for each set of criteria were also listed. The concordance among the three PIM criteria was calculated using kappa tests. Totally, 863 inpatients aged ≥65 years were included. The prevalence of patients receiving at least one PIM was 80.2%, 58.1% and 44.0% according to the Chinese criteria, 2015 Beers criteria and 2014 STOPP criteria, respectively. The Beers and the STOPP criteria indicated a moderate coherence, whereas the Chinese criteria showed poor concordance with the other two criteria. Proton-pump inhibitors in the Beers and STOPP criteria and clopidogrel in the PIM-Chinese accounted for most leading PIMs. The most important factor associated with PIM use by all three sets of criteria was the number of prescribed medications. Data showed a high PIM prevalence among older adults in China, which was associated with the number of prescribed medications. The Chinese criteria had the highest detection rate but a poor concordance with the Beers and STOPP criteria ( <0.001).