Establishment and validation of nomogram prediction model of cefoperazone/sulbactam-induced thrombocytopenia / 中国药房

OBJECTIVE To explore the predictive factors of cefoperazone/sulbactam-induced thrombocytopenia in adult inpatients， and to establish and validate the nomogram prediction model. METHODS Data of adult inpatients treated with cefoperazone/sulbactam in Xi’an Central Hospital from Jun. 30th， 2021 to Jun. 30th， 2023 were retrospectively collected. The training set and internal validation set were randomly constructed in a 7∶3 ratio. Singler factor and multifactor Logistic regression analysis were used to screen the independent predictors of cefoperazone/sulbactam-induced thrombocytopenia. The nomogram was drawn by using “RMS” of R 4.0.3 software， and the predictive performance of the model was evaluated by the receiver operating characteristic curve and C-index curve. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the calibration degree of the model. Using the same standard， the clinical data of hospitalized patients receiving cefoperazone/sulbactam in Xi’an First Hospital in the same period were collected for external validation of the nomogram prediction model. RESULTS A total of 1 045 patients in Xi’an Central Hospital were included in this study， among which 67 patients suffered from cefoperazone/sulbactam-induced thrombocytopenia， with an incidence of 6.41%. After the false positive patients were excluded， 473 patients were included finally， including 331 in the training set and 142 in theinternal validation set. Multifactor Logistic regression analysis showed that age [OR＝1.043， 95%CI （1.017， 1.070）]， estimated glomerular filtration rate （eGFR） [OR＝0.988，95%CI（0.977， 0.998）]， baseline platelet （PLT） [OR＝0.989， 95%CI（0.982， 0.996）]， nutritional risk [OR＝3.863， 95%CI（1.884， 7.921）] and cumulative defined daily doses （DDDs） [OR＝1.082， 95%CI（1.020， 1.147）] were independent predictors for cefoperazone/sulbactam-induced thrombocytopenia （P＜0.05）. The C-index values of the training set and the internal validation set were 0.824 [95%CI （0.759， 0.890）] and 0.828 [95%CI （0.749， 0.933）]， respectively. The results of the Hosmer-Lemeshow test showed that χ 2 values were 0.441 （P＝0.802） and 1.804 （P＝0.406）. In the external validation set， the C-index value was 0.808 [95%CI （0.672， 0.945）]， the χ 2 value of the Hosmer-Lemeshow test was 0.899 （P＝0.638）. CONCLUSIONS The independent predictors of cefoperazone/sulbactam-induced thrombocytopenia include age， baseline PLT， eGFR， nutritional risk and cumulative DDDs. The model has good predictive efficacy and extrapolation ability， which can help clinic identify the potential risk of cefoperazone/sulbactam-induced thrombocytopenia quickly and accurately.

Case analysis of a patient with isavuconazonium-caused pancytopenia / 中国药房

OBJECTIVE To correctly identify and deal with the adverse drug reaction as pancytopenia caused by isavuconazonium and to provide reference for the safe use of isavuconazonium. METHODS Clinical pharmacists analyzed a case of severe infection and renal insufficiency who experienced pancytopenia after using isavuconazonium. Clinical pharmacists screened the drugs used during hospitalization and evaluated the relationship between this adverse drug reaction and isavuconazonium， as well as the possible mechanisms， based on the half-life of the drugs and relevant literature. RESULTS & CONCLUSIONS The relationship between pancytopenia and isavuconazonium was assessed as “possibly related”. When using isavuconazonium， attention should be paid to avoiding the combination of drugs with the same mechanism or potential interaction. For patients who have a course of treatment for more than 2 weeks， have hematological abnormalities or complicated with liver and renal insufficiency， or should use it combined with other drug with same mechanism， it may be considered to increase the frequency of blood routine monitoring.

Renal injury caused by tenofovir disoproxil fumarate in a patient with liver cancer complicated with HBV infection：a case report and literature analysis / 中国药房

Tenofovir disoproxil fumarate （TDF） is a first-line treatment for chronic hepatitis B. With increasing use worldwide， the adverse events of renal injury caused by this drug have also attracted industry attention. This article reports a 61- year-old patient with liver cancer complicated with hepatitis B virus （HBV） infection. The patient started using TDF in mid-March 2022 and developed kidney injury after 2 months of treatment， during which he received 2 courses of donafenib combined with sintilimab chemotherapy and irregular administration of diclofenac for pain relief. In this paper， Naranjo’s assessment scale was used to evaluate the drugs that may be associated with renal injury， including TDF and sintilimab， and the drugs that are suspected to be associated with renal injury are donafenib and diclofenac. The renal injury caused by TDF can be judged according to the changes in the patient’s condition， the incidence of drug-induced renal injury， clinical manifestations， occurrence time， occurrence mechanism， drug combination， and high-risk factors. The changes of serum creatinine in patients with liver cancer complicated with HBV infection after TDF should be dynamically monitored in the clinic， and the dose of antiviral drugs should be adjusted if necessary and other antiviral drugs with less impact on renal function can be selected， to provide individualized medication recommendations for tumor patients， reduce the incidence of TDF-related renal injury.

Clinical Characteristics and Potential Risk Factors Analysis of Liver Injury Related to Epimedii Folium Preparation / 中国实验方剂学杂志

ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Childhood lichenoid granulomatous stomatitis: a case report and literature review / 口腔疾病防治

Objective@#To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.@*Methods@#Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature.@*Results@#The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.@*Conclusion@#There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids.

Aspectos farmacológicos y adherencia al tratamiento antirretroviral en pacientes VIH

Introducción: La adherencia al tratamiento farmacológico favorece la supresión viral y reduce la resistencia a la terapia antirretroviral de gran actividad a largo plazo. Objetivo: Determinar la relación entre los aspectos farmacológicos y la adherencia al tratamiento antirretroviral de una IPS colombiana. Metodología: Estudio analítico transversal en pacientes con diagnóstico de VIH en tratamiento antirretroviral entre los años 2012 a 2020. Se utilizó un modelo de regresión logística binaria múltiple con fines explicativos. Resultados: Se analizaron 9835 pacientes donde la proporción de adherencia fue de 90 % y en el modelo ajustado se evaluó su relación con los antecedentes de no adherencia (ORa:0,52 IC95 °/o:0,40-0,66), grupo farmacológico (2 ITIAN + 1 IP u otro) (ORa:1,22 IC95 %:0,99-1,76), dos tomas al día (ORa:1,02 IC95 %:0,74-1,40), unidades al día (≥ 3) (ORa:0,69 IC95 %:0,47-1,02), reacciones adversas a medicamentos (ORa:0,56 IC95 °%:0,40-0,78), polimedicación (ORa:1,36 IC95 %:1,00-1,85), tiempo TAR (1 a 2 años) (ORa:1,63 IC95 %:1,27-2,09),tiempo TAR (6 a 12 meses) (ORa:1,66 IC95 %:1,27-2,18), tiempo TAR (<6 meses) (ORa:1,36 IC95 %:1,03-1,78), tasa de reclamación de los medicamentos (ORa:0,42 IC95 %:0,32-0,55) y antecedentes PRUM (ORa:0,11 IC95 %:0,09-0,14). Discusión: La proporción de adherencia obtenida es superior a lo descrito para otros países (entre 60-77 %); sin embargo se encuentra que los hallazgos correspondientes al efecto de las variables farmacológicas analizadas son acordes a lo descrito en estudios previos en el tema Conclusión: Los antecedentes de no adherencia, reacciones adversas, tasa de reclamación de los medicamentos y antecedentes de problemas relacionados con el uso de medicamentos son aspectos que reducen la probabilidad de adherencia; mientras que el mayor tiempo de uso del tratamiento aumenta la misma.

Introduction: Adherence to drug treatment promotes viral suppression and reduces long-term resistance to highly active antiretroviral therapy (HAART). Objective: To determine the relationship between the pharmacological aspects and adherence to antiretroviral treatment in a Colombian IPS. Methodology: Cross-sectional analytical study in patients with HIV on antiretroviral treatment between 2012 and 2020. A multiple binary logistic regression model was used for explanatory purposes. Results: A total of 9,835 patients were analyzed where the proportion of adherence was 90 % and in the adjusted model its relationship with history of non-adherence was assessed (ORa: 0,52 95 % CI: 0,40-0,66), pharmacological group (2 NRTI + 1 PI or other) (ORa: 1,22 95 % CI: 0,99-1,76), two doses per day (ORa: 1,02 95 % CI: 0,74-1,40), units per day (≥ 3 ) (ORa: 0,69 95 % CI: 0,47-1,02), adverse drug reactions (ORa: 0,56 95 % CI: 0,40-0,78), polypharmacy (ORa: 1,36 95 % CI : 1,00-1,85), ART time (1 to 2 years) (ORa: 1,63 95 % CI: 1,27-2,09), ART time (6 to 12 months) (ORa: 1,66 95 % CI: 1,27-2,18), ART time (<6 months) (ORa: 1,36 95 % CI: 1,03-1,78), inconsistency in the claim (ORa: 0,42 95 % CI: 0,32-0,55) and PRUM history (ORa: 0,11 95 % CI: 0,09-0,14). Discussion: The proportion of adherence obtained is higher than that described for other countries (between 60-77 %); however, the findings corresponding to the effect of the pharmacological variables analysed are in line with those described in previous studies on the subject. Conclusion: The history of non-adherence, adverse reactions, inconsistencies in the claim fill history and problems related to the use of medications are aspects that reduce the probability of adherence. While the longer time of use of the treatment increases adherence.

Metabolic adverse drug reactions in geriatric patients in Odisha

Background: Geriatric patients are at a greater risk of developing adverse drug reaction (ADR) because of changed metabolic activity and renal status associated with aging. As most of the elderly patients suffer from multiple chronic diseases (Diabetes, Hypertension, Arthritis, constipation, peptic ulcer disease, etc.), they are under polypharmacy and the risk of ADRs is exacerbated by multiple medications. Metabolic ADRs include weight gain, hypoglycemia, hyponatremia, hypokalemia, and the endocrinal abnormality are the frequent cause of hospital admission in geriatric patients. Most metabolic ADRs due to drugs are treatable. There are few such studies conducted in India regarding metabolic ADR in geriatric patients. Hence, this study aims to evaluate the metabolic ADRs encountered in geriatric patients with the following objectives in Odisha. Aim and Objectives: The prevalence and spectrum of metabolic ADRs in geriatric population were studied. The causality assessment, severity assessment, and preventability were done using standard scales. Materials and Method: This was a prospective and observational study conducted from September 2016 to September 2018 in Department of Pharmacology in collaboration with Department of Geriatric Medicine and Department of Medicine of SCB Medical College and Hospital. All geriatric patients (?60 years) with ADR, reporting to the above departments, were included in the study. The detailed information of type of ADRs and its characteristics was filled up in Suspected ADR Reporting Form designed by Indian pharmacopeia commission version 1.3. The incidence and spectrum of metabolic ADRs were observed. Their causality, severity, and preventability were evaluated by the WHO-UMC System, Hartwig’s Severity Scale, and Schumock Thornton Preventability Scale, respectively. Result: A total of 236 ADRs were reported in 2 years, out of which 28.8% were metabolic ADRs. Metabolic ADRs were more reported in young old patients and often encountered ADR was hypoglycemia 73.5% due to use of oral anti diabetics. About 29% of the metabolic ADRs had a causal relation of probable association. About 94.2% were moderate in severity and 89.7% metabolic ADRs could be probably preventable. Conclusion: There was a probable causal association of metabolic ADR with the drug used and they were moderate verity. The metabolic ADRs found in our study can be preventable with appropriate means.

Retrospective study on cutaneous adverse drug reactions in a tertiary care center

Background: Cutaneous adverse drug reactions (CADRs) range from mild-to-severe types and occasionally can become fatal. Hence, these incur additional financial burden both to patients and community. Aim and Objective: The aim of the study was to describe the characteristics of CADRs reported to ADR monitoring center (AMC) of a tertiary care center. Materials and Methods: CADRs reported to the AMC over a period of 2 ½ years were retrospectively studied. This study mainly focused on affected age group, gender, various pattern of CADRs, the group and name of drugs causing CADRs, and severity and causality assessment. Results: CADRs contributed 31.6% of the total ADRs reported to the AMC. Among these, 51.7% were females and 40% were of 51–60 years age group. About 37.9% of CADRs were pruritus. Antibacterial drugs were the most common cause of CADRs and beta-lactam antibiotics were responsible for 30% of CADRs. Stevens Johnson syndrome (SJS) constituted 4.9% of CADRs and 20% of this was due to Paracetamol. Drugs were withdrawn in 89% of cases and 85% cases recovered. On causality assessment, 94% were of probable category. Conclusion: Pruritus was the most commonly observed CADR and antibacterial drugs were the most common cause. Beta lactam antibiotic was the most frequent antibacterial drug to cause CADRs. The most common serious CADR was SJS and Paracetamol was the most frequent culprit drug.

Múltiples reacciones adversas graves a fármacos en un paciente luego de la infección por COVID-19: informe de un caso / Drug-induced severe cutaneous adverse reactions in a patient after COVID-19 infection: case report

Durante la pandemia por COVID-19 se observaron diversas reacciones adversas a fármacos. Esto pudo haber estado relacionado con una mayor susceptibilidad inmunológica de los pacientes con SARS-CoV-2 a presentar este tipo de cuadros, así como también con la exposición a múltiples medicamentos utilizados en su tratamiento. Comunicamos el caso de un paciente con una infección respiratoria grave por COVID-19, que presentó 2 reacciones adversas graves a fármacos en un período corto de tiempo. (AU)

During the COVID-19 pandemic, various adverse drug reactions were observed. This could have been related to a greater immunological susceptibility of patients with SARS-CoV-2 to present this type of symptoms, as well as exposure to multiple drugs used in their treatment. We report the case of a patient with a severe respiratory infection due to COVID-19, who presented 2 serious adverse drug reactions associated with paracetamol in a short period of time. (AU)

PHARMACOVIGILANCE IN INDIA: PAST, PRESENT, AND FUTURE PERSPECTIVE

Its start a decade ago, pharmacovigilance (PV) experienced tremendous development. There have been significant attempts in recent years to transform the current pharmacovigilance systems to meet future expectations. Adverse drug reactions (ADRs) are increasing in frequency, severity, and complexity as novel medication therapies are coming to market more quickly as a result of better laws and regulations. India is the second most popular nation in the world, with around 1 billion active and prospective consumers of pharmaceuticals. Despite being a member of the Uppsala Monitoring Centre, our nation has almost little commitment to the database. This problem is brought on by the inadequate ADR (adverse drug reaction) monitoring system and lack of knowledge among pharmacy associates and medical professionals. The primary objectives of the PV program are patient care, patient safety, and monitoring of negative medication reactions. There is a need for additional clinical preliminary exams and clinical assessments in India to accurately practice PV. A fully functional PV system is essential for the safe and responsible administration of medicines. This review gives a systematic review of pharmacovigilance in India from its origin to its current scenario and also discusses the various strategies and proposals to build, maintain and implement a robust pharmacovigilance system for India in coming years.

Self-assumed Neurologic Related Condition Deviated Metoclopramide-Induced Acute Dystonic of Oculogyric Crisis in a Woman of Childbearing Age: A Case Report

A 26-year-old Malaysian woman (childbearing age) attended a private primary care clinic with a known case of gastroesophageal reflux disease (GERD) and complained of persistent nausea and a few episodes of vomiting. She had no known drug allergy, no surgical history, no hospitalization in the last two years, was a non-smoker, and no history of drug or alcohol abuse. The patient was prescribed Tab metoclopramide 10 mg TDS and Tab ranitidine 150 mg BD for five days. About 30 min after oral administration of both medicines, her eyes rolled involuntary upward, leading to lateral deviation of the eyes, and mouth jaws clenched as if “dislocated jaws.” The patient was immediately brought into an emergency department (ED) of a public tertiary care hospital. A drug challenge test was done which resulted in the withdrawal of metoclopramide. The accompanied sister later disclosed that the patient had taken metoclopramide and ranitidine from a private clinic earlier in the day. The patient self-assumed to have a sudden seizure, due to excessive hot weather and dehydration. A slow intravenous infusion of 50 mg/mL diphenhydramine hydrochloride in 0.9% w/v NaCl 100 mL was administered stat. Consequently, the symptoms vanished after approximately 30 min of the therapy, devoid of relapse. The patient was discharged from ED post 8 hours of monitoring with complete recovery. Physicians frequently prescribe metoclopramide to treat nausea and vomiting, which may cause adverse drug reaction of acute dystonic oculogyric crisis (OGC). Due to its unwanted and unpredictable extrapyramidal symptoms, metoclopramide should be prescribed and dispensed with caution. Thorough history taking at ED is imperative for correct early diagnosis and treatment, as metoclopramide-induced dystonic OGC has a high probability of confusion with other causes of dystonia such as conversion and seizures, encephalitis, tetanus, and hypercalcemic tetany.

Class-imbalance Prediction and High-dimensional Risk Factor Identification of Adverse Reactions of Traditional Chinese Medicine with Centralized Monitoring in Real-world Hospitals / 中国实验方剂学杂志

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Retrospective study on the use of epinephrine in patients with drug-induced anaphylactic shock in Chongqing from 2015 to 2022 / 中国药房

OBJECTIVE To evaluate the rationality of epinephrine in the treatment of drug-induced anaphylactic shock， and to provide a reference for further standardizing the treatment measures of anaphylactic shock. METHODS According to the relevant data of the reports of severe adverse drug reaction （ADR） of drug-induced anaphylactic shock provided by Chongqing ADR Monitoring Center from 2015 to 2022， the selection of treatment drugs， and the application of epinephrine in anaphylactic shock were analyzed retrospectively； the clinical outcomes of anaphylactic shock with different epinephrine administration methods were investigated. RESULTS A total of 1 415 cases of severe ADR related to drug-induced anaphylactic shock were reported， with a male-to-female ratio of 1.04∶1； the drugs that caused allergic shock mainly included anti-infective drugs （47.92%）， TCM injections （9.12%）； the patients who suffered from drug-induced anaphylactic shock within 10 min after medication accounted for 43.96%； 97.24% of patients were cured or improved， and 2.76% of patients died or did not been improved. Among 1 415 patients， 63.39% of patients were treated with epinephrine， and the patients who preferred epinephrine treatment accounted for 53.14%； the intramuscular injection， subcutaneous injection， intravenous injection and intravenous drip accounted for 33.78%， 30.32%， 25.75% and 1.23%， respectively. The initial dose range of epinephrine was 0.01-10 mg， and the most frequent single dose was 1 mg （44.70%）. Excessive single doses of intramuscular injection， subcutaneous injection and intravenous injection accounted for 51.03% （148 cases）， 53.13% （136 cases） and 91.47% （193 cases） respectively， and the risk of overdose in intravenous injection was higher （P＜0.05）. The patients receiving initial treatment with epinephrine had a higher improvement rate/cure rate than those who did not use epinephrine （98.14% vs. 96.23%， P＝0.029）； the patients who preferred epinephrine had a higher improvement rate/cure rate than those who did not preferred epinephrine （98.14% vs. 95.17%， P＝0.031）； the improvement rate/cure rate of patients receiving intramuscular injection of epinephrine was higher than those without intramuscular injection （99.01% vs. 96.69%， P＝0.038）. CONCLUSIONS There are some unreasonable phenomena in the treatment of drug-induced anaphylactic shock， such as inappropriate selection of drugs， insufficient use of epinephrine， delay of administration， inappropriate route of administration and excessive single dose.

Literature analysis of adverse drug reactions induced by dronedarone / 中国药房

OBJECTIVE To analyze the clinical manifestations and characteristics of adverse drug reactions （ADR） induced by dronedarone，and to provide reference for clinically safe drug use. METHODS Retrieved from PubMed database， Wanfang database，CNKI and VIP （up to August 31st， 2022），ADR cases of dronedarone were analyzed retrospectively in respect of patient’s age，gender，nationality，usage and dosage of dronedarone，and occurrence time，clinical manifestations，treatment measures and outcome of ADR，etc. RESULTS A total of 26 case reports were included，with a total of 27 patients. The age of the patients was 41-86 years old，with an average age of 68.8 years. The proportion of patients aged 60-79 was the largest （20 cases，74.1%）. There was no significant difference in the number of males （14 cases） and females （13 cases）. The patients came from 6 countries， of which the United States was the largest （16 cases，59.3%）. The dosage of 14 patients was 400 mg bid；one patient was 200 mg bid；the dosage for 12 patients was not specified. The most ADR cases （16 cases，59.3%） occurred within 1 month，of which 11 cases（40.7%） occurred within 1 week，and there were no ADR reports with medication more than 12 months. Organs/systems involved in ADRs were mainly liver and biliary diseases （7 case times，23.3%），skin and subcutaneous tissue diseases （6 case times， 20.0%），respiratory tract，thoracic and mediastinal diseases （5 case times，16.7%）. In addition，ADR also occurred in heart diseases， kidney and urinary system diseases，vascular diseases，medical examinations and eye diseases. Among 27 patients，there were 3 cases of death，the ADR were bronchiolitis obliterans with organizing pneumonia，toxic epidermal necrolysis and hepatic failure， respectively. One patient underwent liver transplantation. CONCLUSIONS Dronedarone can cause multiple organ system ADR. Before use，it is necessary to improve the examination including ECG，liver function，lung function，etc. and strengthen drug use monitoring within one month after the start of use，especially the ADR of hepatobiliary，skin and respiratory system. The occurrence of severe ADR has no obvious relationship with the duration of medication； even if it is taken safely for a long time，it still needs continuous pharmaceutical monitoring and follow-up to ensure the clinical medication safety of patients.

Efficacy of perioperative use of tigecycline in preventing infection and incidence of hypofibrinogenemia in liver transplant recipients / 器官移植

Objective To evaluate the efficacy of perioperative use of tigecycline in preventing infection and the incidence of hypofibrinogenemia in liver transplant recipients. Methods Clinical data of 40 liver transplant recipients given with tigecycline to prevent infection were retrospectively analyzed. The incidence of infection in recipients and donor-derived infection were analyzed. The changes of clinical indexes in recipients during, upon the completion and (7±2) d after tigecycline treatment were analyzed, respectively. The incidence and treatment of hypofibrinogenemia were summarized. Results Among 40 liver transplant recipients, 2 cases were infected by aspergillus niger and cytomegalovirus, out of the antibacterial spectrum of tigecycline. After adjusting the anti-infection regimen, the infection was properly controlled. Liver allografts were positive for relevant culture in 9 cases, whereas none of them progressed into donor-derived infection. Approximately at postoperative 2 weeks, all 40 recipients restored liver function and were discharged from hospital. Among them, 6 recipients developed hypofibrinogenemia complicated with coagulation disorder at postoperative 2-4 d, whereas transaminase level, bilirubin level and infection-related indexes were gradually decreased after liver transplantation, and albumin level was stable. After supplemented with human fibrinogen and prothrombin complex, coagulation function was improved, but fibrinogen level persistently declined. After terminating use of tigecycline, fibrinogen level was gradually restored to normal range, which might be an adverse drug reaction induced by tigecycline. Conclusions Perioperative anti-infection regimen including tigecycline may reduce the incidence of infection caused by sensitive bacteria in liver transplant recipients. Nevertheless, the incidence of hypofibrinogenemia should be intimately monitored throughout the use of tigecycline.

Analysis of influential factors for blood concentrations and adverse drug reaction in the treatment of lymphoma with high-dose methotrexate / 中国药房

OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate （HD-MTX） and the occurrence of adverse drug reactions （ADR） when treating lymphoma with HD-MTX. METHODS From July 2020 to November 2021， the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis， such as medical record number， age， sex， height， body mass， chemotherapy plan， dosage； test indexes such as alanine transaminase， aspartate transaminase， total bilirubin， creatinine clearance （CrCl）， albumin （ALB） and other indexes were also collected before and after administration. The blood concentrations （c6 h， c24 h， c48 h） of HD-MTX were recorded， drug information of proton pump inhibitors （PPIs） was extracted and used， and ADR occurring within 48 h after administration were all evaluated. Single factor analysis， multiple linear regression and χ2 test were used to analyze the influential factors. RESULTS A total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age， CrCl had an effect on c 6 h （P＜0.05）； age， CrCl and ALB had an effect on c24 h （P＜0.05）； age， body mass index （BMI）， CrCl， combined use of PPIs and ALB had an effect on c48 h （P＜0.05）. The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h （P＞0.05）， age was the main influential factor of c 24 h （P＜0.05）， and CrCl and combined use of PPIs were the main influential factors of c48 h （P＜0.05）； the coefficient of variance expansion was between 1 and 3.5， indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%， of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age， BMI， liver function and CrCl had effect on the incidence of ADR （P＜0.05）. CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma， the patient’s age， CrCl and combined use of PPIs should be considered， and the patient’s blood concentration should be monitored； at the same time， the age of patients， BMI， liver function and CrCl have an impact on the incidence of ADR.

Literature analysis of lung toxicity related to cyclin-dependent kinase 4/6 inhibitors / 中国药房

OBJECTIVE To provide reference for rational use of cyclin-dependent kinase 4/6 （CDK4/6） inhibitors. METHODS Retrieved from Web of Science， PubMed， SpringerLink， CNKI， Wanfang Data and VIP database， and so on， the literature about lung toxicity related to CDK4/6 inhibitors were collected and analyzed statistically with Excel 2013 software. RESULTS A total of 12 literature which met the inclusion and exclusion criteria were included； 13 patients were involved， among which 3 cases were from the United States， 3 from Japan， 2 from India， and 1 from Israel， Spain， France， Australia and Saudi Arabia respectively； all patients were female， aged between 43-89 years， of whom 8 were treated with palbocicilib， 3 with abemacilib， and 2 with ribociclib. The lung toxicity of patients after medication occurred from 1 week to 15 months； the majority of patients were hospitalized with the symptom such as difficulty breathing， chest tightness， shortness of breath， dry cough， etc. The lung toxicity mainly manifested as interstitial lung disease， eosinophilic pneumonia， mediastinal and pulmonary granulomatous reaction， drug-induced pneumonia， diffuse alveolar damage， organizing pneumonia and so on. The shortest treatment duration was 3 weeks， and the longest was 6 months. The treatment measures included drug withdrawal， intravenous use of antibiotics， intravenous use of systemic steroids， oxygen inhalation， and so on； after treatment， 8 patients improved or recovered， and 5 patients died due to deterioration. One patient developed lung toxicity again after reuse of such drugs and must stop drugs permanently. CONCLUSIONS Lung toxicity related to CDK4/6 inhibitors possibly cause mortality. It is necessary to make early judgment， stop the drug in time， and give patients systemic steroids， oxygen inhalation and other treatment measures as soon as possible.

Mining and analysis of risperidone adverse event signals based on FAERS database / 中国药房

OBJECTIVE To provide reference for safe use of risperidone in clinic. METHODS Data mining and analysis of risperidone-related adverse drug event （ADE） reports from the first quarter of 2017 to the third quarter of 2021 in the United States FAERS database were carried out using reported odds ratio and composite criteria methods from Medicines and Healthcare Products Regulatory Agency. RESULTS There were 101 181 ADE reports with risperidone as the primary suspect drug，involving a total of 33 179 patients. Among those reports，the male-to-female ratio was about 6.21 to 1； most of them were ＜18 years old （15.01%）； ADE was mainly reported by consumers （69.74%） and mainly reported by the United States （79.72%）； oral dosage form was the most used，accounting for 83.71%. A total of 409 ADE signals were obtained，including male breast development， pseudogynecomastia，abnormal increase in body mass，hyperprolactinemia and Wellens syndrome，etc. Twenty-six systems and organs were involved，mainly including reproductive system and breast diseases，various injuries，poisoning and operational complications， mental diseases，metabolic and nutritional diseases，and various nervous system diseases，etc. CONCLUSIONS The common ADE signals of risperidone and the system involved are consistent with the instructions，but we should also be alert to the ADE not recorded in the instruction，such as Wellens syndrome，fibroproliferative endocarditis，cavernous degeneration of portal vein，rabbit syndrome，etc.

Pyogenic granuloma of the gums and lips caused by camrelizumab: case report and literature review / 口腔疾病防治

Objective@# To investigate the clinical manifestations, pathological features, and treatment of oral and maxillofacial pyogenic granulomas induced by camrelizumab. @*Methods@# A case of pyogenic granuloma of the gums and lips caused by camrelizumab was reported along with a literature review. @*Results@# After 4 months of treatment with camrelizumab for liver cancer, the patient developed systemic reactive capillary hyperplasia (RCH), followed by multiple masses on the lower lip and gingiva. After periodontal therapy, the masses on the lower lip and the gingiva were removed, and camrelizumab administration was stopped. The pathological result was gingival pyogenic granuloma/granulomatous hemangioma. No new masses were found in the oral cavity during postoperative follow-up. A review of the literature showed that RCH is the most common adverse drug reaction to camrelizumab but it occurs infrequently in the oral cavity. At present, the etiology of RCH has not been clarified, but the research has shown that camrelizumab may trigger tissue proliferation into hemangiomas by activating vascular endothelial cells, and the combined use of camrelizumab is safer than single use. RCH is self-limiting and most cases resolve spontaneously after discontinuation of the drug. If the mass causes dysfunction, surgical excision is feasible.@*Conclusion @#Camrelizumab can cause oral and maxillofacial reactive capillary hyperplasia complicated by pyogenic granuloma.

Literature analysis of ocular adverse drug reactions related to dupilumab / 中国药房

OBJECTIVE To analyze the clinical manifestation and characteristics of ocular adverse drug reaction （ADR） related to dupilumab， so as to provide reference for clinically safe drug use. METHODS Retrieved from CNKI， Wanfang data， VIP and PubMed databases， the case reports about ocular ADR caused by dupilumab were collected， and then analyzed statistically in terms of gender， age， primary disease， drug use， occurrence time of ADR， main clinical manifestations， treatment or outcome， etc. RESULTS A total of 20 pieces of literature were selected， involving 46 patients， among which there were 29 males and 17 females. Mainly patients were under 60 years old. The results of the association evaluation was given as follows： 13 were “very likely” and 33 were “likely”. All patients were treated with dupilumab for atopic dermatitis （AD） without off-label medication. The occurrence time of ADR was 2 weeks to 2 years after administration， mainly within 6 months after medication. All patients received dupilumab monotherapy except that 3 patients with hypertension and 1 patient with chronic obstructive pulmonary disease and human immunodeficiency virus received other drugs simultaneously. Twenty-eight patients had a history of allergic disease， and 11 patients had a history of eye disease. Ocular ADRs were mainly conjunctivitis and uveitis， and the clinical manifestations mainly included conjunctival congestion， swelling， eye secretions， etc. Ten patients developed severe ADR， including uveitis， severe conjunctivitis， and tear point stenosis； 45 patients were improved after symptomatic treatment. AD， serious initial symptoms of AD， allergic disease and underlying ocular diseases might be the high-risk factors of ocular ADR caused by dupilumab. CONCLUSIONS Whether the patient has the history of allergic diseases and basic eye diseases should be asked in detail before clinical use of dupilumab. When using the drug， attention should be paid to monitoring whether the patient has intraocular inflammation， be alert to the occurrence of new or serious ADR， and give timely symptomatic treatment to ensure the safety of drug use.