Signal mining and analysis of adverse drug event signals of darolutamide / 中国药房

OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of darolutamide and provide a reference for its clinical safe use. METHODS ADEs related to darotamide were collected based on the US FDA adverse event reporting system （FAERS） database from the third quarter of 2019 to the third quarter of 2022. Data mining and analysis were conducted by the report odds ratio （ROR） and proportional reporting ratio （PRR） methods. RESULTS A total of 565 ADE reports related to darolutamide were extracted， 356 ADE reports about darolutamide as the primary suspected drug were included， 38 ADE signals with darolutamide as the primary suspected drug were excavated， involving 15 system organ class （SOC）， mainly concentrated in patients over 65 years old. The SOC of darotamide ADE signal mainly focused on various examinations， systemic diseases and various reactions at the administration site， benign/malignant tumors or those with unknown nature （including cystic and polypoid）， kidney and urinary system diseases. A total of 13 ADE signals not mentioned in the instructions included increased prostate-specific antigen， dysphagia， cognitive impairment， erectile dysfunction， rhabdomyolysis， gynecomastia and decreased platelet count， etc. CONCLUSIONS When using darolutamide， in addition to ADE in the drug instruction， we should pay close attention to potential ADE， such as increased prostate-specific antigen， rhabdomyolysis， gynecomastia and decreased platelet count， so as to avoid drug withdrawal or organ damage caused by ADE.

Mining and analysis of acalabrutinib-induced ADE risk signals based on FDA adverse event reporting system / 中国药房

OBJECTIVE To provide reference for the clinically safe application of acalabrutinib by mining and analyzing the risk signals of adverse drug events （ADE）. METHODS The acalabrutinib-induced ADE reports were extracted from the U.S. FDA adverse event reporting system using the OpenVigil 2.1 platform from November 1， 2017 to March 31， 2023. The reporting odds ratio （ROR） method and composite criteria method from the Medicines and Healthcare Products Regulatory Agency （MHRA） were used for detection of ADE signals. RESULTS There were 7 869 ADE reports of acalabrutinib as the primary suspect drug and 142 ADE positive signals were detected from them， involving 20 system organ classes， which was generally consistent with the ADE recorded in the drug instruction of acalabrutinib， mainly involving general disorders and administration site conditions， various inspection， blood and lymphatic system disorders， various neurological disorders and cardiac disorders. In addition， this study identified several new potential ADE signals that were not mentioned in the drug instruction， including sudden cardiac death， pulmonary toxicity， tumor lysis syndrome， pleural effusion， dyspepsia， gastroesophageal reflux disease， bone pain， decreased blood pressure， and abnormal blood sodium， etc. CONCLUSIONS When using acalabrutinib， in addition to paying attention to the ADE recorded in its instructions， the risk of serious ADE that may lead to death， such as sudden cardiac death and pulmonary toxicity， should also be evaluated to avoid or reduce the occurrence of ADE as much as possible.

Hepatotoxicidad inducida por clozapina: reporte de caso y revisión breve de la literatura

Introducción: Los antipsicóticos son medicamentos que pueden producir elevaciones transitorias de las enzimas hepáticas. La clozapina es un antipsicótico atípico usado en el tratamiento de la esquizofrenia refractaria a los antipsicóticos convencionales y existe evidencia que puede producir elevaciones de las transaminasas hepáticas, expresión de dafño hepático con patrón hepatocelular. Métodos: Reporte de caso y revisión no sistemática de la literatura relevante. Presentación del caso: Una mujer de 39 años con diagnóstico de esquizofrenia paranoide acudió a un servicio de urgencias de un hospital general por náuseas, vómitos e ictericia que apareció tras el inicio de clozapina. No hubo mejoría clínica de la paciente durante la hospitalización, que falleció a los 44 días de su ingreso. Revisión de la literatura: La clozapina puede elevar las cifras de función hepática de manera transitoria y asintomática. Hay criterios clínicos para recomendar la suspensión de este antipsicótico. Conclusiones: Este caso es el tercero en la literatura que registra un desenlace fatal tras un cuadro de hepatotoxicidad inducido por clozapina. © 2021 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

Introduction: Antipsychotics are drugs that can produce transient elevations of hepatic enzymes. Clozapine is an atypical antipsychotic used in treatment-resistant schizophrenia and there is evidence that it can produce elevations of hepatic transaminases, expression of liver damage in a hepatocellular pattern. Methods: Case report and non-systematic review of the relevant literature. Case presentation: A 39-year-old woman with a diagnosis of paranoid schizophrenia attended the emergency department of a general hospital for nausea, vomiting and jaundice that appeared after the initiation of clozapine. There was no clinical improvement during hospitalization, and death occurred after 44 days. Literature review: Clozapine can increase the liver enzyme levels transiently and asymptomatically; however, there are clinical criteria that recommend the withdrawal of the antipsychotic. Conclusions: This is the third case reported in the literature of a fatal outcome of clozapine-induced hepatotoxicity.

Factores de riesgo en la Bulimia Nerviosa (BN): elementos claves de seguridad en el cuidado de la salud. Una revisión de la literatura / Bulimia nervosa risk factors (BN): key elements of health care security. A review of the literature

Resumen Se realizó una revisión de literatura con el objetivo de identificar los factores de riesgo de la BN, utiles para que el equipo de salud proteja la seguridad de sus intervenciones y atención a las personas que padecen este trastorno en el ciclo de vida adolescente y joven. Se hizo una búsqueda en bases de datos y repositorios, con uso de términos libres como: BN, adolescente, factor de riesgo, trastorno de conducta alimentaria, en español e inglés, combinados con operadores boleanos (AND, OR, NOT) y de posición (WTH y NEAR). Se incluyeron 72 documentos tras la selección por criterios de inclusión, se hizo depuración de ellos según sus datos bibliográficos, objetivo, tipo de estudio, resultados y conclusión. Los resultados muestran que hay aún factores biológicos por rastrear y analizar, dentro de los sociodemográficos, la edad de afectación principalmente reportada es la adolescencia y adultez joven, no hubo diferencias por raza o nivel socioeconómico. Factores comportamentales como preocupación por la imagen corporal, dietas y ejercicio son documentados. Desde el área psicosocial, la disfuncionalidad individual y los antecedentes de trastornos psicológicos, la familia y el entorno cultural condicionan para que el cuerpo logre su delgadez. La conclusión general sugiere que la seguridad de la atención en la BN está en explorar los antecedentes individuales, biológicos, psicológicos y comportamentales; reconocer dinámicas familiares y la influencia del entorno social. Asimismo, es útil, el trabajo interdisciplinar e integración de red de apoyo familiar para lograr atención segura en la BN.

Abstract Review of literature aimed at recognizing risk factors of BN, useful for the health team to protect the safety of their interventions and care for people suffering from this disorder in the adolescent and young life cycle. It consists of a narrative review, carried out by means of search in databases and repositories, with use of free terms such as: BN, adolescent, risk factor, food behavior disorders, in Spanish and English, combined with bolean operators (AND, OR, NOT) and position (WTH and NEAR). Seventy-two sources were incorporated, documents were selected by inclusion criteria, review according to bibliographic data, objective, type of study, results, and conclusion. The results show that there are still biological factors to be traced and analyzed, within the sociodemographic the age of involvement is adolescence and youth, it does not have differences by race or socioeconomic level. Behavioral factors such as concern for body image, diets and exercise are documented. From the psychosocial area, individual dysfunction and backgrounds of psychological disorders, the family and the cultural environment influence to achieve the thinness of the body. The general conclusion suggests that the safety of care in the BN lies in exploring the individual, biological, psychological and behavioral backgrounds, recognizing family dynamics and the influence of the social environment. It is useful, interdisciplinary work and integration of family support network to achieve safe health care in the BN.

Acute abducens nerve palsy with acute disseminated encephalomyelitis-like presentation following COVID-19 vaccination

We report two adult cases of abducens nerve palsy presenting immediately (within weeks) after they received the first dose of Covishield vaccination. Magnetic resonance imaging (MRI) of the brain obtained after the onset of diplopia demonstrated demyelinating changes. The patients had associated systemic symptoms. Post-vaccination demyelination typically known as acute disseminated encephalomyelitis (ADEM) associated with several vaccines is more common in children. Although the mechanism of the nerve palsy remains unclear, it is suspected to be related to the post-vaccine neuroinflammatory syndrome. Cranial nerve palsies and ADEM-like presentations may represent part of the neurologic spectrum following COVID-vaccination in adults, and ophthalmologists should be aware of these sequelae. Although cases of sixth nerve palsy following COVID vaccination are already reported, associated MRI changes have not been reported from India.

COVID-19 vaccination in children: a public health priority

Abstract Objective: Covid-19 had a direct impact on children's health. The aim of this review was to analyze epidemiological and clinical data, the consequences of the pandemic, and vaccination aspects in this group. Sources of data: The searches were carried out from January 2020 to November 2022, in the MEDLINE databases (PubMed) and publications of the Brazilian Ministry of Health and the Brazilian Society of Pediatrics. Summary of findings: Covid-19 has a mild presentation in most children; however, the infection can progress to the severe form and, in some cases, to MIS-C. The prevalence of the so-called long Covid in children was 25.24%. Moreover, several indirect impacts occurred on the health of children and adolescents. Vaccination played a crucial role in enabling the reduction of severe disease and mortality rates. Children and adolescents, as a special population, were excluded from the initial clinical trials and, therefore, vaccination was introduced later in this group. Despite its importance, there have been difficulties in the efficient implementation of vaccination in the pediatric population. The CoronaVac vaccines are authorized in Brazil for children over three years of age and the pediatric presentations of the Pfizer vaccine have shown significant effectiveness and safety. Conclusions: Covid-19 in the pediatric age group was responsible for the illness and deaths of a significant number of children. For successful immunization, major barriers have to be overcome. Real-world data on the safety and efficacy of several pediatric vaccines is emphasized, and the authors need a uniform message about the importance of immunization for all children.

Ocorrência de pneumotórax como evento adverso relacionado assistência à saúde / Ocorrência de pneumotórax como evento adverso relacionado assistência à saúde / Presence of pneumorax as an adverse event related to health care

Introdução: O acesso venoso central é definido como a colocação de um cateter com sua extremidade posicionada na veia cava ou no átrio direito, tendo diversas funções no manejo do paciente em estado crítico. Pneumotórax causado durante a inserção do cateter é um incidente que resulta em dano ao paciente, sendo assim considerado um evento adverso relacionado à assistência médica. Objetivo: Analisar a ocorrência de pneumotórax como evento adverso relacionado à assistência à saúde após a inserção de um cateter venoso central. Método: Trata-se de um estudo quantitativo, transversal e analítico. Depois de realizar o cálculo amostral para obtenção da amostra, pacientes submetidos à inserção de cateter venoso central na instituição pesquisada no período de abril até setembro de 2022 foram incluídos na pesquisa, a coleta de dados utilizou dados secundários. Resultados: Uma amostra de 103 pacientes foi obtido, dos quais 10 (9,7%) dos pacientes apresentaram pneumotórax relacionado à inserção de cateter venoso central. de pneumotórax. A ocorrência de pneumotórax e o fato de o profissional que inseriu o cateter ser residente. A ocorrência de pneumotórax teve associação significativa (p 0,03) levando ao aumento do tempo de internação. Conclusão: O os resultados encontrados demonstram uma significativa ocorrência do evento adverso relacionado à assistência à saúde pneumotórax, após a inserção do Cateter Venoso Central (CVC). Estratégias voltadas para a segurança do paciente são fundamentais e devem ser perseguidas constantemente.

Introduction: Central venous access is defined as the placement of a catheter with its end positioned in the superior vena cava or in the right atrium, having several functions in the management of the patient in critical condition. Pneumothorax caused during catheter insertion is an incident that results in harm to the patient, thus considered an adverse event related to health care. Objective: To analyze the occurrence of pneumothorax as adverse events related to health care after insertion of a central venous catheter. Method: This is a quantitative, cross-sectional, analytical study. After performing the sample calculation to obtain the sample, patients who underwent insertion of a central venous catheter at the researched institution from April to September 2022 were included in the research, data collection used secondary data. Results: A sample of 103 patients was obtained, of which 10 (9.7%) of the patients had pneumothorax related to the insertion of a central venous catheter. of pneumothorax. The occurrence of pneumothorax and the fact that the professional who inserted the catheter was a resident. The occurrence of pneumothorax had a significant association (p 0.03) leading to increased length of stay. Conclusion: The results found demonstrate a significant occurrence of the adverse event related to pneumothorax health care, after the insertion of the Central Venous Catheter (CVC). Strategies aimed at patient safety are fundamental and must be pursued constantly.(AU)

Introducción: El acceso venoso central se define como la colocación de un catéter con su extremo posicionado en la vena cava superior o en la aurícula derecha, teniendo varias funciones en el manejo del paciente en estado crítico. El neumotórax causado durante la inserción del catéter es un incidente que resulta en daño para el paciente, por lo que se considera un evento adverso relacionado con la atención a la salud. Objetivo: Analizar la ocurrencia de neumotórax como eventos adversos relacionados con la atención a la salud después de la inserción de un catéter venoso central. Método: Se trata de un estudio cuantitativo, transversal, analítico. Después de realizar el cálculo de la muestra para la obtención de la muestra, se incluyeron en la investigación los pacientes que se sometieron a la inserción de un catéter venoso central en la institución investigada de abril a septiembre de 2022, la recolección de datos utilizó datos secundarios. Resultados: Se obtuvo una muestra de 103 pacientes, de los cuales 10 (9,7%) de los pacientes presentaron neumotórax relacionado con la inserción de un catéter venoso central. La ocurrencia de neumotórax y el hecho de que el profesional que insertó el catéter fuera residente. La ocurrencia de neumotórax tuvo una asociación significativa (p 0,03) que condujo a una mayor duración de la estancia. Conclusión: Los resultados encontrados demuestran una ocurrencia significativa del evento adverso relacionado con la atención de salud del neumotórax, después de la inserción del Catéter Venoso Central (CVC). Las estrategias dirigidas a la seguridad del paciente son fundamentales y deben ser seguidas constantemente.(AU)

Complete atrioventricular block secondary to the BBIBP-CorV vaccine The report of a rare adverse event; the first description in Colombia

Introduction: cardiovascular complications due to COVID-19 infection are very frequent. However, these complications are rarely reported as a vaccine reaction. Case presentation: a female patient with no significant cardiovascular history developed functional class deterioration 14 days after her third dose of the BBIBP-CorV vaccine, along with three syncopal episodes. She was seen at a primary care level and an electrocardiogram was ordered which showed Mobitz 2 atrioventricular block which progressed to a complete block. Molecular tests for COVID-19 infection were negative, as were immunological studies for collagen disease, Chagas, and viral myocarditis. A transthoracic echocardiogram showed no regional kinetic disturbances, and the ejection fraction was preserved at 60%. Cardiac magnetic resonance imaging showed edema in the T2-STIR sequences, and subepicardial enhancement in the medial distal lateral region was compatible with acute myocarditis. The patient required a permanent pacemaker. Discussion: electrical or mechanical dysfunction secondary to a COVID-19 vaccine is anecdotal, with few reports in the literature. In a review of both the 2021 European Society of Cardiology and the 2018 American Heart Association Guidelines on cardiac pacing and cardiac resynchronization therapy, no recommendation was found for these types of events associated with COVID-19 or following vaccination. An international network should be created to report these events and thus determine general management guidelines. For now, the recommendations must be individualized for these patients. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2602).

Safety profile of CoviShield (ChAdOx1nCoV-19) vaccine among healthcare workers in a tertiary care hospital

Background: Coronavirus 2019 was declared as a pandemic by the World Health Organization in March 2020. Bereft of specific treatment for the disease, vaccinations and COVID appropriate behavior have come to be the main approaches to combat the pandemic. A number of vaccines have been approved after clearing clinical trials. Hence, it is essential to evaluate the safety profile of each vaccine for ensuring optimum health of the general population. This study was conducted to evaluate the adverse events following CoviShield vaccination in a tertiary care center. Aims and Objectives: The aim of the study was to describe the pattern of adverse effects, treatment given, and comorbidities seen in healthcare workers (HCW) who reported to the adverse drug reaction (ADR) monitoring center in the department of pharmacology Government T.D. Medical College, Alappuzha, following CoviShield vaccination from January 2021 to October 2021. Materials and Methods: A retrospective and descriptive study was carried out at Department of Pharmacology, GTDMCA involving all HCW who reported side effects following CoviShield vaccination in the ADR monitoring centre (AMC) in the Department of Pharmacology, GTDMCA from January 2021 to Oct 2021. Results: Out of 620 HCWs who reported adverse event following vaccination, majority (45%) were from the age group 21–30 years. About 83% of HCWs who reported adverse effect were women. Majority of the respondents (96%) experienced the adverse effects within 24 h. About 88% of respondents experienced these adverse effects after the initial dose alone. Commonly encountered adverse effects were fever (57%), headache (43%), myalgia (38%) etc. Hypertension (7%) was the most common comorbidity seen. Majority of the beneficiaries (70%) took paracetamol for the treatment of the adverse effect. Conclusion: Majority of the vaccinated HCWs experienced minor and self-limiting adverse event following immunization (AEFI) with Chimpanzee Adenovirus Oxford novel CoronaVirus-19. No serious AEFI were reported to the AMC. Despite the record speed at which the vaccine has been developed, it has shown to have a good safety profile considering the millions of doses that have been administered.

Safety of human papilloma virus vaccine based on Vaccine Adverse Event Reporting System from 2006 to 2021 / 中国生物制品学杂志

@#Objective To investigate the characteristics of distribution of adverse event(AE)associated with human papillomavirus(HPV)vaccine by analysis of data on AE collected from the Vaccine Adverse Event Reporting System(VAERS).Methods The data on AE reported in VAERS from January 1st,2006 to December 31st,2021 were analyzed and compared by using Pearson Chi-square test and Mann-Whitney U test.Results A total of 53 571 cases of AE were included in the study,in which the ratio of male to female was 0. 25∶1,and the median age of vaccinees was 15 years. A portion of 36. 1%of AE occurred after the first dose,while 90. 7% occurred within 3 d after vaccination. Both the gender ratios(χ~2=72. 570,P < 0. 001) and the median ages(Z = 4. 255,P < 0. 001)of vaccinees in non-serious and serious adverse event(SAE)showed significant difference. In terms of classification of SAE,hospitalization,prolonged hospitalization and disability were more common in females than in males,of which the percentages decreased with the increasing age. Among the AE,syncope was the most common clinical symptom. In the SAE,the highest proportion of deaths was caused by HPV2 vaccine,which was 19. 0%. The proportion of prolonged hospitalization caused by HPV4 vaccine was higher than that by HPV9vaccine. In general,HPV4 vaccine was more prone to cause SAE than HPV9 vaccine(χ~2=183. 267,P < 0. 001).Conclusion In all the AE,the largest proportion occurred in the age group of 9 ～ 17 years,followed by those in the groups of 18 ～ 26 and 27 ～ 45 years. Most of the AE occurred after the first dose. The clinical symptoms of AE caused by three vaccines were different. The analysis of distribution characteristics of AE may provide a reference for the study on clinical safety of HPV vaccine and optimization of vaccination.

Safety analysis of children of different ages vaccinated with measles, mumps and rubella combined attenuated live vaccine/measles and rubella combined attenuated live vaccine in Jilin Province from 2015 to 2022 / 中国生物制品学杂志

@#Objective To analyze the safety of children of different ages vaccinated with measles,mumps and rubella combined attenuated live vaccine(MMR in brief)/measles and rubella combined attenuated live vaccine(MR in brief)in Jilin Province from 2015 to 2022.Methods The actual vaccination data of MMR and MR from January 1,2015 to December 31,2022 were collected through the Jilin information management system for immunization programming,and all AEFI case information reported after vaccination with MMR and MR in this period was collected through the national adverse event following immunization(AEFI) monitoring and reporting system.The incidence rates of AEFI reports were compared among8-month-old children vaccinated with the first dose of MMR(MMR 8 group) and MR(MR8 group),18-month-old children vaccinated with the first dose of MMR(vaccinated with MR at 8 months old,MMR18-1 group) and the second dose of MMR(vaccinated with the first dose of MMR at 8 months old,MMR18-2 group) to preliminarily evaluate the safety of children vaccinated with MMR and MR at different ages.Results The reported incidence of AEFI in MMR8,MR8,MMR18-1 and MMR18-2 groups were 374.41/100 000,350.81/100 000,101.70/100 000 and 104.91/100 000,respectively,with significant difference among the four groups(χ~2=1 145.47,P=0.00);There was no significant difference between MMR8 and MR8,as well as MMR18-1 and MMR18-2 groups(χ~2=3.780 and 0.194,respectively,each P> 0.05);There were significant differences between MMR8 and MMR18-1,MMR8 and MMR18-2,as well as MR8 and MMR18-1groups(χ~2=920.440,412.110 and 1 021.120,respectively,each P=0.00).Most of the adverse reactions were general reactions,mainly fever,local redness and induration;A few were abnormal reactions,which were mainly allergic reactions(rash,papules,urticaria,etc.).Only one case of coincidence was reported in MMR8 group,and no psychogenic reaction,vaccine quality accident and vaccination accident occurred.All AEFI turned out to be improved or cured.Conclusion The differences of AEFI reported incidence of 8-month-old children vaccinated with MMR and MR were all small,and the difference of AEFI reported incidence of 18-month-old children vaccinated with the second dose of MMR was small regardless of the initial vaccination with MMR or MR.It is safe to use MMR instead of MR for the first vaccination in8-month-old children.

Progress of relationship between cytokines and treatment-related adverse events of immune checkpoint inhibitors in tumors and the clinical values / 肿瘤研究与临床

The use of immune checkpoint inhibitor (ICI) has significantly improved the efficacy of different types of malignancies, but the immune-related adverse event (irAE) callsed by ICI involves multiple organs and systems, affects the treatment, threatens the health of patients and even endangers their life. Therefore, it is necessary to select biomarkers to predict and monitor the occurrence of irAE, assist in the early diagnosis of high-risk patients, and guide individualized treatment. Recent studies have shown that some certain cytokines may be involved in the genesis and development of irAE. The article provides a review of studies related to cytokines and irAE to provide a reference for clinical prediction and monitoring of irAE.

Research progress of just culture in medical institutions / 中华医院管理杂志

As a safety culture placed between a culture of punishment and that of exemption, just culture can effectively improve the reporting rate of medical adverse events, promote medical staff to learn from events, and continuously improve patient safety management. The authors searched for literature on the study of just culture in medical institutions both domestically and internationally, including such databases as CNKI, Wanfang Data, and PubMed from 2001 to January 2023. They reviewed the concept of just culture and its connotation in the field of patient safety management, as well as the current research status of just culture in medical institutions both domestically and internationally. On such basis, they proposed for the construction of just culture in medical institutions in China, for reference in the construction and evaluation of a just culture in such institutions.

Ethical review and management of serious adverse events in anti-tumor drug clinical trials / 中华医学科研管理杂志

Objective:To discuss ethical review and management of serious adverse events in anti-tumor drug clinical trials in a grade A tertiary cancer hospital for timely and effective protection of subjects.Methods:The main contents and ethical management of ethical review on serious adverse events were retrospectively analyzed including the number, distribution rules, and whether they were reported in time in clinical trials conducted in our hospital in 2021.Results:A total of 1 789 serious adverse events in 259 clinical trials were reported, with more male subjects than female, with an average age of 59.95 years, mainly concentrated in the 50~59 age and 60~69 age groups, accounting for 27.45% and 42.37% respectively. Digestive oncology department, thoracic oncology department and renal cancer melanoma department ranked in the top three for the number of clinical trials and reports of serious adverse events. The highest incidence of serious adverse events was hospitalization at 63.44% and the lowest incidence was disability at 0.39%. The highest proportion of serious adverse events possibly related to clinical trials was 35.72%. Expected serious adverse events accounted for 65.85% versus 34.15% unexpected ones, and the difference between different correlations of serious adverse events whether they were expected or not.was statistically significant. Among the measures taken by the investigator for the test drugs due to serious adverse events, drug discontinuation was the most, accounting for 42.54%, while 3.07% of the trial plans modified the study protocol/informed consent. Serious adverse events reported within 24 hours accounted for 87.20%, and those reported in 24 hours and beyond accounting for 12.80%. A statistically significant difference of the reporting time between the registered and investigator initiated clinical trials was observed.Conclusions:The ethics committee should attach importance to ethical review and management of serious adverse events, pay attention to whether they were reported timely and accurately, strengthen supervision, and effectively protect the safety and interests of the subjects.

Immune checkpoint inhibitor-induced eosinophilic fasciitis: a case report and literature review / 中华内科杂志

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×10 9/L to 3.3×10 9/L. Magnetic resonance imaging showed thickened skin of both forearms, while T 2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×10 9/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement ( n=19), joint dysfunction ( n=11), myalgia/muscle weakness ( n=9), and peripheral eosinophilia ( n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

Focusing on the rational application of 0.1% CsA cationic emulsion in ocular surface inflammatory disorder / 中华实验眼科杂志

Ocular surface inflammatory disorder (OSID) is a chronic ocular disease caused by systemic disorders or involving the local immune system.OSID induces persistent inflammatory reaction in the ocular adnexal connective tissues which in turn give rise to tear hypertonicity and ocular surface epithelial damage, leading to dry eye formation or progression.Common immune-related ocular surface diseases include vernal keratoconjunctivitis, Sj?gren syndrome, graft versus host disease, dry eye and immune-related corneal disease, all of which can significantly impact the visual function and quality of life of patients.Current treatments including the use of artificial tears and glucocorticoid eye drops are not always effective and have the risk of adverse events.Cyclosporine A (CsA) is a commonly utilized immunosuppressant that has a strong immunomodulatory effect, but its clinical application is somewhat limited due to the low permeability of its current ophthalmic dosage form.The development of CsA ophthalmic agents has changed the treatment strategy for OSID.The development of 0.1% CsA cationic emulsion has significantly improved the efficacy and safety of topical CsA treatment, which is worth the attention.In order to rationally apply 0.1% CsA cationic emulsion to OSID, ophthalmologists should fully understand the immune-related pathogenesis of each OSID and comprehend the curative effect, indication, application methods and adverse events of topical CsA treatment.

Surveillance of adverse events following immunization with combined attenuated live measles, mumps and rubella vaccines in Huzhou City from 2015 to 2021 / 预防医学

Objective@#To monitor the adverse events following immunization (AEFI) with combined attenuated live measles, mumps and rubella vaccines (MMR) in Huzhou City from 2015 to 2021, so as to provide insights into the implementation of the MMR immunization strategy.@*Methods@#All AEFI caused by MMR immunization in Huzhou City from 2015 to 2021 were captured from the AEFI Monitoring Information Management System of the Immunization Planning System of Chinese Disease Control and Prevention Information System, and the incidence, clinical features and epidemiological features of AEFI were analyzed descriptively.@*Results@#The reported incidence of AEFI caused by MMR immunization appeared a tendency towards a rise in Huzhou City from 2015 to 2021 (χ2trend=124.126, P<0.001). Totally 324 386 doses of MMR vaccines were immunized, and 317 cases with AEFI were reported, with an reported incidence rate of 9.77/104 doses. Following two-dose immunization, the reported incidence of AEFI caused by two-dose MMR immunization was significantly lower than by one-dose immunization (6.01/104 doses vs. 25.43/104 doses; χ2=113.692, P<0.001). The incidence rates of general reactions, abnormal reactions and coincidental events were 6.20/104 doses, 3.42/104 dose and 0.15/104 doses, respectively. Fever and allergic rash were predominant clinical manifestations of AEFI, and no vaccine quality accident, inoculation accident or psychogenic reaction were reported. There were 246 (77.60%) cases with AEFI within 24 hours following vaccination, and among children with AEFI, there were 173 boys (54.57%), and 200 children (63.09%) age ages of less than one year (63.09%). AEFI was reported in each quarter, and 99 cases (31.23%) were reported in the fourth quarter. The largest number of children with AEFI was reported in Wuxing District (78 cases, 24.61%).@*Conclusions@#The safety of MMR vaccination is high in Huzhou City. General reaction is the predominant AEFI, which mainly occurs within 24 hours following vaccination. Two-dose MMR vaccination does not increase the risk of AEFI.

Surveillance of adverse events following immunization with human papillomavirus vaccines in Hangzhou City from 2017 to 2021 / 预防医学

Objective@#To investigate the incidence of adverse events following immunization (AEFI) of human papillomavirus (HPV) vaccines in Hangzhou City from 2017 to 2021, so as to provide insights into safety monitoring and evaluation for HPV vaccines.@*Methods@#The AEFI caused by immunization of bivalent (HPV2), quadrivalent (HPV4) and nonavalent HPV vaccines (HPV9) reported in Hangzhou City from 2017 to 2021 were captured from the AEFI Surveillance Module of Chinese Disease Control and Prevention Information System, and HPV vaccination data were captured from the Zhejiang Municipal Immunization Information Management System. The incidence, temporal distributions and clinical symptoms of AEFI were analyzed.@*Results@#Totally 922 310 doses of HPV vaccines were immunized in Hangzhou City from 2017 to 2021, and 232 cases with AEFI were reported, with an overall incidence rate of 25.15/105 doses. The reported incidence rates of AEFI caused by HPV2, HPV4 and HPV9 vaccination were 31.13/105 doses, 25.93/105 doses and 22.01/105 doses, respectively. General reactions and abnormal reactions were predominant AEFI, and the reported incidence rates of general reactions and abnormal reactions were 21.58/105 doses and 2.60/105 dose, respectively. AEFI predominantly occurred 0 to 1 day post-immunization (165 cases, 71.12%), and the main clinical symptoms included local swelling of injection sites, hard tubercle and fever, with reported incidence rates of 10.30/105 doses, 5.96/105 doses and 6.18/105 doses, respectively. @*Conclusions@#Low incidence of AEFI was reported following HPV vaccination in Hangzhou City from 2017 to 2021, and all AEFI were mild. The safety of HPV2, HPV4 and HPV9 remains high.

Mining and analysis for adverse drug event signals of liver failure in underage population based on the FAERS database / 中国药房

OBJECTIVE To conduct data mining on drugs causing liver failure in underage populations based on the FDA Adverse Event Reporting System （FAERS） database， so as to provide reference for clinical use of related drugs. METHODS The data on reported adverse drug event （ADE） of liver failure in this population （under 18 years old） from the first quarter of 2013 to the third quarter of 2022 were retrieved from the FAERS database for mining and analysis； they were divided into infants（≤1 year old）， young children（＞1-＜6 years old）， children（6-＜12 years old） and adolescents（12-＜18 years old） according to the age. The reporting odds ratio （ROR）， proportional reporting ratio and Bayesian confidence propagation neural network of the proportional imbalance method were used to screen ADE signals. RESULTS A total of 1 051 ADE reports of liver failure were collected from the underage population involving 60 drugs. The highest incidence was found in adolescents （410 cases， 39.01%）， followed by young children （297 cases， 28.26%）. The instructions of 14 drugs did not mention hepatobiliary system injury and liver failure risk， including 31 cases of levetiracetam （2.95%），18 cases of metronidazole （1.71%）， 16 cases of each of topiramate and methylprednisolone （1.52% each）， 12 cases of dexamethasone （1.14%）， 11 cases of tisagenlecleucel （1.05%）， 10 cases of each of ferrous sulfate， metformin and busulfan （0.95% each）， 9 cases of propofol （0.86%）， 8 cases of onasemnogene abeparvovec （0.76%）， 5 cases of each of diphenhydramine and omeprazole （0.48% each）， 4 cases of sebeliesterase α （0.38%）， totaling 165 cases， accounting for 15.70% of the total reported cases. Metformin was contrary to the known liver safety， and E-mail：libingchemical@163.com metronidazole and levetiracetam were new risk signals， which caused more serious clinical outcomes. CONCLUSIONS Fourteen new pharmacovigilance signals which cause liver failure in the underage population are found in this study； the liver function of patients should be closely monitored when using these drugs. Among those drugs， metformin neither undergoes liver metabolism nor has been reported in the relevant literature， and the liver-related ADE caused by metformin deserves further attention. The clinical outcomes caused by metronidazole and levetiracetam are relatively serious and need to be given sufficient attention.

Effect of the area under the curve of carboplatin dosage on therapeutic efficacy and safety in Chinese patients with epithelial ovarian cancer / 西安交通大学学报(医学版)

【Objective】 To retrospectively analyze the average carboplatin dosage and calculate the area under the curve (AUC) using the Calvert formula in first-line chemotherapy in patients with epithelial ovarian cancer in The First Affiliated Hospital of Xi’an Jiaotong University so as to evaluate the effect of the AUC difference in the Chinese population on therapeutic efficacy and safety. 【Methods】 We enrolled patients who underwent first-line chemotherapy with paclitaxel and carboplatin 3-week regimen in our hospital from January 1, 2012 to January 1, 2022. According to the median of AUC, the patients were divided into high-dose group and low-dose group. The overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) were compared. 【Results】 A total of 153 patients were enrolled in this study and the median AUC of carboplatin was 3.981 (range 2.314-5.446). Only 10.46% patients (16/153) had an AUC above 5. There were 77 patients with the AUC0.05). The ORR in the low-dose group and the high-dose group was 59.74% and 57.89%, respectively, and the DCR was 87.01% and 85.53%, respectively. The median PFS of the two groups was 14 and 15.5 months, respectively, and the median OS was 50 and 55 months, respectively. None of the above outcomes were statistically different between the two groups (P>0.05). The two groups showed significant differences in the incidence of anemia, neutropenia, and thrombocytopenia (P<0.05). The incidence of nausea and vomiting, grade 1-2 diarrhea or constipation, and grade 1-2 fever showed significant differences (P<0.05). In addition, the incidence of dose limiting toxicity (DLT), including grade 4 thrombocytopenia and febrile neutropenia (FN), was significantly increased in the high-dose group (P<0.05). 【Conclusion】 Compared with the recommended AUC 5-6 of carboplatin abroad, the actual carboplatin dosage in the first-line chemotherapy for patients with epithelial ovarian cancer was generally insufficient in our hospital. There was no difference in therapeutic efficacy between the patients with AUC<4 and AUC≥4. However, considering the increased risk of some AEs and DLT in the high-dose group, it is not recommended to increase the carboplatin AUC blindly.