Drug-induced Diseases Research Articles

Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French pharmacovigilance database.

Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung diseases (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs. This retrospective study included cases registered in the FPVD from 1st January 1985 to 1st April 2022 which had ADR coded in MedDRA with a High Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged 18 and over. We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and in 13.3% death ensued. Men accounted for 54.4% of the cases. Median age was 69 [18-103] years. The most prevalent ADRs were "ILD" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). "Anti-cancer drugs" (31.2%) and "Cardiovascular drugs" (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%). This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify it properly and discontinue the culprit drug urgently.

Regional diversity in drug-induced lung diseases among the USA, European Union, and Japan.

Drug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base. This retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and cytotoxic agents. Regional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418). The prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.

Navigating Drug-Induced Lung Disease (DILD): A Comprehensive Review on Management and Prevention Strategies.

Drug-induced lung disease (DILD) is a significant and often overlooked adverse effect of pharmacological treatments, encompassing a range of pulmonary disorders triggered by medications. This review provides a comprehensive overview of DILD, focusing on its definition, pathophysiology, and clinical implications. We explore the epidemiology of DILD, highlighting the prevalence of various drugs associated with pulmonary toxicity and the factors influencing susceptibility. The review details the clinical presentation of DILD, including common symptoms and diagnostic challenges, and outlines diagnostic modalities such as imaging, pulmonary function tests, and invasive procedures. Management strategies are discussed, emphasizing the importance of timely drug discontinuation, supportive care, and the role of corticosteroids and novel therapies. Preventive measures, including pre-treatment evaluations and ongoing monitoring, are also addressed. The review concludes by examining future research directions and emerging therapies, aiming to enhance the understanding and management of DILD. This review is intended to aid healthcare professionals in recognizing, managing, and preventing drug-induced lung diseases, ultimately improving patient outcomes and safety.

(136) LABIA MINORA: A COMPREHENSIVE REVIEW

Abstract Introduction The labia minora (LM) is a part of the external female genitalia that varies greatly in form and appearance, and changes at each developmental stage of a woman. Its highly neurovascular nature and proximity to the clitoris allows it to play a vital role in sexual function. Along with the labia majora, it helps to protect the opening of the urethra and vagina. The perception of a normal LM is dependent on cultural and social context and influences the kinds of procedures that are done on the LM. Objective This study aims to comprehensively review labial anatomy, development, pathology, its role in sexual function, perceptions of labial appearance, and labial procedures. The goal is to understand the mechanism and purpose of the evolution of the LM and its effects on anatomical and sexual function. Methods We reviewed journal articles from 1988 to 2023 concerning labial anatomy, physiology, pathology, piercings, tattoos, and labial procedures such as labiaplasty, genital mutilation, episiotomies. We also reviewed cultural perceptions of its structure, its role in sexual function and its composition and function in the transgender population. Results The LM is highly neurovascular and engorges with blood with sexual stimulation. The structural changes are influenced by hormone levels. Perception of normal appearance varies by cultural and societal norms, influencing procedures performed in the area. Due to the histological composition of the LM, it has many manifestations of dermatological diseases. The LM is also susceptible to infectious, neoplastic, drug-induced, inflammatory, autoimmune and other systemic diseases. Limited information exists on LM piercing and tattoos. The size discrepancies of the LM may cause psychological distress, with conflicting research on its impact on sexual sensitivity or function. Labial procedures such as labiaplasty may enhance sexual satisfaction while female genital mutilation may reduce sexual satisfaction. There is a lack of comprehensive documentation of techniques of LM creation in transgender women and a lack of long-term follow-up studies post-vaginoplasty. The lymphatic structure within the LM is poorly understood, emphasizing the need for further research. Conclusions The labia minora is important for arousal and sexual function and its changes over time is dependent on hormone levels. The appearance and structure drive the kinds of labial procedures that are conducted and significantly affects sexual health. There is a need for further studies of the labia minora to understand its complexities and evolution. Disclosure No.

Genetic variants contribute to drug-induced interstitial lung diseases

Genetic variants contribute to drug-induced interstitial lung diseases

Toxicity prediction and classification of Gunqile-7 with small sample based on transfer learning method

Drug-induced diseases are the most important component of iatrogenic disease. It is the duty of doctors to provide a reasonable and safe dose of medication. Gunqile-7 is a Mongolian medicine with analgesic and anti-inflammatory effects. As a foreign substance in the body, even with reasonable medication, it may produce varying degrees of adverse reactions or toxic side effects. Since the cost of collecting Gunqile-7 for pharmacological animal trials is high and the data sample is small, this paper employs transfer learning and data augmentation methods to study the toxicity of Gunqile-7. More specifically, to reduce the necessary number of training samples, the data augmentation approach is employed to extend the data set. Then, the transfer learning method and one-dimensional convolutional neural network are utilized to train the network. In addition, we use the support vector machine-recursive feature elimination method for feature selection to reduce features that have adverse effects on model predictions. Furthermore, due to the important role of the pre-trained model of transfer learning, we select a quantitative toxicity prediction model as the pre-trained model, which is consistent with the purpose of this paper. Lastly, the experimental results demonstrate the efficiency of the proposed method. Our method can improve accuracy by up to 9 percentage points compared to the method without transfer learning on a small sample set.

A rare case of liver regenerative and non-neoplastic lesion resembling a well-differentiated hepatocellular carcinoma

BackgroundNodular regenerative hyperplasia (NRH) is a rare disease that presents pathologically as diffuse hepatic nodules without fibrous septa. It is believed to be caused by vasculopathy against a background of various systemic diseases, such as hematologic, autoimmune, and drug-induced diseases, with various symptoms. In spite of the recent imaging advances, various atypical cases of nodular lesions are observed in daily clinical practice. Cases that do not completely meet these criteria are referred to as -like or -similar lesions in clinical situations, making it difficult to understand their pathogenesis. We present a case in which two hepatic nodular lesions were noted and difficult to differentiate from malignancy preoperatively. The lesions were laparoscopically resected and a pathological diagnosis with non-neoplastic liver regenerative nodules resembling NRH was made.Case presentationA 49-year-old man with no alcohol or drug intake and no past medical history was identified as having liver tumors on screening examination without any symptoms. Contrast-enhanced computed tomography (CT) showed two hepatic tumors; approximately 2-cm tumors at S7 and S8. Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed fat inclusions in their contents. Ethoxybenzyl (EOB) uptake was also observed during the hepatobiliary phase. Based on preoperative examinations, we suspected well-differentiated hepatocellular carcinoma (HCC) and performed laparoscopic S7/8 partial resection for these lesions. Macroscopically, the resected specimens showed a non-cirrhotic yellowish-cut surface containing brownish, ill-defined lesions with irregular borders. Microscopically, these lesions showed zonal necrosis, congestion, and aggregation of hemosiderin-laden macrophages around the central vein. In these areas, the fatty deposition of hepatocytes was lower than that in the surrounding background hepatocytes. Histopathologically, neither neoplastic nor hyperplastic lesions were observed, and he was diagnosed as regenerative hepatic change with centrilobular necrosis.ConclusionsConsidering the pathological results, these lesions were thought to be a type of NRH-like lesion with possible hepatic vessel disorder. However, the lesion’s cause and classification was difficult to determine. The accumulation of these regenerative changes accompanying fatty liver is needed to clarify the mechanism and its clinical significance.

Unravelling the Complex Interplay: Understanding Drug-induced Diseases and Teratogenicity from a Comprehensive Perspective.

Iatrogenic diseases, also referred to as drug-induced diseases (DIDs), represent a recognized yet inadequately investigated phenomenon that may result in enduring afflictions, hospital admissions, pharmacological interventions, protracted pharmaceutical reliance, and health complications. In the contemporary era of personalized medicine, it is imperative for prescribers to remain abreast of the dynamic advancements in the field of toxicology. Iatrogenic disorders may manifest as a result of medical interventions, including diagnostic procedures, therapeutic interventions, or preventative measures. Key factors to be taken into consideration encompass the patient's chronological age, dietary patterns, genetic predisposition, pre-existing medical conditions, diminished host response mechanisms, and pharmacological tolerance. Teratogenicity pertains to the prevalence of congenital anomalies and disorders resulting from exposure to teratogenic agents, environmental influences, and pharmacological interventions. The primary objective of this review is to provide individuals with comprehensive knowledge regarding the potential risks associated with iatrogenic diseases, thereby facilitating the prevention of unforeseen adverse outcomes.

Adult-onset linear IgA bullous dermatosis: a retrospective single-center cohort study of 81 patients and literature review.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder that may be drug-induced or paraneoplastic. We aim to characterize features of LABD and determine differentiating factors among idiopathic, drug-induced, or malignancy-associated diseases. We conducted a single-center retrospective chart review of adult patients with linear IgA bullous dermatosis at a large tertiary referral center and a literature review of adult linear IgA bullous dermatosis. Eighty-one patients were included in the study. Ten patients (12.3%) had comorbid malignancy and nine (11.1%) had inflammatory bowel disease. Median disease duration was significantly shorter in both drug-induced (1.2 vs. 48.8 months; P < 0.001) and malignancy-associated (1.7 vs. 48.8 months; P < 0.001) LABD compared with idiopathic LABD. Recurrent episodes occurred significantly more often in idiopathic LABD compared to those with drug-induced (76.1 vs. 11.5%; P < 0.001) or malignancy-associated disease (76.1 vs. 33.3%; P = 0.019). Time to diagnosis was significantly shorter in the drug-induced (0.2 vs. 5.4 months; P < 0.001) and malignancy-associated groups (0.7 vs. 5.4 months; P = 0.049) compared with idiopathic; similarly, time to improvement was significantly shorter in both drug-induced (0.4 vs. 3.0 months; P < 0.001) and malignancy-associated disease (1.1 vs. 3.0 months; P = 0.016). Clinical morphology was indistinguishable between groups. Limitations included retrospective data collection, data from tertiary referral centers, and limited racial and ethnic diversity. Screening for underlying malignancy, as well as for a predisposing medication or possibly inflammatory bowel disease, may be advisable in patients with LABD, particularly when it is newly diagnosed.

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases

BackgroundDrug-induced interstitial lung disease (DILD) is a lung injury caused by various types of drugs and is a serious problem in both clinical practice and drug development. Clinical management of the condition would be improved if there were DILD-specific biomarkers available; this study aimed to meet that need.MethodsBiomarker candidates were identified by non-targeted metabolomics focusing on hydrophilic molecules, and further validated by targeted approaches using the serum of acute DILD patients, DILD recovery patients, DILD-tolerant patients, patients with other related lung diseases, and healthy controls.ResultsSerum levels of kynurenine and quinolinic acid (and kynurenine/tryptophan ratio) were elevated significantly and specifically in acute DILD patients. The diagnostic potentials of these biomarkers were superior to those of conventional lung injury biomarkers, Krebs von den Lungen-6 and surfactant protein-D, in discriminating between acute DILD patients and patients with other lung diseases, including idiopathic interstitial pneumonia and lung diseases associated with connective tissue diseases. In addition to identifying and evaluating the biomarkers, our data showed that kynurenine/tryptophan ratios (an indicator of kynurenine pathway activation) were positively correlated with serum C-reactive protein concentrations in patients with DILD, suggesting the potential association between the generation of these biomarkers and inflammation. Our in vitro experiments demonstrated that macrophage differentiation and inflammatory stimulations typified by interferon gamma could activate the kynurenine pathway, resulting in enhanced kynurenine levels in the extracellular space in macrophage-like cell lines or lung endothelial cells. Extracellular quinolinic acid levels were elevated only in macrophage-like cells but not endothelial cells owing to the lower expression levels of metabolic enzymes converting kynurenine to quinolinic acid. These findings provide clues about the molecular mechanisms behind their specific elevation in the serum of acute DILD patients.ConclusionsThe serum concentrations of kynurenine and quinolinic acid as well as kynurenine/tryptophan ratios are promising and specific biomarkers for detecting and monitoring DILD and its recovery, which could facilitate accurate decisions for appropriate clinical management of patients with DILD.

A Nonsystematic Review of the Features of Pharmacotherapy in the Elderly at the Stage of Taking Medications.

The human body is subservient to the age-related changes that affect not only the outer appearance but also organs and tissues. They also concern the processes of pharmacokinetics and dynamics. This means that the absorption, distribution, and metabolism of drugs used by an elderly patient will be slowed down. Therefore, it becomes necessary to prescribe a special dosing regimen for older people. An actual problem is also that, with age, many patients require more drugs than young people. This increases the risk of side effects because many drugs are difficult to combine with each other. Pharmacy of our time is a science that is constantly developing and modernizing, which allows changing therapy for the better: prescribing drugs in smaller quantities, with a smaller range of adverse reactions and a better effect. The aim of the work is to analyze the impact and relationship of older age on the pharmacotherapy of patients, as well as the risks of drug-induced diseases. To carry out this work, such research methods as analysis, synthesis, comparative analysis, classification, analogy, abstraction, induction, and generalization were used. The features of the stages of pharmacokinetics and pharmacodynamics in the elderly were considered; we studied the data of clinical studies and literature in geriatrics; and the effects of a combination or increase in the dosage of drugs have been noted. After the collection of research data and the analysis, it turned out that it is real and necessary to avoid the negative consequences of pharmacotherapy in elderly and senile patients. Considering the natural age-related changes in the condition and functioning of organs and systems, constantly monitoring the effectiveness of drugs and undesirable reactions of the body to them, adjusting treatment protocols will have a favorable result and help optimize pharmacotherapy for the elderly and reduce the risk of side effects and diseases caused by medications.

Drug-Induced Diseases in Cardiology

Drug-Induced Diseases in Cardiology

Drug-induced glomerular diseases

Drug-induced kidney diseases represent a wide range of diseases that are responsible for a significant proportion of all acute kidney injuries and chronic kidney diseases. In the present review, we focused on drug-induced glomerular diseases, more precisely podocytopathies-minimal change diseases (MCD), focal segmental glomerulosclerosis (FSGS)-and membranous nephropathies (MN), from a physiological and a pharmacological point of view. The glomerular filtration barrier is composed of podocytes that form foot processes tightly connected and directly in contact with the basal membrane and surrounding capillaries. The common clinical feature of these diseases is represented by the loss of the ability of the filtration barrier to retain large proteins, leading to massive proteinuria and nephrotic syndrome. Drugs such as non-steroidal anti-inflammatory drugs (NSAIDs), D-penicillamine, tiopronin, trace elements, bisphosphonate, and interferons have been historically associated with the occurrence of MCD, FSGS, and MN. In the last ten years, the development of new anti-cancer agents, including tyrosine kinase inhibitors and immune checkpoint inhibitors, and research into their renal adverse effects highlighted these issues and have improved our comprehension of these diseases.

Drug eruption and drug-induced skin diseases in the elderly patients

Drug eruption and drug-induced skin diseases in the elderly patients

OA17 Rheumatoid meningitis - a rare complication of rheumatoid arthritis

Abstract Introduction A wide spectrum of neurological complications can occur in rheumatoid arthritis (RA) including peripheral neuropathy, mononeuritis multiplex and rheumatoid vasculitis. Cerebrovascular disease is also common. We describe a rare neurological complication of RA. Case description The patient was first diagnosed with seropositive RA in 2015 at the age of 68. His rheumatoid factor at presentation was 144 kIU/L and CCP antibodies &amp;gt;340 U/mL. His background include alcohol excess and obstructive sleep apnoea with peripheral neuropathy attributed to alcohol. Nerve conduction studies demonstrated axonal neuropathy. By 2016, he had achieved good disease control with combination methotrexate and sulfasalazine. In 2018, he was admitted to stroke services with right arm weakness and focal neurological deficit on examination. An urgent CT head showed possible right parietal extra dural haemmorhage. His CRP was &amp;lt;5, ESR 24 with a normal ANA. Borrelia, syphilis and HIV screening were normal. Anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Hu, anti-Yo and anti-Ri antibodies were all negative. Lumbar puncture revealed a normal glucose and red blood cells count but the CSF protein was raised at 851 mg/L with a lymphocyte count of 9/ul. Gram stain, culture, viral PCR for HSV, VZV, enterovirus, parechovirus and adenovirus were normal and CSF cytology demonstrated a lymphocyte pleocytosis. Subsequent contrast MRI head scan showed leptomeningeal enhancement with gadolinium contrast. MRI of the cervical spine and brachial plexus was normal and an EMG/NCS of the upper limb demonstrated an incidental ulnar nerve compression at the elbow. Following neurology input, the leptomeningeal enhancement was thought to represent rheumatoid meningitis (RM). He was treated with 1 mg/kg prednisolone and rituximab with prompt and complete recovery. He remains well from both the perspective of his RA and RM. Discussion RM is a rare form of aseptic meningitis. Aseptic meningitis is commonly defined as clinical and CSF evidence of meningeal inflammation in the absence of an infectious aetiology. The vast differential includes malignancies, drug-induced and autoimmune diseases, for example lupus and sarcoidosis. The diagnosis of RM requires a high index of suspicion as well as exclusion of other causes. Historically RM was diagnosed at post-mortem but MRI scanning means pre-mortem diagnosis is possible. It is considered rare but serious manifestation of RA. Case reports suggest RM usually occurs in those with long standing seropositive RA but RM has been described in the early stages of RA and even as a presenting feature. Peripheral disease activity does not correlate with occurrence of RM. The clinical presentations vary depending on the brain structure involved and can include motor or sensory deficits, cognitive disturbance and seizures. It may mimic many other conditions. Radiological findings will not distinguish RM from other causes of aseptic meningitis. CSF finding of lymphocytosis and rheumatoid factor (if available) may help distinguish RM from other causes. Meningeal biopsy can confirm the diagnosis. Due to the rarity of RM, there are no current guidelines on treatment. Historically, corticosteroids are the main induction agent. There are case reports highlighting possible success from the addition of cyclophosphamide and rituximab. Case series also highlight a significant mortality rate in excess of 60% even despite treatment. This may represent publication and historical bias. Key learning points Rheumatoid meningitis (RM) is a rare but serious complication of rheumatoid arthritis. RM may not correlate with disease activity nor disease duration. Diagnosis is a challenge due to its wide clinical phenotype as well as the non-specificity of imaging, lumbar puncture and serological findings. Treatment options are based on case reports and series and include corticosteroids, rituximab and cyclophosphamide.

Analysis of 12 cases of antineoplastic agents-induced interstitial lung disease.

Objective: To summarize the situation of antineoplastic agents-induced interstitial lung diseases (ILD), provide reference for strengthening clinical management of druginduced interstitial lung diseases (DILD). Methods: We retrospectively investigated the medical records of 12 patients with antineoplastic agents-induced ILD in a hospital between January and December 2020. Data collected included patients' characteristic (gender, age, ECOG PS score, smoking history, primary tumor, concurrent diseases or complications.) and treatment conditions (DILD-causing drugs, clinical symptoms, chest CT, DILD treatment drugs, onset cycle, onset time, severity of DILD, DILD course and prognosis.). Results: The median age of 12 DILD cases was 68%, 66.67% of the patients were male, lung cancer accounted for 58.33% (7/12). DILD was induced by cytotoxicity drugs, targeted drugs and immune checkpoint inhibitors (ICIs), of which ICIs accounted for 66.67% (8/12). Scattered patchy, cord-like, grid-like or flocculent shadows were observed on chest CT, mainly under the pleura of lungs. Once DILD occurs, the suspected antineoplastic agents were stopped and glucocorticoid was given, among which 83.33% (10/12) patients were treated with antibiotics. Finally, 16.67% (2/12) were cured, 33.33% (4/12) were improved, 16.67% (2/12) were not cured and 33.33% (4/12) were dead. Conclusion: Antineoplastic agents-induced ILD is mostly found in elderly male lung cancer patients with smoking history. The clinical symptoms of DILD are diverse and lack of specificity. ICIs-ILD has the characteristic of high incidence and poor prognosis compared with other antineoplastic agents. Comprehensive evaluation before medication, regular review, early and adequate glucocorticoid shock therapy after onset can improve the prognosis of DILD patients.

Effects of Emergency Room-specialized Pharmacists on Emergency Medicine

It is difficult to say that pharmacist services in the emergency room (ER) are widespread nationwide. According to a survey of certified emergency pharmacists, the work area they are most commonly engaged in is the intensive care unit. This may be due to the lack of reimbursement for pharmacist services in ERs and the absence of operational guidelines. On the other hand, Sapporo Higashi Tokushukai Hospital has had ER specialized pharmacists (ESPs) since 2016 and has reported on the usefulness of pharmacist services in the ER at conferences and in papers. Among other things, it has been shown that the workload of emergency physicians is reduced by 1.9 h/d through the use of ESPs, and that also contributes to the increase in accurate diagnoses of drug-induced diseases and the treatment of infectious diseases. Reports on the benefits of ESP have also begun to emerge in Japan, including a significant decrease in the number of incident reports. Meanwhile, overseas reports indicate that ESPs have a significant impact on healthcare economics, such as "an annualized cost avoidance effect of more than 400 million yen." Furthermore, reports of improvements in operational guidelines and patient outcomes that support these guidelines indicate that ESPs in other countries are well-established ahead of their counterparts in Japan. We strongly hope that ESPs will increase in number and distribution in Japan in the future through the evaluation of reimbursement and formulation of operational guidelines.

PartII: Interactive case:Drug‐inducedendocrine disorders

Part<scp>II</scp>: Interactive case:<scp>Drug‐induced</scp>endocrine disorders

Prescription of potentially inappropriate medicines and comparison with lists of essential medicines for treatment of chronic disorders in older patients

ObjectivesTo examine the current situation of potentially inappropriate medicines (PIM) for treatment of chronicity in older patients and whether the inappropriate medicines were included in the 22nd World Health Organization (WHO) Model List of Essential Medicines (EMLs), China National Model list of Essential Medicines (China EMLs), or supplementary list of essential medicines in Guizhou Province 2018 (Guizhou EMLs) through real world data, so as to promote the development of lists of essential medicines suitable for older patients and provide a reference for the revision of lists of essential medicines to reduce adverse effects, drug-induced diseases and even possible death due to use of inappropriate medicines existing in lists of essential medicines. MethodsA retrospectively study was conducted. Dispensing records of patients aged ≥ 65 admitted to convenience clinic of a tertiary hospital from January 1, 2021 to December 31, 2021 were extracted through electronic information system. Then, we merged dispensing records of the same patient on the same date as one record and patients with at least one chronic disease were included. The American Geriatrics Society(AGS)/Beers Criteria 2019 (Beers 2019) was used to evaluate the PIM status. Thereafter, the inappropriate medicines were compared with WHO EMLs, China EMLs, and Guizhou EMLs to find out percentages of drugs of PIMs existing in above lists of essential medicines in all drugs of PIMs. The above evaluation was conducted using Excel software (version 2019). ResultsA total of 5314 dispensing reports were included in this study. 5.95% (316/5314), 7.88% (419/5314) of PIMs met Table 2 (medicines that are potentially inappropriate in most older adults), Table 4 (medicines that should be used with caution) of Beers 2019, respectively. Among PIM drugs which met Table 2 of Beers 2019, 47.37%, 78.95%, and 78.95% were respectively included in WHO EMLs, China EMLs, and Guizhou EMLs, and that was 47.06%, 76.47%, and 82.35% for Table 4 of Beers 2019. ConclusionsPIM in older patients is common in clinical practice. Patients with diabetes, hypertension, arthritis, depression and/or anxiety and Parkinson’ diseases were more frequently prescribed drugs of PIM according to Beers 2019. Take older patients into consideration and formulate List of essential medicines special for older patients may be a key way to reduce PIM.

Chemical- and Drug-Induced Allergic, Inflammatory, and Autoimmune Diseases Via Haptenation.

Haptens are small molecules that only elicit an immune response when bound to proteins. Haptens initially bind to self-proteins and activate innate immune responses by complex mechanisms via inflammatory cytokines and damage-associated molecular patterns and the subsequent upregulation of costimulatory signals such as cluster of differentiation 86 (CD86) on dendritic cells. Subsequent interactions between CD86 and CD28 on T cells are critically important for properly activating naive T cells and inducing interleukin 2 production, leading to the establishment of adaptive immunity via effector and memory T cells. Accumulating evidence revealed the involvement of haptens in the development of various autoimmune-like diseases such as allergic, inflammatory, and autoimmune diseases including allergic contact dermatitis, atopy, asthma, food allergy, inflammatory bowel diseases, hemolytic anemia, liver injury, leukoderma, and even antitumor immunity. Therefore, the development of in vitro testing alternatives to evaluate in advance whether a substance might lead to the development of these diseases is highly desirable. This review summarizes and discusses recent advances in chemical- and drug-induced allergic, inflammatory, and autoimmune diseases via haptenation and the possible molecular underlying mechanisms, as well as in vitro testing alternatives to evaluate in advance whether a substance might cause the development of these diseases.