BACKGROUND: Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation.
OBJECTIVE: We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date.
METHODS: We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days.
RESULTS: Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset.
CONCLUSIONS: A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

OBJECTIVE: Endometriosis and adenomyosis are two common diseases that impair women\'s health, and dienogest is one of the pharmacologic treatments which is the first-line therapeutic option for patients with pelvic pain and individuals who have no desire for immediate pregnancy. The goal of this study was to summarize the current evidence of adverse events associated with dienogest as well as the prevalence of these adverse events during treatment with dienogest.
METHODS: Several databases (PubMed, Embase, Cochrane Central and Clinicaltrials.gov, etc.) and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched on May 31, 2023, using the topic words alongside free words of dienogest and \"adverse reaction\". Studies were incorporated into this research if they reported or assessed safety issues or adverse reactions of dienogest during the period of endometriosis treatment or adenomyosis therapy. The extracted information comprised trial design, dienogest and control group demographics, as well as reported side effects.
RESULTS: This systematic review comprehended 39 publications in total. The mean age of patients in the included studies was 34.43 years. The follow-up duration varied from 3 to 60 months. Most adverse reactions were common and not serious, and the most common adverse reactions during dienogest medication were abnormal uterine bleeding (55%, 95% CI 37-73%), amenorrhea (17%, 95% CI 2-42%) and swelling (13%, 95% CI 3-28%). Uncommon adverse reactions included dysmenorrhea (0.2%, n = 1), dyspepsia (0.4%, n = 1), and (lower) abdominal pain (1%, 95% CI 0-3%), urticaria (1%, 95% CI 0-3%) and peritonitis (1%, n = 1). Serious adverse reactions including decreased lumbar spine Bone Mineral Density (BMD), depression, peritonitis and so on have been reported. Heterogeneity assessment revealed that patient number and study design are influencing factors to adverse reaction prevalence. Moreover, abdominal pain, diarrhea, nausea and vomiting, back pain and anemia are side effects reported both in the FAERS database and in the systematic review.
CONCLUSIONS: Dienogest\'s most frequent side effects were not severe. Dienogest is generally safe for treating endometriosis and adenomyosis. Nevertheless, people should be aware of serious adverse reactions, such as decreased lumbar spine BMD and hemorrhagic shock.

Az aminokinolinok egy régóta használt gyógyszercsoport, amely napjainkban is elengedhetetlen számos kórkép, különösen szisztémás gyulladásos kórképek terápiájában. Az éles látásért felelős retinarész, a macula klorokin és hidroxiklorokin által okozott toxikus károsodása már jól ismert mellékhatás volt a múlt században is. Az ilyen gyógyszert hosszú távon szedő krónikus betegek szemészeti szűrése azóta visszatérő kérdéskör, mely az újonnan megjelenő evidenciák által folyamatosan megújuló vizsgálati protokollokban nyilvánul meg. Tanulmányunkban áttekintjük a jelenleg érvényes nemzetközi irányelveket, kitérve arra, hogy az ezekben újonnan történő változtatások milyen új adatokon alapszanak. Ismertetjük a korszerű szemészeti szűrés műszereit (automata látótérvizsgálat, optikaikoherencia-tomográfia [OCT], fundus-autofluoreszcencia [FAF], multifokális elektroretinográfia [mfERG]), valamint a klorokint vagy hidroxiklorokint szedő betegeknél azonosított rizikófaktorokat, melyek hajlamosítanak a maculopathia kialakulására. Végezetül egy hazai viszonyokra adaptált szűrési protokollt szeretnénk bemutatni. Orv Hetil. 2024; 165(30) 1147–1153.

Lorlatinib has been FDA-approved as a systemic therapy for ALK/ROS1-positive non-small cell lung cancer (NSCLC) patients. However, it has been associated with an increased frequency of neurocognitive adverse events (NAEs). Therefore, we conducted a systematic review and meta-analysis to assess the NAEs related to lorlatinib therapy in NSCLC patients. PubMed, Scopus, the Cochrane Library, and prominent conference proceedings were searched for eligible studies of lorlatinib in NSCLC patients. NAEs included cognitive, mood, speech, and psychotic effects. A total of 1147 patients from 12 studies were included; 62% had brain metastases. A pooled analysis of NAEs showed frequencies of cognitive effects of 14.57% (95% CI, 8.37 to 24.14, I2 = 84%), mood effects of 11.17% (95% CI, 5.93 to 20.07, I2 = 84%), speech effects of 7.24% (95% CI, 3.39 to 15.20, I2 = 72%), and psychotic effects of 4.97% (95% CI, 3.27 to 7.49, I2 = 21%). Clinical trials reported a significantly higher frequency of mood effects than was indicated by real-world data. These results highlight the importance of educating patients and healthcare professionals about lorlatinib-related NAEs for early detection and management to improve NSCLC patients\' quality of life.

Acute pancreatitis has been considered a rare potential adverse effect of sodium-glucose co-transporter-2 inhibitors (SGLT-2is), a new class of medications recently approved for use as an add-on therapy in patients with poorly controlled type 2 diabetes mellitus as well as in individuals with heart failure (HF) and chronic kidney disease (CKD). SGLT-2i can effectively reduce cardiovascular mortality and the deterioration of renal function. There are only a few published cases of acute pancreatitis linked to SGLT-2i administration. Our case describes a 58-year-old male who presented to the emergency department with a clinical presentation of acute pancreatitis, with no known risk factors, who was recently started on therapy with dapagliflozin. Following thorough clinical and laboratory testing, the diagnosis of pancreatitis was associated with dapagliflozin. Upon discharge, dapagliflozin was discontinued with no further recurrence of epigastric pain.

Xanthoma disseminatum (XD) is a rare, non-Langerhans cell histiocytosis. While treatment is notoriously difficult, 2-chlorodeoxyadenosine (cladribine) has recently emerged as a potential effective therapeutic option. Here, we describe the case of a 65-year-old male with XD who experienced significant cutaneous improvement after cladribine treatment. We also provide an updated literature review on cladribine use in patients with XD in light of reported adverse effects (AEs). While the efficacy of cladribine in XD is clear, no consensus exists for treatment duration and AE management. Hence, we strongly encourage interdisciplinary discourse involving dermatology and oncology in these cases.

UNASSIGNED: Omalizumab is an established therapy for allergic conditions, yet its neurological effects remain underexplored compared to other biological agents.
UNASSIGNED: A 45-year-old male with asthma developed acute quadriparesis one week after receiving the first dose of omalizumab. Electrophysiological studies have shown partial motor conduction block in multiple nerves, with reduced CMAP amplitudes and absent F-waves in others. CSF showed cyto-albuminous dissociation. The diagnosis was a variant of Guillain-Barré syndrome. Despite intravenous immunoglobulin (IVIG) therapy, the patient experienced persistent neuropathic symptoms.
UNASSIGNED: The patient presented with acute quadriparesis devoid of sensory or cranial nerve involvement, suggestive of a variant of Guillain-Barré syndrome (GBS) known as acute motor conduction block neuropathy (AMCBN). Electrophysiological studies have indicated conduction block without demyelination, implicating axonal degeneration. Despite negative findings for common etiologies, the temporal association between omalizumab administration and symptom onset suggests a potential link, supported by criteria for drug-induced illness. Conflicting evidence exists regarding omalizumab\'s neurological effects, with proposed mechanisms including autoimmune reactions and mast cell dysfunction. Comparisons to TNF-α antagonists highlight similar neuropathy patterns, indicating a need for further research to clarify omalizumab\'s neurotoxicity.
UNASSIGNED: In conclusion, while omalizumab holds promise for allergic conditions, including chronic urticaria, its potential impact on peripheral nerves necessitates vigilance among clinicians. Further studies are imperative to ascertain the risk-benefit profile and elucidate underlying mechanisms and risk factors of neurological complications associated with omalizumab therapy.

BACKGROUND: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, \"Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?\" and CQ #2, \"Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?\".
METHODS: A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain.
RESULTS: Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval.
CONCLUSIONS: This review indicated that G-CSF\'s efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.

UNASSIGNED: The use of herbal medicines (HMs) for the treatment of hypertension (HTN) is increasing globally, but research on the potential adverse effects and safety of HMs in HTN patients is limited. Therefore, this systematic review and meta-analysis aim to determine the global prevalence of HM usage among HTN patients and assess the safety of identified herbs based on current scientific evidence.
UNASSIGNED: The PubMed/MEDLINE, EMBASE (Ovid), and Cumulated Index to Nursing and Allied Health Literature (CINAHL) databases were searched for cross-sectional studies on the use of HM among HTN patients. Our review includes studies published in English up to the year 2023. After extracting and appraising the data from the studies, a meta-analysis was conducted using the Stata version 16.0 to estimate the pooled prevalence of HM use in patients with HTN (PROSPERO: CRD42023405537). The safety classification of the identified HM was done based on the existing scientific literature.
UNASSIGNED: This study analyzed 37 cross-sectional studies from 21 countries and found that 37.8% of HTN patients used HM to manage their health. The prevalence of HM use varied significantly based on publication year and geographical region. Among the 71 identified herbs, Allium sativum L., Hibiscus sabdariffa L., and Olea europaea L. were the most commonly used. However, four herbs were identified as contraindicated, 50 herbs required caution, and only 11 herbs were considered safe for use.
UNASSIGNED: The study highlights the potential risks of toxicities and adverse effects associated with HM use in the treatment of HTN. Ensuring patient safety involves using safe HMs in appropriate doses and avoiding contraindicated HMs. Future research should focus on identifying commonly used herbs, especially in resource-limited countries with poor HTN management, and additional clinical research is required to assess the toxicity and safety of commonly used HMs.

UNASSIGNED: Pulmonary edema is a rare complication occurring after naloxone administration, but the causal relationship remains insufficiently investigated. We aimed to determine the likelihood of naloxone as the causative agent in published cases of pulmonary edema.
UNASSIGNED: A literature search was conducted across multiple databases, utilizing database-specific search terms such as \"pulmonary edema/chemically induced\" and \"naloxone/adverse effects.\" Each case report was evaluated using the Naranjo scale, a standardized causality assessment algorithm.
UNASSIGNED: We identified 49 published case reports of pulmonary edema following naloxone administration. The median total dose of naloxone was 0.2 mg for patients presenting following a surgical procedure and 4 mg for out-of-hospital opioid overdoses. Based on the Naranjo scale, the majority of cases were classified as \"possible\" (n = 38) or \"probable\" (n = 11) adverse reactions, while no \"definite\" cases of naloxone-induced pulmonary edema were identified. Many patients were classified as \"possible\" due to limited patient information or other potential risks, such as fluid administration or airway obstruction. Forty-six of 49 patients survived (94 percent).
UNASSIGNED: Pulmonary edema may occur after both low and high doses of naloxone; however, low doses were primarily reported in the surgical population. Despite this complication, the majority of patients survived. Furthermore, no case report in our analysis was classified as a \"definite\" case of naloxone-induced pulmonary edema which limits the establishment of causality. Future studies should explore patient risk factors, including surgical versus outpatient setting and opioid-naïve versus opioid-tolerant for developing pulmonary edema and employ a causality assessment algorithm.
UNASSIGNED: These case reports suggest pulmonary edema can occur following naloxone administration, irrespective of dose. According to the Naranjo scale, there were no definite cases of naloxone-induced pulmonary edema. Overall, we suggest the benefits of naloxone administration outweigh the risks. Naloxone should be administered to treat opioid overdoses while monitoring for the development of pulmonary edema.