ABSTRACTChronic obstructive pulmonary disease (COPD) and aging both increase the risk of tuberculosis (TB), an important infectious disease in human. Exploring the burden and predictors of latent tuberculosis infection (LTBI) and treatment outcomes for older individuals with COPD is essential to guide LTBI intervention policy. We enrolled patients aged over 60 years with COPD between January 2021 and June 2023 for LTBI screening using interferon-gamma release assay (IGRA). LTBI treatment options included all World Health Organization (WHO)-recommended regimens. The final regimen was selected through shared decision-making between patients and their COPD physicians, leveraging the long-standing rapport being established. We investigated the prevalence of LTBI in this population, identified risk factors using logistic regression analysis, and evaluated treatment outcomes. A total of 810 COPD patients (mean: 72.8-years) underwent LTBI screening, with an IGRA-positive rate of 23.8%. IGRA positivity was correlated with smoking pack-years (adjusted odds ratio [aOR]: 1.02, p < 0.001), current smoking status (aOR 1.40, p = 0.030), COPD duration (aOR 1.10, p = 0.03), inhaled corticosteroid use (aOR 3.06, p < 0.001), and a cumulative equivalent dose of prednisolone exceeding 210 mg over 2 years (aOR 3.13, p < 0.001). Treatment was initiated in 150 patients (77.7%), predominantly with weekly rifapentine plus isoniazid (3HP) (60.7%). The overall completion rate was 82.0%, with adverse reactions being the primary reason for discontinuation. Our findings support that the LTBI intervention is recommended for older patients with COPD, especially those at higher risk, as nearly 25% of them have tuberculosis infection. The high treatment completion rate highlights the safety and feasibility of the WHO-recommended regimens.

Insomnia can be caused by various factors including lack of sleep, stress, sadness, hormonal changes, excessive caffeine, anxiety, mental health disorders, and medications. Treatments include finding the cause, improving sleep patterns, using behavioral therapy, and taking sleeping pills in most cases. However, the drugs often cause worse side effects than insomnia. This study compared the efficacy of initial agomelatine and clonazepam doses with cognitive behavioral therapy for insomnia (CBT-i) in moderate to severe insomnia patients.

This quasi-experiment study involved 230 moderate to severe insomnia patients with group A as clonazepam 0.25 mg and B as agomelatine 25 mg. CBT-i was received by both of the groups and the Insomnia Severity Index (ISI), Subjective Units of Distress Scale (SUDS) score, medication adherence, and Adverse Drug Reactions (ADRs) were followed for up to 24 weeks.

In the comparative analysis between and within groups, group B exhibited a significant reduction in ISI (p = 0.001) and SUDS (p = 0.001) scores at week 24 compared to group A. Overall, both groups demonstrated improved adherence. However, 12 patients in group A and 10 in group B experienced ADR, which included drowsiness, hypersalivation, diarrhea, maculopapular rash, and myotoxicity. The clonazepam-treated group showed reduced efficacy from week 12 onwards in the ISI and from week 16 in the SUDS median score, which was not observed in the agomelatine group.

The initial dose of agomelatine with CBT-i has a better impact on improving moderate to severe insomnia than the initial dose of clonazepam with CBT-i.

The true frequency and severity of myasthenia gravis (MG) exacerbation associated with the usage of fluoroquinolone and macrolide antibiotics remain unknown. We aimed to investigate the association between ciprofloxacin, levofloxacin, azithromycin, and MG exacerbation.

A retrospective review was performed on MG patients seen at a single institution between 2002 and 2022, who received ciprofloxacin, levofloxacin, or azithromycin. Amoxicillin usage was chosen for comparison. The strength of association between antibiotic usage and MG exacerbation was scored using the Adverse Drug Reactions Probability Scale. A mixed-effects logistic regression model was constructed to evaluate predictors of antibiotic-associated MG exacerbation (AAMGE).

365 patients had a total of 918 episodes of antibiotic usage (n = 339 for ciprofloxacin, n = 187 for levofloxacin, n = 392 for azithromycin). Frequencies of MG exacerbation following antibiotic use were: 8 (2.4%) for ciprofloxacin, 3 (1.6%) for levofloxacin, 6 (1.5%) for azithromycin, and 17 (1.9%) for all. Six patients had impending crisis/crisis, and 9 required rescue therapy. MG exacerbation was associated with MG-related hospitalization or ED visit in the preceding 6 months (p = 0.012), female sex (p = 0.023) and diabetes (p = 0.032). Infection was the most common confounder in exacerbations (88.2%). MG exacerbation was seen in 8/603 (1.3%) episodes of amoxicillin use, without a significant difference in frequencies of AAMGE among the four antibiotics (p = 0.68).

Usage of ciprofloxacin, levofloxacin, or azithromycin was associated with MG exacerbation in less than 2.5% of episodes of antibiotic use. Underlying infection may play a role in AAMGE. As AAMGE can be severe, decision-making regarding the use of these antibiotics should be individualized.

We conducted a study to estimate the incidence of adverse drug reactions (ADRs) in the drug-resistant tuberculosis (DR-TB) cohort in Kerala in 2020 and describe the characteristics of the reported ADRs.

A non-concurrent cohort study was conducted among all patients with DR-TB across 14 districts in Kerala from January 1, 2020 to December 31, 2020. We collected data on ADRs from patients, "Nikshay" web-portal, treatment cards, case sheets, and registers. We described ADRs by organ system, causality, severity, preventability, predictability, and seriousness of the reaction using standard tools.

Of the 364 persons initiated on treatment, 304 (83.5%) had at least one of the 28 listed adverse reactions, with an incidence of 27.6 ADR per 100 person-months of treatment. Gastrointestinal disorders had the highest incidence 365 per 1046 (35%). A total of 1001 of 1046 (95.7%) ADRs were non-predictable, and 405 of 1046 (39%) were definitely preventable. A total of 83 of 304 (27.3%) patients had severe ADR, and 56 of 304 (18.4%) had serious ADR. A total of 87 of 304 (28.6%) patients with ADR required interruption of the probable offending drug, with 64 of 87 (73.6%) temporary and 23 of 87 (26.4%) permanent interruptions.

Four-fifths of all patients on therapy had at least one of the 28 listed adverse reaction and one-fifth had serious ADR. ADRs can lead to treatment interruptions. Early detection and prompt management is essential for improving treatment outcomes in patients with DR-TB.

In 2017, reports of adverse drug reactions worldwide reached an estimated 35 million.Chemotherapeutic agents were one of the most often implicated pharmacological classes in inducing adverse drug reactions. Adverse drug reactions increase the overall expense and mortality. Adverse drug reactions increase morbidity, mortality, hospitalization rate and financial expenses. Therefore, this study intended to assess chemotherapy-related adverse drug reactions and associated factors among adult cancer patients.

A facility-based prospective observational study was conducted from July 2022 to October 2022 at Jimma Medical Center's oncology unit. A standard data collection tool (Naranjo's algorithm, modified Hartwig's severity scale, and modified Schumock-Thornton criteria) was used for assessment of causality, severity, and preventability of adverse reactions, respectively. Socio-demographic profile and any adverse drug reactions reported were collected separately. The data was collected by one pharmacist and two nurses after giving training. Data was entered into Epidata version 4.6.0 and analyzed by SPSS version 25. Bivariate and multivariable logistic regression was conducted to identify independent predictors of the pattern of adverse drug reaction occurrence. A P-value of 0.05 was taken as statistically significant.

Out of 154 patients enrolled in the study, 66.2% were female. The mean age of patients was 41.20 ± 13.54 years. From the total, 98 (63.6%) cases developed a total of 198 adverse drug reactions. Out of them, 59.2% were female. The most commonly encountered adverse drug reactions were nausea and vomiting (33.8%) and hair loss (29.3%). Most of the reactions were probable (61.1%) in causality, mild (66.2%) in severity, and not preventable (43.9%) in nature. Female sex (AOR = 1.054; 95% CI= (1.021-1.087); P = 0.001), number of chemotherapy treatments (AOR = 3.33; 95% CI= (1.301-8.52); P = 0.012), and elderly age (AOR = 3.065; 95% CI= (1.01-9.296); P = 0.048) were associated with occurrences of adverse drug reactions.

We can deduce from the data that adverse drug reactions are a significant concern for patients undergoing chemotherapy, with nearly two-thirds experiencing ADRs. The most common reactions are nausea and vomiting, which are mostly mild and probable. Age, gender, and the use of several chemotherapy drugs were associated with an increased risk of adverse drug reactions. Hence all concerned bodies should make an effort for early detection and take preventive measure of chemotherapy-related adverse drug reactions. Where feasible, use chemotherapy protocols with alower risk of ADRs. Evaluate dose adjustments for elderly patients. Implement protocols for risk assessment before initiating chemotherapy.

Hypersensitivity to antipsychotic drugs is one of the supportive features of dementia with Lewy bodies, and side effects to drugs other than antipsychotics are also known to occur frequently. We experienced a case of dementia with Lewy bodies in which hallucinations and delusions repeatedly appeared and disappeared after administration and discontinuation of mirogabalin and pregabalin.

The patient, a woman in her late 70s, developed hallucinations and delusional misidentification of places and persons immediately after receiving a prescription of mirogabalin (15 mg daily) for neuropathic pain. After discontinuation of mirogabalin, her hallucinatory delusions improved but remained. Mild dementia and mild parkinsonism were associated, cognitive fluctuations were evident, and dopamine-transporter scintigraphy showed bilateral striatal uptake reduction. Residual psychosis resolved with donepezil. Later, when the pain worsened, pregabalin (25 mg daily) was administered, and the psychosis recurred and resolved with discontinuation.

Although pregabalin-induced psychosis has been reported at higher doses (300-450 mg daily), it has not been reported at doses as low as those used in this patient. Gabapentinoids may cause psychosis in patients with dementia with Lewy bodies even at low doses, likely due to hypersensitivity to gabapentinoids in DLB.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, with a rising incidence in the elderly. BP is associated with multiple triggering factors, including drug exposure. However, evidence in this respect is limited, and the underlying immune mechanisms remain unknown. Our study aims to identify the role of specific drugs in BP pathogenesis using in vitro lymphocyte transformation tests (LTT) and in vivo patch testing, aiding in the differentiation between truly associated drugs and coincidental associations.

Thirty-three patients with suspected BP and no ongoing systemic treatment were enrolled. LTT and patch tests were conducted 3 months after diagnosis. BP disease activity was assessed using the Bullous Pemphigoid Disease Activity Index (BPDAI) at diagnosis and at follow-up visits at 3 and 6 months.

LTT results were positive in 60% of patients for dipeptidyl peptidase 4 inhibitors, loop diuretics, hydrochlorothiazide, levetiracetam, nivolumab, enalapril, and amlodipine. Patients showed a reduction in BPDAI over the study period, regardless of LTT results. Although limited by the low sample size, positive LTT patients showed a trend toward clinical improvement when the implicated drug was discontinued. Patch testing was positive in one patient, who also had a corresponding positive LTT.

Our findings demonstrate the existence of a potential role for certain drugs in BP pathogenesis, suggesting that these drugs may trigger the disease in genetically predisposed individuals. Although further studies are needed, LTT may serve as a useful and available tool in the management of BP patients in the future.

IntroductionThe combination nivolumab-relatlimab has demonstrated therapeutic benefits for patients with metastatic melanoma. However, its adverse effects can affect various organs, including the eye.Case reportWe present the case of an 80-year-old man who developed complete color blindness after the 2nd dose of nivolumab-relatlimab for advanced cutaneous melanoma. He also had significant blurry vision. Fundoscopy identified bilateral serous macular detachment. Ocular coherence tomography confirmed serous infiltration within the macula. After a thorough investigation, causality assessment linked this retinal effect to nivolumab-relatlimab (probable relationship via Naranjo criteria).Management and outcomeThe patient was treated with corticosteroids, intravenous immunoglobulin (IVIG), rituximab, and plasmapheresis, with improvement in blurry vision. However, he continued to experience persistent absence of color perception ("black and white vision") at a follow-up visit six months later.Discussion/conclusionFurther studies are necessary to understand the exact pathophysiology of this process. We hypothesize that it involves direct toxicity to the photoreceptors or retinal ganglion cells, leading to irreversible color vision loss. Effective strategies for preventing this significant, life-changing toxic effect of nivolumab-relatlimab should be sought.

Dysphagia, a well-recognised adverse effect in many different antipsychotics, is not a formally acknowledged side effect in zuclopenthixol. This case report describes a patient with known bipolar affective disorder who had been recently stabilised on zuclopenthixol decanoate and presented with sudden onset severe oropharyngeal dysphagia. Symptoms spontaneously resolved with the discontinuation of the medication, and this report explores the suggested underlying mechanisms from literature.

Systemic glucocorticoids are widely used in the treatment of various inflammatory and autoimmune conditions. This report describes the first known case of drug-induced hypesthesia following dexamethasone administration in a patient without prior neurological conditions.

A 38-year-old female patient presented with bothersome and intolerable tinnitus and was diagnosed with sudden sensorineural hearing loss. She was treated with dexamethasone (10 mg IVGTT once daily) for 6 days. On the 5th day of treatment, the patient began experiencing fatigue, followed by decreased sensitivity to pain, temperature, and touch, anhidrosis, and lack of satiety.

Drug-induced hypesthesia.

Dexamethasone was discontinued after completing the 6-day treatment course. The patient was then prescribed omeprazole and mecobalamin for supportive care.

The patient's sensory impairment began to resolve 3 days after stopping dexamethasone. Follow-up 1 week later confirmed complete recovery without recurrence of hypesthesia.

This case highlights the importance of monitoring patients for hypesthesia during dexamethasone therapy, even in the short term. Clinicians should be aware of this potential adverse effect and consider alternative treatments if necessary. Mecobalamin may be a supportive option for managing hypesthesia in such cases.

This study aimed to identify patterns of direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) use in hospitalized patients and to examine their association with in-hospital haemorrhagic complications and mortality.

An observational cross-sectional study was conducted among hospitalized patients ≥18 years from 2018 to 2022. Data on hospital discharges were obtained from the minimum data set and were matched with pharmacy records to identify patients treated with DOACs or VKAs. In-hospital haemorrhagic complications and mortality rates were calculated for study groups. Multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs), adjusting for age, sex and comorbidities. Analyses were stratified by medical and surgical profiles. Statistical significance was set at .05.

The study included 74 190 patients, with 4774 receiving DOACs and 1768 VKAs. During the study period, DOAC use increased by 45.11%. DOAC-treated patients had lower complication rates than those treated with VKAs (1.9 vs. 2.8%, respectively; P = .032). DOAC use was linked to a lower risk of haemorrhagic complications in surgical patients (OR = 0.65; 95%CI: 0.35-0.91), while in medical patients, the reduction in risk was not statistically significant (OR = 0.59; 95%CI: 0.33-1.10). No effect on mortality risk was observed among medical and surgical patients.

The increased use of DOACs among hospitalized patients showed a protective effect against haemorrhagic complications in surgical patients, supporting their increasing use in hospital settings.

Endoscopic procedures are essential for diagnosing and managing gastrointestinal conditions, often requiring sedation for patient comfort. Propofol is a common choice for outpatient sedation due to its rapid onset and predictable recovery time. Although propofol has an established safety profile, adverse drug reactions (ADRs) can still occur. This study investigated the prevalence and risk factors associated with ADRs related to nurse-administered propofol sedation during outpatient endoscopic procedures at a private hospital in Peru.

We conducted a retrospective study. The clinical records of 919 Peruvian patients who underwent endoscopic interventions under propofol sedation were reviewed. This study included patients between the ages of 18 and 69 years who had American Society of Anesthesiologists (ASA) physical status classification scores of I-III and who were hemodynamically stable with an oxygen saturation (SO2) > 90% before the procedure. Sedation was nurse-administered using standardized protocols. ADR data, including severity and causality assessment data, were collected. Data were collected and analyzed by SPSS, Inc., and the statistical significance was calculated at the p < 0.05 level.

A total of 693 patients were included in the study, 30.9% of whom experienced at least one ADR, predominantly cardiovascular or respiratory events such as hypotension and hypoxia, with causality scores classified as probable or definitive. Among the ADRs, 35.8% (n = 87) were moderately severe, and 64.2% (n = 143) were mildly severe. There were no reports of any serious adverse events. An ASA class III status (p = 0.048, PR adjusted (PRa) = 1.73, 95% CI: 1.01-2.99) and a procedure time of more than 20 min (p < 0.0001, PRa = 2.05, 95% CI: 1.53-2.73) were significant risk factors for ADR occurrence. Patients with ADRs had longer recovery times than did those without ADRs (22 min ± 22.5 vs. 14 min ± 8, respectively; p < 0.001).

In our work, moderate propofol sedation administered by trained nursing staff to outpatients undergoing interventional endoscopic procedures was generally safe but not free from risks. Vital parameters should be monitored regularly during long-term interventions and when patients are classified as ASA III.

To investigate the incidence and clinical characteristics of drug-induced movement disorders(DIMDs)in a large group of hospitalized patients.

A retrospective study was conducted among hospitalized patients in 2022, utilizing the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II). After the operation and manual selection, DIMDs cases were identified for analysis of incidence, associated drugs, and clinical characteristics.

Among 102,914 hospitalized patients, 504 cases were identified as DIMDs, with an incidence of 0.49%. There were more males than females.Most patients were over 65 years old.A total of 158 associated drugs across 15 classes were identified, with the top three classes being antibiotics(12.10%), antiepileptics(8.13%), and calcium channel blockers (7.14%).The top three drugs were sodium valproate(1.67%),meropenem(0.58%)and pregabalin (0.55%).The clinical manifestations were primarily shakiness, tremor and tic. Different manifestations are difficult to distinguish.It's necessary to make a thorough record and consult specialists.

For the first time, this study found that the incidence of DIMDs in hospitalized patients in general hospitals was 0.49%, occurs occasionally. Clinicians should pay close attention to the manifestations and identification of involuntary movements. Enhanced monitoring is recommended when using valproate, meropenem and pregabalin.

Andexanet alfa, a Food and Drug Administration (FDA)-approved antidote for apixaban and rivaroxaban, is used to manage life-threatening or uncontrolled bleeding. In patients undergoing cardiopulmonary bypass (CPB), preoperative exposure to andexanet can cause severe heparin resistance, necessitating effective mitigation strategies. A comprehensive review of such strategies remains lacking.

This study aimed to systematically review and characterize cases of andexanet-induced heparin resistance in patients undergoing CPB and to evaluate management strategies.

A systematic search was conducted across multiple databases via the Ovid interface, Cochrane Central Register of Controlled Trials, and the FDA Adverse Event Reporting System. Quality appraisal was performed using a validated instrument for case reports and series describing drug-induced adverse events.

Fourteen discrete patient cases met inclusion criteria. After andexanet administration, the mean initial activated clotting time (ACT) was 199.5 seconds, falling short of a target of ≥400 seconds despite additional heparin dosing (mean total, 1123 U/kg). Moreover, 35.7% of all cases involved thrombus formation in the reservoir, 2 of which required a circuit replacement. Antithrombin (AT) concentrate was administered to 75% of those received an adjunct therapy. A prophylactic AT use (mean, 49.9 IU/kg) resulted in an ACT over 400 seconds, while its effects in low dose after the occurrence of thrombosis varied on ACT values. Nafamostat mesylate was used in some cases reported from Japan.

Heparin resistance following andexanet exposure poses significant procoagulant risk during CPB. Pre-emptive high-dose AT therapy may improve ACT values. Further studies are needed to understand the mechanisms and optimize management of this condition.

Although hyperlipidemia is a well-known adverse event associated with lorlatinib treatment, lorlatinib-associated hyperglycemia is less common but can be potentially life-threatening. We present the case of a 65-year-old male patient with anaplastic lymphoma kinase-positive lung cancer and preexisting type 2 diabetes mellitus who developed diabetic ketoacidosis (DKA) after switching from alectinib to lorlatinib. After initiating lorlatinib treatment, the patient's glycemic control deteriorated rapidly, with the glycated hemoglobin levels increasing from 6% to 11.5% within three months. The patient was admitted and received intensive insulin therapy along with temporary discontinuation of lorlatinib, which successfully resolved DKA. After a 2-week interruption, lorlatinib was resumed at a reduced dose with satisfactory glycemic control. This case highlights the importance of vigilant glucose monitoring for patients receiving lorlatinib, especially those with preexisting diabetes, to prevent life-threatening complications such as DKA.

Morbilliform eruptions, which are a clinical reaction pattern characterized by erythematous macules and papules coalescing into patches that cover most of the skin surface, are one of the most common cutaneous findings in the inpatient setting. In the hospital setting, most causes are benign and due to low-risk drug exanthems; however, morbilliform eruptions may also be a sign of high-risk diseases, including Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, acute generalized exanthematous pustulosis, and graft-versus-host disease. Proper identification of the etiology and risk stratification of a morbilliform eruption is critical to ensure proper management and optimize patient outcomes. In this review, we discuss the key features that differentiate high-risk from low-risk morbilliform eruptions, as well as specific characteristics that differentiate the different high-risk eruptions. Additionally, we offer a clinical algorithm that may be applied in the management of a patient who presents with a morbilliform rash.

Transient myoclonic state (TMS) is a rare type of myoclonic jerks occurring predominantly in the upper extremities involving the head and commonly associated with asterixis. The present study performed a systematic review of published articles on this condition. For this purpose, six databases were searched by two reviewers to identify reports on TMS published online until November, 2024. A total of 17 reports containing 78 cases were found. Almost all the reports were from Japan, apart from one case reported in the USA. The mean age of the patients was 75.67 years (standard deviation, 5.8 years) and the median age was 75 years (range, 54 to 84 years). Sex was reported in 74 reports, and 60.8% of the patients were males. A precipitating factor, such as an infectious disease or the introduction of a new medication was observed in 24 cases (30.7%). All individuals achieved full recovery; however, 53 patients (67.9%) required benzodiazepine therapy, while the remaining individuals improved spontaneously. In summary, the present systematic review demonstrates that TMS is a rare condition, and is mainly encountered in Japan by unknown factors. There are likely genetic and environmental factors involved in its development; however, no specific geolocation related to the occurrence of TMS in Japan was found. It has a benign course and usually improves with the prescription of benzodiazepines. Management strategies include ensuring adequate multidisciplinary care coordination, as well as educating patients and their families about TMS. Future studies are required to describe the cases of TMS, including videos of the phenomenology. It is also recommended to perform whole genome sequencing analysis in patients with TMS.

Acne vulgaris is a common inflammatory condition that is often treated by dermatologists with isotretinoin. Isotretinoin has a number of effects on inflammatory pathways, with clear efficacy in managing acne vulgaris. There are also well-documented side effects of isotretinoin, including hyperlipidemia; however, the overall cardiovascular risk is unclear. This systematic review revealed low evidence for major adverse cardiovascular events associated with the use of isotretinoin in acne patients. Despite this low evidence, rare events may be associated and should still be considered when using isotretinoin in acne patients.

The frequency of cefaclor-induced immediate hypersensitivity reactions has increased in Korea. Skin prick tests (SPTs) and intradermal tests (IDTs) using cephalosporins are not as well validated as those using penicillin. Limited data are available regarding the diagnostic value of SPTs and IDTs for cefaclor-induced immediate hypersensitivity reactions.

To compare the clinical utility of the SPT and IDT with that of the ImmunoCAP test in patients with cefaclor-induced immediate hypersensitivity reactions.

We conducted a retrospective analysis of participants from a tertiary hospital in Korea with a history of suspected immediate hypersensitivity reaction to cefaclor who had undergone SPT, IDT, and ImmunoCAP.

A total of 155 patients with a diagnosis of cefaclor-induced immediate hypersensitivity reactions were included in the analysis. Of those, 81 patients tested positive for both the SPT/IDT and the ImmunoCAP test. Sixty patients were positive for the SPT/IDT but negative for the ImmunoCAP test. Seven patients tested positive only for the ImmunoCAP test. Positivity for SPT/IDT and that for SPT were significantly higher in cases of anaphylaxis compared with urticaria; however, ImmunoCAP positivity did not differ based on the severity of the reaction.

Skin prick tests and IDTs are more sensitive than ImmunoCAP for diagnosing cefaclor-induced immediate hypersensitivity reactions, particularly in cases of anaphylaxis. The positivity of SPT/IDT varies depending on the severity of the hypersensitivity reaction. Therefore, SPT/IDT should be considered for diagnosing cefaclor-induced anaphylaxis.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD) with a low incidence of adverse effects. However, bradycardia is not commonly recognized as an adverse effect of rTMS. In this case report, we present the first documented instance of a patient with MDD and premature ventricular contractions (PVCs) who developed severe bradycardia following rTMS treatment.

We report the case of a 46-year-old Chinese woman with a 7-year history of MDD and a 6-year history of PVCs. She had been taking paroxetine, tandospirone citrate, and metoprolol long-term without experiencing bradycardia. After initiating rTMS treatment, she developed severe bradycardia. Even after discontinuing metoprolol, the severe bradycardia persisted for several days. Notably, the severe bradycardia disappeared one day after pausing rTMS therapy. When rTMS was resumed, the bradycardia reoccurred and subsequently resolved again upon pausing the rTMS treatment.

The influence of rTMS on heart rate (HR) is likely mediated through the autonomic nervous system (ANS). Currently, severe arrhythmias are not widely recognized as adverse effects of rTMS. While the exact mechanisms by which rTMS affects the cardiovascular system remain unclear, this case underscores the necessity for caution when using rTMS to treat psychiatric patients with arrhythmias.

Activating mutations of FMS-like Tyrosine Kinase 3 (FLT3) occur in a subset of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Gilteritinib, an oral FLT3 inhibitor approved for the treatment of relapsed or refractory AML, has been shown to improve survival and remission rates compared with salvage chemotherapy. This case report presents two patients initiated on gilteritinib for relapsed AML who developed new onset left ventricular systolic dysfunction. After ruling out other common etiologies, gilteritinib was discontinued due to concern for cancer therapy-related cardiac dysfunction with subsequent improvement in ejection fraction. These cases demonstrate a rare but serious adverse effect of gilteritinib, cardiotoxicity manifested as left ventricular systolic dysfunction, for which more studies are needed to elucidate the underlying pathophysiology.

The glucagon-like peptide-1 receptor agonist (GLP-1RA) class of medications are widely prescribed for management of diabetes mellitus as well as obesity or weight management. Although there have been rare reports of skin hypersensitivity associated with GLP-1RA medications, no published reports have documented allodynia or skin pain to the touch.

We report 4 cases of allodynia associated with dose escalation of the GLP-1RA medication semaglutide. Each patient was prescribed semaglutide for management of obesity and developed symptoms of allodynia with the 2.4-mg subcutaneous once-weekly dose. Therapy was stopped in 2 patients, both of whom had resolution of symptoms. Two patients opted to continue semaglutide despite the adverse effect, with one experiencing resolution after 4 months. No pharmacological mechanism was identified for this unique adverse drug reaction. There was a clear temporal and dose-response relationship in each of the 4 cases.

The 4 cases presented had scores of 5 or 6 (probable) on the Naranjo scale. It is not known whether this is a class effect of the GLP-1RA medications or if the adverse effect will consistently resolve or improve with continuation.

Liver injury in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is a multifaceted disorder, lacking cohort homogeneity due to a variety of potential causes, including drugs, arsenic and other heavy metals, glyphosate, infections, and ultraviolet radiation. The goals of this review were (1) to analyze the role of diagnostic algorithms in assessing causality for potential culprits involved in the development of liver injury associated with immune-mediated SJS and TEN, which represent immune-based variant disorders within a continuous spectrum. Milder forms are classified as SJS or SJS/TEN overlap, while TEN is known as the most serious form; and (2) to interpret the findings that allow for the characterization of the different types of these disorders. The manuscript is based on an extensive literature search for single case reports, case cohorts, and review articles. Search terms included: Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and specific diagnostic algorithms such as the Roussel Uclaf Causality Assessment Method (RUCAM) and the Algorithm of Drug Causality for Epidermal Necrolysis (ALDEN). For the purpose of basic feature description, the uniform term SJS/TEN is used in the current analysis. SJS/TEN presents with five different cohort types: SJS/TEN type (1), which refers to a cohort of SJS/TEN caused by drugs, as assessed by both ALDEN and RUCAM; type (2), representing SJS/TEN due to drugs and assessed by ALDEN only, but not by RUCAM; type (3), which includes a cohort of SJS/TEN caused by drugs, assessed by non-ALDEN and non-RUCAM tools; type (4), which focuses on a cohort of SJS/TEN caused by non-drug culprits, assessed by various tools; and type (5), which considers a cohort of SJS/TEN caused by unknown culprits. Using this new SJS/TEN typology will help better characterize individual features, personalize treatment, and clarify pathogenetic specifics for each of the five disease types. This new SJS/TEN typology provides clarity by replacing issues of inhomogeneity with cohort homogeneity.

Voriconazole is a widely used antifungal agent for invasive aspergillosis; however, hepatotoxicity is a significant concern. While hepatocellular toxicity is well documented, cholestatic liver injury remains relatively rare. We report a case of voriconazole-induced cholestatic hepatotoxicity in a patient with fungal pneumonia. The patient developed elevated alkaline phosphatase and gamma-glutamyl transpeptidase levels beyond the therapeutic range. Voriconazole was discontinued, and the patient was switched to posaconazole, leading to a decline in cholestatic markers. This report underscores the importance of therapeutic drug monitoring and highlights posaconazole as a safer alternative in patients experiencing voriconazole-induced hepatotoxicity.

The benefit of high-dose trimethoprim/sulfamethoxazole (trimethoprim component ≥ 8 mg/kg/day) treatment for Stenotrophomonas maltophilia infections remains unclear. We aimed to evaluate the effect of high-dose trimethoprim/sulfamethoxazole treatment on outcomes in patients with S. maltophilia bacteraemia.

We conducted a single-centre retrospective cohort study (2004-23) that included patients treated with trimethoprim/sulfamethoxazole for monomicrobial S. maltophilia bacteraemia. The patients were categorized into two groups based on the trimethoprim/sulfamethoxazole dose: high-dose (trimethoprim component ≥ 8 mg/kg/day) and low-dose (trimethoprim component < 8 mg/kg/day) groups for comparison. The primary endpoint was 30-day mortality. Adverse drug events between groups were also compared. Multivariable logistic regression and inverse probability of treatment weighting (IPTW) analysis were performed.

A total of 143 patients treated with trimethoprim/sulfamethoxazole for S. maltophilia bacteraemia were included: 41 (28.7%) received the high-dose regimen, and 102 (71.3%) received the low-dose regimen. There was no significant difference in 30-day mortality between the high- and low-dose group (39.0% versus 26.5%; P = 0.139). Multivariable regression revealed that high-dose trimethoprim/sulfamethoxazole therapy was not associated with mortality (adjusted OR 1.96, 95% CI 0.75-5.10; P = 0.167) after adjustment. The IPTW-adjusted regression yielded consistent results. More adverse drug events were reported in the high-dose group (31.7% versus 12.7%, P = 0.008).

High-dose trimethoprim/sulfamethoxazole for S. maltophilia bacteraemia was not associated with improved outcomes while more frequent adverse drug events were observed. The sample size and retrospective design limit the study's conclusions. Future studies that address these limitations are needed to confirm the results.

Drug-induced liver injury (DILI) is an underrecognized cause of hepatic disease in dogs and cats. Successful identification of cases requires an initial suspicion by the practitioner, a thorough drug exposure history, and knowledge of the toxic potential for common veterinary drugs. This article reviews the pathogenesis, classification, and diagnosis of DILI in small animals. It also discusses the clinical presentation, prevalence, and outcomes of DILI for several drugs important in veterinary medicine including azathioprine, azole antifungals, carprofen, diazepam, doxycycline, lomustine, methimazole, phenobarbital, rifampin, sulfonamide antibiotics, and zonisamide, as well as the toxic potential for nutraceuticals and herbal preparations.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that typically presents with ocular symptoms. Isolated bulbar symptoms, such as dysphagia and dysarthria, are rare, and most commonly seen in men with late-onset MG. We report one such rare case of MG in an 82-year-old male presenting with progressive bulbar weakness, seemingly triggered by levofloxacin use.

An 82-year-old male with multiple comorbidities presented with progressive weakness, dysphagia, and drooling following levofloxacin therapy. Examination revealed neck drop, weak lower facial muscles, and dysarthria. Initial neuroimaging and labs were inconclusive. Neurology initiated pyridostigmine with rapid improvement. Elevated acetylcholine receptor antibodies confirmed MG. He was started on efgartigimod alfa in the outpatient setting with improvement in MG composite scores.

Atypical bulbar MG can mimic other neurologic disorders and is prone to delayed diagnosis, especially in the elderly. Clinicians should maintain a high index of suspicion, particularly when symptoms worsen after medication exposures like fluoroquinolones. Early diagnosis and appropriate treatment can significantly improve outcomes and quality of life.

Levofloxacin can exacerbate or unmask myasthenia gravis.

Tirzepatide is one of the commonly used combined glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonists for weight loss in recent years. There are significant advantages of these medications for weight reduction, improved glycaemic control and cardiorenal benefits. However, these medications come with serious adverse events and need closer monitoring once they are initiated.

We present a case of a 35-year-old female with no comorbidities taking tirzepatide for weight loss. She developed severe rhabdomyolysis that required hospitalisation; muscle biopsy revealed necrotising myopathy. Her rhabdomyolysis resolved after stopping tirzepatide and conservative management with intravenous fluids. Since no other contributing factor could be identified, we believe tirzepatide may have increased her risk of rhabdomyolysis.

In patients presenting with rhabdomyolysis, consideration should be given to GLP-1 agonists as a potential contributing factor for the development of rhabdomyolysis.

Clinicians need to be aware of unusual side effects of glucagon-like peptide-1 (GLP-1) agonists like rare occurrence of rhabdomyolysis potentially associated with the use of tirzepatide.Risks versus benefits of these medications should be discussed in detail with patients before prescribing.Close patient follow-up and monitoring for adverse events is necessary, especially after prescribing relatively newer medications such as GLP-1 agonists with evolving knowledge of adverse event profile.

The military's approach to medication use often evolves in response to operational issues that have the potential to impact the medical readiness and combat effectiveness of active duty service members (ADSMs). Historically, medications have been considered problematic because they serve as surrogate markers for deployment limiting health conditions or due to factors that make sustainment challenging in military/austere environments. This study aims to identify key concepts that capture the aspects of a medication that make it problematic in ADSMs. The goal of this effort would be to inform a future policy and establish criteria for Problematic Medications in Active Duty Servicemembers (ProMADS) to enhance the readiness and deployability of ADSMs.

Concepts of ProMADS were elicited from 8 key informants (KIs). Key informants included care providers and care recipients from the Army, Navy, Air Force, and Defense Health Agency. Semi-structured interviews were conducted, and a phenomenological approach was used to summarize KI perspectives, and thematic analysis identified core elements and sub-elements.

Five core elements were identified: (1) Adverse cognitive or behavioral effects, (2) sustainment issues, (3) controlled substance compliance and risk mitigation, (4) medication-related hemostasis interference, and (5) combat-readiness inhibitors. Key sub-concepts were related to whether a medication might impact cognition, cause sedation, have complex monitoring requirements (e.g., laboratory, adverse drug reactions, etc.), is temperature sensitive, or impacts the functioning of the immune system.

This study generated core medication-related concepts and sub-concepts that KIs believe make a medication innately problematic among ADSMs. These findings can guide consensus-driven efforts to identify ProMADS which would enable Military Departments and Combat Support Agencies to create programs that improve lethality, warfighting, and readiness by optimizing medication use.

This case report presents the first documented instance of vaginal candidiasis linked to the intake of a hair, skin, and nails supplement.

A 64-year-old Caucasian female patient, with a history of chronic kidney disease and multiple comorbidities, developed symptoms of vaginal yeast infection after beginning the supplement. The adverse event was evaluated using the Naranjo Adverse Drug Reaction Probability Scale, scoring a 5, indicating a probable association. Despite extensive literature searches, no similar cases were found, suggesting this might be a unique reaction. This report highlights potential safety concerns with dietary supplements, particularly those not regulated by the Food and Drug Administration, underscoring the need for further investigation into their adverse effects.

The case emphasizes the importance of considering dietary supplements as potential contributors to adverse health events, especially in patients with complex medical histories.

In patients with hematologic malignancies, the combination of triazole antifungals and vincristine can lead to severe neurological toxicity. We attempted to assess the adverse events (AEs) associated with these interactions, particularly ileus.

We retrieved AEs data from FAERS database (2004-2023) focusing on the combination of four triazoles (fluconazole, itraconazole, voriconazole, posaconazole) with vincristine. Case reports of AEs were collected for retrospective analysis up to 31 December 2023.

The FAERS database indicated that neurological and gastrointestinal systems were most commonly involved systems when combined use triazole antifungals and vincristine, with ileus being the most frequently reported AE. The highest signal strengths for ileus were with itraconazole. AEs associated with concomitant use of triazole antifungal drugs and vincristine were identified through retrospective analysis of 42 clinical case reports, of which itraconazole, posaconazole, and voriconazole were involved in 66.7%, 28.6%, and 4.8% of cases, respectively. Patients who received the two-drug combination experienced AEs within one month in 88.1% of cases. Almost all patients improved within one month after discontinuing or switching antifungal drugs.

Ileus is the most common AE associated with the combination of triazole antifungals and vincristine, with itraconazole showing the highest risk.

Acute pancreatitis is an inflammatory condition of the pancreas that can result from various aetiologies, one of them being drug-induced pancreatitis, a relatively rare cause. Drug-induced pancreatitis should be considered in patients presenting with epigastric pain, elevated pancreatic enzymes, and imaging findings consistent with acute pancreatitis, in the absence of any common precipitants such as alcohol, gallstones, trauma. We report a case of acute pancreatitis following the initiation of baclofen therapy, with no other identifiable risk factors. A probable drug adverse reaction was established through the Naranjo Adverse Drug Reaction Probability Scale. This case highlights the need for physicians to consider baclofen as a potential cause of acute pancreatitis.

Given the patient's presentation following baclofen initiation and absence of other identifiable causes, this case suggests a probable association between baclofen and acute pancreatitis.Physicians should recognize the potential of baclofen to cause this inflammation when prescribing it and consider it as a differential diagnosis in cases of unexplained acute pancreatitis.

Ritonavir-boosted nirmatrelvir (Paxlovid) is a treatment for COVID-19. However, ritonavir, a cytochrome P450 (CYP) CYP3A4 inhibitor, poses a risk of significant drug-drug interactions. In our case, coprescribed nirmatrelvir-ritonavir and verapamil, with concomitant acute kidney injury, resulted in complete heart block and shock. Following fluid resuscitation, blood pressure support with norepinephrine, and calcium therapy for verapamil toxicity, the patient recovered and was discharged home in normal sinus rhythm. To our knowledge, only 2 cases with this drug-drug interaction have been documented, making this a rare, but serious interaction poorly described in the literature. Understanding the pharmacokinetic relationship between these 2 medications and the risks of coprescribing them is crucial for both diagnosing toxicity and reducing preventable morbidity and mortality.

Levodopa is competitively inhibited by amino acids for absorption across the intestinal wall and blood-brain barrier. An acute withdrawal of levodopa increases the risk of Parkinsonism-hyperpyrexia syndrome, a life-threatening condition characterized by muscular rigidity, mental status changes, hyperthermia, and autonomic instability. This report discusses the case of a patient with Parkinson's disease who was critically ill who developed Parkinsonism-hyperpyrexia syndrome while receiving enteral and parenteral nutrition support. Clinicians should be aware of this potential drug-nutrient interaction when prescribing nutrition support to patients taking levodopa.