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.

Immune-related adverse events typically occur during the early phases of immune checkpoint inhibitor therapy. However, late-onset immune-related adverse events can still arise long after the immune checkpoint inhibitor therapy has ended. Immune checkpoint inhibitor-related pneumonitis warrants special attention for risk assessment and early detection due to its potential for serious outcomes, including hospitalization and death. Despite its rarity, late-onset immune checkpoint inhibitor-related pneumonitis should be considered in the differential diagnosis for dyspnea in patients with a history of immune checkpoint inhibitor therapy to prevent morbidity and mortality. In this case report, we present a case of an 84-year-old female patient suffering from locally advanced triple-negative breast cancer and late-onset immune checkpoint inhibitor-related pneumonitis requiring hospitalization 104 days after the last cycle of pembrolizumab. Following successful treatment of late-onset immune checkpoint inhibitor-related pneumonitis with corticosteroids, a recurrence of immune checkpoint inhibitor-related pneumonitis occurred a month later. Corticosteroid therapy was reinitiated, gradually tapered after radiological improvement, and eventually discontinued. The patient remains in remission from breast cancer. For patients with a history of immune checkpoint inhibitor therapy, medical vigilance, accurate diagnosis, and timely management of late-onset immune checkpoint inhibitor-related pneumonitis are crucial.

Effective hypertension management requires medication adherence to prevent complications. However, adverse drug reactions (ADRs) can undermine adherence and negatively affect patients' quality of life. Limited research has explored the association between ADRs, medication adherence, and health-related quality of life (HRQoL) in individuals with hypertension.

To investigate the association between ADRs, medication adherence, and HRQoL among patients with hypertension.

A cross-sectional study using telephone interviews and medical record reviews was conducted in 11 primary care facilities in Indonesia. The causality of reported ADRs was assessed using the Naranjo algorithm, validated by a panel of experts in pharmacy practice and medication safety. The severity of ADRs was classified using the Hartwig scale. Adherence to antihypertensive drugs was estimated using the Medication Adherence Report Scale-5 (MARS-5). The EuroQoL EQ-5D-5L was used to measure HRQoL. The association between ADRs and medication adherence was assessed using multivariate logistic regression, while the association with HRQoL was evaluated through the Tobit regression model.

A total of 507 patients were included in this study. We found that 20.32% (n = 103) of the patients experienced ADRs, with the most commonly reported ADRs being polyuria and urgency, gastrointestinal symptoms, leg swelling, dizziness/hypotension, palpitations, and dry cough. The majority experienced mild ADRs (n = 75, 72.82%), while 27.18% (n = 28) had reactions of moderate severity. Experiencing ADRs was associated with reduced medication adherence (adjusted odds ratio (OR) 7.15, 95% CI 4.07-12.55) and decreased HRQoL (coefficient: - 0.037).

Patients experiencing ADRs were seven times more likely to be non-adherent to their medication regimen and reported a reduced quality of life compared to those without ADRs, placing them at a higher risk of suboptimal treatment outcomes. This finding highlights the need for additional monitoring and education for patients affected by ADRs, particularly through more frequent clinical and laboratory assessments, timely management of ADRs, and personalized education on the importance of adherence to prevent hypertension-related complications.

The objective of this project was to develop a standardized list of renally eliminated and potentially nephrotoxic drugs that will help inform initiatives to improve medication safety. Several available lists of medications from the published literature including original research articles and reviews, and from regulatory agencies, tertiary references, and clinical decision support systems were compiled, consolidated, and compared. Only systemically administered medications were included. Medication combinations were included if at least 1 active ingredient was considered renally dosed or potentially nephrotoxic. The medication list was reviewed for completeness and clinical appropriateness by a multidisciplinary team of individuals with expertise in critical care, nephrology, and pharmacy. An initial list of renally dosed and nephrotoxic drugs was created. After reconciliation and consensus from clinical experts, a standardized list of 681 drugs is proposed. The proposed evidence-based standardized list of renally dosed and potentially nephrotoxic drugs will be useful to harmonize epidemiologic and medication quality improvement studies. In addition, the list can be used for clinical purposes with surveillance in nephrotoxin stewardship programs. We suggest an iterative re-evaluation of the list with emerging literature and new medications on an approximately annual basis.

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.

Dasatinib is an effective agent in the treatment of bcr-abl positive acute lymphoblastic leukemia and chronic myeloid leukemia cases. Various skin reactions may occur when tyrosine kinase inhibitors are used. The severity of side effects increases in phototoxic reactions with sunlight. In this case, a phototoxic rash that developed in a 78-year-old bcr-abl positive acute lymphoblastic leukemia patient is presented. This case supports that phototoxic reactions may occur with dasatinib and emphasizes that clinicians should be alert for this side effect.

Antiphospholipid antibody syndrome (APS) may rarely present with isolated thrombocytopenia that may be diagnosed and treated as immune thrombocytopenic purpura. A 32-year-old woman was given eltrombopag (a thrombopoietin receptor agonist) to treat presumed immune thrombocytopenic purpura. She developed catastrophic APS, with multiple ischaemic infarcts, microvascular coronary thrombosis and digital gangrene. She improved after stopping eltrombopag and starting immunotherapy (corticosteroids, intravenous immunoglobulin and rituximab) but was left with significant neurological morbidity.

Interstitial pneumonitis is a potentially fatal complication of cancer-related therapy. However, data regarding the risk factors, prognosis and safety and benefit of rechallenge treatment are scarce.

Patients diagnosed with pancreatic cancer were retrospectively enrolled, and those with pneumonitis were identified. We investigated the incidence and etiology of pneumonitis, potential risk factors, and impact of treatment rechallenge on clinical outcomes.

A total of 809 patients were diagnosed with pancreatic cancer, among whom 62 (7.7%) were diagnosed with interstitial pneumonitis. Risk factors identified through competing risk analysis included nab-paclitaxel, gemcitabine, erlotinib, and previous lung diseases such as pre-existing ILD, asthma, chronic obstructive pulmonary disease, tuberculosis, primary lung cancer, metastasis, or pneumonia. Among these patients, 33 experienced acute respiratory distress syndrome, resulting in 15 deaths during pneumonitis episodes. After rechallenge therapy in 33 patients, pneumonitis recurred in 3 (9%). The median overall survival was longer in patients with pneumonitis than in those without. Subgroup analysis further revealed that overall survival was significantly better in the rechallenge group.

Most cases of pneumonitis are not directly induced by cancer therapy. Therefore, treatment rechallenge is considered a reasonable approach, potentially resulting in improved survival outcomes.

The burden of substandard antibiotics is high in low-middle income countries including Malawi. These poor-quality antibiotics may cause deleterious effects on patients and promote drug resistance. We assessed the quality of antibiotics and the associated clinical outcomes among hospitalized patients in southern Malawi.

A cross-sectional study involving review of retrospective records was conducted among hospitalized adult patients at Zomba central, Machinga and Nsanje district hospitals in October 2022 and January 2024. Trained pharmacy personnel recorded the parenteral antibiotics that were issued to the medical wards. We used these records for matching and sampling of the administered medicine batches to the patient files. In total, we reviewed 224 patient management files for eligible patients, aiming to assess the patient recovery and the occurrence of adverse drug reactions (ADRs) using a global trigger tool. We collected nine medicine samples of ceftriaxone and benzylpenicillin which were administered to these patients and subjected them to tests for the content of active pharmaceutical ingredients using methods adapted from the United States Pharmacopeia. For each sample, we collected at least ten dosage units and used Agilent® 1120 High Performance Liquid Chromatography for quality analysis.

Of the 224 reviewed files, ADRs occurred in 18.3% % (n = 41) of patients while 12.05% (n = 27) did not recover from their illness. One benzylpenicillin sample was found out of specifications with only 61.8% of declared amount of active ingredients. Among patients who received benzylpenicillin with optimal API content, 15.8% experienced ADRs while 10.5% failed to recover from illness. For patients who received benzylpenicillin containing lower than required amount of API, only 7.1% experienced an ADR while 14.3% failed to recover from illness. These differences were, however, not statistically significant. Patient outcomes were significantly associated with the patient's age and Charlson comorbidity index (CCI), p < 0.05.

The present findings did not reveal statistically significant differences in patient outcomes based on the assessed medicine quality. Therefore, we recommend a larger prospective study to further validate these results and encourage stakeholders to be more vigilant on the quality of antibiotic medicines, as this is a crucial measure for improving clinical outcomes and preventing antibiotic resistance in Malawi.

Priapism is a urologic emergency that is defined as a prolonged erection in the absence of sexual stimulation. Ischemic priapism is the most common form and is characterized by low arterial blood flow and absent venous outflow. Some potential triggers of ischemic priapism include malignancy, sickle cell disease, illicit drug use, and certain medications. Prazosin, an alpha-1 adrenergic antagonist, is used for the treatment of chronic hypertension, benign prostate hyperplasia, and (post-traumatic stress disorder (PTSD) related nightmares. The alpha-adrenergic antagonistic effect of prazosin results in decreased venous blood flow, including to the smooth muscle tissue located within the corpus cavernosum. Slowly titrating prazosin allows the body to adapt to the vasodilatory effects of the medication. Without titration, a dysregulation in blood flow to the penile vasculature can result in prolonged erection. We report a case of priapism that resulted due to rapid titration of prazosin.

Introduction: Dicyclomine is an antimuscarinic agent approved for treatment of irritable bowel syndrome-associated abdominal pain. Intravenous (IV) administration should be avoided due to potential for thrombosis, but real-world evidence is generally lacking. This case report presents a thrombotic complication associated with inadvertent IV administration of dicyclomine. Case: A 43-year-old man with chronic colitis and recurrent Clostridioides difficile infections presented to a community hospital complaining of moderate-severe suprapubic abdominal pain and nausea/vomiting/diarrhea for 5 days. Computed tomography showed descending colonic wall thickening and proctitis, without perforation or abscess. Initial orders consisted of ketorolac 15 mg IV and dicyclomine 20 mg intramuscularly. The nurse inadvertently mixed ketorolac and dicyclomine in the same syringe and administered them simultaneously. Ultrasound subsequently confirmed a non-occlusive right axillary vein thrombosis and an occlusive superficial right basilic vein thrombosis. The patient was started on therapeutic enoxaparin subcutaneously. He was enrolled in a patient assistance program and was discharged on rivaroxaban dispensed from the hospital's outpatient pharmacy. Discussion: Dicyclomine is more selective for the M1 and M3 receptors, and the M3 receptor causes nitric oxide activation. As dicyclomine was unintentionally administered IV, the inhibition of nitric oxide could potentially lead to clotting. The simultaneous administration of ketorolac promoted a pro-thrombotic state, via cyclo-oxygenase-2-mediation vasoconstriction. Naranjo algorithm assessment indicated "possible" potential for a drug-induced adverse event. The pharmacist submitted an adverse drug event report and revisions to barcode medication administration were implemented. Conclusion: Thrombotic complications are possible following IV dicyclomine administration and pharmacy personnel must implement safeguards to prevent inadvertent administration.

To describe the clinical features of a case series of patients with Vogt-Koyanagi-Harada (VKH)-like disease secondary to anticancer treatment.

Retrospective, non-interventional multicentre case-series study. Seventeen patients (34 eyes) with VKH-like disease secondary to anticancer treatment, seen between 2014 and 2023. Main outcome measures were patients' extraocular and ophthalmic clinical features, treatment, visual outcome, and complications.

Fourteen out of 17 patients presented with skin melanoma. The main anticancer therapies were BRAF/MEK inhibitor (8/17 patients) and PD1 inhibitor (4/17 patients). Fifteen patients presented with ocular symptoms within 16 weeks after initiating anticancer therapy. Most of the eyes exhibited anterior chamber cells (n = 30), flare (n = 20), and vitritis (n = 11). All patients had subretinal fluid, and 24/34 eyes had foveal involvement. The mean subfoveal choroidal thickness measured by EDI-OCT was 483.42 ± 262.46 µm. In 12 cases, the oncology team decided to stop the anticancer therapy, and all but one patient was treated with high-dose oral corticosteroids for a median of 16 weeks. At the last follow-up visit, control of ocular inflammation had been achieved in 16 cases (median follow-up: 62 weeks, range 16-104 weeks). The most common complications were cataract and ocular hypertension (10 patients).

VKH-like features in the context of emerging novel anticancer therapies represent a unique clinical phenotype in which the cornerstone of management should include high doses of systemic corticosteroids, using immunomodulatory therapy as a second-line treatment in patients with a refractory disorder. In addition, a comprehensive multidisciplinary approach, including an oncologist, should consider the safety of anticancer treatment cessation.

Leukocytoclastic vasculitis (LCV) is a small-vessel inflammatory condition that can rarely occur as an adverse drug reaction (ADR). Vancomycin-induced LCV is an uncommon but potentially serious complication, particularly in patients with pre-existing renal impairment.

This case report describes a patient with end-stage renal disease (ESRD) who developed LCV following vancomycin therapy for a catheter-related infection. The report emphasizes the diagnostic challenges and the importance of prompt and appropriate management of this ADR. A 53-year-old male with ESRD developed skin lesions and systemic symptoms after receiving vancomycin for catheter-related infection. The diagnosis of LCV was confirmed through a skin biopsy. Discontinuation of vancomycin with initiation of mycophenolate mofetil and prednisolone resulted in significant improvement in the patient's condition.

The presented case underlines the recognition of vancomycin-induced LCV, especially in the vulnerable population of patients with ESRD. It emphasizes the need for a high degree of suspicion of drug-related adverse events and early diagnosis and management to achieve good outcomes.

Not applicable.

Crotalidae polyvalent immune Fab (CroFab) is an antivenin that is FDA approved and commonly used to treat envenomations caused by North American pit vipers. Although CroFab has been widely used since the early 2000s, hypersensitivity reactions like type I, type IV, and angioedema have been reported in the literature. We present a case of CroFab induced hypersensitivity reaction in a 41-year-old male shortly after starting CroFab infusion. Furthermore, this patient developed anaphylaxis symptoms including: difficulty breathing, oropharyngeal edema, dysphagia, wheezing, and chest tightness. This was resolved upon stopping CroFab infusion and administering epinephrine, methylprednisolone, diphenhydramine, and famotidine. The reaction occurred again when CroFab was re-introduced despite infusing it at a much slower rate. Interestingly, this patient successfully tolerated crotalidae immune F(ab')2 (equine) antivenom (ANAVIP) upon switching him from CroFab. Hypersensitivity reactions to CroFab can be life-threatening and warrant immediate attention and treatment in a multidisciplinary setting.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and potentially lethal adverse drug reaction. Its clinical complexity and heterogeneity pose challenges for diagnosis and management.

We retrospectively reviewed the medical records of patients with DRESS who were admitted to our hospital between 2013 and 2022. Data on demographics, culprit drugs, clinical manifestations, laboratory findings, and treatments were collected.

Fifty-one patients were included in the final analysis, with 16 probable and 35 definite cases. The most common causative drugs were antiepileptic drugs (15.7%), anti-tuberculosis drugs (15.7%), and Chinese herbs (9.8%). Common skin manifestations included extensive skin involvement (76.5%), facial edema (66.7%), polymorphic maculopapular lesions (66.7%), and exfoliation (56.9%). Eosinophilia and atypical lymphocytes were noted in 96.1% and 68.6% of the patients, respectively. The liver is the most frequently affected organ. Facial edema, extensive skin involvement, and atypical lymphocytes were correlated with higher Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scores (P<0.05). DRESS induced by antiepileptic drugs, antituberculosis drugs, and Chinese herbs exhibited significant differences in platelet and lymphocyte counts, C-reactive protein (CRP) levels, and transaminase levels (P<0.05).

Clinical manifestations of DRESS are complex. Facial edema, extensive skin involvement, and atypical lymphocytes have emerged as significant diagnostic indicators.

Dear Editor, the number of cases of cancer patients diagnosed as having immune checkpoint inhibitor-mediated polymyalgia rheumatica has been steadily rising in published reports. However, the lack of a validated scale or algorithm is still a relevant methodological limit in diagnosing this nosologic entity...

Nephrotoxicity is one of the most common complications of vancomycin use in clinical practice. Silymarin has potential to be a renoprotective agent for nephrotoxic drugs due to its antioxidant, anti-inflammatory, and anti-apoptotic effects. The aim of this clinical study is evaluating the potential effects of silymarin on preventing vancomycin nephrotoxicity. A multicenter, randomized, double-blinded, placebo-controlled, clinical trial was conducted on patients with the indication of systemic vancomycin for at least 7 days. Patients were screened daily and those who met the inclusion criteria were selected and randomly assigned into either silymarin or placebo groups. Accordingly, 140 mg silymarin tablet (Livergol®) or placebo was given orally three times daily. Silymarin or placebo were provided in conjunction with vancomycin for at least 7 days. If vancomycin therapy was extended beyond 7 days, the administration of silymarin or placebo was continued until the end of vancomycin treatment. Malondialdehyde, glutathione, and total antioxidant capacity were measured in the serum on days 0 and 7. A trough level of vancomycin was assessed 30 min before the fifth dose of vancomycin. Acute kidney injury (AKI) was monitored in each patient daily during the course of vancomycin treatment. The causality assessment of all identified cases of vancomycin associated AKI was performed by the Naranjo scale. The primary endpoint was vancomycin nephrotoxicity. It was defined based on the KDIGO 2012 criteria for AKI as either an increase of 0.3 units or more in serum creatinine level during 48 h or 50% (1.5-fold) or more during 7 days compared to baseline values. During the study period, 34 patients in the silymarin group and 32 patients in the placebo group completed the clinical trial. Demographic, baseline clinical, and laboratory characteristics were comparable between placebo and silymarin groups. The number of patients with AKI on days 5, 6, 7, 11,12, 13, and 14 in the placebo group was significantly higher than that in the silymarin group (p-value < 0.05). The incidence of acute tubular injury on the day  5 and 7 of vancomycin treatment was significantly lower in the silymarin group (p-value = 0.005 and p-value = 0.032, respectively). Antioxidant indexes including serum total antioxidant capacity and glutathione significantly increased in the silymarin group (p-value < 0.001 for both indexes). In contrast, serum malondialdehyde as an end product of lipid peroxidation pathway significantly decreased in the silymarin group during 7 days (p-value < 0.001). The results of the present pilot, clinical trial suggested that silymarin co-administration may prevent vancomycin nephrotoxicity.

The diagnosis of idiosyncratic drug-induced liver injury (DILI) is a challenging task due to the lack of specific features or definitive diagnostic tools. A minimum of clinical and pharmacological information is required, together with laboratory and imaging tests to exclude other causes of liver injury. Several standardized methods have been developed to support clinical judgement and establish causality assessment, the most widely used being the Roussel Uclaf Causality Assessment Method-RUCAM-and structured Expert Opinion. More recently, an evidence-based, revised RUCAM, Electronic Causality Assessment Method-RECAM-has been developed and, although still a work in progress, may replace RUCAM scoring in the future. International collaborative networks and ongoing research efforts are key to advancing biomarker qualification and validation and developing new in vitro patient-based methods that will help improve DILI diagnosis and move towards a personalized medicine approach.

IntroductionEtoposide phosphate is a chemotherapeutic agent used to treat various malignant neoplasms. Hypersensitivity reactions may occur with its use, and in rare cases, an anaphylactic reaction can manifest. Available options for patients experiencing hypersensitivity reactions include premedication, changing treatment, or undergoing desensitization. Various pediatric desensitization protocols have been described, ranging from six to fifteen steps, while published adult cases are rare.Case ReportWe report the case of a 61-year-old woman with small-cell lung cancer and brain metastases. In November 2019, she underwent the second cycle of cisplatin and etoposide phosphate treatment. While receiving etoposide phosphate, she experienced dyspnea and suffered a cardiorespiratory arrest, leading to cardiopulmonary resuscitation and subsequent admission to the Intensive Care Unit. Her acute tryptase levels were notably elevated at 18 µg/L (compared to a baseline tryptase level of 6,6 µg/L) during the reaction.Case ManagementWe implemented a 16-step desensitization protocol (without premedication) under close monitoring in an intermediate care unit. The protocol was successfully executed over three cycles until tumor progression mandated a modification in systemic treatment.DiscussionTo our knowledge, this is the first documented case of successful desensitization to etoposide phosphate in a patient who experienced cardiac arrest during a hypersensitivity reaction. Although protocols of varying lengths have been published, we emphasize the importance of individualizing each protocol to fit the severity of the reaction and the resources and experience of each unit.

Drug-induced thrombocytopenia, hemolytic anemia, and leukopenia are serious, and sometimes fatal, complications of common medications. These conditions are challenging to diagnose in patients with polytrauma injuries due to the presence of multiple potential etiologies. In such clinical scenarios, sepsis-induced disseminated intravascular coagulation is a more frequent diagnosis. The clinical manifestations of these conditions can be indistinguishable. We present the case of a 32-year-old man who sustained a left open grade 2 leg fracture and 18% to 20% second-degree superficial electrical flash burns on his right leg. Following primary management, skin testing for antibiotic sensitivity was performed, and prophylactic therapy with ceftriaxone, gentamycin, and metronidazole was initiated for the grossly contaminated wounds. On the second day of emergency admission, the patient developed hepatorenal dysfunction accompanied by severe thrombocytopenia (<30×103/mm3). The suspected antimicrobial agents were discontinued by the third day. Within 48 hours, the patient's hepatorenal function markedly improved; however, the blood dyscrasia progressed to severe pancytopenia over the next few days. Despite worsening parameters, the patient's vitals were maintained, and he exhibited no overt bleeding. On the fourth day, the patient developed opportunistic fungal bronchopneumonia, indicated by bilateral lower lobe infiltrates on chest x-ray and an elevated serum galactomannan level. He received supportive care, broad-spectrum antibiotics, and antifungal treatment, with a full recovery within 2 weeks. Antibiotic toxicity must be distinguished from other medical conditions to ensure appropriate management and a favorable prognosis.

IntroductionBreast cancer, the most prevalent cancer among women, often requires chemotherapy with docetaxel being a key agent. However, docetaxel-inducted peripheral neuropathy (DIPN) can adversely impact patients' quality of life. This case discusses an unusual instance of severe DIPN leading to wheelchair dependence in a 35-years old woman undergoing neoadjuvant treatment for locally advanced breast cancer.CaseFollowing anthracycline and cyclophosphamide cycles without neurological symptoms, docetaxel administration resulted in progressive neuropathy. Despite dose reduction, the patient developed severe paraesthesias, foot weakness, and eventually wheelchair dependence.Management and outcomeDocetaxel's microtubule-stabilizing mechanism, vital for cell division, may disrupt axonal structures, causing sensory and motor neuropathy. While rare, severe motor neuropathy, leading to wheelchair dependence, poses a significant challenge. The frequency of DIPN varies, with docetaxel exhibiting lower neuropathy rates than other taxanes. Risk factors include age, diabetes mellitus, cumulative dose, and genetic polymorphisms in GSTP1 and ABCB1. In our case, despite the patient being young, fit and without diabetes, severe DIPN occured, suggesting a potential genetic predisposition. Genetic variations, such as GSTP1 polymorphisms have been associated with DIPN. Our patient carried GSTP1 (I1e105Val) mutations, emphasizing the need for further research to establish their role as risk factors.DiscussionThis case underscores the importance of recognizing severe DIPN, even in atypical patient profiles. Genetic factors, like GSTP1 polymorphisms, may contribute to DIPN risk. Large-scale studies are crucial to establishing the significance of these genetic variations in DIPN susceptibility.

In 2018, the European Medicines Agency issued some risk minimisation measures related to unresolved adverse drug reactions (ADRs) reported for fluoroquinolones, including sensory ADRs. Spontaneous reporting databases frequently report unresolved outcomes for gustatory, olfactory and auditory (GOA) ADRs. However, such a high volume of unresolved GOA ADRs could reflect an under-investigated clinical issue or an intrinsic difficulty in the outcome assessment.

The objectives of the study were: (1) to investigate whether unresolved outcomes are reported more frequently for GOA ADRs than for other ADRs to systemic antibiotics and (2) to identify possible signals of unresolved GOA ADRs for systemic antibiotics.

We used the EudraVigilance database to extract the number of ADRs to systemic antibiotics of the Anatomical Therapeutic Chemical class J01 up to February 2019. We classified ADRs in "non-GOA ADRs" and "GOA ADRs". Adverse drug reactions were categorised in three groups according to the outcome: defined, persistent/permanent (unresolved) and undetermined ADRs. We performed disproportionality analyses with the case/non-case methodology, by calculating the crude reporting odds ratio (ROR) and 95% confidence interval (CI). Cases were all persistent/permanent ADRs, and non-cases were defined and undetermined ADRs. For the first objective, index groups were gustatory or olfactory or auditory ADRs, while reference group included all non-GOA ADRs. For the second objective, we performed a disproportionality analysis by using the sub-set of GOA ADRs. Index and reference groups varied with subgroups of drugs and drug class, so that each drug and drug class was compared with the others. We conducted two sensitivity analyses for each analysis by varying the case definition.

We extracted 748,798 ADRs, including 10,770 GOA ADRs. The first analysis showed that GOA ADRs were reported more frequently as unresolved events compared with all other ADRs (ROR: 2.68 95% CI 2.51-2.85; ROR: 5.20 95% CI 4.66-5.81; and ROR: 2.64 (95% CI 2.51-2.79, respectively). Gustatory ADRs were reported more frequently as unresolved for doxycycline (ROR: 1.69, 95% CI 1.18-2.41, p = 0.0038), azithromycin (ROR: 2.07, 95% CI 1.58-2.72, p < 0.0001) and levofloxacin (ROR: 1.59, 95% CI 1.22-2.07, p < 0.001) compared with GOA ADRs of all other antibiotics. Olfactory ADRs were reported more frequently as unresolved for doxycycline (ROR: 2.4, 95% CI 1.26-4.58, p = 0.0078) and levofloxacin (ROR: 1.92, 95% CI 1.28-2.86, p = 0.0014). Auditory ADRs were reported more frequently as unresolved for doxycycline (ROR: 1.52, 95% CI 1.09-2.12, p = 0.013) and clarithromycin (ROR: 1.31, 95% CI 1.09-1.59, p = 0.0049).

We tested and used an appropriate expected frequency standard, which allows us to identify possible signals of unresolved GOA ADRs to antibiotic drugs in the EudraVigilance database. This approach could be used to generate signals of persistent or even irreversible events for other drugs or adverse reactions. However, these signals must be confirmed with a thorough clinical assessment.

Compulsive drinking of excessive quantities of water, called psychogenic polydipsia (PP), is a challenging complication of chronic psychotic disorders, which can lead to hyponatremia and downstream morbidity or mortality. Treatments include behavioral modifications such as free water restriction, medications to modify free water excretion, and psychotropic medications to target psychotic symptoms. However, in many cases, these options remain ineffective and/or intolerable, necessitating chronic institutionalization with poor patient quality of life. Here we report the use of an acute course of 8 sessions of bilateral electroconvulsive therapy (ECT) in a 57-year-old man with chronic schizophrenia, PP, and moderate hyponatremia refractory to standard treatments in an inpatient psychiatric setting. Serum sodium normalized and remained stable during and immediately following his ECT course, despite chronic hyponatremia with high variability for months prior to ECT initiation. A literature review found remarkably few reported cases of ECT for PP in chronic schizophrenia, a surprising result given the use of this modality for patients with psychotic illness in many countries. Our findings support future investigation into the clinical utility and mechanism of ECT for PP in this patient population.

IntroductionLeukemia, a complex hematological malignancy, requires a multidisciplinary treatment approach, with clinical pharmacists playing a crucial role. However, their involvement in clinical practice is not well-documented in the literature. This study aimed to examine the characteristics of clinical pharmacy interventions (CPIs) reported by clinical pharmacists.MethodThis retrospective study involved extraction of CPIs entered into a pharmacy documentation database "Quantifi®" between January 2019 and June 2023. These CPIs included direct clinical pharmacist interventions (DCPIs), detected medication errors (MEs) and adverse drug reactions (ADRs).ResultsA total of 6286 CPIs were extracted, of which DCPIs, MEs and ADRs accounted for 5701 (90.7%), 357 (5.7%) and 228 (3.6%) reports, respectively. The most prevalent DCPIs were drug therapy discontinuation (n = 1080, 18.9%). Antimicrobials were the most common medications associated with DCPIs (n = 1991, 34.9%). Physicians accepted 99.4% of DCPIs and 64.1% (n = 3656) of direct interventions were considered significant. Among detected MEs, antimicrobials were the most reported medications (n = 158, 44.3%), with pharmacy internal errors being the most prevalent cause of the events (n = 172, 48.2%). Among the reported ADRs, hematological reactions were the most common (n = 81, 35.5%), and antineoplastic agents were the most frequently associated medications with ADRs (n = 164, 71.9%).ConclusionThis study highlights the crucial role of clinical pharmacists in managing leukemia patients, emphasizing their key interventions and ability to identify MEs and ADRs. Further research is needed to explore the clinical outcomes and financial impact of their involvement.

Bone cement implantation syndrome characteristically involves acute alterations in the function of respiratory and cardiovascular systems. We present a case report of cement reaction with unusual presentation, that is, hypoxia, hypertension and tachycardia. A 74-year-old hypertensive male on regular medications sustained a slip and fall, presented with a right intertrochanteric neck of femur fracture, now posted for cemented hemiarthroplasty. Intraoperatively, after applying bone cement, the patient developed sweating, dyspnoea, bilateral wheezing and tachypnoea and desaturation of up to 80%-84%. Respiratory symptoms were associated with tachycardia (140-160 bpm) and hypertension (220/110 mm Hg). The surgeon was alerted about the event, the patient was reassured, and respiration was assisted with positive pressure ventilation with supplementation of 100% oxygen.

Several mechanisms have been proposed, such as the toxic effect of systemically absorbed methyl methacrylate, exothermic reaction, fat and marrow embolism, high marrow pressure during cementing and anaphylactic reaction. The administration of adrenaline, which can worsen the clinical picture, is the mainstay in managing anaphylaxis.

The association of hypertension and tachycardia with bone cement implantation syndrome, previously not reported, can have distinct pathomechanisms and cause a diagnostic and management dilemma.

Hormonal fluctuations during pregnancy increase susceptibility to Candida infections, typically presenting as vulvovaginal candidiasis, but rarely as oropharyngeal candidiasis. We report a rare case of a woman being pregnant for 27 + 1 weeks with twins with oropharyngeal candidiasis, likely attributed to nutritional anemia and adverse reactions of amoxicillin. Following a thorough literature review and evaluation of medication safety during pregnancy regarding route, dosage, and gestational stage, we treated the patient with fluconazole and piperacillin-tazobactam. The patient fully recovered and successfully delivered two infants via cesarean section at term, with no adverse reactions noted during a six-month follow-up.

IntroductionThe use of Complementary Alternative Medicine (CAM) in patients with cancer is increasing. CAM is associated with potential toxicity and drug interactions, particularly with chemotherapy. Here, we report a case of cytolysis and hepatic cholestasis in a patient who was self-medicated with a mushroom powder-based alternative therapy containing Agaricus blazei Murril (ABM) during cancer treatment.Case ReportA 43-year-old woman with metastatic colorectal cancer and hepatic metastases was admitted to our hospital for intravenous chemotherapy. Markers of hepatic grade 3 cytolysis and cholestasis were identified during the pretreatment consultation. The baseline results were within normal limits.Management and OutcomeThe chemotherapy was immediately canceled, and further tests were performed. After the investigation, the patient reported taking three mushroom powder-based capsules per day since November 2023. The dietary supplement contained ABM and Hericium erinaceus (HE) powder. After Pharmaceutical analysis, treatment with the supplement was discontinued, and the patient has not resumed. The changes in liver function were also favorable.DiscussionIn our case, given the improvement in liver function after CAM discontinuation, hepatic cytolysis appeared to be linked to ABM consumption despite the patient's liver metastases. Pharmaceutical analysis of CAM is essential to ensure the safety and optimization of cancer treatments. Patients should also communicate their CAMs to healthcare professionals and be aware of the consequences of consuming these dietary supplements. Finally, collaboration between pharmaceutical teams and oncologists is essential for optimal management of cancer patients.

Raynaud syndrome (RS) is a peripheral vasculopathy characterised be impaired acral perfusion typically manifesting as skin discolouration with pallor, cyanosis and/or erythema, and increased sensitivity to cold. RS may be primary or secondary to systemic disease, lifestyle and environmental factors or medication. RS has been reported with medication to treat ADHD, but we found no recent comprehensive overview of the literature. The aim of this review is to evaluate the evidence in the published literature for Raynaud syndrome associated with medication for ADHD.

We systematically searched PubMed and Embase from inception to 12 June 2024 for articles published in English describing cases of RS in individuals treated with stimulant medication, atomoxetine, guanfacine or clonidine. Identified cases were assessed against the Naranjo Adverse Drug Reaction Scale criteria to determine the probability of a causal relationship with the medication.

The initial search identified 197 articles. A total of 61 cases were identified from 15 case reports, 5 case series, 1 retrospective case-control study, and 1 retrospective cohort study. No randomised, controlled studies were identified. Implicated medications included methylphenidate, (dex)amfetamine and, more rarely, atomoxetine. Most cases were mild and resolved within weeks of discontinuation, dose reduction or switch to an alternative medication. A few cases associated with systemic disease were reported, leading to ulceration, gangrene and the need for amputation or revascularisation in some individuals. Assessment of 28 cases using the Naranjo criteria suggested a 'possible' causative role of ADHD medication in 13 cases, a 'probable' role in 13 cases and a 'definite' role in two cases.

Due to the uncontrolled nature of all but one of the available studies, a causal relationship between medication for ADHD and RS could not be determined reliably. However, in view of the possibility of severe sequelae, albeit in rare cases, routine monitoring for signs of RS is recommended in individuals treated with CNS stimulants or atomoxetine, especially when initiating treatment or increasing the dose. Large database studies in which individuals act as their own controls should be conducted to clarify any association between treatment with these medications and RS, controlling for confounding factors.

Irinotecan is chemotherapeutic agent often used in abdominal cancers such as colorectal and pancreatic cancers. While often associated with non-central nervous system (CNS) adverse effects, in rare cases it may present with paresthesias and dysarthrias. In one case, a patient received an irinotecan-containing regimen (fluorouracil, irinotecan, oxaliplatin) and experienced several neurotoxic effects, which was successfully managed.

A female patient with newly-diagnosed pancreatic cancer was started on fluorouracil, irinotecan, and oxaliplatin (modified FOLFIRINOX). She developed dysarthrias early on in the course. Causality assessment was conducted via the Naranjo criteria, yielding a score of 6, indicating a probable adverse reaction.

Initially managed with steroids and lorazepam, she was eventually given a prophylactic strategy of atropine 0.4 mg and a longer infusion time of 3 h instead of 90 min with as needed lorazepam. This strategy alleviated the dysarthrias and the patient was able to complete 12 cycles of therapy, resulting in a partial response at the end of treatment.

Prolonging the infusion and giving prophylactic atropine may help to prevent these rare adverse effects of irinotecan.

Immune checkpoint inhibitors (ICIs)-associated cardiotoxic events (CEs) are of increasing concern. Existing research about glucocorticoids (GCs) on immunotherapy focused on ICIs' efficacy and patients' outcome. The influence of GCs on ICIs-associated CEs and myocardial damage (MD) remains unknown.

This single-center retrospective study included patients treated with ICIs from 2018 to 2022, with follow-up period ending on 30 June 2023. The incidence, risk factors of ICIs-associated CEs, especially MD were described. Additionally, the impact of baseline GCs was assessed by propensity score matching (PSM) to mitigate intergroup differences and ensure comparability.

Among 1018 patients, 204 (20.04%) experienced ICIs-associated CEs, including 71 (6.97%) with MD. The mean follow-up time was 40.39 (95% CI 38.47-42.31) weeks. The median time to onset of MD was the shortest at 12.57 weeks (IQR 5.29-25.14). Tumor type, co-medication with platinum and angiogenesis inhibitors may be influential factors of MD. After PSM, the relative risks of CEs (OR 0.4625,95%CI 0.2514-0.7235, p = 0.0020) and MD (OR 0.3254, 95% CI 0.1190-0.8898, p = 0.0378) in GCs1 ≥ 20 mg group were both significantly lower than those in GCs1 < 20 mg.

GCs ≥ 20 mg during the first ICIs treatment cycle is significantly associated with the reduced risks of both ICIs-associated CEs and MD.

Optimal rates of positive tuberculosis (TB) treatment outcomes are crucial for patient well-being and preventing the emergence of drug-resistant strains. Unfavourable outcomes present significant challenges to healthcare systems worldwide, making it essential to identify factors that influence treatment success. This study aimed to assess treatment outcomes and explore determinants of success to inform effective interventions and contribute to TB eradication efforts. Patients with active TB were monitored from treatment initiation to completion between January 2021 and December 2021. Data were collected using a Redcap-based tool to capture demographics, adverse reactions to antitubercular medications, and treatment outcomes. Quality of life was assessed using the Short-Form 12 version 2 questionnaire at baseline, the second month, and the sixth month. Logistic regression was performed to analyse associations between participant characteristics and treatment success, with odds ratios indicating the strength of associations at a 0.05 significance level. Among 378 participants, 77.3% achieved successful treatment outcomes, while 13.5% were lost to follow-up, 0.5% experienced treatment failure, and 8.7% died. Key factors influencing treatment success included baseline body weight, weight gain during treatment, HIV status, adverse drug reactions, and mental well-being at treatment initiation. Multivariate analysis revealed that gaining at least 3 kg during treatment and having no risk of depression at baseline significantly increased the likelihood of treatment success.

Systemic lupus erythematosus (SLE) can affect multiple organs or systems. The involvement of the central nervous system can result in the manifestation of epilepsy, an acute confusional state, and other rare neuropsychiatric presentations, such as catatonia.

We present a case of an adolescent male patient with first-onset SLE who presented with neuropsychiatric symptoms including epilepsy and delirium. The initial utilization of olanzapine to alleviate symptoms of agitation precipitated the emergence of catatonia, which was mitigated by discontinuing olanzapine and supplementing with lorazepam. In this case, whether the catatonia was secondary to the utilization of antipsychotics or to an organic disease is a question that warrants differential diagnosis.

Multidisciplinary collaborative management is the cornerstone for the successful management of severe cases of SLE.

To report a case highlighting the uncommon presentation of Frosted Branch Angiitis (FBA) in Behçet's Disease (BD), notably in a patient who received a COVID vaccine one month prior to the onset of symptoms. We explore the possible role of vaccination in unmasking BD.

A comprehensive evaluation of a 45-year-old patient with FBA post-COVID vaccination was undertaken.

The patient exhibited characteristic features of FBA, with classic perivascular sheathing, optic disc edema, and retinal ischemia, which manifested one month after receiving the Pfizer/BioNTech COVID vaccine. Despite a history of recurrent oral aphthosis, systemic workup for autoimmune conditions was unremarkable. Diagnosis of presumptive Behçet's Disease was made based on clinical criteria. Treatment with intravenous methylprednisolone and infliximabn (5 mg/kg) led to complete resolution of ocular symptoms and retinal signs.

FBA is an uncommon presentation of BD. This case also serves as a stark reminder of the potential consequences of vaccination on immune-mediated diseases. However, the correlation between FBA onset, COVID vaccination, and Behçet's Disease diagnosis necessitates cautious interpretation. Successful use of methylprednisolone and infliximab in achieving resolution of visual symptoms highlights potential therapeutic considerations in similar cases.

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.