VKH-like uveitis during donafenib therapy for hepatocellular carcinoma: a case report and review of the literature.

Background: The incidence of uveitis has risen with the use of targeted therapies, particularly prevalent in the administration of immune checkpoint inhibitors and MAP-kinase pathway inhibitors. We report the first case of VKH-like uveitis linked to Donafenib employed for the primary hepatocellular carcinoma, highlighting the necessity of ophthalmological follow-up in patients undergoing treatment with Donafenib. Case presentation: A 55-year-old man developed VKH-like symptoms, including sporadic white patches, tinnitus, headache, and mild bilateral vision reduction, after 18 months of treatment with Donafenib and Sintilimab for hepatocellular carcinoma. Based on ophthalmological examinations that fundus fluorescein angiography images demonstrating multiple focal areas of pinpoint hyperfluorescence, along with pooling indicative of neurosensory detachment and disc leakage in both eyes, choroid thickening in swept-source optical coherence tomography, and "sunset-glow" fundus appearance, a tentative diagnosis of VKH-like uveitis was made. Initially, his best-corrected visual acuity (BCVA) was 20/200 in the right eye and 20/80 in the left eye. Upon discontinuing Donafenib and starting a 3-month course of oral glucocorticoids, his BCVA improved to 20/30 in the right eye and 20/40 in the left eye. Conclusion: Targeted drugs have been commonly used for cancer treatment in recent years, but challenges of ocular side effects emerged gradually. To optimize patient outcomes, regular ophthalmological follow-ups are essential for those undergoing treatment with targeted therapies like Donafenib.

Safety assessment of brexanolone in the FAERS database: real adverse event analysis and discussion of side effects.

BACKGROUND: Postpartum depression (PPD) is linked to hormonal changes. Brexanolone, the first FDA-approved drug for PPD, is a potential treatment. This study analyzes Brexanolone's safety using the FAERS database, highlighting its adverse effects and potential risk factors. METHODS: We analyzed FAERS data from Q3 2019 to Q3 2023, evaluating adverse reactions to Brexanolone. The analysis includes demographics, reporting regions, reporter identities, and types of adverse reactions. RESULTS: Most reports are from the United States, with consumers and physicians as primary reporters. Adverse reactions mainly involve severe systemic diseases, administration site reactions, injuries, intoxication, operational complications, and mental disorders. Specific adverse reactions include incorrect drug monitoring, PPD, intrusive thoughts, delayed treatment efficacy, sedation complications, product discontinuation, misuse, infusion site leakage and pain, and medication errors. CONCLUSION: The study confirms known safety information about Brexanolone and provides comprehensive data for medical practices and public health decisions. However, relying on spontaneous reports may introduce biases and incomplete information. Continued monitoring and reporting of adverse reactions to newer drugs like Brexanolone remain crucial.

The radiologist's role in detecting systemic anticancer therapy-related interstitial lung disease: an educational review.

Systemic anticancer therapies (SACTs) are the leading cause of drug-induced interstitial lung disease (ILD). As more novel SACTs become approved, the incidence of this potentially life-threatening adverse event (AE) may increase. Early detection of SACT-related ILD allows for prompt implementation of drug-specific management recommendations, improving the likelihood of AE resolution and, in some instances, widening the patient's eligibility for future cancer treatment options. ILD requires a diagnosis of exclusion through collaboration with the patient's multidisciplinary team to rule out other possible etiologies of new or worsening respiratory signs and symptoms. At Grade 1, ILD is asymptomatic, and thus the radiologist is key to detecting the AE prior to the disease severity worsening. Planned computed tomography scans should be reviewed for the presence of ILD in addition to being assessed for tumor response to treatment, and when ILD is suspected, a high-resolution computed tomography (HRCT) scan should be requested immediately. An HRCT scan, with < 2-mm slice thickness, is the most appropriate method for detecting ILD. Multiple patterns of ILD exist, which can impact patient prognosis. The four main patterns include acute interstitial pneumonia / acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, and non-specific interstitial pneumonia; their distinct radiological features, along with rarer patterns, are discussed here. Furthermore, HRCT is essential for following the course of ILD and might help to determine the intensity of AE management and the appropriateness of re-challenging with SACT, where indicated by drug-specific prescribing information. ILD events should be monitored closely until complete resolution. CRITICAL RELEVANCE STATEMENT: The incidence of potentially treatment-limiting and life-threatening systemic anticancer therapy-related interstitial lung disease (SACT-related ILD) events is likely increasing as more novel regimens become approved. This review provides best-practice recommendations for the early detection of SACT-related ILD by radiologists. KEY POINTS: Radiologists are crucial in detecting asymptomatic (Grade 1) ILD before severity/prognosis worsens. High-resolution computed tomography is the most appropriate method for detecting ILD. Drug-induced ILD is a diagnosis of exclusion, involving a multidisciplinary team. Familiarity with common HRCT patterns, described here, is key for prompt detection. Physicians should highlight systemic anticancer therapies (SACTs) with a known risk for interstitial lung diseases (ILD) on scan requisitions.

Transient Hyperglycemia in a Patient With Type 2 Diabetes After COVID-19 Messenger RNA Vaccination: A Case Report.

The development of new vaccines against the SARS-CoV-2 virus in response to the COVID-19 pandemic represents a milestone in the history of public health. However, due to the rapid development and short duration of these new vaccines, the full spectrum of side effects is not yet known. A 76-year-old man presented to the clinic for follow-up after being discharged from the emergency department for hyperglycemia. His medical history included well-controlled type 2 diabetes for two years, hypertension, and hyperlipidemia. He had recently noticed high home blood glucose readings over 400 mg/dL, and his hemoglobin A1c (mean 90-day glucose level) had increased from 6.5% to 12.6%. Notably, the patient reported having excellent health behaviors, including daily exercise, a closely monitored healthy diet, and regular blood glucose testing. After extensive endocrinology workup, the rapid change in blood glucose was thought to be due to his having recently received the COVID-19 messenger RNA (mRNA) vaccine. He was started on long- and short-acting insulin and a glucagon-like peptide-1 agonist (novel injectable type 2 diabetes medication), with improvement in blood glucose. He was tapered off all medications and remains on metformin 1,000 mg twice daily after one year.Whether the new COVID-19 mRNA vaccines directly incur hyperglycemia within certain groups of patients with diabetes is not known; thus, studies exploring the relationship between vaccine antigen binding and pancreatic function are needed.

Real-world smartphone data can trace the behavioural impact of epilepsy: A case study.

BACKGROUND: Neurobehavioural comorbidities have a detrimental effect on the quality of life of people with epilepsy, yet tracking their impact is challenging as behaviour may vary with seizures and anti-seizure medication (ASM) side effects. Smartphones have the potential to monitor day-to-day neurobehavioural patterns objectively. We present the case of a man in his late twenties with drug-resistant focal epilepsy in whom we ascertained the effects of ASM withdrawal and a convulsive seizure on his touchscreen interactions. METHODS: Using a dedicated app, we recorded over 185 days the timestamps of 718,357 interactions. We divided the various smartphone behaviours according to the next-interval dynamics of the interactions by using a joint interval distribution (JID). During two ASM load transitions, namely before versus during tapering and tapering versus restarting medication, we used cluster-based permutation tests to compare the JIDs. We also compared the JID of the seizure day to the average of the previous 3 days. RESULTS: The cluster-based permutation tests revealed significant differences, with accelerated next-interval dynamics during tapering and a reversal upon medication restart. The day of the convulsion exhibited a marked slowing of next-interval dynamics compared to the preceding 3 days. CONCLUSION: Our findings suggest that the temporal dynamics of smartphone touchscreen interactions may help monitor neurobehavioural comorbidities in neurological care.

Treatment-emergent sexual dysfunctions due to antidepressants: A primer on assessment and management strategies.

Antidepressants (ADs) are among the most commonly prescribed drugs worldwide. Persons with mental illness taking ADs commonly report sexual dysfunction (SD) related to treatment. A brief discussion on the neurobiology of sexual functioning and mechanism of treatment-emergent SD (TESD) was performed. The incidence of prevalence of TESD in various studies has been reviewed. TESD impacts patients as it frequently leads to nonadherence, while psychiatrists have challenges in proceeding forward with treatment in such patients. Assessment of patients with suspected TESD is described with a focus on practical tips for clinicians. Five strategies (watchful waiting, drug holiday, downward titration, switching, and add-on therapy) to manage TESD have been extensively discussed with evidence in the literature. Each strategy comes with its own bag of advantages and drawbacks, which have been pointed out for simplicity. A detailed discussion on individual pharmacological strategies is given, and options for non-pharmacological management that can be tried are enlisted. Common clinical case scenarios have been discussed to incorporate the implementation of this literature.

Clinical Outcomes of Electroconvulsive Therapy (ECT) for Depression in Older Old People Relative to Other Age Groups Across the Adult Life Span: A CARE Network Study.

INTERVENTION: Electroconvulsive therapy (ECT) is a commonly used treatment for severe psychiatric illness in older adults, including in the 'older old' population aged 80 years and above. However, there can sometimes be a reluctance to treat the 80+ year old age group with ECT due to medical comorbidities, frailty, and concerns about cognition. OBJECTIVE, DESIGN, SETTING, AND PARTICIPANTS: This multi-site, longitudinal Australian study aimed to investigate the effectiveness and safety of ECT in older old people compared with younger age groups. Data from 310 people receiving ECT for depression at three participating hospitals was collected in a naturalistic setting, between 2015 and 2022. MEASUREMENTS: Clinical ratings were conducted pre-ECT and end-acute ECT using the Montgomery-Åsberg Depression Rating Scale (MADRS). Cognitive outcomes were assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Older old adults demonstrated a significant reduction MADRS scores at post-treatment. They were more likely to meet remission criteria compared with the younger age groups. Older old adults were also less likely to show clinically significant cognitive decline post-ECT, and were more likely to show clinically significant cognitive improvement post-ECT compared with younger age groups. CONCLUSIONS: ECT is highly effective in treating severe psychiatric illness in older old adults. Relative to the younger age groups, the older old group were more likely to remit with ECT and a greater proportion showed cognitive improvement post-ECT. These findings suggest that ECT should be considered as a valuable and safe treatment option for older old individuals with depression.

S2k-Guideline Non-hormonal Contraception, Part 1: Natural Family Planning, Lactational Amenorrhea, Barrier Methods, Coitus Interruptus: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015 - 095, January 2024).

Aim This official guideline was published and coordinated by the DGGG, OEGGG and SGGG with the involvement of other medical societies. The aim was to provide a consensus-based overview of non-hormonal forms of contraception based on an evaluation of the relevant literature. The first part of these summarized statements and recommendations presents natural family planning methods such as lactational amenorrhea, barrier methods and coitus interruptus. The second part will focus on intrauterine devices and sterilization methods. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, OEGGG and SGGG using a structured consensus process. Recommendations The guideline provides recommendations on the indications for, safety of use, benefits, and limitations of the different methods as well as recommendations on providing advice and other aspects of non-hormonal contraception. Natural family planning methods, lactational amenorrhea, barrier methods and coitus interruptus are discussed.

S2k-Guideline Non-hormonal Contraception, Part 2: Intrauterine Devices and Sterilization: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015 - 095, January 2024).

Aim This official guideline was published and coordinated by the DGGG, OEGGG and SGGG with the involvement of other medical societies. The aim was to provide a consensus-based overview of non-hormonal forms of contraception based on an evaluation of the relevant literature. The first part of these summarized statements and recommendations presents natural family planning methods such as lactational amenorrhea, barrier methods and coitus interruptus. The second part focuses on intrauterine devices and sterilization. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, OEGGG and SGGG using a structured consensus process. Recommendations The guideline provides recommendations on the indications for, safety of use, benefits, and limitations of the different methods as well as recommendations on providing advice and other aspects of non-hormonal contraception. This summary presents recommendations and statements about intrauterine devices and female and male sterilization.

Patient-Centered Care in Action: How Clinicians Respond to Patient Dissatisfaction with Contraceptive Side Effects.

Patient-centered care is widely cited as a component of quality contraceptive health care, but its operationalization in clinical interaction is contested. This article examines patient-centered care as an interactional phenomenon using the case of patient dissatisfaction with side effects of hormonal contraceptive medications. Drawing on transcript data from 109 tape-recorded reproductive health visits, I find that provider responses to treatment dissatisfaction range from patient-centered to relatively authoritarian. Providers typically offer patient-centered responses that validate patient experiences and integrate them into contraceptive counseling and method selection. At the same time, explicit communication about patients' contraceptive priorities is rare. In its absence, providers use patient-centered communication to smooth the interactional path toward uptake of highly effective hormonal methods, mostly ignoring the possibility that some patients may prefer less effective methods. Patient-centered contraceptive care was circumscribed by the clinical goal of pregnancy prevention.

The Impact of COVID-19 Vaccination Side-Effects on Work Attendance among Saudi Healthcare Workers.

OBJECTIVE: This cross-sectional-survey-based study aimed to investigate the severity of side-effects from Coronavirus disease (COVID-19) mRNA (Pfizer, Moderna), viral vector DNA (Oxford-AstraZeneca, J&J/Janssen), inactivated virus (Sinopharm, Sinovac), and other vaccines among healthcare workers (HCWs) in Saudi Arabia, focusing on their impact on work attendance. METHODS: A total of 894 HCWs residing in Saudi Arabia participated in this study from March 2023 to May 2023. Participants completed an online questionnaire assessing demographic information, vaccination status, comorbidities, vaccine side-effects, and missed work information after vaccination. Descriptive statistics and chi-square tests were used for data analysis. RESULTS: The majority of participants were female (83.7%) and aged 25-34 years (42.8%). Most participants were predominantly vaccinated with mRNA vaccines. Common side-effects included pain at the injection site, fatigue, fever, and chills. However, no significant association was found between vaccine type, side-effects, and work absenteeism. While demographic factors such as age and healthcare profession did not influence work absenteeism, variations were observed among different racial groups. CONCLUSION: COVID-19 vaccination among HCWs in Saudi Arabia is associated with common side-effects, but their impact on work attendance is not significant. Understanding these implications can inform strategies to support the healthcare workforce and mitigate the impact on patient care and staffing during the ongoing COVID-19 pandemic.

Changing Gadolinium-Based Contrast Agents to Prevent Recurrent Acute Adverse Drug Reactions: 6-Year Cohort Study Using Propensity Score Matching.

OBJECTIVE: To determine the preventive effect of changing gadolinium-based contrast agents (GBCAs) to reduce the recurrence of GBCA-associated acute adverse drug reactions (ADRs). MATERIALS AND METHODS: This retrospective, observational, single-center study-conducted between January 2016 and December 2021-included 238743 consecutive GBCA-enhanced MRI examinations. We focused on a subgroup of patients who experienced acute GBCA-associated ADRs during any of these examinations and subsequently underwent follow-up GBCA-enhanced MRI examinations up until July 2023. The follow-up examinations involved either the same (non-change group) or different (change group) GBCAs compared to the ones that initially caused the acute ADR. Baseline participant characteristics, generic profile of the GBCAs, administration of premedication, history of prior ADR to iodinated contrast media, and symptoms of GBCA-associated acute ADRs were retrospectively analyzed. Multivariable logistic regression with generalized estimating equations and propensity score matching were used. RESULTS: A total of 1042 instances of acute ADRs (0.44%; 95% confidence interval [CI]: 0.41%-0.46%) were reported. Three-hundred and seventy-three patients underwent GBCA-enhanced MRI examinations after experiencing GBCA-associated acute ADRs within the study period; 31.9% (119/373) reexperienced acute ADRs at any of the follow-up examinations. The ADR recurrence was significantly lower in the GBCA change group than in the non-change group according to multivariable logistic regression (adjusted odds ratio [OR]: 0.35; 95% CI: 0.13-0.90; P = 0.03) and analysis with propensity score matching (14.3% [6/42] vs. 36.9% [31/84], respectively; OR: 0.32, 95% CI: 0.11-0.94; P = 0.04). A history of an ADR to iodinated contrast media (OR: 1.14, 95% CI: 0.68-1.90; P = 0.62) and premedication (adjusted OR: 2.09, 95% CI: 0.93-4.68; P = 0.07) were not significantly associated with GBCA-associated acute ADR recurrence. A separate analysis for recurrent allergic-like hypersensitivity reactions demonstrated similar results (adjusted OR: 0.20, 95% CI: 0.06-0.65; P < 0.01). CONCLUSION: Changing GBCAs may reduce the risk of GBCA-associated acute ADR recurrence.

Sequential Moderate Hypofractionated Boost in Breast Cancer Patients: A Monoinstitutional Analysis of Late Side Effects.

BACKGROUND/AIM: In breast cancer (BC) patients who have received breast-conserving surgery, moderate hypofractionation is standard of care for whole-breast irradiation (HF-WBI). On the other hand, the fractionation schedule for the boost is less well defined. A previous prospective study of our group aimed at evaluating acute and late cutaneous and subcutaneous side effects related to a sequential hypofractionated boost (HB) in patients who had received HF-WBI. The present study aimed at evaluating late side effects at a longer follow-up. PATIENTS AND METHODS: From 2014 to 2015, 219 BC patients received moderate HF-WBI (42.4 Gy in 16 fractions) at the Radiation Oncology Section of the University of Perugia. Patients with negative prognostic factors received a HB (2.65 Gy for 4 or 5 fractions). Late side effects were assessed using the Common Terminology Criteria for Adverse Events v5.0. Univariate and multivariate analyses estimated predictive factors for late toxicity. RESULTS: Median follow-up was 8.6 years (range=6.7-9.6). One hundred and sixty-five patients were evaluable in the present analysis; HB was administered to 47.3% of them. Late cutaneous and subcutaneous side effects occurred in 26/165 patients (15.8%); and all were G1. In univariate analysis ≥10 excised lymph nodes and HB administration emerged as risk factors for late side effects (p=0.003 and p=0.041, respectively). In multivariate analysis only ≥10 excised lymph nodes were confirmed as a risk factor for side effects (OR=3.431; 95%CI=1.209-9.737). CONCLUSION: HB after HF-WBI was safe and well-tolerated, even at a long-term follow-up; consequently, it can be used in routine practice.

Risk factors for severe sting reactions and side effects during venom immunotherapy.

Understanding the risk factors leading to severe systemic sting reactions (SSR) is crucial for initiating venom immunotherapy (VIT) and for educating affected individuals and their families. Some of these risk factors are well-established, some are no longer considered risk factors, and some remain controversial. Well-established risk factors for severe SSR include clonal mast cell disease, high baseline serum tryptase, and advanced age. The absence of skin symptoms and the rapid onset of symptoms are indicators of severe SSR. Recent publications indicate that antihypertensive treatment and stings in the head and neck area are not risk factors for severe SSR. VIT is the only available treatment that can potentially prevent further anaphylactic reactions. Although rare and generally manageable, individuals undergoing VIT may experience systemic adverse events (sAE). More sAE are expected in patients undergoing bee VIT compared to vespid VIT. The role of elevated baseline serum tryptase as a risk factor for sAE remains debated, but if it is a factor, the risk is increased by only about 1.5-fold. Rapid up-dosing protocols, depending on the specific regimen, can also be associated with more sAE. Severe initial SSR, antihypertensive medication, high skin test reactivity, and high specific IgE levels are not risk factors for sAE.

Toxic-metabolic encephalopathy induced by metronidazole and disulfiram: classics never die.

A 53-year-old male with recovering alcohol dependency, diagnosed with bipolar disorder and recurrent episodes of diverticulitis, came to the emergency department with disorientation and confusion after 3 days of treatment with metronidazole 250 mg/12 hours and ciprofloxacin 500 mg/12 hours for acute diverticulitis. In the hospital emergency department, he presented moments of agitation, fluctuations of attitude, increased basal tremor, with rhythmic movement of the left arm and leg, as well as generalised rigidity with an episode of tonic-clonic seizure of 1.5-2 min duration. After performing different diagnostic tests, significant brain findings were ruled out. The pharmacy department recommended the discontinuation of one of the two drugs. As a result, the on-call doctor adjusted the patient's treatment: disulfiram and previous antibiotic therapy (metronidazole and ciprofloxacin) were discontinued, and amoxicillin/clavulanic acid 2 g/8 hour was prescribed instead. The patient progressed well and fully recovered.

Medication reviews by emergency department pharmacists in patients hospitalised for an adverse drug event: a cost study.

OBJECTIVE: To perform a cost study of pharmacist-led medication reviews in patients with an acute hospitalization for adverse drug events. METHOD: Emergency department pharmacists performed medication reviews in patients hospitalized after visiting the emergency department for an adverse drug event (ADE). Control patients were hospitalized after an emergency department visit not related to an ADE and received usual care. The costs of the intervention were labour costs of the junior emergency department pharmacist and the cost savings consisted of costs of medication that was stopped or reduced during six months after the intervention. Sensitivity analyses were performed to evaluate different scenarios. RESULTS: In the intervention group (n = 104) 113 medication changes led to stopping or reducing medication, accounting for averted costs of €22,850. In the control group (n = 112) 39 medication changes led to stopping or reducing medication, accounting for averted costs of €299. The mean labour costs of the intervention were €138 per patient, resulting in saved costs of €61 per patient per six months. Sensitivity analyses showed that if the intervention would be performed by a senior clinical pharmacist, there are no cost savings (€-21), if parts of the intervention would be executed by pharmacy technicians (e.g. administrative tasks), cost savings would be augmented to €87, if outliers in costs associated with medication reduction would be excluded, there are no cost savings (€-35) and if the costs of reduced medication were extrapolated to one year, cost savings would be €260. CONCLUSION: In this study, medication reviews by junior emergency department pharmacists in patients hospitalized after an emergency department visit for an ADE lead to a cost reduction over a six month period. TRIAL REGISTRATION: The main study is registered on the ISRCTN registry with trial ID ISRCTN12506329 on 06-03-2022.

Examining the association of vaccine-related mindsets and post-vaccination antibody response, side effects, and affective outcomes.

Background: Although vaccines are largely effective and safe, there is variability in post-vaccination experience regarding antibody response, side effects, and affective outcomes. Vaccine mindsets, specific beliefs about the vaccine, may be associated with post-vaccination experience. This is important since mindsets are malleable and may help decrease vaccine hesitancy and improve post-vaccination experience. Methods: In a prospective study, we measured overall positive vaccine mindset and specific mindsets regarding efficacy, body response, and side effects. We tested whether vaccine mindsets before vaccination predicted neutralizing antibody response, side effects, vaccine-related stress, and affective outcomes (general stress, sadness, and happiness). Antibody response was assessed one month and six months after participants completed a SARS-CoV-2 vaccination series. Side effect experience and affective reactions were assessed daily on the vaccination day and the subsequent five days. Results: There was no significant association between the aggregate vaccine mindset score and neutralizing antibody response; however, people with a more positive vaccine mindset reported fewer side effects, less same-day vaccine-related anxiety, and improved affective outcomes after vaccination. In secondary analyses, when specific mindsets were explored, the mindset that vaccine side effects are a sign of treatment efficacy predicted higher antibodies, but not side effects experience and vaccine-related anxiety. Vaccine efficacy and body-response mindsets predicted fewer side effects, vaccine-related anxiety, and improved affective outcomes after vaccination. Conclusion: These findings underscore the potential of vaccine mindsets in enhancing the overall post-vaccination experience and, in some cases, increasing antibody response.