Safety of subcutaneous immunotherapy with Novo-Helisen-Depot in the children: a retrospective analysis from a single center in Northern China.

Background: Little is known about the safety of mite extract product Novo-Helisen Depot (NHD) as subcutaneous immunotherapy (SCIT) in the children with mite allergy especially immediate/late local reaction (LRs). Methods: We conducted a retrospective study analyzing the adverse events of the children undergoing subcutaneous immunotherapy with NHD. Adverse events included local and systemic adverse reactions (SRs) at the very early and late stage. The correlation of the basic characteristics, laboratory analysis results, LRs and SRs were analyzed. Results: Two hundred and eighty-seven patients received at least 15 months of subcutaneous immunotherapy with NHD were included in the analysis. Skin-prick testing (SPT) results of D. pteronyssinus was associated with an increased risk of immediate LRs in build-up phase (OR = 1.53, 95% CI: 1.02, 2.37) and delayed LRs in maintenance phase (OR = 1.58, 95% CI: 1.05, 2.46), while SPT results of D. farinae was associated with an increased risk of SRs (OR = 3.22, 95% CI: 1.17, 10.00) and severe SRs (OR = 7.68, 95% CI: 1.13, 109.50). Serum IgE level of D. pteronyssinus was associated with an increased risk of SRs (OR = 1.01, 95% CI: 1.00, 1.03). Patients with both asthma and allergic rhinitis was associated with an increased risk of SR, and severe SRs (P < 0.05). Conclusion: NHD as SCIT is safe. The children with higher SPT level with D. farinae or D. pteronyssinus, higher serum IgE level of D. pteronyssinus, children with both asthma and allergic rhinitis, and the children with treatment interruption had higher risk of adverse events.

Safety of cardiovascular disease drugs approved between 2014 and 2021 in the US: a pharmacovigilance analysis.

BACKGROUND: Recently FDA-approved drugs for cardiovascular disease (CVD) require robust post-marketing surveillance. The objective of this study was to assess their safety using a large pharmacovigilance database. RESEARCH DESIGN AND METHODS: We analyzed adverse event (AE) reports for 17 drugs approved from 2014 to 2021, utilizing the FDA Adverse Event Reporting System (FAERS). Descriptive and disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and its 95% confidence interval. RESULTS: Among the 43,664,773 AE reports 97,702 (0.22%) were related to newly approved CVD drugs. No AEs were reported for finerenone and evinacumab. The results from the disproportionality analyses revealed potential risks of acute kidney injury (ROR = 8.24, 95% CI: 6.05-11.22), cardiac failure (ROR = 4.80, 95% CI: 3.82-6.05), and hypotension (ROR = 3.98, 95% CI: 3.44-4.61) among sacubitril/valsartan users. Additionally, ivabradine was found to be associated with tachycardia (ROR = 11.94, 95% CI: 8.35-17.08), abnormal feeling (ROR = 4.40, 95% CI: 2.70-7.18), and dizziness (ROR = 2.56, 95% CI: 1.68-3.90). CONCLUSIONS: This study identified specific safety concerns related to recently approved CVD drugs. Further research is required to understand the underlying mechanisms and clinical implications of these findings.

Corticosteroid-induced hyperammonaemic encephalopathy in a woman with late-onset ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is a rare, X linked disorder that can manifest in late adulthood in heterozygous females as severe hyperammonaemia following environmental stressors. We present a case of hyperammonaemic encephalopathy that was triggered by glucocorticoid administration in an adult woman with heterozygous OTCD with clinical response to haemodialysis, ammonia scavengers and a high-calorie, low-protein diet.

Polymyxin B-induced Bartter syndrome.

Bartter syndrome is a genetic disorder characterised by chloride-unresponsive metabolic alkalosis, hypokalaemia, hypomagnesaemia and hypercalciuria. While it commonly presents antenatally or in early infancy, sometimes, drugs can induce a state similar to Bartter syndrome in any age group, called acquired Bartter syndrome. Polymyxins and aminoglycosides are the most commonly implicated drugs. Polymyxin B and polymyxin E (popularly known as colistin) are the two chemically similar polymyxins that are commonly used clinically. While colistin is frequently associated with nephrotoxicity, polymyxin B is generally considered less nephrotoxic. This difference is due to the way these two drugs are handled by the kidneys. In this case report, we discuss a middle-aged male who developed Bartter syndrome due to polymyxin B, which resolved on discontinuation of the drug, and re-appeared after its re-introduction later. This case exemplifies the nephrotoxicity caused by polymyxin B and the need for vigilance when using this drug.

Significant elevation of serum CA19-9 and CA242 levels induced by dulaglutide.

The use of dulaglutide, a common medication for managing type 2 diabetes, rarely causes elevated pancreatic tumour markers. Here, we report the case of a woman in her mid-60s with diabetes for over 10 years. The patient presented with markedly elevated serum CA19-9 and CA242 levels revealed during a routine health examination despite being asymptomatic. She had been receiving dulaglutide injections for 16 months. Imaging and interventional assessments did not reveal any hepatobiliary, gastrointestinal or pancreatic neoplasm. After excluding alternate diagnoses, the patient was determined to exhibit an adverse reaction to dulaglutide use. Management involved the discontinuation of dulaglutide, which resulted in normalisation of serum CA19-9 and CA242 levels within 6 weeks. This case underscores the importance of discontinuing dulaglutide and monitoring changes in the biomarker levels in asymptomatic patients receiving dulaglutide, rather than immediately resorting to imaging and endoscopic examinations.

Immune checkpoint inhibitor associated diarrhoea.

A man in his 80s was undergoing immunotherapy with pembrolizumab, an anti-PD-1 monoclonal antibody, following his diagnosis of adenocarcinoma of primary lung origin. 24 weeks into treatment, the patient reported experiencing loose stools associated with malaise and poor appetite but no further symptoms. This progressed in frequency and a clinical diagnosis of grade 2 immune checkpoint inhibitor colitis was made. Management with oral prednisolone was commenced but symptoms persisted. Common enteric infections had been ruled out, as were coeliac disease and hyperthyroidism. Flexible sigmoidoscopy and colonoscopy results were not in keeping with colitis, having revealed normal looking mucosa. Following this, a faecal elastase level was found to be low. A diagnosis of pembrolizumab-induced pancreatic exocrine insufficiency was made, and stool frequency and consistency swiftly improved following the use of pancreatic enzyme replacement therapy.

A study of hemodynamic effects, postoperative recovery, and safety of esketamine (right handed) during flexible bronchoscopy under general anesthesia.

OBJECTIVE: Flexible bronchoscopy during general anesthesia has become an indispensable tool. Anesthetics are widely utilized in flexible bronchoscopy (FB). This study delved into the application value of a subanesthetic dose of esketamine (ES) (right handed) in flexible bronchoscopy during general anesthesia. METHODS: A sample of 160 patients who underwent flexible bronchoscopy during general anesthesia were selected as study subjects and were equally divided into the control and ES groups, with clinical baseline data (age, sex, body mass index, American Society of Anesthesiologists grading) collected. Hemodynamic parameters (mean artery pressure, heart rate, pulse blood oxygen saturation) at different time points, the onset time of anesthesia, surgery time, analgesia maintenance time, anesthesia awakening time, and perioperative adverse reactions were recorded. Visual analogue scale (VAS), Mini-Mental State Examination (MMSE), and quality of recovery-40 (QoR-40) scales were utilized for assessing post-surgery satisfaction, cognitive function, and post-surgery early recovery quality. RESULTS: The hemodynamics were stable at each time point, but patients in the ES group were more stable than those in the control group. Patients in the ES group exhibited faster onset and awakening time of anesthesia, longer duration of analgesia, and lower total incidence of adverse reactions versus the control group. The patients' QoR-40 total scores in the ES group were improved versus the control group at 1 day after surgery. CONCLUSION: Compared with fentanyl, the use of ES (right handed) in flexible bronchoscopy during general anesthesia produces more stable hemodynamics, faster onset and recovery time of anesthesia, longer duration of analgesia, lower incidence of adverse reactions, and improved early postoperative recovery quality in patients.

Improving clinical practice through patient registries in allergy and immunology.

Patient registries are a mechanism for collecting data on allergic and immunologic diseases that provide important information on epidemiology and outcomes that can ultimately improve patient care. Key criteria for establishing effective registries include the use of a clearly defined purpose, identifying the target population and ensuring consistent data collection. Registries in allergic diseases include those for diseases such as inborn errors of immunity, food allergy, asthma and anaphylaxis, pharmacological interventions in vulnerable populations, and adverse effects of pharmacologic interventions including hypersensitivity reactions to drugs and vaccines. Important insights gained from patient registries in our field include contributions in phenotype and outcomes in inborn errors of immunity, the risk for adverse reactions in food-allergic patients in multiple settings, the benefits and risk of biologic medications for asthma during pregnancy, vaccine safety, and the categorization and genetic determination of risk for severe cutaneous adverse reactions to medications. Impediments to the development of clinically meaningful patient registries include the lack of funding resources for registry establishment and the quality, quantity, and consistency of available data. Despite these drawbacks, high-quality and successful registries are invaluable in informing clinical practice and improving outcomes in patients with allergic and immunological diseases.

Comparative analysis of the prevalence 3-HIT concept in people living with HIV and seronegative patients with chronic conditions. Cross-3HIT Project.

OBJECTIVES: This study aimed to assess and compare the occurrence of 3-HIT in people living with HIV (PLWH) and seronegative patients. Additionally, the study investigated whether HIV infection could serve as a predictor of the presence of 3-HIT. METHODS: A cross-sectional study was conducted between December 2022 and January 2023 to compare PLWH with a group of seronegative patients with chronic diseases attending an outpatient hospital pharmacy service. The 3-HIT concept encompasses the simultaneous presence of non-adherence to concomitant treatment (NAC), drug-drug interactions (DDIs), and high pharmacotherapeutic complexity in polymedicated patients. The assessment of 3-HIT compliance included NAC, evaluated using both the Morisky-Green questionnaire and electronic pharmacy dispensing records. DDIs were analysed using the Liverpool University and Micromedex databases. Pharmacotherapeutic complexity was measured using the Medication Regimen Complexity Index (MRCI) tool. Logistic regression analysis was performed to identify independent factors related to 3-HIT. Additionally, an explanatory logistic model was created to investigate whether HIV infection, along with other adjustment variables, could predict compliance with the 3-HIT concept. RESULTS: The study included 145 patients: 75 PLWH and 70 seronegative patients. The median age was 40 versus 39 years, respectively (p=0.22). Seronegative patients exhibited a higher prevalence of NAC (p<0.01). HIV infection was identified as a protective factor in the context of DDIs (p<0.01). Male sex (p<0.01) and age (p=0.01) were identified as being associated with an MRCI ≥11.25 points. A higher prevalence of 3-HIT was observed in seronegative patients (18.7% vs 48.6%, p<0.01). However, the developed regression model identified HIV infection as a risk factor associated with an increased likelihood of 3-HIT (OR 4.00, 95% CI 1.88 to 8.52, p<0.01). CONCLUSIONS: The 3-HIT concept exhibited a high prevalence among seronegative patients with chronic diseases, with HIV infection identified as a predicted risk factor for NAC and the development of 3-HIT.

Influence of medications on fall risk assessment in maintenance hemodialysis patients: A cross-sectional study.

Background: Multiple factors influence the fall risk in end-stage kidney disease. This study aims to investigate how medication factors influence the interpretation of fall risk due to age, gender, and years of dialysis treatment among patients undergoing hemodialysis (HD). Methods: A cross-sectional study was carried out in 2023 using the Johns Hopkins Fall Risk Assessment tool. Participants were recruited from the HD unit at a tertiary care academic medical center in Ajman, UAE. Data were analyzed between different ages, genders, and years on HD categories with or without medication factors. Results: Data were collected and analyzed for 44 patients. The fall risk of the study population assessed with the Kruskal-Wallis test showed no difference between different age groups (P = 0.43) but did show a significant difference when the score of medication factor was removed from the fall risk estimation (P = 0.002). A pairwise analysis showed fall risk score of the age group 46-60 years was differing from the age cohort >60 (P < 0.001). A positive moderate correlation (Spearman's correlation coefficient 0.514 was found, with a P < 0.001) was seen with an increase in age and fall risk only when the medication factor was removed from the fall risk estimation. Results on gender or duration of dialysis were insignificant. Conclusion: Medication factors being a significant contributor to fall risk among the study population was found to mask the fall risk difference between age groups 46-60 years and >60 years. Such influence was not found for gender or duration of dialysis.

Hospitalisation and adverse drug events in a geriatric oncology setting: A systematic review of the literature.

BACKGROUND: Geriatric Oncology is a specialty where a multidisciplinary approach can address the unmet needs of older adults with cancer. Older adults are at increased risk of adverse drug events (ADE) due to age-related changes in pharmacokinetics and pharmacodynamics, increasing treatment complexity, and medication burden. OBJECTIVES: To review the literature to determine the incidence of unplanned hospitalisation due to ADE for all medications, both systemic anticancer therapy (SACT) and non-SACT medications. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search included the following databases: PubMed, CINAHL, and Embase. A manual search of Scopus was then performed. Study quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, Mixed Methods Appraisal Tool (MMAT) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. RESULTS: Overall, three studies were included. One observational study reported 19 % of unplanned hospital admissions due to ADE in patients aged ≥70 years with cancer. The first retrospective study reported 24 % of unplanned hospital admissions are due to ADE in patients aged ≥70 years with cancer, and the second retrospective study reported 26 % of patients with metastatic melanoma treated with immune checkpoint inhibitors had an unplanned hospital admission due to an ADE. CONCLUSION: There is a paucity of studies assessing unplanned hospitalisation due to ADE in older adults with cancer. Future studies are needed and should account for the reporting of potential ADE relative to supportive care, ancillary medications, and indeed chronic medications used to treat long-standing comorbidities.

Guillain-Barré Syndrome After a SARS-CoV-2 Vaccine.

The worldwide mass vaccination campaign against COVID-19 has been the largest one ever undertaken. Although the short-term safety profile of the different vaccines has been well established, neuroinflammatory complications have been described, including rare cases of acute demyelinating inflammatory polyneuropathy. We report a 63-year-old man who presented to the emergency department with proximal muscle weakness and paresthesia. He had received the first dose of the AZD1222 SARS-CoV-2 vaccine (Oxford, AstraZeneca) two weeks before presentation. The diagnosis of Guillain-Barré syndrome (GBS) was confirmed by clinical features, cerebrospinal fluid analysis, and electromyography. On the second hospital day, progression to flaccid tetraplegia, cranial nerve involvement, and respiratory failure, requiring invasive mechanical ventilation, were noted, and he was admitted to the intensive care unit. Despite the prompt diagnosis and immunosuppressive treatment initiation, the patient was left with severe disability. Although the COVID-19 vaccination was generally safe and socially beneficial, individual adverse reactions, including neuroinflammatory severe complications, may occur.

Prediction of adverse drug reactions in geriatric patients admitted to intensive care units.

INTRODUCTION: Intensive care units (ICUs) pose challenges in managing critically ill patients with polypharmacy, potentially leading to adverse drug reactions (ADRs), particularly in the elderly. OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU. METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. ADR screening was performed daily through the identification of ADR triggers. RESULTS: 1295 triggers were identified (median 30 per patient, IQR=28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001). CONCLUSIONS: These data suggest that employing the severity and clinical prognosis scores used in ICUs is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

Paradoxical reaction to IL-17A inhibitor: a case report and literature review.

Objective: A case of pustular psoriasis after treatment with secukinumab in a patient with plaque psoriasis is reported, which is the first case in China. To summarize the clinical characteristics of patients who developed the rare paradoxical reaction and treatment options received IL-17A antagonist therapy, we conducted a further literature review. Methods: Data were analyzed from a patient with plaque psoriasis who developed pustular psoriasis after treatment with secukinumab. A comprehensive review of relevant domestic and international literature was conducted, focusing on cases that met our inclusion criteria for analysis and synthesis. Results: Anti IL-17A therapy may lead to type conversion, with reported cases more prevalent in women and varying in onset time, predominantly involving palmoplantar pustulosis. Conclusion: Given the increasing use of IL-17A antagonists in psoriasis treatment, it is crucial to monitor for rare adverse reactions, including the paradoxical induction of pustular psoriasis.

Nivolumab-associated immune-related filamentary keratitis.

A woman in her late 50s presented to the ophthalmology clinic having bilateral eye pain and discharge for the last month. Her medical history was significant for lung adenocarcinoma, for which she was being treated with nivolumab. Filamentary keratitis was evident at the slit-lamp examination. Regardless of ophthalmic reasons, nivolumab was suspended. Prednisolone ointment was started, with a complete remission. We present a case of steroid-responsive filamentary keratitis triggered by nivolumab. We aim to highlight the importance of prompt ophthalmology referral and the use of therapies targeting ocular surface inflammation in immune checkpoint inhibition therapy.

Three-year efficacy and safety of omidenepag isopropyl in patients with normal tension glaucoma.

PURPOSE: To retrospectively evaluate the 3-year efficacy and safety of single-agent omidenepag isopropyl in patients with normal tension glaucoma (NTG). STUDY DESIGN: Retrospective. METHODS: One hundred patients (100 eyes) who had newly been administered omidenepag isopropyl were enrolled in this study. Intraocular pressure (IOP) was compared at baseline and 6, 9, 12, 18, 24, 30, and 36 months after administration. The mean deviation values at baseline and 12, 24, and 36 months measured using the Humphrey visual field test (30-2 Swedish Interactive Threshold Algorithm standard) were compared. Adverse reactions and dropouts were assessed. RESULTS: IOP significantly decreased from 15.5±2.7 mmHg at baseline to 13.8 ±2.3 mmHg after 6 months, 13.9± 2.3 mmHg after 12 months, 13.9±2.3 mmHg after 18 months, 13.8±2.1 mmHg after 24 months, 13.9±2.0 mmHg after 30 months, and 13.6±1.7 mmHg after 36 months (P < 0.0001). There was no significant difference in the mean deviation values at baseline (-3.66±3.49 dB), 12 months (-3.41±3.80 dB), 24 months (-3.13±3.81 dB), and 36 months (-3.06±3.30 dB). Adverse reactions occurred in 11 patients (11.0%), including conjunctival hyperemia in 6 patients. Fifty-two patients (52.0%) were excluded from the analysis because they discontinued treatment either due to IOP measurement by NCT or the use of additional drugs. CONCLUSION: After the administration of omidenepag isopropyl, IOP in patients with NTG decreased within 3 years, visual fields were maintained, and safety was satisfactory. Thus, omidenepag isopropyl can be used as the first-line treatment for patients with NTG.

Pityriasis Rosea Eruption Following the Administration of Oxford-AstraZeneca Vaccine.

The coronavirus disease 2019 (COVID-19) infection has led to accelerated development and utilization of vaccines to prevent its implications on health. One of these vaccines is a vector-based, Oxford-AstraZeneca Vaccine (AZD1222). Frequently reported side effects are related to host-immune response. While dermatologic manifestation is peculiar in nature and denotes a serious eruption that might defer future vaccination. Herein, we present a case of a medically free 37-year-old female who developed clinical and histological evidence of pityriasis rosea (PR) after administration of a second-dose vaccination of AZD1222. The first dose of vaccination was administered as Pfizer BioNTech COVID-19 mRNA (BNT162b2) vaccine. This case is unique in nature as this patient developed AZD1222-induced PR, while some reports in the literature have linked PR to the BNT162b2 vaccine. This patient continued to receive a booster vaccination with BNT162b2 with no reportable side effects.