Risk Factors For Adverse Reactions Research Articles

Detection and Quantification of Drug-Protein Adducts in Human Liver.

Covalent protein adducts formed by drugs or their reactive metabolites are risk factors for adverse reactions, and inactivation of cytochrome P450 (CYP) enzymes. Characterization of drug-protein adducts is limited due to lack of methods identifying and quantifying covalent adducts in complex matrices. This study presents a workflow that combines data-dependent and data-independent acquisition (DDA and DIA) based liquid chromatography with tandem mass spectrometry (LC-MS/MS) to detect very low abundance adducts resulting from CYP mediated drug metabolism in human liver microsomes (HLMs). HLMs were incubated with raloxifene as a model compound and adducts were detected in 78 proteins, including CYP3A and CYP2C family enzymes. Experiments with recombinant CYP3A and CYP2C enzymes confirmed adduct formation in all CYPs tested, including CYPs not subject to time-dependent inhibition by raloxifene. These data suggest adducts can be benign. DIA analysis showed variable adduct abundance in many peptides between livers, but no concomitant decrease of unadducted peptides. This study sets a new standard for adduct detection in complex samples, offering insights into the human adductome resulting from reactive metabolite exposure. The methodology presented will aid mechanistic studies to identify, quantify and differentiate between adducts that result in adverse drug reactions and those that are benign.

Feline blood donation: Description and adverse reactions from 29 201 donation events between 2019 and 2023.

Feline blood transfusion is required for the treatment of various illnesses in cats, and the safety of donor cats is vital. Donor adverse reactions can include cardiorespiratory, venepuncture-related, and behavioral abnormalities. To describe a large number of feline blood donation events and document use of sedation and anxiolysis, record volume of blood collected and describe the frequency, type, and risk factors for, adverse reactions. The study included 7812 individual cats and 29 201 donation events at a blood banking center over 5 years. Retrospective analysis of donation event records with signalment, donation volume, sedation status, donation number, and adverse reactions (acute and caregiver reported) recorded. Risk factors for adverse reactions were examined by stratifying data according to groups exposed to relevant predictors and calculating odds ratios with 95% and 99% confidence intervals (CIs). Adverse reactions were uncommon (0.29%, 2.88/1000 donor events) and most commonly were cardiorespiratory (0.08%, 0.75/1000 donor events) or behavioral (0.06%, 0.62/1000 donor events). The only risk factor significantly associated with adverse reactions was conscious donation, with conscious donors 4.4 times more likely to have an adverse reaction (95% CI, 2.5-7.9, P ≤ .0001). Feline blood donation is associated with a low rate of adverse reactions. Sedation should be considered to reduce adverse reactions, and the environment and interactions optimized to reduce donor stress. Caregiver education on care postdonation could reduce behavioral adverse reactions.

Exploring Risk Factors for Adverse Reactions in Children with an Acute Psychotic Episode Using the Global Trigger Tool: Does Age Matter?

Aim: To establish significant risk factors for the development of adverse drug effects (ADEs) in children and adolescents with an acute psychotic episode taking antipsychotics. Materials and Methods: The research team randomly selected 15 patient records each month for 3 years (2016-2018). Overall, 450 patient records were included (223 boys and 227 girls, mean age was 14.52 ± 2.21 years). Adverse effects were identified using the standard algorithm of the Global Trigger Tool method. A "trigger" is an indication that an adverse reaction is likely to occur, e.g., an antihistamine prescription on a prescribing list. When a trigger was detected, the case history was studied in further detail to confirm the occurrence of ADEs. We divided patients into two groups: the "children" group (under 12 years old) and the "adolescents" group (13 years and older). Data were analyzed using the statistical package IBM SPSS Statistics 23.0. Results: Of the 450 patient records, 402 (89.3%) had at least one trigger detected. In total, 126 case histories contained evidence of ADE (28%). The total number of ADEs per 1000 patient days was 5.39 and the number of ADEs per 100 admissions was 32.0. Among adolescents, two or more triggers per patient were significantly more frequently identified (61.3% vs. 44.6%; p = 0.001). ADEs were rare in "Children" compared with "Adolescents" (13.8% vs. 30.4%; p = 0.006). The logistic regression analysis confirmed high predictive role of "Adolescence" (odds ratio [OR] = 2.58; 95% confidence interval [CI] 1.22-5.4; p = 0.013), "Polypharmacy" (OR = 1.96; 95% CI 1.23-3.1; p = 0.004), and "First-life hospitalization" (OR = 2.17; 95% CI 1.34-3.48; p = 0.001) for ADE fact in patient records. Conclusion: We found that significant risk factors for ADEs to antipsychotics in patients with acute psychotic episode were adolescence (13 years and older), polypharmacy, and first-life hospitalization. The fact that children (i.e., younger than 13 years of age) are less likely to experience ADEs was not associated with high-risk drugs or higher doses in our study.

Young Age, Female Sex, and No Comorbidities Are Risk Factors for Adverse Reactions after the Third Dose of BNT162b2 COVID-19 Vaccine against SARS-CoV-2: A Prospective Cohort Study in Japan.

Background: This study compared the adverse events (AEs) of the second and third doses of BNT162b2, as well as investigated the impact of vaccine recipients’ background and vaccination interval on the AEs of the third dose. Methods: We conducted a questionnaire survey of AEs among health care workers at Osaka University Dental Hospital. Chi-square tests were performed to compare AEs to the administration of second and third vaccine doses. Logistic regression analyses were conducted to identify factors influencing the presence of AEs using age, sex, comorbidities, and the vaccination interval. Spearman’s rank correlation coefficient was calculated to investigate the correlation between age, vaccination interval, and severity of each AE. Results: The third dose of BNT162b2 was associated with significantly more frequent or milder AEs than the second dose. Logistic regression analyses detected significant differences in six items of AEs by age, three by sex, two by comorbidities, and zero by vaccination interval. Consistently, the risk of AEs was greater among younger persons, females, and those without comorbidities. Significant negative correlations were detected between age and vaccination interval, and between age and the severity of most AEs. Conclusions: Young, female, and having no comorbidities are risk factors for AEs after the third dose of BNT162b2, while vaccination interval is not.

Clinical Effect of Open Reduction and Internal Fixation for Femoral Neck Fracture in Young Adults and Related Factors of Femoral Head Necrosis.

Objective The purpose of this article is to analyze the clinical effect of open reduction and internal fixation on femoral neck fracture in young adults and to explore the related factors of femoral head necrosis. Methods The subjects were young and middle-aged femoral neck fracture patients admitted to our hospital from July 2019 to July 2021. 90 patients were randomly divided into two groups according to different treatment methods. The control group (n = 45) was treated with open reduction and internal fixation with hollow nails, while the observation group (n = 45) was treated with closed reduction and internal fixation with hollow nails. The clinical effects and adverse reactions of the two groups and the risk factors of avascular necrosis of femoral head were analyzed. Results Compared with the control group, the operation time of the observation group was significantly shortened (P < 0.05), the amount of bleeding during the operation was significantly reduced (P < 0.05), and the incidence of total adverse reactions was significantly reduced (P < 0.05). The HSS score and Harris score of the two groups were significantly decreased after treatment (P < 0.05), but there was no significant difference in the above scores between the two groups before and after treatment (P > 0.05). The related risk factors of necrosis included gender, Garden classification, time from injury to operation, and time of weight bearing after operation (P < 0.05) but not related to age and cause of injury (P > 0.05). Conclusion Open and closed reduction and internal fixation can effectively treat femoral neck fracture in young adults. The risk factors of adverse reactions of osteonecrosis include gender, Garden classification, time from injury to operation, and weight-bearing time after operation.

GADOLINIUM-INDUCED CARDIOPULMONARY ARREST IN A 57-YEAR-OLD FEMALE

TOPIC: Allergy and Airway TYPE: Medical Student/Resident Case Reports INTRODUCTION: Magnetic resonance contrast agents are used to better characterize disease processes during Magnetic Resonance Imaging (MRI). Gadolinium based contrast agents (GBCA) are widely used due to their safety profile. The incidence of adverse events after receiving GBCAs is less than 2%, most being mild and transient [1,2]. Here, we see a patient who developed cardiopulmonary arrest after GBCA administration. CASE PRESENTATION: A 57 year old female with a past medical history of asthma, hypertension, diabetes, hyperlipidemia and mild COVID19 infection, presented to outpatient brain MRI for evaluation of new hearing loss. After receiving Gadobutrol, she developed shortness of breath, abdominal pain, and emesis. In the emergency department, the patient was hypothermic, tachypneic, and hypoxic;no urticaria or rash noted. She was placed on non-invasive ventilation and treated for presumed anaphylaxis, but remained hypoxic and in respiratory distress. Subsequent intubation (without angioedema visualized) was complicated by cardiac arrest, requiring six minutes of cardiopulmonary resuscitation. Initial imaging was significant for CT chest showing diffuse ground glass and consolidative opacities and normal CT head. Despite standard care treatment, the patient's neurological exam worsened, one week into her admission she was observed to have minimal brainstem reflexes, with head CT showing findings of anoxic brain injury, cerebral edema and possible uncal herniation. She worsened clinically and expired thirteen days after admission. Autopsy performed showed clinicopathological correlation attributing anoxic brain injury secondary to anaphylaxis. DISCUSSION: Gadobutrol is approved for multiple indications in most ages. It was introduced in 1998, its safety profile has been studied in patients worldwide. The incidence of adverse events of GBCA has been reported to be 0.32-3.8%, commonly nausea, vomiting, urticaria and dizziness. Risk factors include patients' history of respiratory allergic disease, asthma, COPD, or prior history of reactions to iodinated contrast media [1,2]. The incidence of serious adverse drug reactions (ADR) involving the cardiopulmonary system is reported to be <0.1%;from 1998-2012 there were 614 cases of ADR of which 7.2% were fatal [3]. Our case presentation shows a severe ADR to gadolinium contrast for MRI. Though the patient's pre-existing history of asthma put her at slightly higher risk, proven safety of gadolinium contrast significantly weighs towards continued use of contrast enhanced MRI. Nevertheless, awareness and timely response to possible contrast-induced ADR is important for all clinicians. CONCLUSIONS: GBCA are widely used agents with good safety profiles. Although severe adverse events are rare, it's important for physicians to have a high index of suspicion and use caution in patients that are identified with risk factors for adverse reactions to these agents. REFERENCE #1: [1] Marie-France Bellin. MR contrast agents, the old and the new. European Journal of Radiology volume 60, Issue 3, 2006, 314-323. doi.org/10.1016/j.ejrad.2006.06.021. REFERENCE #2: [2] Endrikat, Jan MD, PhD*†;Vogtlaender, Kai PhD‡;Dohanish, Susan RA§;Balzer, Thomas MD, PhD∥;Breuer, Josy MD, PhD*Safety of Gadobutrol, Investigative Radiology: September 2016 - Volume 51 - Issue 9 - p 537-543 doi: 10.1097/RLI.0000000000000270 REFERENCE #3: [3] Raisch, D. W., Garg, V., Arabyat, R., Shen, X., Edwards, B. J., Miller, F. H.,… West, D. P. (2013). Anaphylaxis associated with GADOLINIUM-BASED contrast AGENTS: Data from the food and DRUG Administration's adverse event reporting system and review of case reports in the literature. Expert Opinion on Drug Safety, 13(1), 15-23. doi:10.1517/14740338.2013.832752 DISCLOSURES: No relevant relationships by Lauren Blackwell, source=Web Response No relevant relationships by Rostislav Gorbatov, source=Web Response No relevant relationships by Chinazor Iwuaba, source=Web Response

The Relationship between Serum Leukotriene B4 and High-Sensitivity C-Reactive Protein Expression Levels and Adverse Reactions in Patients with Colon Cancer During Perioperative Blood Transfusion

To explore the predictive value of serum high-sensitivity C-reactive protein and leukotriene B4 in perioperative blood transfusion patients with colon cancer in patients with adverse blood transfusion reactions. 168 patients undergoing colon cancer surgery in a hospital from March 2018 to March 2020 were selected as the research objects and checked the levels of high-sensitivity C-reactive protein and leukotriene B4 in the venous blood of all patients. There were 73 cases in the adverse blood transfusion group (experimental group) and 95 cases in the non-transfusion reaction group (control group). The serum levels of high-sensitivity C-reactive protein and leukotriene B4 in the two groups were compared. Based on the analysis of the basic data of the two groups of patients, serum high-sensitivity C-reactive protein and leukotriene B4 are independent risk factors for perioperative adverse reactions in colon cancer patients. The levels of serum high-sensitivity C-reactive protein and leukotriene B4 in the experimental group are higher than those in the normal group and there are differences, both were statistically significant (p<0.05); receiver operating characteristic curve results showed that the area under the curve of high-sensitivity C-reactive protein and leukotriene B4 alone and in combination to predict adverse transfusion reactions were 0.733, 0.819 and 0.877, respectively. The area under the curve of combined factor diagnosis was greater than single diagnosis; serum high-sensitivity C-reactive protein≥14.64 mg/l and leukotriene B4≥18.86 pg/l are risk factors for adverse reactions in patients with colon cancer perioperative blood transfusion. Elevated serum high-sensitivity C-reactive protein and leukotriene B4 in patients with colon cancer during perioperative blood transfusion are risk factors for adverse blood transfusion reactions. High-sensitivity C-reactive protein≥14.64 mg/l and leukotriene B4≥18.86 pg/l suggest that adverse blood transfusion reactions may occur. The combination of the two can increase the incidence of adverse blood transfusion reactions.

Adverse reactions to 1% cyclopentolate eye drops in children: an analysis using logistic regression models.

To determine the frequency, symptoms and risk factors for adverse reactions to two-times instillation of 1% cyclopentolate in children. Prospective, observational study. The subjects were 646 patients who underwent cycloplegic refraction with cyclopentolate (mean age; 7.0±3.5years, age range; 0-15years). Five minutes after instillation of 0.4% oxybuprocaine hydrochloride, a 1% cyclopentolate eye drop was instilled twice, with an interval of 10min. Fifty minutes later, two certified orthoptists evaluated adverse reactions using a questionnaire and interviewed the patients' guardians. The relationship between the adverse reaction rates and age, gender, additional instillation, complications of the central nervous system (CNS), time of day and season were analysed using binominal and polytomous logistic regression models. The overall frequency of adverse reactions was 18.3% (118/646 patients). The main symptoms included conjunctival injection (10.5%, 68/646), drowsiness (6.8%, 44/646) and facial flush (2.2%, 14/646). The odds ratio (OR) of conjunctival injection increased with patient's age (p<0.05), in boys (p<0.01) and in winter (p<0.001). In contrast, the OR of drowsiness decreased with age (p<0.001). Facial flush was observed mostly in children younger than 4years. CNS complications were not a significant risk factor for any of the symptoms. Adverse reactions to 1% cyclopentolate eye drops were more frequent than previously expected, but all were mild and transient. The probability of each symptom was associated with a clear age-specific trend.

Oral Immunotherapy with Cow's Milk Allergy: Five Years' Experience from a Single Center in Turkey

Background:Oral immunotherapy for cow’s milk allergy is an effective treatment option because of its ability to increase the threshold for clinical reactions.Aims:To present our experience of oral immunotherapy for cow’s milk allergy in the pediatric allergy outpatient clinic, and to evaluate the long-term efficacy of oral immunotherapy and risk factors for adverse reactions during oral immunotherapy.Study Design:Single-center retrospective cohort study.Methods:Forty-two patients with Immunoglobulin-E-mediated cow’s milk allergy who complied with the oral immunotherapy protocol were evaluated in this study. The treatment consisted of a rapid escalation phase with an oral food challenge step that included milk doses. During the build-up phase, increasing quantities of cow’s milk were administered until the patient was able to consume 200 mL of cow’s milk daily.Results:The mean age of starting the oral immunotherapy was 40.2±3.2 (range, 36-156) months, and 54.8% (n=23) of the patients were males. The mean duration of the build-up phase was 18.1±5.6 (range, 9-41) weeks, and the mean maintenance phase was 29.1±11.6 (range, 12-63) months. During the oral immunotherapy, 36 adverse reactions (78% mild and 22% moderate) occurred in 16 (38%) patients. There were no differences in the age of starting the oral immunotherapy (p=0.19), cow’s milk-specific Immunoglobulin-E levels (p=0.17), and cumulative provocative doses of oral food challenges (p=0.78) between the two groups of patients with and without adverse reactions. The wheal diameters to cow’s milk were higher in the group with adverse reactions (p=0.03). There was no difference in the oral immunotherapy onset age between patients with and without a history of anaphylaxis (p=0.38). The patients with a history of anaphylaxis had more adverse reactions (p=0.04) and a higher number of reactions during the oral immunotherapy (p=0.01), and a higher mean duration of the up-dosing phase (p=0.04) compared with patients without anaphylaxis.Conclusion:Oral immunotherapy is a treatment option in patients with cow’s milk allergy because of its high efficacy. Adverse reactions occur in about 40% of cases and are mostly mild. It should be administered with caution to patients with a history of anaphylaxis and a higher wheal diameter to cow’s milk in the skin prick test.

Analysis of Related Factors of Adverse Transfusion Reactions

To investigate the related factors of adverse reactions of blood transfusion, and clinical precautions so as to reduce the adverse reactions. Data of 2108 patients with allogeneic transfusion in our hospital from January 2017 to June 2017 collected and analyzed. These patients received 15 244 time of blood transfusion, and 213 time of adverse reactions occurred in 178 patients in totality, the incidence is 1.4%, and there was no significant difference between the male (1.31%) and female (1.53%). The main type of transfusion reaction were allergy (73.23%), FNHTR (11.74%) and TACO (10.80%). Among all kinds of blood components, the incidence of adverse reactions of apheresis platelet transfusion was the highest (4.31%), significantly higher than that of cryoprecipitate and other blood components. The incidence rate of adverse reactions of blood transfusion in the hematopathy patients was 2.56%, significantly higher than that of immune diseases (1.48%), cancer diseases (1.28%) and other diseases (1.08%), (P＜0.01). The rate of transfusion history of apheresis platelets was 42.67% (the incidence of adverse reactions was 4.31%), significantly higher than other groups (P＜0.01); the rate of transfusion history of cryoprecipitate was 4.11% (the incidence of adverse reaction was 0.45%), significantly lower than other groups (P＜0.05). Among the disease types, the rate of transfusion history in the hematopathy patients was 48.79% (the incidence of adverse reaction was 2.56%), significantly higher than that of other groups (P＜0.01). The incidence of drug allergy in patients with the adverse reactions to blood transfusion was 11.25%, significantly higher than that of patients without adverse reactions (4.71%) (P＜0.01). The main risk factors of adverse reactions of blood transfusion are as follows: blood varieties, disease type, transfusion history and drug allergy history. For the patients with transfusion, multiple factors should be controlled, so as to reduce the adverse reactions.

Knowledge and practices of cardiopulmonary arrest and anaphylactic reactions in the radiology department.

BackgroundEmergencies in the radiology department may arise in critically ill patients who are brought to the department for imaging, interventional procedures or as a result of adverse reactions to contrast media used for imaging. Adverse reactions to contrast media range from minor to severe life-threatening effects and initial, prompt management decreases complications. Radiology staff must possess knowledge of the management of anaphylactic or anaphylactoid contrast reactions and cardiopulmonary arrest (CPA) as they are likely to be the first responders.ObjectivesTo determine the knowledge and practices amongst radiologists, radiology residents and radiographers in the management of CPA and adverse reactions to contrast media.MethodThis cross-sectional study was performed between March and August 2016 at Kenyatta National Hospital using a questionnaire.ResultsEighty participants were enrolled. None answered all the questions correctly, with only 55% of radiologists, 35% of residents and 39% of radiographers scoring above 50%. The majority (82%) of participants had adequate knowledge regarding the symptoms, signs and risk factors of adverse reactions to contrast media; however, only 30% knew that intravenous epinephrine is the recommended therapy for a severe anaphylactic reaction. Shortcomings in terms of adequate training were found in this study, with the majority of respondents having not attended any life support course in the preceding 5 years.ConclusionHealth providers within the radiology unit had knowledge about identifying both mild and severe symptoms of anaphylactic reactions. However, there were knowledge gaps regarding the management of these reactions.

Systemic and large local reactions during subcutaneous grass pollen immunotherapy in children.

Subcutaneous immunotherapy (SCIT) is the allergen-specific curative treatment of allergic rhinitis. Adverse effects, most of which are local, can be observed during the immunotherapy. These adverse effects have been reported more frequently during the pollen season. The purpose of this study was to estimate the rate of local, large local, and systemic reactions during the treatment, to determine the relationship between adverse reactions and the season in which these reactions occur, as well as the risk factors for adverse reactions during the grass pollen-specific SCIT treatment in children. We retrospectively collected and analyzed the data of 261 children who administered grass pollen SCIT between 2008 and 2018. A total of 261 children (177, 67.8% male), who received grass pollen SCIT, with a mean (±SD) age of 12.0±3.0years at the initiation of SCIT were enrolled to the study. The number of the patients who experienced local and large local reactions was 109 and 30, respectively. In addition, the number of the patients with systemic reactions was 35. After the 12284 injections, local reactions occurred in 357 (2.9%), and this was followed by systemic reaction as 55 (0.4%) and large local reactions as 40 (0.3%). Frequency of local (P<.001) and systemic reactions (P=.003) was higher during grass pollen season than out of the grass pollen season. In multivariate analysis, initiation of SCIT during the grass pollen season [OR:7.351, 95%CI:1.532-35.279, P=.013] and experiencing local reactions [OR:4.214, 95%CI:2.159-8.224, P<.001] were independent predictors for the development of large local and systemic reactions. SCIT, in which only mild-to-moderate systemic reactions occurred, is safe for the treatment of allergic rhinitis in children. Our study revealed that previous local reactions and initiation of immunotherapy during the grass pollen season were the predictors for large local and systemic reactions during SCIT in children.

Efficacy, safety and satisfaction of sedation-analgesia in Spanish emergency departments

ObjectivesTo offer analgesia and sedation should be a priority in paediatric emergency departments. The aim of this study was to determine the effectiveness and safety of the sedation-analgesia procedure, as well as the satisfaction of the doctors, patients and parents. MethodsA multicentre, observational, and prospective analytical study was conducted on the sedation-analgesia procedure performed on children younger than 18 years old in 18 paediatric emergency departments in Spain from February 2015 until January 2016. ResultsA total of 658 procedures were recorded. The effectiveness was good in 483 cases (76.1%; 95% CI: 72.7–79.4%), partial in 138 (21.7%; 95% CI: 18.5–24.9%), and poor in 14 (2.2%; 95% CI: 1.1–3.4). The effectiveness was better when the doctor in charge was an emergency paediatrician (OR: 3.14; 95% CI: 1.10–8.95), and when a deeper level of sedation was achieved (OR: 2.37; 95% CI: 1.68–3.35). Fifty two children (8.4%) developed adverse drug reactions, more usually gastrointestinal, neurological or respiratory ones (89.9% were resolved in <2h). One patient was intubated. The older child and a deeper level of sedation were found to be independent risk factors for adverse reactions (OR: 1.18; 95% CI: 1.09–1.28 and OR: 1.86; 95% CI: 1.22–2.83, respectively). Thirteen children (5%) developed late adverse drug reactions, more commonly, dizziness and nauseas. A combination of midazolam/ketamine had been used in all the cases (RR: 24.46; 95% CI: 11.78–50.76). The perceived satisfaction level (0–10) was obtained from 604 doctors (mean: 8.54; SD: 1.95), 526 parents (mean: 8.86; SD: 1.49), and 402 children (mean: 8.78; SD: 1.70). ConclusionsThe sedation-analgesia procedure performed in paediatric emergency departments by trained paediatricians seems to be useful, effective and safe, as well as satisfactory for all participants.

Risks of leukapheresis and how to manage them—A non-systematic review

Leukapheresis is like any other preparative apheresis, except it isn’t: Leukapheresis typically takes much longer, larger blood volumes are processed and, consequently, larger ACD-A volumes are administered. Blood component donors and leukapheresis subjects are also quite different populations. Allogeneic donors tend to be younger and many are first-time donors, both of which are risk factors for adverse reactions during blood donation. Moreover, more than half of all leukapheresis collections are performed in patients. Here it is the age distribution, including patients at the extremes of age, as well as the underlying disease and co-morbidities which may expose them to higher, or different, risks compared to donors. Both groups thus have good reasons why adverse effects to leukapheresis might be more frequent, more severe, or even different in nature altogether. Compared to other preparative apheresis types like platelet or plasma apheresis, the risks of leukapheresis have been studied less extensively, as it is in comparison a relatively low-frequency intervention. Often leukapheresis remains a domain of hematologists who have a different sense of procedural safety than transfusionists. Furthermore, G-CSF mobilized “stem cell” aphereses by a wide margin outnumber unmobilized aphereses, so that the very strong signal from adverse reactions to G-CSF all but drowns out signals from the apheresis proper. This focused review assesses observations from leukapheresis as well as extrapolation of observations from other forms of preparative apheresis in an attempt to gauge the safety of leukapheresis and identify potential approaches to its further improvement. In short, the overall impression is one of a very satisfactory safety record of leukapheresis, with occasional issues with venous access or vasovagal problems, and frequent, but highly responsive and rarely limiting ACD-A toxicity.

Prevalence, incidence and factors associated with adverse reactions to foods in Cuban infants. A population-based cohort study

The prevalence of asthma and allergic diseases in Cuban children is high, but little is known about adverse reactions to foods. To determine the prevalence, incidence and risk factors for adverse reaction to foods in children. Population-based cohort study carried out in Havana, Cuba, in a three-year period. Parents of 1543 children provided medical and lifestyle information from the first to the third year of age, which was collected using a questionnaire. An adverse reaction to foods was defined by medical diagnosis reported by the parents or caregivers. Annual cumulative incidence was 5.7%, 1.9% and 0.8%, whereas annual prevalence was 5.7%, 4% and 2.5% at 1, 2 and 3 years of age, respectively; 8% of infants had experienced an adverse reaction to foods when they turned 3 years of age. Cow milk was the most commonly implicated food. Main risk factors were allergenic food consumption, use of antibiotics, factors related to the presence of allergens, maternal history of overweight during pregnancy and allergy to insect bites. Adverse reaction to food is a significant clinical problem in children from Havana. Modifiable risk factors were identified, the understanding of which will help to direct effective intervention strategies.

Clinical safety and efficacy of “filgrastim biosimilar 2” in Japanese patients in a post-marketing surveillance study

We conducted a post-marketing surveillance to evaluate the safety and efficacy of TKN732, approved as "filgrastim biosimilar 2", in Japanese patients who developed neutropenia in the course of cancer chemotherapy or hematopoietic stem cell transplantation. A total of 653 patients were registered during the 2-year enrollment period starting from May 2013, and 627 and 614 patients were eligible for safety and efficacy analyses of the G-CSF biosimilar, respectively. Forty-three adverse drug reactions were reported in 33 patients (5.26%). Back pain was most frequently observed and reported in 20 patients (3.19%), followed by pyrexia (1.28%) and bone pain (0.96%). Risk factors for adverse reactions identified by logistic regression analyses were younger age, presence of past medical history, and lower total dose at the onset of adverse reactions. Among the 576 cancer patients who developed Grade 2-4 neutropenia after chemotherapy, recovery to Grade 1/0 was reported in 553 patients (96%) following filgrastim biosimilar 2 treatment. The median duration of neutrophil counts below 1500/μL was 5 days. In addition, all 11 patients who underwent hematopoietic stem cell transplantation had good responses to filgrastim biosimilar 2. In conclusion, this study showed that filgrastim biosimilar 2 has a similar safety profile and comparable effects to the original G-CSF product in the real world clinical setting.

TLR1 polymorphisms are significantly associated with the occurrence, presentation and drug-adverse reactions of tuberculosis in Western Chinese adults.

BackgroundObtaining further knowledge regarding single nucleotide polymorphisms in the Toll-like receptor1 gene is of great importance to elucidate immunopathogenesis and management of tuberculosis.ResultsRs5743565 and rs5743557 were significantly associated with reduced predisposition to TB regarding the mutant allele in additive and dominant models with odds ratios (ORs) ranging from 0.61 to 0.83. There was increased tuberculosis risk associated with the haplotype CAG (rs4833095/rs76600635/rs5743596) [OR (95% CI) = 1.33 (1.07–1.65)] and with haplotype GG (rs56357984/rs5743557) [OR = 1.21 (1.02–1.43)]. The erythrocyte and hemoglobin levels were significantly higher in TB patients with the rs5743557 GG genotype than for AA and/or AG genotype carriers (p = 0.006 and 0.020, respectively). The occurrence rates of chronic kidney damage and hepatotoxicity were 21.56% and 10.32%, respectively. Rs5743565 seemed to pose a higher risk of anti-TB-induced hepatotoxicity under the dominant model [OR = 2.17 (1.17–4.05)], and rs76600635 GG/AG genotypes were clearly correlated with the development of thrombocytopenia [OR = 2.98 (1.26–7.09)].ConclusionsRs5743565 and rs5743557 in the TLR1 gene may contribute to decreased risk for tuberculosis susceptibility in a Western Chinese population. Rs5743565 and rs76600635 are potential risk factors for adverse reactions to anti-TB drugs.MethodsWe enrolled 646 tuberculosis patients and 475 healthy controls from West China. Six single nucleotide polymorphisms in Toll-like receptor1 gene were genotyped in every individual and were analyzed for their association with tuberculosis susceptibility and clinical presentation. The prospective follow-up was performed to determine whether these single nucleotide polymorphisms are associated with adverse reactions to anti-tuberculosis drugs.

Adverse reactions to fillers should be published - on the consensus statement on adverse effects following hyaluronic acid-based fillers.

By Philipp-Dormston et al.1 Aesthetic procedures are two faced. On one side, we see fabulous or at least okay results and on the other side adverse reactions from – when it comes to fillers – abscesses to blindness. Thankfully, these adverse reactions are – for most fillers – rare. Being rare, however, makes things not easier as the knowledge on risk factors for adverse reactions and treatment of adverse reactions are based mostly on expert opinion – and experts might err. Therefore, to reduce errors and misconceptions, it is of uttermost importance that we publish these cases! Based on the discussed paper, the group has been treating several hundreds of patients with adverse reactions to fillers. These cases need to be accessible! Even a single case report as a quite recent one from Spain which points to an increased risk of hyaluronic acid (HA) fillers based on the Vycross technology is helpful. Specifically, as in this case report the delayed! filler reaction was reproducible in a skin test with the Vycross products the patient did receive before.2 This very simple case reports invalidates (in my humble expert opinion) all discussions on biofilm in HA fillers and instead points to an increased risk of a specific HA filler family. Besides the biofilm issue, the paper is as good as an expert consensus paper can be and should rise awareness to the dark side of HA fillers. Only one very small comment at last. What I did not understand was – why it was necessary to fund this consensus paper by two companies? This is a simple expert consensus guideline which in my opinion does not need external funding as it is not based on an extensive literature search. Being funded by only two companies raises further the question (honi soit qui mal y pense) if there was a specific interest behind for the two companies to fund this consensus.

СПЕКТР И ФАКТОРЫ РИСКА НЕЖЕЛАТЕЛЬНЫХ ПОБОЧНЫХ РЕАКЦИЙ ПРИ ЛЕЧЕНИИ ВПЕРВЫЕ ВЫЯВЛЕННЫХ БОЛЬНЫХ ТУБЕРКУЛЕЗОМ

In order to evaluate the frequency and risk factors of adverse reactions, the monitoring results of clinical and laboratory tests of 435 new cases of respiratory tuberculosis being on the intensive phase of chemotherapy have been analyzed. 95.2% of patients had adverse reactions (95% CI 92.7-96.9); 48.7% demonstrated severe adverse reactions and in 72.7% treatment regimen had to be changed. Regarding the profile of adverse reactions, hepatotoxic ones prevailed (59.3%), they were followed by allergic reactions (53.6%), gastrointestinal reactions (35.6%) and hyperuricemia (61.6%). Certain risk factors have been identified for each of the above types of adverse reactions, making it possible to predict and prevent them prior to the start of chemotherapy.

Systematic Screening of Adverse Reactions to Metal Debris after Recap-M2A-Magnum Metal-on-Metal Total Hip Arthroplasty.

An adverse reaction to metal debris is a known complication after large diameter head metal-on-metal total hip arthroplasty. However, the failure rate varies depending on the implant design. Therefore, we investigated the prevalence of adverse reaction to metal debris, as well as the symptoms and risk factors after undergoing a ReCap-M2a-Magnum large diameter head metal-on-metal total hip arthroplasty. Between 2005 and 2012, 1188 patients (1329 hips) underwent ReCap-M2a-Magnum total hip arthroplasty at our institution. Systematic screening for adverse reaction to metal debris was arranged using the Oxford Hip Score questionnaire, hip and pelvic radiographs, and assessments of the serum chromium and cobalt ion levels. Clinical evaluation and magnetic resonance imaging were performed for the symptomatic patients, as well as those with either chromium or cobalt ion levels ⩾5 µg/L. The prevalence of adverse reaction to metal debris after ReCap-M2a-Magnum total hip arthroplasty was assessed, and the risk factors for adverse reaction to metal debris were evaluated using logistic regression. The mean follow-up time was 5.2 (0.003-9.1) years. This study was an extension of a previous study conducted at our institution with 80 patients. In total, 33 patients (33 hips, 2.5% of all hips) required a revision operation due to adverse reaction to metal debris. Moreover, 157 hips exhibited definitive adverse reaction to metal debris, but a revision operation was not performed (157 of 1329 hips, 11.8% of all hips). Overall, 190 out of 1329 (14.3%) hips had definitive adverse reaction to metal debris. Pain, subluxation sensation, clicking, swelling, a small head size, and a fair/poor Oxford Hip Score were associated with definitive adverse reaction to metal debris. We found a high prevalence of adverse reaction to metal debris in the ReCap-M2a-Magnum total hip arthroplasty patients in this study; however, most of the patients did not require revision operations.