Utilising primary care electronic health records to deliver the ALABAMA randomised controlled trial of penicillin allergy assessment.

BACKGROUND: Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. METHODS: A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. RESULTS: An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The 'ALABAMA unit' within SystmOne was also created and provided a secure efficient environment to access participants' EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. CONCLUSIONS: ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.

Aspirin Desensitization and Percutaneous Coronary Intervention in a Patient with Aspirin Hypersensitivity and Acute Coronary Syndrome: A Case Report.

Hypersensitivity to aspirin is rare disorder occurring in 1.88% of the patients. Aspirin-hypersensitive patients requiring single antiplatelet agent may be treated with clopidogrel, an alternative antiplatelet agent. However, aspirin desensitization is more cost-effective than the usage of clopidogrel in these patients. Furthermore, aspirin desensitization is of greater value in patients requiring dual antiplatelet therapy, for example following procedures like percutaneous transluminal coronary angioplasty (PTCA) instead of using non-aspirin-based combinations. Herein, we report a 74-year-old hypertensive male presented with features of acute coronary syndrome and planned for percutaneous transluminal coronary angioplasty of RCA followed by dual antiplatelet therapy. Since he had aspirin allergy, desensitization was done using rapid desensitization protocol for which he responded well. This case highlights the importance of aspirin-desensitization in patients with aspirin allergy instead of choosing non-aspirin based antiplatelet agents.

Predictors of immediate and delayed cutaneous hypersensitivity reactions to paclitaxel.

Paclitaxel is one of the first-line treatments for breast, ovarian, and lung cancers. However, its use is limited by the high frequency of hypersensitivity reactions. In this retrospective chart review at Memorial Sloan Kettering Cancer Center, we assess clinical factors associated with immediate and delayed hypersensitivity reactions to paclitaxel and characterize delayed hypersensitivity reactions to paclitaxel in patients with breast cancer. 12,274 patients were treated with paclitaxel. 6,165 had breast cancer and 1,233 were seen by a dermatologist. 734 patients (11.9%) developed an immediate hypersensitivity reaction. Age (p < 0.001), race (p < 0.001), and prior history of allergy (p = 0.05) were associated with immediate hypersensitivity reactions. 147 patients (4.0%) had a rash of interest. The most common phenotypes were maculopapular (52%) and urticaria (36%). Race (p < 0.001) and history of allergy (p < 0.001) were associated with development of a cutaneous reaction. Patients with an immediate hypersensitivity reaction were more likely to have developed a delayed cutaneous reaction (OR = 1.80). Risk factors for development of immediate hypersensitivity reactions in this study were younger age, race, and history of allergy. Patients who developed an immediate hypersensitivity reaction were more likely to develop a delayed hypersensitivity reaction. Risk factors for development of the rash included Asian race and history of allergy. Identification of risk factors is critical to guide care coordination. Awareness of these clinical factors which are associated with development of a rash could guide providers in choosing treatment with paclitaxel or nab-paclitaxel. If the cutaneous reactions are bothersome to the patient, the transition of treatment from paclitaxel to nab-paclitaxel may be warranted, or a consideration of re-challenge or desensitization may be discussed.

Preventing Overrides of Severe Drug Allergy Alerts Initiative: an Implemented System Upgrade.

Administering medications to patients with documented drug hypersensitivity reactions (DHR) poses a significant risk for adverse events, ranging from mild reactions to life-threatening incidents. Electronic healthcare systems have revolutionized the modern clinical decision-making process, with built in warnings. However, as these alerts become a routine part of healthcare provider's workflow, alert fatigue becomes a challenge. This study was conducted within the Ministry of National Guard Health Affairs (MNGHA), a government healthcare system in Saudi Arabia. A taskforce of experts was formed to develop an electronic path that would prevent unintentional overrides of severe drug allergy alerts. The system underwent rigorous testing, and monitoring parameters were established. We outline the implementation of a system upgrade designed to trigger an alternative interruption in the computerized physician order entry (CPOE) process, distinct from the regular allergy pop-up alerts. The alternate path is activated upon a CPOE with a drug-to-drug match and a documented severe drug allergy symptom, necessitating co-signature form another prescriber before proceeding. The adopted upgrade is a proactive approach to enhance medication safety in electronic healthcare systems, ensuring that serious allergy-related warnings are not overridden, ultimately enhancing patient safety. Further monitoring will confirm the safety and effectiveness of this measure. This study provides a model for institutions seeking to prevent allergy-related harm within their patient population.

Iodine and Gadolinium Contrast Reactions: What Is the Risk and Role of Premedication, Abbreviated Protocols, Prior History of Reactions, and Cross-Reactivity?

Immediate hypersensitivity reactions to iodinated contrast media and gadolinium-based contrast media can be life-threatening. While corticosteroid premedication or agent-switching may mitigate risk, evidence is largely indirect and based on historical studies; recent literature refutes the efficacy. Guidance on premedication varies between organizations worldwide. No strategy eliminates reactions, and indirect consequences of premedication are substantial. Accelerated regimens are often used for emergencies, but are of questionable efficacy. Identifying "high-risk" patients is complex, but a history of reactions (to the same contrast class) is the biggest risk factor.

Characteristics of childhood anaphylaxis in different age groups.

BACKGROUND: Anaphylaxis is a severe systemic hypersensitivity reaction that usually has a rapid onset and can be fatal. Presentations of childhood anaphylaxis vary widely in accordance with the triggers and the patient's age, geographical region and dietary and lifestyle habits. METHODS: The medical records of 177 paediatric patients diagnosed with anaphylaxis between January 2021 and January 2024, whose disease progression was monitored at a single tertiary care centre, were reviewed retrospectively. RESULTS: The study included 177 patients diagnosed with anaphylaxis (107 males and 70 females with a median age of 48 months). The most common allergen responsible was food (53.7%). Egg allergy was the most common source of anaphylaxis, afflicting 35 patients (19.3%), while beta-lactam provoked the most common drug allergy, affecting 24 patients (13.6%). The most common organ involved was the skin (92.7%). When the patients were analysed by age group, there were more males in the infancy, preschool and school age groups, while there were more females in the adolescent group (p = 0.44). Food-induced anaphylaxis became less common with increasing age, whereas the rate of drug-induced anaphylaxis increased (p = 0.01 and p = 0.01, respectively). Cardiovascular system findings were observed more frequently in adolescents compared to other age groups (p = 0.003). Most cases stemming from a food allergy were mild, whereas most drug-induced cases were moderate or severe (p < 0.05). When severity was analysed by age group, mild cases in infants were more common than moderate to severe cases. CONCLUSION: The aetiological and clinical manifestations of childhood anaphylaxis vary among different age groups.

"What if the patient has a severe reaction, and it is my fault?" A qualitative study exploring factors for sustainable implementation of penicillin allergy delabelling.

BACKGROUND: Penicillin allergy delabelling (PAD), the process of evaluating penicillin allergy labels, is a key target in antibiotic stewardship, but uptake of the procedure outside clinical studies is limited. We aimed to explore factors that need to be addressed to sustainably implement a clinical pathway for PAD. METHODS: We conducted a qualitative study based on semi-structured interviews with focus groups consisting of a purposive sample of twenty-five nurses and physicians working in four different hospitals in Western Norway. Systematic text condensation was applied for analysis. RESULTS: Psychological safety was reported as crucial for clinicians to perform PAD. A narrative of uncertainty and anticipated negative outcomes were negatively associated with PAD performance. Education, guidelines, and colleague- and leadership support could together create psychological safety and empower health personnel to perform PAD. Key factors for sustainable implementation of PAD were facilitating the informant's profound motivation for providing optimal health care and for reducing antimicrobial resistance. Informants were motivated by the prospect of a simplified PAD procedure. We identified three main needs for implementation of PAD: (1) creating psychological safety; (2) utilising clinicians' inherent motivation and (3) optimal organisational structures. CONCLUSION: A planned implementation of PAD must acknowledge clinicians' need for psychological safety and aid reassurance through training, leadership, and guidelines. To implement PAD as an everyday practice it must be minimally disruptive and provide a contextually adaptive logistic chain. Also, the clinician's motivation for providing the best possible healthcare should be utilised to aid implementation. The results of this study will aid sustainable implementation of PAD in Norway. ETHICS: The study was approved by the Western Norway Regional Committee for Medical Research Ethics (Study No:199210).

Factors influencing implementation and adoption of direct oral penicillin challenge for allergy delabelling: a qualitative evaluation.

BACKGROUND: Over 95% of penicillin allergy labels are inaccurate and may be addressed in low-risk patients using direct oral penicillin challenge (DPC). This study explored the behaviour, attitudes and acceptability of patients, healthcare professionals (HCPs) and managers of using DPC in low-risk patients. METHODS: Mixed-method, investigation involving patient interviews and staff focus groups at three NHS acute hospitals. Transcripts were coded using inductive and deductive thematic analysis informed by the Theoretical Domains Framework. FINDINGS: Analysis of 43 patient interviews and three focus groups (28 HCPs: clinicians and managers) highlighted themes of 'knowledge', 'beliefs about capabilities and consequences', 'environmental context', 'resources', 'social influences', 'professional role and identity', 'behavioural regulation and reinforcement' and a cross-cutting theme of digital systems. Overall, study participants supported the DPC intervention. Patients expressed reassurance about being in a monitored, hospital setting. HCPs acknowledged the need for robust governance structures for ensuring clarity of roles and responsibilities and confidence. CONCLUSION: There were high levels of acceptability among patients and HCPs. HCPs recognised the importance of DPC. Complexities of penicillin allergy (de)labelling were highlighted, and issues of knowledge, risk, governance and workforce were identified as key determinants. These should be considered in future planning and adoption strategies for DPC.

Allergies to antibiotics among US women with uncomplicated urinary tract infection.

Uncomplicated urinary tract infections (uUTI) are generally treated empirically with antibiotics. However, antibiotic allergies limit the available oral treatment options for some patients. We assessed the proportion of self-reported antibiotic allergies among US women with uUTI. We performed a cross-sectional survey of US women (≥18 years) with a self-reported uUTI in the previous 60 days and an oral antibiotic prescription. Participants completed an online questionnaire about their most recent uUTI episode. Descriptive self-reported allergy data were stratified into subgroups by whether the participant had recurrent UTI (≥2 uUTIs in the past 6 months or ≥3 uUTIs in past 12 months, including the index episode), the number of different antibiotics given for the index episode (1, 2, ≥3), and whether the treatment was clinically aligned according to Infectious Diseases Society of America uUTI guidelines. Overall, 375 participants completed the questionnaire. The most commonly prescribed antibiotics were trimethoprim-sulfamethoxazole (SXT; 38.7%), ciprofloxacin (22.7%), and nitrofurantoin (18.9%). Most participants (62.7%) received only 1 antibiotic for their uUTI, and most (56.5%) were classified as having a non-recurrent uUTI. No antibiotic allergies were reported for most participants (69.3%), with 24.0% reporting 1 antibiotic allergy and 6.7% reporting ≥2 antibiotic allergies. Allergies to ≥2 antibiotic types were more common among participants classified as having recurrent uUTI, or who used multiple antibiotics to treat their uUTI. The most common allergy was to SXT (15.7%), followed by amoxicillin-clavulanate (8.3%) and ciprofloxacin (5.3%). Similar allergy trends were seen across subgroups, except higher rates of ciprofloxacin allergy were seen in participants given multiple antibiotics. Antibiotic allergies were relatively frequent in this uUTI cohort and the most common allergy was to SXT, which was the most prescribed antibiotic. Allergies to antibiotics reduce the available treatment options for uUTI in some patients.

Tryptase: The Silent Witness of Past and Ongoing Systemic Events.

Introduction: Tryptase is an important biomarker widely used in the laboratory confirmation of severe hypersensitivity reactions, especially anaphylaxis. It also plays a crucial role in the diagnosis, risk stratification, management and prognostic evaluation of many other mast cell-related conditions. Aim: This paper aims to highlight the role of serum tryptase, both in allergic disorders and other mast cell-related conditions. Two clinical cases regarding timely serum tryptase acquisition (in drug hypersensitivity reactions during the imaging procedure and perioperative anaphylaxis) are meant to emphasize the clinical potential of this protease. Method: We performed a comprehensive literature search of the PubMed/Medline and Scopus databases. From a total of 640 subject related publications, dating from 1940 to 2024, 45 articles written in English were selected. Literature search results: Total serum tryptase is a simple, cost-effective analysis with a normal baseline tryptase (sBT) level below 8.4 µg/L. Elevated sBT can indicate hereditary alpha-tryptasemia (HαT), mastocytosis and other non-allergic disorders. Patients with higher sBT levels, especially with insect venom allergy, have an increased risk of severe reactions and thereby require a prolonged treatment. All immediate systemic hypersensitivity reactions require a correlation between serum acute tryptase (sAT) and sBT. According to the guidelines, measuring sAT 30 min to 2 h after the symptom onset and sBT 24 h after the resolution, using the 20 + 2 rule and an sAT/sBT ratio of 1.685, improves the diagnostic accuracy in anaphylaxis. Conclusions: Tryptase levels should be acquired in all cases with clinical suspicion of MC degranulation. Given the increasing clinical relevance, elevated baseline serum tryptase levels require a multidisciplinary approach and further investigation.

Eosinophilia highly probable induced by carbapenems: A case report.

Eosinophilia is a challenge to our everyday clinical practice. There are multiple causes to consider when diagnosing eosinophilia, and drug hypersensitivity must be taken into account. It is especially difficult to manage it in hospitalized patients with multiple complications and infections. Allergy tests are not always as helpful as we would like, so we rely on clinical observation and laboratory analysis to establish our diagnosis. We present a unique clinical case because the same patient presented two clinical episodes of eosinophilia after the administration of Carbapenems in the context of abdominal infection.

Progestogen hypersensitivity: successful use of progesterone desensitisation and omalizumab to facilitate in vitro fertilisation.

Hypersensitivity to exogenous or endogenous progesterone presents with a variety of clinical, usually cutaneous, manifestations. The condition can occur at any age during the reproductive years, causes debilitating symptoms and can impact the use of exogenous hormones. Management strategies include symptom control or hormonal manipulation via desensitisation. Strategic testing confirms the diagnosis, while targeted intervention can significantly and positively impact quality of life and further childbearing.

Frequency and diagnostic findings of type I and type IV reactions to beta-lactam antibiotics - significance of the time interval between clinical reaction and skin testing.

BACKGROUND: The prevalence of allergies to beta-lactam antibiotics is significantly overestimated based on anamnestic data - with significant medical and economic consequences. The aim of the study was to determine the frequency of immediate and delayed type reactions to beta-lactam antibiotics in order to optimize diagnostics and therapy. One focus was on the time interval between reaction and testing. PATIENTS AND METHODOLOGY: Anamnestic and diagnostic data of patients with suspected allergy to beta-lactam antibiotics who were examined in our department between 2020 and 2022 were analyzed. RESULTS: 27/116 (23%) patients reacted in the skin tests. Type I sensitizations were detected in 4/35 patients (11%), type IV sensitizations in 23/83 (28%). In the case of negative in vitro diagnostics and skin testing, inpatient provocation tests were performed in 41/89 (46%). Type I allergies were confirmed in two of the 13 provoked patients (15%) with immediate type reactions, type IV allergies in three of 29 (10%) with delayed type reactions. The results were clearly related to the time interval after reaction. At less than one year, 19% (22/116) reacted, whereas only 4% (5/116) reacted at more than one year (for type I reaction 9% vs. 3%; for type IV reaction 23% vs. 5%).  CONCLUSIONS: The importance of the time interval between clinical event and allergological testing supports the guideline recommendation for skin testing within one year. Guideline recommendations on the diagnostic procedure for unclear reactions that occurred in the more distant past are desirable in order to rule out allergies to beta-lactam antibiotics.

Allergic reactions to enzyme replacement therapy in children with lysosomal storage diseases and their management.

OBJECTIVES: Human recombinant enzyme replacement therapy, given to compensate for genetic enzyme deficiency in lysosomal storage diseases, delays the progression of the disease and improves the quality of life. However, enzyme replacement therapy may cause hypersensitivity reactions. Within the scope of this research, we aimed to elucidate the frequency and clinical features of hypersensitivity reactions against enzyme replacement therapy in children with lysosomal storage diseases and clarify the management of these reactions. METHODS: Medical records of pediatric patients with lysosomal storage disease and receiving enzyme replacement therapy were retrospectively reviewed, and patients who experienced allergic reactions were included in the study. The demographic characteristics of the patients, their diagnosis, the responsible enzyme, the time at which the reaction started and at what dose, the signs and symptoms associated with the reaction, diagnostic tests, the management of the reaction, and the protocol applied for the maintenance of enzyme replacement therapy after the reaction were recorded. RESULTS: Hypersensitivity reactions developed in 18 of 71 patients (25.3 %) who received enzyme replacement therapy. The most common cutaneous findings were observed. Anaphylaxis developed in 6 of 18 patients. Patients who experienced recurrent hypersensitivity reactions with premedication or a slower infusion rate, those with positive skin test results, and patients who developed anaphylaxis were given enzyme replacement therapy with desensitization. CONCLUSIONS: HSR may develop during enzyme replacement therapy, which are vital in lysosomal storage diseases, and discontinuation of enzyme replacement therapy is a significant loss for patients with metabolic disorders. These reactions can be treated with premedication and long-term infusions, but some patients may require desensitization protocols for continued treatment.

Not a Benign (Mis)Label: Penicillin Allergy Education for the Nonallergist.

Introduction: Up to 20% of the US population carries a penicillin allergy label; however, over 95% of those patients can safely tolerate penicillin. This discrepancy has important personal and public health consequences. There is no published curriculum for medical trainees that covers penicillin allergy history taking, risk assessment, and antibiotic prescribing. Methods: We created a 60-minute, interactive curriculum that targeted medical students during their internal medicine rotation. We employed learning strategies including didactics, case-based learning, and role-playing. We compared self-efficacy and knowledge before and after the intervention using paired t tests. Results: A total of 28 medical students participated, with 25 completing both the pre- and postworkshop surveys. There was a statistically significant improvement in student-rated preparedness to prescribe antibiotics to patients with a penicillin allergy label (p < .001) and determine whether a patient has a history of an allergic reaction that was severe or life-threatening (p < .001). There was additionally a statistically significant increase in students' perception that penicillin allergy labels carry important health consequences (p = .005), as well as increase in their total knowledge scores (p = .006). Discussion: The workshop employs adult learning techniques to improve self-efficacy and knowledge regarding penicillin allergy in medical students. Further work is needed to refine the curriculum, seek external validity, and determine the impact of this workshop on clinical outcomes.

Additional use of extrinsic warmer for intravenous CT contrast media and its impact on incidence of contrast extravasations and allergic like reactions: a prospective observational case control study.

AIMS: To prospectively determine whether extrinsic warming of the low-osmolality CT contrast media (Iohexol 350, Iodixanol 320, Iopromide 300, and Iopamidol 300) to 37°C prior to intravenous administration affects extravasation and allergic-like reaction rates. MATERIALS AND METHODS: This large scale prospective case control study of adverse events included all the patients between the age group of 15-80 years undergoing routine contrast-enhanced computed tomographic (CECT) examinations from April 2018 to March 2020 at our institute. Ex vivo experiments were also performed to demonstrate change in contrast viscosity and fluid dynamics in relation to temperature. RESULTS: A total of 24,379 CECTs were conducted during the study period. Extrinsic warming showed a significant decrease in extravasation rates for Iohexol 350 at flow rates <3.5 mL/sec (P=0.037). No significant difference was observed with Iopromide 300 (P=0.432). Overall, a significant decrease in allergic reactions and overall contrast-related reactions (excluding physiologic reactions) was noted (P<0.001), with Iohexol 350. However, no significant difference was found with Iopromide 300. The most common physiological reaction was a sense of warmth, more prevalent in the warmed group, aligning with ex-vivo experiments demonstrating decreased viscosity with contrast warming. CONCLUSIONS: Extrinsic warming of contrast helps reduce the incidence of allergic-like reactions and extravasations for Iohexol 350, but no significant difference was noted with Iopromide 300 even at low injection rates (<3.5 mL/sec).

Leveraging implementation science theories to develop and expand the use of a penicillin allergy de-labeling intervention.

BACKGROUND: Penicillin allergy is the most frequently reported drug allergy, yet most patients can tolerate the drug if challenged. Despite this discrepancy, large scale penicillin allergy de-labeling interventions have not been widely implemented in many health care systems. The application of a multi-method implementation science approach can provide key tools to study this evidence to practice gap and provide insight to successfully operationalize penicillin allergy evaluation in real-world clinical settings. METHODS: We followed a four-step process that leverages qualitative analysis to design evidence-based, actionable strategies to develop an intervention. First, we specified the clinician-perceived barriers to penicillin allergy de-labeling (intervention targets). We then mapped intervention targets onto Theoretical Domains Framework (domains and constructs) and found the root causes of behavior. Next, we linked root causes of behavior with intervention functions (BCW). In the final step, we synthesized participants' suggestions for process improvement with implementation strategies aligning with the intervention functions. RESULTS: Evidence-based strategies such as focused education and training in penicillin allergy evaluation can address knowledge and confidence barriers reported by frontline clinicians. Other key strategies involve developing a system of champions, improving communications systems, and restructuring the healthcare team. Implementation mapping can provide a powerful multi-method framework to study, design, and customize intervention strategies. CONCLUSION: Empowering clinicians beyond allergy specialists to conduct penicillin allergy assessments requires designing new workflows and systems and providing additional knowledge to those clinicians.