Prevention of Allergic-like Reactions at Repeat CT: Steroid Pretreatment versus Contrast Material Substitution.

Background It is unclear whether steroid premedication is an effective means of preventing repeat allergic-like reactions in high-risk patients with a previous allergic-like reaction to iodinated contrast material (ICM). Purpose To compare the effectiveness of ICM substitution (ie, using iohexol in a patient with a previous iopromide reaction) with 12- and 2-hour steroid premedication for preventing repeat acute allergic-like reactions in high-risk patients. Materials and Methods This retrospective study identified all high-risk (ie, having a previous allergic-like reaction) adult and pediatric patients who underwent a contrast-enhanced CT examination at the institution from June 1, 2009, to May 9, 2017. Prophylactic treatments and repeat reactions were identified using chart review. The effectiveness of prophylactic treatments on repeat reaction rates was examined with multivariable regression models that used generalized estimating equations. Results A total of 1973 high-risk patients who underwent 4360 subsequent ICM-enhanced CT examinations were included. Of the 4360 examinations, a total of 280 allergic-like reactions occurred (6%) in 224 of the 1973 patients (11% of patients), with only 19 of 280 reactions (7%) that were more severe than the previous reaction being demonstrated. After adjustment, patients who received a different ICM with and without steroid premedication had a significantly lower rate of repeat reactions than did patients who received steroid premedication and the same ICM (same ICM and steroid premedication: 80 of 423 examinations [19%]; different ICM and no steroid premedication: 10 of 322 examinations [3%]; odds ratio [OR], 0.14 [95% CI: 0.06, 0.33]; P < .001; different ICM and steroid premedication: five of 166 patients [3%]; OR, 0.12 [95% CI: 0.04, 0.36]; P < .001). When examining the first scan only, patients who received the same ICM had a similar risk of repeat reactions regardless of whether they received steroid premedication (steroid premedication: 44 of 172 patients [26%] vs no premedication: 73 of 298 patients [25%]; OR, 1.00 [95% CI: 0.64, 1.57]; P = .99). Conclusion In this cohort, using an iodinated contrast material (ICM) substitution was more effective for preventing repeat allergic-like reactions than using steroid premedication and the same ICM that caused the previous reaction. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Davenport and Weinstein in this issue.

Acute Adverse Events Following Gadolinium-based Contrast Agent Administration: A Single-Center Retrospective Study of 281 945 Injections.

Background Acute allergic-like and physiologic reactions occur following administration of gadolinium-based contrast agents (GBCAs) for MRI examinations. Because these reactions are uncommon, it is challenging to compare reaction rates between GBCAs and to determine risk factors. Purpose To compare reaction rates between the four GBCAs gadodiamide, gadobutrol, gadobenate dimeglumine, and gadoterate meglumine, and to determine potential risk factors for reactions. Materials and Methods This retrospective study identified all intravenous GBCA injections for MRI examinations performed at a single institution from June 1, 2009, to May 9, 2017. Reactions were identified by reviewing records from the MRI technologist, MRI nursing staff, radiologist, emergency department, and provider. Reactions were classified as allergic-like or physiologic and as mild, moderate, or severe by using American College of Radiology criteria. GBCA reaction rates and other potential risk factors were examined by using multivariable regression models with generalized estimating equations. Results Analysis included a total of 158 100 patients (median age, 55 years [interquartile range, 40-67 years], 51% women) who received a total of 281 945 GBCA injections (140 645 gadodiamide, 94 109 gadobutrol, 39 138 gadobenate, and 8053 gadoterate). At multivariate analysis, gadobenate or gadobutrol had higher rates of allergic-like reactions compared with gadodiamide (gadobenate: odds ratio [OR], 3.9 [95% confidence interval {CI}: 3.0, 5.1]; P < .001; gadobutrol: OR, 2.3 [95% CI: 1.8, 2.9]; P < .001) or gadoterate (gadobenate: OR, 4.8 [95% CI: 1.0, 23]; P = .049; gadobutrol: OR, 2.8 [95% CI: 0.6, 14]; P = .20). Physiologic reactions were more frequently observed with gadoterate (OR, 7.7 [95% CI: 2.3, 25; P = .001), gadobenate (OR, 1.8 [95% CI: 1.3, 2.5; P < .001), and gadobutrol (OR, 1.6 [95% CI: 1.3, 2.1; P < .001) administration compared with gadodiamide. Six severe allergic-like reactions (three gadobutrol, three gadobenate) occurred requiring hospitalization. Patient age (P values .025 to < .001), sex (P < .001), location (P = .006), and MRI type (P = .003 and P = .006) were associated with acute reactions. Conclusion Gadobenate and gadobutrol are associated with higher rates of allergic-like reactions compared with gadodiamide or gadoterate, and gadoterate, gadobenate, and gadobutrol are associated with higher rates of physiologic reactions compared with gadodiamide. Patient sex, age, location, and MRI type correlate with acute reaction rates. © RSNA, 2019 Online supplemental material is available for this article.

The effectiveness of training physical therapists in pain neuroscience education on patient reported outcomes for patients with chronic spinal pain: a study protocol for a cluster randomized controlled trial.

BACKGROUND: Chronic spinal pain affects many in the United States and is associated with rising healthcare costs - but not improved outcomes. Education and self-care promotion are hallmarks of the recommended approach for this condition. Pain Neuroscience Education (PNE) is a method of educating patients about the neurophysiology of pain that aims to reconceptualize pain from an indicator of damage to an interpretation of input signals by the brain and nervous system. PNE has shown efficacy in controlled situations when delivered by experts, but its effectiveness has not been investigated among trained clinicians in a pragmatic setting. METHODS: A cluster randomized trial will randomly assign 16 clinic regions to either receive PNE training or continue with usual care. Patients with chronic neck or back pain will be enrolled to provide outcome data. Measures will be collected at baseline, 2 weeks, and 12 weeks. The primary outcome will be the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function computer-adapted test (PF-CAT). Pre-specified statistical analyses will compare outcomes between clinic regions assigned to PNE treatment or usual care while using random effects to account for region-level clustering. DISCUSSION: Pain Neuroscience Education has been shown efficacious for a variety of patient-centered outcomes for those with chronic pain, but it has not yet been investigated outside of controlled settings. This trial has the potential to promote PNE as a low-cost intervention for chronic spinal pain and affect physical therapy education. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03168165 , registered May 30, 2017.

Premedication of patients for prior urticarial reaction to iodinated contrast medium.

PURPOSE: The purpose of this study was to determine whether premedication of patients with a history of urticaria after low osmolality contrast media (LOCM) results in fewer subsequent reactions, and if a benefit is seen, to determine which premedication regimen results in the fewest reactions. MATERIALS AND METHODS: The subsequent contrast enhanced studies of patients who experienced urticaria after intravenous LOCM between 2002 and 2009 were reviewed to determine whether an additional reaction occurred. Patients undergoing subsequent studies received either no premedication, or premedication with diphenhydramine alone, corticosteroid alone, or corticosteroid plus diphenhydramine. Reactions occurring without premedication were termed repeat reactions and reactions occurring after premedication were termed breakthrough reactions. RESULTS: Fifty patients with a history of urticaria after LOCM met the inclusion criteria and underwent 133 subsequent contrast enhanced studies. Repeat reactions occurred in 7.6% (5/66) of subsequent studies in patients receiving no premedication. Breakthrough reactions occurred in 8% (2/25), 46% (12/26), and 44% (7/16) of subsequent studies in patients receiving premedication with diphenhydramine, corticosteroid, and corticosteroid plus diphenhydramine, respectively. All subsequent reactions consisted of urticaria as the most severe manifestation; no hemodynamic instability or respiratory compromise occurred. In multivariate analysis, premedication with corticosteroid was significantly associated with higher rate of breakthrough reaction relative to no premedication (OR 14.3, 95% CI: 4.1-50.4), as was premedication with corticosteroid plus diphenhydramine (OR 8.3, 95% CI: 1.8-37.9). CONCLUSION: The results suggest that premedication of patients with a history of urticaria after LOCM may not be necessary.

Prevalence and extent of low back pain and low back-related disability in non-care-seeking working-age adults.

OBJECTIVE: To explore the prevalence and extent of low back pain (LBP) and low back-related disability in working-age adults not seeking care. METHODS: A convenience sample of 101 working-age adults not seeking care for LBP completed the Oswestry Disability Index (ODI) and Roland-Morris Disability Questionnaire (RMDQ) as measures of disability and completed questionnaires that collected information on various demographic and health-related variables. Those reporting current LBP also completed a Numeric Pain Rating Scale (NPRS). Prevalence was assessed based on a dichotomization of whether any disability or pain was reported and also as a continuous variable to assess the extent of pain and disability present for each participant. RESULTS: Of the 101 participants, 72.3% reported some level of disability (ODI mean = 7.91%, RMDQ mean = 2.63) and 46.5% reported some level of pain (NRPS mean = 3.68). Previous care-seeking for LBP was associated with increased odds of reporting disability (ODI odds ratio [OR] 7.91, 95% confidence interval [CI], 2.43 to 31.18; RMDQ OR 2.69, 95% CI, 1.05 to 7.24), as was reporting any current LBP (ODI OR 9.45, 95% CI, 3.15 to 33.21; RMDQ OR 7.03, 95% CI, 2.82 to 18.89). No other demographic or health-related variables were associated with the presence or extent of pain or disability. CONCLUSION: Many non-care-seeking individuals reported some level of LBP and/or disability, suggesting that some level of pain and disability may be considered normal, acceptable, or manageable. One-third of individuals with no pain reported some disability.

Effectiveness of training physical therapists in pain neuroscience education for patients with chronic spine pain: a cluster-randomized trial.

ABSTRACT: Chronic spinal pain poses complex challenges for health care around the world and is in need of effective interventions. Pain neuroscience education (PNE) is a promising intervention hypothesized to improve pain and disability by changing individuals' beliefs, perceptions, and expectations about pain. Pain neuroscience education has shown promise in small, controlled trials when implemented in tightly controlled situations. Exploration of promising interventions through more pragmatic methodologies is a crucial but understudied step towards improving outcomes in routine clinical care. The purpose was to examine the impact of pragmatic PNE training on clinical outcomes in patients with chronic spine pain. The cluster-randomized clinical trial took place in 45 outpatient physical therapist (PT) clinics. Participants included 108 physical therapists (45 clinics and 16 clusters) and 319 patients. Clusters of PT clinics were randomly assigned to either receive training in PNE or no intervention and continue with usual care (UC). We found no significant differences between groups for our primary outcome at 12 weeks, Patient-Reported Outcomes Measurement Information System Physical Function computer adaptive test {mean difference = 1.05 (95% confidence interval [CI]: -0.73 to 2.83), P = 0.25}. The PNE group demonstrated significant greater improvements in pain self-efficacy at 12 and 2 weeks compared with no intervention (mean difference = 3.65 [95% CI: 0.00-7.29], P = 0.049 and = 3.08 [95% CI: 0.07 to -6.09], P = 0.045, respectively). However, a similar percentage of participants in both control (41.1%) and treatment (44.4%) groups reported having received the treatment per fidelity question (yes or no to pain discussed as a perceived threat) at 2 weeks. Pragmatic PT PNE training and delivery failed to produce significant functional changes in patients with chronic spinal pain but did produce significant improvement in pain self-efficacy over UC PT.

Maintenance dosing for sublingual immunotherapy by prominent European allergen manufacturers expressed in bioequivalent allergy units.

BACKGROUND: Sublingual immunotherapy (SLIT) has become established in Europe, and its efficacy is being evaluated in the United States. The doses used for SLIT in Europe today are difficult to evaluate, because each manufacturer expresses the potency of its extracts differently. OBJECTIVES: To compare in vitro European SLIT maintenance solutions against US licensed standardized allergenic extract concentrates and to determine the monthly SLIT doses delivered expressed in bioequivalent allergy units ([B]AU). METHODS: We studied Dermatophagoides pteronyssinus, timothy grass pollen, cat (hair) and short ragweed pollen allergen extracts. The SLIT maintenance solutions of 4 leading European manufacturers and standardized concentrate extracts of 3 US manufacturers were analyzed with the following assays: protein content, relative potency (immunoglobulin E [IgE]-binding enzyme-linked immunosorbent assay [ELISA] inhibition) and major allergen content. The relative monthly allergen dose in (B)AU was calculated for each recommended SLIT schedule. RESULTS: Relative potency was approximately 10 times higher for US concentrate standardized extracts-which are meant to be diluted-than for European SLIT maintenance solutions of D pteronyssinus and timothy grass pollen. For cat (hair) and short ragweed pollen, the difference was less. Measurements of relative potency and major allergen content correlated well. In our assays, European mite extracts contain a very low quantity of Der p 2 compared with US mites. CONCLUSION: Recommended SLIT doses in Europe vary widely among the manufacturers, but are consistently lower (Eur1) or higher (Eur4) over all four allergens tested. SLIT efficacy probably depends on additional factors apart from the exact dose. SLIT dose finding studies should be done for each product.

Temozolomide desensitization followed by metronomic dosing in patients with hypersensitivity.

PURPOSE: Temozolomide is the most effective chemotherapy for malignant glioma. Hypersensitivity requiring interruption of therapy may significantly impact patient survival. We have successfully employed temozolomide desensitization followed by metronomic dosing of temozolomide. Our purpose was to report patient characteristics and outcomes in patients with glioma (Grade 2-4) and temozolomide hypersensitivity managed by desensitization and metronomic dosing. METHODS: We performed an observational study of 15 patients at Mayo Clinic (Rochester) with a diagnosis of glioma who underwent temozolomide desensitization with subsequent metronomic dosing from May 2012 to January 2017. We calculated overall and progression-free survival using the Kaplan-Meier method, and log-rank analyses to assess for differences in survival by WHO Grade or treatment initiation. RESULTS: Median age at time of desensitization was 49.3 years (26.8-64.7 years). Median follow-up after desensitization was 35.5 months. One patient (6.7%) was unable to resume temozolomide due to recurrent allergy. The median time from first desensitization to discontinuation of metronomic temozolomide was 4.2 months (0-15.2 months). Median OS and PFS for the whole sample were 181.7 months and 44.9 months. For Grade 4, OS was 100% at 1 year, 40% at 3 years, 20% at 5 years; and PFS was 60% at 1 year, 40% at 3 years, and 20% at 5 years. CONCLUSION: Our results suggest that rapid-desensitization followed by metronomic temozolomide should be considered in patients with glioma who experience hypersensitivity. This strategy provides comparable outcomes to therapy with standard protocols, with the majority of patients able to tolerate temozolomide after desensitization with favorable disease control.

Common variable immunodeficiency: a new look at an old disease.

Primary immunodeficiencies comprise many diseases caused by genetic defects primarily affecting the immune system. About 150 such diseases have been identified with more than 120 associated genetic defects. Although primary immunodeficiencies are quite rare in incidence, the prevalence can range from one in 500 to one in 500 000 in the general population, depending on the diagnostic skills and medical resources available in different countries. Common variable immunodeficiency (CVID) is the primary immunodeficiency most commonly encountered in clinical practice, and appropriate diagnosis and management of patients will have a significant effect on morbidity and mortality as well as financial aspects of health care. Advances in diagnostic laboratory methods, including B-cell subset analysis and genetic testing, coupled with new insights into the molecular basis of immune dysfunction in some patients with CVID, have enabled advances in the clinical classification of this heterogeneous disease.

Acute kidney injury in patients with inactive cytochrome P450 polymorphisms.

Medications are a major source of acute kidney injury, especially in critically ill patients. Medication-induced renal injury can occur through a number of mechanisms. We present two cases of acute kidney injury (AKI) where inactive cytochrome P450 (CYP) polymorphism may have played a role. The first patient developed a biopsy-proven allergic interstitial nephritis following urethrotomy. Genetic testing revealed the patient to be heterozygous for an inactivating polymorphism CYP2C9*3 and homozygous for an inactivating polymorphism CYP2D6*4. Patient had received several doses of promethazine, which is metabolized by CYP2D6*4. Another patient developed AKI on several occasions after exposure to lansoprazole and allopurinol. CYP testing revealed the patient to be homozygous for inactivating polymorphism CYP2C19*2, which is responsible for the metabolism of lansoprazole. These are the first two cases of AKI associated with non-functional polymorphisms of cytochrome P450 superfamily. While the exact mechanism has not been worked out, it introduced the possibility of a new source of kidney injury.

Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase.

Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro.

Vaccine allergy: diagnosis and management.

As a group, vaccines provide a safe and effective way of preventing infectious and allergic illness. Allergic reactions to vaccines and drug products have become important and common features of practice and demand heightened awareness. Serious adverse effects of vaccines are rare but have been reported to various components of different vaccines. Although there are few precise diagnostic tests available, patients usually can be diagnosed accurately after careful attention to the history and physical findings. Better understanding of these reactions can lead to proper vaccine selection and can improve immunization acceptance rates in the community. Prevention, avoidance, use of alternative agents, desensitization, and premedication remain the mainstays of therapy, even as more refined diagnostic and management tools are developed. VAERS data, in addition to the traditional uses (signal detection, large registry of rare vaccine adverse events), can serve as a source of cases for epidemiologic (eg, case-control) studies that evaluate biologic factors that may be related to vaccine-related adverse reactions. Additional studies that are aimed at identifying other causes of immediate hypersensitivity after immunization with live virus vaccines are warranted.

Perioperative angioedema: background, diagnosis, and management.

Angioedema is a potentially life-threatening condition that may present at any point in the perioperative care of patients. It requires prompt recognition and diagnosis; the primary concern during acute attacks is airway management. The pathophysiology, various causes of angioedema, and treatment strategies according to underlying etiology are presented.

Masqueraders of angioedema and urticaria.

OBJECTIVES: Reading this article will remind the reader that some patients presenting with complaints of urticaria and angioedema may not have urticaria or angioedema at all, but may have other causes, often unusual, sometimes treatable. It will also increase the reader's ability to recognize masqueraders of angioedema, urticaria, and facial swelling thought to be angioedema. DATA SOURCES: Data for this article come mainly from the authors' personal experiences and selected references to illustrate points made in the article. STUDY SELECTION: The criteria used are patients and articles from the authors' experiences that illustrate the point of this article that patients presenting with urticaria and angioedema may have other diseases and some of these are treatable. RESULTS: The objectives will be met by patient presentations plus pertinent literature review. CONCLUSIONS: Some patients presenting as angioedema and urticaria have swelling and skin lesions attributable to other causes. Although they are uncommon, they are sometimes treatable. Not all patients referred to an allergist for angioedema have angioedema.