mRNA COVID-19 Vaccine Anaphylaxis: Epidemiology, Risk Factors, and Evaluation.

PURPOSE OF REVIEW: The COVID-19 vaccines have proved essential in our defense against the COVID-19 pandemic. However, concerns regarding allergic reactions to the vaccines persist to this day. Herein, we review the data regarding the frequency of allergic reactions to the COVID-19 vaccines, the epidemiology, and the management of patients reporting vaccine allergic reactions. RECENT FINDINGS: Although initial reports emphasized a high risk of anaphylaxis to the COVID-19 vaccines, more recent data demonstrate similar rates of anaphylaxis to the COVID-19 vaccines as to other vaccines. Alternative explanations for increased rates of apparent allergic reactions are discussed, including the role for stress-related and nocebo responses. COVID-19 vaccines and mRNA vaccine technology are overwhelmingly safe and well-tolerated by most patients. Careful history and case review will enable the discerning physician to safely vaccinate most patients. Rare patients with objective signs and symptoms of anaphylaxis may be candidates for alternatives to vaccination including monoclonal antibodies.

Penicillin allergy delabeling: Opportunities for implementation and dissemination.

Although existing as a safety measure to prevent iatrogenic harm, unconfirmed penicillin allergy labels have a negative impact on personal and public health. One downstream effect of unconfirmed penicillin allergy is the continued emergence and transmission of resistant bacteria and their associated health care costs. Recognizing the consequences of inaccurate penicillin allergy labels, professional and public health organizations have started promoting the adoption of proactive penicillin allergy evaluations, with the ultimate goal of removing the penicillin allergy label when the allergy is disproved, also known as penicillin allergy "delabeling." A penicillin allergy evaluation includes a comprehensive allergy history often followed by drug challenge, sometimes with preceding skin testing. Currently, penicillin allergy delabeling is largely carried out by allergy specialists in outpatient settings. Penicillin allergy delabeling is performed on inpatients, albeit rarely, often at the time of need, as a point-of-care procedure. Access to penicillin allergy evaluation services is limited. Recent studies demonstrate the feasibility of expanding penicillin allergy evaluations and delabeling to internists, pediatricians, emergency medicine physicians, infectious diseases specialists, and clinical pharmacists. However, reducing the impact of mislabeled penicillin allergy will require comprehensive efforts and new investments. In this review, we summarize the current practices of penicillin allergy delabeling and discuss expansion opportunities for penicillin allergy delabeling as quality improvement.

Supportive Oncology Care at Home Intervention for Patients With Pancreatic Cancer.

PURPOSE: We sought to determine the feasibility of delivering a Supportive Oncology Care at Home intervention among patients with pancreatic cancer. METHODS: We prospectively enrolled patients with pancreatic cancer from a parent trial of neoadjuvant fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX). The intervention entailed (1) remote monitoring of patient-reported symptoms, vital signs, and body weight; (2) a hospital-at-home care model; and (3) structured communication with the oncology team. We defined the intervention as feasible if ≥ 60% of patients enrolled in the study and ≥ 60% completed the daily assessments within the first 2-weeks of enrollment. We determined rates of treatment delays, urgent clinic visits, emergency department visits, and hospitalizations among those who did (n = 20) and did not (n = 24) receive Supportive Oncology Care at Home from the parent trial. RESULTS: From January 2019 to September 2020, we enrolled 80.8% (21/26) of potentially eligible patients. One patient became ineligible following consent because of moving out of state, resulting in 20 participants (median age = 67 years). In the first 2 weeks of enrollment, 65.0% of participants completed all daily assessments. Overall, patients reported 96.1% of daily symptoms, 96.1% of daily vital signs, and 92.5% of weekly body weights. Patients receiving the intervention had lower rates of treatment delays (55.0% v 75.0%), urgent clinic visits (10.0% v 25.0%), and emergency department visits/hospitalizations (45.0% v 62.5%) compared with those not receiving the intervention from the same parent trial. CONCLUSION: Findings demonstrate the feasibility and acceptability of a Supportive Oncology Care at Home intervention. Future work will investigate the efficacy of this intervention for decreasing health care use and improving patient outcomes.

Feasibility of implementing an exercise intervention in older adults with hematologic malignancy.

Older adults with Hematologic Malignancy (HM) are vulnerable to functional decline secondary to disease and treatment. Interventions for physical deconditioning, in concert with routine hematology care are limited. The feasibility of accrual, retention, and demand for an exercise intervention among a high-risk HM population was piloted. METHODS: Older adults with HM, on active treatment, with functional impairment were recruited prospectively to participate in a 6-month Otago Exercise Programme (OEP). Measures of motivation, self-efficacy, patient identified barriers to exercise, barriers to clinical trial enrollment, study satisfaction, and serious adverse events were captured. RESULTS: 63 patients were approached, 18 declined trial enrollment, 45 consented, 30 patients enrolled in the exercise program. The main barrier for trial enrollment was transportation/travel concerns (n = 15). Of the 45 consented participants, 8 (12.7%) dropped out due to clinical deterioration, 5 (7.9%) withdrew, and 2 (3.2%) were ineligible prior to exercise-intervention intiation. The median age was 75.5 years (range 62-83) with plasma cell dyscrasia (63%), non-Hodgkin lymphoma (20%) and leukemia (17%). Retention of the physical therapist (PT) led-OEP was 76.6% of patients (n = 23/30), and end-of-study retention was 66.7% (n = 20/30). Of the evaluable patients, 23/29 completed the PE-led OEP yielding a completion rate of 79%. Participants were extremely motivated (72.4%) and strongly intended (89.7%) to engage in regular physical activity. Exercising when tired increased from a median score of 50 at Visit 1 to 70 at Visit 2, but dropped significantly to 45 at Visit 3 (p < 0.001). Participants reported significantly lower self-efficacy to exercise over the next 6 months from Visit 1 to Visit 3 (p = 0.001). CONCLUSIONS: Older patients with HM had higher completion of in-person, PT-led exercise compared to at-home, independent exercise. Older adults were motivated and found the program acceptable, yet the ability to sustain a structured exercise program was challenging due to changes in health status. ClinicalTrials.gov Identifier: NCT02791737.

Characterizing inclusion and exclusion criteria in clinical trials for chimeric antigen receptor (CAR) T-cell therapy among adults with hematologic malignancies.

OBJECTIVE: Restrictive eligibility criteria are a known barrier to patient enrollment into clinical trials. With the introduction of chimeric antigen receptor T-cell (CAR-T) therapy, it is imperative to ensure trials are generalizable to the intended population with appropriate safety guiderails. METHODS: Using the U.S. National Library of Medicine's clinical trial database, we identified 84 clinical trials and characterized inclusion/exclusion criteria for CAR-T therapy in hematologic malignancies with a focus on age, performance status, and comorbidities, and the relationship to sponsorship, disease type, and study phase. RESULTS: The overwhelming majority of CAR-T trials imposed restrictions on upper age (n = 54, 64%), performance status (n = 72, 86%), and renal function (n = 76, 90%). Institution-sponsored studies were more likely to have age restrictions (n = 29) than industry-sponsored (n = 20), (83% vs 45%, p < 0.01). There was no relationship between study phase and use of upper age limit restriction or study phase and affiliation with performance status restrictions. Inclusion criteria for renal function was highly variable and ambiguous; creatinine <1.2-3.0 mg/dL, creatinine clearance >20-60 mL/min, and GFR >30-70 mL/min. CONCLUSION: These results suggest highly variable inclusion/exclusion criteria for early phase CAR-T studies that may limit patient accessibility to therapy and emphasize the need for a standardized, evidence-based approach to patient enrollment.

Factors predicting the need for vaginal replacement at the time of primary reconstruction of a cloacal malformation.

BACKGROUND: A subset of patients with cloacal malformations requires vaginal replacement during their primary reconstruction, increasing the surgical complexity. Identifying factors which predict the need for vaginal replacement would facilitate operative planning. METHODS: We retrospectively reviewed patients who underwent primary cloacal reconstruction at our Center (2014-2018) and assessed the length of the common channel, urethra, and vagina. The presence of hydrocolpos at birth, Müllerian anomalies, sacral ratio, and tethered cord were also assessed between patients who did and did not require vaginal replacement. RESULTS: 50 patients were identified. 17/50 patients (34%) underwent a total urogenital mobilization (TUM), and none required vaginal replacement. 33/50 (66%) patients underwent a urogenital separation. 19/33 (58%) required vaginal replacement. This group had a shorter vagina (4.2 cm vs 6.6 cm, p < 0.01). There was no difference in urethral or common channel length, number of cervices, sacral ratio, presence of a vaginal septum, hydrocolpos, or tethered cord between those who did and those who did not require vaginal replacement. CONCLUSIONS: Urethral and common channel lengths were used to successfully determine the operative plan (TUM or urogenital separation) to reconstruct cloacal malformations. The need for urogenital separation and a shorter vaginal length were predictive of the need for vaginal replacement. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Case series with no comparison groups.

Are Senna based laxatives safe when used as long term treatment for constipation in children?

BACKGROUND AND AIM: Senna is a stimulant laxative commonly used by pediatricians, pediatric gastroenterologists, and pediatric surgeons. Many clinicians avoid Senna for reasons such as tolerance or side effects but this has little scientific justification. We recently found several patients we were caring for developed perineal blistering during the course of Senna treatment. Because of this we chose to review the literature to identify side effects in children taking this medication as well as to analyze our Center's experience with Senna's secondary effects. METHODS: We performed a literature review (MEDLINE, PUBMED) using the keywords of Senna, sen, sennosides and children, and pediatric and functional (idiopathic) constipation. We looked for articles with information regarding perineal blisters related to Senna as well as other secondary effects of Senna laxatives in children when used on a long-term basis. We also reviewed the charts of our patients who had previously taken Senna or are currently taking Senna, looking for adverse reactions. RESULTS: Eight articles in the literature reported perineal blisters after administration of Senna laxatives in 28 patients. Of those occurrences, 18 patients (64%) had accidental administration of Senna and 10 (36%) had Senna prescribed as a long term treatment. All of the blistering episodes were related to high dose, night-time accidents, or intense diarrhea with a long period of stool to skin contact. At our institution, from 2014 to 2017, we prescribed Senna and have recorded data to 640 patients. During the study period, 17 patients (2.2%) developed blisters during their treatment. Patients who developed blisters had higher doses 60mg/day; 60 [12-100] vs. 17.5 [1.7-150] (p<0.001). All of the blistering episodes were related to night-time accidents, with a long period of stool to skin contact. 83 (13%) patients presented minor side effects such as abdominal cramping, vomiting or diarrhea which resolved once the type of laxatives were changed or enemas were started. The doses of Senna was not significantly different in these patients 15mg/day [4.4-150] vs. 17.5mg/day [1.5-150]. There were no other long-term side effects from Senna found in the pediatric literature for long-term treatment besides abdominal cramping or diarrhea during the first weeks of administration. We found no evidence of tolerance to Senna in our review. CONCLUSION: There is a paucity of information in the literature regarding side effects of sennosides as a long-term therapy, and to our knowledge, this is the first review of Senna side effects in children. Senna induced dermatitis is rare, but may occur when patients need a higher dose. All of the cases described had a long period of exposure of the skin to stool. Besides the perineal rash with blisters, we could find no other described major side effect with Senna administration in the pediatric population or evidence of the frequently mentioned concern of the development of tolerance to Senna. Pediatric caregivers should advise families of the rare side effect of skin blistering and educate them to change the diaper frequently in children who are not toilet- trained to reduce stool to skin exposure. We can conclude from this review that Senna is a safe treatment option for constipation in children. LEVEL OF EVIDENCE: IV.