The Impact of Prior Authorization on Clinical Practice and Patient Care Outcomes: A Work Group Report of the AAAAI Prior Authorization Task Force.

The Prior Authorization Task Force of the American Academy of Allergy, Asthma & Immunology (AAAAI), a presidential initiative of David Khan, MD, FAAAI, was established to develop an AAAAI position statement outlining ways to improve health care for our patients, to support legislation that advocates for prior authorization (PA) reform and identify the impact PA has on its membership using a questionnaire survey. This article describes the results of this survey. An electronic anonymous survey questionnaire was developed to assess the impact and burden of PA on AAAAI members and their staff and patients. Surveys were sent to randomly selected members and fellows of the AAAAI in the United States. Descriptive statistics were used to analyze the results by the Information Services team of the AAAAI and the authors of this work group report. The questionnaire responses from allergy immunology specialists demographically reflected the AAAAI membership and indicate that PAs can significantly affect patient care delivery and increase administrative burden to clinical practices, leading to serious adverse events in some circumstances. Differential responses regarding PAs for various medication classes likely reflect the physician's patient population, which can shift prescribing patterns. Prior authorization is a serious health care problem that is wasting financial resources and needlessly placing patients in danger when they are unable to access medications or medical services required for clinical management. The results of this questionnaire study support the recommendations made in the recent AAAAI position statement on PA.

Management of rhabdomyolysis: A practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: The treatment of rhabdomyolysis remains controversial. Although there is no question that any associated compartment syndrome needs to be identified and released, debate persists regarding the benefit of further therapy including aggressive intravenous fluid resuscitation (IVFR), urine alkalization with bicarbonate, and the use of mannitol. The goal of this practice management guideline was to evaluate the effects of bicarbonate, mannitol, and aggressive intravenous fluids on patients with rhabdomyolysis. METHODS: A systematic review and meta-analysis comparing treatments in patients with rhabdomyolysis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of evidence and to create evidence-based recommendations regarding the use of bicarbonate, mannitol, and aggressive IVFR in patients with rhabdomyolysis. RESULTS: A total of 12 studies were identified for analysis. On quantitative analysis, IVFR decreased the incidence of acute renal failure (ARF) and need for dialysis in patients with rhabdomyolysis. Neither bicarbonate nor mannitol administration improved the incidence of acute renal failure and need for dialysis in patients with rhabdomyolysis. Quality of evidence was deemed to be very low, with the vast majority of the literature being retrospective studies. CONCLUSION: In patients with rhabdomyolysis, we conditionally recommend for aggressive IVFR to improve outcomes of ARF and lessen the need for dialysis. We conditionally recommend against treatment with bicarbonate or mannitol in patients with rhabdomyolysis.

Work Group Report: COVID-19: Unmasking Telemedicine.

Telemedicine adoption has rapidly accelerated since the onset of the COVID-19 pandemic. Telemedicine provides increased access to medical care and helps to mitigate risk by conserving personal protective equipment and providing for social/physical distancing to continue to treat patients with a variety of allergic and immunologic conditions. During this time, many allergy and immunology clinicians have needed to adopt telemedicine expeditiously in their practices while studying the complex and variable issues surrounding its regulation and reimbursement. Some concerns have been temporarily alleviated since March 2020 to aid with patient care in the setting of COVID-19. Other changes are ongoing at the time of this publication. Members of the Telemedicine Work Group in the American Academy of Allergy, Asthma & Immunology (AAAAI) completed a telemedicine literature review of online and Pub Med resources through May 9, 2020, to detail Pre-COVID-19 telemedicine knowledge and outline up-to-date telemedicine material. This work group report was developed to provide guidance to allergy/immunology clinicians as they navigate the swiftly evolving telemedicine landscape.

Quality measures in acute kidney injury.

PURPOSE OF REVIEW: Quality measure assessment and reporting is evolving in end-stage renal disease care and is inchoate in ambulatory nephrology clinic care. Acute kidney injury (AKI) quality measures have not received sufficient attention, yet deserve consideration in view of the substantial proportion of effort nephrology providers devote to AKI care. RECENT FINDINGS: Accumulating literature permits consideration of timing of nephrology consultation, follow-up after AKI hospitalization, early detection, medication dosing, hospital readmissions and length of stay, cost, and mortality as potential AKI quality measures. SUMMARY: We review candidate AKI quality measures and assess the strength of evidence supporting the use of each measure as a standard for AKI care.

Reducing Environmental Allergic Triggers: Policy Issues.

The implementation of policies to reduce environmental allergic triggers can be an important adjunct to optimal patient care for allergic rhinitis and allergic asthma. Policies at the local level in schools and other public as well as private buildings can make an impact on disease morbidity. Occupational exposures for allergens have not yet been met with the same rigorous policy standards applied for exposures to toxicants by Occupational Safety and Health Administration. Further benefit may be obtained through policies by local, county, state, and national governments, and possibly through international cooperative agreements. The reduction of allergenic exposures can and should be affected by policies with strong scientific, evidence-based derivation. However, a judicious application of the precautionary principle may be needed in circumstances where the health effect of inaction could lead to more serious threats to vulnerable populations with allergic disease. This commentary covers the scientific basis, current implementation, knowledge gaps, and pro/con views on policy issues in reducing environmental allergic triggers.

Indoor Environmental Control Practices and Asthma Management.

Indoor environmental exposures, particularly allergens and pollutants, are major contributors to asthma morbidity in children; environmental control practices aimed at reducing these exposures are an integral component of asthma management. Some individually tailored environmental control practices that have been shown to reduce asthma symptoms and exacerbations are similar in efficacy and cost to controller medications. As a part of developing tailored strategies regarding environmental control measures, an environmental history can be obtained to evaluate the key indoor environmental exposures that are known to trigger asthma symptoms and exacerbations, including both indoor pollutants and allergens. An environmental history includes questions regarding the presence of pets or pests or evidence of pests in the home, as well as knowledge regarding whether the climatic characteristics in the community favor dust mites. In addition, the history focuses on sources of indoor air pollution, including the presence of smokers who live in the home or care for children and the use of gas stoves and appliances in the home. Serum allergen-specific immunoglobulin E antibody tests can be performed or the patient can be referred for allergy skin testing to identify indoor allergens that are most likely to be clinically relevant. Environmental control strategies are tailored to each potentially relevant indoor exposure and are based on knowledge of the sources and underlying characteristics of the exposure. Strategies include source removal, source control, and mitigation strategies, such as high-efficiency particulate air purifiers and allergen-proof mattress and pillow encasements, as well as education, which can be delivered by primary care pediatricians, allergists, pediatric pulmonologists, other health care workers, or community health workers trained in asthma environmental control and asthma education.

Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF.

Nonvitamin K-dependent oral anticoagulant agents (NOACs) are currently recommended for patients with atrial fibrillation at risk for stroke. As a group, NOACs significantly reduce stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with warfarin. All NOACs are dependent on the kidney for elimination, such that patients with creatinine clearance <25 ml/min were excluded from all the pivotal phase 3 NOAC trials. It therefore remains unclear how or if NOACs should be prescribed to patients with advanced chronic kidney disease and those on dialysis. The authors review the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <30 ml/min) and those on dialysis. The authors frame the evidence in terms of risk versus benefit to bring greater clarity to NOAC-related major bleeding and efficacy at preventing stroke specifically in patients with creatinine clearance <30 ml/min.

Severity of Anemia Predicts Hospital Length of Stay but Not Readmission in Patients with Chronic Kidney Disease: A Retrospective Cohort Study.

The aim of this study was to examine the relationship of severe anemia to hospital readmission and length of stay (LOS) in patients with chronic kidney disease (CKD) stage 3-5. Compared with the general population, patients with moderate CKD have a higher hospital readmission rate and LOS. Anemia in patients with moderate CKD is associated with higher morbidity and mortality. The influence of anemia on hospital outcomes in patients with moderate CKD has not been characterized.We conducted a retrospective cohort study at Maine Medical Center, a 606-bed academic tertiary care hospital. Patients with CKD stages 3-5 and not on dialysis admitted during February 2013 to January 2014 were eligible. Patients with end stage renal disease on hemodialysis or peritoneal dialysis, kidney transplant, acute kidney injury, gastrointestinal bleeding, active malignancy, pregnancy, and surgery were excluded. The cohort was split into severe anemia (hemoglobin ≤9  g/dL) versus a comparison group (hemoglobin >9 g /dL), and examined for differences in 30-day hospital readmission and LOS.In this study, the data of 1141 patients were included, out of which 156 (13.7%) had severe anemia (mean hemoglobin 8.1 g/dL, SD 0.8). Severe anemia was associated with increased hospital LOS (mean 6.4 (SD 6.0) days vs mean 4.5 (SD 4.0) days, P < 0.001). The difference was 1.7 day longer (95% CI 0.94, 2.45). There was no difference in readmission rate (mean 11.5% vs 10.2%, P = 0.7).Patients with moderate CKD and severe anemia are at risk for increased hospital LOS. Interventions targeting this high-risk population, including outpatient management of anemia, may benefit patient care and save costs through improved hospital outcomes.

Correlation of bivalirudin dose with creatinine clearance during treatment of heparin-induced thrombocytopenia.

STUDY OBJECTIVES: To evaluate steady-state bivalirudin dosing requirements in patients with a wide range of kidney function who were being treated for heparin-induced thrombocytopenia (HIT)-related disorders. DESIGN: Retrospective medical record review. SETTING: Academic medical center. PATIENTS: Sixty-four adults with varying degrees of renal function who were receiving bivalirudin for at least 48 hours for HIT-related disorders between March 2007 and May 2010. MEASUREMENTS AND MAIN RESULTS: Steady-state conditions were defined as a constant bivalirudin infusion dose for at least 12 hours, with serum creatinine concentration varying less than 20% for 48 hours (for patients not receiving renal replacement therapy) and at least two therapeutic activated partial thromboplastin time (aPTT) values (60-80 sec). Patients were assigned to five groups based on Cockcroft-Gault-estimated creatinine clearance (Clcr) of less than 30, 30-60, or greater than 60 ml/minute, or by type of renal replacement therapy-intermittent hemodialysis or continuous venovenous hemofiltration (CVVH). For Clcr greater than 60 ml/minute, the median bivalirudin dose was 0.15 mg/kg/hour (interquartile range [IQR] 0.11-0.15 mg/kg/hr), which was greater than median doses for Clcr 30-60 ml/minute (0.10 mg/kg/hr, IQR 0.06-0.13 mg/kg/hr, p=0.004), Clcr less than 30 ml/minute (0.08 mg/kg/hr, IQR 0.04-0.1 mg/kg/hr, p=0.001), CVVH (0.06 mg/kg/hr, IQR 0.03-0.10 mg/kg/hr, p=0.046), and hemodialysis (0.04 mg/kg/hr, IQR 0.03-0.05 mg/kg/hr, p=0.0001). Bivalirudin doses correlated with Clcr (Spearman r = 0.58, p<0.01). The median aPTT value of 70 seconds (IQR 63-74 sec) was similar in all groups. Thrombosis was present before bivalirudin therapy in 18 (28%) of 64 patients, and two patients (3%) developed thromboemboli during bivalirudin therapy. Clinically significant bleeding related to bivalirudin and leading to discontinuation of bivalirudin occurred in four patients (6%). The median international normalized ratio increased from 1.5 (IQR 1.3-1.7) before bivalirudin therapy to 1.9 (IQR 1.8-2.1) during bivalirudin therapy (p=0.002) in 11 patients who were not receiving warfarin. CONCLUSION: Bivalirudin dosing requirements increased with increasing Clcr values. The high degree of variability suggests that dosing in individual patients will require careful titration to achieve adequate anticoagulation.

Proteinases as molecular adjuvants in allergic airway disease.

BACKGROUND: Asthma and related respiratory tract allergic diseases are among the most common chronic diseases of adults and children. Despite their importance, disease course cannot be predicted and treatment remains non-specific and potentially hazardous, with no means for cure. Improved clinical management of asthma will require an improved understanding of the fundamental factors that initiate allergic inflammation, especially T helper type 2 (T(H)2) cell induction. SCOPE OF REVIEW: In this review, we explore the Proteinase Hypothesis of allergic airway disease, considering specifically how organismal proteinases contribute to the expression of allergic disease and potentially important proteinase signaling pathways. MAJOR CONCLUSIONS: Proteinases from diverse sources (bacteria, fungi, plants) may cause occupational asthma by acting as immune adjuvant factors that specifically elicit T(H)2 cell-dependent allergic inflammation. However, more conventional allergic airway diseases (asthma, allergic sinusitis) are more likely to arise from contained fungal or viral infections of the airway in which proteinases are produced and serve as major virulence factors. Proteinases may elicit allergic disease by disrupting numerous cellular proteins, potentially including Toll like receptor (TLR) 4, but critical proteinase-activated signaling pathways remain largely unknown. GENERAL SIGNIFICANCE: Clarification of how proteinases cause allergic disease, specifically confirming an infectious basis for airway proteinase exposure, will likely radically advance how asthma and related respiratory tract disorders are diagnosed and treated. This article is part of a Special Issue entitled Biochemistry of Asthma.

Respiratory tract allergic disease and atopy: experimental evidence for a fungal infectious etiology.

Allergic asthma is an obstructive lung disease linked to environmental exposures that elicit allergic airway inflammation and characteristic antigen-specific immunoglobulin reactions termed atopy. Analyses of asthma pathogenesis using experimental models have shown that T helper cells, especially T helper type 2 (Th2) cells and Th2 cytokines such as interleukin 4 (IL-4) and IL-13, are critical mediators of airway obstruction following allergen challenge, but the environmental initiators of lung Th2 responses are less defined. Our studies demonstrate that fungal-derived proteinases that are commonly found in home environments are requisite immune adjuvants capable of eliciting robust Th2 responses and allergic lung disease in mice. We have further shown that common household fungi readily infect the mouse respiratory tract and induce both asthma-like disease and atopy to otherwise innocuous bystander antigens through the secretion of proteinases. These findings support the possibility that asthma and atopy represent a reaction to respiratory tract fungal infection, suggesting novel means for diagnosis and therapy of diverse allergic disorders.

The Certified Asthma Educator: The United States Experience.

Asthma is responsible for significant healthcare costs in the United States. Although advances in pharmacology and environmental science have provided many opportunities to improve asthma control, asthma remains a major cause of missed school days, acute care visits, and hospitalizations. Patient education is a key component of asthma care. The National Asthma Educator Certification Board was established in February 2000 and charged with the mission of "promoting optimal asthma management and quality of life for individuals with asthma, their families and communities by advancing excellence in asthma education through the certified asthma educator process." This study was performed to describe the workforce of certified asthma educators (AE-Cs®) by surveying a sample of educators who completed the recertification process. AE-Cs® who had completed the recertification process were invited to participate in an anonymous online survey. Sixty five of 135 (48%) recertificants completed the survey. The primary training of respondents was in respiratory therapy (51.6%) and nursing (42.2%). Respondents were primarily female (92.3%) and Caucasian (95.4%). The majority worked in specialty care outpatient (59.3%) or hospital inpatient (40.7%) settings. Twenty percent reported an increase in job responsibilities as a result of achieving their initial certification as an AE-C®. Most AE-Cs® have their basic training in either respiratory therapy or nursing. The workforce of AE-Cs® does not reflect the racial or ethnic percentages seen in the asthma population in the United States. More educators are needed to serve the growing numbers of individuals with asthma. Achievement of certification as an AE-C® resulted in additional job responsibilities in 20% of survey respondents.

Vaccine-acquired rotavirus in infants with severe combined immunodeficiency.

Live pentavalent human-bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients.

Outcomes of patients with severe combined immunodeficiency treated with hematopoietic stem cell transplantation with and without preconditioning.

BACKGROUND: The effect of pretransplantation conditioning on the long-term outcomes of patients receiving hematopoietic stem cell transplantation for severe combined immunodeficiency (SCID) has not been completely determined. OBJECTIVE: We sought to assess the outcomes of 23 mostly conditioned patients with SCID and compare their outcomes with those of 25 previously reported nonconditioned patients with SCID who underwent transplantation. METHODS: In the present study we reviewed the medical records of these 23 consecutive, mostly conditioned patients with SCID who underwent transplantation between 1998 and 2007. RESULTS: Eighteen patients (median age at transplantation, 10 months; range, 0.8-108 months) received haploidentical mismatched related donor, matched unrelated donor, or mismatched unrelated donor transplants, 17 of whom received pretransplantation conditioning (with 1 not conditioned); 13 (72%) patients engrafted with donor cells and survive at a median of 3.8 years (range, 1.8-9.8 year); 5 (38%) of 13 patients require intravenous immunoglobulin; and 6 of 6 age-eligible children attend school. Of 5 recipients (median age at transplantation, 7 months; range, 2-23 months) of matched related donor transplants, all 5 engrafted and survive at a median of 7.5 years (range, 1.5-9.5 year), 1 recipient requires intravenous immunoglobulin, and 3 of 3 age-eligible children attend school. Gene mutations were known in 16 cases: mutation in the common gamma chain of the IL-2 receptor (IL2RG) in 7 patients, mutation in the alpha chain of the IL-7 receptor (IL7RA) in 4 patients, mutation in the recombinase-activating gene (RAG1) in 2 patients, adenosine deaminase deficiency (ADA) in 2 patients, and adenylate kinase 2 (AK2) in 1 patient. Early outcomes and quality of life of the previous nonconditioned versus the present conditioned cohorts were not statistically different, but longer-term follow-up is necessary for confirmation. CONCLUSIONS: Hematopoietic stem cell transplantation in patients with SCID results in engraftment, long-term survival, and a good quality of life for the majority of patients with or without pretransplantation conditioning.

Hemophagocytic lymphohistiocytosis in a patient with x-linked lymphoproliferative disease.

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency affecting approximately 1 to 3 per million live male births. Patients are generally healthy until facing a viral infection such as Epstein-Barr Virus and then may develop fulminant infectious mononucleosis and die. XLP patients are also at increased risk of hemophagocytic lymphohistiocytosis (HLH), which may be triggered by assorted viruses. Here we report a novel case of HLH in a patient with XLP. Significant to his presentation is a paradoxical increase in natural killer (NK) cell activity. We hypothesize that this indicates that Parvovirus B19 activates NK cells via a signaling lymphocytic activation molecule-associated protein (SAP)-independent mechanism. Our case demonstrates an important etiology to consider in the differential diagnosis of XLP patients with nonfocal findings and febrile illnesses.