Treatment of idiopathic anaphylaxis with dupilumab: a case report.

BACKGROUND: Anaphylaxis is an acute, potentially life-threatening allergic reaction that typically occurs after exposure to a trigger, while idiopathic anaphylaxis (IA) occurs in the absence of a trigger. Acute management of both triggered anaphylaxis and IA relies on the use of epinephrine. In some patients with recurrent IA, glucocorticoid prophylaxis with prednisone can be effective. While there is currently no high quality evidence for the use of other prophylactic options to prevent recurrent IA, evolving data exists to support the consideration of biologics that target IgE or the Th2 pathway. CASE PRESENTATION: We present the case of a 28 year old female with no atopic or autoimmune history with recurrent episodes of IA since childhood occurring up to twice weekly. There was improvement in acute symptoms with administration of first or second generation antihistamines and/or intramuscular epinephrine. Without an identifiable trigger, she was diagnosed with IA and frequent idiopathic urticaria and omalizumab was added to her treatment regimen with improvement in symptom frequency. After being lost to follow up, she had recurrence of symptom frequency and severity without omalizumab therapy and subsequently presented to our institution. Her workup at this point was negative for food allergy, alpha gal syndrome, systemic mastocytosis, hereditary alpha tryptasemia, carcinoid syndrome, and pheochromocytoma, and she was trialed on dupilumab with near resolution of her symptom frequency over a six month time period. CONCLUSION: Recurrent IA is a diagnosis of exclusion that is associated with high morbidity. Prophylaxis remains an area of uncertainty, although prednisone has been effective in some cases. When prednisone is contraindicated or ineffective for the prevention of IA, biologic therapies that target IgE or the Th2 pathway may present a reasonable consideration. This case adds support to the suggestion that dupilumab may be a logical off-label consideration for prophylaxis of recurrent IA. The data for dupilumab in this clinical scenario is still very limited, and further research is required before any recommendation can be made.

Clinical Characteristics and Prognostic Value of Ro52/SSA Antibodies in Idiopathic Inflammatory Myopathies.

BACKGROUND/PURPOSE: Anti-Ro52 are myositis-associated antibodies found in idiopathic inflammatory myopathies (IIMs). This chart review aims to evaluate the frequency, significance, and associated clinical characteristics of Ro52/SSA positivity in IIM patients. METHODS: We performed a chart review of IIM patients diagnosed between January 2006 and December 2020. All patients met either the 1975 Bohan and Peter or the European League Against Rheumatism/American College of Rheumatology classification criteria for probable or definite myositis. Demographics, clinical and serologic parameters, treatments, and outcomes were compared in patients with anti-Ro52/SSA antibodies and patients without anti-Ro52/SSA antibodies. RESULTS: One hundred eighty-nine patients with IIM were tested for either Ro52 or SSA, with 45 positive for Ro52/SSA (23.8%). Patients with IIM and Ro52/SSA+ were younger at age at onset of disease (44.8 vs. 51.2 years, p = 0.008). Ro52/SSA+ was more common in antisynthetase syndrome (p < 0.001; odds ratio [OR], 4.44; 95% confidence interval [CI], 2.11-9.33) and not frequently identified in clinically amyopathic dermatomyositis (CADM) (p = 0.02; OR, 0.13; 95% CI, 0.02-0.96) or immune-mediated necrotizing myopathy (p = 0.003; OR, 0.14; 95% CI, 0.03-0.63). Of the extraskeletal muscle manifestations, interstitial lung disease (ILD) was strongly associated with Ro52/SSA+ (p < 0.001; OR, 6.61; 95% CI, 3.15-13.86), as was dysphagia (p = 0.006; OR, 2.73; 95% CI, 1.31-5.71). Interstitial lung disease pattern and pulmonary function testing impairment did not differ based on antibody status. There was no significant difference in outcomes between groups. CONCLUSION: In this myositis cohort, Ro52/SSA+ was present in nearly one-fourth of the population and had a strong association with the antisynthetase syndrome subtype, ILD, and dysphagia. Although these disease manifestations are associated with significant morbidity, in our cohort, they were not associated with increased mortality or more severe ILD.

Consensus statement for the management of incidentally found brain white matter hyperintensities in general medical practice.

INTRODUCTION: There is a paradigm shift in our understanding of white matter hyperintensities (WMH) found on brain imaging. They were once thought to be a normal phenomenon of ageing and, therefore, warranted no further investigation. However, evidence now suggests these lesions are markers of poor brain and cardiovascular health, portending an increased risk of stroke, cognitive decline, depression and death. Nevertheless, no specific guidelines exist for the management of incidentally found WMH for general medical practitioners and other clinicians ordering brain magnetic resonance imaging scans for diverse clinical indications. Informed by a literature review and expert opinion gleaned from stroke neurologists, medical and imaging specialists, and general practitioners, we present our consensus statement to guide the management of incidentally found WMH in adults. MAIN RECOMMENDATIONS: When incidental WMH are found on brain imaging: Perform a detailed history and examination to screen for neurological events. Investigate for potential undiagnosed or undertreated cardiovascular risk factors, especially hypertension and diabetes mellitus. Commence intensive and individualised cardiovascular risk management when risk factors are uncovered. Treat underlying risk factors via accepted guidelines but note that antiplatelet and anticoagulant medications should not be prescribed for incidental WMH in the absence of an alternative indication. CHANGES TO MANAGEMENT AS A RESULT OF THIS CONSENSUS STATEMENT: A brain health opportunity. We consider the discovery of incidental WMH on brain imaging to represent an opportunity to investigate for common cardiovascular risk factors and to optimise brain health. This can be commenced and monitored by the general practitioner or physician without delay in waiting for an outpatient neurology review.

Improving a Leadership Scale: Applying Rasch Analysis to Student Pharmacists' Attitudes and Beliefs About Leadership.

OBJECTIVE: Leadership development is necessary for student pharmacists to become pharmacist leaders, but no readily usable standard measurement of student attitudes toward and beliefs about leadership exists. To assess the reliability and validity evidence for using the Leadership Attitudes and Beliefs Scale (LABS-III), originally developed and validated in Malaysia, for use with student pharmacists in the United States. METHODS: The 2-unit leadership course was piloted among second- and third-year students in a public college of pharmacy with a 4-year doctor of pharmacy curriculum. The participating students completed the LABS-III during the first and last classes as part of a quality improvement measure for course enhancement. Rasch analysis was then used to assess the reliability and validity evidence for the LABS-III. RESULTS: A total of 24 students participated in the pilot course. The pre and postcourse surveys had 100% and 92% response rates, respectively. After Rasch analysis model fit was achieved, the item separation for the 14 nonextreme items was 2.19 with an item reliability of 0.83. The person separation index was 2.16 with a person reliability of 0.82. CONCLUSION: The Rasch analysis revealed that the number of LABS-III items should be decreased and that the 3-point response scale should be used to improve functionality and use in classroom settings for PharmD students in the United States. Further research is needed to augment the reliability and validity evidence of the modified instrument for use at other United States colleges of pharmacy.

Telestroke Assessment With Perfusion CT Improves the Diagnostic Accuracy of Stroke vs. Mimic.

Background and Purpose: CT perfusion (CTP) has been implemented widely in regional areas of Australia for telestroke assessment. The aim of this study was to determine if, as part of telestroke assessment, CTP provided added benefit to clinical features in distinguishing between strokes and mimic and between transient ischaemic attack (TIA) and mimic. Methods: We retrospectively analysed 1,513 consecutively recruited patients referred to the Northern New South Wales Telestroke service, where CTP is performed as a part of telestroke assessment. Patients were classified based on the final diagnosis of stroke, TIA, or mimic. Multivariate regression models were used to determine factors that could be used to differentiate between stroke and mimic and between TIA and mimic. Results: There were 693 strokes, 97 TIA, and 259 mimics included in the multivariate regression models. For the stroke vs. mimic model using symptoms only, the area under the curve (AUC) on the receiver operator curve (ROC) was 0.71 (95% CI 0.67-0.75). For the stroke vs. mimic model using the absence of ischaemic lesion on CTP in addition to clinical features, the AUC was 0.90 (95% CI 0.88-0.92). The multivariate regression model for predicting mimic from TIA using symptoms produced an AUC of 0.71 (95% CI 0.65-0.76). The addition of absence of an ischaemic lesion on CTP to clinical features for the TIA vs. mimic model had an AUC of 0.78 (95% CI 0.73-0.83) Conclusions: In the telehealth setting, the absence of an ischaemic lesion on CTP adds to the diagnostic accuracy in distinguishing mimic from stroke, above that from clinical features.

Stroke in Older Survivors of Ischemic Stroke: Standard Care or Something Different?

Stroke is one of the leading causes of death and disability and it is more likely to occur in those who are older. Because people are living longer, the definition of "old" continues to evolve. Age alone should not influence the healthcare that a patient receives, however, evidence indicates that this does occur, especially in older patients. On the basis of the available evidence, it is time to reconsider whether or not stroke care should differ in older survivors of stroke and if so, why. This is a narrative review of stroke-related health care in those with a recent ischemic stroke. It seeks to answer the following question: Should patients aged ≥80 years who have experienced a recent ischemic stroke receive standard care or something different, and if they should receive something different, what should they receive and why? The review focusses on long-term survival, hyper-acute care, secondary prevention, and rehabilitation. The authors propose a number of recommendations in relation to stroke care in older survivors of a recent ischemic stroke.

CT perfusion source images improve identification of early ischaemic change in hyperacute stroke.

CT perfusion scanning produces dynamic contrast-enhanced brain images, but to generate and interpret the colour maps of cerebral perfusion from these source images requires specialist neuroimaging knowledge. We hypothesized that physicians without such training might still utilise the CT perfusion source images (CTPSI) to diagnose early ischaemic change. Fifteen patients had cerebral non-contrast CT (NCCT) and perfusion CT within 6 hours of hemispheric stroke onset. We tested 15 non-stroke clinicians and radiology trainees, plus three experts, in assessing the presence and extent of early ischaemic change on NCCT versus CTPSI. Day 5-7 CT or MRI was used as the gold standard. Agreement with follow-up imaging was poor for both detection, and extent of early ischaemic change on NCCT (kappa = 0.01-0.11). There was a marked improvement in agreement for both the presence and extent of early ischaemic change on CTPSI (kappa = 0.67-0.83). CTPSI were much more accurate than NCCT in identifying acute ischaemic change. 'Less expert' users accurately identified major early ischaemic change on acute CTPSI. These findings suggest that such physicians might utilise CTPSI to screen potential thrombolysis candidates.

Perfusion computed tomography: prediction of final infarct extent and stroke outcome.

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) has not been previously applied to perfusion CT (CTP). Five raters assigned ASPECTS to baseline noncontrast CT (NCCT), CT angiography source images (CTA-SI), CTP source images (CTP-SI), and CTP maps of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) from 37 consecutive patients with less than 6-hour anterior circulation ischemic stroke. Major reperfusion was identified on follow-up imaging. Mean baseline ASPECTS was compared with follow-up imaging ASPECTS. Rates of favorable outcome were compared for dichotomized baseline ASPECTS. In patients with major reperfusion, mean CBV and CTP-SI ASPECTS closely predicted final infarct ASPECTS. In patients without major reperfusion, mean CBF and MTT ASPECTS best predicted final infarct ASPECTS. There were significant increases in rates of favorable outcome for CTP-SI and CBV ASPECTS of greater than 6, versus less than or equal to 6, but not for other baseline CT modalities. ASPECTS applied to CTP is more accurate at identifying the extent of reversible and irreversible ischemia and at predicting final clinical outcome than NCCTor CTA-SI.