Implementation of a prospective screening strategy to identify adults with a telomere biology disorder among those undergoing lung transplant evaluation for interstitial lung disease.

INTRODUCTION: Patients with interstitial lung disease (ILD) secondary to telomere biology disorders (TBD) experience increased morbidity after lung transplantation. Identifying patients with TBD may allow for personalized management to facilitate better outcomes. However, establishing a TBD diagnosis in adults is challenging. METHODS: A TBD screening questionnaire was introduced prospectively into the lung transplant evaluation. Patients with ILD screening positive were referred for comprehensive TBD phenotyping and concurrent telomere length measurement and germline genetic testing. RESULTS: Of 98 patients, 32 (33%) screened positive. Eight patients (8% of total; 25% of patients with a positive screen) met strict TBD diagnostic criteria, requiring either critically short lymphocyte telomeres (<1st percentile) (n = 4), a pathogenic variant in a TBD-associated gene (n = 1), or both (n = 3) along with a TBD clinical phenotype. Additional patients not meeting strict diagnostic criteria had histories consistent with TBD along with telomere lengths <10th percentile and/or rare variants in TBD-associated genes, highlighting a critical need to refine TBD diagnostic criteria for this patient population. CONCLUSION: A TBD phenotype screening questionnaire in patients with ILD undergoing lung transplant evaluation has a diagnostic yield of 25%. Additional gene discovery, rare variant functional testing, and refined TBD diagnostic criteria are needed to realize the maximum benefit of testing for TBD in patients undergoing lung transplantation.

Treatment barriers in PANS/PANDAS: Observations from eleven health care provider families.

INTRODUCTION: Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) are severe but highly treatable postinfectious inflammatory brain conditions. Despite published diagnostic and treatment guidelines for this condition, there are long delays in obtaining appropriate care. The reasons for these delays are poorly understood. We sought to identify health care system barriers to timely treatment by examining cases of PANDAS/PANS occurring in children of health care professionals. METHOD: We recruited families via e-mail request through the PANDAS Physicians Network. Participating parents completed a structured questionnaire and provided a written case description. RESULTS: Eleven families completed data collection, representing a broad spectrum of disease (child disease onset age 4-15, 7 males/4 females, mild to severe). Parents included 11 physicians, 2 mental health professionals, 2 nurses, and a PharmD. Nine cases (82%) had "very delayed" diagnosis and treatment (>4 weeks after onset). The most commonly encountered causes for treatment delay were clinician lack of awareness (82%), clinician skepticism (82%), overdependence on diagnostic testing (91%), and out-of-pocket expenses >$100 US (82%). Other common challenges included difficulties finding a provider to spearhead care (64%), psychological misdiagnosis (55%), and children's suppression of behaviors during assessments (55%). CONCLUSIONS: We found numerous barriers to treatment of PANDAS/PANS among children of health care providers. Our findings suggest that even among the medically sophisticated, PANDAS/PANS diagnosis and treatment remains challenging. Improvement in PANDAS/PANS education of clinicians who may encounter children with this disorder is 1 key step toward addressing our identified barriers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).