A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence-based literature. We present a consensus statement and comprehensive literature review that proposes a standard of care practices for the management of AS at a critical time when therapeutics to alter the natural history of the disease are on the horizon. METHODS: We compiled the key recognized clinical features of AS based on consensus from a team of specialists managing patients with AS. Working groups were established to address each focus area with committees comprised of providers who manage >5 individuals. Committees developed management guidelines for their area of expertise. These were compiled into a final document to provide a framework for standardizing management. Evidence from the medical literature was also comprehensively reviewed. RESULTS: Areas covered by working groups in the consensus document include genetics, developmental medicine, psychology, general health concerns, neurology (including movement disorders), sleep, psychiatry, orthopedics, ophthalmology, communication, early intervention and therapies, and caregiver health. Working groups created frameworks, including flowcharts and tables, to help with quick access for providers. Data from the literature were incorporated to ensure providers had review of experiential versus evidence-based care guidelines. CONCLUSION: Standards of care in the management of AS are keys to ensure optimal care at a critical time when new disease-modifying therapies are emerging. This document is a framework for providers of all familiarity levels.

Deployment of an Interventional Radiology Telemedicine Program During the COVID-19 Pandemic: Initial Experience With 10,056 Visits.

OBJECTIVE: To evaluate the clinical, operational, and financial effects of using telemedicine services in an academic interventional radiology setting during the coronavirus disease 2019 pandemic and to identify potential barriers to equitable telemedicine access for patients. METHODS: Evaluation and management (E&M) data over a 104-week period from September 2019 to August 2021 were reviewed. Data related to the visits were recorded including visit type, billing provider, patient demographic information, Current Procedural Terminology code charged, and reimbursement received. The ZIP code pertaining to the patient's primary residence was matched with median household income from the US Census Bureau. RESULTS: In all, 14,754 E&M encounters were performed over the study period, of which 10,056 were conducted using telemedicine. Twenty-two percent of visits were performed with interactive video; the remainder were performed using audio only. Female patients were more likely than male patients to use interactive video visits for telemedicine encounters (23.7% versus 20.4%, P < .001). Patients availing of video visits (mean age, 58.1 years, SD = 14.0) were also significantly younger than those patients who used audio-only (telephone) encounters (mean age, 62.5 years, SD = 13.3). Patients with private insurance and those living in neighborhoods with higher median household income were more likely to avail of interactive video visits (P < .001). Professional E&M monthly revenue was between 23.3% and 53.2% of peak prepandemic levels (mean 37.7%). CONCLUSION: Telemedicine services allowed for rapid restoration of E&M encounter volumes over the study period. Further work is required to determine the potential implementation barriers to increasing the use of video visits.

Hebrew version of the Jansari assessment of Executive Functions for Children (JEF-C©): Translation, adaptation and validation.

The Jansari assessment of Executive Functions for Children (JEF-C©) is a non-immersive computerized assessment of executive functions (EFs). This study aimed to create a cross-culturally adapted Hebrew version, JEF-C(H)© and to assess reliability and validity in the Israeli context. Forty typically developing Israeli children and adolescents, aged 11-18 years, were assessed with JEF-C(H)©. In addition, participants and their parents filled in the Behaviour Rating Inventory of Executive Function (BRIEF). JEF-C(H)© was found to be feasible in Israeli children and adolescents. The internal consistency was acceptable (Cronbach's alpha = 0.79). Most of the JEF-C(H)© subtests and the Average score showed significant positive moderate to high correlations with age, ranging from 0.40 to 0.78 demonstrating construct validity. Multiple significant correlations were also found between the JEF-C(H)© Average score and the BRIEF indices as well as total score in the Parent and Self-report questionnaires. These preliminary findings support the reliability and validity of this version. Current findings demonstrate the potential clinical utility of JEF-C(H)© as an ecologically valid tool for Israeli children and adolescents in the assessment of EFs.

Simultaneous detection of hepatitis C virus (HCV) core antigen and anti-HCV antibodies improves the early detection of HCV infection.

To evaluate whether a new enzyme immunoassay developed for the simultaneous detection of hepatitis C virus (HCV) core antigen (Ag) and anti-HCV antibodies (anti-HCV Ab) (Monolisa HCV Ag/Ab ULTRA; Bio-Rad) could improve the early detection of HCV infection, we compared its sensitivity to that of anti-HCV, HCV core Ag, and HCV RNA assays. The populations studied included 12 blood donor samples positive for HCV RNA and HCV core Ag but negative for anti-HCV antibodies and 23 hemodialysis patients who developed anti-HCV Ab (seroconversion) during the follow-up. From these 23 individuals, 83 samples sequentially collected prior to seroconversion and 108 samples collected after seroconversion were tested. Six of 12 blood donations were positive by the HCV Ag/Ab assay. In the hemodialysis cohort, the 24 HCV RNA-negative samples were negative by the HCV Ag/Ab assay and 23 of the 59 HCV RNA-positive samples (39%) were positive. The HCV Ag/Ab assay detected HCV infection on average 21.6 days before the most sensitive antibody assay. The HCV Ag/Ab assay did not detect HCV infection as early as the HCV RNA assay (mean delay, 30.3 days) or HCV Ag assay (mean delays, 27.9, and 16.3 days by the HCV core Ag quantification assay and the HCV Ag blood screening assay, respectively). This new assay provides a notable improvement for the early detection of HCV infection during the so-called window period compared with anti-HCV Ab assays and could be a useful alternative to HCV RNA detection or HCV core Ag assays for diagnosis or blood screening when nucleic acid technologies or HCV core Ag detection are not implemented.

Control of blood pressure and other cardiovascular risk factors at different practice settings: outcomes of care provided to diabetic women compared to men.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes. To determine the proportion of patients who met the American Diabetes Association guidelines for control of CVD risk factors and to assess the achievement of these guidelines in women compared with men, we conducted a cross-sectional study of 3678 diabetic cohorts followed at seven medical centers, two Veteran Administration hospitals, three urban clinics, and two suburban clinics. Overall, 28% met the target blood pressure of <130/80 mm Hg, 48.8% achieved a goal low-density lipoprotein cholesterol of <100 mg/dL, and 35.8% had hemoglobin A1c of <7%. Gender comparisons of 2788 diabetic patients at urban and suburban centers showed that women had a lower percentage of low-density lipoprotein cholesterol <100 mg/dL (45.8 vs. 51.3, p<0.01) and a lower percentage of screening for retinopathy (54 vs. 60, p<0.01) and nephropathy (37 vs. 49, p<0.01). However, overall there were no gender differences in the percentage of patients who achieved a goal blood pressure <130/80 mm Hg or hemoglobin A1c <7%. Control of blood pressure and other CVD risk factors in diabetic patients was largely suboptimal, especially for diabetic women. These observations underscore the need for better strategies for control of CVD risk in the diabetic population in general, and women in particular.

Follicular thyroid cancer presenting as a sellar mass: case report and review of the literature.

OBJECTIVE: To describe an uncommon initial manifestation of well-differentiated follicular carcinoma of the thyroid in an unusual metastatic site. METHODS: We present clinical, laboratory, and imaging findings in our patient and review related data from the literature. RESULTS: A young healthy woman presented with headache and diplopia. Magnetic resonance imaging of the brain showed a complex mass in the sellar region. Endocrine evaluation was remarkable only for a modestly high serum prolactin level. Transsphenoidal biopsy of the sellar mass revealed metastatic follicular thyroid carcinoma. On subsequent examination, a thyroid nodule was palpated. She underwent total thyroidectomy and ablative therapy with 131I, after which her symptoms gradually subsided and the sellar mass ultimately decreased in size. Although well-differentiated thyroid cancer generally manifests as a thyroid nodule, metastatic disease is present at the time of initial assessment in approximately 1% of cases, and the lungs and the skeleton are the most frequent sites of involvement. Only a few cases of thyroid cancer metastasizing to the sella have been reported. Described cases occurred mainly in elderly patients with previously diagnosed thyroid cancer. The most common malignant tumors that metastasize to the sella and pituitary are lung cancer in men and breast cancer in women. Metastatic tumors frequently manifest with cranial nerve palsies or diabetes insipidus and occur in elderly patients. CONCLUSION: Follicular thyroid cancer can manifest initially as a distant metastatic tumor in young patients. Metastatic lesions should always be in the differential diagnosis of a sellar mass, even in young patients.

A new HCV core antigen assay based on disassociation of immune complexes: an alternative to molecular biology in the diagnosis of early HCV infection.

BACKGROUND: An EIA based on immune complex disassociation of nucleocapsid proteins of HCV has been developed to detect and quantify HCV core antigen. STUDY DESIGN AND METHODS: To evaluate whether this new assay (trak-C, Ortho Clinical Diagnostics) could be an alternative to NAT during the window period, its sensitivity in this context was assessed, and its performance was compared with that of a first-generation HCV core antigen assay dedicated to the blood screening (HCV core antigen ELISA). Studied populations included nine HCV RNA-positive, HCV antibody-negative blood donors and 23 hemodialysis patients who underwent an HCV seroconversion. From these individuals, 81 samples (23 HCV RNA-negative and 58 HCV RNA-positive) sequentially collected during the phase before seroconversion were tested. RESULTS: The nine blood donor samples were positive for the presence of HCV core antigen by the trak-C, and 6 of 8 tested were positive for the presence of HCV core antigen by blood screening ELISA. In the hemodialysis cohort, the 23 HCV RNA-negative samples were negative with the two HCV core antigen assays. Among the 58 HCV RNA-positive samples, 46 of 57 (80.7%) tested were positive for the presence of HCV core antigen with the blood screening assay, and 57 of 58 (98.2%) were positive for the presence of HCV core antigen with the trak-C. The mean delays in detecting HCV infection between trak-C and the appearance of HCV antibodies, between HCV RNA testing and trak-C, and between trak-C and HCV core antigen ELISA were 58.2, 0.24, and 3.33 days, respectively. CONCLUSION: Trak-C was more sensitive than the blood screening assay and had similar performance to HCV RNA assay in the window period. Trak-C could constitute an alternative to NAT for the diagnosis of HCV infection during the window period, especially when molecular biology procedures cannot be implemented.

Outbreak of hepatitis C virus infection in a hemodialysis unit: potential transmission by the hemodialysis machine?

OBJECTIVE: To identify the routes of transmission during an outbreak of infection with hepatitis C virus (HCV) genotype 2a/2c in a hemodialysis unit. DESIGN: A matched case-control study was conducted to identify risk factors for HCV seroconversion. Direct observation and staff interviews were conducted to assess infection control practices. Molecular methods were used in a comparison of HCV infecting isolates from the case-patients and from patients infected with the 2a/2c genotype before admission to the unit. SETTING: A hemodialysis unit treating an average of 90 patients. PATIENTS: A case-patient was defined as a patient receiving hemodialysis with a seroconversion for HCV genotype 2a/2c between January 1994 and July 1997 who had received dialysis in the unit during the 3 months before the onset of disease. For each case-patient, 3 control-patients were randomly selected among all susceptible patients treated in the unit during the presumed contamination period of the case-patient. RESULTS: HCV seroconversion was associated with the number of hemodialysis sessions undergone on a machine shared with (odds ratio [OR] per additional session, 1.3; 95% confidence interval [CI95], 0.9 to 1.8) or in the same room as (OR per additional session, 1.1; CI95, 1.0 to 1.2) a patient who was anti-HCV (genotype 2a/2c) positive. We observed several breaches in infection control procedures. Wetting of transducer protectors in the external pressure tubing sets with patient blood reflux was observed, leading to a potential contamination by blood of the pressure-sensing port of the machine, which is not accessible to routine disinfection. The molecular analysis of HCV infecting isolates identified among the case-patients revealed two groups of identical isolates similar to those of two patients infected before admission to the unit. CONCLUSIONS: The results suggest patient-to-patient transmission of HCV by breaches in infection control practices and possible contamination of the machine. No additional cases have occurred since the reinforcement of infection control procedures and the use of a second transducer protector.