Distinguishing Incubation and Acute Disease Stages of Mild-to-Moderate COVID-19

While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1⁺ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched, whereas all other parameters returned to baseline. Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcomes.     

Effects of Tafamidis on Transthyretin Stabilization and Clinical Outcomes in Patients with Non-Val30Met Transthyretin Amyloidosis

This phase II, open-label, single-treatment arm study evaluated the pharmacodynamics, efficacy, and safety of tafamidis in patients with non-Val30Met transthyretin (TTR) amyloidosis. Twenty-one patients with eight different non-Val30Met mutations received 20 mg QD of tafamidis meglumine for 12 months. The primary outcome, TTR stabilization at Week 6, was achieved in 18 (94.7 %) of 19 patients with evaluable data. TTR was stabilized in 100 % of patients with non-missing data at Months 6 (n?=?18) and 12 (n?=?17). Exploratory efficacy measures demonstrated some worsening of neurological function. However, health-related quality of life, cardiac biomarker N-terminal pro-hormone brain natriuretic peptide, echocardiographic parameters, and modified body mass index did not demonstrate clinically relevant worsening during the 12 months of treatment. Tafamidis was well tolerated. In conclusion, our findings suggest that tafamidis 20 mg QD effectively stabilized TTR associated with several non-Val30Met variants.     

Self-treatment of bulimia nervosa: A pilot study

Twenty-eight patients with ICD-10 bulimia nervosa or atypical bulimia nervosa were given a cognitive-behavioral treatment handbook and were reassessed 4-6 weeks later, On a clinician-rated global improvement scale 12 patients had much improved and 8 patients had somewhat improved. Fifteen patients were abstinent of vomiting or laxatives at reassessment as opposed to five patients before treatment. Of the 21 patients who were hinging before treatment, 7 had a 75– 700% reduction of binges and 5 had a 50–75% reduction of binges. Patients' nutritional knowledge increased significantly. A patient-administered handbook may be a useful first intervention in the treatment of patients with bulimia nervosa. © 1993 by John Wiley & Sons, Inc.     

Association of Race and Neighborhood Disadvantage with Patient Engagement in a Home-Based COVID-19 Remote Monitoring Program

BackgroundCOVID-positive outpatients may benefit from remote monitoring, but such a program often relies on smartphone apps. This may introduce racial and socio-economic barriers to participation. Offering multiple methods for participation may address these barriers.Objectives(1) To examine associations of race and neighborhood disadvantage with patient retention in a monitoring program offering two participation methods. (2) To measure the association of the program with emergency department visits and hospital admissions.DesignRetrospective propensity-matched cohort study.ParticipantsCOVID-positive outpatients at a single university-affiliated healthcare system and propensity-matched controls.InterventionsA home monitoring program providing daily symptom tracking via patient portal app or telephone calls.Main MeasuresAmong program enrollees, retention (until 14 days, symptom resolution, or hospital admission) by race and neighborhood disadvantage, with stratification by program arm. In enrollees versus matched controls, emergency department utilization and hospital admission within 30 days.Key ResultsThere were 7592 enrolled patients and 9710 matched controls. Black enrollees chose the telephone arm more frequently than White enrollees (68% versus 44%, p = 0.009), as did those from more versus less disadvantaged neighborhoods (59% versus 43%, p = 0.02). Retention was similar in Black enrollees and White enrollees (63% versus 62%, p = 0.76) and in more versus less disadvantaged neighborhoods (63% versus 62%, p = 0.44). When stratified by program arm, Black enrollees had lower retention than White enrollees in the app arm (49% versus 55%, p = 0.01), but not in the telephone arm (69% versus 71%, p = 0.12). Compared to controls, enrollees more frequently visited the emergency department (HR 1.71 [95% CI 1.56–1.87]) and were admitted to the hospital (HR 1.16 [95% CI 1.02–1.31]).ConclusionsIn a COVID-19 remote patient monitoring program, Black enrollees preferentially selected, and had higher retention in, telephone- over app-based monitoring. As a result, overall retention was similar between races. Remote monitoring programs with multiple modes may reduce barriers to participation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07207-4.KEY WORDS: ambulatory monitoring, COVID-19, race factors, facilities and services utilization     

Patterns of punitiveness in women with eating disorders

The level and direction of hostility in patients with bulimia nervosa, anorexia nervosa and a comparison group were measured using the Hostility and Direction of Hostility Questionnaire. A semistructured interview developed by Harris, Brown, and Bifulco (Psychological Medicine, 16, 641-659, 1986) was used to assess childhood care to examine whether a link exists between childhood exposure to aggression or parental neglect and adult hostility. Patients with eating disorders had significantly higher hostility levels and were significantly more intropunitive than the comparison group. Patients with bulimia nervosa were significantly more intropunitive than the comparison group. Patients with bulimia nervosa were significantly more hostile than patients with anorexia nervosa. Anorexia nervosa patients were more likely to direct hostility inwardly, rather than outwardly, when compared with bulimia nervosa patients. Impulsivity was associated with extrapunitiveness whereas intropunitiveness was associated with depression. Although some measures of poor childhood care correlated with adult hostility levels no clear pattern emerged. © 1995 by John Wiley & Sons, Inc.     

Correction to: Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Journal of Neurology - The original version of this article unfortunately contained a mistake.     

Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.