RESUMO
Introduction: Our study assessed the effectiveness of tele-coaching over written information in educating patients with chronic heart failure (CHF) at high risk of hospitalization about corona virus disease 2019 (COVID-19). We analyzed the impact on number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and self-reported behavior change. Methods: In April 2020, a tele-coaching module and written summary about COVID-19, risk-reduction measures for prevention of COVID-19, and appropriate consultation of medical attention during the pandemic were integrated into an established tele-coaching program. Three hundred seventy-eight patients who had received both tele-coaching and written information 3 weeks earlier were interviewed using a structured questionnaire and compared with 1,748 patients who had only received written information at this point. Results: Tele-coaching had no short-term effect on numbers of SARS-CoV-2 infections. However, patients receiving tele-coaching reported significantly more behavioral changes, including increased room ventilation (88% vs. 78%, p < 0.0001), surface cleaning (80% vs. 70%, p = 0.0006), wearing of face masks (59% vs. 51%, p = 0.013), and reduced usage of public transport (77% vs. 68%, p = 0.0003), despite no observed difference in recall about risk-reduction measures. Moreover, tele-coaching improved patients' knowledge about how to seek medical help in an emergency (46% vs. 36%, p = 0.0006), with a significant reduction in self-reported doctors' appointments (304 vs. 413 per 1,000 patients, p = 0.002) and hospital visits (50 vs. 87 per 1,000, p = 0.033) during the first peak of the pandemic. Conclusion: In a population of patients with CHF at high risk of hospitalization, COVID-19-specific tele-coaching effectively supported behavioral changes and significantly reduced face-to-face medical contacts in a short-term follow-up period.
Assuntos
COVID-19 , Insuficiência Cardíaca , Tutoria , COVID-19/epidemiologia , Doença Crônica , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Pandemias , Comportamento de Redução do Risco , SARS-CoV-2RESUMO
Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.
Assuntos
Neoplasias , Sequenciamento Completo do Genoma , Humanos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/diagnóstico , Criança , Masculino , Pré-Escolar , Feminino , Adolescente , Lactente , Testes Genéticos/métodos , Genoma Humano/genética , Genômica/métodos , Recém-NascidoRESUMO
BACKGROUND: Hypoketotic hypoglycaemia with suppressed plasma fatty acids and detectable insulin suggests congenital hyperinsulinism (CHI). Severe hypoketotic hypoglycaemia mimicking hyperinsulinism but without detectable insulin has recently been described in syndromic individuals with mosaic genetic activation of post-receptor insulin signalling. We set out to expand understanding of this entity focusing on metabolic phenotypes. METHODS: Metabolic profiling, candidate gene and exome sequencing were performed in six infants with hypoketotic, hypoinsulinaemic hypoglycaemia, with or without syndromic features. Additional signalling studies were carried out in dermal fibroblasts from two individuals. RESULTS: Two infants had no syndromic features. One was mistakenly diagnosed with CHI. One had mild features of megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, one had non-specific macrosomia, and two had complex syndromes. All required intensive treatment to maintain euglycaemia, with CHI-directed therapies being ineffective. Pathogenic PIK3CA variants were found in two individuals - de novo germline c.323G>A (p.Arg108His) in one non-syndromic infant and postzygotic mosaic c.2740G>A (p.Gly914Arg) in the infant with MCAP. No causal variants were proven in the other individuals despite extensive investigation, although rare variants in mTORC components were identified in one. No increased PI3K signalling in fibroblasts of two individuals was seen. CONCLUSIONS: We expand the spectrum of PI3K-related hypoinsulinaemic hypoketotic hypoglycaemia. We demonstrate that pathogenic germline variants activating post-insulin-receptor signalling may cause non-syndromic hypoinsulinaemic hypoketotic hypoglycaemia closely resembling CHI. This distinct biochemical footprint should be sought and differentiated from CHI in infantile hypoglycaemia. To facilitate adoption of this differential diagnosis, we propose the term "pseudohyperinsulinism".
Assuntos
Hiperinsulinismo Congênito , Proteínas Proto-Oncogênicas c-akt , Lactente , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Insulina , Hiperinsulinismo Congênito/genética , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
OBJECTIVE: Genetic activation of the insulin signal-transducing kinase AKT2 causes syndromic hypoketotic hypoglycaemia without elevated insulin. Mosaic activating mutations in class 1A phospatidylinositol-3-kinase (PI3K), upstream from AKT2 in insulin signalling, are known to cause segmental overgrowth, but the metabolic consequences have not been systematically reported. We assess the metabolic phenotype of 22 patients with mosaic activating mutations affecting PI3K, thereby providing new insight into the metabolic function of this complex node in insulin signal transduction. METHODS: Three patients with megalencephaly, diffuse asymmetric overgrowth, hypoketotic, hypoinsulinaemic hypoglycaemia and no AKT2 mutation underwent further genetic, clinical and metabolic investigation. Signalling in dermal fibroblasts from one patient and efficacy of the mTOR inhibitor Sirolimus on pathway activation were examined. Finally, the metabolic profile of a cohort of 19 further patients with mosaic activating mutations in PI3K was assessed. RESULTS: In the first three patients, mosaic mutations in PIK3CA (p.Gly118Asp or p.Glu726Lys) or PIK3R2 (p.Gly373Arg) were found. In different tissue samples available from one patient, the PIK3CA p.Glu726Lys mutation was present at burdens from 24% to 42%, with the highest level in the liver. Dermal fibroblasts showed increased basal AKT phosphorylation which was potently suppressed by Sirolimus. Nineteen further patients with mosaic mutations in PIK3CA had neither clinical nor biochemical evidence of hypoglycaemia. CONCLUSIONS: Mosaic mutations activating class 1A PI3K cause severe non-ketotic hypoglycaemia in a subset of patients, with the metabolic phenotype presumably related to the extent of mosaicism within the liver. mTOR or PI3K inhibitors offer the prospect for future therapy.