The Importance of Self-Management in the Context of Personalized Care in COPD

Despite current guidelines and decades of evidence on the benefits of a self-management approach, self-management of COPD remains relatively under-utilized in clinical care compared with other chronic diseases. However, self-management interventions can play a valuable role in supporting people with COPD to respond to changing symptoms, and thereby make appropriate decisions regarding the management of their own chronic condition. In this review, we discuss the history and evolution of the concept of self-management, assess current multidisciplinary support programs and clinical interactions designed to optimize self-management, and reflect on how effective these are in terms of clinical and humanistic outcomes. We also evaluate the mechanisms for encouraging change from protocol-based care towards a more personalized care approach, and discuss the role of digital self-management interventions and the importance of addressing health inequalities in COPD treatment, which have been accelerated by the COVID-19 pandemic. Reflecting on the importance of self-management in the context of symptom monitoring and provision of educational support, including information from patient organizations and charities, we discuss the ideal components of a self-management plan for COPD and provide six key recommendations for its implementation: 1) better education for healthcare professionals on disease management and consultation skills; 2) new targets and priorities for patient-focused outcomes; 3) skills gap audits to identify barriers to self-management; 4) best practice sharing within primary care networks and ongoing professional development; 5) enhanced initial consultations to establish optimal self-management from the outset; and 6) negotiation and sharing of self-management plans at the point of diagnosis

Whole exome sequencing identifies novel mutations in relapsed or refractory acute promyelocytic leukaemia failing treatment with oral arsenic trioxide

Conference abstracts will be published in Haematologica in the near futurepostprin

Three-year findings of the HORIZON trial: a Schlemm canal microstent for pressure reduction in primary open angle glaucoma and cataract

OBJECTIVE: To report 3-year outcomes of the HORIZON study comparing cataract surgery with Hydrus Microstent versus cataract surgery alone. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Five hundred fifty-six eyes from 556 patients with cataract and POAG treated with ≥ 1 glaucoma medication, washed out diurnal intraocular pressure (DIOP) 22-34 mmHg and no prior incisional glaucoma surgery. METHODS: Following phacoemulsification, eyes were randomized 2:1 to receive a Hydrus® Microstent (Ivantis, Inc.) or no stent. Follow-up included comprehensive eye examinations through 3 years postoperatively. MAIN OUTCOME MEASURES: Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts. RESULTS: 369 eyes were randomized to microstent treatment (HMS) and 187 to cataract surgery only (CS). Preoperative IOP, medication usage, washed out DIOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 in the HMS group and 17.0 ± 3.4 in the CS group (p=0.85). The number of glaucoma medications was 0.4 ± 0.8 in the HMS group and 0.8 ± 1.0 in the CS group (p<0.001), and 73% of eyes in the HMS group were medication free compared to 48% in the CS group (p<0.001). The HMS group had a higher proportion of eyes with IOP ≤18 mmHg without medications compared to CS (56.2% vs. 34.6%, p<0.001) as well as IOP reduction of at least 20, 30 or 40 percent compared to CS alone. The cumulative probability of incisional glaucoma surgery was lower in the HMS group (0.6% vs. 3.9%, hazard ratio = 0.156, 95% CI 0.031 to 0.773, p=0.020). There was no difference in postoperative corneal endothelial cell loss between groups. There were no procedure or device related serious adverse events resulting in vision loss in either group. CONCLUSIONS: Combined cataract surgery and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtrations surgery than cataract surgery alone at 3 years

Addressing a system failure to diagnose COPD and asthma

To provide high-quality guideline-based care for patients with asthma or chronic obstructive pulmonary disease (COPD) we must first establish the correct diagnosis. The National Asthma and COPD Audit Programme (NACAP) has highlighted an important issue across England, Scotland, and Wales that potentially undermines care for many people with airways disease

Interactions of Catalytic Enzymes with n-Type Polymers for High-Performance Metabolite Sensors

The tight regulation of the glucose concentration in the body is crucial for balanced physiological function. We developed an electrochemical transistor comprising an n-type conjugated polymer film in contact with a catalytic enzyme for sensitive and selective glucose detection in bodily fluids. Despite the promise of these sensors, the property of the polymer that led to such high performance has remained unknown, with charge transport being the only characteristic under focus. Here, we studied the impact of the polymer chemical structure on film surface properties and enzyme adsorption behavior using a combination of physiochemical characterization methods and correlated our findings with the resulting sensor performance. We developed five n-type polymers bearing the same backbone with side chains differing in polarity and charge. We found that the nature of the side chains modulated the film surface properties, dictating the extent of interactions between the enzyme and the polymer film. Quartz crystal microbalance with dissipation monitoring studies showed that hydrophobic surfaces retained more enzymes in a densely packed arrangement, while hydrophilic surfaces captured fewer enzymes in a flattened conformation. X-ray photoelectron spectroscopy analysis of the surfaces revealed strong interactions of the enzyme with the glycolated side chains of the polymers, which improved for linear side chains compared to those for branched ones. We probed the alterations in the enzyme structure upon adsorption using circular dichroism, which suggested protein denaturation on hydrophobic surfaces. Our study concludes that a negatively charged, smooth, and hydrophilic film surface provides the best environment for enzyme adsorption with desired mass and conformation, maximizing the sensor performance. This knowledge will guide synthetic work aiming to establish close interactions between proteins and electronic materials, which is crucial for developing high-performance enzymatic metabolite biosensors and biocatalytic charge-conversion devices

Prognostic value of clinically important deterioration in COPD: IMPACT trial analysis

Introduction: Clinically important deterioration (CID) is a multicomponent measure for assessing disease worsening in chronic obstructive pulmonary disease (COPD). This analysis investigated the prognostic value of a CID event on future clinical outcomes and the effect of single-inhaler triple versus dual therapy on reducing CID risk in patients in the IMPACT trial. Methods: IMPACT was a phase III, double-blind, 52-week, multicentre trial. Patients with symptomatic COPD and at least one moderate/severe exacerbation in the prior year were randomised 2:2:1 to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg, FF/VI 100/25 µg or UMEC/VI 62.5/25 µg. CID at the time-point of interest was defined as a moderate/severe exacerbation, ≥100 mL decrease in trough forced expiratory volume in 1 s or deterioration in health status (increase of ≥4.0 units in St George's Respiratory Questionnaire total score or increase of ≥2.0 units in COPD Assessment Test score) from baseline. A treatment-independent post hoc prognostic analysis compared clinical outcomes up to week 52 in patients with/without a CID by week 28. A prospective analysis evaluated time to first CID with each treatment. Results: Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52 (all p<0.001), and increased risk of all-cause mortality after week 28 versus patients who were CID-free. FF/UMEC/VI significantly reduced CID risk versus dual therapies (all p<0.001). Conclusions: Prevention of short-term disease worsening was associated with better long-term clinical outcomes. FF/UMEC/VI reduced CID risk versus dual therapies; this effect may improve long-term prognosis in this population

Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis

The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in response to increased ceramide for sustenance of high energy demanding organ functions like the heart