Once-Daily Triple Therapy in Patients with COPD: Patient-Reported Symptoms and Quality of Life

Introduction

Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies. The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses. FULFIL co-primary endpoint data have been previously reported.

Methods

FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β₂-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations. A subset participated for 52 weeks. Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD? (E-RS: COPD), St George’s Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.

Results

FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period. FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR. At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).

Conclusion

These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR. The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.

Trial registration

ClinicalTrials.gov number: NCT02345161.

Funding

GSK.

     

Ethical implications of home telecare for older people: a framework derived from a multisited participative study

Context

Telecare and telehealth developments have recently attracted much attention in research and service development contexts, where their evaluation has predominantly concerned effectiveness and efficiency. Their social and ethical implications, in contrast, have received little scrutiny.

Objective

To develop an ethical framework for telecare systems based on analysis of observations of telecare‐in‐use and citizens’ panel deliberations.

Design

Ethnographic study (observation, work shadowing), interviews, older citizens’ panels and a participative conference.

Setting

Participants’ homes, workplaces and familiar community venues in England, Spain, the Netherlands and Norway 2008–2011.

Results

Older respondents expressed concerns that telecare might be used to replace face‐to‐face/hands‐on care to cut costs. Citizens’ panels strongly advocated ethical and social questions being considered in tandem with technical and policy developments. Older people are too often excluded from telecare system design, and installation is often wrongly seen as a one‐off event. Some systems enhance self‐care by increasing self‐awareness, while others shift agency away from the older person, introducing new forms of dependency.

Conclusions

Telecare has care limitations; it is not a solution, but a shift in networks of relations and responsibilities. Telecare cannot be meaningfully evaluated as an entity, but rather in the situated relations people and technologies create together. Characteristics of ethical telecare include on‐going user/carer engagement in decision making about systems: in‐home system evolution with feedback opportunities built into implementation. System design should be horizontal, ‘two‐way’/interactive rather than vertical or ‘one‐way’. An ethical framework for telecare has been developed from these conclusions (Table 1).     

Plant growth-promoting hormones activate mammalian guanylate cyclase activity

In vivo injections of plant growth-promoting hormones increase the growth of animals as well as plants. Plant growth-promoting hormones and positive plant growth regulators are known to increase RNA and protein synthesis. Since cyclic GMP also increases RNA and protein synthesis, the object of the present investigation was to determine whether physiological levels of plant growth-promoting hormones and positive plant growth regulators have part of their mechanism(s) of action through stimulation of the guanylate cyclase (EC 4.6.1.2)-cyclic GMP system. Representatives of the three classes of growth-promoting hormones were investigated. Thus, auxins (indole-3-acetic acid, indole-3-butyric acid, beta-naphthoxyacetic acid, and 2,4,5-trichlorophenoxy acetic acid), gibberellins (gibberellic acid), and cytokinins [N6-benzyl adenine, kinetin (6-furfuryl aminopurine), and beta-(2-furyl) acrylic acid] all increased rat lung, small intestine, liver, and renal cortex guanylate cyclase activity 2- to 4-fold at the 1 microM concentration. Dose response curves revealed that maximal stimulation of guanylate cyclase by these plant growth regulators was at 1 microM; there was no augmented cyclase activity at 1 nM. The guanylate cyclase cationic cofactor manganese was not essential for augmentation of guanylate cyclase by these plant growth-promoting regulators. The antioxidant butylated hydroxytoluene did not block the enhancement of guanylate cyclase by these plant growth-promoting factors. These data suggest that guanylate cyclase may play a role in the mechanism of action of plant growth-promoting hormones and even of positive plant regulators at the cellular level.     

In vivo Doppler optical coherence tomography of mucocutaneous telangiectases in hereditary hemorrhagic telangiectasia

BACKGROUND: Hereditary hemorrhagic telangiectasia is characterized by mucocutaneous telangiectases and visceral arteriovenous malformations. Knowledge is limited concerning the development hemodynamics of mucocutaneous telangiectases. Doppler optical coherence tomography can demonstrate microvascular blood flow at flow rates as low as 20 microm/second, which is up to approximately 100 times more sensitive than Doppler US. The aims of this study were to collect in vivo Doppler optical coherence tomography images of mucocutaneous telangiectases and normal surrounding mucosa and skin, and to gain experience for an in vivo GI endoscopic study. It was hypothesized that visibly normal areas may have occult telangiectases and that mucocutaneous telangiectases that have bled may have a higher rate of blood flow than mucocutaneous telangiectases with no history of bleeding. METHODS: Twelve patients with hereditary hemorrhagic telangiectasia and mucocutaneous telangiectases were studied. Two to 3 visible mucocutaneous telangiectases on the digits, lips, and tongue were imaged with Doppler optical coherence tomography, along with visually normal surrounding areas at each site. The Doppler optical coherence tomography images were obtained in 0.5 second by using 1310 nm light. RESULTS: A total of 67 mucocutaneous telangiectases from the 12 patients were imaged (38 digit, 16 lip, 13 tongue). Blood flow was demonstrated within every mucocutaneous telangiectasis imaged. Doppler optical coherence tomography did not identify any abnormal vasculature within visually normal areas. Mucocutaneous telangiectases with a history of bleeding (n = 18) were situated closer to the surface, compared with mucocutaneous telangiectases with no bleeding history (n = 49), but there was no difference in the Doppler flow appearance. CONCLUSIONS: Visually normal areas in patients with hereditary hemorrhagic telangiectasia did not appear to have abnormal vasculature. Mucocutaneous telangiectases with a history of bleeding were more superficial but were otherwise similar to mucocutaneous telangiectases with no bleeding history.     

Attachment style and coping in relation to posttraumatic stress disorder symptoms among adults living with HIV/AIDS

Research indicates that a significant proportion of people living with HIV/AIDS report symptoms of posttraumatic stress disorder (PTSD). Moreover, attachment style has been associated with psychological and behavioral outcomes among persons living with HIV/AIDS. Attachment style may influence the ability to cope with traumatic stress and affect PTSD symptoms. To examine the association between attachment style and coping with PTSD symptoms, we assessed 94 HIV-positive adults on self-report measures of posttraumatic stress, coping, and attachment style. In multiple regression analysis, avoidant attachment and emotion-focused coping were positively and significantly associated with greater PTSD symptomatology. Support was also found for the moderating effects of avoidant and insecure attachment styles on emotion-focused coping in relation to greater PTSD symptoms. Taken altogether, these results suggest that interventions that develop adaptive coping skills and focus on the underlying construct of attachment may be particularly effective in reducing trauma-related symptoms in adults living with HIV/AIDS.     

The match-play running performance of elite Camogie players across halves of play

Sport Sciences for Health - Camogie is one of the most popular female sports in Ireland, yet the demands of match-play are unknown. The current study aimed to examine the match-play running...     

Impact of a Low-Glucose Peritoneal Dialysis Regimen on Fibrosis and Inflammation Biomarkers

♦ Background: The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated.♦ Methods: In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, soluble-intracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF).♦ Results: At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF.♦ Conclusion: Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.     

Optimizing the management of patients with spinal myeloma disease

Myeloma is one of the most common malignancies that results in osteolytic lesions of the spine. Complications, including pathological fractures of the vertebrae and spinal cord compression, may cause severe pain, deformity and neurological sequelae. They may also have significant consequences for quality of life and prognosis for patients. For patients with known or newly diagnosed myeloma presenting with persistent back or radicular pain/weakness, early diagnosis of spinal myeloma disease is therefore essential to treat and prevent further deterioration. Magnetic resonance imaging is the initial imaging modality of choice for the evaluation of spinal disease. Treatment of the underlying malignancy with systemic chemotherapy together with supportive bisphosphonate treatment reduces further vertebral damage. Additional interventions such as cement augmentation, radiotherapy, or surgery are often necessary to prevent, treat and control spinal complications. However, optimal management is dependent on the individual nature of the spinal involvement and requires careful assessment and appropriate intervention throughout. This article reviews the treatment and management options for spinal myeloma disease and highlights the value of defined pathways to enable the proper management of patients affected by it.