MHealth and perceived quality of care delivery: a conceptual model and validation.

BACKGROUND: The objective of this research is to examine, conceptualize, and empirically validate a model of mobile health (mHealth) impacts on physicians' perceived quality of care delivery (PQoC). METHODS: Observational quasi-experimental one group posttest-only design was implemented through the empirical testing of the conceptual model with nine hypotheses related to the association of task and technology characteristics, self-efficacy, m-health utilization, task-technology fit (TTF), and their relationships with PQoC. Primary data was collected over a four-month period from acute care physicians in The Ottawa Hospital, Ontario, Canada. The self-reported data was collected by employing a survey and distributed through the internal hospital channels to physicians who adopted iPads for their daily activities. RESULTS: Physicians' PQoC was found to be positively affected by the level of mHealth utilization and TTF, while the magnitude of the TTF direct effect was two times stronger than utilization. Additionally, self-efficacy has the highest direct and total effect on mHealth utilization; in the formation of TTF, technological characteristics dominate followed by task characteristics. CONCLUSION: To date, the impact of utilized mHealth on PQoC has neither been richly theorized nor explored in depth. We address this gap in existing literature. Realizing how an organization can improve TTF will lead to better PQoC.

Matrix Remodeling in Pulmonary Fibrosis and Emphysema.

Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-ß1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema.

An aberrant leukotriene A4 hydrolase-proline-glycine-proline pathway in the pathogenesis of chronic obstructive pulmonary disease.

RATIONALE: Chronic neutrophilic inflammation is a hallmark in the pathogenesis of chronic obstructive pulmonary disease (COPD) and persists after cigarette smoking has stopped. Mechanisms involved in this ongoing inflammatory response have not been delineated. OBJECTIVES: We investigated changes to the leukotriene A4 hydrolase (LTA4H)-proline-glycine-proline (PGP) pathway and chronic inflammation in the development of COPD. METHODS: A/J mice were exposed to air or cigarette smoke for 22 weeks followed by bronchoalveolar lavage and lung and cardiac tissue analysis. Two human cohorts were used to analyze changes to the LTA4H-PGP pathway in never smokers, control smokers, COPD smokers, and COPD former smokers. PGP/AcPGP and LTA4H aminopeptidase activity were detected by mass spectroscopy, LTA4H amounts were detected by ELISA, and acrolein was detected by Western blot. MEASUREMENTS AND MAIN RESULTS: Mice exposed to cigarette smoke developed emphysema with increased PGP, neutrophilic inflammation, and selective inhibition of LTA4H aminopeptidase, which ordinarily degrades PGP. We recapitulated these findings in smokers with and without COPD. PGP and AcPGP are closely associated with cigarette smoke use. Once chronic inflammation is established, changes to LTA4H aminopeptidase remain, even in the absence of ongoing cigarette use. Acrolein modifies LTA4H and inhibits aminopeptidase activity to the same extent as cigarette smoke. CONCLUSIONS: These results demonstrate a novel pathway of aberrant regulation of PGP/AcPGP, suggesting this inflammatory pathway may be intimately involved in disease progression in the absence of ongoing cigarette smoke exposure. We highlight a mechanism by which acrolein potentiates neutrophilic inflammation through selective inhibition of LTA4H aminopeptidase activity. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).

Therapeutic targeting of SRC kinase in myofibroblast differentiation and pulmonary fibrosis.

Myofibroblasts are effector cells in fibrotic disorders that synthesize and remodel the extracellular matrix (ECM). This study investigated the role of the Src kinase pathway in myofibroblast activation in vitro and fibrogenesis in vivo. The profibrotic cytokine, transforming growth factor ß1 (TGF-ß1), induced rapid activation of Src kinase, which led to myofibroblast differentiation of human lung fibroblasts. The Src kinase inhibitor AZD0530 (saracatinib) blocked TGF-ß1-induced Src kinase activation in a dose-dependent manner. Inhibition of Src kinase significantly reduced α-smooth muscle actin (α-SMA) expression, a marker of myofibroblast differentiation, in TGF-ß1-treated lung fibroblasts. In addition, the induced expression of collagen and fibronectin and three-dimensional collagen gel contraction were also significantly inhibited in AZD0530-treated fibroblasts. The therapeutic efficiency of Src kinase inhibition in vivo was tested in the bleomycin murine lung fibrosis model. Src kinase activation and collagen accumulation were significantly reduced in the lungs of AZD0530-treated mice when compared with controls. Furthermore, the total fibrotic area and expression of α-SMA and ECM proteins were significantly decreased in lungs of AZD0530-treated mice. These results indicate that Src kinase promotes myofibroblast differentiation and activation of lung fibroblasts. Additionally, these studies provide proof-of-concept for targeting the noncanonical TGF-ß signaling pathway involving Src kinase as an effective therapeutic strategy for lung fibrosis.

Orbital Rosai-Dorfman disease with subperiosteal bone involvement mimicking eosinophilic granuloma.

The presentation of RDD as an anterior subperiosteal orbital mass with bone involvement has, to the authors' knowledge, not been previously reported. We describe a case of Rosai-Dorfman disease (RDD) presenting as an anterior superolateral subperiosteal orbital mass with erosion of overlying bone mimicking eosinophilic granuloma. It was debulked using endoscopic-guided curettage and the patient was given both local and systemic corticosteroids. Careful histological analysis revealed the diagnosis of RDD and the patient remains asymptomatic and recurrence free at 16 months follow-up. Involvement of the pituitary gland, a recognized yet unusual finding in this condition was also noted. RDD should be considered in the differential diagnosis of a soft tissue mass of the superolateral orbit.

Delayed hypersensitivity reaction to Restylane ® SubQ.

PURPOSE: To report on 4 patients who developed delayed hypersensitivity reactions to Restylane(®) SubQ and their management. To our knowledge, no cases of delayed hypersensitivity to Restylane(®) SubQ have been previously reported. METHODS: A retrospective case series of 4 patients who were treated with preperiosteal Restylane(®) SubQ to their cheeks, for facial volume augmentation. All 4 patients were subsequently referred with delayed hypersensitivity reactions over a 4-month period. RESULTS: The hypersensitivity reactions occurred from 1 week to 4 months' post-cheek augmentation using Restylane(®) SubQ. All patients had previously (and some since) been treated with other non-animal stabilized hyaluronic acid (NASHA) products without adverse effect. Hyaluronidase led to fast and effective resolution in all cases, although 2 of the patients required repeat treatment. CONCLUSION: Hyaluronidase was effective at treating the inflammatory reaction and breaking up the retained Restylane(®) SubQ in all patients. Although Restylane(®) SubQ should be avoided in these patients, in our experience this does not preclude them from using other similar NASHA products.

Our experience with the masquerade procedure for total eyelid loss.

PURPOSE: To describe our experience of the Masquerade Procedure, a historical procedure that is poorly described in the modern literature. METHODS: We performed a masquerade procedure in two complex surgical cases where traditional methods of eyelid reconstruction or closure were not possible. The first case suffered a partial de-gloving injury with a right sided anterior exenteration and loss of the upper and lower eyelids. On the left side, he lost the lower forehead and brow as well as the entire left upper eyelid leaving superior bulbar conjunctiva only. The cornea of the left eye was completely exposed and required urgent coverage. The second case was involved in a light aircraft crash and suffered extensive facial burns with periocular involvement bilaterally. On the left side, there was complete loss of the upper and lower eyelids and fornices extending to the bulbar conjunctiva. The cornea was keratinized and vascularised due to chronic exposure. RESULTS: In the first patient, poor eyelid closure led to corneal ulceration and scarring. A repeat procedure involved the use of a cheek rotation flap, and ultimately the fashioning of a small port-hole aperture inferiorly to avoid corneal exposure. The patient maintains navigational vision. The second patient had two attempts at a masquerade procedure, however the poor blood supply led to complete and partial failure of the first and second procedures respectively. CONCLUSION: The masquerade procedure may be considered in extreme circumstances, however in our experience, multiple interventions and further reconstructive surgery may subsequently be required.

N-alpha-PGP and PGP, potential biomarkers and therapeutic targets for COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder for which new diagnostic and therapeutic approaches are required. Hallmarks of COPD are matrix destruction and neutrophilic airway inflammation in the lung. We have previously described two tri-peptides, N-alpha-PGP and PGP, which are collagen fragments and neutrophil chemoattractants. In this study, we investigate if N-alpha-PGP and PGP are biomarkers and potential therapeutic targets for COPD. METHODS: Induced sputum samples from COPD patients, healthy controls and asthmatics were examined for levels of N-alpha-PGP and PGP using mass spectrometry and for the ability to generate PGP de novo from collagen. Proteases important in PGP generation in the lung were identified by the use of specific inhibitors in the PGP generation assay and by instillation of proteases into mouse lungs. Serum levels of PGP were compared between COPD patients and controls. RESULTS: N-alpha-PGP was detected in most COPD sputum samples but in no asthmatics or controls. PGP was detected in a few controls and in all COPD sputum samples, where it correlated with levels of myeloperoxidase. COPD sputum samples had the ability to generate N-alpha-PGP and PGP de novo from collagen. PGP generation by COPD sputum was blocked by inhibitors of matrix metalloproteases (MMP's) 1 and 9 and prolyl endopeptidase. MMP's 1 and 9 and prolyl endopeptidase acted synergistically to generate PGP in vivo when instilled into mouse lungs. Serum levels of PGP were also significantly higher in COPD patients than in controls CONCLUSION: N-alpha-PGP and PGP may represent novel diagnostic tests and biomarkers for COPD. Inhibition of this pathway may provide novel therapies for COPD directed at the chronic, neutrophilic, airway inflammation which underlies disease progression.

Interfering with extracellular matrix degradation to blunt inflammation.

Chemoattractant properties of matrix proteins, like collagen and elastin, for neutrophils and monocytes in vitro have long been recognized. This activity often resides in fragments of these proteins. These peptides may play a role in diseases of the lung matrix, such as chronic obstructive pulmonary disease. Recent advances include the elucidation of the structure of chemotactic collagen fragments and the demonstration that their activity may reside in a structural relatedness to CXC chemokines. Collagen and elastin fragments have been demonstrated to have a role in in vivo lung pathophysiology and have been quantified in patients with chronic lung diseases where they may activate autoimmune pathways. Elucidation of these pathways may provide novel biomarkers and therapeutic targets for chronic lung diseases.

Angiotensin-converting enzyme defines matrikine-regulated inflammation and fibrosis.

The neutrophil chemoattractant proline-glycine-proline (PGP) is generated from collagen by matrix metalloproteinase-8/9 (MMP-8/9) and prolyl endopeptidase (PE), and it is concomitantly degraded by extracellular leukotriene A4 hydrolase (LTA4H) to limit neutrophilia. Components of cigarette smoke can acetylate PGP, yielding a species (AcPGP) that is resistant to LTA4H-mediated degradation and can, thus, support a sustained neutrophilia. In this study, we sought to elucidate if an antiinflammatory system existed to degrade AcPGP that is analogous to the PGP-LTA4H axis. We demonstrate that AcPGP is degraded through a previously unidentified action of the enzyme angiotensin-converting enzyme (ACE). Pulmonary ACE is elevated during episodes of acute inflammation, as a consequence of enhanced vascular permeability, to ensure the efficient degradation of AcPGP. Conversely, we suggest that this pathway is aberrant in chronic obstructive pulmonary disease (COPD) enabling the accumulation of AcPGP. Consequently, we identify a potentially novel protective role for AcPGP in limiting pulmonary fibrosis and suggest the pathogenic function attributed to ACE in idiopathic pulmonary fibrosis (IPF) to be a consequence of overzealous AcPGP degradation. Thus, AcPGP seemingly has very divergent roles: it is pathogenic in its capacity to drive neutrophilic inflammation and matrix degradation in the context of COPD, but it is protective in its capacity to limit fibrosis in IPF.

Age and sex profile of patients having cataract surgery between 1986 and 2003.

PURPOSE: To investigate the age and sex profile of patients having cataract surgery by 2 consulting ophthalmic surgeons over an 18-year period. SETTING: Waterford Regional Hospital, Waterford, Republic of Ireland. METHODS: Operating theater logbooks were reviewed, and all patients having cataract surgery between January 1986 and December 2003 in Waterford Regional Hospital were identified. The following data were recorded for each patient: age, sex, and type of cataract surgery. Patients having cataract surgery were categorized according to the date of the procedure as follows: Group 1: 1986-1991; Group 2: 1992-1997; Group 3: 1998-2003. RESULTS: Eight thousand two hundred fifty-seven patients who had cataract surgery during the study period were identified. The mean age of patients was 72.32 years +/- 12.21 (SD) and 74.89 +/- 11.03 years of men and women, respectively. The age profile of patients having cataract surgery was statistically comparable in Groups 1, 2, and 3 (mean age; Group 1: 72.33 +/- 13.03 years; Group 2: 73.72 +/- 11.78 years; Group 3: 74.57 +/- 10.69 years), indicating that the age profile of patients did not change significantly with the passage of time (analysis of variance, F<1). The proportion of women having cataract surgery rose significantly over the duration of the study period (1986-1991: 55.13%; 1992-1997: 57.68%; 1998-2003: 59.43% (chi-square test, P<.01)). CONCLUSIONS: The age profile of 8257 patients having cataract surgery did not change over the 18-year study period. A small but significant increase in the proportion of women having cataract surgery was noted in latter years. This data is useful to those involved in health care planning.

Renal replacement therapy III: IHD, CRRT, SLED.

Acute renal failure in critically ill patients is a growing clinical problem. Options for renal replacement therapy in these patients use convective and diffusive clearance and may be intermittent, as in classic hemodialysis, or continuous. New ways of delivering dialysis in the intensive care unit, such as sustained low-efficiency dialysis, are also under development. It may be that renal replacement therapy needs to be tailored to the needs of each individual patient. Current and future research studies should provide the answers to many of these questions.

Oxidant-antioxidant balance in acute lung injury.

ARDS is a disease process that is characterized by diffuse inflammation in the lung parenchyma. The involvement of inflammatory mediators in ARDS has been the subject of intense investigation, and oxidant-mediated tissue injury is likely to be important in the pathogenesis of ARDS. In response to various inflammatory stimuli, lung endothelial cells, alveolar cells, and airway epithelial cells, as well as activated alveolar macrophages, produce both nitric oxide and superoxide, which may react to form peroxynitrite, which can nitrate and oxidize key amino acids in various lung proteins, such as surfactant protein A, and inhibit their functions. The nitration and oxidation of a variety of crucial proteins present in the alveolar space have been shown to be associated with diminished function in vitro and also have been identified ex vivo in proteins sampled from patients with acute lung injury (ALI)/ARDS. Various enzymes and low-molecular-weight scavengers that are present in the lung tissue and alveolar lining fluid decreased the concentration of these toxic species. The purpose of this brief chapter is to review the results from various studies demonstrating increased levels of reactive oxygen-nitrogen intermediates in the alveolar spaces of patients with ALI/ARDS.

Sputum PGP is reduced by azithromycin treatment in patients with COPD and correlates with exacerbations.

RATIONALE: Proline-glycine-proline (PGP), a neutrophil chemoattractant derived from the enzymatic breakdown of collagen, is elevated in sputum of patients with chronic obstructive pulmonary disease (COPD) and may contribute to disease progression. Whether sputum levels of PGP respond to therapy for COPD or predict outcomes is unknown. OBJECTIVES: We conducted a study ancillary to a multicenter trial of the efficacy of azithromycin treatment for 1 year in preventing COPD exacerbations to test whether sputum levels of PGP were altered by treatment or associated with exacerbation frequency. METHODS: We collected remnant sputa from trial participants and assayed them in a blinded fashion for PGP, myeloperoxidase and matrix metalloproteinase (MMP)-9 and for the ability to generate PGP from collagen ex vivo. Once the parent trial was unblinded, the results were correlated with use of azithromycin or placebo and exacerbations in participants. RESULTS: Azithromycin treatment significantly reduced sputum levels of PGP and myeloperoxidase in patients with COPD, particularly with increased duration of therapy. We found no difference in sputum MMP-9 or PGP generation between participants taking azithromycin or placebo. Sputum PGP levels were highest around the time of an exacerbation and declined with successful treatment. CONCLUSIONS: These data support a role for PGP in the airway and parenchymal neutrophilic inflammation that drives COPD progression and exacerbations, and provide new information on the anti-inflammatory properties of macrolides. PGP may have potential as a target for novel anti-inflammatory therapies in COPD and as a biomarker for clinical trials.

A review of combined orbital decompression and lower eyelid recession surgery for lower eyelid retraction in thyroid orbitopathy.

BACKGROUND/AIMS: Eyelid retraction in thyroid orbitopathy is traditionally managed with staged surgery after orbital decompression. We review the benefit of concurrent inferior retractor recession at the time of orbital decompression when closing a swinging-eyelid flap. METHODS: A retrospective, comparative, non-randomised clinical audit of 34 eyes of 22 patients with thyroid orbitopathy over a 3-year period was carried out. Patients were divided into a combined orbital decompression and inferior retractor recession (with lateral horn release) group (RG, n=13) and an orbital decompression non-recession group (NRG, n=21). Groups were matched for age, walls decompressed, volume of intraconal fat excised and improvement in exophthalmometry. Surgery involved one to three wall decompressions and intraconal fat excision via a swinging eyelid and transcaruncular approach. We report outcomes at 6 months based on postoperative standard photographs. Lower eyelid height, inferior scleral show and lower eyelid lateral flare were recorded by two blinded, independent assessors. RESULTS: The RG achieved a greater improvement in lower eyelid elevation (1.8 ± 0.8 mm) compared to the NRG (1.1 ± 0.8 mm) (p=0.042). The RG (58%) and NRG (40%) had improvement of lower lid lateral flare. Mean scleral show improved in both the RG (1.3 mm) and NRG (0.9 mm). No lower eyelid complications occurred. CONCLUSION: Combining orbital decompression with concurrent inferior retractor recession at the time of swinging-eyelid flap closure is safe and improves lower lid height postoperatively compared to decompression alone.

Towards improved healthcare performance: examining technological possibilities and patient satisfaction with wireless body area networks.

This paper investigates the benefits of using less intrusive wireless technologies for heart monitoring. By replacing well established heart monitoring devices (i.e. Holter) with wireless ECG based Body Area Networks (BAN), improved healthcare performance can be achieved, reflected in (1) high quality ECG recordings during physical activities and (2) increased patient satisfaction. A small scale clinical trial was conducted to compare both technologies and the results illustrate that the wireless ECG monitor was able to detect ECG signals intended for arrhythmia diagnostics. Furthermore, from a patient's perspective, both technologies were evaluated using three dimensions, namely; hygienic aspects, physical activity, and skin reactions. Results demonstrate that the wireless ECG BAN showed better performance, especially regarding the hygienic aspects. It was also favourable for use during physical activities, and the signal quality of the wireless sensor system demonstrated good performance regarding signal noise and artefact disturbances. This paper concludes that wireless cardiac monitoring systems have significant benefits from a patient's perspective, and further clinical trials should be conducted to further evaluate the new ECG based BAN system, to identify the possibility of widespread adoption and utilisation of wireless technology for arrhythmia diagnostics.

Augmentation of macular pigment following implantation of blue light-filtering intraocular lenses at the time of cataract surgery.

PURPOSE: (Photo)-oxidative stress is believed to play a role in the pathogenesis of age-related macular degeneration (AMD), with the threshold for retinal damage being lowest for short-wavelength (blue) light. Macular pigment (MP), consisting of the carotenoids lutein (L), zeaxanthin (Z) and meso-Z, has a maximum absorption at 460 nm and protects the retina from (photo)-oxidative injury. This study was designed to investigate whether the blue light-filtering properties of the Alcon AcrySof Natural intraocular lens (ANIOL) implanted during cataract surgery affects MP optical density (MPOD). METHODS: Forty-two patients scheduled for cataract surgery were recruited for the study. These patients all had a preoperative best corrected visual acuity rating (BCVAR) of at least 0.5 (logMAR) in the study eye. The patients were randomized to have either the standard Alcon AcrySof three-piece acrylic intraocular lens (AIOL) (controls) or the ANIOL implanted at the time of cataract surgery. The spatial profile of MPOD (i.e., at 0.25 degrees, 0.5 degrees, 1.0 degrees, and 1.75 degrees eccentricity) was measured with customized heterochromatic flicker photometry (cHFP) 1 week before and 1 week after surgery, and at 3, 6, and 12 months after surgery. Serum concentrations of L and Z were also measured at each study visit. RESULTS: There was a highly significant and positive correlation between all MPODs (e.g., at 0.25 degrees) recorded 1 week before and after surgery in eyes with an AIOL implant (r = 0.915, P < 0.01; paired samples t-test, P = 0.631) and in those ANIOL implants (r = 0.868, P < 0.01; paired samples t-test, P = 0.719). Average MPOD across the retina increased significantly with time (after 3 months) in the ANIOL group (repeated-measures, general linear model, P < 0.05), but remained stable in the AIOL group (repeated-measures, general linear model, P > 0.05). There were no significant time or lens effects observed for serum L over the study period (P > 0.05). There was a significant time effect for serum Z over the study period (P < 0.05), but not a significant time/lens interaction (P > 0.05). CONCLUSIONS: Customized HFP can reliably measure the MPOD spatial profile in the presence of lens opacity, and cataract surgery does not artifactually alter MPOD readings. This study also provides evidence that implanting an IOL that filters blue light is associated with augmentation of MPOD in the absence of raised serum concentrations of L and Z. However, further and longitudinal study is needed to assess whether the observed increase in MPOD after implantation of blue-filtering IOLs is associated with reduced risk of AMD development and/or progression.

Neutrophils contain prolyl endopeptidase and generate the chemotactic peptide, PGP, from collagen.

Prolyl endopeptidase (PE), a protease that cleaves after proline residues in oligopeptides, is highly active in brain and degrades neuropeptides in vitro. We have recently demonstrated that PE, in concert with MMP's, can generate PGP (proline-glycine-proline), a novel, neutrophil chemoattractant, from collagen. In this study, we demonstrate that human peripheral blood neutrophils contain PE, which is constitutively active, and can generate PGP de novo from collagen after activation with LPS. This novel, pro-inflammatory role for PE raises the possibility of a self-sustaining pathway of neutrophilic inflammation and may provide biomarkers and therapeutic targets for diseases caused by chronic, neutrophilic inflammation.