The role of high-flow nasal therapy in bronchiectasis: a post hoc analysis.

High-flow nasal therapy significantly reduces exacerbation rates and improves quality of life in patients with stable bronchiectasis. High-flow nasal therapy is therefore a potential treatment option for patients with bronchiectasis. https://bit.ly/2JFXuQc.

Recurrent hypertrophic pulmonary osteoarthropathy in an adult with bronchiectasis.

Hypertrophic pulmonary osteoarthropathy (HPOA) is a well-documented complication of pulmonary malignancy and cystic fibrosis (CF). However, HPOA associated with exacerbations of non-CF bronchiectasis has only been reported once previously in an adolescent. We describe a case of an adult patient with bronchiectasis and HPOA, whose joint symptoms flared during pulmonary exacerbations and improved with treatment of each exacerbation.

Radial-probe endobronchial ultrasound outcomes in the investigation of peripheral pulmonary lesions: a New Zealand perspective.

BACKGROUND: Radial-probe endobronchial ultrasound (radial-EBUS) is becoming an important investigation for peripheral pulmonary lesions (PPL). A key advantage of radial-EBUS is the favourable risk profile compared with current gold-standard computerised tomography-guided biopsy. AIM: To investigate the diagnostic yield, predictors of positive yield and radial-EBUS safety in a New Zealand institution. We also determined whether molecular analysis was possible on the same tissue samples. METHODS: We performed a retrospective analysis of all patients (n = 68) from Middlemore Hospital, Auckland, undergoing radial-EBUS with guide-sheath for PPL from March 2015 to August 2016. Clinical, radiological and procedural data were collected. Radial-EBUS diagnostic yield was determined for malignant and benign diagnoses, and molecular analysis yield was determined on appropriate malignant samples. Logistic regression was used to determine factors predicting successful radial-EBUS. RESULTS: Overall diagnostic yield of radial-EBUS was 55.9% (95% confidence interval (CI): 44.3-67.9). Malignant diagnostic sensitivity was 60.8% (95% CI: 46.1-74.2) and benign diagnostic sensitivity was 50% (95% CI: 23-77). Lesions close to the hilum (P = 0.039), concentric radial-probe positioning (P = 0.008) and the use of forceps as first instrument (P = 0.0049) significantly predicted successful diagnostic yield. Of the malignant cases 81.0% (95% CI: 58.1-94.6) were sufficient for molecular analysis. Pneumothorax occurred in 4.4% (95% CI: 0.9-12.4), none required chest drain intervention. There were no cases of significant pulmonary haemorrhage. CONCLUSION: Radial-EBUS was shown to be safe with diagnostic yield similar to international reports. Important predictors of success include distance from hilum, probe position and forceps as first instrument. We also demonstrated that molecular analysis is possible in radial-EBUS obtained samples.

The Auckland keratoconus study: identifying predictors of acute corneal hydrops in keratoconus.

BACKGROUND: The aim was to identify potential factors associated with acute corneal hydrops in a New Zealand population with keratoconus referred to a hospital eye service. METHODS: In a single hospital centre, in a retrospective review, demographic and clinical features of subjects with keratoconus and corneal hydrops over a 17-year period were compared with an age- and gender-matched control group of subjects with keratoconus but no history of corneal hydrops. RESULTS: One hundred and one eyes of 101 subjects (mean age 24.6 ± 8.4 years) were identified with keratoconus-related corneal hydrops. Subjects were more likely to be of Pacific but less likely to be of New Zealand European ethnicity than control subjects (n = 101). In comparison, Maori ethnicity was not found to have a significantly positive or negative association with hydrops. The pre-hydrops visual acuity (VA) of affected eyes was poorer than that of controls (p < 0.001) at first presentation to our tertiary referral corneal and contact lens service. Hydrops typically developed approximately four years after diagnosis of keratoconus. Subjects with hydrops were more likely to have a history of eye-rubbing (p = 0.011) but less likely to have a family history of keratoconus (p = 0.05). In 31 cases, the acute hydrops event was their first optometric/ophthalmologic contact. There were no statistically significant differences in the prevalence of atopic disease, contact lens wear or overall corneal transplantation rate between the two groups. CONCLUSIONS: Pacific ethnicity, history of eye-rubbing, poor VA at first hospital presentation and lack of family history were statistically associated with developing acute corneal hydrops in keratoconus in a New Zealand population. Greater understanding of such predisposing risk factors may help develop early management strategies to delay or prevent progression of this disease.

Immunolocalization of gap junction protein connexin43 (GJA1) in the human retina and optic nerve.

PURPOSE: Gap junctions are intercellular channels that have been implicated in the pathogenesis of neuronal death after central nervous system injury. This study determines the expression pattern of gap junction protein connexin43 in the human retina and optic nerve. METHODS: An affinity-isolated polyclonal antibody to the C-terminal segment of the cytoplasmic domain of human connexin43 was used to determine connexin43 localization. Postmortem human eyes were examined by immunohistochemical staining of frozen sections using antibodies to connexin43. Antibody binding was detected using confocal microscopy and fluorochrome-conjugated secondary antibodies. Double-label immunohistochemistry identified the cell types expressing connexin43. RESULTS: Connexin43 immunoreactivity was detected in the human retina on glial fibrillary acidic protein (GFAP)-positive astrocytes in the retinal ganglion cell layer and, to a lesser extent, on the processes of glutamine synthetase-labeled Müller cells. The retinal and choroidal circulations showed strong connexin43 immunolabeling. Dense connexin43 immunoreactivity was present between adjacent cells of the retinal pigment epithelium, and there was diffuse connexin43 immunoreactivity on GFAP-positive astrocytes in the optic nerve. CONCLUSIONS: In the human retina and optic nerve, connexin43 is present on glia, blood vessels, and epithelial cells. An understanding of the distribution of connexin43 in the normal retina and optic nerve may be used to evaluate changes associated with retinal and optic nerve disease.

Effectiveness of Alora estradiol matrix transdermal delivery system in improving lumbar bone mineral density in healthy, postmenopausal women.

OBJECTIVE: To determine the lowest effective dose of an estradiol (E ) matrix-type transdermal delivery system (EMTDS; Alora) for preventing bone loss in postmenopausal women. DESIGN: This double-blind, double-dummy, randomized, placebo-controlled, multicenter study enrolled 355 nonosteoporotic postmenopausal women who had been hysterectomized with or without oophorectomy at least 12 months earlier. Participants were randomly assigned to one of three doses of the EMTDS (0.025, 0.05, or 0.075 mg/day) or placebo administered twice weekly. Lumbar bone mineral density (LBMD) was measured by dual-energy x-ray absorptiometry at screening and after 1 and 2 years of treatment. Safety was assessed at regularly scheduled visits. RESULTS: EMTDS provided statistically significant and clinically meaningful changes in LBMD relative to placebo. At 2 years, LBMD declined from baseline by 0.59% in the placebo group, but it increased from baseline by 1.65% ( = 0.0065), 4.08% ( = 0.0001), and 4.82% ( = 0.0001) in the EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. The corresponding responder rates (defined as no change or increase in LBMD at endpoint) were 39.7% for placebo, 59.6%, 79.3%, and 83.9% in the EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. Mean serum E concentrations were proportional to the dose of the E transdermal system and did not accumulate over the course of the study. Adverse events were generally comparable across treatment groups, with the majority being mild or moderate in severity and unrelated to study medication. Mammogram findings and other safety assessments were also comparable across groups and did not reveal any safety concerns with 2-y transdermal E treatment. CONCLUSIONS: The EMTDS (Alora) administered twice weekly improves lumbar bone mineral density in healthy postmenopausal women, with the benefit of treatment evident by 1 year. The lowest effective dose is 0.025 mg/day.

Application of a Stable Isotope Technique for the Bioequivalency Study of Two Transdermal Nitroglycerin Systems.

A bioequivalency study of an experimental transdermal nitroglycerin system relative to the commercial Transderm-Nitro 0.4 mg/h system was performed on eight healthy volunteers by using an innovative stable isotope technique. Plasma clearance changes for nitroglycerin (NTG) during patch application were corrected with simultaneously administered intravenous infusion of (15)N-labeled nitroglycerin ((15)N-NTG) solution. The total amount of NTG transdermally absorbed (AUC x CL) during a 22-h application for the experimental system was not statistically different from that for the commercial system (9.7 plus minus 3.3 versus 8.1 plus minus 2.6 mg; p = 0.41). The analysis of residual drug content in the used system revealed that the difference in amounts of NTG delivered from the experimental and commercial systems were not significant (12.2 plus minus 3.1 versus 10.8 plus minus 3.1 mg; p = 0.29). With the isotope-labeled method, the absorption rate was evaluated at each time interval during the system application. The peak concentration values were 0.52 plus minus 0.21 mg h(minus sign1) at 1 h for the experimental system and 0.41 plus minus 0.15 mg h(minus sign1) at 2 h for commercial systems. After the peak concentrations, the absorption rates remained constant for both systems over the 16-h period. There was no statistical difference in absorption between the two systems at any sampling time. In this study, substantial fluctuations in the plasma concentrations of both NTG and (15)N-NTG were observed within and between subjects. In addition, the variability in plasma concentrations of NTG correlated well with that of (15)N-NTG for all participating subjects. The momentary changes of clearance, estimated from (15)N-NTG plasma data, were found to be responsible for the fluctuation of NTG in plasma.