Modifying and Validating a Quality of Life Measure to Fit Your Patient Population

Introduction: A well-developed quality of life (QoL) instrument is valuable in identifying the burden of illness. We were interested in exploring whether existing QoL instruments were suitable for patients in our medical setting and, if not, whether this could be rectified by adapting an existing valid and reliable instrument to meet the specific needs of our patient population. For the purposes of this study, we chose to evaluate the quality of life of patients with breast cancer. Specifically, we were interested in two aspects of QoL in women with breast cancer. The first was whether existing instruments were pertinent to the women in our venue. The second research interest was dependent upon the first. If current instruments were found wanting, could this be rectified through the creation and validation of new domains of relevance to these patients? Method: First, five patients were interviewed to ascertain QoL issues pertinent to women in our medical setting. Second, to determine regional appropriateness of existing breast cancer QoL instruments, a search was conducted to identify and review existing breast cancer specific QoL instruments. Third, an addendum was created (to be used in conjunction with an existing instrument identified through the search) that contained three QoL domains not typically found: Financial, Spirituality and Satisfaction with Medical Care. The addendum was then tested along with an existing instrument (FACT-B). Results: Internal consistency for the new scales, Satisfaction with Medical Care, Spirituality, and Financial had alpha coefficients of 0.81, 0.80, and 0.63 respectively. The total score for FACT-B plus addendum was 0.69. Pearson’s correlation coefficients were 0.49 for Financial, 0.64 for Satisfaction with Medical Care, and 0.70 for Spirituality. Total test/retest was 0.71

Neuro-vascular coupling and heart rate variability in patients with type II diabetes at different stages of diabetic retinopathy

Aims/Hypothesis: There is evidence that diabetes is accompanied by a break-down of functional hyperemia, an intrinsic mechanism of neural tissues to adapt blood flow to changing metabolic demands. However, to what extent functional hyperemia is altered in different stages of diabetic retinopathy (DR) in patients with type II diabetes is largely unknown. The current study set out to investigate flicker-induced retinal blood flow changes in patients with type II diabetes at different stages of DR. Materials and methods: A total of 76 subjects were included in the present parallel-group study, of which 56 had diabetes with either no DR or different stages of non-proliferative DR (n = 29 no DR, 12 mild DR, 15 moderate to severe DR). In addition, 20 healthy subjects were included as controls. Retinal blood flow was assessed before and during visual stimulation using a combined measurement of retinal vessel calibers and blood velocity by the means of Doppler optical coherence tomography (OCT). To measure systemic autonomic nervous system function, heart rate variability (HRV) was assessed using a short-term orthostatic challenge test. Results: In healthy controls, retinal blood flow increased by 40.4 ± 27.2% during flicker stimulation. Flicker responses in patients with DR were significantly decreased depending on the stage of the disease (no DR 37.7 ± 26.0%, mild DR 26.2 ± 28.2%, moderate to severe DR 22.3 ± 13.9%; p = 0.035, ANOVA). When assessing systemic autonomous neural function using HRV, normalized low frequency (LF) spectral power showed a significantly different response to the orthostatic maneuver in diabetic patients compared to healthy controls (p < 0.001). Conclusion/Interpretation: Our study indicates that flicker induced hyperemia is reduced in patients with DR compared to healthy subjects. Further, this impairment is more pronounced with increasing severity of DR. Further studies are needed to elucidate mechanisms behind the reduced hyperemic response in patients with type II diabetes. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT03 552562].Published versionFinancial support from the Austrian Science Foundation FWF Projects Grant numbers: KLI529 and KLI721 are gratefully acknowledged

The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects—A Randomized Clinical Trial

It has been hypothesized that besides its intraocular pressure (IOP) lowering potential, tetrahydrocannabinol (THC) may also improve ocular hemodynamics. The aim of the present study was to investigate whether single oral administration of dronabinol, a synthetic THC, alters optic nerve head blood flow (ONHBF) and its regulation in healthy subjects. The study was carried out in a randomized, placebo-controlled, double-masked, two-way crossover design in 24 healthy subjects. For each study participant, 2 study days were scheduled, on which they either received capsules containing 5 mg dronabinol or placebo. ONHBF was measured with laser Doppler flowmetry at rest and while the study participants performed isometric exercise for 6 minutes to increase mean arterial blood pressure (MAP). This was repeated 1 hour after drug intake. Ocular perfusion pressure (OPP) was calculated as 2/3MAP-IOP. Dronabinol was well tolerated and no cannabinoid-related psychoactive effects were reported. Neither administration of dronabinol nor placebo had an effect on IOP, MAP, or OPP. In contrast, dronabinol significantly increased ONHBF at rest by 9.5 ± 8.1%, whereas placebo did not show a change in ONHBF (0.3 ± 7.4% vs. baseline, P < 0.001 between study days). Dronabinol did not alter the autoregulatory response of ONHBF to isometric exercise. In conclusion, the present data indicate that low-dose dronabinol increases ONHBF in healthy subjects without affecting IOP, OPP, or inducing psychoactive side effects. In addition, dronabinol does not alter the autoregulatory response of ONHBF to an experimental increase in OPP. Further studies are needed to investigate whether this effect can also be observed in patients with glaucoma.Published versionThis study was funded by the Austrian Science Fund (FWF) (KLI 340)

Retinal oxygen metabolism and haemodynamics in patients with multiple sclerosis and history of optic neuritis

Vascular changes and alterations of oxygen metabolism are suggested to be implicated in multiple sclerosis (MS) pathogenesis and progression. Recently developed in vivo retinal fundus imaging technologies provide now an opportunity to non-invasively assess metabolic changes in the neural retina. This study was performed to assess retinal oxygen metabolism, peripapillary capillary density (CD), large vessel density (LVD), retinal nerve fiber layer thickness (RNFLT) and ganglion cell inner plexiform layer thickness (GCIPLT) in patients with diagnosed relapsing multiple sclerosis (RMS) and history of unilateral optic neuritis (ON). 16 RMS patients and 18 healthy controls (HC) were included in this study. Retinal oxygen extraction was modeled using O2 saturations and Doppler optical coherence tomography (DOCT) derived retinal blood flow (RBF) data. CD and LVD were assessed using optical coherence tomography (OCT) angiography. RNFLT and GCIPLT were measured using structural OCT. Measurements were performed in eyes with (MS+ON) and without (MS-ON) history for ON in RMS patients and in one eye in HC. Total oxygen extraction was lowest in MS+ON (1.8 ± 0.2 μl O2/min), higher in MS-ON (2.1 ± 0.5 μl O2/min, p = 0.019 vs. MS+ON) and highest in HC eyes (2.3 ± 0.6 μl O2/min, p = 0.002 vs. MS, ANOVA p = 0.031). RBF was lower in MS+ON (33.2 ± 6.0 μl/min) compared to MS-ON (38.3 ± 4.6 μl/min, p = 0.005 vs. MS+ON) and HC eyes (37.2 ± 4.7 μl/min, p = 0.014 vs. MS+ON, ANOVA p = 0.010). CD, LVD, RNFLT and GCIPL were significantly lower in MS+ON eyes. The present data suggest that structural alterations in the retina of RMS patients are accompanied by changes in oxygen metabolism, which are more pronounced in MS+ON than in MS-ON eyes. Whether these alterations promote MS onset and progression or occur as consequence of disease warrants further investigation. Clinical Trial Registration: ClinicalTrials.gov registry, NCT03401879.Published versionSupport by the Austrian Science Fund (grant numbers KLI 721 and KLI 529) is gratefully acknowledged

Effect of hyperoxia and hypoxia on retinal vascular parameters assessed with optical coherence tomography angiography

To investigate the response of the superficial and deep capillary plexuses to hyperoxia and hypoxia using optical coherence tomography angiography (OCT-A) and retinal vessel analyzer.Agency for Science, Technology and Research (A*STAR)National Research Foundation (NRF)Published versionThis work was funded by grants from the Austrian Science Foundation (FWF Project No. KLI 721), the National Medical Research Council (CG/C010A/2017; OFIRG/0048/2017; OFLCG/004c/2018; and TA/MOH-000249-00/2018), the National Research Foundation Singapore, A*STAR (A20H4b0141), the Singapore Eye Research Institute & Nanyang Technological University (SERI-NTU Advanced Ocular Engineering (STANCE) Program) the Duke-NUS Medical School (Duke-NUSKP(Coll)/2018/0009A), the SERI-Lee Foundation (LF1019-1) Singapore